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Bast RC Jr, Kufe DW, Pollock RE, et al., editors. Holland-Frei Cancer Medicine. 5th edition. Hamilton (ON): BC Decker; 2000.

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Holland-Frei Cancer Medicine. 5th edition.

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Chapter 32Principles of Surgical Oncology

, MD, PhD and , MD.

Surgery is the oldest modality of cancer therapy and still forms the mainstay of treatment in solid tumors. It remains a paradigm that more patients are cured by surgery when used as a single treatment, as compared with any other type of cancer therapy. Even in the contemporary multi-modality cancer therapy milieu, it is the rare patient with solid tumor whose care does not include a surgical component. To be maximally effective, the cancer surgeon must function as a member of the oncology team, in which the cancer surgeon is frequently the first oncology specialist that a patient will consult. The cancer surgeon is commonly charged with the responsibility to establish a tissue diagnosis of a suspicious lesion, where it will be a surgical decision whether an operative procedure is needed versus an image-directed or other biopsy approach. The cancer surgeon will usually bear the responsibility for securing diagnostic-quality tumor tissue, establishing the diagnosis, communicating the findings to the patient, completing the procedures needed to stage the patient, and initiating the interaction between the now diagnosed and staged patient and other members of the multi-modality oncology team. Because of these responsibilities, it is most often the cancer surgeon who initially explains to the patient the sequence and rationale of the various treatment components that will be used to manage their specific malignancy. As a result, the cancer surgeon must be aware of the different therapeutic options, the natural history of a given malignancy, and how these factors will be integrated into sequencing the various treatment modalities. It is usually the cancer surgeon’s responsibility to provide initial information about prognosis and make decisions about follow-up care and surveillance to detect tumor recurrence. In these regards, the cancer surgeon is unlike almost any other surgical specialist, in that the commitment to a given patient is both for the acute as well as the long-term components of their disease process.

Over the years, the practice of surgical oncology has come a full circle. Originally, surgeons attempted to treat cancer conservatively by removing only the gross lesion. Unfortunately, this led to unacceptable rates of local recurrence and subsequent patient mortality. In the late 19th century, surgeons began to undertake complete en bloc resections and amputations to treat patients with malignant lesions. These techniques yielded improved results, but the procedures were ablative and mutilating. With the advent of complementary and effective treatment modalities, notably radiation therapy in the 1920s and chemotherapy after the 1940s, the orientation of surgical resection is once again becoming conservative.

Adjuvant chemotherapy, alone or in combination with radiation therapy, has improved disease-free survival and prolonged life for patients who have been rendered free of gross disease by surgery but who still have a high likelihood of recurrence due to microscopic residual metastases. Randomized clinical trials have demonstrated the benefit of adjuvant chemotherapy in a variety of tumors, including breast cancer, colon cancer, osteogenic sarcoma, testicular cancer, ovarian cancer, and certain lung cancers. In some cancers, (e.g., sarcoma), the benefit of adjuvant therapy is modest; however, in other tumor systems, such as testicular and bone cancer, it has resulted in two- and three-fold improved survival rates.

Surgery is most effective in the treatment of localized primary tumor disease and associated regional lymphatics. This is accomplished by en bloc surgical procedures, which attempt to encompass gross and microscopic tumor in all contiguous and adjacent anatomic locations. Intuitively, it appears logical that surgery should have little role in disease management once a neoplasm has spread from the primary location to a distant site. However, prolonged survival is possible following the surgical resection of some metastases in the lung, liver, or brain. For example, a 5-year survival rate up to 40% can be anticipated after surgical resection of solitary colorectal metastasis in the liver.

Surgery operates by zero-order kinetics, in which 100% of excised cells are killed. In contrast, chemotherapy and radiation therapy operate by first-order kinetics, and only a fraction of tumor cells are killed by each treatment. These zero- and first-order processes are complementary. Surgical resection reduces the tumor burden, which hopefully increases the efficacy of nonsurgical adjuvant therapies intended to eliminate microscopic residual disease, thereby decreasing the risk of recurrence.

During the past two decades, major improvements in both operative techniques and in the use of combined modality therapy have significantly reduced the morbidity and mortality associated with the surgical treatment of solid neoplasms. For example, breast-preserving surgery has become an alternative to mastectomy in patients with breast carcinoma, limb salvage is often possible in patients with bone and soft tissue sarcomas, and sexual potency/urinary continence can be preserved for patients with prostate cancer. Because surgery is increasingly combined with other treatment modalities, it is essential that most patients with solid neoplasms have their treatment planned by a multi-disciplinary team, which includes radiation and medical oncologists as well as surgical oncologists. The successful surgical oncologist must be able to coordinate and integrate the efforts of the entire oncologic team if he or she is to retain a primary role in the management of the cancer patient.

Historical Considerations

Oncology (from the Greek words onkos, meaning mass or tumor, and logos, meaning study) is the study of neoplastic diseases. Early authors suggested that certain families, races, and working classes were predisposed to neoplastic transformations. In 1862, Edwin Smith, an American Egyptologist, discovered the apparently earliest recordings of the surgical treatment of cancer.1 Written in Egypt circa 1600 B.C., this treatise was based on teachings possibly dating back to 3000 B.C. The Egyptian author advised surgeons to contend with tumors that might be cured by surgery but not to treat those lesions that might be fatal.

Hippocrates (460–375 B.C.) was the first to describe the clinical symptoms associated with cancer. He advised against treating terminal patients, who would enjoy a better quality of life without surgical intervention.2 He also coined the terms carcinoma (crab legs tumor) and sarcoma (fleshy mass). In the second century A.D., Galen published his classification of tumors, describing cancer as a systemic disease caused by an excess of black bile.3 Galen cautioned that as a systemic disease, cancer was not amenable to cure by surgery, which was often promptly followed by patient death. This strong admonition against surgery persisted for more than 1,500 years until pathologists in the 18th century discovered that cancer often grew locally before spreading to other anatomic sites. Prior to the advent of safe general anesthetics, surgery was used primarily to manage trauma or severe infectious problems, that is, drainage of abscesses. In that era, cancer surgery primarily consisted of amputation or cauterization of surface tumors of the trunk or extremities. Patients were usually unwilling to submit to the pain of tumor surgery, when there was so little likelihood of positive survival impact.

During the 18th and 19th centuries, advances in pathologic techniques led to an increase in autopsies, which, in turn, resulted in a better understanding of human physiology. The early work of Morgagni, Le Dran, and Da Salva established that there was an initial period of local tumor growth prior to distant dissemination. This led to the understanding that not all tumors were systemic, and that certain lesions cause death solely by local invasive growth. Percival Pott (1714–1788) was the first to describe a specific etiologic factor associated with cancer development. In 1775, Pott demonstrated a high incidence of cancer of the scrotum in chimney sweeps who had reached puberty, and recommended wide local resection for cure. In 1829, the French Surgeon Joseph Recamier (1774–1852) first described the complicated process of tumor dissemination. The first recorded elective tumor resection was performed in 1809 by Ephraim McDowell, an American surgeon. He successfully removed a 22-pound ovarian tumor from a patient, who subsequently survived 30 years. McDowell’s work, which included 12 more ovarian resections, stimulated greater interest in elective surgery for cancer patients.

Surgeons were initially hindered by the extreme discomfort that patients experienced during surgical procedures as well as the lack of agents that could reduce the incidence of infection. Crawford Long (1815–1878) was the first to use ether for general anesthesia in 1842, but it was the reported work of John Collins Warren (1778–1856) and William T.G. Morton (1819–1868) that brought the potential of anesthesia to public attention. The surgical procedure in Warren’s first published account of ether anesthesia (1846) was the elective removal of a tongue carcinoma for which submaxillary gland resection and partial glossectomy were performed. Warren was also responsible for the first American-authored textbook of tumor surgery. Entitled Surgical Observations on Tumors, this work was published in 1838. Joseph Lister (1827–1912) was the first to report the successful use of antisepsis during elective surgery. In 1867, Lister applied Pasteur’s concept that bacteria caused infection, when he introduced the use of carbolic acid as an antiseptic agent in conjunction with heat sterilization of surgical instruments. Lister is also credited with the introduction of absorbable ligatures as well as the placement of drainage tubes to control secretions and dead space in surgical wounds. Robert Wood Johnson developed the individual sterile dressing pack in 1876, which also remarkably improved postoperative wound contamination problems.

