ANTIVIRAL STRATEGY AGAINST AIDS
For tackling AIDS, the following two approaches have been suggested:
- Suppress the virus as much as possible from the onset by continually using strong antiviral drugs.or
- Delay antiviral therapy until CD4+ T cell count falls below a critical level (when CD4 count drops below 250 percubic millimeter, antiviral drug is continued until the count rebounds above 350).
A study to determine which one of the two approaches is better has begun in January 2002 at 21 US locations and several sites in Australia.1
SMARTs (Strategies for management of antiretroviral therapies) will eventually enroll 6000 people who will be monitored for up to 9 years. The study is being conducted by the Community Programmes for Clinical Research on AIDS (CPCRA), a network of community based researchers funded by the National Institute of Allergy and Infectious Diseases (NIAID).
SMARTs enrollment criteria are broad. Teenagers as well as adults are eligible.
- NIH News Release. J Am Coll Surgeons 194: 552,2002.
HYDATID DISEASE OF BONE
The osseous manifestation of hydatid disease is rare and its management difficult. Effective cure requires surgical excision or debridement in combination with antihelminthic chemotherapy.1,2 Local recurrence is inevitable if there is contamination at the operative site with cyst spillage and inadequate debridement of the infected tissue.
Booz3 in 1972 advocated the local curettage of hydatid lesions with formalin swabbing, and where necessary, autologous bone grafting. Success in longterm eradication was reported in one of his 12 cases; short-term success with 2 years follow up was reported in 5 of the other cases and 3 cases were lost to the follow up. Sapkas et al reported a series of 8 cases of hydatid bone disease in 1998. Here, patients received both surgical debridement and an antihelminthic drug (mebendazole). Three of the 8 cases were reported free, however the remainder had local recurrence and underwent multiple surgical debridement. Szypryt et al reported successful eradication of osseous disease with surgical debridement and albendazole in 3 out of 5 cases.
Both these workers suggested that to achieve cure, radical excision of the infected bone with wide margins of normal tissue, avoiding contamination of the operative site and adequate chemotherapy is required. This would however entail replacement by total bony prosthesis, a technically demanding procedure. Metcalfe and Grimer4 reported a case of radical excision and restoration of function in a difficult case. A 27-year-old with a pathological fracture of the left humerus at the surgical neck was seen. Hydatid disease had affected the left humerus for 10 years. X-rays showed a gross expansible lytic process affecting most of the humerus. It was decided to excise the whole humerus and adjacent involved tissue. The nerves were identified and preserved. A custom made humeral endoprosthesis was then inserted. Soft tissue coverage of the prosthesis and skin closure was achieved. The patient had a full course of albendazole postoperatively.
- Szypryt E, Morris D, Mullholland R: Combined chemotherapy and surgery for hydatid disease. J Bone Joint Surg Br 69: 141,1987.
- Sapkas G, Stathakpoulos D, Babis G et al: Hydatid disease of bone and joints. Acta Orthop Scand 69: 189,1998.
- Booz M: The management of hydatid disease of bone and joint. J Bone Joint Surg Br 54: 698,1972.
- Metcalfe JE, Grimer RJ: Tackling osseous hydatidosis using orthopaedic oncology techniques. Ann R Coll Surg Engl 82: 287,2000.
BILIOUS VOMITING IN THE NEWBORN
In a prospective audit of 63 neonates presenting consecutively with bilious vomiting over a two years period, Godoble and Stringer1 identified 24 (38%) as having surgical pathology. Diagnoses included Hirschsprung's disease, small bowel and colonic atresia, meconium ileus and intussusception. In addition, 4 children had intestinal malrotation. Of these patients 19 had abdominal signs and 23 had an abnormal radiograph. After definitive surgery, all 24 infants were well at a median of 14 months. Those 39 children with no surgical cause had symptom resolution with conservative treatment.
Harold Nixon of Great Ormond Street made a statement in 1961 that “bilious vomiting in the neonate should be considered as due to mechanical intestinal obstruction until proven otherwise” remains sound advice and should mandate thorough investigation.
Prof Parthapratim Gupta from the Institute of Child Health, Calcutta has given a lucid account of Neonatal Intestinal Obstruction in this issue of Recent Advances.
- Godoble P, Stringer MD: Bilious vomiting in the newborn. How often is it pathological? J Paed Surg 37: 909, 2002.
EXTRAHEPATIC BILIARY ATRESIA (EHBA)
Extrahepatic biliary atresia is the absence of patent bile ducts draining the liver. The atretic ducts consist of solid fibrous cords that may contain islands of biliary epithelium. Satisfactory bile drainage can be achieved by Kasai portoenterostomy (PE). The obliterated bile duct and surrounding fibrosis is dissected off the portal vein into the hilum of the liver. The extrahepatic biliary tissue is transected and anastomosed as Roux-en-y to an isoperistaltic retrocolic jejunal loop at the hepatic hilum.1
Factors which influence the success of the operation include age at surgery, experience of the surgical team, histology of the liver and ductal remnants at the porta hepatis. Successful biliary drainage following Kasai PE is achieved in infants who do not have liver cirrhosis, portal hypertension, intrahepatic-biliary cholangiopathy and those who have no extrahepatic anomalies.1,2 In the UK, the median age at surgery has fallen from 63 to 54 days with only 5 per cent of cases operated being older than 12 weeks.3,4 It is important for EHBA to be considered in the differential diagnosis of neonatal jaundice. Late referral is usually due to repeated reassurance by medical staff that jaundice is physiological, parents who ignore jaundice because the infant is thriving, inadequate follow up of neonatal jaundice and parental reluctance to accept referral. Early recognition and referral of infants with conjugate hyperbilirubinaemia is important to ensure early Kasai PE.
The only alternative to Kasai PE for EHBA is liver transplantation. During a 10 years follow-up of Kasai PE, about 30 per cent will require liver transplantation in the first 12–14 months, another 30 per cent in their teens and the rest will live with some degree of liver disease.5 Kasai PE prolongs the pretransplant interval in selected patients and allows weight gain, growth and immunisation. It improves donor availability due to increased recipient size, decreased allograft complications. It moreover prepares the family for liver transplant.6 Liver transplant is indicated when symptoms of endstage liver disease occur, including recurrent cholangitis, progressive jaundice, portal hypertension complications, ascites and growth/nutritional failure.7 Kasai PE and liver transplant should be considered as complimentary procedure to be used sequentially and not as rival procedures.8 Children with EHBA who do not undergo Kasai PE evolve more rapidly into end stage liver disease. Kasai PE may therefore be considered as a palliative bridge to liver transplant. However, primary liver transplant may be considered for children who present beyond 3 months of age.
- Kasai M, Kimuira S, Asakura Y et al: Surgical treatment of biliary atresia. J Pediatr Surg 3: 665,1968.
- Tan CE, Davenport M, Diver M et al: Does the morphology of the extrahepatic biliary remnants influence survival? A review of 205 cases. J Pediatr Surg 29: 1459,1994.
- Mickiernan PJ, Baker AJ, Kelly DA: The frequency and outcome of biliary atresia in the UK and Ireland. Lancet 355: 25,2000.
- McClement JW, Howard ER, Mowat AP: Results of surgical treatment for extrahepatic biliary atresia in United Kingdom 1982–82: Survey conducted on behalf of the British Paediatric Association Gastroenterology Group and British Association of Paediatric Surgeons. BMJ 290: 345,1985.
- Balistreri WF, Grand R, Hoofnagle JA et al: Biliary atresia: Current concepts and research directions: Summary of symposium. Hepatology 23: 1682,1996.
- Ryckman F, Fisher R, Pedersen S et al: Improved survival in biliary atresia patients in the present era of liver transplantation. J Pediatr Surg 290: 345,1995.
- Bates MD, Bucuvalas JC, Alonso MH et al: Biliary atresia: Pathogenesis and treatment. Semin Liver Dis 18: 281,1998.
RETROGRADE EMBOLISATION OF VARICOCELE IN THE PAEDIATRIC AGE GROUP
For vericocele, multiple techniques have been advocated including varicocelectomy, low ligation, high ligation and laparoscopic ligation. Over the past 2 decades, however, the trend has moved towards embolising varicocele as a minimally invasive and safe procedure with fairly low morbidity. Sivanathan and Abernethy from the UK1 studied 40 boys (age range, 6–16 years) with varicocele diagnosed both clinically and sonographically and were treated by retrograde embolisation. All of them had left sided varicocele. All of them underwent venography of left renal vein to check the retrograde filling into internal spermatic vein. Through the right femoral vein, a Cobra II catheter was introduced and contrast injected after manoeuvring into left renal vein. Those who demonstrated retrograde filling into the internal spermatic vein had embolisation done using complex microcatheter. Patients who did not show retrograde filling were not embolised.
Four patients were declared nonembolisable after spermatic venography; none of them demonstrated venous reflux. All of them underwent surgical ligation. Four patients had recurrence: 3 of them had successful repeat embolisation and one patient declined further treatment.
The results suggest that embolisation is valuable as a first line of treatment for paediatric varicocele if a skilled interventional radiologist is available. This procedure is less invasive, avoids general anaesthetic, involves minimal postoperative pain and allows an earlier return to normal activity. However, 35 per cent of patients did eventually require conventional surgery for primary failure of embolisation or late recurrence.
- Sivanathan C, Abernethy LJ: Retrograde embolisation of varicocele in the paediatric age group: a review of 10 years experience. Ann R Coll Surg Engl 85: 50, 2003.
SURGERY FOR INGUINAL HERNIA
From the 58 randomised controlled trials analysed by the EU Hernia Trialists Collaboration1 the use of prosthetic mesh has emerged as superior to other techniques. It reduces recurrence and reduces both early and late postoperative pain. There are, however, certain unanswered queries:
- At what age should mesh repair replace childhood herniotomy? There is no clear answer from the literature but a recent consensus has reckoned 18 years as the watershed.2
- Should asymptomatic, readily reducible direct hernia in the elderly be repaired at all? The answer is probably not. However, randomised studies should provide evidence to answer this question with greater emphasis.
- Should mesh be inserted by an open or laparoscopic technique. The EU Hernia Trialists meta-analysis suggested an advantage for laparoscopic technique, less postoperative pain, an early return to normal activity and a lower incidence of chronic pain.1 However, laparoscopic repair is difficult to learn and the longer learning curve has deterred many surgeons, who while conceding that there are statistically significant advantages in terms of pain and recovery, see these as clinically marginal. Moreover, laparoscopic approach is more expensive, requires greater anaesthetic and recovery room output than an open mesh repair under local anaesthetic.
- Is such additional expense justified by better outcome? When performed by an experienced team the laparoscopic approach has clear advantages for patient with recurrent or bilateral hernia.
- Literature does not provide guidance about the best laparoscopic approach. The National Institute for Clinical Excellence (NICE)3 in the UK favours the total extraperitoneal repair (TEP) because it is safer. This view is based on a small number of visceral and vascular complications in the early days of the transabdominal (TAPP) approach. A recently published series of 8000 patients, however, has shown that the TAPP procedure can be performed successfully in large number of patients without serious morbidity.4
- Mesh though is the clear procedure of choice, however, those seeking guidance from the literature about which open mesh technique to use will be disappointed. There is some evidence from randomised study that plug and patch technique or the Prolene Hernia System (Ethicon) may confer advantage over the standard Lichtenstein repair. Further studies, however, are clearly indicated.
- The EU Trialists Collaboration: Repair of groin hernia with synthetic mesh meta-analysis of randomised controlled trials. Ann Surg 235: 322,2002.
- Jarret M: Hernia repair. Should the posterior wall be repaired routinely at a certain age. 24th Congress of European Hernia Society. Amsterdam 2002 (abstract).
- National Institute for Clinical Excellence: Guidance on the use of laparoscopic surgery for inguinal hernia. NICE London 2001.
- Bittner R, Schmedt CG, Scwartz J et al: Laparoscopic transperitoneal procedure for routine repair of groin hernia. Br J Surg 89: 1062,2002.
Obturator hernia is called the “skinny old lady hernia” because it is found in emaciated women in their seventh or eighth decades. A possible explanation is the wider and more obliquely inclined pelvis and the relatively greater transverse diameter (4 cm) of the obturator foramen in women compared with 3.5 cm in men.1 Obturator hernia is seldom bilateral. The emergency surgery requires an abdominal operation and this also facilitates bowel resection if necessary.
The most common presentation is intestinal obstruction of unknown cause in an elderly emaciated women with no earlier abdominal operations. The sign specific to strangulated hernia is the Howship-Romberg sign, characterised by pain in the medial thigh and is due to compressing the obturator nerve against hernia.
CT, ultrasonography and MRI can reliably make the diagnosis of obturator hernia. Use of CT in suspected cases can improve diagnostic accuracy up to 90 per cent.
Oral contrast can opacify the herniated loop if it is not totally obstructed, but the process is time consuming, in fact CT can provide an entirely adequate image of a non-opacified bowel. CT is well suited for diagnosis if the diagnosis is uncertain. US is also fast and readily available.2
When strangulation is suspected, contrast barium studies are contraindicated because barium can leak and cause chemical peritonitis. Use of a water soluble contrast medium is safer, but this should be supplemented by results of CT because of additional time needed. Herniography has no place in the emergency diagnosis of obturator hernia. It is used only in elective cases.
- Bergstein JM, Condon RE: Obturator hernia, current diagnosis and treatment. Surgery 119:133,1996.
VIDEO ASSISTED THYROIDECTOMY (VAT)
Thyroidectomy is one of the very common operation throughout the world. Conventional surgery leaves a visible scar on the anterior surface of the neck. The use of minimal invasive surgery (MIS) for thyroid was primarily motivated by the attempt to improve the cosmetic result of the operation.
MIS should, however, guarantee better postoperative outcome. It should, however, be pointed out that these procedures are not easy or feasible in all clinical settings. They are technically demanding and require a team skilled in both endocrine and endoscopic surgery.
The procedure is performed by a totally gasless video-assisted technique through a single 1.5 to 2.0 cm skin incision. Dissection is performed under endoscopic vision.
The patient under general anaesthesia is placed in the supine position. The neck is slightly extended but not hyperextended. A 15 to 20 mm skin incision is performed about 2 cm about the sternal notch in the midline. The cervical linea alba is then opened as much as possible, taking care to avoid any bleeding. The thyroid lobe on the affected site is then carefully dissected from the strap muscles. Two small conventional retractors are used to medially retract the thyroid and to laterally retract the strap muscles to maintain the operative space. The endoscope (5 mm, 30°) is then inserted through the skin incision. Endoscopic magnification allows for easy identification and careful dissection of neck structures is performed under endoscopic vision.
53 VATs were attempted on 47 patients by Bellantone et al.1 Mean operative time was 86.8 minutes for lobectomy, 116.0 minutes for total thyroidectomy. Conversion rate was 7.5 per cent. The postoperative results were good and with excellent cosmetic results. The procedure, however, is technically demanding.
Nodule size and thyroid volume are the most important limiting factors for VAT. Obviously large thyroid glands cannot be removed by 1.5 to 2.0 cm skin incision. Only small thyroid nodules in small or normal thyroid glands can be approached by VAT.
It is better to avoid thyroid malignancy,2 though Bellantone et al have safely performed VAT for small papillary carcinoma.
Pradeep Chowbey, a pioneer in the field of Minimal Access Surgery in India has given a lucid account of this newer development in surgery in this issue of Recent Advances.3
- Bellantone R, Lombardi CP, Raffaelli M et al: Video assisted thyroidectomy. J Am Coll Surg 194:610,2002.
- Gagner M, Inabnet WB: Endoscopic thyroidectomy for solitary thyroid nodules. Thyroid 11:161,2001.
MEDICAL ANTISHOCK TROUSERS
Medical antishock trousers (MAST), an inflatable overall, enclosing the lower extremities and abdomen have been advocated for some injured patients in the hope that the cardiac output will be distributed to more vital areas. The garment compresses veins in the lower limbs and abdomen and displaces blood centrally to increase venous return to the heart until definitive care could be given. The equipment, however, is expensive and may have adverse effects.
