Abeloff's Clinical Oncology, 4th Edition

Part I – Science of Clinical Oncology

Section D – Preventing and Treating Cancer

Chapter 28 – Surgical Interventions in Cancer

John E. Niederhuber

SUMMARY OF KEY POINTS

  

   

Surgeon is part of a multidisciplinary team.

  

   

Surgeon is frequently the “entry point” for patients who are newly diagnosed with cancer.

  

   

Surgeon must have knowledge of the biology and natural history of the cancer to be treated.

  

   

Surgeon must be technically experienced in diagnostic procedures and operative interventions.

  

   

Surgeon must have appropriate knowledge base in medical and radiation oncology.

  

   

Patients treated in a multimodality setting have improved outcomes.

  

   

Training of surgical oncologist must encompass the following:

  

   

Etiology and genetic predispositions of cancer

  

   

Prognostic factors and natural history of specific tumors

  

   

Understanding of how to provide cost-effective treatment

  

   

Skills to develop, conduct, and manage clinical trials

  

   

Guidance in management of advanced disease

  

   

Guidance in offering compassionate support

  

   

Guidance in determining and evaluating outcomes

  

   

Surgical oncologist should be a participant in clinical trials, providing guidance in design and monitoring of quality control aspects of surgical intervention component as well as overall leadership design and implementation.

  

   

Surgical oncologist should be an educational resource in the community.

  

   

Surgical oncologist plays an important role in prevention and screening.

INTRODUCTION

Historically, surgery was the sole method used for treating cancer. However, with the introduction of ionizing radiation and the development of anticancer drugs, cancer therapy has rapidly progressed to involve the careful integration of an extensive array of therapeutic options in the treatment of both primary and recurrent tumors. As a result, the cancer surgeon no longer works alone but is part of a multidisciplinary team involved in the treatment of most solid tumors and in the design and implementation of clinical trials.

The surgeon must have a clear understanding of the biology of cancer and its natural history and must also be experienced in the technical procedures needed to accurately diagnose and appropriately resect primary cancers and, when indicated, locally recurrent and metastatic tumors. The cancer surgeon must also be prepared, in many cases, to function as the primary cancer care provider, or cancer-oriented “family physician,” for the patient. The surgeon must provide for the patient a focus of treatment integration among the various cancer specialists. Cancer surgeons find that it is common for patients to call or visit them for advice about all aspects of their treatment, which often leads to a lifelong relationship of continued care and follow-up.

HISTORICAL PERSPECTIVE

In medicine, professional and public acceptance of a subspecialty has historically depended largely on accomplishment. The development of the surgical oncology subspecialty is no exception and has been intimately tied to the history of surgery. In fact, surgical treatment of cancer has been significantly responsible for the role of surgery in modern medicine. The earliest discussion of surgical treatment of tumors appears in the E.S. Papyrus (ca. 1600 BC), but it is believed to be based on earlier writings dating back to 3000 BC.[1]

Despite this early mention, surgery was primarily reserved for the treatment of abscesses and for managing trauma before the introduction of anesthesia. The few operations performed for tumors were amputations. Not only did patients suffer excruciating pain in the absence of anesthesia, but also, before the advent of antisepsis, the death rate from infection was extraordinarily high. As a result, few patients were willing to undergo such intense pain electively, with so little chance of survival. The development of anesthesia and the introduction of antisepsis made elective surgical techniques for the treatment of cancer much more acceptable, and rapid developments in cancer surgery began to occur during the second half of the nineteenth century as tumor-specific elective surgeries were undertaken and refined. [2] [3]

Anesthesia

Some of the first “clinical trials” of ether anesthesia took place in the parlor of Crawford Long, a dentist practicing in Georgia during the early 1840s. Long is said to have invited his friends over for “ether parties” to enjoy a temporary “loss of Southern inhibitions.” Long witnessed that his friends lost not only their inhibitions, but also pain sensation. He is said to have used ether anesthesia in his dental practice as early as 1842. Unfortunately, Long's use of ether was not brought to the attention of the medical public.

John Collins Warren is responsible for two significant benchmarks in oncologic surgical history. He published the first American work on tumors in 1838, entitled “Surgical Observations on Tumors with Cases and Operations,”[4] and he was the surgeon in the first published account of the use of ether anesthesia for removal of a tongue cancer from Gilbert Abbott in 1846.[2] The anesthesia was administered by a dentist, William T. Morton, who had developed the technique. The operation involved excision of the submaxillary gland and part of the tongue.[5]

Antisepsis

Despite the advances made in anesthesia in the 1840s, sepsis remained a major barrier to successful surgery until Joseph Lister (subsequently Baron Lister), an accomplished surgeon, introduced the concept of bactericidal therapy with carbolic acid in 1867.[3] This was an outgrowth of Pasteur's theory that bacteria caused infection. Using carbolic acid as an antiseptic agent in conjunction with heat sterilization of instruments, Lister dramatically decreased the rate of postoperative fatalities. He also developed absorbable ligatures and the drainage tube; both represent significant advances for surgical management of wounds and incisions.

Lister was indirectly responsible for the introduction of the first ready-to-use surgical dressings in 1886. Robert Wood Johnson heard an address in 1876 by James Lister; as a result, he developed sterile dressings wrapped in individual packages suitable for immediate use without the risk of contamination.

Although the value of Lister's contributions was not recognized by his senior colleagues, they were quickly adopted by William Stewart Halsted,[6] the first professor of surgery at The Johns Hopkins Hospital. Halsted introduced the meticulous techniques of tissue handling during surgery and the antiseptic methods proposed by Lister to the United States. Halsted, who had a major interest in cancer, was strongly supported in his work by his close friend and colleague at Hopkins, Sir William Osler. Osler was a student of abdominal malignancies, and the collaboration of these two great American physicians represents one of the earliest occurrences of the multidisciplinary approach to cancer treatment.