Even with the advent of antisepsis and general anesthesia, surgical oncology in the second half of the 19th and early 20th centuries was still associated with high patient mortality rates. Cancer was rarely diagnosed in the early stages; consequently, few patients were considered candidates for curative surgery. Those surgeons who did attempt surgical excision of malignant lesions were hindered by poor anesthesia, which was also independently associated with high patient mortality. Antibiotics were not yet available, and surgical instruments were crude. The importance of the microscope to evaluate frozen tissues for surgical margins was not yet appreciated, and surgeons had great faith in their own unaided gross visual assessment of the tumor perimeter. However, several important developments in this era led to rapid advancements in surgical oncology. Emphasizing meticulous surgical technique, gentle tissue handling, and applications of Listerian principles, pioneers such as Albert Theodore Bilroth (first gastrectomy, laryngectomy, and esophagectomy), William Stewart Halsted (en bloc resection, radical mastectomy), as well as many other more contemporary surgeons defined and advanced the boundaries of surgical oncology, as summarized in Table 32.1.2,3

Table 32.1. Landmark Advances in Surgical Oncology.

Table 32.1

Landmark Advances in Surgical Oncology.

Ongoing current surgical innovations continue to advance effective primary tumor control linked to improved surgical outcomes and better quality of life. Advances in microvascular surgery now permit the free transfer of complex autologous tissues, such as free jejunal grafts to reconstitute the upper aerodigestive system or osseomyocutaneous flaps to reconstruct extremities and other mobile body parts such as the jaw. Automatic stapling devices as well as endoscopic instrumentation coupled with high-resolution fiberoptics have remarkably advanced intra-abdominal and pelvic tumor surgery, resulting in less morbid procedures that require significantly less patient recuperation time and effort. Enhanced biomedical monitoring and the emergence of critical care medicine have made it possible to safely undertake increasingly complicated surgical procedures. A more sophisticated awareness of the patterns of tumor progression have made possible less invasive surgical approaches. Examples include sentinel node biopsy as a replacement for formal lymphadenectomy in early stage carcinoma of the breast, and the introduction of radiofrequency ablation with ultrasound guidance which has markedly enhanced surgical cancer control of multi-focal liver disease while minimizing patient morbidity.

The Contemporary Role of Surgical Oncology

Surgical oncologists are surgeons who devote most of their time to the study and treatment of malignant neoplastic disease. They must possess the necessary knowledge, skills, and clinical experience to perform both the standard as well as extraordinary surgical procedures required for patients with cancer. Surgical oncologists must be able to diagnose tumors accurately and to differentiate aggressive neoplastic lesions from benign reactive processes. In addition, surgical oncologists should have a firm understanding of radiation oncology, medical oncology, and hematology. They must also be capable of organizing interdisciplinary studies of cancer. Surgical oncologists should be trained in pathology as well, since they will be called on to excise appropriate tumor samples for pathologists and make decisions about adequacy of surgical margins. Surgical oncologists have a shared role with medical oncologists as the “primary-care physicians” of cancer treatment. Almost all cancer patients will initially be managed by one of these two specialists who will bear the ultimate responsibility for coordinating appropriate multi-modality care for the individual patient.

Not surprisingly, given the complexity of contemporary multi-disciplinary approaches to the cancer patient, free-standing cancer centers have developed facilities to provide the needed planning expertise, clinical care, patient support services, and access points to clinical trials. Cancer center professional staff share the exclusive goal of eradicating neoplastic disease. Comprehensive cancer centers are frequently (but not invariably) affiliated with academic medical institutions and offer the complete spectrum of oncology therapies, clinical trials, rehabilitation and social services, as well as basic and translational research programs to move new knowledge from the laboratory bench to the patient bedside. In this contemporary milieu, the role of the surgical oncologist has expanded while the overall impact of noncancer surgical specialists has declined.

Surgical oncology, per se, is more of a cognitive than a technical surgical specialty. With the exception of a small cluster of index operations, such as regional pancreatectomy, limb salvage and retroperitoneal sarcoma surgery, isolated limb perfusion, and multi-segment liver resection, most of the surgical procedures that are performed by surgical oncologists are similar to those performed by a surgeon not oncologically trained. What frequently differentiates these two types of surgeons is not merely knowledge about how to do a specific operation, but an awareness of how and when to do that operation, that is, the cognitive knowledge of contemporary multi-modality cancer care. In addition to understanding chemotherapy, radiotherapy, immunotherapy, clinical trials, and cancer prevention, surgical oncologists have a focused knowledge of cancer in its presenting and recurring forms. A solid knowledge of cancer biology, including an awareness of the molecules driving tumor proliferation and dissemination, is also part of the special cognitive database of the surgical oncologist.

As part of the larger surgical community, the surgical oncologist is a critical conduit of cancer information to colleagues in general surgery. This function is performed by academic presentations at large surgical meetings, such as those of the American College of Surgeons or the Society of Surgical Oncology, as well as by service in directing hospital-based tumor boards and direct consultation for individual cancer patients. Because of their leading role in early diagnosis of cancer, it is not surprising that surgical oncologists are also frequently in leadership roles in cancer prevention and screening programs. Nationally based multi-modality clinical trial groups also depend on surgical oncology expertise to help in trial design, establish criteria of surgical quality control, educate trial participants regarding standards of surgical care (including indications for procedures), as well as assistance in accurate data collection, analysis, and presentation of trial results.

Combined Modality Therapy

Pediatric oncologists pioneered the use of combined modality therapy (radiation in combination with chemotherapy and surgery) to effectively manage childhood neoplasms. Control of localized retinoblastoma in children has been dramatically increased using multi-modality therapy (see Chapter 139). The cure rate for patients with Wilms’ tumor is 75%, if surgical therapy is followed by radiation and chemotherapy, an increase of 40% over operation alone. Embryonal rhabdomyosarcoma responds best to combinations of radiation, chemotherapy, and operation.

Until recently, the effectiveness of multi-modality therapy was only occasionally demonstrable for adult neoplasms. A striking example is the approach to skeletal and soft tissue sarcomas (see Chapters 121 and 122). Surgical therapy, the accepted method for local management of most skeletal and soft tissue sarcomas of the extremities, has been associated with frequent treatment failure, if used alone. In the past, approximately 50% of patients with soft tissue sarcomas and 80% of those with bone sarcomas eventually succumbed to distant metastases, even after amputation of the extremity bearing the primary tumor. Multi-modality treatment regimens were developed to improve these results. Preoperative therapy with intra-arterial doxorubicin followed by radiation resulted in extensive tumor cell necrosis in as many as 75% of patients.4 The effectiveness of this preoperative therapy permitted local resection of the sarcoma and salvage of a viable functional extremity. Local recurrence rates were as low as with amputation, and long-term results were functionally and psychologically superior. In addition, there was no decrease in survival rate.

Multi-modality therapy may also be effective for small, localized breast cancers. In several studies, radiation and minimal surgery were as effective as mastectomy in the control of small breast cancers. Survival and local recurrence rates were the same for both groups, and patients treated with multi-modality therapy were spared the physical deformity and psychological problems of mastectomy (see Chapter 118).

An emerging component of the multi-modality approach is tumor immunotherapy. The concept of immunostimulation with biologic response modifiers or nonspecific immunomodulators is not new in cancer therapy. Nearly a century ago, William B. Coley developed the basis for nonspecific cancer immunotherapy using mixed bacterial vaccines (Coley’s toxin). Since then, whole cell or cell fragment tumor vaccines have been introduced for active specific immunotherapy of neoplastic disease, and some of these have reached phase III clinical trials (see Chapter 61). In melanoma, which is the focus of most cancer vaccine research, immunochemotherapy is now used as an adjuvant to surgery for local and regional neoplastic disease, as well as to prolong the survival of patients with distant metastases (see Chapter 120). Cytokines, such as interferon, are being used to modulate the immune response (see Chapter 62) and have proved effective in some diseases, such as myeloid leukemia (see Chapter 125) and hairy cell leukemia (see Chapter 128). Use of the colony-stimulating factor (CSF) is invaluable in accelerating hematopoietic recovery from high-dose chemotherapy as well as in conjunction with bone marrow transplantation protocols.