Two randomised controlled trials were identified. These included 1202 patients in total; however data for only 1075 of these was available. Duration of hospitalisation and intensive care unit stay was longer in the MAST treated group. Reviewer's conclusion1 was that there is no evidence to suggest that MAST application reduces mortality, length of hospitalisation or length of ICU stay in trauma patients and it is possible that it may increase these. The data does not support the continued use of MAST in the situation described. However, it should be recognised that due to poor quality of the trials, conclusion should be drawn with caution.
- Dickinson K, Roberts I: Medical antishock trousers (pneumatic antishock garments) for circulatory support in patients with trauma. Cochrane Review. In the Cochrane Library Issue 3, Oxford, 2002.
HUMAN POLYMERISED HAEMOGLOBIN
Human polymerised haemoglobin (Poly Heme, Northfield Labs, Evanston, IL) is a universally comatible, more easily available, disease free oxygen carrying resuscitative fluid. It has been developed as a red cell substitute for urgent blood loss.
Poly Heme is a sterile, pyrogen free, isotonic and iso-oncotic solution. It can play an important role as a novel oxygen carrying resuscitative fluid.
For acute blood loss in trauma and surgery, restoration of circulating volume and maintenance of sufficient oxygen carrying capacity to tissues is essential. Resuscitation involves initial volume replacement with salt solution followed by red cell transfusions when compatible blood is available. But there are occasions when red cells are temporarily unavailable, inadequate in supply or cannot be used because of incompatibility or religious objection (Jehovah Witness). An alternative oxygen carrier that could provide immediate life sustaining therapy until adequate red blood cell haemoglobin levels could be restored would be clinically useful. Poly Heme increases survival by maintaining total haemoglobin in the absence of red cell transfusion. Poly Heme should be useful in the early treatment of urgent blood loss and resolve the dilemma of unavailability of red cells. Physiologically, Poly Heme loads and unloads oxygen similarly to red cells. Its use to provide life sustaining therapy by maintaining adequate haemoglobin during haemorrhage is appropriate. Moreover, Poly Heme has a shelf life of greater than 1 year at 2 to 8°C.
A study by Gould et al1 assessed survival in 171 patients with urgent blood loss who received Poly Heme in lieu of red cells as their initial oxygen carrying replacement. The study design provides unique opportunity to assess the physiologic activity of Poly Heme in urgently bleeding patients in the virtual absence of any circulating red cells. The 171 patients received rapid infusion of 1 to 20 units of Poly Heme in lieu of red cells. The 30 days mortality was 25.0 per cent (10/40 patients) compared with 64.5 per cent (20/31 patients) in historical controls of 30 patients who refused red cells on religious grounds. A potential criticism of this study is the use of historical data for comparison. An appropriate control group would have been concurrent patients not receiving red cells or any other oxygen carrying replacement. Such a design would be unethical in setting where red cells were available2 and therefore the historical comparison was selected.
Poly Heme can play an important role. It has the potential to simplify and facilitate early treatment of urgent blood loss by immediate, rapid volume expansion and haemoglobin replacement without red cell transfusion. Poly Heme is an effective therapeutic option that should be useful in the early treatment of urgent blood loss resolving the dilemma of unavailability of red cells.
- Gould SA, Moore EE, Hoyt DB et al. Life sustaining capacity of human polymerised haemoglobin when red cells might be unavailable. J Am Coll Surg 195: 445,2002.
- Huston P, Peterson R. Withholding proven treatment in clinical research. N Engl J Med 345:912,2001.
RADIOFREQUENCY ABLATION OF METASTATIC COLORECTAL TUMOURS IN THE LIVER
Liver resection is the standard therapy for treatment of patients with a small number of liver metastases. The 2 years actuarial survival for patients after resection of metastases is about 40 per cent. Moreover all metastases must be completely resected for there to be any chance of cure. If even microscopic residual tumour remains, resection does not carry benefit either in prolongation of life or cure.3 Generally it is not feasible to resect more than five hepatic metastases.
Percutaneous radiofrequency (RF) ablation was first used for hepatic neoplasms in an animal model by MacGahan et al in 1972.1 The technique was then effectively used for primary and recurrent liver tumours and some satisfactory clinical results were reported.2 Radiofrequency (RF) ablation is a thermal treatment. Owing to the ‘heat sink effect’ the heat generated is partly carried away by liver blood flow. By temporarily occluding both the portal vein and the hepatic artery (Pringle manoeuvre) during RF ablation, the cooling effect of blood flow can be reduced. Both Rossi et al3 and Patterson et al4 showed that total vascular inflow increases with all RFA lesion dimensions in procine liver in vivo.
Radiofrequency (RF) ablation has recently received approval for use in liver tumours by the FDA. RF ablation creates a zone of ablation in the liver and FDA gave it approval for general use in patients not eligible for surgical resection.
RF ablation could be applied appropriately to patients who are ineligible for surgical liver resection. Alternatively, it may be applied to patients who have resectable lesions, but the risk benefit ratio for patients in these two groups must be considered.
In those, ineligible for resection, the benefit of RF ablation is the potential for cure where no other possibility exists. But for those who are eligible for resection there is possibly greater risk that RF is less effective treatment for cancer.
The question of the route of RF ablation also needs to be discussed. The least invasive approach is percutaneous, the laparoscopic route is more invasive and open surgery is the most invasive. Patients with comorbid illness may be treated by the less invasive method, but for the rest, open surgery would carry a potential oncologic benefit that would outweigh its inconvenience. Open surgery is the most effective way to detect all lesions.4
- MacGahan JP, Brock JM, Tesluk H et al: Hepatic ablation with use of radiofrequency electrocautery in the animal model. J Vasc Interv Radiol 3: 291,1991.
- Solbiati L, Ieraca T, Goldberg SN et al: Percutaneous ultrasound guided radiofrequency ablation of liver metastases. Treatment and follow up in 16 patients. Radiology.
- Rossi S, Garbagnati F, Francesco I et al: Relationship between the shape and size of radiofrequency induced thermal lesions and hepatic vascularisation. Tumori 85:128,1999.
- Patterson EJS, Scudamore CH, Owen DA et al: Radiofrequency ablation of porcine liver in vivo, effects of blood flow and treatment time on lesion size. Ann Surg 227:559,1998.
Barrett's oesophagus (BE) is a metaplastic response of the lining mucosa of the oesophagus to chronic gastro-oesophageal reflux. The treatment of choice in BE is still controversial. Some suggest that surgery could be more effective than medical treatment in preventing BE from progressing to dysplasia and carcinoma, however, detailed studies are necessary to answer this question.1 101 patients were included in a randomised prospective study, 43 with medical treatment and 58 with antireflux surgery. All patients underwent clinical, endoscopic and histological assessment. Functional studies were performed in all the operated patients and in a subgroup of patients receiving medical treatment. The median follow-up was 5 years (range 1–18) in the medical treatment group and 6 years (range 1–19) in the surgical treatment group.
Satisfactory clinical results (excellent to good) were achieved in 39 of 43 patients (91%) undergoing medical treatment and in 53 of 58 patients (91%) following antireflux surgery. The persistence of added inflammatory lesions was significantly higher in the medical treatment group. The metaplastic segment did not disappear in any case. Postoperative functional studies showed significant decrease in the median per centage of total time with pH below 4, although 9 of 58 patients (15%) showed pathologic rates of acid reflux. High grade dysplasia appeared in 2 of 43 patients (5%) in medical treatment and in 2 of 58 patients (3%) in the surgical treatment group. In the latter both patients presented with clinical and pH metric recurrence. There was no case of malignancy after successful antireflux surgery. This shows that there is no difference between the two types of treatment with respect to preventing BE from progressing to dysplasia and adenocarcinoma. However, successful surgery proved to be more effective than medical treatment in the sense perhaps it controls acid and biliopancreatic reflux to the oesophagus.
In younger patients with mild dysplasia, it is wise to do antireflux surgery. When severe dysplasia is present, this should be viewed as “adenocarcinoma in situ”. Therefore for this condition and for established adenocarcinoma, oesophagogastrectomy should be undertaken if the patient is fit for surgery.
In older patients or patients unfit for surgery, there are many non-surgical alternatives for reflux disease like endoscopic pleating or injection of Teflon or the use of a radiofrequency probe. For the patient with severe dysplasia, laser ablation, mucosal resection, photodynamic therapy, cryosurgery, argon beam and perhaps radiofrequency ablation are the possible techniques that can be employed.
- Parrilla P, Martinez de Haro LF, Oritz A et al: Long-term results of a randomised prospective study comparing medical and surgical treatment of Barrett's oesophagus. Ann Surg 237: 291,2003.
OESOPHAGEAL CANCER: BEING ABLE TO SWALLOW DOES HAVE ITS PRICE
It would appear that in terms of normal food taken and durability of relief, oesophageal resection would be the best option. The restoration of swallowing function provides good quality life. Oesophageal resection, however, incurs the highest operative mortality of elective operations and the price is a heavy one. Improvements however, have been made over time. Wong et al1 graphically relate their experience. In the last 20 years, more than 2000 patients were managed at Queen Mary Hospital, Hong Kong, a teaching hospital where uninsured patients pay a negligible fee and staff are remunerated with salaries only. Patients are referred directly by family doctors, public general clinics and other specialists and a good proportion are self referred to the emergency room when dysphagia is advanced, disease terminal, or a major postoperative complication has occurred in another hospital.
Male patients predominate and almost all are from the lower or lowest socioeconomic strata. Weight loss is considerable and one in eight patients has pulmonary tuberculosis. Most suffer from stage III or IV disease. Most patients agreed to or even requested resection despite all the risks fully explained to them.
Preoperative care consists of cessation of smoking and physiotherapy. Epidural analgesia for pain control is advocated; minimal trauma at intubation with a double lumen tube, subcostal incision, limited muscle spanning thoracotomy, reduced blood loss with meticulous technique. Most patients are extubated in the operating room at the end of the procedure. Patients sit out of bed on the first postoperative day, receive daily bronchoscopy for about 3 days and physiotherapy. The nasogastric tube and chest drain are removed early. Patients are usually sent back to the ward on 3rd or 4th postoperative day and are commenced on a liquid diet.
It is important to be vigilant to surgical complications. These are now rare but for the whole series, in chronological order of appearance, they are postoperative bleeding (2.3%), gangrene of conduit (0.5%), chylothorax (0.8%), anastomotic leakage (4%), empyema (1.8%), wound infection (10%) and outlet obstruction (2.4%). The key to their management is early recognition and aggressive treatment.
A tracheostomy is performed either at the time of operation when the coughing effort is inadequate or for those with serious co-existing pulmonary problems.
In the last 409 patients (from October 1993), there has been no 30 days mortality and in the last 124 patients (from March 1999), there has been no hospital death. There has been one death in 289 patients since September 1995.
Anastomotic leakage is a feared event. In specialised centres, leakage rates of less than 5 per cent are achieved, and what is more important is the death directly attributable to leakage can be avoided by timely and appropriate interventions.2 A leak presenting early (less than 72 hours) is likely to be associated with necrosis of some part of the conduit, the stomach being the most commonly used organ. Early reoperation is mandatory. Anastomotic leakage should now be an uncommon event but the level of suspicion must remain high when the patient is not doing well after resection, e.g. develops atrial fibrillation and respiratory complications.
Anastomotic recurrence after resection of a squamous cancer is highly predictable and is margin-dependent.3 This is also true for adenocarcinoma of the cardia, although the association is less absolute. A margin of 6 cm or more measured in situ before transection of the oesophagus (risk of recurrence, 1.3% for a 6 cm margin) is a reasonable compromise and serves as a guideline if it is a matter of deciding on whether to extend the oesophageal extirpation from the thoracic cavity to the neck, and, in the case of adenocarcinoma, whether to perform a thoracotomy. For cancer of the superior mediastinal segment or cervical oesophagus, the trade off is whether a laryngectomy should be performed. It is Wong et al practice not to sacrifice voice for margin alone, because radiotherapy after resection can be effective.
Another major impediment to satisfactory oral intake is outlet obstruction at the pylorus when the stomach is used as the substitute. This is best managed by pyloroplasty, rather than pyloromyotomy.4
As for the optimal site for placement of the conduit, it is better to use the orthotopic route, it is functionally better and the length of conduit required is also shorter. The exception to this is however, in a palliative resection. When disease is left in the mediastinum and in this situation postoperative radiotherapy is indicated.5 In these circumstances, conduit is placed retrosternally because radiation to the orthotopically placed stomach can damage and even compromise survival.
In recent years, bypass procedures have virtually been abandoned because of the effectiveness of self-expanding stents, which could achieve very reasonable palliation of dysphagia without excessive morbidity and mortality associated with bypass in this group of poor-risk patients. Neoadjuvant and adjuvant chemotherapy or radiotherapy alone have not contributed substantially to the longer survival. Randomised controlled trials for preoperative radiotherapy have shown no improvement over surgical resection alone.5 Randomised controlled trials on postoperative radiotherapy demonstrated a worse prognosis for the treatment group.7
After the generally disappointing results of single modality additional treatment, the current thrust is on combined therapy, using chemoradiotherapy preoperatively. A number of trials have been reported. These trials suggested that combined therapy can hold more promise than single modality treatment8 but the verdict will not be forthcoming for sometime yet. For a condition that has been associated with the highest operative mortality and lowest survival rates, it must be the surgeon's task to improve outcome. Wong et al have rather been liberal in the choice of resectional surgery even in those with palliative intent.
There are two approaches a surgeon can take. The first is to bring the patient through an appropriately selected operation with curative or palliative intent, or to palliate those with no chance of cure using oesophageal stents, and so pay the lowest price. The second is to introduce additional treatment.
Self expanding metallic stents can achieve reasonable palliation of dysphagia. Neoadjuvant and adjuvant chemotherapy or radiotherapy alone however have not contributed substantially to long survival.6 The current thrust is on combined therapy, using chemoradiotherapy preoperatively.8 However, additional treatments must be studied scrupulously as benefits may accrue only to some but may be harmful to others.9
- Wong J, Law S: Esophageal cancer: What price swallowing: J Am Coll Surg 196:347,2003.
- Whooley BP, Law S, Murthy SC et al: Analysis of reduced death and complication rates after oesophageal resection. Ann Surg 233:338,2001.
- Law S, Arcilla C, Chu KM et al: The significance of histologically infiltrated resection margin after esophagectomy for esophageal cancer. Am J Surg 176:286,1998.
- Law S, Cheung MC, Foik M et al: Pyloroplasty and pyloromyotomy in gastric replacement of the esophagus after esophagectomy: A randomised controlled trial. J Am Coll Surg 184:630,1997.
- Fok M, Sham JS, Choy D et al: Postoperative radiotherapy for carcinoma of the esophagus, a prospective randomised controlled study. Surgery 113:138,1993.
- Teniere P, Hay JM, Fingerhut A et al: Postoperative radiotherapy does not increase survival after curative resection for squamous cell carcinoma of the middle and lower oesophagus as shown by a multicentre controlled trial. Sur Gynecol Obstet 173:123,1991.
- Kelsen DP, Ginsberg R, Rajak TF et al: Chemotherapy followed by surgery compared with surgery alone for localised esophageal cancer. N Engl J Med 339:1979,1998.
- Walsh TN, Noonan N, Hollywood D et al: A comparison of multimodal therapy and surgery for oesophageal adenocarcinoma. N Engl J Med 335:462,1996.
ACUTE CHOLECYSTITIS: EARLY VERSUS DELAYED CHOLECYSTECTOMY
The two main treatment options for acute cholecystitis in patients fit for surgery, are either initial conservative treatment followed by delayed cholecystectomy, most commonly 6–8 weeks after discharge, or planned early cholecystectomy during the initial hospital admission.
