Surgical Oncology: Fundamentals, Evidence-based Approaches and New Technology David L Bartlett, Pragatheeshwar Thirunavukarasu, Matthew D Neal, Phil Bao
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1Introduction and Background

Surgical Oncology—Definition, History, Scope, Philosophy1

Kamran Idrees,
David L Bartlett,
Bernard Fisher
 
Introduction
The history of surgical oncology dates back to the ancient times where reports of cancer and cancer therapy appeared in the Edwin Smith and Ebers Papyri between 1600 and 1700 BC. Included in these reports is a brief description of cautery destruction of cancer as a surgical approach. Hippocrates in the 5th century BC made observations about breast cancer, but he had a pessimistic view on the role of surgical management, cautioning that surgery would shorten survival. It was not until the 5th century AD when Leonidas, a Greek physician, described a formal operation for cancer, this being a mastectomy. Because of the limitations of surgical technique, surgical treatment was limited to superficial tumors of the skin and breast at that time. Surgical oncology seemed to be at a standstill through the dark ages of medicine, which lasted from the 5th till the 17th century.
John Hunter (1728–1793) is considered as the father of the modern surgery and believed that cancer was a localized process and amenable to curative surgical removal (Figure 1-1). He stressed the importance of wide excision, which would include the potential areas of lymphatic spread. Many of his ideas were later expressed by Dr William Stewart Halsted in the late 1800s. The major advances in surgical oncology required the refinement of anesthesia, which was first used by Crawford Long in 1842 and was effectively demonstrated for major surgery by Morton in 1846 at Massachusetts General Hospital. Similarly, the advancement of antisepsis by Lister in 1867 was another necessary requirement for more advanced surgical oncology procedures. Once anesthesia and antisepsis were introduced, major abdominal surgery for cancer became feasible. The latter half of the 1800s, therefore, saw the development of multiple surgical procedures for cancer. The description of the optimal technique for surgical management of cancer by William Halsted of Johns Hopkins Hospital and his description of the radical mastectomy for breast cancer in 1891 defined the principles behind the surgical treatment of cancer for most of the 1900s (Figure 1-2). It was not until the 1970s when, as a result of randomized clinical trials from the National Surgical Adjuvant Breast Project (NSABP) under Dr Bernard Fisher, the empiricism of Halsted was replaced with the scientific results defining cancer as a systemic disease requiring less extensive surgery combined with adjuvant radiation and/or chemotherapy.
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Figure 1-1: John Hunter (1728–1793)
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Figure 1-2: William Halsted (1852–1922)
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The Society of Surgical Oncology
Dr James Ewing was appointed as Pathologist of the Memorial Hospital in New York City in 1912, and became Director of the Hospital in 1931. He was instrumental in developing the field of radiation therapy, and focusing Memorial Hospital as a cancer hospital. He developed fellowship training programs in oncology and trained numerous physicians who practiced across the world the techniques learned at Memorial Hospital. In the mid 1930s, Dr Hayes Martin and the Superintendent of Memorial Hospital, Mr George Holmes, took the initial steps to develop an alumni association for those who had trained at Memorial Hospital. This took the form of a formal society in 1940, under the chairmanship of William MacComb. Dr Ewing reluctantly approved the name of this society as “The James Ewing Society”, and it was established with a constitution and by laws approved in 1941. The first James Ewing Society's Cancer Symposium was held in 1948 at Memorial Hospital, consisting of scientific sessions, clinical demonstrations and scientific displays. Eventually the decision was made to expand the membership eligibility to cancer specialists not trained at Memorial, and to hold annual meetings at locations other than Memorial Hospital.
Under the chairmanship of Edward Scanlon, in 1975, the decision was made to change the name of the society to the Society of Surgical Oncology (SSO). This was necessary to attain national recognition by the American Medical Association and other national medical organizations. The James Ewing Foundation was developed as the primary foundation associated with the SSO. The SSO has grown to a membership of 2400 in 2009, with 24 standing committees and an annual meeting that attracts 1600 attendees. The journal, Annals of Surgical Oncology, under the editorship of Charles Balch was launched as the official journal of the SSO in 1994. This journal has steadily grown in stature and reputation, and has become an important aspect of the society. The annual meeting continues to be a vibrant display of basic science and clinical studies in the field of surgical oncology. One of the original tenets in 1947 was the establishment of a subspecialty board of oncology of the American Board of Surgery. This continues to be a goal of the society today, but has not been achieved.
 