In selecting appropriate therapy, surgery and radiation are still the most successful means of treating cancer localized to the primary site and/or regional lymph nodes. Since these forms of therapy exert their effects locally, neither is usually considered curative once the disease has metastasized beyond the loco-regional site. However, both methods are frequently useful as palliative treatments, and occasional long-term survival follows surgical resection of single-organ metastases.

Unlike surgery and radiation therapy, chemotherapy and other systemic therapies, such as immunotherapy, hormonal therapy, and cytokines, are treatments that can kill tumor cells that have already metastasized to distant sites. These systemic modalities have a greater chance of curing patients who have minimal tumor burden, as compared with those with clinically evident disease. Consequently, surgery and radiation therapy may be useful in decreasing a given patient’s tumor burden, thereby maximizing the impact of subsequent systemic therapy.

Whether the goals of therapy should be cure or palliation depends on the stage of a specific cancer. If the cancer is localized without evidence of spread, the goal is to eradicate the cancer and cure the patient. When the cancer has spread beyond local cure, the goal is to control symptoms and maintain maximum activity and quality of life for as long as possible. Patients are generally judged incurable if they have distant metastases or evidence of extensive local infiltration of critical adjacent structures. However, some patients are potentially curable even though they have distant metastases. For example, patients with solitary pulmonary, hepatic, or cerebral metastases may still be curable by resection, and patients with widespread choriocarcinoma metastases may still be cured using chemotherapy. Histologic proof of distant metastases should be obtained before the patient is deemed incurable. Occasionally, an exploratory celiotomy or thoracotomy may be necessary to determine the histology of ambiguous lesions in the lungs or liver. In rare situations, the clinical situation may point so overwhelmingly to distant metastases that the patient may be considered incurable without biopsy. For each anatomic site, there are certain local criteria that place the patient unequivocally in an incurable status, whereas other anatomic constraints may imply a poor prognosis but are not an absolute indication of incurability per se. In equivocal situations where extensive studies fail to demonstrate metastatic or incurable local extension, the patient deserves the benefit of the doubt and should be treated for cure.

The selection of therapeutic modalities depends not only on the type and extent of cancer, but also on the patient’s general condition and the presence of any coexisting disease. For example, surgery may be contraindicated in a patient who has had a recent myocardial infarction. A patient with pre-existing diabetes will be much more susceptible to the toxic effects of hormonal therapy with corticosteroids. Renal disease may increase the toxicity of some of the chemotherapeutic agents, such as methotrexate or ifosfamide. In addition, acute or chronic infection or bleeding may make any form of cancer therapy dangerous and must be addressed before initiating definitive oncology treatment.

The patient’s psychologic make-up and life situation also must be considered. A patient who is unable to accept the realities of a given treatment should be offered other treatment options, if possible. Consultation with a psychiatrist experienced in cancer (a psycho-oncologist) may help the patient deal with the reality of the disease and its treatment (see Chapter 69). This is particularly true for surgical procedures that significantly alter the patient’s appearance, such as mastectomy, or those that involve a change of organ function, such as colostomy. Experimental forms of therapy should also be avoided in some patients whose potential noncompliance might jeopardize both themselves as well as the clinical trial. For example, patients who are unwilling to tolerate the inconvenience of an intra-arterial catheter (and might therefore remove it themselves) should not undergo treatment that depends on this form of angioaccess.

Extensive staging procedures may indicate that a tumor is localized to a primary site and/or regional lymph nodes. This malignancy may be curable by local therapy (either surgery or radiation). However, about 60% of localized malignant tumors ultimately recur, suggesting that such patients must have had subclinical metastases at the time of initial diagnosis. The probability of cure may be improved if systemic approaches are coupled with the local treatments. Chemotherapeutic drugs must be given when the number of tumor cells is low enough to permit their destruction at doses that can be tolerated by the patient. The opportunity for cure is most likely during the early stage of disease or immediately after surgery when the tumor burden has been minimized. Adjuvant chemotherapy has significantly improved surgical results, primarily due to cytocidal effects on clinically undetectable neoplastic cells outside the operative field. Neoadjuvant or induction chemotherapy that is initiated prior to local and regional treatments also can affect micrometastatic distant disease while significantly damaging the primary tumor. After a course of neoadjuvant chemotherapy, the tumor may be surgically resected with or without concomitant preoperative or postoperative radiotherapy.

Classically, surgery has been first in the sequence of therapies for solid neoplasms, but increasing evidence suggests that it should be the last. Chemotherapy and radiation therapy both work by first-order kinetics. However, due to tumor cell heterogeneity, it can be anticipated that resistant clones of viable neoplastic cells will persist in the primary tumor after these therapies. Such clonal heterogeneity is more likely in large tumors that are both poorly perfused by chemotherapeutic agents and are also relatively hypoxic and therefore resistant to radiation therapy. Since surgery works by zero-order kinetics, it effectively removes the local residual primary tumor cells that are resistant to these other modalities. In addition, this sequence of preoperative therapies can cause shrinkage of tumor mass due to the destruction of chemo- and radiosensitive tumor cells. The frequent possibility of less ablative surgery resulting in tissue (and function) preservation is a major dividend of this preoperative cytoreduction by neoadjuvant treatment. There have been promising results from clinical trials that have applied these concepts in bone and soft tissue sarcomas, locally advanced breast cancer, and other neoplasms.

A growing neoplasm can evade immune attack by producing specific and nonspecific immunosuppression.5 Specific immunosuppression can be caused by antigens shed from the tumor into the blood. These antigens, which circulate alone or as antigen-antibody complexes, can inhibit the lymphocyte-mediated destruction of tumor cells in vitro and may play a similar role in vivo.6 Nonspecific or generalized immunosuppression is attributed to humoral factors produced by or in response to the neoplasm. Any therapeutic maneuver that lowers tumor burden may reverse specific and nonspecific immunosuppression, thereby altering the immune balance in favor of the patient (Figure 32.1).5 In this respect, cancer surgery is immunotherapy, in that it effectively removes the immunosuppressive cancer cell mass. Once the tumor mass has been removed, the patient’s immune system then may be able to destroy subclinical micrometastases. This premise suggests that local disease should be considered a manifestation of systemic illness, whether or not the patient has clinically overt metastases. Surgery for apparently localized tumors can favorably affect the host-tumor relationship and may even cure the patient with subclinical distant metastases.

Figure 32.1. The four mechanisms for dissemination of cancer cells from a malignant tumor.

Figure 32.1

The four mechanisms for dissemination of cancer cells from a malignant tumor. (From Cole et al. with permission.)

Cancer Management

Prevention

The old adage that “an ounce of prevention is worth a pound of cure” certainly applies to solid tumor oncology. As the role of genetic mutations that predispose to subsequent cancer development is established, one can anticipate that prophylactic surgery will be extended to encompass these conditions. In these situations, it is imperative that the surgical oncologist becomes intimately knowledgeable about the indications, limitations, and ethical considerations regarding genetic counseling, if only because it will be the responsibility of the surgeon to alert other family members at risk and arrange for appropriate testing.

The above emerging indications are being added to the already established role for prophylactic surgery in conditions such as cryptorchidism associated with subsequent testicular carcinoma, longstanding ulcerative colitis or familial polyposis associated with colon carcinoma, multiple endocrine neoplasia syndromes associated with the development of medullary carcinoma of the thyroid, and oral leukoplakia associated with subsequent development of squamous cell carcinoma. Assessing the risk: benefit ratio of prophylactic surgery is critical yet is frequently difficult to accomplish with precision. With the future advent of inexpensive and reliable genetic screening technologies, coupled with emerging insights derived from the new field of molecular epidemiology, one can anticipate remarkably more unequivocal definitions of the benefits of prophylactic surgery in cancer prevention for populations at risk.