Randomised controlled trials have shown that early cholecystectomy has significant benefits over delayed surgery in acute cholecystitis, whether this is performed by open surgery.1,2 or by laparoscopic technique.3,4 Early cholecystectomy is more cost effective, with patients having a shorter total hospital stay and recuperation time compared to delayed surgery. In addition, there were no significant differences in the complication rate between the early and delayed cholecystectomy groups, or the conversion rate in the laparoscopic trials. A randomised controlled trial comparing open and laparoscopic early cholecystectomy for acute cholecystitis recently reported an advantage for early laparoscopic cholecystectomy in terms of reduced total hospital stay and time off work.5
Delaying cholecystectomy after presentation with acute cholecystitis may remain attractive to surgeons struggling to provide emergency services with insufficient resources. Yet this approach may not avoid emergency readmission of complications which may occur in these cases within 6 weeks waiting period and this strongly suggests that early cholecystectomy during the index admission is the correct management of acute cholecystitis.6
- Jarvinen HJ, Hastbacka J: Early cholecystectomy for acute cholecystitis. A prospective randomised study. Ann Surg 191:501,1980.
- Norrby S, Herlin P, Holmin T et al: Early or delayed cholecystectomy in acute cholecystitis? A clinical trial. Br J Surg 70:163,1983.
- Lai PBS, Kwong KH, Leung KL et al: Randomised trial of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Br J Surg 85:764,1998.
- Lo CM, Liu CL, Fan ST et al: Prospective randomised study of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Ann Surg 227:461,1998.
- Kiviluoto T, Siren J, Lukkonen P et al: Randomised trial of laparoscopic versus open cholecystectomy for acute and gangrenous cholecystitis. Lancet 351:321,1998.
Its aetiology is obscure. Cholelithiasis is a common risk factor but the mode of carcinogenesis is not clear. Chronic irritation of the gallbladder mucosa may induce epithelial dysplasia which in turn leads to carcinoma.1 An important objection to the above hypothesis is the histological nature of cancer. Adenocarcinoma is the commonest variety and not the squamous which one would expect following metaplasia due to chronic irritation.
In gallbladder cancer, curative resections are possible only in very few due to the advanced stage of disease at the time of diagnosis. The majority of early gallbladder cancers are diagnosed incidentally on histopathological examination. Japanese series, however, report preoperative diagnosis in more than a third of patients.2,3 The rest of the world however, has reported a much lower incidence.4,5 The Japanese results may well be due to the predominance of protruding lesion that can be better identified on ultrasonography and the lower incidence of gallstones which otherwise interfere with the ultrasonographic imaging of the gallbladder.2,3,6 Simple cholecystectomy is adequate only in mucosal cancers (pT1a)7 and patients, with cancer infiltrating upto the muscularis (pT1b), require extended cholecystectomy.
The conventional imaging modality (US and computerised tomography) does not help in accurate preoperative staging and is unable to distinguish between T1a and T1b and between T1 and T2 lesions. In this era of laparoscopic cholecystectomy, if there is any preoperative suspicion of malignancy, open cholecystectomy should be preferred to avoid the hazards of tumour dissemination and in case of suspicion during laparoscopy, it should be converted to an open operation.8 Diagnosis of malignancy may be substantiated by intraoperative frozen section, FNAC or imprint cytology, and in case of malignancy, extended cholecystectomy should be performed.
For incidental gallbladder cancer, a simple cholecystectomy is curative in pT1a lesion. For pT1b lesion, a relaparotomy with wedge resection of liver and hepatoduodenal lymph node clearance is advised. For reoperation for laparoscopically discovered incidental cancer, there is need for excision of laparoscopic port sites because of the risk of dissemination.8
- Kijima H, Watanabe H, Iwafuchi M et al: Histogenesis of gallbladder carcinoma from investigation of early carcinoma and microcarcinoma. Acta Path Jpn 39:235,1989.
- Shirai Y, Yoshida K, Tsukada K et al: Early carcinoma of the gallbladder. Eur J Surg 158:545,1992.
- Onoyama H, Sugawara T, Ono H et al: Diagnostic imaging of early gallbladder cancer, retrospective study of 53 cases. World J Surg 23:708,1999.
- Benoist S, Panis Y, Fagniez PL: Long-term results after curative resection for carcinoma of the gallbladder. Am J Surg 175:118,1998.
- Kapoor VK, Pradeep R, Haribhakti SP et al: Early carcinoma of the gallbladder: an elusive disease. J Surg Oncol 62:284,1996.
- Kimura W, Shimoda HA: A case of gallbladder carcinoma with infiltration into the muscular layer that resulted in relapse and death from metastasis to the liver and lymph nodes. Hepatogastroenterology 37:86,1990.
- Vibbenmeyer LA, Wade TP, Chen RC et al: Laparoscopic cholecystectomy can disseminate in situ carcinoma of the gallbladder. J Am Coll Surg 181:504,1995.
Obscure GI bleeding has been defined as bleeding from a source that cannot be readily determined by conventional investigations such as barium studies and endoscopic investigation.1 In some series, it can account for up to 5 per cent of all haemorrhages, and the source is often elusive because the culprit lesions are anatomically inaccessible, small or subtle. Among the causes of obscure GI bleeding, Dieulafoy's lesions are more serious, because bleeding is often massive and recurrent. It is now generally acceptable that the bleeding is caused by an abnormally large artery running within the submucosa. The vessel has a tortuous course. The most accepted theory about what triggers the bleeding is that a superficial mucosal erosion is the primary event. In the colon, solid and hard faeces can contribute to mucosal stercoral ulceration over an abnormally dilated submucosal arteriole and subsequent rupture and haemorrhage. Age related mucosal atrophy might also add to the process. Mucosal injury as a result of ingestion of non-steroidal anti-inflammatory drugs or alcohol has also been suggested.
Lesions typically occur within 6 to 10 cm of gastro-oesophageal junction generally along the lesser curve. Similar lesions have been identified in the oesophagus, duodenal bulb, jejunum, ileum, caecum, right colon, transverse colon, left hemicolon, rectum, anal canal and bronchus.
A history of gastric complaints is usually absent and the association with heavy smoking, alcohol consumption and intake of NSAIDs is not consistently well documented. Dieulafoy's lesion is seen twice as frequently in men. It can occur at any age. The most common presentation is haematemesis associated with malaena. The mucosal defect typically occurs within an area of otherwise normal mucosa. There is no surrounding inflammations, exudates or ecchymosis. Frequently, isolated intraluminal blood is suggestive of recent bleeding.
Until recently, surgery was the only effective management. During the past few years, less invasive approaches have gained widespread acceptance. If the lesion can be endoscopically documented, attempts should be made to achieve haemostasis by electro-coagulation, heater probe, noncontact laser photocoagulation, injection sclerotherapy and band ligation. In those where endoscopy fails to identify the bleeding site, arteriography can localise the lesion and subsequent elective arterial embolisation can successfully control the bleeding.
Surgery is now reserved for lesions that cannot be controlled by endoscopic or angiographic technique. Dieulafoy's lesions should always be included in the differential diagnosis of gastrointestinal bleeding, especially when a definitive source is not found on routine investigation.2
- Spencer J: Obscure gastrointestinal bleeding. In. Gastroenterology: Clinical Science and Practice, Vol. 2. WB Saunders, London: 1008, 1993.
- Chaer RA, Helton WS: DieuLafoy's disease. J Am Coll Surg 196:290,2002.
ROLE OF LAPAROSCOPY IN PERFORATED PEPTIC ULCER
Robertson et al1 compared 20 consecutive laparoscopic repairs of perforated peptic ulcers with a concurrent group of 16 consecutive open repairs. The mean duration of surgery in the open group was 72 minutes compared with a mean of 77 minutes in the laparoscopy group.
Laparoscopy avoids the painful upper abdominal incision improving patient comfort and cosmetic appearance. There were no postoperative infected intra-abdominal collections diagnosed in either group confirming that laparoscopic lavage under vision is at least as effective as that at open surgery. It does not support the suggestion that laparoscopy might disseminate infection within the peritoneal cavity making such complications more likely.
There is undoubtedly a learning curve. The tissues are much more friable than normal. The reduced tactile feedback during laparoscopy demands extra care to avoid damage to adjacent structure and to avoid undue tension on sutures saving them from cutting out.
A greater concern has been the pathophysiological effects of laparoscopy in elderly patients with peritonitis. Such patients may already have borderline renal, respiratory and cardiac function and the additional insult of a CO2 tension pneumoperitoneum for upto 2 hours might, in theory, precipitate multiorgan dysfunction syndrome.
The changes in cardiovascular and respiratory function during laparoscopy are relatively well documented.2 There is also good evidence that an increase in intra-abdominal pressure to as little as 12 mmHg can lead to a reduction in blood flow and glomerular filtration rate and lead to anuric renal failure.3 It reduces mesenteric arterial blood flow and intestinal mucosal blood flow producing intramucosal acidosis4 and perhaps increasing bacterial translocation from the gut. It is possible that laparoscopy may induce depression in cell mediated immunity.
All this does create sufficient uncertainty over the risk/benefit ratios of laparoscopy in patients with generalised peritonitis particularly those who are systemically unwell. This calls, for a randomised controlled trial. Robertson's study1 was not randomised and the laparoscopy was being performed by more experienced surgeons. However, laparoscopic repair is clearly feasible.
Siu, Leong and Law5 conducted a randomised controlled trial. 130 patients with a clinical diagnosis of perforated peptic ulcer were randomly assigned to undergo either open or laparoscopic omental patch repair. Patients with previous abdominal surgery, concomitant evidence of bleeding from the ulcer, or gastric outlet obstruction were excluded from the study. Patients with clinically sealed off perforations without signs of peritonitis were treated without surgery. Laparoscopic procedure included thorough lavage of the peritoneal cavity along with closure of perforation using a single 3,0 polygalactin full thickness stitch. The suture was passed through the omental patch and tied.
Out of the initial 130 patients, 63 patients in the laparoscopic group and 58 patients in the open group entered the final analysis. Both the groups were similar in age, sex distribution and ASA classification. Laparoscopic repair was completed in 54 patients. There were 9 conversions. Three had perforated non-pyloric ulcers, 3 had unidentified perforations, 2 had perforations larger than 10 mm and 1 had bleeding during suturing. The mean operative time for laparoscopic repair was 42 minutes, significantly shorter than for open repair (52.3 minutes). The laparoscopic group also required significantly less parenteral analgesics than the open group. There was no difference between the two groups in the timing of removal of nasogastric tube, discontinuing IV fluids or resumption of full diet. There were significantly fewer chest complications and wound complications in the laparoscopic group than in the open group.
The mortality in the laparoscopic and open groups were 1 and 3 respectively. Patients in the laparoscopic group were discharged earlier and returned to normal activity sooner than the open group.
- Robertson GSM, Wemyss Holden SA, Maddern GJ: Laparoscopic repair of perforated peptic ulcer. The role of laparoscopy in generalised peritonitis. Ann R Coll Surg Engl 82:6,2000.
- Westerband A, Van De Water HM, Amazallag M et al: Cardiovascular changes during laparoscopic cholecystectomy. Surg Gynecol Obstet 175:535,1992.
- Hashikura Y, Kawasaki S, Munakata Y et al: Effects of peritoneal insufflation on hepatic and renal blood flow. Surg Endosc 8:759,1994.
- Kotazampassi K, Kapanidis N, Kazamias P et al: Haemodynamic events in the peritoneal environment during pneumoperitoneum in dogs. Surg Endosc 7:494,1993.
- Siu WT, Leong HT, Law BK: Laparoscopic repair for perforated peptic ulcer. A randomized controlled trial. Ann Surg 235:313,2002.
In 1889 Charles McBurney described McBurney's incision and the procedure for appendicectomy.1 For almost a century thereafter the treatment of acute appendicitis has remanded essentially unchanged and it was in 1983 that Kurt Semm suggested an alternative to open surgery and described laparoscopic appendicectomy.2
McBurney's operation, however, is well established and benefits of laparoscopic appendicectomy have been difficult to establish. A Cochrane Review was published in early 2002 which analysed 45 randomised controlled trials. The therapeutic outcome favouring laparoscopic appendicectomy included reduction in wound infection rate, postoperative pain on day 1, time to return of bowel function, length of hospital stay and early return to work. The advantages are that it is quicker, less painful and better cosmesis. There is, however, greater incidence of intra-abdominal abscess after laparoscopy and there is belief that laparoscopic appendicectomy is less likely to cause intraperitoneal adhesions than open surgery.3
Laparoscopic appendicectomy is not being practised widely, there is perhaps general reluctance. Pressures of time on emergency lists may play a part in deciding which method to use. Operating time is longer for the laparoscopic approach but with experience this may get sorted out. Cost and availability of equipment may also be an issue. Its increased use, however, is likely to require changes in the organisation of emergency surgical commitments, with greater opportunity for teaching by the senior surgeon experienced in the procedure. Where feasible, laparoscopy should be undertaken in those when appendicitis is suspected provided that local expertise is available.
- McBurney C: Experience with early operative interference in cases of disease of the vermiform appendix. New York Medical Journal 1:676,1889.
- Semm K: Endoscopic appendicectomy. Endoscopy 15:59,1983.
- Sauerland S, Lefering R, Neugebaur EAM: Laparoscopic versus open surgery for suspected appendicitis (Cochrance Review). Cochrane Database Syst Rev CD001546. 1: 2000.
SHOULD WE REMOVE THE NORMAL LOOKING APPENDIX?
At an open operation, when there is no other intra-abdominal pathology, what should be done with a normal appendix? Orthodox teaching is that the normal looking appendix should be removed and most would accept a histological appendicectomy rate of 10 to 25 per cent as reasonable.
With laparoscopy, there are two schools of thought. Chung et al1 suggest removal on the grounds that laparoscopic inspection alone does not accurately reflect histological appendicitis; having a sensitivity and specificity of 84 and 57 per cent respectively. Moreover, Di Senasriano et al2 have suggested that appendiceal pain may arise in an appendix that appears normal owing to neuroimmune mechanism associated with an abnormal content of neuropeptides and neuronal sprouting within the appendix wall. On the other hand, there are those who feel that a normal appendix should be left alone. Van den Broek et al3 followed 44 patients in this way for a median duration of 4.4 years; only one developed acute appendicitis. There is perhaps need for further studies to be able to arrive at a definite conclusion.
- Chung KMT, Poon M, Chick WK et al: Laparoscopic appendicectomy in young female patients; should we remove the normal looking appendix. Ann Coll Surg Hongkong 3:85,1999.
- DiSebastiano P, Fink T, di Mola FF et al: Neuroimmune appendicitis. Lancet 354:461,1999.
Nasogastric intubation is routinely used postoperatively by many surgeons to prevent myriad possible problems, including postoperative nausea, vomiting, abdominal distension, wound dehiscence and anastomotic leak. The intubation is however, associated with increased incidence of postoperative fever, atelectasis and pneumonia. It has also been shown that postoperative pneumonia in patients with nasogastric tube directly correlates with gastric microbial contents in the pulmonary tree, indicating the possibility of gastro-oesophageal reflux induced by the nasogastric tube.
Manning et al1 performed a prospective randomised case controlled study in 15 patients undergoing elective abdominal surgery. Half of the patients had nasogastric tube placed after induction of anaesthesia, the other did not. All had pH probes placed for measurement of postoperative reflux for a period of 24 hours. The patients with nasogastric tube had 137 episodes of reflux and those without had only 8; the duration of episodes of reflux were 100 fold higher in patients with nasogastric tube. This data reveals increased risk for GE reflux with the use of nasogastric tube and its routine use is not justified.
- Manning BJA, Winter DC, McGreal G et al. Nasogastric intubation causes gastro-oesophageal reflux in patient undergoing elective laparotomy. Surgery 130:788,2001.
Nipple discharge is a common presentation to breast clinic. Management of a spontaneous single duct nipple discharge with no associated mass and normal mammography remains controversial. One study suggests an expectant policy whilst others advocate microdochectomy in all such patients.1,2 Historically, major duct excision has been recommended as the treatment of choice in postmenopausal women, with microdochectomy reserved for premenopausal women. Burton et al3 explored the safety of doing microdochectomy in all women with spontaneous single duct nipple discharge and found it a safe and effective treatment in women over 50 years.