Clinical Trial Programs
Dr Sydney Farber, Mary Lasker and others proposed in 1955 that congress begin funding a clinical trials program. In response, congress appropriated five million dollars to the NCI for the establishment of the Chemotherapy National Service Center. By 1957, 17 institutional networks had been organized forming the seed for the cooperative group programs. These cooperative groups became organized and evolved into the 10 cooperative groups in existence today in the United States. The groups along with their founding year are listed in Table 1-1.
Surgeons became involved in a major way in 1957 with the initiation of the National Surgical Adjuvant Breast Project (NSABP) under the direction of Rudolph Noer. Dr Bernard Fisher took over the directorship in 1967 and performed landmark studies of breast and colon cancer, shaping the way cancer is managed today. The landmark NSABP study which changed the paradigm of surgical therapy for cancer and cemented the surgical oncologist's role in clinical research was the B-04 study in 1971 which demonstrated the equivalency of total mastectomy versus radical mastectomy. This was followed in 1976 with B-06 which demonstrated that lumpectomy, axillary dissection and radiotherapy was equivalent to mastectomy and much less disfiguring. To date, the NSABP investigators have enrolled over 110,000 patients and the program consists of over 1,000 university hospitals, major medical centers, large oncology practice groups and health maintenance organizations in the United States, Canada, Puerto Rico, Ireland and Australia.
TABLE 1-1   Cooperative Groups supported by the NCI for clinical trials
Cooperative Group
Year
Eastern Cooperative Oncology Group (ECOG)
1955
Cancer and Leukemia Group B (CALGB)
1956
National Surgical Adjuvant Breast and Bowel Project (NSABP)
1957
Southwest Oncology Group (SWOG)
1958
Radiation Therapy Oncology Group (RTOG)
1968
Gynecologic Oncology Group (GOG)
1970
North Central Cancer Treatment Group (NCCTG)
1977
American College of Surgeons Oncology Group (ACOSOG)
1998
American College of Radiology Imaging Network (ACRIN)
1999
Children's Oncology Group (COG)
2000
5As a result of Dr Fisher's leadership, the role of the surgical oncologist has evolved into that of being a leader in clinical trial research.
In the late 1990s, the American College of Surgeons under the leadership of Dr Samuel A Wells, Jr. formed the American College of Surgeons Oncology Group (ACOSOG). This program was designed specifically to evaluate the surgical management of patients with malignant solid tumors and has accrued thousands of patients to numerous clinical trials to date. The group was originally housed at the American College of Surgeons office in Chicago, but moved to Duke University in 2001. While this is the only group specifically focused on surgical oncology, surgical leadership plays an important role for most of the cooperative groups funded through the National Cancer Institute. The SSO has also recognized the importance of clinical trials, supporting clinical research through grants and presenting clinical trial updates at their annual meeting.
 
Biologic Research Leading to the Alternative Hypothesis
The significance of the change from Halsted's empiricism to Fisher's hypothesis driven scientific evidence for the surgical management of cancer deserves special consideration in the history of surgical oncology. For almost a century, surgical practice was dictated by the idea that cancer progressed and spread via direct extension into lymph nodes with a predictable pattern. Virchow in 1863 formulated a theory that lymph nodes could provide an effective barrier to the passage of tumor cells and perhaps based on this, Halsted formulated the theory that all tumor spread was related to lymphatics. He stated “… the metastases to bone, to pleura, to liver, are probably parts of the whole and that the involvements are almost invariably by process of lymphatic permeation and not embolic by way of the blood … It must be our endeavor to trace more definitely the routes traveled in the metastases to bone, particularly to the humerus, for it is even possible in case of involvement of this bone that amputation of the shoulder joint plus a proper removal of the soft parts might eradicate the disease. So, too, it is conceivable that, ultimately, when our knowledge of the lymphatics traversed in cases of femur involvement becomes sufficiently exact, amputation at the hip joint may seem indicated.” This was an appropriate theory based on the biology and anatomy understood at the time, but surgical principles did not change and were not studied as new biology was defined. These principles ultimately led to super-radical surgery for cancers as seen in Figure 1-3.
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Figure 1-3: Examples of super-radical surgery: (A) radical neck dissection; (B) forequarter amputation; (C) radical mastectomy; (D) hemipelvectomy; (E and F) hemicorporectomy.(Reproduced with permission from Fisher B. Biological research in the evolution of cancer surgery: a personal perspective. Cancer Research. 2008 Dec 15;68(24):10007–20).
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Dr Bernard Fisher and his brother Edwin Fisher began in 1957 to study the biology of tumor metastases (Figure 1-4). Based on their experiments, they concluded that there was no orderly pattern to tumor spread and that intrinsic factors in tumor cells combined with a multiplicity of host and organ factors to result in metastases. They were also able to demonstrate that cells could traverse through a lymph node, gaining access to the bloodstream and efferent lymphatic vessels. The lymph nodes had important biologic and immunologic significance and were not simply “mechanical receptacles”. Dr Fisher developed the Alternative Hypothesis (Table 1-2). He then developed a series of clinical trials through the NSABP to test his hypotheses. The B-04 trial compared the outcome of almost 2,000 women comparing Halsted's radical mastectomy with lesser operations and demonstrated no difference in survival. A follow up study, B-06, compared lumpectomy, lumpectomy plus radiation and mastectomy, and demonstrated no difference in survival with 20-year follow-up. These trials effectively validated the alternative hypothesis, which changed the paradigm of surgical management for all cancers. En bloc radical resections were not warranted, and adjuvant chemotherapy should be considered when the risk of metastases is significant.
TABLE 1-2   Comparison of the tenets comprising the Halsted and Fisher's alternative hypothesis
Halstedian hypothesis (1894)
Alternative hypothesis (1968)
Tumors spread in an orderly, defined manner based on mechanical considerations
Tumor cells traverse lymphatics to lymph nodes by direct extension, supporting en bloc dissection.
The positive lymph node is an indicator of tumor spread and is the instigator of distant diseases.
RLNs are barriers to the passage of tumor cells.
RLNs are of anatomical importance.
The bloodstream is of little significance as a route of tumor dissemination.
A tumor is autonomous of its host.
Operable breast cancer is a locoregional disease.
The extent and nuances of operation are the dominant factors influencing patient outcome.
No consideration was given to tumor multicentricity in the breast.
There is no orderly pattern of tumor cell dissemination.
Tumor cells traverse lymphatics by embolization, challenging the merit of en bloc dissection.
The positive lymph node is an indicator of a host-tumor relationship that permits development of metastases rather than the instigator.
RLNs are ineffective as barriers to tumor cell spread.
RLNs are of biologic importance.
The bloodstream is of considerable importance in tumor dissemination.
Complex host-tumor inter-relationships affect every facet of the disease.
Operable breast cancer is a systemic disease.
Variations in locoregional therapy are unlikely to substantially affect sruvival.
Multicentric foci of occult tumor are not of necessity a precursor of clinically overt cancer.
Abbreviation: RLN—regional lymph node
Fisher et al, J Clin Oncol, Jan 20;28(3):366–74. Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
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Figure 1-4: Bernard and Edwin Fisher – 1957
 