SURGICAL ONCOLOGIST

Surgical oncology has emerged to play an increasingly important role in the treatment of cancer ( Table 28-1 ). There are many reasons for this evolution of subspecialization within general surgery, but the most significant are: (1) the increasing complexity of multidisciplinary cancer care; (2) the opportunities for clinical and laboratory investigation of cancer biology; (3) the rapid increase in the number of medical and radiation oncologists, which threatens to diminish significantly the traditional role of the surgeon in coordinating the management of cancer patients (even those with early disease); and (4) the expectation of patients that surgeons have the latest information and newest treatment options.[7]

Table 28-1   -- Role of the Surgical Oncologist

  

 

CONSULTANT

  

 

Special training or skills

  

 

Tumor board

  

 

ORGANIZER AND LEADER

  

 

Cancer programs

  

 

Cancer committee

  

 

Tumor registry

  

 

Oncology section

  

 

EDUCATOR

  

 

Cancer conferences

  

 

Teaching programs

  

 

RESEARCHER

  

 

Clinical protocols

 

 

Today, the surgical oncologist is really a “cancer physician” who interacts with all other members of the cancer therapy team in a knowledgeable and confident manner ( Box 28-1 ). This role requires a sound knowledge of cancer biology (including cancer prevention and the biology of metastasis), imaging technologies, chemical and biologic therapy, and radiation therapy.

Box 28-1 

CANCER SURGEON

Care Provider

  

 

Brings surgical skill and compassionate care to patients

  

 

Leads screening, prevention, and risk assessment programs

  

 

Facilitates molecular characterization of tumor and surrogate tissues

  

 

Coordinates multidisciplinary clinical care teams

Researcher

  

 

Facilitates laboratory research

  

 

Coordinates epidemiologic studies

  

 

Conducts clinical trials research

  

 

Develops novel approaches to education

Teacher

  

 

Ensures excellence in surgical care

  

 

Leads a multidisciplinary team to implement integrated oncology training

In a 1996 address before the American College of Surgeons, Murray Brennan of Memorial Sloan-Kettering Cancer Center in New York stated, “In defining what might be considered the role of the surgeon in cancer care, there are at least seven important areas that I believe need to have renewed emphasis.”[8] Brennan used his experience with soft-tissue sarcoma to illustrate the importance of the following performance objectives for the cancer surgeon: (1) understands etiology and genetic predisposition; (2) understands prognostic factors and natural history; (3) performs cost-effective treatment; (4) develops clinical trials; (5) guides advanced disease management; (6) guides compassionate support; and (7) evaluates outcome. Brennan's analysis of the cancer surgeon's role as a member of today's therapy team is an excellent real-life description of the responsibilities involved and the opportunities to provide real leadership in cancer care.

The surgical oncologist thus provides the leadership for cancer care, cancer research, and cancer teaching within the academic or hospital-based surgical community. This is an extremely important role, and it has become increasingly clear that programs that emphasize strong cancer leadership from surgical oncologists have developed solid research and clinical programs for patients seeking cancer treatment.

As part of the greater medical community, the surgical oncologist has the responsibility of introducing to the surgical community new information, new approaches to cancer diagnosis, and new approaches to therapy. The surgical oncologist is most often the one involved in the early stages of cancer diagnosis, an ideal position to provide significant institutional leadership in developing community interest in cancer prevention, including screening and early diagnosis.

In addition to local responsibilities, much ongoing work in national clinical trials depends heavily on surgical oncology leadership directed at establishing quality control of the surgical aspects of multidisciplinary protocols. Cancer surgeons have historically provided significant leadership in the conduct of clinical trials. Most noteworthy have been the National Surgical Adjuvant Breast and Bowel Project (NSABP), initially under the direction of Bernard Fisher, and more recently, the American College of Surgeons Oncology Group (ACOSOG), originally led by Samuel Wells. Surgeons have also been active participants in several other cooperative groups. The success of these surgeon-sponsored clinical trials placed surgeons as significant contributors to the clinical trials agenda of these groups, and showed the importance of surgical involvement in designing clinical trials and maintaining control of the quality of surgery when it was part of the study. Standardizing and maintaining the quality of surgical intervention has proved especially important in evaluating studies of adjuvant therapy.

The surgical oncologist is an important member of the design team and is critical to providing education to participating surgeons about standards of care, technical guidelines for the operative procedure, and collection of data. The surgeon member of the team is also essential for reviewing the staging data submitted by participating surgeons as well as information provided by quality control reports. When surgery is part of the therapy being evaluated in a clinical trial, it must be performed in a uniform manner by surgeons specifically trained and competent to deliver the procedure in a quality manner.

Surgeons and Surgical Research

Surgeons have been somewhat notorious for the introduction of new surgical procedures and devices without evidence of a random assignment prospective evaluation. Perhaps it is the nature of what we do. We learn from the experience of repeated procedures, and from that experience comes new ideas we believe will improve patient outcomes. Though not wishing in any way to hinder this category of innovation, the surgical oncologist does find it necessary to hasten the introduction of evidence-based results in dealing with such new technologies to eradicate tumors, with lesser operative procedures (e.g., sentinel lymph nodes) and now with the various approaches to minimally invasive surgery.

Training in Surgical Oncology

Historically, training in surgical oncology occurred at the small number of large standalone cancer hospitals in the United States, primarily with the goal of preparing a select group of general surgeons to work as cancer specialists in university hospitals or at large medical centers.