The surgical options for the treatment of nipple discharge are either single or multiple duct excision. Mansel recommends major duct excision in women over 45 years as a safe, effective procedure with good cosmesis when performed well and provision of maximal histological information.4 However, several studies advocate microdochectomy as the treatment of choice.5
- Locker AP, Gaba MH, Ellis IO et al: Microdochectomy for single duct discharge from the nipple. Br J Surg 75:700,1988.
- Burton S, Li WY, Himpson R et al: Microdochectomy in women aged over 50 years. Ann R Coll Surg Engl 85:47,2003.
- Mansell Nipple Discharge. In Benign diseases of the breast. Saunders London: 171–86, 1999.
- Berna JD, Madrigal M, Guirao J et al: Microdochectomy: the precise identification of the suspicious duct. Br J Surg 77:1217,1990.
EXTRAMAMMARY PAGET'S DISEASE
Although Paget described the breast lesion that bears his name but also suggested to a similar possibility involving other parts of the body.1
Extramammary Paget's disease (EMPD), a rare clinical entity, appears as a pale grey plaque with surrounding induration. The patient complains of irritation or pruritis. It is a cutaneous adenocarcinoma, usually of epidermal apocrine gland origin. An underlying visceral malignancy has also been described.2 The epidermis is infiltrated by irregular large pale cells scattered between compressed squamous epithelial cells of otherwise normal appearance.3 The lesion is predominantly found on vulva but may also occur in the perianal area. These patients are at increased risk of tumours of the genitourinary system and of colorectal carcinoma. Although other locations of EMPD such as groin, scrotum and axilla are very rare, but an association with secondary malignancy for lesion in these areas has also been reported.4
Pierre et al in a retrospective analysis of 33 patients at Massachusetts General Hospital Boston from 1971 to 1988 found lesions predominantly on the vulva (25 patients) and in perianal area in eight patients.5
- Paget J: On disease of mammary areola preceding cancer of the mammary gland. St Barth Hosp Rep 10:87,1874.
- Chanda JJ: Extramammary Paget's disease. Prognosis and relationship to internal malignancy. J Am Acad Dermatol 13:1009,1985.
- Goldblum JR, Hart WR: Vulvar Paget's disease: A clinicopathological and immunohistochemical study of 19 cases. Am J Surg 21:1178,1997.
- Yugueros P, Keeney GL, Bite U: Paget's disease of the groin report of seven cases. Plast Reconst Surg 100:336,1997.
- Jean Pierre, Pierie EN, Choudry U et al: Prognosis and management of extramammary Paget's disease and the association with secondary malignancies. J Am Coll Surg 196:45,2003.
- Berardi RS, Lee S, Chen HP: Perianal extramammary Paget's disease. Surg Obset Gynecol 167:359,1988.
INTERNATIONAL CONSENSUS ON MANAGEMENT OF NON-PALPABLE IMAGE DETECTED BREAST CANCER
Focussing on non-palpable image detected breast cancer, an international multidisciplinary team presented their experience at the International Consensus Conference at Palm Beach, Florida in March 2001.1 Melvin J Silvestein of Van Nuys Breast Centre compiled a report2 and the following are the excerpts.
Certain Accepted Basic Concepts
- Terms “early disease” or “late” are misleading. It is better to employ objective measures like tumour size, histologic type and grade, nodal status and biological markers to ensure uniformity in description and between clinical studies.
- There is scientific evidence from randomised controlled trials that screening with mammography significantly lowers mortality from breast cancer.
- Breast cancer is a progressive disease at all its stages and timely treatment and early detection can alter the natural course of the disease.
- Recognition and adequate treatment of ductal carcinoma in situ (DCIS) prevents future invasive events.
Imaging and Biopsy
Fine needle aspiration biopsy may spare as many as 80 per cent of patients with histologically benign image detected abnormalities from undergoing open biopsy procedures.
Breast ultrasonography is a valuable tool. MRI is useful in determining the extent of disease when physical examination and conventional imaging (i.e. mammography and ultrasonography) cannot accurately determine the extent. Examples would include diagnosis of invasive ductal carcinoma in very dense glandular tissue and women diagnosed with infiltrating lobular carcinoma.
Pathology and Prognostic Issues
Specimen radiography of all microcalcifications and surgically excised masses should be part of the work up of all mammographically detected abnormalities. Surgeon should present the pathologist with an oriented specimen. Margins should be inked to preserve the orientation of the specimen.
The prognostic value of tumour size depends on the size of the invasive component. The size of the entire lesion is useful in making decision about breast conservation surgery.
Oestrogen receptor status, progesterone receptor status and HER-2/neu (c-erb B2) have clinical usefulness as tumour markers. These should be obtained on all patients with invasive breast cancer. They currently have no role in the management of patients with DCIS.
The panel encourages permanent storage of tissue blocks as a safeguard for the individual patient and as unique source for future investigations.
Sentinel Node Biopsy
In the last decade, the sentinel node biopsy has been introduced as a potential alternative to conventional axillary dissection for patients with invasive breast cancer. Clinical trials are ongoing in the US and Europe. These trials will determine the effect on survival, regional control, staging and morbidity of sentinel node biopsy compared with axillary dissection.
Consensus of the College of American pathologists is that evaluation of lymph nodes by immunohistochemical or molecular methods to detect metastases should be considered investigational at present. Such information should not be used to upstage patients or guide therapy unless metastases are confirmed by haematoxylin and eosin staining and are larger than 0.2 mm.
For the population of image detected breast cancer patients the probability of nodal involvement is approximately 10 to 15 per cent. The impact of nodal therapy on survival or regional control in this subgroup is small. For these patients, avoiding nodal treatment by conventional axillary dissection or nodal irradiation is a reasonable consideration. So the panel agrees that for image detected invasive cancer with low probability of axillary lymph node involvement, sentinel lymph node biopsy may be a valuable alternative to axillary dissection.
Randomised Trial Data for DCIS
There are three prospective randomised trials comparing excision alone with excision plus radiotherapy for the treatment of patients with DCIS. Currently there are no differences in distant disease, breast cancer specific survival or overall survival rates between the arms in any of the three trials.
Two completed trials have examined the use of tamoxifen to treat DCIS. Both trials found that tamoxifen reduced the risk of ipsilateral local failure in patients treated with excision plus radiotherapy. But, the absolute magnitude of the benefit was small. In the contralateral breast, tamoxifen reduced the risk of breast cancer development. Again no differences in distant disease, breast cancer specific survival, or overall survival were found between those patients treated with or without tamoxifen in these trials. Tamoxifen may cause life altering (e.g. hot flushes, vaginal dryness) and life-threatening (e.g. increased incidence of endometrial cancers, thromboses and pulmonary embolism) side effects. So, the role of tamoxifen in the treatment of patients with DCIS remains uncertain.
Standard Treatment of Invasive Breast Cancer Less than 10 mm in Diameter
Tamoxifen and systemic chemotherapy have been shown to provide benefit to patients with invasive breast cancer. But for patients with very small (< 10 mm) oestrogen receptor positive or low grade tumours, data supporting routine use of tamoxifen or systemic chemotherapy are limited, and decision about treatment needs to be balanced by concerns about treatment morbidity.
All patients with invasive tumours treated conservatively currently receive postoperative radiotherapy. Data are accruing that suggest certain subgroups of patients have failure rates sufficiently low that the benefits of radiotherapy may be outweighed by its complications or side effects.
Partial Breast Irradiation
Traditional radiotherapy calls for treating the entire breast with the option of giving an addition “boost” dose to the primary tumour excision site. It has however, been observed that the great majority of local failures after breast conserving therapy (with or without radiotherapy) are located at or near the primary tumour site. Interest in partial breast irradiation has therefore increased, because much of the potential morbidity of radiotherapy (fibrosis leading to breast shrinkage and pulmonary and cardiac effects) might be avoided if only a portion of the breast were irradiated. In addition, partial breast irradiation may lend itself to a substantial reduction in the overall treatment time. It eliminated the inconvenience of 6 weeks of traditional external beam radiotherapy.
Very encouraging studies of this approach using interstitial implantation (brachytherapy) have been reported. The consensus panel believes that the approach of accelerated partial breast irradiation, if proved successful has the potential to reduce the time, inconvenience and cost of radiotherapy to the patient with image detected breast cancer. It is suggested that comparison of whole breast radiotherapy with brachytherapy and conformal external beam therapy should be pursued.
In cases where mastectomy is indicated, the panel recommends that immediate breast reconstruction be available.
Minimally Invasive Breast Surgery
Tools for complete percutaneous removal are being currently developed. Techniques of interstitial thermal therapy currently under investigation include laser interstitial therapy, radiofrequency, therapeutic ultrasound and microwaves. One or more of these approaches may become effective alternative to conventional open excision in the future. The techniques are currently investigational.
- International Consensus Conference: Image detected breast cancer: State of the art diagnosis and treatment. J Am Coll Surg 193:297, 2001.
- Silverstein MJ: The Van Nuys Breast Center: The first free standing multidisciplinary breast center. Surg Oncol Clin N Am 9:159,2000.
OCCULT BREAST CANCER
On rare occasions, a breast cancer may present with large glands in the axilla but no evidence of primary in the breast. In 1954 Owen et al1 found 25 cases in 5461 patients with the disease, an incidence of 0.3 per cent. With modern imaging, however, many of these primary carcinomas would have been located and these are perhaps the ‘apparent occult cancers’ and not ‘true occult cancers’.
Lloyd and Nash2 made a retrospective review of all TON1MO carcinomas at the Breast Unit at the Royal Marsden Hospital London which sees up to 750 new cancers each year. Between the years 1979 and 1999, 6 cases were selected from the audit data base who presented as true ‘occult’ primaries. Neither mammograms or ultrasound scans had shown any evidence of a suspicious lesion in either breast. None of the patients had MRI scans. All six patients underwent axillary dissection and showed confirmation of adenocarcinoma compatible with a breast primary. Five patients received chemotherapy and one had radiotherapy to the ipsilateral breast and axilla. All have been followed up and primary site has still not been found. No recurrence has occurred over a time period ranging from 8 to 168 months. The mean disease free survival time is 57 months from date of diagnosis (approximately 5 years).
Very little has been written on the use of MRI in patients with axillary metastases of occult breast cancer. In 1997 however, at the University Hospital Rotterdam,3 4 women with clinically and mammographically occult breast tumour were investigated by MRI. MRI detected a single lesion in each of the three women and two lesions in the ipsilateral breast of the fourth women. MRI fine needle aspiration cytology confirmed all the 5 lesions detected as breast carcinomas. The true occult cancer therefore in which imaging totally fails to show the primary is extremely rare.
- Owen HW, Dockerty MB, Gray HK: Occult carcinoma of the breast. Surg Gynecol Obstet 98:302, 1954.
- Lloyd MS, Nash AG: Occult breast cancer. Ann R Coll Surg Eng 83:420,2001.
- Tilanus-Linthorst MMA, Obdeijn AIM et al: MRI in patients with axillary metastases of occult breast carcinoma. Breast Cancer Res Treat 42:179,1997.
Due to widespread acceptance of liver transplant as the primary treatment for end stage liver disease, the growing disparity between organ availability and the number of patients awaiting transplantation has assumed great importance1
Living donor liver transplantation remains fairly controversial. The use of adult to child liver transplantation and split liver transplantation in which a left lateral segment services a paediatric recipient has eliminated deaths of children awaiting transplantation.2 More recently, interest has shifted to the use of a larger graft for adult recipients: either an extended left lobe, right lobe, or extended right lobe. Large number of successful donor partial hepatectomies have been performed in Asian centres, although serious complications have been reported.3
The limits of safety for the donor have not been defined. Extensive preoperative imaging defines the vascular and biliary anatomy in donors. It appears that the enormous demand for transplants will outweigh concern about the risk of donation. As of the end of 2001, it is estimated that at least 600 adult to adult living donor transplants have been performed. There have been two unpublished, but recognised deaths in donors in the United States and an additional donor requiring transplantation as a consequence, the death risk is thought to be in the range of 1 in 500. Long-term consequences of live liver donor donation are unknown, giving rise to concern about the safety of the procedure.4 In addition to the short and long-term, physical health risks of removing a portion of the liver of live donor transplantation, the well-being and quality of life of donor require assessment. A recent study of 48 donors of right lobe grafts indicated overall satisfaction with the procedure and a sense of well-being that related to the recipient outcome.5
The highly publicised death of a living donor was the subject of an editorial in New York Times by Ronald Munsen defending the right of the donor to take a risk. But some of the criticism is towards exposure to harm of a healthy person.6
In the United States, the issues of donor safety, education and advocacy have been raised within the federal government. Secretary of Health suggested development of guidelines to ensure safety of the live donors. Donor must be adequately informed and that the donor should fully understand the risks involved.7,8
- Malago M, Hertl M, Testa G et al: Split liver transplantation: future use of scarce donor organs. World J Surg 26:275,2002.
- Grewal HP, Thistlewaite JR, Loss GE et al: Complications in 100 living liver donors. Ann Surg 228:214,1998.
- Fan ST, Lo CM, Liu CL et al: Safety of donors in live donor liver transplantation using right lobe grafts. Arch Surg 135:336,2000.
- Basuttil RW: How safe are donors in adult to adult living related liver transplantation? Liver Transpl 8:121,2002.
- Cronin DC, Millis JM, Siegler M: Transplantation of liver grafts from living donors into adults too much too soon. N Engl J Med 344:1633,2001.
- Kim-Schluger L, Florman SS, Schiano T et al: Quality of life after lobectomy for adult liver transplantation. Transplantation 73:1593,2002.
- Munson R: The donor's right to take a risk. NY Times Jan 19,2002.
- Ascher Nancy L: Transplantation. J Am Coll Surg 196:778,2003.
SMALL BOWEL TRANSPLANTATION
Isolated small bowel transplantation can be considered a life saving procedure in individuals with intestinal failure. Intestinal transplantation has reached a state of maturity thanks to increased experience, refined immunosuppressive protocols and improved postoperative management. Reports from Pittsburgh indicate that continued improvement in outcome has been possible using sirolimus as part of the immunosuppressive regimen.2 One major technical question is regarding venous outflow of the graft which can be directed either into portal or the systemic circulation. In theory, portal drainage will be better physiologically but technically more demanding.
Berney1 reviewed 36 patients who had 37 small bowel transplants (January 1995 to Auguest 2001) and portal drainage was performed for 19 and systemic drainage in 18 patients. Median follow-up was 531 days. All patients in both groups had similar ICU stay (median 7 vs 9 days). All current survivors with the exception of one in each group are independent from parenteral nutrition. Liver function tests were similar in both groups. There was two-fold increase in tacrolimus dosage in the portal drainage group to achieve similar trough levels indicating a ‘first pass’ hepatic clearance effect. Graft and patient survival rates were similar in both groups. Attention, however, needs to be paid to an impaired clearance of intestinal bacterial translocation after systemic drainage.
- Berney T, Kato T, Nishida S et al: Portal venous systemic drainage of small bowel allografts, comparative assessment of survival function, rejection and bacterial translocation. J Am Coll Surg 195:804, 2002.
- Sindhi R, Webber S, Venkataramanan R et al: Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus. Transplantation 72:851,2001.
Xenotransplantation is being viewed by many as a potential solution to the organ shortage afflicting the field of transplantation. But the use of Xenograft in the clinical setting was initially hindered by a severe type of rejection termed hyperacute xenograft rejection (HAR).1 HAR is a process mediated by the binding of xenoreactive antibodies of the IgM isotype with subsequent complement activation resulting in graft failure within minutes to hours after exposure of the transplanted organ to the recipient's heterologous blood.2,3 The main antigenic determinant recognised by xenoreactive antibodies is Gal × 1–3Gal (alphaGab) present in all mammals except apes, humans and old world monkeys.4,5 In addition, complement regulatory proteins in the transplanted organ are less effective in controlling heterologous complement heightening the susceptibility of xenografts to HAR.5 These concepts have fairly influenced the field of xenotransplantation and facilitated development of therapeutic techniques that effectively interfere with the occurrence of HAR in heart and kidney transplantation. Organs from transgenic pigs (genetically modified to express human complement regulatory proteins) transplanted into primates are protected against human complement mediated cytotoxicity.