Historic Operations
The technical feats which set the stage for routine performance of complex surgical oncology procedures are discussed by organ site below and see Table 1-3 for a complete review.
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TABLE 1-3   Historical advances in cancer surgery according to tumor site
Nervous System
Craniotomy
Harvey Cushing
1910
Cordotomy for pain
E. Martin
1912
Trans-sphenoidal craniotomy
Harvey Cushing
1920
Head and Neck
Total Laryngectomy
Theodor Billroth
1873
Thyroidectomy#
Theodore Kocher
1883
Radical neck dissection
George W Crile
1906
Functional/Modified radical neck dissection
Osvaldo Suarez
1963
Breast
Radical mastectomy
William S Halsted
1891
Lung
One-stage lobectomy£
Harold Brunn
1928
First one-stage pneumonectomy£
Evarts A Graham
1933
Segmental resection
Edward Churchill
1939
Thoracoscopic lobectomy
Ralph J. Lewis
1991
Esophagus
Cervical esophagectomy
Czerny
1877
Transthoracic esophagectomy£
Franz Torek
1913
Transhiatal esophagectomy
George G Turner
1933
Two-field esophagectomy
Ivor Lewis
1946
Three-field esophagectomy
K McKeown
1962
Laparoscopic transhiatal esophagectomy
AL DePaula
1995
Stomach
First gastrectomy
Theodor Billroth
1881
Total gastrectomy
Carl Schlatter
1897
Liver
Hepatic resection
D Langenbuch
1888
Right hepatic lobectomy with hilar ligation
W Wendel
1911
True anatomic hepatic resection with vascular control (Right hepatic lobectomy)
J Lortat-Jacob
1952
Laparoscopic hepatic resection
W Wayand
1993
Pancreas
Transduodenal ampullectomy
William S Halsted
1898
Two-stagepancreaticoduodenectomy£
W Kausch
1909
One-stage pancreaticoduodenectomy
Allen O Whipple
1945
Total pancreatectomy
EW Rockey
1943
Laparoscopic pancreaticoduodenectomy
M Gagner
1994
Colon and Rectum
Rectal resection with end-colostomy
R Von Volkmann
1878
Abdomino-perineal resection (APR)*
Vincent Czerny
1884
Colectomy with end-colostomy
Robert Weir
1885
Contd.
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Contd…
Trans-sacral rectal excision
P Kraske
1885
Total mesorectal excision
R Heald
1982
Laparoscopic colectomy
Moi ses Jacobs
1990
Laparoscopic APR
J Sackier
1992
Adrenal
Open adrenalectomy
Sargent
1914
Open bilateral adrenalectomy
Young
1936
Laparoscopic adrenalectomy
M Gagner
1992
Prostate
Perineal prostatectomy
George Goodfellow
1891
Radical perineal prostatectomy
JJ Young
1904
Radical retropubic prostatectomy
Millin
1945
Laparoscopic radical prostatectomy
A Raboy
1997
Gynecologic
Oophorectomy
Ephraim McDowell
1809
Vaginal hysterectomy
Conrad Langenbeck
1813
Abdominal hysterectomy
WA Freund
1878
Radical abdominal hysterectomy $
John G Clark
1895
Laparoscopic hysterectomy
Harry Reich
1988
# Thyroidectomy performed for goiter
£ “Successful” defined as the patient survived the postoperative period
* W Ernest Miles perfected and popularized abdominoperineal resection (APR)
$ Ernst Wertheim perfected and popularized radical hysterectomy
 