During the 1970s there was more interest in developing the subspecialty of surgical oncology within academic surgery training programs and in obtaining board certification, as had been done for other oncologic subspecialties. This effort by several prominent cancer surgeons encountered considerable difficulties in the ensuing years, and surgical oncology has yet to achieve recognition as a board-certified subspecialty.

There are many reasons for this. First and foremost is that surgical cancer care in the community almost always falls to the general surgeon. Even in the university hospital setting, cancer surgery has not been the exclusive right of the surgical oncologist. The surgical oncologist, as a result, has always been viewed as somewhat redundant by general surgical colleagues. Furthermore, each of the boarded surgical subspecialties also deals with cancer treatment.

To address some of these issues, a conference was held at the National Cancer Institute (NCI) in 1979. It was the consensus of this conference that training in surgical oncology should involve a 2-year period after completion of a general surgery residency.[9] The committee charged a national organization, the Society of Surgical Oncology (SSO), with developing training guidelines and a review and approval process for identifying qualified training programs. Clearly, the hope of those involved was that expertise in surgical oncology could be increased in significant numbers and disseminated more broadly in the community practice arena, not just in academic centers. Further, it was hoped that the development of a number of university training programs would eventually lead to board certification. Guidelines established by the SSO in 2001 call for 12 months of training in the surgical management of cancer cases, with a minimum number of procedures established for specific anatomic categories. In addition to surgical cases, trainees must also gain experience in the other aspects of the multidisciplinary management of cancer. Nonsurgical experience is required in radiation oncology, surgical pathology, medical oncology, and supportive and rehabilitative care. Clinical research on human subjects is required, and participation in laboratory research is encouraged.[10] There are currently 14 approved surgical oncology fellowship programs.

The effort to enhance training in surgical oncology, broaden available training opportunities, and provide a measure of qualification or certification of competence has been supported and nurtured by the SSO, which was founded in 1940 as the James Ewing Society.[11] This society has become the leading academic oncologic society for surgeons around the world. In assuming this leadership role, the SSO has developed and disseminated optimal guidelines for the multidisciplinary care of patients with cancer, provided an important resource for continuing education through its annual meeting, initiated and supported a monthly journal (The Annals of Surgical Oncology), and actively stimulated cancer research.[12] The Society has willingly taken on the responsibility of evaluating and approving fellowship programs. It embraced the recommended guidelines proposed by the 1979 NCI Committee and, in 1982, approved the first three training sites.[13] In 1992, the World Federation of Surgical Oncology Societies was inaugurated and immediately worked to develop “standards of education, training, and practice” in surgical oncology. [14] [15] These guidelines were published and are summarized in Table 28-2 . It is through efforts of the SSO and the World Federation of Surgical Oncology Societies that excellent training opportunities now exist for a significant number of general surgery graduates. Standardization of the process of review and accreditation ensures that more well-qualified cancer surgeons will be available to serve as experts in cancer care within multidisciplinary teams. The SSO deserves much praise and credit for its untiring and expert leadership in the training of future surgical oncologists.


Table 28-2   -- Guidelines for Training of Surgical Oncologists in Europe

  

   

Receive training to a high level of technical competence and attain the clinical skills needed to manage common and complex cancers.

  

   

Receive training in the evolving understanding of tumor biology, mechanisms of spread of disease, and other oncologic principles.

  

   

Understand the principles, scope, and limitations of different modalities of radiation therapy.

  

   

Be conversant with the theoretical and practical applications of cytotoxic chemotherapy.

  

   

Be prepared to study and evaluate evidence from clinical trials and thereby be in a position to propose new avenues of research and study, both in the clinical setting and in the laboratory.

  

   

Be trained to be discriminating in the application of modern technology in the investigation and treatment of malignant disease.

  

   

Be involved, as a member of a team, in each step of the decision-making process in planning the strategy for the patient's care.

Adapted from O'Higgins N: Towards a high standard of surgical oncology throughout Europe. Eur J Cancer 1995;31A(Suppl 6):S22. © 1995 Elsevier Science, with permission.

 

 

Although the SSO and other such organizations have taken on a leadership role in surgical oncology education, all surgical oncologists have an educational reponsibility and a role in teaching that should extend to their hospital staff, students, residents, fellows, colleagues, and the community. The surgical oncologist should have the capacity to develop effective training programs, laboratory research programs, treatment guidelines, clinical trials, and protocols. In addition, surgical oncologists must teach other surgeons and surgical residents how to incorporate oncology principles into their practice.

SURGEON'S ROLE IN CANCER MANAGEMENT

Prevention and Screening

The most effective weapons against cancer are prevention and early detection. Much of the debate about prevention has focused on the cost of delivering cancer prevention and screening services and the availability of enough adequately trained individuals to perform the appropriate screening test. Furthermore, the application of a screening test is a complex process ( Table 28-3 ), and multiple layers of evaluation are needed to prove test efficacy. Clearly, a screening test must be applied at the right time and to the appropriate population to be effective. Moreover, the screening test itself is merely designed to identify a possible condition that needs further in-depth evaluation. For the surgeon, the effectiveness and cost of screening are directly related to the strategies used to address positive test results.