- Perper RJ, Nafarian JS: Experimental renal heterotransplant in widely divergent species. Transplantation 4:377,1966.
- Dalmasso AP, Vercelloti GM, Fischel RJ et al: Mechanism of complement activities in the hyperacute rejection of porcine organ transplanted into primate recipients. Am J Pathol 140:1157,1992.
- Platt JL, Fischal RJ, Matas AL et al: Immunopathology of hyperacute xenograft rejection in a swine to primate model. Transplantation 52:214,1991.
- Good AH, Cooper DKC, Malcolm AJ et al: Identification of carbohydrate structures that bind human antiporcine antibodies: Implications for discordant xenography in humans. Transplant Proc 24:559,1992.
- McCurry KR, Kooyman DL, Alvardo CG et al: Human complement regulatory proteins protect swine to primate cardiac xenografts from humoral injury. Nat Med 1:423,1995.
Most patients do benefit from the present day advanced management of acute myocardial infarction but end stage heart failure may result from the irreversible destruction of cardiomyocytes which do not have the capacity to regenerate. When heart failure becomes refractory to medical management, the available surgical options are limited and the only real effective treatment is cardiac transplantation. However, with the problems inherent to the procedure, namely, organ shortage and immunological rejection, it cannot be used in all potential candidates. More than 4000 Americans on any given day are waiting for a heart transplant. Because of shortage of donors, more than a third of them will die before a suitable replacement can be found.1
The patients awaiting transplant are maintained as long as possible on either oral or intravenous medication. If no donor heart is available the patient may be a candidate for placement of a left ventricular assist device.2 The patient should have adequate right heart function if a left ventricular assist device (LVAD) is being considered. While on LVAD, a time may come when a donor becomes available when brain death criteria are met. After these issues have been resolved, the donor undergoes an echocardiogram to confirm that cardiac function is good and no significant valvular anomalies are present. Also at this time the donor heart is being matched to appropriate recipient based on ABO compatibility as well as size.
On December 3,1967, Christian Barnard performed the first human heart transplant in Cape Town's Groote Schurr Hospital. Louis Washkansky, the recipient was 55 years old diabetic with incurable heart disease. The donor was Denise Darvall, a 25 years old who stopped to buy a cake, was hit by a car and was pronounced brain dead by the doctors. With the permission of her father, 60 seconds after the respiration was turned off, a team led by Hamilton Naki* went to work, a 48 hours marathon. A second team led by Christian Barnard placed the organ inside Washkansky. The heart was beating strongly and even though Washkansky died of pneumonia 18 days later, the operation was hailed as success.
*Hamilton Naki's role in the first cardiac transplantation in the world is a saga of apartheid in the racist state of South Africa. Naki was a surgeon considered by colleagues to be the most technically gifted of the hospital team. Without him the transplant might never have happened.
Naki was born in 1926. He had no formal education. He hitch-hiked to Cape Town at the age of 14 to seek work. The University of Cape Town hired him as a gardner and for the next decade he maintained the Tennis lawns.
Punctual, diligent and dapper, Naki was chosen by the foreman in 1954 when a doctor in the under funded medical faculty, Robert Goetz, said he needed help with the laboratory animals.
From cleaning cages Naki progressed to weighing, shaving and injecting the animals, mostly dogs, rabbits and pigs and from anaesthetics to machines which allowed Goetz to operate on animals. By the early 1960, Naki was operating on animals himself and colleagues admired his steady hand. Naki was the obvious assistant to choose when Barnard, an ambitious cardiac surgeon, returned from the US to introduce new open heart surgery techniques to South Africa. “He had probably more technical skill than I had”, Barnard said of Naki decades later. Naki was therefore the obvious choice to lead the team for preparing the donor heart when need arose.
Religious, Hamilton Naki trusted in God and accepted his status and remained friendly with Christian Barnard. Maintaining the fiction that he was a menial worker, the state allowed him to operate and give lectures to medical profession until his retirement officially as a gardener in 1991. In December 2002 Government of South Africa included him in national honours, a belated recognition to a remarkable man.
Guardian London 25th April 2003
Traditionally, organ donors have been limited to patients less than 55 years old, with negative hepatitis serology and no history of systemic illness (e.g. hypertension, diabetes). Recently, donor criteria have been expanded to include older donors and those with history of hypertension, as well as those seropositive for hepatitis C. If the donor is older or if hypertension is present, the heart is usually evaluated with a coronary angiogram to exclude coronary atherosclerosis in the donor heart.3
Procurement of the heart is usually performed in conjunction with a multiple organ harvest, involving from two to four organ procurement teams.4 Both the abdomen and the chest are opened in the midline. The sternum is divided, as is the pericardium, and the heart is examined. If this inspection reveals no contraindication to use of the heart for transplantation, then dissection of the heart in preparation for harvest is begun. At donor cardioctomy, the heart is arrested with cold potassium cardioplegia and stored in a balanced electrolyte solution at 4°C. It is transported as quickly as possible to the recipient hospital or adjoining theatre facility with the team waiting to receive the transplant.
The recipient procedure typically begins at approximately the same time as the donor procedure with the induction of anaesthesia and the placement of monitoring lines. The initial incision is made 30 minutes to 1 hour prior to the anticipated arrival time of the donor heart. If the recipient has previous cardiac procedures, as is often the case, the incision is made up to 1 hour sooner, to allow time for the lysis of adhesions. The logistic goal is to minimise ischaemic time for the donor heart as well as pump time for the recipient.
After cardiopulmonary bypass is established, the patient is systemically cooled to moderate hypothermia (28 to 38°C). When fibrillation occurs, the aorta is cross-clamped and excision of the recipient heart is performed. The donor heart is then anastomosed to the recipient heart residue in a defined order.
Early postoperative management is similar to that for any postoperative cardiac surgical patient. However, transplant patients are routinely given isoproterenol and dobutamine to maintain heart rate and cardiac index at acceptable levels. Patients typically remain in the intensive care unit for 2 to 3 days and then stay on the floor for another week, until their immunosuppressive regimen has been established.
Immunosuppression is initiated preoperative with azathioprine and cyclosporine. Solu-Medrol is then given intraoperatively and continued postoperatively until the patient can take oral prednisone.
Currently, in the US, more than 15,000 patients per year could benefit from cardiac transplantation, but only approximately 2,000 donor hearts are available annually.5 Some of the possibilities to correct this deficit include improved LVAD technology, which might allow a more permanent cardiac assist device to be implanted, perhaps even with no external connections.*
*Originally only people, who were already on waiting list for a heart transplant, could get on LVAD. The pumps simply were not designed to be permanent. But so many have done so well on the newer generation devices playing golf or even tennis that clinicians are considering whether to expand their use.
-US Time Magazine Vol.158, No. 4, July 30, 2001
- US Time Magazine Vol. 158, No.4, 30 July 2001.
- Griffith BP, Kormos RL, Nastala CJ et al: Results of extended bridge to transplantation. Window into the future of permanent ventricular assist device. Ann Thorac Surg 61:396,1996.
- Span JC, Van Meter C: Cardiac transplantation. Surg Clin North Am 78:679,1998.
- Starzl TE, Hakala TR, Shaw BW et al: A flexible procedure for multiple cadaveric organ procurement. Surg Gynecol Obstet 158:223,1984.
- Evans RW: The actual and potential supply of organ donors in the United States. Clin Transplant 329–41,1990.
CELLULAR TRANSPLANTATION FOR THE FAILING HEART
End stage heart failure results from the irreversible destruction of cardiomyocytes which do not have the capacity to regenerate. The heart attempts to compensate for cardiomyocyte loss after myocardial infarction by further hypertrophy of viable cells, but this maladaptive response frequently results in pathologic ventricular remodelling.1
Transplantation of myogenic cells into the damaged myocardium is an emerging therapeutic alternative to manage the problem. In rodents, foetal and neonatal cardiac cells injected into infarcted myocardium survive within host myocardium, incorporate through intercalated discs and gap junctions2 and improve heart function.
Despite the successful animal studies with foetal cell transplantation, both foetal and neonatal human cells remain in short supply. Embryonic stem cells, however, are another potential source. These pluripotent stem cells can be derived from aborted foetuses and from human embryos resulting from in vitro fertilisation.3 Embryonic stem cells transplanted into myocardial infarct of rats differentiate into phenotypically mature cardiomyocytes and improve ventricular function.4
Public concern and government restriction on human embryo derived stem cell investigation has, however, essentially eliminated this source. Because of the above mentioned drawbacks, the search for an alternative strategy to replenish damaged myocardium has been made. Among the cells with the great therapeutic potential are the autologous bone marrow cells and skeletal myoblasts.
Bone marrow contains multipotential progenitor cells in an undifferentiated state. Tomita and colleagues5 have reported that autologous bone marrow cells transplanted into rat myocardial infarct differentiate into cardiomyocytes and induce angiogenesis in the scar, resulting in improved cardiac function. The number of myocardial progenitor cells that reside in the bone marrow under normal conditions, however, are quite low and the number circulating in the bloodstream might be lower. Obtaining a quantity of these cells sufficient to fully colonise diseased myocardium, therefore, may not be possible.
The precursors of skeletal muscle fibres, the myoblasts are present in adult animals as quiescent cells and may become activated, proliferate and differentiate upon muscle injury (in vivo) or following tissue dissociation (in vitro) in culture. In a myocardial infarction model in rats created by coronary artery ligation, Scorsin et al6,7 showed that one month after myoblast transplantation the treated group displayed a significant improvement of function, primarily manifested as a limitation of post-infarction ventricular remodelling, compared with non-transplanted controls. A phase one trial concerning myoblast transplantation in patients with severe heart failure has started in France. The results in the first clinical case were very promising.8 After transplanting 8 × 10 cells in the inferior wall of a two-year-old myocardial infarction scar (nonreversible and akinetic by dobutamine echocardiography, with absence of viability by positron emission tomography PET), the akinetic wall became contractile (echocardiographic positive response by one grade to dobutamine stress), improving the ejection fraction from 20 to 38 per cent. This was associated with marked increase in metabolism in the previously nonviable area as assessed by PET.
Another important issue to be stressed is the ideal number of cells to be transplanted. Based on an experimental study in rats, a direct relationship between the number of cells and the improvement of function has been demonstrated.9 In the French clinical case, it appears that to restore the viability of a medium-sized myocardial infarct (loss of 20–30% of the left ventricle mass) approximately one billion cells cultured for two weeks in a myogenic-specific culture medium are required, thus precluding its use in emergencies.
Angiogenic growth factors (as basic fibroblast growth factor and vascular endothelial growth factor) and gene encoding angiogenic factors are being delivered to the infarcted area to induce growth of new blood vessels.10-13 Increased perfusion has also been observed after endothelial cell transplantation even though this was not associated with improved ventricular function nor modification of ventricular remodelling, suggesting that angiogenesis alone, without myogenesis, would be less beneficial in patients with extensive, transmural myocardial infarction.14
Despite encouraging results, the exact mechanism responsible for improved heart function after cellular transplantation remains undetermined. There are a number of hypotheses that have been put forward to try to explain the results.
- Induction of local angiogenesis: Injected cells could release growth and/or angiogenic factors that could partially explain engrafted cell survival. This has not been demonstrated to be significant and is confounded with the triggering of angiogenesis by epicardial-puncture alone.
- Cell contractility: Transplantation of cells with inherent contractile properties suggests that their contractions would contribute to the improved function. Indeed, myotubes have been demonstrated in zones of injected cells up to one year after transplantation. Furthermore, these fibres express slow myosin. This change of phenotype suggests their ability to resist fatigue and sustain a cardiac workload. The cells must contract in synchrony with the adjacent myocardium. The mechanism to explain transmission of electric impulses from the native myocardium to the engrafted cells has not been elucidated. Stimulus exerted by surrounding cardiomyocytes could induce the contraction.
Cellular transplantation into an infarcted myocardium definitely resulted in improvement of its function and it provides a strong rationale for using this technique in patients. Animal studies have demonstrated that myoblasts can be extracted from skeletal muscle, expanded in culture and injected into damaged myocardium.15 Menasche et al8 successfully applied this therapy in a patient. During coronary bypass surgery, skeletal myoblasts which had been extracted from the patient 2 weeks before the operation and cultured in vitro were injected into areas of myocardium. At 9 months postoperatively, evidence of both viability and function within the grafted scar was demonstrated by echocardiography and positron emission tomography (PET). A phase one clinical trial of this exciting new treatment is underway.16 Preliminary reports suggest that this technique is both safe and feasible, but ventricular arrhythmias have recurred in some patients. This might be due to the failure of the transplanted cells to form electromechanical junctions with the host cardiomyocytes.17
- Weisman HF, Bush DE, Mannisi JA et al: Global cardiac remodelling after acute myocardial infarction: a study in the rat model. J Am Coll Cardiol 5:1355,1985.
- Loer J, Patterson M, Quinones MJ et al: Transplantation of foetal myocardial tissue into the infarcted myocardium of rat. A potential method for repair of infarcted myocardium? Circulation 94:11332,1996.
- Watt FM, Hogan BL: Stem cells and their niches. Science 287:1427,2000.
- Min JY, Yand Y, Converso KL et al: Transplantation of embryonic stem cells improves cardiac function in post infarcted rats. J Appl Physiol 92:288,2002.
- Tomita S, Li RK, Weisel RD et al: Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100:11247,2000.
- Scorsin M, Hagege A, Marotte F et al: Does transplantation of cardiomyocytes improve function of infarcted myocardium? Circulation 96 (Suppl. II):188,1997.
- Scorsin M, Hagege A, Dolizy I et al: Can cellular transplantation improve function in doxorubicin induced heart failure? Circulation 98 (Suppl. II):151,1998.
- Menasche P, Scorsin M, Hagege A et al: Myoblast transplantation for heart failure. Lancet 357:279,2001.
- Pouzet B, Vilquin J, Mesas E et al: Factors affecting functional outcome following autologous skeletal myoblast transplantation. Ann Thorac Surg 71:844,2001.
- Banai S, Jaklitsch MT, Shou M et al: Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs. Circulation 89:2183,1994.
- Yanagisawa-Miwa A, Uchida Y, Nakamura F et al: Salvage of infarcted myocardium by angiogenic action of basic fibroblast growth factor. Science 257: 1401,1992.
- Unger EF, Banai S, Shou M et al: Basic fibroblast growth factor enhances myocardial collateral flow in a canine model. Am J Physiol 266:H1588,1994.
- Shou M, Thirumurti V, Rajanayagam S et al: Effect of basic fibroblast growth factor on myocardial angiogenesis in dogs with mature collateral vessels. J Am Coll Cardiol 29:1102,1997.
- Jain M, Dersimonian H, Brenner DA et al. Cell therapy attenuates deleterious ventricular remodelling and improves cardiac performance after myocardial infarction. Circulation 103:1920,2001.
- Menasche P. Cell transplantation for treatment of heart failure. Semin Thorac Cardivasc Surg 14:157,2002.
- Reinecke H, Murry CE: Transmural replacement of myocardium after skeletal myoblast grafting into the heart. Too much of a good thing? Cardiovasc Path 9:337,2000.
EMBRYONIC STEM CELL RESEARCH PLUS REHABILITATION FOR SPINAL CORD INJURY: WHISPERS OF HOPE
Until about 10 years ago, it was believed that the adult nervous system (i.e. the brain and spinal cord) was incapable of regeneration. Management focussed on rehabilitation in the immediate post injury phase to maximise existing function.1 Although immediate injury treatment is still important, more recent studies suggest that regeneration of the nervous system is possible. Workers at Washington University, for example, believe that “encouraging patients to use their injured body parts helps them to recover lost function”. The rationale behind this logic is that “forced movements stimulate damaged cells to relearn their jobs”.2 This logic is the basis for the Washington University School of Medicine's Activity Based Recovery Programme. Now research is underway to determine if rehabilitation promotes neurogenesis, the growth of nerve cells and the recovery of damaged cells. The rehabilitation programme consists largely of training on a functional electric stimulation bicycle and aqua therapy.