Biopsy Diagnosis of Tumors

The diagnosis of solid tumors depends on locating and performing a biopsy of the lesion. Biopsy evidence will be used to determine the histology and/or grade of a tumor, which is a prerequisite for planning definitive therapy. Significant therapeutic errors have been made when biopsy confirmation of malignancy was not obtained prior to treatment, as in the radical mastectomies that were performed for nodular fat necrosis. Even when biopsy reports from another hospital are available, the slides of the previous biopsy must be obtained and reviewed prior to the institution of therapy. This is essential because not infrequently (and particularly in rare neoplasms) an erroneous interpretation may have been made in the initial pathology assessment.

Biopsy is easiest when the tumor is near the surface or involves an orifice that can be examined with appropriate visualizing instruments, such as the bronchoscope, colonoscope, or cystoscope. Carcinomas of the breast, tongue, or rectum can be seen or palpated and a portion can be excised for definitive diagnosis. In contrast, deep-seated lesions may grow to quite a large size before causing symptoms. Ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) are all useful techniques for localizing such lesions at the time of invasive biopsy. However, while image-directed needle biopsy may be useful in some patients, exploratory surgery is often required to obtain a definitive biopsy that establishes the exact histologic diagnosis. Fortunately, such procedures can now be frequently performed on an outpatient basis, using minimally invasive technology, such as laparoscopic surgical approaches.

Three methods are commonly used to biopsy suspicious lesions; these include needle biopsy and open incisional or excisional biopsy. Regardless of the method used, the pathologic interpretation of the tumor mass will be valid only if a representative section of tumor is obtained. The surgical oncologist must be aware that a sampling error can occur with needle and incisional biopsies where only small portions of the total tumor mass is submitted for pathologic examination. It is the surgeon’s task to provide adequate tissue for diagnosis. Orientation of the specimen, as may be necessary, is also the responsibility of the surgeon. It is axiomatic that adequate tissue can provide the basis for diagnosis by an adequate pathologist, whereas inadequate tissue will be insufficient for diagnosis by an adequate or inadequate pathologist.

Fine-needle aspiration (FNA) is a cytologic technique in which cells are aspirated from a tumor using a needle and syringe with the application of negative pressure. The technique can also be performed using image-directed guidance and is particularly helpful in the diagnosis of relatively inaccessible lesions, such as deep visceral tumors. The aspirated tissue consists of disaggregated cells rather than intact tissue. Diagnosis of malignancy, therefore, usually depends on detection of abnormal intracellular features, such as nuclear pleomorphism, and so the margin of error is higher than with other biopsy techniques. In addition, because of the lack of intact tumor architecture, FNA cannot distinguish invasive from noninvasive malignancy. Consequently, other types of biopsy may be more appropriate, depending on the clinical context, such as distinguishing carcinoma in situ from an infiltrating malignancy.

Cutting core biopsy is the simplest method of pathologic (as opposed to cytologic) diagnosis and may be useful for biopsy of subcutaneous masses, muscular masses, as well as some internal organs, such as liver, kidney, and pancreas (Figure 32.2). The added benefit is that this method is inexpensive and causes minimal disturbance of the surrounding tissue. Cutting core biopsies are performed with a large-bore needle, such as the Vim Silverman or Tru Cut type. This technique retrieves a small piece of intact tumor tissue, which allows the pathologist to study the invasive relationship between cancer cells and the surrounding microenvironment. The danger of implanting tumor cells in a needle track during biopsy is extremely small. This risk can be avoided altogether if the needle track is positioned so that it can be excised en bloc at the time of the definitive surgical procedure. Needle biopsy may be less appropriate if the specimen is small, which increases the likelihood of the needle missing the lesion or the biopsy not being representative of the entire tumor. Consequently, a needle biopsy report that is negative for malignant disease should be viewed with skepticism if it is inconsistent with the clinical presentation and should be followed by incisional or excisional biopsy.

Figure 32.2. Laparoscopic ultrasound of dome of liver with cutting needle biopsy prior to resection of hepatic colorectal metastases.

Figure 32.2

Laparoscopic ultrasound of dome of liver with cutting needle biopsy prior to resection of hepatic colorectal metastases. Note ultrasound unit in left lower foreground, percutaneously placed biopsy needle in the liver, and diaphragm in the background. (more...)

Incisional biopsy for pathologic examination involves removal of a small portion of the tumor mass. It is best performed under circumstances where the incisional wound can be totally excised in continuity with the definitive surgical resection, in the event that any tumor cells are spilled at the time of biopsy. Incisional biopsy is indicated for deeper subcutaneous or intramuscular tumor masses when initial needle biopsy fails to establish a diagnosis. Incisional biopsy includes the instrument removal of tumor portions during endoscopic examination of the bronchus, esophagus, rectum, or bladder, and also includes suction or currettage of the endometrium as well as laparoscopic biopsy.7

An incisional biopsy is also indicated when a tumor is so large that total local excision would violate wide tissue planes and negatively impact on a subsequent wide local resection for curative purposes. If possible, an incisional biopsy should retrieve a deep section of tumor as well as a margin of normal tissue. Incisional biopsies suffer from the same disadvantages of needle biopsies, in that the removed portion may not be representative of the entire tumor. Consequently, a negative biopsy does not preclude the possibility of cancer in the residual mass.

Excisional biopsy completely removes the local tumor mass. It is used for small, discrete masses that are 2 to 3 cm in diameter, where complete removal will not interfere with a subsequent wider excision that may be required for definitive local control. Excisional biopsy allows the pathologist to examine the entire lesion. However, this method is contraindicated in large tumor masses because the biopsy procedure could scatter tumor cells throughout a large surgical field that would need to be widely and totally encompassed by the ultimate surgical resection. For this reason, excisional biopsy is usually contraindicated for skeletal and soft tissue sarcomas, whereas it is very useful for superficial squamous or basal cell carcinomas or malignant melanomas.

The excisional method is also used for polypoid lesions of the colon, for thyroid and breast nodules, for small skin lesions, and when the pathologist cannot make a definitive diagnosis from tissue removed by incisional biopsy. An unbiopsied lump is also surgically removed when the suspicious character of the lesion, the need for its removal (whatever the diagnosis), and the nonmutilating nature of the operation render such an approach feasible. Examples of such procedures include hemithyroidectomy for thyroid nodules and a right hemicolectomy for a cecal mass that might be either inflammtory or neoplastic. In the latter instance, colonoscopic biopsy is informative, only if positive for neoplasm.

Surgeons should always mark the excisional biopsy margins with sutures or metal clips so that if removal is incomplete and further excision is needed the margin of previous excision can be properly located. Orientation of biopsy incisions is also extremely important. Ill-conceived incisions can unnecessarily open up additional tissue planes, necessitating subsequent wider radiotherapy fields or more extensive ultimate surgical resections. Tumors of the extremities are best biopsied using incisions that run parallel to the long axis of that limb. This will facilitate a definitive en bloc resection that encompasses the biopsy track. Biopsy incisions should be closed using meticulous hemostasis because a hematoma can lead to widespread infiltration of tumor cells with contamination of tissue planes. Instruments, gloves, gowns, and drapes should be discarded and replaced with unused substitutes, if the definitive surgical resection immediately follows the biopsy procedure.

Lymph nodes should be carefully selected for biopsy. Axillary nodes may be preferable to groin nodes if both are enlarged due to a decreased likelihood of postoperative infection. Other caveats are also noteworthy. For example, lymph node specimens preserved in formaldehyde cannot be analyzed for cytogenetics. The laboratory work-up for lymphoma usually requires sterile tissue. Cervical lymph nodes should not be biopsied until a careful search for a primary tumor has been made using nasopharyngoscopy, esophagoscopy, and bronchoscopy. Enlargement of the upper cervical nodes by metastases is usually caused by laryngeal, oropharyngeal, and nasopharyngeal primary neoplasms. In contrast, supraclavicular nodes are more frequently enlarged due to metastases from primary tumors of the thoracic or abdominal cavities or breast.