Table 28-3   -- Common Predisposing Conditions and Associated Malignancies

Condition

Genes Tested

Associated Malignancy

Cryptorchid testis

 

Testicular

Chronic ulcerative colitis

 

Colon

Familial adenomatous polyposis

APC

Colon and rectum

Hereditary nonpolyposis colon cancer

MSH2

Colon and rectum

 

MSH6

 

 

MLH1

 

 

PMS1

 

 

PMS2

 

Family history of colon cancer

 

Colon and rectum

Multiple endocrine neoplasia Type 1

MEN1

Pancreatic islet cell, anterior pituitary

Multiple endocrine neoplasia Type 2

RET gene

Medullary cancer of the (types II and III) thyroid

Leukoplakia

 

Squamous

Family history of breast cancer

BRCA1 and BRCA2

Breast and ovary

Family history of ovarian cancer

BRCA1 and BRCA2

Ovary and breast

 

 

The level and quality of prevention and screening services may be increased through a greater consensus about goals for cancer prevention, better organization to provide these services more efficiently to large populations, and improvement of health education. Social problems like unemployment, poverty, and limited medical coverage for a large number of people have significantly influenced access to services, and in the poor regions of the world, screening is not even something to be considered. The agenda for the future in cancer prevention should include fundamental research, intervention research, program delivery, patient access through free choice, and surveillance and monitoring. [16] [17]

Certain conditions, often congenital or inherited genetic traits, are associated with the subsequent manifestation of cancer. Genetic testing has made it possible to accurately identify the carriers of mutations that increase the risk of the occurrence of certain cancers. Genetic tests available include that for the RET proto-oncogene present in multiple endocrine neoplasia type 2 (MEN-2), for the CDH1 mutation in hereditary diffuse gastric cancer, the APC gene in colorectal cancer, and the BRCA1 and BRCA2 mutations in breast and ovarian cancers. In patients in whom these syndromes are known to be present by occurrence or genetic testing, and in whom cancers are likely to occur in nonvital organs, it may become necessary to remove the organ to prevent possible malignancy. In these instances, the surgeon has a responsibility to inform and educate the patient about the condition and to alert the family to the hereditary nature of the disorder and its possible occurrence in other family members. The surgeon should also discuss the availability of genetic testing for family members at risk. Table 28-4 outlines some common predisposing conditions, genes associated with these conditions, and their corresponding malignancies.


Table 28-4   -- Ten Criteria for Cancer Screening Programs

1. Is the disease an important health problem?

Probably yes

2. Is there effective therapy for patients with localized disease?

Probably yes

3. Are treatment facilities for further diagnosis and treatment readily available?

Probably yes

4. Is there an identifiable latent period or early symptomatic stage of the disease?

Probably yes

5. Is there an effective screening technique?

Probably yes

6. Are the tests acceptable to the screened population, particularly groups at increased risk for disease?

Probably yes

7. Is the natural history of the disease, from its development to clinical manifestation, sufficiently known?

Probably yes

8. Is there a generally acceptable strategy to identify patients who should receive treatment versus careful observation alone?

Probably yes

9. Are the costs of screening acceptable?

Probably yes

10. Does the treatment of early-stage disease have a favorable effect on prognosis?

Probably yes

Adapted from Littrup PJ: Prostate cancer screening: Appropriate choices? Cancer 1994;74(Suppl):2016. © 1994 American Cancer Society, with permission.

 

 

 

As an example, 2% of adult women have a family history pattern that is associated with the BRCA1 or BRCA2 genes. For these women, the U.S. Preventive Services Task Force recommends referrals for genetic counseling and evaluation for BRCA testing.[18] The lifetime risk of developing breast cancer is 35% to 85 % for women with BRCA mutations as compared with a lifetime risk of 13.2% in the general population. The numbers for ovarian cancer are 10% to 50% vs. 1.7%. Prophylactic oophorectomy has been shown to reduce the ovarian cancer and breast cancer risk among such women by 83% and 70%, respectively.[19] Prophylactic mastectomy alone has been shown to reduce the breast cancer risk by 90% and in combination with oopherectomy, by 95%.[20] These are a number of options available for the patient, each with its own benefits and drawbacks. The surgeon plays a large role in informing the decisions of women at risk. The lethality of the disease, the risk of cancer, the efficacy of the screening tool, and the availability of effective surveillance options such as mammography in breast cancer, should all be considered in reaching a decision about prophylactic surgery. Even in the absence of an available genetic test, the same analysis can be applied to other high-risk patients.

Cryptorchidism is associated with a higher incidence of testicular cancer, which is often prevented by early prophylactic surgery. Patients with ulcerative colitis (with total and partial colonic involvement) are likely to have cancer of the colon if resection is not performed. The patient and surgeon must carefully balance the benefits and hazards of surgery with an understanding of the factors involved in determining increased risk (see Chapter 26 ).

Diagnosis

Evaluation for surgical cure should be based on a histologically confirmed diagnosis of a treatable cancer confined to local or regional tissues. The diagnosis of cancer cannot be proven without a biopsy, and biopsy should be repeated if the diagnosis is questionable. There have been remarkable advances in imaging technologies to improve the execution and outcome of selected biopsy procedures. Computed tomography (CT), ultrasonography, and magnetic resonance imaging are now frequently used to enhance needle guidance and placement. These techniques improve the accuracy and safety of needle placement along the target path, while avoiding injury to other structures. The use of three-dimensional stereotactic CT-guided biopsy is becoming increasingly widespread as a diagnostic tool. Stereotactic biopsy is appropriate for any lesion located in the brain stem, pons, or medulla.[21] This technology is also widely used to evaluate nonpalpable mammographically detected breast abnormalities. The use of these guidance techniques requires the surgeon to be familiar with the device and the approach.

Four techniques are currently in use for obtaining tissue for diagnosis:

  

1.   