Breast
Breast cancer and its treatment are first described in the Edwin Smith Papyrus (3000 BC). In this era, treatment consisted of either cauterization (with fire drills or caustic agents such as sulfuric acid) or amputation of the ulcerated, locally advanced disease. Roman physicians, especially Galen, recommended surgical excision of breast cancer rather than cauterizing it and emphasized achieving clear margins with occasional removal of pectoralis muscles. Vesalius provided the first detailed anatomical description of the breast that facilitated the surgeons' dissection and control of bleeding. In this pre-anesthesia era, several instruments were developed to aid in rapid amputation of the diseased breast. In the 18th century, the French surgeon Petit and German surgeon Heister recommended en bloc removal of the primary tumor with surrounding normal breast tissue, the pectoralis fascia, enlarged axillary lymph nodes and pectoralis muscle or chest wall if involved.
Breast cancer has contributed greatly to our understanding of the lymphatic system and its role in the metastatic process. In the 16th century, Ambrose Pare was one of the first surgeons to observe metastatic involvement of axillary lymph nodes in patients with breast cancer, while Michael Servetus was the first to propose lymph node removal along with breast resection. Most of these findings went unnoticed till the 17th century when Jean Louis Petit, first president of the French Academy of Surgery, advocated routine removal of enlarged axillary lymph nodes along with resection of breast tumor. Joseph Pancoast is credited for describing the operative technique of axillary dissection in 1844. However, it was Charles Hewitt Moore who promoted routine complete axillary lymphadenectomy irrespective of clinically palpable lymph nodes in 1867. This change was based on his observations of high local recurrence rate at or near incision sites and that lymph nodes can harbor metastases even though they might not be clinically palpable. But the true credit for widely popularizing axillary lymphadenectomy goes to William Halsted and Willie Meyer who concurrently published, in 1894, their meticulous and systematic operative technique of in-continuity removal of the entire breast with axillary tissue. Halsted described the technique of “classical” radical mastectomy that involved the en bloc removal of the entire breast, axillary lymph nodes and pectoralis muscles. It is thought that Halsted was greatly influenced by the 9German School of Surgery, including Volkmann, Kuster and Heidenhain and went on to incorporated their philosophy and techniques to develop the “complete” breast operation. With his technique, he reported 5-year overall survival of 45% and for patients with node-negative disease the 5-year survival of 72%. Halsted's radical mastectomy remained the classical surgical approach for breast cancer for the first three quarters of the 20th century and the Halstedian principle of en bloc lymphadenectomy were applied to surgery of other organ sites as discussed above.
In the mid-20th century, Taylor, Wallace, Handley, Urban and Wangensteen extended the limits of radical mastectomy by routinely performing supraclavicular, internal mammary and mediastinal lymphadenectomy along with en bloc chest wall resection. However, this concept of supraradical mastectomy was never widely adopted. Cushman D Haagensen of New York wrote the textbook of “Diseases of the Breast” which was regarded as the gold standard in the management of breast cancer. His criteria for inoperability are regarded as a landmark in the field of surgical oncology. He realized that surgical intervention offered little or no benefit to survival if the breast cancer involved skin (ulcerated or inflammatory), was fixed to the chest wall, or if advanced axillary lymphadenopathy (matted or fixed to chest wall) was present.
In 1912, JB Murphy in his published report argues against radical mastectomy and his approach is regarded as an early attempt at the modified radical mastectomy. However, it was DH Patey of London who coined the term “modified radical” mastectomy for an operation in which he removed the entire breast, axillary lymph nodes and pectoralis minor but preserved the pectoralis major. Later on, Auchincloss and Madden further modified this operation by saving both the pectoralis major and minor. The results of the modified radical mastectomy were comparable to that of the classic radical mastectomy and this operation became standard of care during the 1970s in North America. This transition was also partly as a result of utilization of external beam radiation as adjuvant therapy in the treatment of breast cancer.
George Crile, Jr., of Cleveland helped pave the way for breast conservation surgery. In his published reports in 1965 and 1971, he demonstrated similar 5-year survival results with local excisions compared to mastectomy in carefully selected patients. It was not until Dr Fisher carried out his landmark randomized studies through the NSABP, that lumpectomy plus radiation became the standard of care for breast cancer, as discussed above.
The management of axillary lymph nodes has evolved from the radical en bloc resection of all lymph nodes, to the excision of a single, sentinel lymph node for sampling. The principle of complete resection of all axillary lymph nodes to prevent recurrence has evolved into the evaluation of lymph nodes as a marker for systemic metastases and as an indication for systemic chemotherapy. The complete three level axillary dissection which was popular until the 1980s and early 1990s was replaced by axillary sampling in the late 1990s and finally the sentinel lymph node biopsy in the first decade of the 21st century. Sentinel lymph node mapping was initially utilized in melanoma, parotid and penile cancers. Krag and Guiliano introduced the concept of sentinel lymph node mapping in breast cancer in the early 1990s. This technique has evolved into the best method of assessing lymph node involvement in breast cancer resulting in a decrease in the number of axillary lymphadenectomies performed and thus a reduction in its associated morbidity.
 
Head and Neck Cancer
In 1847, Sims is credited for performing the first successful superior maxillectomy for a tumor and a mandibulectomy for an osteosarcoma. Theodor Billroth of Vienna not only performed the first successful gastrectomy but also pioneered total laryngectomy in 1873 (Figure 1-5). Theodor Kocher received the recognition for his contributions to our understanding of the pathophysiology and surgery of the thyroid gland and was bestowed with the Nobel Prize. It was the first Nobel Prize awarded to a surgeon.
It was the seminal work of George Washington Crile, founder of the Cleveland Clinic, which established the importance of radical neck dissection in the management of patients with head and neck cancers. His meticulous surgical technique was described in a beautifully illustrated article published in Journal of the American Medical Association in 1906. Because of the functional morbidity and cosmetic deformity of radical neck dissection, there was gradual change in the viewpoint of head and neck surgeons in the management of these cancers.
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Figure 1-5: Theodor Billroth (1829–1894)
10Osvaldo Suarez, an Argentinean surgeon, is credited for proposing removal of all the lymphatic tissue within fascial compartments with preservation of uninvolved neck structures including the spinal accessory nerve, sternocleidomastoid muscle and internal jugular vein. This approach was known as “functional neck dissection”. A better understanding of the nodal spread, the biology of the disease and improvement of adjuvant therapies led to further modification to the extent and approach to neck dissection now classified as selective and modified radical neck dissections. This approach was advocated by Jesse and colleagues from M.D. Anderson Cancer Center and has completely replaced the need for radical neck dissection without compromising the oncologic outcome.
 