The tumor specimen may be prepared for pathologic examination by either frozen or permanent section. Frozen sections are made at the time of biopsy, and pathologic diagnosis can be obtained within 10 to 20 minutes. Frozen sections are used when the diagnosis is required to assess resectability at the time of major surgery, or to check tumor margins intraoperatively. Frozen section biopsy–proven carcinomatosis may mandate abandoning a procedure with a curative intent in favor of a palliative approach. Occasionally, mediastinoscopy, laparoscopy (peritoneoscopy), thoracoscopy, exploratory thoracotomy, or even laparotomy is necessary to obtain adequate representative tissue samples for microscopic examination to confirm diagnosis or tumor stage.

Staging

Tumor staging is a system used to describe the anatomic extent of a specific malignant process in an individual patient. Staging systems cluster relevant factors about the primary tumor, such as size and grade, as well as information about dissemination to regional sites, such as lymph nodes or distant metastatic loci. Accurately staging a cancer is absolutely essential in designing an appropriate therapeutic program and advising about prognosis. Without acurate staging, it is not possible to compare meaningfully the results of therapies administered in different centers. New forms of therapy can be appropriately evaluated only by comparison with the impact of current therapy of neoplasms of equivalent stage.

The recognized importance of staging has led to a variety of international and national attempts to standardize the staging of the patient with cancer. To date, no single system has been universally accepted. The American Joint Committee on Cancer (AJCC) has recommended a staging system ranging from stage I (small, localized carcinoma ) to stage IV (distant metastatic spread). Both the AJCC and the Union Internationale Contre Cancer (International Union Against Cancer, UICC) have adopted a TNM system that defines a cancer in terms of the primary tumor (T), the presence or absence of nodal metastases (N), and the presence or absence of distant metastases (M). Increasing numerals after the T, such as T1, T2, T3, or T4, indicate lesions of increasing size that are usually associated with a poorer prognosis. The absence of nodal metastasis is designated as N0, the presence of nodal metastasis is N1, and for more extensive nodal involvement, additional numbers may be used. Finally, distant metastases are indicated by adding the numeral 1 following M for metastases, or the numeral 0 signifying their absence. Thus, a small lesion that has neither spread to regional nodes nor metastasized to distant sites would be designated as T1 N0 M0. A larger lesion that involved regional nodes but not distant sites might be identified as T2 N1 M0. A large neoplasm associated with both regional and distant metastases would be designated T3 N1 M1. For some tumor types, such as soft tissue sarcoma, a G for grade of malignancy is added. High-grade tumors are less-differentiated and tend to metastasize sooner.

The TNM system has four chronologic classifications.8 The clinical classification (cTNM or TNM) represents the extent of the disease prior to first definitive treatment, as determined from physical examination, imaging studies, endoscopy, biopsy, surgical exploration, and any other relevant findings. The pathologic classification (pTNM) incorporates the additional information available at the time of surgery or derived from pathologic examination of a completely resected specimen. This is especially useful in planning adjuvant therapy. The re-treatment classification (rTNM) is used to stage a cancer that has recurred after a disease-free interval; it includes clinical and/or pathologic evidence of recurrence. Finally, the autopsy classification (aTNM) is based on postmortem examination.

Surgical Therapy

Preoperative Preparation

The preoperative patient is frequently in relatively poor physical condition. Many malignant tumors have toxic effects on the host that are disproportionate to the size of the lesion. Patients may have a poor nutritional status because of interference with normal alimentary function, as is often encountered with cancers of the mouth, pharynx, esophagus, intestinal tract, and appended glandular organs, such as the pancreas. Pain may contribute to anorexia and consequent severe electrolyte disorder. Every effort should be made to correct nutritional deficiencies, restore depleted blood volume, and correct hypoproteinemia prior to extensive surgical procedures. Total parenteral nutrition (TPN) can be used to prepare the malnourished patient for a major operation, although reconstitution is a slow process, and TPN may chiefly serve to interrupt further deterioration by restoring positive nitrogen balance (see Chapter 141). Surgical morbidity and mortality following extensive cancer operations will predictably be excessive if critical physiologic and biochemical deficiencies are not first corrected.

Determining the risk inherent in a given operation is a complicated and inexact assessment based on a number of factors. The physical status of the patient, including cardiopulmonary reserve, comorbid conditions, debility inherent to a specific operation, hepatic and renal function, and the intent of surgical procedure (curative versus palliative) are all pertinent to this assessment. The technical complexity of an operation, the type of anesthetic used, and the relative experience of the involved health-care personnel can all impact on the complications of a procedure. Various schema for risk assessment, such as the five-level physical status classification of the American Society of Anesthesiologists (Table 32.2) and the Eastern Cooperative Oncology Group five-step performance scale (Table 32.3) may be useful in assessing the utility of a given operation for a specific patient.

Table 32.2. American Society of Anesthesiologists: Physical Status Classification.

Table 32.2

American Society of Anesthesiologists: Physical Status Classification.

Table 32.3. Eastern Cooperative Oncology Group: Performance Scale and Corresponding Karnofsky Rating.

Table 32.3

Eastern Cooperative Oncology Group: Performance Scale and Corresponding Karnofsky Rating.

Operative mortality is defined as mortality that occurs within 30 days of an operative procedure. In cancer patients, the underlying disease is a major determinant of operative mortality. While it is true that comparable operations are usually more morbid in the geriatric age group as compared with other adults, advanced age per se should not disqualify patient from a potentially curative surgical procedure. Because of their high-risk nature, decisions about the indications for palliative surgical procedures are particularly difficult. For example, palliative surgery in the contexts of florid metastatic disease or to relieve patients who are suffering from intestinal obstruction secondary to carcinomatosis has a 20 to 30% perioperative mortality. In such circumstances, the risk:benefit ratio and ultimate surgical objectives must be defined as clearly as possible and accepted by patient, family, and surgeon.

Patterns of Tumor Spread

In general, a malignant tumor may spread (1) by infiltrating surrounding tissue, (2) via the lymphatics, (3) by vascular invasion, or (4) by implantation in serous cavities. However, many cancers spread by more than one route, and an orderly course of metastasis is not predictably certain. For example, patients with breast cancer or melanoma can manifest distant metastatic disease in the lungs, liver, or skeleton without ever developing evidence of lymph node metastases. Metastatic patterns of various human tumors are summarized in Table 32.4.

Table 32.4. Patterns of Neoplastic Spread for Common Human Cancers.

Table 32.4

Patterns of Neoplastic Spread for Common Human Cancers.

Cancer cells may also spread by direct extension through tissue spaces. Some neoplasms, such as soft tissue sarcomas and adenocarcinomas of the stomach or esophagus, may extend for a considerable distance (10 to 15 cm) along tissue planes beyond the palpable tumor mass. Other neoplasms, such as a basal cell carcinoma of skin, rarely extend for more than a few millimeters beyond the visible margin. Even though most central nervous system (CNS) tumors infrequently metastasize, they may penetrate nearby brain tissue, and their location can cause death by interfering with vital CNS functions.

Tumor cells can readily enter the lymphatics and extend through these channels by permeation or embolization to the lymph nodes. Permeation is the growth of a colony of tumor cells along the course of the lymphatic vessel. This commonly occurs in the skin lymphatics in carcinoma of the breast and in the perineural lymphatics in carcinoma of the prostate.Lymphatic involvement is extremely common in epithelial neoplasms of all types, except basal cell carcinoma of the skin, which metastasizes to regional lymphatics in less than 0.1% of cases, or mesenchymal neoplasms, such as sarcomas, which metastasize to lymph nodes in only 2 to 5% of cases.

Spread along the lymphatics by embolization to regional or distant lymph nodes is of great clinical importance. Tumor cells travel within anastomosing lymphatics and can spread to proximal nodal basins via the collateral lymphatic channels. Lymph node metastases are first confined to the subcapsular space; at this stage, the node is not enlarged and may appear normal to the naked eye. Gradually, the tumor cells permeate the sinusoids and replace the nodal parenchyma. There is little direct spread from node to node, because the nodal capsule is not penetrated until a late stage. However, when an involved lymph node is more than 3 cm in diameter, tumor has usually extended beyond the capsule into the perinodal fat, indicating an ominous prognosis.