Needle aspiration biopsy. This approach involves aspirating tissue fragments through a needle guided into an area in which disease is suspected. It can usually be performed using local anesthesia or, possibly, no anesthesia. Sampling can be guided by various imaging modalities, including CT and ultrasound. A study of the usefulness of CT-guided fine-needle aspiration in the diagnosis of malignancy in small pulmonary lesions showed 82% sensitivity, 100% specificity, and 88% accuracy.[22] The disadvantage of aspiration biopsy is that it seldom yields a sufficient specimen for histologic diagnosis. As a result, there is always a margin of error in individual cell analysis, even with an exceptionally skilled cytopathologist. Cytology has the disadvantage of being unable to distinguish between invasive and noninvasive cancers, so a more detailed histologic diagnosis is usually necessary.

  

2.   

Needle (core) biopsy. This technique entails the retrieval of a small core of tissue, using a specially designed “core-cutting” needle. This specimen is usually sufficient for histologic diagnosis of most tumor types. Like aspiration biopsy, this technique is relatively cost-effective and can usually be performed using a local anesthetic.

  

3.   

Incisional biopsy. This technique involves surgical retrieval of a small segment of a larger tumor for diagnosis. The advantage of the procedure is that it yields enough histologic material to provide analysis of tumor markers. It is also often possible to perform this procedure in an outpatient setting using local anesthesia. Incisional biopsies are particularly useful in the diagnosis of sarcomas, large tumors, and unresectable tumors, and when the preferred treatment is nonsurgical. The disadvantages of incisional biopsy include possible sampling errors, the risk of trauma to the tumor, the possible risk of tumor spread, and the need for excisional biopsy if no cancer is diagnosed. Precise technique is essential.

  

4.   

Excisional biopsy. This technique is total removal of all suspicious tumor tissue, with little or no margin. The circumstances of the procedure dictate the use of local or general anesthesia. This procedure is the most definitive diagnostic tool of the four described. It provides adequate treatment for nonmalignant tumors and involves minimal trauma to the cancer. It is necessary to perform excisional biopsy if the results of incisional biopsy or core needle biopsy are inconclusive. One of the disadvantages is that it is generally limited to small tumors (e.g., lymph nodes, parotid tumors). It also involves a deeper area of dissection, which necessitates wider margins.

The proper placement of a biopsy incision is vital. Misplacement can compromise subsequent surgical procedures, because the definitive operation will include excision of the surgical tract of the prior incisional or excisional biopsy. The evidence concerning tumor spread from incisional and excisional biopsy is inconclusive. However, the surgeon should take extreme care to avoid using contaminated instruments on new tissue planes and to secure proper hemostasis of biopsy sites to avoid the spread of tumor along tissue planes.

The biopsy technique selected should be appropriate for the suspected lesion and should yield an adequate tissue sample for proper histologic diagnosis. Orientation of the specimen, if applicable, should be marked clearly and carefully by the surgeon to facilitate proper histologic interpretation. Proper handling of excised tissue is the surgeon's responsibility and the surgeon must be knowledgeable regarding procedures required to provide optimal specimens for tissue banking. Although such banking procedures thus far have been ad hoc, the NCI has in place a set of First-Generation Guidelines for the biorepositories that it supports.[23] It is NCI's plan that to qualify for grant support, investigations must use tissue samples from NCI-accredited facilities.[24] Therefore, the surgeon is well advised to be familiar with these guidelines.

In addition to knowledge of such guidelines, it is also important for the surgeon to maintain a close relationship with the pathologist. They are able to provide guidance before staging procedures with regard to tissue requirements. Furthermore, if the patient has a pathologic diagnosis from an outside source, it is always necessary to have the diagnosis confirmed. It may even be necessary to obtain tissue blocks to prepare more slides, to perform more extensive cytologic marker studies, and occasionally, to perform additional biopsies to obtain a definitive diagnosis.

Staging

Staging is the classification of the anatomic extent of cancer in an individual. Specific stage groups categorize cancers of particular anatomic sites. Staging is essential in the treatment process and requires an understanding of the biology of cancer as well as the extent of disease. The tumor-node-metastasis (TNM) classification, detailed in Table 28-5 , is the global standard in cancer staging.


Table 28-5   -- TNM Classification System

TNM SYSTEM

Describes the anatomic extent of disease based on assessment of three components

T

Primary tumor size and extent

N

Regional lymph node involvement

M

Distant metastasis absent or present

Primary tumor (T)

TX

Primary tumor cannot be assessed

T0

No evidence of primary tumor

Tis

Carcinoma in situ

T1, T2

Increasing size or local extension

T3, T4

Increasing extent of primary tumor

Regional lymph nodes (N)

NX

Regional lymph nodes cannot be assessed

N0

No regional lymph node metastasis

N1, N2, N3

Increasing involvement of regional lymph nodes

Distant metastasis (M)

MX

Presence of distant metastasis cannot be assessed

M0

No distant metastasis

M1

Distant metastasis (may be further specified according to site of occurrence)

HISTOPATHOLOGY

Qualitative assessment of category of tissue or cell type based on appearance

Histopathology grade (G)

GX

Grade cannot be assessed

G1

Well differentiated

G2

Moderately well differentiated

G3

Poorly differentiated

G4

Undifferentiated

ADDITIONAL DESCRIPTIONS

cTNM (or TNM)

Clinical, increasing size or local extension

pTNM

Pathologic

rTNM

Recurrence of tumor after disease-free interval

aTNM

First determined at autopsy

STAGE GROUPING

0

Tis, N0, M0

I

T1, N0, M0

IIA

T0, N0, M0

 

T1, N1, M0

 

T2, N0, M0

IIB

T2, N1, M0

 

T3, N0

From Rodary C, Flamont F, Donaldson SS: An attempt to use a common staging system in rhabdomyosarcoma: a report of an international workshop initiated by the International Society of Pediatric Oncology (SIOP). Med Pediatr Oncol 1989;17:210.

