The Washington Manual of Oncology, 3 Ed.

Principles and Practice of Surgery in Cancer Therapy

Amber Traugott • Rebecca L. Aft

 I. THE CHANGING ROLE OF THE SURGICAL ONCOLOGIST IN THE 21ST CENTURY. Early cancer therapy centered on surgical excision as the primary treatment modality for solid tumors. It was theorized that cancer spread occurred sequentially from the primary site to the regional lymph nodes and then on to distant sites. Therefore, it was hypothesized that complete local excision of all cancerous cells would lead to effective disease control. In patients with untreated cancer, median survival was frequently measured in months. Early en bloc resection of tumors with contiguous normal surrounding tissue and lymph nodes led to improved overall survival. As a consequence, increasingly aggressive and extensive resections of malignant tumors were performed. As the initial improvement in survival began to plateau, it became apparent that successively larger resections to obtain locoregional control of larger tumors did not necessarily translate into further survival benefit. This led to the testing and development of screening strategies and adjuvant therapies. As medical and surgical care of the cancer patient has become increasingly refined, surgeons have also been able to develop surgical approaches that decrease perioperative morbidity and mortality, while providing the same oncologic outcome. Neoadjuvant protocols are being used in many cancers to reduce the extent of resection needed to gain locoregional control of tumors, or to identify patients with aggressive tumor biology who are unlikely to benefit from surgery with curative intent. In addition, minimally invasive surgical techniques now enjoy widespread use in the surgical treatment of a wide variety of solid tumors. The current role for the surgeon in the management of patients with cancers involves a broad spectrum of surgical procedures for diagnosis, local control, cure, and palliation.