Esophagus
Theodore Billroth performed the first cervical esophageal resection in dogs in 1871. In 1877, Czerny performed the first cervical resection with re-anastomosis in humans. Mickulicz-Radecki then performed cervical esophagectomy with reconstruction of the cervical esophagus with a skin flap in 1886. Franz Torek performed the first successful transthoracic esophagectomy for squamous cell carcinoma of thoracic esophagus in 1913. Interestingly, the gastrointestinal continuity was reestablished with a rubber tube connected externally between a cervical esophagostomy and a gastrostomy (Figure 1-6). Amazingly the patient survived both the operation and the cancer for another 13 years. Yet routine esophageal surgery remained decades away because of the lack of a durable esophageal replacement.
In 1933, George Grey Turner performed the first transhiatal esophagectomy for cancer. The gastrointestinal continuity was restored with an ante-thoracic skin tube at a second stage. Ohsawa performed a similar procedure with an ante-thoracic esophagogastric anastomosis. William Adams and Dallas Phemister were the first to describe the immediate reconstruction with an esophagogastric anastomosis after distal esophagectomy in the United States in 1938. It was Richard Sweet in 1945 who described the esophagogastric anastomosis utilizing stomach as a conduit with the blood supply based on the right gastroepiploic vascular pedicle. A year later, Ivor Lewis published his technique of utilizing a laparotomy incision for gastric mobilization and a right thoracotomy incision for the resection of the esophagus and intra-thoracic reconstruction. McKeown later in 1962 reported his “three stage esophagectomy” with a midline laparotomy incision, right thoracotomy and left cervical incision followed by cervical esophagogastrostomy. In 1978, Mark Orringer at University of Michigan modified and then popularized the transhiatal esophagectomy, initially described by Turner, without the morbidity of a thoracotomy for esophageal cancer.
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Figure 1-6: The first patient to have successful transthoracic esophagectomy for squamous cell carcinoma. Notice patient has a rubber tube as a conduit. Patient lived for 13 years
 
Lung
Hugh Davies reported the first anatomic lobectomy in 1912, however, his patient died 27 days later. Brunn published the first successful lobectomy in 1929 for lung cancer. Rudolf Nissen performed the first total pneumonectomy in 1931, but it is Evart Graham (1933) who is credited for the first successful one-stage pneumonectomy for lung cancer. In the 1940s, Oschner and DeBakey postulated the role of lymph node dissection in the treatment of lung carcinoma. Later on, Allison followed by Cahan described performing hilar and mediastinal lymphadenectomy with pneumonectomy. In 1939, Edward Churchill first reported segmental resection followed by a 20-year retrospective review of their surgical experience in the treatment of lung cancer suggesting equivalent survival results for lobectomy compared to total pneumonectomy. This was subsequently validated by the work of Watson, Johnson and Cahan.
 
Gastric Cancer
In 1875, Pean reported the first gastrectomy for gastric cancer, however, his patient died in the immediate postoperative period. The first reported successful gastrectomy 11for gastric cancer was performed in 1881 by Theodore Billroth, who is regarded as the father of gastric surgery. He reported his accomplishment of performing pylorectomy in a letter with an end-end gastroduodenostomy (known as Billroth I reconstruction to this day) a few days later. His patient survived the operation but subsequently died of gastric recurrence. He later published a variation of his previous gastric reconstruction in 1885. In this modification, he described performing a bypass between the gastric remnant and a loop of jejunum (Billroth II reconstruction) and the technique of blind duodenal stump closure. It was many years later that Carl Schlatter performed the first successful total gastrectomy in Zurich, Switzerland. Despite the significant contributions of both Billroth and Schlatter to the surgery of the gastric cancer, most of these procedures were not regularly performed because of associated high morbidity and mortality.
It was in the second quarter of the 20th century that gastric surgery was performed more commonly and safely with the introduction of antibiotics and advancement of anesthesia. Pioneering work by Balfour and Broder demonstrated that one half of all gastric ulcers are cancerous and gross appearance is misleading in establishing whether an ulcer is benign or malignant. Based on these observations, Balfour suggested wider resections for the operative management of gastric ulcers in case they turn out to be malignant. This was subsequently substantiated by Vanbrugghen. The work of Coller and his colleagues was instrumental in illustrating the increased predilection of gastric cancers to spread to lymph nodes in the perigastric and peripancreatic region. Autopsy studies on patients with previous gastrectomies validated high local recurrences in the proximal stomach and duodenal stump but also revealed a high incidence of regional lymph node disease.
McNeer and his colleagues at Memorial Hospital in New York contributed significantly to the surgical management of gastric cancer. They carefully and meticulously tabulated the operative mortality, recurrence pattern and survival in 1315 gastric resections. Because of a high local recurrence with limited resections, McNeer advocated for extended gastric resections including total gastrectomy with lesser and greater omentectomy, splenectomy and distal pancreatectomy. He also recommended en bloc resection of involved organs. McNeer reported improved survival in patients with distal gastric cancers but operative mortality remained high. With inability to reproduce similar results and high surgical mortality, others including Longmire and Gilbertsen questioned this approach. However, it was the collective contributions of McNeer, Pack, Longmire and Lahey that broadened the field of gastric surgery.
 