 

 

 

Over the past decade, there has been a move to using minimally invasive techniques for the staging of a tumor. For instance, although staging for pancreatic cancer has been traditionally done by CT, peritoneal spread of the disease is difficult to interpret by this method. A minimally invasive laparoscopy allows for such a determination and can help detect inoperable candidates.[25] One center's negative exploration rate was reduced from 65% to 24% after the introduction of staging laparoscopy in the treatment protocol.[25] In breast cancer, routine axillary dissection has been replaced by sentinel lymph node biopsy as the standard of care.[26] In validation studies for the procedure, accuracy rates ranged from 95% to 100%, yet carried significantly less morbidity than axillary dissection. Only patients with positive sentinel lymph nodes currently undergo the more extensive procedure. Sentinel lymph node biopsy is also now routinely used in the staging of melanoma and shows promise as a procedure in colorectal cancer. [27] [28]

Recently, the role of molecular characterization of sampled lymph node tissue has been shown to demonstrate evidence of tumor when standard cytology and histology cannot. The importance of such findings remains to be demonstrated and certainly will vary depending on the tumor. Increasingly however, molecular characterization will determine therapy.[29]

Multidisciplinary Management

Although the management of cancer formerly involved surgery alone, most solid tumors, even very early cancers, are treated by more than one modality. This multidisciplinary approach to treatment requires the input and coordination of multiple specialists. To complicate matters even further, often more than one therapeutic option exists. This requires the specialists involved to agree on the treatment regimen to be followed.

Although the advances in multimodal therapy have changed the role of the surgeon in the diagnosis and treatment of cancer, the surgeon continues to be the primary care provider for most patients with cancer and frequently coordinates care with other oncology specialists including radiation and medical oncologists. Like the surgeon, the radiation oncologist provides an important modality of local and regional cancer therapy. Often, radiation therapy is used after surgery to improve local disease control rates, or even before surgery, to reduce tumor bulk or downstage the tumor. It is also increasingly common for radiation to be combined with simultaneous administration of chemotherapy or radiation sensitizer agents. The medical oncologist's responsibilities include administering and monitoring the patient's chemotherapy, hormone therapy, and in some instances, biologic therapy. Medical oncologists manage the toxicities of intravenous and oral anticancer therapy, and as a result, provide considerable supportive care, especially as new agents have been developed to better control nausea and fatigue.

It is important and beneficial to the patient that these various caregivers work in a coordinated and collaborative effort toward the optimum outcome. There is evidence that the multidisciplinary approach to cancer management leads to increased survival. A study in the United Kingdom examining standards of care in head and neck cancer[30] showed increases in 2-year survival for patients assessed in a multidisciplinary clinic. An earlier study also confirmed the benefits of multimodal management.[31] Patients with skeletal and soft-tissue sarcomas of the extremity were treated with preoperative intra-arterial doxorubicin and radiation therapy, radical surgical resection, and postoperative chemotherapy or chemoimmunotherapy, resulting in the preservation of a functional extremity in 13 of 14 patients. Seven of eight patients with stage IIIA and IIIB soft-tissue sarcomas that were managed with preoperative intra-arterial doxorubicin and radiation therapy followed by en bloc soft-tissue resection and six patients with bone sarcomas that were managed with preoperative treatment followed by bone resection and replacement with cadaver bone allografts remained free of disease for 4 to 34 months. The results of the combined-modality approach were significantly better than those obtained in patients managed with surgical resection alone or with a combination of surgery and another single modality, in terms of both short-term recurrence-free survival and salvage of a functional extremity.[31]

The surgical oncologist not only is involved with medical oncologists and radiation oncologists in developing the treatment plan but is also responsible for recognizing the need for input from other surgical cancer specialists in other surgical specialties (thoracic, urologic, plastic, head and neck, gynecologic, and orthopedic surgery) or the appropriateness of referring a patient to a clinical trial. Participation in clinical trials has been shown to be of enormous benefit to patients. One study in patients with sarcoma noted that longer survival was associated with clinical trial participation in all age groups studied.[32]Although the clinical trials may lack a surgical component, the surgical oncologist can help to provide this benefit by keeping abreast of trials and enrolling eligible participants.

Advancing the development of multidisciplinary cancer care is a growing trend toward freestanding cancer care centers. The critical components of these centers are multidisciplinary cancer care, direct care and support services, a commitment to clinical trials, and a comprehensive program for quality assurance.[33] Comprehensive cancer centers affiliated with academic medical centers have an array of clinically focused investigations, including programs designed to test new therapies and research programs investigating the biology of cancer. These academic comprehensive cancer centers, some 61 supported in part by grants from the NCI, attract the elite of cancer clinician-scientists and basic scientists. As a result, patients receive better cancer care and greater support from experienced ancillary services. This translates into better quality of life as well as a longer life and greater hope for cure.

SURGICAL TREATMENT OF CANCER

Surgical Risk

Assessment of surgical risk is based on several factors. The physical status of the oncologic patient and the debilities that often accompany the disease process present specific challenges to the surgical team. Patients should undergo a complete evaluation before surgery, and any history of cardiac, pulmonary, hepatic, or renal disease should be documented. Emphasis should be placed on physiologic function rather than chronologic age. A study conducted at the Mayo Clinic in 1989 showed that patients 90 years of age and older tolerated the stress of a surgical procedure fairly well.[34] The physical status of the patients in the study was assessed using the American Society of Anesthesiologists Physical Status Classification ( Table 28-6 ).