Lymph from the abdominal organs and lower extremities drains into the cisterna chyli and then into the thoracic duct, which finally opens into the left jugular vein. Using this route, tumor cells can pass freely from the lymphatic system into the bloodstream. Oncologists originally believed that solid neoplasms first involved regional lymph nodes and then spread into the bloodstream by drainage into the thoracic duct and then to other parts of the body. An alternative explanation now favored by most oncologists assumes that the presence of cancer cells in regional lymph nodes indicates an unfavorable host-tumor relationship and the concomitant high likelihood of distant (albeit subclinical) metastases.

Cancer cells may reach the bloodstream either through the thoracic duct or by direct invasion of blood vessels. Capillaries offer no resistance to tumor cell transgression. Small veins are frequently invaded, whereas thicker-walled arteries are rarely violated. Veins frequently form a plexus extending to the subendothelial regions, which provide a portal of entry through the thin vein wall. When the vascular endothelium is destroyed, a thrombus can form that is quickly invaded by tumor. This combination of thrombus and tumor may detach to form large tumor emboli. Vascular invasion is common in both carcinomas and sarcomas and is associated with a poor prognosis. Some types of neoplasms have a remarkable tendency to grow as a solid column along the course of veins. For example, renal cell carcinoma can grow into the renal vein and up the inferior vena cava extending to the right atrium. In this situation, a spectacular en bloc removal requiring cardiopulmonary bypass may still result in long-term survival or even cure.

Tumor cells occasionally gain entrance to serous cavities by growing through the wall of an organ. Many tumor cells can grow in suspension without a supporting matrix and may widely spread within the peritoneal cavity or attach to serous surfaces. Thus, widespread peritoneal seeding is common with gastrointestinal neoplasms and ovarian tumors. Similarly, malignant gliomas may spread widely within the CNS via the cerebrospinal fluid.

Host Response to Tumor Invasion

Although much is known about the routes of tumor spread, the mechanisms underlying this process remain unclear. Some cancers are metastatic at the time of clinical discovery, whereas others of the same type and in the same organ tissue may remain localized for years. Metastases may dominate the presenting clinical picture while the primary tumor remains latent and asymptomatic or even undetectable. For example, cerebral metastases from silent cancers in the bronchus or the breast are often mistaken for primary benign CNS neoplasms.

A surgical oncology resection is designed to remove the primary neoplasm and the usual contiguous lymphatic and vascular routes of tumor spread with the intent to ablate every cancer cell in the body. According to this view of surgical therapy, cure is achieved by the mechanical removal of all cancer cells. However, cancer cells are frequently found in operative wound washings or in the drainage from postoperative wounds. In that many of these patients never develop recurrent cancer, host immune defenses must be effective in destroying any tumor cells missed at the time of resection.5,9 Similarly, the demonstrably viable tumor cells that are frequently found in the blood or lymphatics of cancer patients seldom lead to metastatic implants.

Prolonged remission is also evidence of effective immune defenses. Rapidly progressive cancer sometimes recurs 10 or more years after successful treatment of the primary tumor. During the preceding long period of clinical remission, the growth of tumor cells has presumably been inhibited by host defenses. Host immune mechanisms may also have a role in the salvage of patients undergoing resection of metastases in distant organs, such as the lung or liver. It is likely that these patients have other subclinical metastases, which presumably are destroyed by host immune mechanisms in that subset of post-resection patients who subsequently become disease-free long-term survivors.

There is a correlation between cell-mediated immunologic reactivity and the postoperative course of cancer patients.10,11 In one study, only 72% of all potential candidates for definitive cancer surgery were able to be sensitized to dinitrochlorobenzene (DNCB), whereas the remaining 28% exhibited cutaneous anergy to this chemical.12 More than 95% of the anergic patients either were found to have inoperable disease because of local or metastatic spread or developed recurrent disease within 6 months of surgical resection. In contrast, 84% of the DNCB-reactive group had localized tumors that could be resected, and these patients remained free of disease for at least 6 months following surgery.

The immunosuppression caused by cancer appears to be the result of humoral factor(s) released by the cancer cell or secondary to the host response to the invasive cancer process. Lymphocytes from cancer patients exhibit depressed functions as compared with those from normal individuals, and the degree of depression correlates with the extent of the cancer.13,14 Serum factors derived from cancer patients can inhibit the in vitro function of normal lymphocytes. These factors undoubtedly contribute to the immunosuppression observed in cancer patients.15,16

Operative Considerations

Once a decision has been made to proceed with surgical therapy, the operative procedure itself must be carefully planned for the specific surgical patient. It is essential to realize that the best (and often the only) opportunity for cure is with the first resection, at the time of initial tissue plane, lymphatic, and blood vessel potential exposure to tumor cells that may be dislodged within the operative field (Figure 32.3). A subsequent recurrence may be difficult to distinguish from the normal postsurgical inflammatory reaction and scarring.

Figure 32.3. The seeding of cancer cells during operative procedure.

Figure 32.3

The seeding of cancer cells during operative procedure. (From Cole et al. with permission.)

When a preliminary biopsy has been performed, the entire operative field should be re-prepared after the biopsy incision is closed. The risk of implanting cancer cells into the wound is greatly increased if the tumor is inadvertently entered during an operative procedure with curative intent. Should this happen, the cut surface of the tumor must be electrocauterized and isolated from the remainder of the wound. Only then can the operation continue, preferably through a new plane of dissection that allows a much wider margin around the tumor. Many different cytotoxic preparations, such as sodium hypochlorite solution, nitrogen mustard, and thiotepa, have been used to irrigate the wound following cancer surgery in an effort to sterilize the operative site. None has proven to be effective in decreasing local recurrence rates, with the exception of 0.5% formaldehyde that is useful in preventing local recurrence in carcinoma of the cervix.

Local recurrence is an unfavorable prognostic factor and is usually, although not invariably, associated with systemic disease. For all types of malignancy, approximately 20% of patients whose local recurrence can be widely resected survive at least an additional 5 years. Local recurrence can occur despite every effort to isolate the tumor or avoid spilling cancer cells into the operative field. For example, malignant cells in local lymphatics may be unrecognized at the time of the initial operation, or blood-borne cells may implant into the fresh wound. Manipulation of the tumor at any time during the surgical procedure can greatly increase the number of cancer cells recovered from the bloodstream. Likewise, it is also important to use an appropriately large incision so as to minimize unnecessary manipulation of the tumor. There have been reports of a correlation between the presence of tumor cells in the bloodstream during the operative procedure and local recurrence. This possibility could be secondary to perioperative tumor cell implantation, which, in turn, may be facilitated by immunosuppression induced by surgery and anesthesia.17

Types of Cancer Operations

Wide local resection with removal of an adequate margin of normal peritumoral tissue may be adequate treatment for low-grade neoplasms that very rarely metastasize to regional nodes or widely infiltrate adjacent tissues. Basal cell carcinomas and mixed tumors of the parotid gland are examples of such tumors. In contrast, neoplasms that spread widely by infiltration into adjacent tissues, such as soft tissue sarcomas and esophageal and gastric carcinomas, must be excised with a wide margin of normal tissue. This wide tissue margin between the line of excision and the tumor mass may also act as a protective barrier against intraoperative tumor cell traversal into severed lymphatics and vessels. Tumor cells may have been implanted in the incision when an incisional biopsy alone had been previously performed. To encompass potentially contaminated tissues, it is therefore extremely important to remove a wide segment of skin and underlying muscle, fat, and fascia to extend beyond and encompass the limits of this original incision.