Functional Electric Stimulation (FES) involves a specially designed recumbent bicycle system that uses controlled electrodes placed on a patient's legs to stimulate leg muscles in specific patterns. Using this technology, a paralysed person, despite the fact that he is unable to voluntarily control his leg muscles, can use bicycle pedals. This activity provides the basic beneficial physical exercise-building muscle mass and bone density, reducing spasticity and a cardiovascular workout.
Aqua therapy is a type of physical therapy performed in water. Once muscle recovery had been stimulated through the use of the bicycle, aqua therapy is added to the exercise programme. Aqua therapy not only enhances the workout of these muscles, but because effects of gravity are greatly reduced in water, small body movements are easily detected. This increased ability to detect small body movements helps the treating team to study recovery more easily and to distinguish deliberate movement from movement caused by gravity.
The above rehabilitation programme has been successful for Mr. Christopher Reeve. Mr. Reeve is a famous actor, director and activist. Reeve's film credits include “superman” in 1978 and the subsequent sequels “Death Trap” and “Bostonians”. His stage credits include “The Marriage of Figaro”, “Summer and Smoke” and “The Aspern Papers”. Reeve was seriously injured while competing in an equestrian contest on May 27,1995. Reeve's horse stopped suddenly. Reeve was thrown forward, head first over the horse and landed on the ground in a near perpendicular position. The top two cervical vertebrae were shattered and the spinal cord was severely damaged. Magnetic resonance imaging (MRI) showed that he had severe injury at C-2 level that left a central fluid filled cyst surrounded by a narrow doughnut-shaped rim of white matter.
For the first five years after the accident, Reeve had no sensation or motor function from the neck down. Three years later, after activity based recovery exercise programme, Reeve's condition has improved. He is able to distinguish between a pinprick and the light touch over most parts of his body. He is also able to move some of his joints without assistance (his right hand, the fingers of his left hand and feet). Though called by some a “medical marvel” it is important to note that Mr. Christopher Reeve is by no means normal yet and it is not clear if the improvement will continue. There is, however, a possibility that a small number of nerves around the site of injury were undamaged and the exercise programme may be reactivating these fibres, allowing signals to pass between body and brain, or the exercise activity is inducing new nerve connections to grow around the site of injury.3 In February 2002 University of Arkansas in USA also reported that a quadriplegic who had been confined to a wheel chair was now able to walk about 1000 feet with only moderate fatigue.4 The key to this transformation also was functional electrical stimulation (FES) that delivered low frequency pulses which then stimulated walking movement. However, before the FES programme he had trained for four months on a moving treadmill which passively moved his legs.
Christopher Reeve is the Chairman of Christopher Reeve Paralysis Foundation and is devoted to funding research for cure for paralysis caused by spinal cord injury and other central nervous system disorders. Stem cell research holds significant promise for people living with spinal cord injury and Christopher Reeve Foundation is committed to fund research in this direction.
Embryonic stem cells are pluripotent and have remarkable therapeutic potential to restore cells damaged by trauma or disease. They have the capacity to become any cell in the body. An intense activity has focussed on embryonic stem cells in an attempt to induce directed differentiation to define cell types in culture, for example by exposing the cells to signaling molecules such as retinoid acid,5 specific cytokines as wells as by genetic manipulation.6 Data is now emerging that embryonic stem cells can be directed into the neuronal cell pathway to form mature nerves and glia.7 Other cell types such as insulin secreting β cells,8 cardiomyocytes and numerous other cell types have been identified by various workers. It has been reported by a team from Johns Hopkins University that stem cells were injected into cerebrospinal fluid of paralysed mice. The cells then home into the damaged area in the ventral horn, a region of the spinal cord containing the bodies of motor nerve cells and stimulate neurogenesis thus restoring some movement within eight weeks in most of the rodents.9
In an attempt to avoid any immune rejection that may occur in stem cell transplantation it is possible to form customised stem cells that are completely patient compatible by using nuclear transfer of the patient's somatic cells into enucleated donor oocytes termed therapeutic cloning10 or by gene knock out. Stem cells derived from an embryo created by this technique can then be used for the patient. However, several ethical barriers still need to be overcome before therapeutic cloning can become a reality. Furthermore, in vitro differentiation of embryonic stem cells transduced with gene trap vectors can be used to discover novel developmentally regulated genes that are important in tissue specific differentiation.10,11
Research on embryonic stem cells is considered by some, unethical and morally unacceptable. One criticism is that the stem cells are derived from embryos and retain the ability to form a complete embryo. This is however, incorrect as once the embryonic cell is isolated from the cell colony, it loses any memory of axis formation and can no longer form a body plan.12 The second criticism is based on the harvesting procedure of embryonic stem cells which destroys the embryo and hence, this research has got entangled in the abortion debate. Human embryos used in such research, however, are blastocytes of only about 100 cells, long before an abortion would be performed and long after one could rationally attribute individual identity in any but the bare genetic sense.
In December 2002, the Senate of the Australian Federal Parliament approved a bill allowing the use of stem cells from 70,000 surplus IVF embryos currently held in Australian Infertility clinics. Christopher Reeve is an ardent campaigner to promote therapeutic cloning in humans as a means of obtaining stem cells. However, the Federal Government in Australia has imposed a three years ban on human therapeutic cloning. In March 2002 President Bush decided to allow federal funding for human embryonic stem cell research on a limited basis and appointment of an Advisory Council on stem cell research and National Institute of Health guidelines will ensure public scrutiny of this research.
National Institute of Health (NIH) has identified eleven laboratories from United States, Australia, Sweden, Israel and India that meet President Bush's criteria for research on embryonic stem cells. Because of the President's decision, it may now be upto US Congress to enact legislation to enable scientists to fully explore the potential of human embryonic stem cell research.
Given the scientific and medical benefits that accrue, the Christopher Reeve Foundation supports the responsible pursuit of human pluripotent stem cells within the strict scientific and ethical framework stipulated in the NIH guidelines involving pluripotent stem cells.
- McDonald J, Becker D, Sadowsky C et al: Late recovery following spinal cord injury. J Neurosurg: Spine 97:252,2002.
- Washington University in St. Louis School of Medicine (September 2002) Questions and answers about Christopher Reeve's recovery of movement and the Washington University Spinal Cord Injury Programme.
- Blakeslee S: Actor regains some movement. New York Times, September 12,2002.
- Schuldiner M, Yanuka O, Itskovitz-Eldor J et al: Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. PNAS 97:11307,2000.
- Li M, Perny L, Lowell-Badge R et al: Curr Biol 8:971,1998.
- Bain G, Kitchens D, Yao M et al. Embryonic stem cells express neuronal properties in vitro. Dev Biol 168:342,1995.
- Lumelsky N, Blondel O, Laeng P et al: Differentiation of embryonic stem cells to insulin secreting structures similar to pancreatic islets. Science 18:1389,2001.
- Stem cells show improvement in animal spinal cord injury experiment. Brainwork this week 2000,1,http://www.dana.org/books/press/bwtw/bwtw-1100-2.cfm.
- Totey SM, Kulkarni AB: Gene targeting in immunology. Indian J Exp Biol 38:733,2000.
- Thorey IS, Muth K, Russ AP et al: Selective disruption of genes transiently induced in differentiating mouse embryonic stem cells by using gene trap mutagenesis and site specific recombination. Mol Cell Biol 18:3081,1998.
- Trounson A, Pera M: Human embryonic stem cell. Fertil Steril 76:660,2001.
ARTIFICIAL ENDOCRINE PANCREAS
Long-term complications associated with diabetes may result from lack of blood glucose control. Many diabetic patients receive daily injections of insulin but this may not provide a stable control.
Pancreatic transplantation seems to be the ultimate therapeutic option for serious diabetic patients because a normal blood glucose level can be achieved without administering exogenous insulin. There are, however, many problems associated with the use of whole or segmental pancreatic transplantation. These include limited availability of donor organs and need for immunosuppressive therapy. Transplantation of isolated human islet allografts offers a partial solution but still involves the use of immunosuppressive therapy and difficulty of obtaining a significant number of purified human islets.
Albisser et al1,2 first reported an artificial endocrine pancreas in 1974. A sensor electrode repeatedly measures the blood glucose level. The information feeds into a small computer that energises an infusion pump and from a small reservoir, controlled amounts of insulin enter the patient's circulation. This minute to minute regulation of insulin provision modulates the blood glucose by negative feedback and ideal metabolic control is achieved. With sufficient miniaturisation, this apparatus can be implanted into the human body. An excellent blood glucose sensor, an insulin pump and a control system can thus result in a simulated pancreas, to provide stable control of blood glucose levels.
The concept of the present artificial pancreas is about 30 years old but this is not a satisfactory device. The ultimate therapy for diabetes should provide glycaemic regulation similar to that normally provided by pancreatic islets. The four major islet hormones are insulin, C-peptide, glucagon and pancreatic polypeptide (PP). The artificial pancreas should attempt to reproduce the normal physiologic milieu of the endocrine pancreas rather than focussing on unihormonal replacement.3
New computer controlled injection pumps combined with several islet cell functions (not only B cells but also non-B cells) may play a pivotal role in the improvement of long-term glucose homeostasis with amelioration of insulin resistance. Development of technology relating to glucose sensors, injection pumps and computer systems will bring out a sophisticated artificial endocrine pancreas. It is hoped that in the near future when placed in the human body, the new artificial pancreas shall be helpful for patients with diabetes mellitus.4
- Albisser AM, Leibel BS, Ewart TG et al: An artificial endocrine pancreas. Diabetes 23:389,1974.
- Albisser AM, Leibel BS, Ewart TG et al: Clinical control of diabetes by the artificial pancreas. Diabetes 23:397,1974.
- Brunicardi FC, Dyen Y, Brostron L et al: The circulating hormonal milieu of the endocrine pancreas in healthy individuals, organ donors and the isolated perfused human pancreas. Pancreas 21:203,2000.
- Hanazaki K, Nose Y, Brunicardi FC: Artificial endocrine pancreas. J Am Coll Surg 173:310,2001.
PROGRESS IN CORONARY ARTERY SURGERY: “OFF PUMP” SURGERY
Surgical bypass of obstructive lesions in the coronary arteries for patients of angina has been a success story. Traditionally, this has been achieved with the aid of cardiopulmonary bypass to allow an immobile bloodless operative field. Angina is abolished for 5 years after surgery in over 80 per cent of those referred for treatment of angina and at 10 years over 60 per cent are still angina free.1
It has long been recognised that cardiopulmonary bypass by exposing the patient's blood to the foreign surfaces of the pump oxygenator circuit induces impairment of function of the lungs, kidney and brain. The modern equipment, however, has minimal injurious effects but there is a move to avoid its use. Anastomosis of conduits to the distal coronary arteries is possible while the heart is beating and supporting the circulation. “Beating heart” surgery (Off pump surgery) requires careful positioning of the beating heart, local stabilisation of the target coronary artery with special retractors, local occlusion of the artery to keep blood out of the operative field. The use of intracoronary stents has solved the problem of distal myocardial perfusion and has improved the visibility at the arteriotomy site. The use of mister blowers further improves visibility and keeps the field clear during the construction of anastomosis. Few randomised trials of the two techniques have been undertaken and show reduction in blood loss and transfusion requirement for the “beating heart” group.2 “Off pump” coronary bypass surgery, therefore, has now become a widely accepted method for coronary revascularisation. In a randomised controlled trial from Netherlands3 281 patient were randomly assigned “off pump surgery” (n = 142) or “on pump surgery” (n = 139). “Off pump” patients had better cognition 3 months after the procedure but there was no difference in two groups at 12 months. This is an important study and it is advised that additional documentation of adverse side effects after bypass procedures should continue.
The drawback to early coronary bypass surgery was the late occlusion of saphenous vein conduits. By 10 years, about 50 per cent of venous conduits have been shown to have occluded. The arterial conduits are superior to veins in long-term patency. The value of the left internal mammary artery, as a bypass conduit to the left anterior descending artery has had long patency rates of about 95 per cent at 10 years.4
Use of atleast one of the internal mammary arteries is almost mandatory nowadays and it has however, stimulated search for other aterial conduits which have included the gastroepiploic artery (as a pedicled graft) and the inferior epigastric artery (as a free graft). The radial artery recently has been shown as a practical and effective conduit, with graft patency at 5 years approaching that of the internal mammary artery.5
Towards the end of 1970s, about 10 years after the advent of coronary bypass surgery, balloon angioplasty provided reasonable treatment for simple short obstruction in one or two coronary arteries with risk of restenosis in 25 to 30 per cent cases. The recent technological progress has resulted in intracoronary stents which maintain patency following balloon dilatation and the problem of stent occlusion has been solved to a fair extent by periprocedural antiplatelet and antithrombotic therapy. Angioplasty and stenting are now able to achieve revascularisation in a large proportion of patients and the number of patients proceeding for surgery is bound to become less and the number of invasive cardiological interventions will rise year by year.
- ACC/AHA: Guidelines for coronary artery bypass graft surgery. J Am Coll Cardiol 34:1202,1999.
- Ascione R, Williams S, Lloyd CT et al: Reduced postoperative blood loss and transfusion requirement after beating heart coronary operations: a prospective randomised study. J thorac Cardiovasc Surg 121:689,2001.
- Van Difk D, Jansen EW, Hifman R et al: Cognitive outcome after off pump and on pump coronary artery bypass graft surgery: A randomised trial. JAMA 287:1405,2002.
- Buxton BF, Ruengsakulrach P, Fuller J et al: The right internal thoracic artery graft. Benefits of grafting the left coronary system and native vessels with a high grade of stenosis. Eur J Cardiothorac Surg 18:255,2000.
- Acar C, Ramsheyi A, Pagny JY et al: The radial artery for coronary artery bypass grafting: Clinical and angiographic results at 5 years. J Thorac Cardiovasc Surg 116:981,1988.
DYNAMIC CARDIOPLASTY FOR A FAILING HEART
When heart failure becomes refractory to medical management, the available treatment options are limited and the only real effective treatment is cardiac transplantation. However, with the problems inherent to the procedure, namely, organ shortage and immunological rejection, it cannot be used in all conditions.
As the list for those awaiting heart transplant grows and the disparity between donors and recipients widens, less aggressive surgery may be proposed, aiming to reshape the left ventricle back to its normal oval from the rounded shape of a dilated ventricle. This is dynamic cardioplasty and consists of wrapping the heart with skeletal muscle (the latissimus dorsi). The electrostimulated latissimus dorsi (LDM) may be wrapped around the heart. It is used as an option to restore myocardial contractility. This has advantage of not requiring a heart donor and involves much less expense. However, it has yielded rather inconsistent results basically due to atrophy of the skeletal muscle. There is risk of partial ischaemia of the muscle. Partial ischaemia followed by atrophy of the middle and distal part of the latissimus dorsi were observed in 30 per cent of clinical cases after LDM flap elevation from its origin.1 The local administration of growth factors at the LDM/epicardial interface to improve muscle vascularisation and trophicity has been studied.2 The growth factors being basic fibroblast growth factor (BFGF) or vascular endothelial growth factor (VEGF).
- Macgovern GJ, Simpson KA: Clinical cardiomyoplasty. Review of 10 years United States experience. Ann Thorac Surg 61:413,1996.
- Jessup M: Dynamic Cardiomyoplasty. Expectations and results. J Heart Lung Transplant 19:68,2000.
It is a valuable imaging modality for the vascular surgeon.1 It became possible with the advent of miniaturised fibreoptic catheters of acceptable flexibility and sterilisable videocamera with reliable optic qualities. The diameter of a multilumen angioscope is between 2 and 3 mm. It has an integrated channel for irrigation of the vessel lumen with saline to clear blood from the field of view. The flow surface of a normal native vessel is smooth, glistening and white. Upon saline irrigation all red blood cells should be easily cleared. The ostia of tributaries are well defined. Early atherosclerotic changes include a yellow colouration to areas of the flow surface. As atherosclerosis progresses, plaque projects into the lumen. Erosion of plaque surface may result in small areas of adherent thrombus. Progression of these lesions may result in thrombosis of the vessel. Embolic occlusion of a vessel has a “cork in a bottle” configuration at the point of lodgement, often at the point of arterial bifurcation. Presence of peripheral arterial dissection can be seen on angioscopy. The intimal flap of dissection can be seen floating into the lumen causing partial or complete obstruction of the lumen.