Table 28-6   -- American Society of Anesthesiologists Physical Status Classification

Class

Description

I

Healthy patient

II

Mild systemic disease, no functional limitation

III

Severe systemic disease, definite functional limitation

IV

Severe systemic disease that is a constant threat to life

V

Moribund patient unlikely to survive 24 hours with or without operation

From Miller RD: Principles and Practice of Anesthesia, 2nd ed. New York, Churchill Livingstone, 1986, with permission.

 

 

 

The performance scales most widely used by oncologic specialists are the Eastern Cooperative Oncology Group Performance Scale (ECOG-PS) and the Karnofsky Performance Status (KPS) rating. These performance scales are also useful to surgeons and anesthesiologists in determining operative risk. A comparison of the ECOG-PS and KPS ratings showed both methods to be valid prognostic indicators of functional status, but the ECOG-PS seemed slightly superior. If necessary, each can be converted to the other with sufficient accuracy.[35] These two classifications are outlined in Table 28-7 .


Table 28-7   -- Eastern Cooperative Oncology Group Performance Scale and Corresponding Karnofsky Rating

ECOG-PS Grade

Description

Karnofsky Rating

0

Fully active, able to carry on all predisease activities without restriction

100

1

Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work)

80–90

2

Ambulatory and capable of all self-care, but unable to carry out any work activities; up and about more than 50% of waking hours

60–70

3

Capable of only limited self-care; confined to bed or chair 50% or more of waking hours

40–50

4

Completely disabled; cannot carry on any self-care; totally confined to bed or chair

≤30

ECOG-PS, Eastern Cooperative Oncology Group performance scale.

 

 

 

Mortality caused by anesthetic complications is most often related to the physical status of the patient. Highly sophisticated techniques of anesthesia have increased the safety of major oncologic procedures, and many of these advances have their basis in modern cardiac surgery and in transplantation, especially liver transplantation. The choice of anesthetic technique and agent should be appropriate for both the procedure and the patient. For example, surgery in the lower abdominal area, lower extremities, or pelvis may be performed with general or spinal anesthesia, depending on the patient's health status. The risk to the patient who has evidence of congestive heart failure would probably be increased by the use of general anesthesia as opposed to spinal anesthesia. However, patients with a history of ischemic heart disease may become agitated during a surgical procedure in which they are awake, thereby causing myocardial stress. The surgeon should work closely with the anesthesiologist to ensure proper selection of anesthetic application. Epidural-assisted general anesthesia is frequently used for abdominal surgery and provides an opportunity for improved pain management during postsurgical recovery.[36]

The oncologic patient is a particularly challenging surgical candidate. Operative mortality is usually defined as mortality that occurs within 30 days of a major operative procedure. The operative mortality statistics for oncologic patients can be deceptive. For example, patients who undergo a palliative procedure have a very high operative mortality rate, even if the surgery is successful. The cancer surgeon is ultimately responsible for ensuring that surgical intervention is safely undertaken, with an awareness of the possible risks and complications.

Surgery for Primary Cancer

At times, the cancer surgeon alone will be responsible for patient outcome, whereas at other times a combination of therapeutic modalities may enhance the prospect of cure or quality of life. Surgery should always be extended or restricted with these considerations in mind. The cancer surgeon must think first as an oncologist and attempt to envision the entire course of a particular disease and its treatment. The ultimate approach for the patient is multispecialty consultation that develops a consensus-based optimized course of therapy in the context of available clinical trials (the tumor board concept).[37] If surgery is indeed the best treatment option, then the surgeon may act on that conclusion.[38]

Appropriate treatment of primary cancer varies with the individual cancer type and the area involved. The cardinal principle of surgical cure is total removal of neoplastic tissue. This involves avoiding implantation of loose tumor cells; minimizing iatrogenic, lymphatic, and vascular dissemination of cancer cells; and obtaining a complete margin of normal tissue around the primary tumor ( Table 28-8 ).


Table 28-8   -- Adequate Margins of Resection

  

 

A complete margin of normal tissue around the primary lesion

  

 

Frozen sections used to evaluate tissue margins in instances of doubt

  

 

Complete removal of involved regional lymph nodes

  

 

Resection of involved adjacent organ

  

 

En bloc resection of biopsy tracts and tumor sinuses

 

 

As is the case for staging, minimally invasive procedures have been adopted for the treatment of several malignancies. The main benefits of laparoscopic procedures are a reduction in perioperative trauma, shorter hospital stays, and more rapid recovery. Laparoscopic procedures have been shown to be as effective as open surgery in cancers of the pancreas (lesions left of the portal vein), esophagus, liver, gynecologic malignancies, and colorectal cancer, among others. [39] [40] [41] [42] The last has been the subject of debate, due to reports of port site metastases when the procedure was initially introduced.[42]However, later studies reported no increase in recurrence rates for laparoscopic procedures as opposed to open procedures.[43]

Laparoscopic procedures have been enhanced by the use of surgical robots that allow for three-dimensional viewing and greater control over the manipulation of surgical instruments. Robotic surgery has been utilized to enhance laparoscopic procedures in a variety of cancers. [42] [44] The advantages afforded by robotic assistance in laparoscopic surgery have not generally been achieved in open procedures. However, there has been success in utilizing robotic assistance in prostatectomy.[42]

Surgical treatment is often combined with other modalities to improve outcome. To coordinate the appropriate care of the patient, the surgeon must fully understand the indications, risks, and benefits of using systemic and radiologic therapy, especially when the benefits of such modalities have been adequately studied in prospective clinical trials.