Pancreas
Surgery of the pancreas lagged behind other organs secondary to lack of complete understanding of the pathophysiology and difficult anatomic location. In 1878, MacBurney performed the first papillotomy via a duodenotomy for choledocholithiasis. It was roughly two decades later that Kocher described his technique of extracting gallstones through a transduodenal papillotomy after lateral mobilization of the duodenum, now known as the Kocher maneuver. Utilizing the technique described by MacBurney and Kocher, William Halstead in 1898 performed the first transduodenal ampullectomy for a periampullary neoplasm.
At the end of the 19th century, several surgeons attempted pancreatic resections but without success because of a lack of appreciation for pancreatic secretory physiology and adequate knowledge of blood supply to the head of the pancreas and duodenum. These factors along with high immediate postoperative mortality swayed the surgeons away from pancreatic resections and toward palliative bypasses such as cholecystogastrostomy, gastrojejunostomy and choledochojejunostomy. It was the knowledge acquired from the technical refinement of these bypasses combined with the better understanding of the anatomy and physiology which subsequently paved the way for pancreatic resections, especially pancreaticoduodenectomy. Codvilla, in 1898, is credited for the first true pancreaticoduodenectomy. In his procedure, he resected the common bile duct, head of the pancreas and duodenum with biliary and gastric diversion. There was no pancreatic anastomosis performed and the patient died in the immediate postoperative period. The first successful pancreaticoduodenectomy was performed in two stages by Kausch in 1909. The first stage of the procedure entailed cholecystojejunostomy (to relieve jaundice and associated coagulopathy) followed by resection 6 weeks later. However, it was Allen Whipple and his colleagues at Memorial Hospital in New York who popularized pancreaticoduodenectomy. They published their surgical experience in the treatment of ampullary carcinoma in 1935 describing various procedures including common bile duct resection, duodenectomy and a two-stage pancreaticoduodenectomy. This operation underwent numerous anatomic modifications over several years by many others surgeons including Hunt, Brunschwig and Trimble. In 1945, Whipple reported the first case of a single stage procedure for a periampullary cancer. It was the numerous noteworthy contributions of Whipple to the field of pancreatic surgery that pancreaticoduodenectomy is still known as the “Whipple procedure”. Rockey, in 1943, reported the first total pancreatectomy for pancreatic cancer obviating the 12morbidity of a pancreatic leak and the possibility of recurrence by removing the entire pancreas. Although Whipple in his original description of pancreaticoduodenectomy preserved the pylorus, it was Traverso and Longmire, in 1978, who reintroduced the concept of pylorus-preserving pancreaticoduodenectomy to decrease the morbidity from marginal ulcers.
 
Colon and Rectum
In the late 18th century, fecal diversion was preformed for an obstructing rectal cancer with a cecostomy by Pillore. Most of colorectal cancers at that time (late 1800s and early 1900s) were treated with a two staged procedure consisting of fecal diversion with a colostomy initially followed by resection of tumor a few weeks later. The first transrectal removal of rectal tumor was performed by Kraske in 1885. However, these procedures were extremely morbid and associated with a high recurrence rate. Czerny is credited with the first combined abdominal and perineal resection (APR) of a rectal cancer. He performed this procedure out of necessity after failing to remove the rectal tumor through a perineal approach. Subsequently, two French surgeons Chalot and Quenu reported planned APR in late 19th century while Charles Mayo published his series in early 20th century. Unfortunately, because of the high morbidity and mortality of this procedure, this approach was not commonly practiced.
In 1908, Ernest Miles reported his technique of abdominoperineal resection in a landmark paper which popularized this approach for the carcinoma of the rectum that is still being performed to this date for low rectal tumors in which sphincter salvage is not possible. However, Dr Miles realized the high local recurrence rate (~95%) in his patients which he largely thought were because of incomplete lymph node removal. He subsequently modified his technique to incorporate more radical lymphadenectomy (from the origin of the IMA proximally to the ischiorectal fat below the levator ani distally). He reported three patients surviving beyond three years without local recurrence with this approach.
In the ensuing years, the clinical capability of whole blood transfusions and the two-team approach in Lithotomy-Trendelenburg position, as described by Llyod-Davies, were instrumental in decreasing the high mortality rate. In the 1960s, Turell pioneered the use of endoscopy for evaluation of the colon and rectum. In 1966, Mark Ravitch at the University of Pittsburgh introduced the use of surgical staplers for intestinal anastomosis in the United States.
During the 1970s and 1980s, the advent of doubled-stapled technique for low anterior resection and the development of the coloanal anastomosis paved the way for sphincter preservation. In 1972, Parks reported the technique of hand-sewn coloanal anastomosis while Griffen and Knight described the use of an EEA stapler for a low anterior resection in 1980. This led to an increase in the number of sphincter preservation procedures for rectal cancer patients who would otherwise undergo permanent colostomies. The local pelvic recurrence rates after resection of rectal cancer remained high (35–38%) during 1950s to early 1980s. However, this changed dramatically when Heald and his colleagues described the concept of total mesorectal excision (TME) in 1982. The total mesorectal excision resulted in significant reduction in positive lateral (circumferential resection) margins reducing local failure rates to 5–7% after rectal resection.
 