1. DIAGNOSTIC PROCEDURES: ACQUISITION OF MATERIAL FOR DIAGNOSIS. Once a lesion has been identified, one role of the surgical oncologist is to provide adequate material for definitive diagnosis. The method of biopsy requires consideration of the differential diagnosis, amount of tissue needed for definitive diagnosis, location of the lesion, and potential forms of treatment. It is preferable to perform biopsies of lesions at the periphery where viable tumor is located, because the cores of solid tumors may be necrotic. This also allows the pathologist to evaluate the invasion into normal tissue since some tumors (thyroid) have low mitotic rates and bland cytologic features, which are insufficient for determining malignancy. General principles for biopsy include sampling representative tissue, obtaining adequate tissue for diagnosis, procuring viable tissue, minimizing contamination of adjacent uninvolved tissues, orienting the tissue for margin analysis, and providing tissue to the pathologist in the appropriate conditions (fresh or fixed).
2. Fine needle aspiration cytology. Fine needle aspiration (FNA) yields a smear of single cells and aggregates for cytologic analysis. The biopsy is performed using a 22- to 25-gauge needle, which can be percutaneously guided to most anatomic sites. Imaging guidance (including endoscopic or endobronchial ultrasound [EUS/EBUS]) may be used to improve the accuracy of sampling for nonpalpable lesions or lesions in deep tissues. Although the track of the needle is theoretically contaminated with malignant cells, in practice, FNA-track metastases are rarely a clinical problem. Diagnosis is based on the cytologic features of the cells including cohesiveness, nuclear and cytoplasmic morphology, and number. An advantage of FNA is that a wide area of the tumor can be sampled. The limitations of FNA include (a) small sample size; (b) lack of information on histologic architecture that cannot distinguish between in situ and invasive tumors (breast, thyroid); (c) inability to obtain grade of tumors; and (d) interpretation of certain immunohistochemical stains. FNA can be useful for diagnosing recurrent lymphoma; however, for a primary diagnosis of lymphoma, more tissue may be required.
3. Core needle biopsy. Core needle biopsies yield fragments of tissue, which allow the evaluation of tumor architecture. The biopsy is performed using 14- to 16-gauge needles specifically designed for this purpose (Tru-Cut, Biopsy). Larger biopsy specimens that sample larger areas of tissue can be obtained with vacuum-assisted devices (Vicora, Mammotome). Core needle biopsies can also be combined with imaging such as mammography (stereotactic core biopsy), computed tomography (CT), or ultrasonography. A false-negative biopsy may result if the needle misses or skives (pares) the malignant tumor, which may occur with very sclerotic cancers such as in the breast. The most common complication of core needle biopsies is bleeding, and the procedure should be cautiously performed in patients with coagulopathies. In addition, masses near large vascular structures, hollow organs, or in the central nervous system (CNS) are not amenable to this procedure.
4. Cutaneous punch biopsy. Punch biopsies are used to obtain tissue from cutaneous lesions using 2- to 6-mm round surgical blades. A full-thickness skin specimen including subcutaneous fat is obtained. The procedure is simple to perform, with few complications, and is useful for obtaining tissue for pathologic diagnosis from suggestive skin lesions (melanoma, basal cell, or squamous cell carcinoma) that may subsequently require definitive surgical resection.
5. Open biopsy
6. Incisional biopsy. Occasionally, neoplasms are not amenable to percutaneous needle biopsy because of anatomic location, requirements for large amounts of tissue for diagnosis (sarcomas), or concern regarding sampling errors in diffuse lesions. An incisional biopsy is the most expedient method for obtaining tissue for definitive diagnosis. These procedures are usually performed in an outpatient surgical setting. A wedge of tissue large enough for accurate diagnosis is removed from the periphery of the lesion. Excellent hemostasis must be obtained to avoid hematogenous seeding. The biopsy incision should be planned such that it can be included in the tissue to be removed by subsequent definitive surgery (longitudinal for limb sarcomas) because some tumors have a propensity for seeding the biopsy incision. A biopsy site that is far removed from the potential operative incision can severely jeopardize later attempts for surgical control of the tumor or potential limb-sparing procedures and can result in a compromised surgery.
7. Excisional biopsy. Excisional biopsies remove the entire lesion and are best suited for small lesions, particularly when a needle biopsy is inappropriate for technical, safety, or diagnostic reasons, or where the gross architecture of the lesion impacts the diagnosis. This may be curative for small cancers (melanoma, breast cancer, sarcoma, and basal cell carcinomas). Depending on the size of the lesion and the closure required, excisional biopsies can be performed as an office-based procedure or in the operating room. All specimens should be oriented for accurate margin assessment. This allows the surgeon to resect additional tissue for inadequate or close margins.

 III. STAGING: DETERMINING THE EXTENT OF DISEASE AND RESECTABILITY. When distant disease is suspected, most cancers can be staged with CT, positron emission tomography (PET), magnetic resonance imaging (MRI), or bone radionuclide scans. However, surgical staging procedures for melanoma, breast cancer, a subset of abdominal malignancies, and thoracic malignancies are more sensitive than currently available radiographic modalities and alter patient management in a large percentage of cases.