Malignant neoplasms are usually not truly well encapsulated. The tumor is commonly encased by a pseudocapsule which is composed of a compression zone of normal tissue interspersed with neoplastic cells. This pseudoencapsulation offers a great temptation for simple enucleation, in that the tumor may be easily dislodged from its bed. However, this approach must be resisted because microscopic extensions of tumor from the primary through the pseudocapsule will be left behind after simple enucleation, dooming the patient to a local recurrence. Ideally, the surgeon should operate through normal tissues at all times and never encounter or even directly visualize the neoplasm during its removal. Dissection should proceed with meticulous care to avoid tumor cell spillage. Surprising amounts of skin, subcutaneous fat, and muscle can usually be sacrificed with little functional loss. However, tumor involvement of major vessels, nerves, joints, or bones may require sacrifice of these structures. Occasionally, even amputation may be necessary as an initial surgical procedure, if a curative result is to be obtained. The extent of operation must be based solely on the extent of resection needed to achieve negative margins and not by plans for subsequent surgical reconstruction. The problem of reconstruction should be approached as a separate surgical procedure. This usually requires the participation of plastic and reconstructive surgeons and other surgical specialists who have been consulted prior to the resection so that an appropriate reconstructive strategy can be articulated.

During the operation, enhanced awareness of tumor extent and/or pathologic evaluation of resected margins may indicate that an alteration is needed in the initial operative plan. Decisions regarding the extent of resection are difficult and require experienced judgment. It is usually better to proceed with a potentially curative extirpation of the tumor mass, unless there is unequivocal histologic confirmation that the lesion has extended beyond the boundaries of curative surgical resection.

Many neoplasms metastasize via the lymphatics, and operations have been designed to remove the primary neoplasm and draining regional lymph nodes in continuity with all intervening tissues. Circumstances favor this type of operative approach when the lymph nodes draining the neoplasm lie adjacent to the tumor bed or when there is a single avenue of lymphatic drainage that can be removed without sacrificing vital structures. It is important to avoid cutting across involved lymphatic channels, which markedly increases the possibility of local recurrence.

At the present time, it is generally agreed that en bloc regional lymph node dissection is indicated for clinically demonstrable nodal involvement with metastatic tumor. However, in many cases, the tumor has already spread beyond regional nodes. Although the cure rates following resection in such circumstances may be quite low (20–50%), undue pessimism should not prevent such patients from receiving appropriate surgical treatment. En bloc removal of the involved lymph nodes may offer the only chance for cure and can at least provide significant palliative local control. Regional lymph node involvement should therefore not be viewed as a contraindication to surgery but as a possible indication for adjuvant therapies, such as radiation or chemotherapy.

The routine dissection of regional nodes in close proximity to the primary malignancy is recommended even when these structures are not clinically involved with tumor. This recommendation is based on the high rate of loco-regional recurrence following surgical resection when multiple lymph nodes are microscopically involved and the high error rate when palpation alone is used to assess possible of lymph node involvement with tumor. Microscopic tumor dissemination to regional lymph nodes can be detected in 20 to 40% of clinically node-negative carcinomas and melanomas.

The validity of elective or prophylactic lymph node dissection has been challenged because it is not clear whether cure rates are improved if subclincally positive lymph nodes are removed before they become clinically palpable. Actively accruing prospective randomized clinical trials are currently addressing this question for many types of neoplasms. Regardless of direct therapeutic benefit, knowledge of regional node tumor status can impact on staging and subsequent treatment. In many neoplasms, prognosis depends on the status of the lymph node basin draining the primary tumor. Some breast cancer patients with metastases to regional nodes derive significant survival benefit from adjuvant chemotherapy or hormonal therapy. Some patients with melanomas may become eligible for investigational adjuvant trials only if lymph node metastases can be demonstrated. Finally, a comparison of experimental results from different institutions depends on accurate staging at the time when therapy is in initiated.

In addition to questions of timing, the extent of lymph node dissection is also controversial. Sentinel lymphadenectomy is a promising new technique for detection of early nodal disease and is currently under investigation in multi-center trials. Detection of the sentinel node (i.e., the first lymph node draining a primary tumor) was introduced by Morton for melanoma18 and is now being applied to breast carcinoma19 and other neoplasms.20. Initially, the technique relied on the injection of a vital blue dye at the tumor site and visual tracking of this dye along the lymphatics draining to the nodal basin (Figure 32.4). Recently, sentinel node mapping has been facilitated by adding a radiolabeled isotope to the dye and monitoring its path using a handheld gamma probe.21,22

Figure 32.4. Sentinel node mapping.

Figure 32.4

Sentinel node mapping. Intense blue staining of axillary sentinel lymph node; note afferent lymphatic channel draining into the sentinel lymph node that also stains blue. (Courtesy of Dr. Jeffrey Gershenwald, Department of Surgical Oncology, University (more...)

Advances in surgical technique, anesthesia, and supportive care (blood transfusion, antibiotics, and fluid and electrolyte management) have permitted more radical, extensive and lengthy operative procedures. Such procedures offer a chance for a cure that cannot be achieved by other means and are justified in selected situations, if there is no evidence of distant metastases. For example, some slow-growing primary tumors may reach an enormous size and widely infiltrate locally without metastasizing to distant sites. Supraradical operative procedures should be considered undertaken for these extensive and nearly inoperable tumors because the occasional patient is cured (see Plate 8, Figure 32.4). However, such operations should be undertaken only by experienced surgeons who can select those patients most likely to benefit. As an example of carefully indicated radical surgery, pelvic exenteration is a well-conceived operation capable of curing patients with radiation-treated recurrent cancer of the cervix and certain well-differentiated and locally extensive adenocarcinomas of the rectum. This operation removes all pelvic organs (bladder, uterus, and rectum) and soft tissues within the pelvis. Bowel function is restored with colostomy. Urinary tract drainage is established by anastomosis of the ureters into a segment of the bowel (ileum or sigmoid colon). The 5-year relapse-free survival is 25% when pelvic exenteration is used to manage this problem. It is also imperative that the surgical oncologist be willing to accept the responsibility to help optimize the postoperative emotional and psychological rehabilitation of the patient prior to embarking on extensive resections, such as hemipelvectomy, forequarter amputation, mutilating operations for head and neck carcinomas, or total pelvic exenteration.

Surgical resection of selected localized recurrent neoplasms may produce a long period of remission. Surgical procedures are frequently successful in controlling recurrent soft tissue sarcomas, anastomotic recurrences of colon cancer, certain basal and squamous carcinomas of skin and local breast cancer recurrence following segmental mastectomy. However, surgical resection of locally recurrent tumors in patients with synchronous metastatic disease is usually not indicated unless the entire local recurrence can be completely excised and there is also some form of not previously used (yet effective) therapy available to control the metastases.

Historically, routine second-look operations to detect early recurrence of colon cancer were advocated by Gilbertsen and Wangensteen. However, the improvement in outcome after these second-look procedures has not been sufficient to justify their routine use. In contrast, more recent longitudinal follow-up strategies using tumor markers, such as carcinoembryonic antigen (CEA), have been more useful in selecting patients likely to benefit from reoperation.

Although logic might suggest that once a neoplasm has metastasized to a distant site, it is no longer curable by surgical resection, experience has shown otherwise. The removal of metastatic lesions in the lung, liver, or brain has occasionally produced a clinical cure. Resection of disseminated tumor may be indicated in selected patients with slowly growing metastasis, especially if the lesion is solitary. Even multiple metastases may be successfully resected if their growth rate is slow, or if regional or systemic chemotherapies administered before surgery have resulted in disease stabilization or tumor shrinkage. Prior to undertaking resection, an extensive work-up should be performed to rule out metastatic spread to other body sites outside of the proposed operative field.

Some patients with isolated liver metastases may benefit from surgical resection. Resection is recommended for the patient whose primary tumor has been controlled, who has no evidence of extrahepatic metastases, and who has a solitary liver metastasis or metastases located in one hepatic lobe. While only a minority of patients with colon cancer metastatic to the liver will meet these requirements of operability, approximately 25% of these operable patients will survive more than 5 years after resection. In certain circumstances, the results for resection of pulmonary metastatic lesions have also been very satisfactory. For example, resection of a solitary or limited pulmonary metastasis for some tumor types, such as osteogenic sarcoma, results in a higher survival rate than does resection of primary bronchogenic carcinoma of the lung. Resection of pulmonary metastases may be indicated even when more than one metastatic lesion is present, particularly if the metastases have been demonstrably responsive to systemic or regional therapies prior to surgery.