Uterus, Cervix and Ovaries
The first Oophorectomy was performed by Ephraim McDowell for a massive ovarian tumor in the patient's home in 1809. Conrad Langenbeck, Surgeon-General to the Hanoverian army, performed the first vaginal hysterectomy for endometrial cancer in 1913 while Sauter performed this procedure for cervical cancer in 1821. In 1895, John G Clark performed the first hysterectomy for cancer at Johns Hopkins Hospital. Although Ernest Wertheim was not the first to describe the procedure, his significant contributions to the field resulted in his name being virtually synonymous with the procedure of radical hysterectomy.
Alexander Brunschwig, a professor of Surgery at the University of Chicago, performed the first pelvic exenteration for cervical carcinoma in 1946. Subsequently, as a chief of gynecological service he continued to perform these radical operations for uterine and cervical carcinomas. In 1950, Eugene M Bricker at Ellis Fischel State Cancer Hospital in Missouri described the ileal conduit for urinary diversion—a major advancement in the field of pelvic surgery. Brunschwig in New York, Meigs in Boston, Bricker in St. Louis and Appleby in Vancouver continued these radical surgeries for these otherwise incurable advanced gynecological cancers with the possibility of cure in selected patients.
 
Soft Tissue Sarcoma
The surgical management of extremity sarcoma was the epitome of “radical surgery” in the late 19th and first three quarters of the 20th century. The first successful forequarter amputation was performed by Grosby in 1836. The first hemipelvectomy was performed by Theodore Billroth in 1891, but unlike his other successful endeavors such as the first total laryngectomy, the first gastrectomy, the first prostatectomy and the first suprapubic cystectomy, his hemipelvectomy patient died in the immediate postoperative period. The first successful 13hemipelvectomy was detailed by a Frenchman, Charles Girard, in 1895. Both these procedures were performed for osteosarcoma. The most “radical” of all surgeries, the hemicorporectomy, was proposed by Frederick Kredel. However, the first successful operation of this kind was performed by Aust and Absolon in 1961. It was Bowden and Booher, in 1958 who challenged the need for amputation for all cases of soft tissue sarcomas. This was further validated the work of Shiu and his colleagues. It was the seminal work at the National Cancer Institute Surgical branch by Rosenberg and his colleagues who demonstrated equivalent results between amputations and limb-sparing surgery in a prospective randomized trial. This laid the foundation for the role of limb sparing surgery in the treatment of soft tissue sarcoma in combination with radiation and chemotherapy.
 
Liver
The first liver resection was performed by Berta who removed part of the liver in a trauma patient. The first planned liver resection was a left lobectomy in a patient presenting with a liver mass, performed by D Langenbuch in 1888 in Germany.
L Tiffany performed the first hepatic resection for cancer in the United States in 1890. The largest series of hepatic resections in the 19th century was reported by William W Keen, Professor of Surgery at the Jefferson Medical College, when he described 76 liver resections of which 37 were for benign or malignant tumors with a mortality of 17%. In 1908, J Hogarth Pringle described the technique of compression of the portal triad to decrease bleeding from the liver. Interestingly, in his original description of eight patients, all of them died either during or in the immediate postoperative period. However, Pringle was able to successfully utilize this maneuver later on—which now bears his name. Despite these developments, most of the surgeons were hesitant to perform liver operations because of its friability and high propensity to bleed.
It was the improved understanding of surgical anatomy of the liver which contributed greatly to the advent of liver surgery. Initial anatomic studies were performed by Rex and Cantlie but it was the seminal work of Claude Couinaud who introduced the concept of segmental hepatic anatomy—the basis for segment-oriented hepatic resections. Wendel, in 1911, performed the first true anatomic right hepatic lobectomy using hilar ligation along the Cantlie's line. But the true credit goes to the French surgeon, Jean Louis
Lortat-Jacob, who in 1952 performed a successful anatomic liver resection with vascular inflow and outflow control (right hepatic lobectomy) through a thoracoabdominal incision. He performed this procedure on a patient with metastatic colorectal cancer without any blood transfusion. Around the same time, JK Quattlebaum from Savannah, Georgia, reported his case of right lobectomy for a hepatoma at the Southern Surgical Association's meeting, likely unaware of Lortat-Jacob's procedure.
 
Nonsurgical Advances
It is also important to mention some of the nonsurgical advances that made it possible to perform some of these radical surgeries for various cancers at the end of the 19th century and in the first half of the 20th century. The importance of the discovery of ether in the 1840s as an anesthetic to perform various operations cannot be understated. Subsequent advancements in anesthetic drugs and monitoring made it possible to perform more and more extensive surgeries safely. Utilizing carbolic acid in 1867, John Lister applied the concepts of Louis Pasteur to surgery and subsequently described the principles of antisepsis. This greatly improved the safety of all operations.
The discovery of blood types by Karl Landsteiner led to the ability to transfuse blood during and after surgery. This made radical cancer surgery feasible by reducing intraoperative and postoperative mortality. The work of John Scudder and Charles Drew further advanced the field of transfusion medicine. Further important advances after World War II included antibiotic therapy, anesthesia, blood transfusion, nutritional support and intensive cardiopulmonary monitoring reducing the perioperative morbidity and mortality associated with radical procedures such as the radical mastectomy, pelvic exenteration, pancreaticoduodenectomy, forequarter amputations, hemipelvectomy and even hemicorporectomy.
The development of the pressure-differential chamber for the management of pneumothorax was an essential factor in allowing lung resections. The device was invented by Ferdinand Sauerbruch in 1908, followed shortly by the development of insufflation for intratracheal anesthesia by Samuel Meltzer. These developments allowed the expansion of the lung after a thoracotomy.
Other important non-surgical advances included the discovery of insulin, allowing safe resection of the pancreas and the discovery of thyroid hormones for replacement therapy after thyroidectomy. While Theodore Kocher had mastered the technical aspects of thyroidectomy, his patients had “turned to cretins, saved for a life not worth living”. Only after replacement therapy was identified, and could a total thyroidectomy be performed.
All of these nonsurgical milestones made it possible to extend the horizon of surgery which otherwise would have become dormant despite better anatomical understanding and the exceptional technical skills of the surgeons.14
 