Surgery for Metastases

In many cases, patients in whom a single site of metastatic disease has been detected can undergo resection with a reasonable rate of success. Many patients with a limited number of metastases to sites such as the liver, brain, or lung can be cured by surgical resection. For example, published experience indicates that resection of colorectal metastases to the liver should be performed when: (1) the number of liver tumors is fewer than four, (2) extrahepatic tumor is not demonstrable, and (3) a tumor-free margin of at least 10 mm can be obtained. The 5-year survival rate is 30% to 40% when all of these criteria are met.[45] The current management of metastatic colorectal cancer is a good example of a more aggressive approach to recurrent disease where ablative procedures added to metastectomy have greatly extended the options (see Chapter 81 ). Resection of pulmonary metastases in patients with soft-tissue and bony sarcomas can cure as many as 30% of patients. The surgeon must consider several elements before undertaking surgery for metastatic disease. These include tumor histology; disease-free interval; tumor-doubling time; and the location, size, and extent of disease.

Surgery for Debulking

The results of experimental studies suggest that cytoreduction, or debulking of recurrent cancer, has important potential benefits. In the laboratory setting, reduction of the tumor increases the sensitivity of the remaining tumor to chemotherapy and radiation therapy by increasing the proportion of proliferating tumor cells, decreasing the number of therapeutic cycles necessary to eradicate the tumor, increasing cellular distribution of oxygen and nutrient within the tumor, and reducing the likelihood that resistant clones will develop.[46]

Evidence of human clinical benefit seems to be more limited. The benefits of cytoreduction are most dramatic when accompanied by effective chemotherapy or radiation; therefore, the value of cytoreduction has been acknowledged in pediatric solid tumors, lymphoma, and carcinoma of the ovary. Widespread application of cytoreduction, either alone or combined with other treatment modalities, lacks firm clinical support for common carcinomas.

Radiofrequency ablation (RFA) has also been used to some effect for debulking in patients with liver metastases, meeting selection criteria, of primary colorectal, breast and neuroendocrine tumors. Patients treated with RFA had longer median survival times than patients undergoing chemotherapy for the metastases.[47] Among primary tumors the use of RFA appears promising in hepatocellular carcinoma, renal cell carcinoma, and pulmonary neoplasia.[47]

Palliative Surgery

Palliative surgery is undertaken to relieve symptoms in the absence of cure. It is specifically designed to improve quality of life and must be undertaken with this in mind. Examples of palliative surgery include relief of intestinal obstruction, removal of tumors to control pain or hemorrhage, and introduction of a feeding jejunostomy to permit adequate nutrition.

Reconstructive and Rehabilitative Surgery

Quality of life is an important consideration in the care of the patient with cancer. The cancer surgeon has the unique responsibility to attend to the patient's cosmetic as well as curative surgical needs. Breast reconstruction after mastectomy, transfer of tissue after head and neck surgery, and lysis of contractures or muscle transposition to restore muscular function after radiation therapy are examples of techniques that offer the patient with cancer a higher degree of comfort and improved quality of life. Today, it is essential that the reconstructive surgeon be involved with the multispeciality team in planning the course of treatment so as to optimize reconstructive outcomes.

Vascular Access

Placement of short-term and long-term indwelling central venous catheters has become a common surgical procedure performed on cancer patients. These catheters provide venous access for chemotherapeutic infusion and withdrawal of blood. Several important developments in implantation technique and catheter design have decreased operative time and rendered this an almost exclusively outpatient procedure (see Chapter 52 ).

Surgery for Oncologic Emergencies

The patient with cancer presents a unique surgical risk. These patients are often neutropenic and thrombocytopenic, and have a high risk of hemorrhage and sepsis. The most common emergencies involve hemorrhage, perforation, intestinal obstruction, infection, or vital organ failure (see Chapter 53 ). When presented with an oncologic surgical emergency, the cancer surgeon must carefully assess the situation.

FUTURE DIRECTIONS

As evidenced throughout the preceding discussion, the role of the surgeon in the management of cancer, and therefore that of the surgical oncologist, has continued to evolve and grow. Advances in cancer management demand an increasing supply of surgical oncology specialists who can fulfill a wide variety of functions in the rapidly changing environment of cancer care. The scope of these advances requires knowledge across several disciplines and an increased understanding of basic science, especially as it relates to the molecular and cellular processes of cancer development and metastases, and genetics. The completion of the Human Genome Project marked the start of a new era of molecular medicine. Already there are cancers that have been characterized by specific genetic defects, and patients characterized in terms of response to treatment by specific genetic variations. Such knowledge is being used to design highly specific and individual therapy. Greater understanding of the tumor microenvironment as well as the role that tumor stem cells might play in the initiation, metastasis, and recurrence of cancer has the potential to transform the treatment landscape even further.

For the cancer surgeon there will be a greater requirement to work in a multidisciplinary fashion in patient care. The cancer surgeon will need to play an increasing role in risk assessment, management of genetic screening, and cancer prevention. As a result, cancer surgeons must be well trained in the fundamentals of cancer biology, pharmacogenetics, and genetics. The cancer surgeon must possess experience and skills in the design and management of clinical trials, monitoring of adverse events, and statistical evaluation of endpoints. The types of cancer operations and the scope of surgical resection may also change as molecular techniques enhance oncologic treatment.[48]

The French philosopher Albert Camus said, “Real generosity toward the future lies in giving all to the present.” Care of the patient with cancer is a complex process that requires devotion to the principle that each patient must be provided with the best treatment possible. Surgical oncology is a specialized core body of knowledge that is used to evaluate the best treatment and management options for each patient. The surgical oncologist attends to the future by providing leadership in education and research and forming meaningful partnerships with other oncologic disciplines to continue to provide the best possible patient care.

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