1. Mediastinoscopy. Mediastinoscopy is used for the preoperative staging of bronchogenic carcinoma and evaluation of mediastinal adenopathy. It is the most accurate method for staging mediastinal lymph nodes. The procedure is performed under general anesthesia. A transverse surgical incision is made above the sternal notch, and a mediastinoscope is inserted along the trachea. Lymph node can be biopsied from the pretracheal, subcarinal, and paratracheal node stations and examined for metastatic disease. The procedure is highly sensitive (100%) and specific (90%) in staging of bronchogenic carcinoma and has low morbidity and mortality. Endoscopic ultrasound (EUS) and endobronchial ultrasound (EBUS) can also be used to obtain needle biopsies of mediastinal lymph nodes. Together, these techniques (EUS, EBUS, and mediastinoscopy) are important tools to help stage mediastinal lymph nodes.
2. Laparotomy. Radiographic staging and laparoscopy have largely replaced laparotomy. Laparotomy is used selectively for staging ovarian and nonseminomatous testicular cancers. The procedure is performed under general anesthesia through a midline incision. The procedure has low morbidity and short recovery. Complications include infection, bleeding, wound dehiscence, and rare events related to exploration of the intra-abdominal contents and general anesthesia.
3. Laparoscopy. Laparoscopic approaches to the staging of patients with cancer are now routine for a number of intra-abdominal malignancies (liver, pancreas, stomach, and medullary thyroid carcinoma). Laparoscopy has been shown to decrease the incidence of unnecessary laparotomies for unresectable disease in up to 70% of patients with abdominal malignancies. Diagnostic laparoscopy for staging is usually performed at the time of a planned laparotomy or laparoscopic excision with curative intent. If distant or unresectable disease is found, then an unnecessary laparotomy or extensive laparoscopic dissection is avoided. The procedure is performed under general anesthesia. Biopsies of solid organs, lymph nodes, and suggestive lesions can be obtained. When laparoscopy is combined with intraoperative ultrasonography, lesions deep in the parenchyma of an organ can be identified, as well as tumor invasion into adjacent structures, such as major blood vessels. This is especially useful in evaluation of the liver and pancreatic malignancies and may be the most sensitive imaging technique for the detection of liver metastases. The procedure has few complications and may be performed on an outpatient basis. Port-site metastasis and intra-abdominal spread by the pneumoperitoneum, although of theoretical concern, are rare (less than 1% of cases).
4. Lymphadenectomy. The location, type of cancer, and clinical evidence of nodal involvement are the major considerations in performing lymphadenectomy. Presence and extent of nodal involvement is the most accurate risk indicator of distant disease development for many cancers. In general, regional lymph nodes should be removed when the likelihood of metastases is high or if lymph nodes are found by clinical examination to be involved. If possible, regional lymph nodes should be removed at the time of the primary surgery. If a lymph node is found to exceed 3 cm in size, the tumor likely has extranodal extension and involves the perinodal fat. These lymph nodes should be resected with surrounding fat and, if of low morbidity, the adjacent nerves (i.e., intercostal brachial sensory nerve of the axilla). The survival benefit of lymphadenectomy varies from malignancy to malignancy; it is heavily influenced by the effectiveness of adjuvant chemotherapy for the cancer in question. Therefore, the goal of lymphadenectomy for all cancers is to obtain sufficient lymph node tissue to adequately stage the patient. For those cancers where lymphadenectomy improves survival, the optimal extent of resection provides the best oncologic outcome without subjecting the patient to unnecessary surgical morbidity or mortality. In some cases, such as in gastric adenocarcinoma, this ideal extent of lymphadenectomy is the subject of ongoing study and controversy. The major morbidity of regional lymphadenectomy for axillary or inguinal lymphadenectomy is limb lymphedema and injury to adjacent nerves. More extensive lymphadenectomies within the chest or abdomen can result in increased surgical mortality, as well as injury to surrounding organs or major neurovascular structures.
5. Sentinel lymph node biopsy. Sentinel lymph node biopsy (SLNB) is based on data demonstrating hierarchical lymphatic drainage occurring from the primary tumor to the first draining lymph node (sentinel lymph node [SLN]) and then to the remaining nodes in the regional lymphatic basin. Numerous studies have demonstrated that localized malignancies metastasize to the SLN before involving other nodes in the basin. Therefore, the presence or absence of metastatic disease in the SLN predicts the status of the entire regional lymphatic basin. SLNB is currently used for staging the axilla in breast cancer and regional nodal basins in melanoma. It is under investigation for a number of other malignancies (gynecologic, head, and neck). Two techniques are used for lymphatic mapping, which may be used independently or in combination. The first technique involves the injection of a radiolabeled colloid around the lesion, which is followed radiographically and/or intraoperatively by using the gamma probe. The second technique employs blue dye (isosulfan blue, lymphazurin blue, and methylene blue), which is injected intraoperatively around the tumor and allowed to percolate through the lymphatics. In both techniques, an incision is made at the edge of the nodal basin, and the SLN is identified by tracing blue or radioactive lymphatic channels to the first blue or radioactive node. If more than one nodal basin is potentially involved, then preoperative lymphoscintigraphy may be performed to identify the draining nodal basins. In experienced hands, the procedure has very high specificity and sensitivity. The advantages of SLNB are selective lymph node dissections in those patients who would benefit most, avoiding the morbidity associated with lymph node clearance in those patients with low risk of disease, and the ability to perform immunohistochemical stains or polymerase chain reaction (PCR) to detect micrometastatic disease. Disadvantages of SLNB are related to the skill of the operator, which may result in a significant false-negative rate.