The growth rate of a tumor can be assessed by measuring the time it takes for the tumor to double in volume. The tumor doubling time (TDT) correlates with biologic aggressiveness and can be used to help determine the likelihood of benefit from surgical resection of metastatic disease. In essence, the TDT represents the balance between the intrinsic proliferative rate of the tumor and the patient’s host defense mechanisms. In 1956, Collins first described a method for determining the growth rate of human neoplasms using serial radiographs.23 In 1971, Joseph, Morton, and Adkins reported the prognostic significance of TDT in evaluating the operability of lung metastases.24 Figure 32.5 illustrates the method for calculating the TDT of pulmonary nodules.24 Successive chest radiographs are used to measure the increasing diameters of the lesion. The greater and lesser diameters are averaged and then plotted versus time, using semilogarithmic paper to account for three-dimensional tumor growth. The slope of the line drawn between any two points represents the rate of tumor growth. The horizontal distance between any two doubling points represents the TDT in days. Although the TDT may vary from 8 to more than 600 days, most metastatic pulmonary tumors double in 20 to 100 days. In general, patients presenting with a short TDT (< 20 days) have aggressive and fast-growing metastatic lesions. In contrast, patients with long doubling times (≥ 40 days) usually have more indolent lesions that may be amenable to surgery (Figure 32.6).

Figure 32.5. Method of calculating tumor doubling time based on direct measurement of the changing diameters of metastatic pulmonary nodules.

Figure 32.5

Method of calculating tumor doubling time based on direct measurement of the changing diameters of metastatic pulmonary nodules. (From Joseph with permission.)

Figure 32.6. Survival curves in 89 untreated patients following the onset of pulmonary metastases, showing three groups defined by tumor doubling time.

Figure 32.6

Survival curves in 89 untreated patients following the onset of pulmonary metastases, showing three groups defined by tumor doubling time. (From Joseph with permission.)

Surgical procedures are sometimes indicated to palliate symptoms without attempting to cure the patient, thereby prolonging a useful and comfortable life. A palliative operation may be justified to relieve pain, hemorrhage, obstruction, or infection, when it can be done without untoward risk to the patient. Palliative surgery may also be applicable when there are no better nonsurgical means of palliation, or when the procedure will improve the quality of life, even if it does not result in prolonged survival. In contrast, surgery that only prolongs a miserable existence is not of benefit to the patient. Examples of indicated palliative surgical procedures include (1) colostomy, enteroenterostomy, or gastrojejunostomy to relieve obstruction; (2) cordotomy to control pain; (3) cystectomy to control hemorrhagic tumors of the bladder; (4) amputation for intractably painful tumors of the extremities; (5) simple mastectomy for carcinoma of the breast, when the tumor is infected, large, ulcerated, and locally resectable, (even in the presence of distant metastases), (6) potentially obstructing colon resection in the presence of hepatic metastases, and (7) destruction of liver metastases using radiofrequency ablation (Figure 32.7 and Figure 32.7b). Surgery for residual disease is a special application of palliative surgery. In some patients, extensive yet isolated local spread of malignancy precludes gross total resection of all disease. In these patients, cytoreductive surgery may be of benefit provided that (1) other forms of effective treatment are available for use after surgery, and (2) that reduction of tumor bulk will enhance the effectiveness of these postsurgical therapies.

Figure 32.7. Radiofrequency ablation (RFA) of liver: A.

Figure 32.7

Radiofrequency ablation (RFA) of liver: A. radiofrequency needle. (Courtesy of Dr. Steven Curley, Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center.)

Figure 32.7B. Intraoperative open placement of RFA needle.

Figure 32.7B

Intraoperative open placement of RFA needle. (Courtesy of Dr. Steven Curley, Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center.)

Problems with exsanguinating hemorrhage, perforated viscus, abscess formation, or impending obstruction of a hollow viscus, such as gastrointestinal organs, critical blood vessels, or respiratory structures, are sometimes amenable to emergency surgical intervention. Emergency surgery may also be indicated to decompress tumors that are invading the CNS or destroying critical neurologic components by exerting pressure in closed spaces. The cancer patient being evaluated for emergency surgery may be neutropenic or thrombocytopenic due to recent myelosuppressive chemotherapy. Sometimes, a potential catastrophe can be avoided by operating on such patients expectantly just after they have gone through the nadir of their most recent myelosuppressive chemotherapy. Because of the high risks involved, each patient and his/her family must be made aware of the dangers and benefits of the proposed surgery as well as other potentially effective treatments that might be available if the patient survives this emergency operation.

Reconstructive surgery after tumor resection has remarkably improved the quality of life for many cancer patients. The routine application of microvascular anastomotic techniques has enabled the free transfer of composite grafts containing skin, muscle, and/or bone to surgically created bodily defects. Breast reconstruction after mastectomy, tissue transfers as part of extremity surgery for sarcoma, and aerodigestive reconstruction using jejunal free grafts are examples of these dramatic improvements in the combined surgical management of complex cancer problems (Figure 32.8). In the future, applications of the new discipline of tissue engineering will remarkably extend the reconstructive armamentarium. Using these approaches in the future, it may be possible to custom grow nerve, fat, muscle, bone cartilage, or other body components as replacements for tissues that will need to be resected as part of a composite cancer procedure.25 After resection, the tissue-engineered prostheses will then be implanted, thereby avoiding the constraints of only having dispensable autologous body parts available for reconstructive purposes.

Figure 32.8. Tissue-engineered vascularized osseus graft.

Figure 32.8

Tissue-engineered vascularized osseus graft. This graft was grown in vivo in a biodegradable strut that had been implanted into the rib of a sheep. In the future, such cultured tissues might be useful in reconstructive procedures, thereby avoiding dependency (more...)

Surgical Oncology in the Future

Shortly after we enter the new millennium, cancer is predicted to replace cardiovascular disease as the most prevalent killer of Americans on an annual basis. Given that there are no more than approximately 30 to 40 surgical oncologists produced yearly in the United States, it is clear that the traditional surgical oncology educational roles in academic medical centers as well as the larger health-care community will continue and perhaps come under increasing pressure to expand.

As multi-modality care grows in complexity and chemotherapy/radiotherapy move more prominently into the neoadjuvant position, surgical oncologists will have to become increasingly involved in clinical trial design. To be effective in this arena, understanding the natural history of specific malignancies will require an expanded knowledge base about the mutated genes and their cognate proteins that drive solid tumor proliferation and metastasis. Surgical oncologists will have to become more knowledgeable about these factors, both during training and as a life-long commitment to self-education.

In light of these changing demographics and increasing pressures for cognitive knowledge, it is perhaps unfortunate that the Accreditation Council for Graduate Medical Education (ACGME) has not yet granted formal subspeciality status to surgical oncology. This inaction may temporarily impede the growth of surgical oncology by discouraging some from entering the specialty. This prospect is unfortunate, given the emerging need for an expanded cadre of trained surgical oncologists who will be committed to working with other cancer specialists in developing new combined modality treatment programs.

It is also certain that surgical oncologists will be unable (and do not desire) to perform all of the increasing number of cancer resections that will be needed by the United States population in the future. In the final analysis, the most important consideration may be the willingness of surgical oncologists to think innovatively about surgery as part of multi-modality care, while preserving and even improving the quality of the surgical product that is being offered. Fortunately, many of the most talented surgical trainees being produced in the United States have embraced this challenge and are gravitating to postresidency surgical oncology fellowship training. Surgical fellowship programs focusing on oncology are now available in nearly all of the surgical specialties. This favorable state of surgical oncology as a “superspecialty” bodes well for the future. Our patients and our medical colleagues expect this of us (and the solid tumor challenge demands this of us) if we are to work together and succeed in eliminating cancer as the major public health hazard that it currently represents.

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© 2000, BC Decker Inc.
Bookshelf ID: NBK20873

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