Summary and Recent Advances
The practice of cancer surgery is as old as medicine itself, dating back to 1700 BC. The evolution of the field required advances in anesthesia, antisepsis, blood transfusions, insulin therapy, ventilator management and more. Figure 1-7 provides a timeline of important advances in surgical oncology. Surgeons began attempting bigger and better surgeries as patients were able to survive them and the technical prowess of the surgeon improved. The culmination of this was the successful pancreaticoduodenectomy for pancreas cancer described by Kausch in 1909 and major hepatectomies and pneumonectomies, described by Wendel in 1911 and Graham in 1933. A preliminary understanding of the biology of cancer led to Halsted's recommendation of en bloc resection of draining lymph nodes with the primary tumor, leading to the description of the radical mastectomy in 1891. The trend continued with wider resections of all primary cancers.
Dr Bernard Fisher shifted the paradigm of increasing radicalism and through hypothesis driven randomized cooperative group clinical trials established that cancer is a systemic disease and that survival equivalence could be obtained with lesser operations.
zoom view
Figure 1-7: Timeline of advances in surgery.(Reproduced with permission from Fisher B. Biological research in the evolution of cancer surgery: a personal perspective. Cancer Research. 2008 Dec 15;68(24):10007–20.
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The advantage associated with postoperative adjuvant radiation therapy and chemotherapy became established for breast cancer therapy with landmark trials from the NSABP. This principle has been applied to other cancers where effective chemotherapy has been defined.
As surgeons refined the techniques for the management of the primary tumors, they turned their technical expertise onto the management of metastatic tumors, including hepatic and pulmonary metastasectomy for colorectal cancer and sarcoma and the regional delivery of chemotherapy for regionally confined metastatic cancers. This includes isolated limb perfusion described by Creech and Krementz in 1958 and hepatic arterial infusion therapy described by Sullivan in 1964. The field of intraperitoneal chemotherapy and the treatment of peritoneal carcinomatosis has been developed by many, but perhaps Paul Sugarbaker has been most instrumental in developing this field over the last three decades, with a focus on combined surgical cytoreduction and regional chemotherapy for pseudomyxoma peritonei, colon carcinomatosis and peritoneal mesothelioma. He published his first randomized trial of intraperitoneal 5-FU versus intravenous 5-FU in 1985.
Technological advances have led to new options for the surgical treatment of cancer. For instance, cryotherapy had been explored as a means of treating superficial skin tumors since the 1960s, but with the development of cryoprobe technology this technique could be applied to liver tumors as described by Morris in 1989. Radiofrequency ablation was developed as an alternative to cryotherapy for liver tumors, with the advantage of using smaller probes and increasing the size of safe ablations. These techniques improved the safety and minimized the physical insult to the patient, expanding the patient population that could undergo surgical management of cancer.
The current trend is to move toward minimally invasive and robotic approaches to cancer surgery, minimizing the nutritional and immunologic insult to the patient while maintaining the principles of margin negative resection of tumors. The patient with cancer often requires adjuvant therapy and may be of advanced age. Minimally invasive approaches minimize the insult to the patient, expand the eligibility and help lessen the time to initiation of adjuvant therapy. An important survival equivalency study was performed in colon cancer by Nelson et al in 2004. This study demonstrated that minimally invasive cancer surgery could be performed with equivalent cancer related survival to open surgery, with many advantages in terms of quality of life. This has opened the door leading to complex minimally invasive procedures, such as robotic pancreaticoduodenectomies, representing the ultimate fusion of technology and advanced surgical cancer care.
The importance of studying the history of surgical oncology lies in learning from our predecessors and not repeating past mistakes. The most striking lesson is that we must not base our practice on empiricism or anecdotes. We should use the anecdotes to develop hypotheses and use the basic science laboratory and the clinical trial “laboratory” to test our hypotheses. The cooperative group clinical trial programs must be well supported and utilized to definitively answer questions with regards to surgical procedures in the future.
Landmark Papers
  1. Ellis H. A History of Surgery. Cambridge University Press;  Cambridge:  2001.
  1. Fisher B. Biological research in the evolution of cancer surgery: A personal perspective. Cancer Res 2008; 68: 10007–20.
  1. Fisher B. The evolution of paradigms for the management of breast cancer: A personal perspective. Cancer Res 1992; 52:2371–83.
  1. Lawrence W History of Surgical Oncology. In: Norton (Ed). Surgery: Basic Science and Clinical Evidence. Springer;  New York:  2008:1889–1900.
  1. Lopez M. The evolution of radical cancer surgery. Surg Oncol Clin N Am 2005; 14:441–649.