- White JV, Eid I: Diagnostic and interventional angioscopy. Surg Clin North Am 78:539,1998.
In 1972, PK Sen and his team from Bombay1 reported on 101 cases of nonspecific aortoarteritis. This was the first detailed study from India of the so called pulseless disease also known as Takayasu's disease, named after the Japanese clinician Takayasu.2 The clinical features of the disease are quite varied owing to the differences in the site and extent of involvement of the aorta and its major branches. Various aetiologic agents may under different circumstances act upon the aorta. It occurs in the young, more common in female and is of insidious onset. Progressing gradually with episodes of constitutional symptoms like fever, malaise, arthralgia resulting in extensive involvement of aorta and major arteries. There is heavy periaortic fibrosis and lymphatic involvement. The segmented predilection results in aneurysmal and/or occlusive disease with a propensity to rupture or critical ischaemia, respectively.
Unnikrishnan Menon and Ramesh3 have recently reported on 48 patients of Takayasu disease from India who underwent surgical intervention. Clinical staging of the disease was based on the angiographic classification as decided in the International Conference on Takayasu's Disease, Japan in 19944 (Table 1.1). Out of the 48 patients, 11 belonged to type 1, 1 to type IIA, 2 to type II B, 12 to type III and 22 to type IV. There were no patients belonging to type V.
Patients with minimal disease with acute generalised symptoms may require steroids and other supportive treatment for about 6 months to 1 year. Others may present with symptomatic aneurysms and/or occlusive disease, manifesting with critical neurological symptoms or intractable renovascular hypertension. Four patients in Unnikrishanan's series underwent prosthetic graft reconstruction of carotid bifurcation with ascending aorta as the inflow source. Renal artery stenosis calls for angioplasty with or without stenting for control of hypertension and to improve renal function. Twenty-two patients belonging to type IV group and long segment suprarenal or infrarenal occlusion required aortic endarterectomy with prosthetic patch reconstruction in the suprarenal group and aortobifemoral graft reconstruction for infrarenal disease. This report, probably the first from India, represents the comprehensive surgical approach to the problem with good results. Extensive disease involving the thoracic and abdominal aorta, periaortic fibrosis, calcification, multiple sacculations and ostial disease pose great challenge during surgery.
- Sen PK: Nonspecific Aortoarteritis. A Monograph Based on a Study of 101 cases. Tata McGraw Hill Publishing Co Ltd, Bombay 1972.
- Takayasu U: A case with unusual changes of the central vessels in the retina. Acta Soc Ophthalmol Jap 12:554,1908.
- Unnikrishnan Menon M, Ramesh KH: Surgical interventions for patients with Takayasu's disease. Ind J Surg 64:258,2002.
- Massimo Vanoli, Giulia Bacchiani, Origgi L et al: Takayasu's arteritis: A changing disease. J Nephrol 14:497,2001.
CHRONIC VENOUS DISEASE OF LOWER LIMB
Chronic venous disease of the lower limb continues to remain a challenge though the newer haemodynamic assessment has considerably improved our understanding.
Duplex scan allows direct visualisation of the veins. The examination performed with the patient standing provides a comprehensive map and blocked or incompetent veins maybe readily identified. In those with deep vein thrombosis, the presence of thrombus can be seen.
Photoplethysmography detects changes in blood content of the skin vessels on the basis of the varying amounts of light reflected from red blood cells. A probe is attached to the skin to assess venous filling of the surface venules by measuring light transmission of the skin. The filling of these vessels reflects pressure in the superficial veins of the leg. The patients is studied in the sitting position and a stable baseline obtained. The patient is asked to contract calf muscles actively by a series of 10 dorsiflexions at the ankle. Normally the blood content of the leg skin decreases in response to calf muscle exercise and slowly recovers to the baseline over a period of 20 to 30 seconds when the limb is at rest. In patients with venous incompetence veins also fill via reflux and recovery time is rapid. The application of tourniquet in primary varicose veins corrects the abnormal recovery time but in post-thrombotic deep vein incompetence the tourniquet does not correct the abnormal recovery time.
Venography is an accurate reflection of the disordered venous function but this invasive technique is somewhat cumbersome and noninvasive methods are more practical to quantify altered haemodynamics. It may, however, be reserved for the potential surgical candidate for correction of deep vein reflux or extensive obstruction.
Tripathi from Bangalore has analysed his experience of chronic venous disease.1 Eighty-four per cent of the patients had varicose veins-23 per cent with skin changes and 14 per cent with ulceration. In these cases, 86 per cent were due to post-thrombotic secondary disease. Reflux was the pathophysiologic mechanism that produced the clinical problem in 86 per cent. Anatomically, the superficial veins were abnormal in 88 per cent while the perforator and deep veins were abnormal in 16 and 29 per cent respectively. In those with ulceration, the finding of perforator and deep disease was fairly high.
Eradication of reflux and or relief of obstruction my relieve most problems of chronic venous disease. The success of saphenous and perforator surgery as seen in the recent times has been remarkable. Over 70 per cent of primary deep venous reflux can be successfully treated by deep venous valve repair techniques of Kistner,2 Raju,3 Sottiurai4 and Tripathi.5 Deep reflux is amenable to surgical repair in the same way that perforator and saphenous reflux is repairable with good results. Even post-thrombotic reflux can be surgically repaired but the long-term results show a higher recurrence rate (50%) than is found in primary disease.
Post-thrombotic valve reflux has been traditionally attributed to destruction of the valve structure by the organising process, but valve cusps in about 25 per cent of cases have been found to be intact despite clear evidence of trabecular and other post-thrombotic changes around them and direct repair of these valves is feasible.1 In some other cases, a sleeve of perivenous fibrosis appears to propagate from the area of thrombus spreading to envelope adjoining valve segments not directly involved in the thrombotic process. This results in secondary incompetence and is amenable to direct valve repair technique.
Multiple valve reconstructions or transplantation of valve containing segments from other areas in the body, such as the configuration of basilic, brachial and axillary confluence should be available for use.1,6 Tripathi, however, found that 30 to 40 per cent of axillary valves were leaking in situ and he recommends its repair before transfer.1
Tripathi advocates stripping of superficial veins even though deep veins are not seen on preoperative venograms. It is his premise that the limb cannot survive on a superficial venous network alone and adequate deep veins are bound to be present inspite of not being visible on venogram. Exploration of the femoral area in the groin has yielded patent repairable valve segments in the majority of such cases. The saphenous vein was irreflexive and was stripped without any adverse clinical or haemodynamic sequelae and also with ulcer healing.
At times, obstructed or stenosed iliac venous segments may be stented before valve reconstruction. If stenting does not help, the valve reconstruction may be done.
As detailed by Ramesh Tripathi from Bangalore, the progress in the understanding of chronic venous disease has been fairly remarkable and there is a choice of various methods towards repair of primary or secondary venous abnormality in the lower limb.
- Tripathi Ramesh: New concepts in the management of chronic venous disease. Ind J Surg 64:240,2002.
- Kistner RL: Surgical repair of the incompetent femoral vein valve. Arch Surg 110:1336, 1975.
- Sottiurai VS: Technique in direct venous valvuloplasty. J Vasc Surg 8:646,1988.
- Tripathi R, Ktenidis K: Trapdoor internal valvuloplasty, a new technique for primary deep vein valvular incompetence. Eur J Vasc Surg 22:86,2001.
- Raju S, Negien PN, Doalittle J et al: Axillary vein transfer in trabeculated post-thrombotic veins. J Vasc Surg 29:1050,1999.
SCREENING FOR PROSTATE CANCER
The absolute risk of death from prostate cancer is low, 1.33 per cent in the Netherlands for example.1 Here, even a very optimistic risk reduction of 25 per cent would produce an absolute risk reduction of 0.33 per cent. Over three screening rounds, about 900 men would be exposed to the hazards of prostate cancer management to delay one death. However, this situation will change once high risk population can be identified.
For early prostate cancer there have been no controlled trials good enough to show whether survival is increased by active intervention with radical prostatectomy, radiation or hormonal therapy. In light of uncertain, delayed survival benefit and known immediate harm, it is no wonder that clinician's recommendations vary.
The balance of proof must be high to justify exposing men older than 50 years to a process where, of 1 million men, about 110,000 with raised prostate specific antigen (PSA) will face anxiety over possible cancer, about 90,000 will undergo biopsy and 20,000 will be diagnosed with cancer.1 If 10,000 men underwent surgery, about 10 would die of the operation, 300 will develop severe urinary incontinence, and even in the best hands 4,000 will become impotent. The number of men whose prostate cancer would have impinged on their lives is unknown. Strong evidence that might support the view that screening is worthwhile is therefore absent.
On the basis of the evidence, national programme of prostate cancer screening is not justified. Yet routine prostate cancer screening is commonly advocated2,3 and even where concern is expressed about the wisdom of routine screening, the ambiguous recommendations that emerge offer little counterweight to the momentum behind routine PSA testing.4,5
Prostate cancer screening may be relevant to four groups of men.6 First those whose cancer emerges clinically, whose outcome is not affected by being treated at that time and for whom screening would not change the situation. Second, those, whose cancer is advancing so rapidly that screening would not improve outcome. Third, those whose screen detected disease would otherwise never have manifested and who may be exposed to unnecessary treatment. Fourth asymptomatic individuals who receive beneficial treatment that otherwise would have been denied. The difficulty in identifying men in the fourth group renders the current case for screening very weak. However, as the capacity to identify men in this fourth group increases, the case for screening will strengthen accordingly.
At the movement there are no scientific grounds for performing prostate cancer screening outside research programmes designed to assess its effectiveness and help identify the groups who might benefit.7
- Bonneux L: Screening populations at low risk carries high risks. BMJ 326:53,2003.
- American Urological Society Executive Committee Report, Baltimore American Urological Association, 1992.
- Ferrini R, Woolf SH: Screening for prostate cancer in American men. American College of Preventive Medicine Practice Policy Statement. American Cancer Society Prostate Cancer Screening Guideline Conference May 4–6,2000 Atlanta.
- Donovan JL, Frankel SJ, Neal DE et al: Screening for prostate cancer in the UK. BMJ 323:763,2001.
- American Medical Association Report of the Council of Scientific Affairs. Screening and early detection of prostate cancer 2000.
- Fossa SD, Eri LM, Skovlund E et al: Randomised trial of prostate cancer screening in Norway. Lancet 2:741,2001.
- Sellay S, Donovan JL, Faulkner A et al: Diagnosis, management and screening of early localised prostate cancer. NHS R and D HTA Programme. Health Tech Assess 1:1–156,1997.
THERMO-EXPANDABLE INTRAPROSTATIC STENTS IN FRAIL PATIENTS
TURP in the over 80 years old is associated with significant morbidity. Perry et al1 have shown that elderly men can have their bladder outflow obstruction relieved successfully by stent, a minimally invasive procedure. The stent can be temporary or permanent. Those with prostate cancer can have radiotherapy whilst the stent is in situ. The stent has been shown to be specially useful in patients who have a tendency to pullout their catheters. Perry et al1 have described a study of 211 men fitted with 217 thermo-expandable intraprostatic stents over eight years. Their exclusion criteria included bladder carcinoma, calculi or detrusor failure. There was a low incidence of complications and a greater per centage of men died with their stents in situ than outlive the usefulness of the stent.
- Perry MJA, Roodhouse AJ, Gidlow AB et al: Thermo-expandable intraprostatic stents in bladder outlet obstruction: An 8 years study. BJU International 90:216,2002.
LASER DEPILATION OF THE NATAL CLEFT FOR PILONIDAL DISEASE
Excessive hair growth in the natal cleft is considered a key factor in the genesis of pilonidal sinus. Hairs are often found trapped in the base of the pilonidal sinus. Surgical treatment remains controversial and recurrence is common. Regular shaving of the area involved is recommended in an attempt to prevent recurrence. It is, however, inconvenient and often difficult to access.1
Hair destruction by laser may be achieved by selective abruption of light frequency by melanin in dark hairs.2 Both the Alexandrite and ruby lasers have been used. These machines deliver pulses of monochromatic light to areas of skin 5–10 mm in diameter. Each spot of light treats hairs within the target area. The light is delivered at between 1–5 pulses allowing large areas impunging to be treated rapidly. The flick of the light impunging on the skin in most zones of the body causes little discomfort. However, perianal area is more sensitive and anaesthetic cream or local anaesthetic may be helpful. Odili and Gault3 used laser depilation of the natal cleft in 14 patients with recurrent pilonidal disease over a 5 years period. It allows the sinuses to heal rapidly. Though laser depilation of the natal cleft is by no means a cure of pilonidal disease. This is a safe and straightforward procedure with the appropriate training. Protective eye wear is required for the operator, assistant and the patient. Hair removal is achieved in the most awkward crevices of the natal cleft. The sinus is given an opportunity to heal by prolonging the hair free interval. This treatment is worth considering especially for recurrent disease where patients are disenchanted with conventional surgery.
- Allen-Mersh TG: Pilonidal sinus, finding the right track for treatment. Br J Surg 77:123,1990.
- Haywood RM, Wardman P, Gault DT et al. Ruby laser irradiation of human skin biopsies: Assessment by electron spin resonance spectroscopy of free radical production and oxidative stress during laser depilation. Photochem Photobiol 70:348,1999.
- Odili J, Gault D: Laser depilation of the natal cleft-an aid to healing the pilonidal sinus. Ann R Coll Surg Engl 84:29,2002.
HAEMORRHOIDECTOMY WITH A CIRCULAR STAPLER
Traditionally, first and second degree haemorrhoids are treated by conservative nonoperative measures including increased dietary fibre, rubber band ligation, injection sclerotherapy and infrared coagulation. Patients with third and fourth degree haemorrhoids are generally advised to undergo surgical treatment which has traditionally meant extirpation.
Open operation for haemorrhoids described by Milligan and Morgan1 has been accepted worldwide but is a painful procedure and demands long hospital stay and local care. The new treatment with a circular stapler, however, has significant advantages. Arnaud et al2 conducted a large preoperative randomised study to determine the efficacy and the safety of the new procedure with a long-term follow-up. From April 1998 to August 1998, 140 patients underwent correction of haemorrhoids using a circular stapler. The degree of haemorrhoids managed were: 3 cases of degree II, 97 cases of degree III and 40 cases of degree IV. Thirty-eight patients had associated skin tags.
The procedure can be carried out under local or regional anaesthesia. Antibiotic prophylaxis with a single dose of metronidazole was given preoperatively. Patients were placed in Lloyd Davis position. An anal retractor was used. The dentate line was easily identified. Starting from the anterior rectal wall at a distance of 4 to 5 cm from the dentate line the longitudinal folds of mucosa were raised in clockwise succession and pierced at the base with monofilament. Thus a purse string suture was carried out including only the mucous and submucous membrane through the entire circumference of the distal portion of the rectal ampulla. An Ethicon Endosurgery Circular Stapler in maximum open position was inserted into the rectum so that the head passed the purse string. The purse string was tied around the stapler shaft. The stapler was closed slowly and tightly. The stapler was then fixed and gently withdrawn. The excised tissue had the appearance of a soft cylinder, 3 to 4 cm in height and contained only mucous and submucous membrane and haemorrhoids. After the stapler was extracted, haemostasis was assured with an additional stitch or two. The excised tissue is histologically examined to exclude any entrapment of rectoanal muscle fibres.
The procedure does not excise haemorrhoidal tissue at the anus but is an excision of a circumferential column of mucosa and submucosa above the haemorrhoids. The prolapsed haemorrhoidal tissue is drawn back into a physiologic position within the anal canal. The blood supply to the haemorrhoidal tissue is interrupted by excision and stapling of the submucosal layer in which these vessels run. Stapled procedure does not involve dissection and excision of the perineal skin and thus contributes to reduced pain score.
Although the cost of the stapler device is high but the hospital stay and the off work period is short. The absence of local care and less postoperative pain are clear advantages. At 18 months, 95.7 per cent of the patients were fully satisfied with the results.
- Milligan ETC, Morgan CN, Jones LE et al: Surgical anatomy of the anal canal and the operative treatment of haemorrhoids. Lancet 1:119,1973.
- Arnaud JP, Pessaux P, Huten N et al: Treatment of haemorrhoids with circular stapler, a new alternative to conventional methods. A prospective study of 140 patients. J Am Coll Surg 193:161,2001.
SURGICAL CARE IN SPACE
Experience of surgical care in space is fairly limited at this time and a surgical procedure has never been required or performed during space flight. However, with increase in both the crew size and the duration of mission with the international space station, the likelihood of surgical events might increase. The physiologic changes and deconditioning effects of prolonged weightlessness (zero g) do impact disease and treatment in various ways.1
Early space flights had only rudimentary medical kits on board and a minor surgery kit for laceration closure was available. Currently, on board the International space station, there is an advanced life support pack2 to provide cardiac life support including ventilation and defibrillation, and advanced trauma life support (ATLS).
The definitive care time on the International Space Station is 6 to 24 hours because of the presence of a medical evacuation spacecraft (initially a Russian Soyuz and later the US Crew Return Vehicle). So the surgical capabilities of the medical care system do not need to be extensive. The Russian experience has shown that medical evacuation occurred in three Soviet space flights.
The Soviets performed limited animal surgical procedures in the zero g of parabolic flight in 1967.3 The United States parabolic flight research studies have shown that surgical procedures in zero g can be performed with no more technical difficulty than in the one g Earth environment, if the principle of restraint of patient, operating personnel, and surgical hardware is adhered to.4
Most surgical bleeding can be adequately controlled by local methods such as sponges and suction. Simulations involving part preparation, draping, equipment layout, lighting, exposure and conventional suturing have been evaluated and successfully performed in the zero gravity. The use of commercial sterile surgical drape that has an adhesive surface and can be directly applied to the skin greatly simplified the otherwise cumbersome procedure of draping in zero g.5
Need for Restraint
Restraint of the patient, operating personnel and all surgical hardware is important. Patient even if fully awake, conscious and co-operative must be rigidly restrained. Operating personnel must be securely restrained, yet have complete freedom of movement of their arms and hands.
A system of waist belts and shoes cleats that engaged an omnigrid floor was proposed for operator restraint but was considered too complex and was discarded. Currently, a floor level Crew Medical Restraint System is available and can provide for a minor surgical procedure. Sterile instruments and supplies should be restrained in a way to allow performance of a procedure in an efficient manner and maintain sterile technique. The surgical overhead canopy would be useful for uncontrolled arterial bleeding if a large amount of surgical debris was generated, if a large amount of irrigation was used, or if pus was encountered.
There is a theoretic concern of contamination during space flight surgery with a relatively dirty space craft atmosphere. Coliforms have been cultured from spacecraft atmosphere and there is some evidence that the particulates have a faecal origin. A surgical overhead canopy with a laminar flow device has been shown to greatly decrease particle counts.3
Recent parabolic flights have investigated laparoscopy and thoracoscopy using animal models. Laparoscopic surgery has been performed in the zero gravity of parabolic flight. The technical difficulty of establishing pneumoperitoneum, laparoscopic support hardware and availability of trained crew are issues that prevent laparoscopy from being a practical component of any present in-flight medical care system.
It is important that an injured crew member in space is adequately resuscitated before medical evacuation. Development of haemoglobin based oxygen carrier (artificial blood) could have potential advantages in being able to resuscitate an injured crew member before medical evacuation.6
For management of the surgical abdomen, studies have shown that only 10 per cent of all blunt trauma to the abdomen requires exploratory laparotomy. Non-operative treatment requires diagnostic imaging and the ability to monitor the patient. It also assumes the ability to surgically intervene if conservative treatment is unsuccessful. The limited surgery to control major bleeding and enteric spillage may be planned as an initial procedure. This is a better logistic planning, gives time for additional speciality consultation from the ground and possibly medical evacuation to a higher level of care.7
Closed head injuries are not expected to do well in space as zero g is physiologically similar to being in a continuous 6 degree head down tilt. Intracerebral pressure has never been measured in space, but it could be increased similar to the increase in intraocular pressure that occurs in zero g and could adversely affect neurologic trauma. The management of head trauma has not been seriously pursued so far.
Diagnosis of fractures is based on clinical and physical examination alone unless imaging capability such as DRIS (digital radiological imaging system) is present. Most closed fractures can be adequately splinted with flexible aluminium splints and elastic bandages.
Anaesthesia in Space
Inhalation anaesthetics cannot be used because volatile gas would quickly contaminate and overwhelm the closed loop environment. In one g, spinal anaesthesia is commonly administered using lighter or heavier local anaesthetic solution and spread of anaesthetic in cerebrospinal space is controlled by positioning the patient. In zero g, the spread of local anaesthetics is unaffected by patient position and would act the same as isobaric solution in one g. But isobaric solutions do not produce anaesthesia cephalad to T-12 dermatome. This means that spinal anaesthesia at zero g has limited applicability. Intravenous anaesthesia using ventilator support and monitoring however, is feasible but requires full attention of a trained crew member. Local anaesthetics present no additional difficulty in zero g and have been provided in medical kits.
Future of Health Care in Space
Currently, clinical care in space is limited in scope and the most likely response is early evacuation, if an astronaut experiences serious injury. The time to reach definitive care is only 24 hours for the International Space Station but 7 days for Lunar base and more than 9 months for a Mars expedition. For the next decade, operational priorities will be to develop the capabilities of the International Space Station to enable safe human space travel beyond low earth orbit (LEO). Such a mission will be fairly different from that in low earth orbit as astronauts might be committed to a voyage of 3 years or longer with no option for early return to Earth.
For long duration space flight such as Mars expedition, the medical care system will need to be fairly autonomous and self sufficient and such an undertaking will require the ability to diagnose and treat serious life-threatening injuries. A system with more surgical capability and resources will need to be provided along with some newer technology such as telemedicine and telerobotics.
An ultrasonographic system is at present available at the International Space Station and can be used for clinical diagnostic studies. Now and into the near future, ultrasonography will be the only medical imaging modality available to address thoracoabdominal injuries. It is a noninvasive, repeatable, teletransmittable imaging tool that can screen for the presence of intracavitary haemorrhage or visceral leakage. Astronaut Crew Medical Officers, who are not required to be clinicians, may perform the examination in space. Ultrasound telemonitoring can be used in low earth orbit but communication delays will make telemonitoring impractical for a Mars mission. Transmission between Earth and Mars bound crew would take between 8 and 50 minutes, depending on the orbital configuration.
With future Mars mission being man's greatest challenge, basic technical developments will be crucial to support and sustain a very vulnerable crew.
- Davis JR: Medical issues for a mission to Mars. Aviat Space Environ Med 70:162,1998.
- Barratt M: Medical support for the International Space Station. Avait Space Environ Med 70:155,1998.
- McCuaig K, Houtchens B: Management of trauma and emergency surgery in space. J Trauma 33:610,1992.
- Campbell MR, Billica RD, Johnston SL: Animal surgery in microgravity. Aviat Space Environ Med 64:58,1993.
- McCuaig K: Surgical problems in space: An overview. J Clin Pharm 34:513,1994.
- Kirkpatric AW, Dulchavsky SA, Boulanger BR et al: Extraterritorial resuscitation of haemorrhagic shock: fluid. J Trauma 50:162,2001.
- Kirkpatric A, Campbell M, Brenneman F: Trauma laparotomy in space. 28th International Conference on Environmental Systems, 1998.
ROBOTICS IN SURGERY
Unlike traditional open surgery, in laparoscopy, the action of the surgeon's hand is mediated by rigid, unarticulated instruments, and the visual access is not direct, but is mediated by a camera. Obviously, these limitations increase laparoscopic surgeon's difficulty, operative time, and risk of complications.
To improve surgical technique by avoiding some of the disadvantages of laparoscopy, robotics have been introduced in surgery. This gives the surgeon the same quality of information and manipulation as they have when performing open surgery. Instruments and manipulators with all degrees of freedom and improved visual access by the magnification of the three digital camera.
A surgical robot has been defined as a “powered computer-controlled manipulator with artificial sensing that can be reprogrammed to move and position tools to carry out a range of surgical tasks”.1 A robot is an automatic device that seems to perform mechanical functions normally ascribed to humans, providing greater accuracy and precision. A robot is especially useful where the incision is small and surgery is being performed in depth where guidance and steadiness in instrument handling of deep structures is important.
The first use for robot in surgery on humans was transurethral resection of the prostate and was developed at the Imperial College London.2 Its second generation “Prorobot”3 possesses, a transurethral ultrasonographic probe at its tip to measure the gland at the beginning of the procedure. This permits a three dimensional model of the prostate to be built up. The surgeon can then mark which parts are to be removed. The robot then calculates trajectories of cutting and follows them.
Neurosurgery has made much use of robotics. After positioning, the neurosurgeon is able to make a burr hole at a point marked by the robot and have a straight line access to a tumour for biopsy. The robot has a series of tools on a carousel, which rotates. Once the appropriate tool is chosen it can be advanced under CT imaging to provide greater accuracy. Robotic microscope has been used on what were considered to be inoperable brain-stem tumours.4
In minimal access surgery, the two systems developed for clinical use (for cardiac procedures and abdominal procedures) are the Zeus System of Computer Motion Inc and the “da Vinci” System of Intuitive Surgical Inc. Both systems have a rigid endoscopic camera with two separate manipulator arms. The da Vinci system has seven degrees of freedom movement thus helping with more complex tasks. The addition of wrists permits the surgeon to mimic his own movements, rather than experience the limitations of the rigid laparoscopic instrument and has obvious advantages in terms of dexterity and complexity of movements.5 The limitations of the application of minimal access techniques in cardiac surgery for beating heart bypass have been aided by the use of telemanipulators. Left anterior descending coronary artery is identified. Robotic dissection mobilisation of the left internal mammary artery is performed and the graft anastomosis follows.6 The totally endoscopic coronary artery bypass operations (TECAS) have been performed at the Imperial College (St. Mary's) London.7 Four robotic arms are inserted through the ribs. One of the arms contains a camera which sends back clear 3 D images of the heart onto a screen. It has between 12 and 15 times magnification. Another arm is for a stabiliser which is used to hold the diseased coronary artery in place while the bypass is performed. The other two are the right and left hand arms which are used to hold the microvascular instruments to perform anastomosis. The “da Vinci” robot has an endo-wrist which is as flexible as a human wrist and holds the instruments in place as they perform the graft anastomosis. Currently only patients who require a single vessel bypass are considered suitable for surgery, though surgeons have high hopes of increasing its use for double or even triple bypass surgery.
The “da Vinci” system has also been used to undertake a number of general surgical procedures, including laparoscopic cholecystectomy and Nissen fundoplication. Robotic fundoplication has shown certain advantages to the operating surgeon. The articulated robotic arms seem to allow easier passage around and ehind the oesophagus during its dissection and easier mobilisation of the curvature of the stomach. Suturing the wrap and the crura are more straightforward because of the increased mobility and dexterity of the system.8
- Davies BL: A review of robotics in surgery. Proc Inst Mech Eng (H) 214:129,2000.
- Davies BL, Hibberd RD, Wickham JEA: A surgeon robot prostatectomy. Its laboratory evaluation. J Med Eng Technol 13:273,1989.
- Davies BL, Hibberd RD, Ng WS et al: The development of a surgeon robot for prostatectomies. Proc Inst Mech Eng 205:35,1991.
- Levesque M: Guided resection of diffuse brainstem neoplasms. Stereotact Funct Neurosurg 73:15,1999.
- Falk V, Walther T, Diegeler A: Dexterity enhancement in endoscopic surgery by a computer controlled wrist mechanical wrist. Minim Invasive Therapy and Allied Technol 8:235,1999.
- Vassiliades TA Jr, Rogers EW, Nielsen JL et al: Minimally invasive direct coronary artery bypass grafting. Intermediate term results. Ann Thorac Surg 70:1063,2000.
- Revill JO: Heart surgery by robot. Observer, London, May 18,2003.
- Costi R, Himpens J, Vruyns J et al: Robotic fundoplication. J Am Coll Surg 197: 500, 2003.
CYBERNETICS AND SURGERY
Professor Kevin Warwick, Professor of Cybernetics at the University of Reading in the UK, is carrying out research in artificial intelligence and robotics. Prof. Warwick shocked the international scientific community through a series of experiments by having a silicon chip transponder surgically implanted in his left arm.1 On 20th April 1998, a glass capsule about 23 milimeter long and 3 milimeter wide containing an electromagnetic coil and a silicon chip was inserted in his arm. The implant sent signals to the computer which identified Warwick. Computer was programmed to open the doors, switch on lights depending on where he was and also gave spoken, running tally of the mail in his e-mail box. The chip merely sent out an identifying signal and was not tied into Warwick's nervous system but was still a step forward since his body has not rejected the foreign substance yet. There was hope that future chips could even be tied directly into the nervous system of the host, in order to eliminate computer key boards and facilitate direct communication with a CPU.
Professor Warwick improved upon the above mentioned experiment by a new device and on 14th of March 2002, a hundred electrode array was surgically implanted into the nerve fibres of the median nerve in the left arm of Professor Warwick. The operation was carried out at Radcliffe infirmary Oxford, by a medical team headed by the neurosurgeons A Shad and Peter Teddy. The procedure which took a little over 2 hours, involved inserting a guiding tube into a two inch incision made above the wrist, inserting the microelectrode array into this tube and firing it into the nerve fibres of the median nerve below the elbow joint.2
In the new improved device, the connection with nerve fibres in the left arm was through a matrix of pins injected into the membrane that surrounds the nerve fibres and from here there was connection to the main parts of the implant. The main implant carried a battery, a radiotransmitter and receiver and a processing unit. Professor Warwick's median nerve was thus linked to a radiotransmitter reciver to send signals from his nervous system to a computer and vice versa. Prof Warwick also later linked the nervous system in his wife's left arm to a radiotransmitter receiver to send signals.
A number of experiments have been carried out by Professor Warwick using the signals detected by the array, most notably Prof was able to control an electric wheelchair and an intelligent artificial hand, developed by Dr Peter Keyboard using the neural interface. In addition to being able to measure the nerve signals transmitted down Warwick's left arm, the implant was also able to create artificial sensation by stimulating individual electrodes within the array.3 This was demonstrated with the aid of Professor's wife Irene and a second less complex implant connecting to her nervous system.
It is possible that in future a person's nervous system may be directly linked to the computer network and thought communication may be possible. Emotion of one kind or another may be recorded and when played down on to the nervous system, the signals could recreate feelings. The computer stores data and pain appears as an electronic signal. Emotions such as anger, shock and excitement can be investigated because distinct signals are apparent. It may be possible to remove the effects of pain and this may be a breakthrough in pain relief. Electronic signals to remove headache may provide a tranquiliser effect and thus an immediate pain killer.
Professor Warwick wishes to link up more closely with the brain. He wants to look at the possibility of people communicating between each other from one nervous system to another; this could mean (electronic) thoughts from one person's brain to another possibly across the internet. This will change the way we communicate between humans.
A person's brain directly linked to a computer network may provide an extra memory and processing capabilities and thus cybernetics may offer man a technological upgrade. The technology might change humans into superhumans. A half human, half machine with new senses and abilities. A thought which does send shudder down this editor's spine.
- Mamtas Nick, Kevin Warwick: Cyborg professor (firstname.lastname@example.org) July 28, 2002.
- Warwick, Gasson MN, Hutt BD et al: Microelectrode arrays: Results from an application study. Proceedings 6th IBRO World Congress on Neurosciences, Prague 2003.
- Warwick, Gasson MN, Hutt BD et al: Neural implants for artificially generated sensation and feedback control. 10th International Conference on Human Computer Interaction, Crete, Greece June 22–27,2003.