 IV. SURGICAL TREATMENT. Surgical planning involves consideration of the tumor stage and location, the general health of the patient, expected morbidity and mortality of the procedure, probability of successful treatment, and the availability and effectiveness of other treatment modalities. Surgical resection of solid tumors provides excellent local control and is currently the only curative option for most solid tumors.

1. Primary resection
2. Principles of Surgical Resection. The primary goal of cancer surgery is the complete extirpation of local and regional disease for local control and for decreasing the risk of local recurrence. This involves removing the primary lesion with adequate margins of normal surrounding tissue to minimize the risk of local recurrence. The stage, mechanisms of local spread, morbidity, and mortality of the procedure must be taken into consideration before any surgical procedure is undertaken. In patients with metastatic disease, long-term control may not be as important as it is in patients who have localized disease, which may be surgically curable, although in these cases surgery can be palliative. Knowledge of the most common avenues of spread for the various histologic types of cancers is essential for successful local control. Depending on the cell of origin, cancers may spread mucosally, submucosally, along fascial planes, or along nerves (Table 3-1). With advances in anesthesia, minimally invasive surgical approaches, postoperative care, and reconstructive procedures, large surgical procedures can be performed safely in elderly patients and patients with multiple comorbid conditions. Intraoperatively, successful resection requires good exposure, excision of previous biopsy sites, maintaining a bloodless surgical field to visualize the extent of tumor spread, and en bloc resection of the tumor and surrounding normal tissue. Local recurrence or wound seeding can be theoretically minimized by minimal manipulation of the tumor, confining dissection to normal tissue, and early ligation of major feeding vessels at their origin. Complete removal of the tumors has many favorable effects, including minimizing residual disease and eliminating hypoxic, poorly vascularized cells, which are drug and radiation resistant.
3. Premalignant lesions and prophylactic surgery. Surgery is indicated for premalignant lesions and noninvasive cancers of the skin, mouth, cervix, colon, breast, and thyroid, although only a proportion of such lesions may progress to malignancy (Table 3-2). Several inherited disorders associated with increased cancer risk have been described. Surgery can significantly reduce cancer occurrence (Table 3-3).
4. Operative principles
5. Anatomy. The anatomic location of cancers is an important consideration in surgical planning. Some tumors cannot be adequately treated by surgical resection alone because of anatomic constraints, which may result in incomplete excision (nasopharynx). Residual microscopic disease after surgical resection can sometimes be treated effectively with adjuvant radiation therapy to decrease local recurrence. Those patients whose lesions are intimately involved with major blood vessels (lung/aorta) or bilaterally involve an essential organ (liver) or those with a limited life expectancy due to the natural history of the disease may not benefit from surgical resection.

FMTC, familial medullary thyroid cancer; MEN, multiple endocrine neoplasia.

2. Neoadjuvant therapy before resection. If a lesion is resectable and localized at the time of diagnosis, then surgery should be performed. Large lesions or lesions invading into surrounding structures that are not initially resectable may be amenable to volume reduction with initial (neoadjuvant) chemotherapy or radiation therapy. This strategy has allowed successful but more limited, less morbid resections or function-preserving resections of many cancers (colorectal, breast, larynx, and pancreatic cancers). In addition, the response to neoadjuvant therapy is useful for monitoring response to various treatment regimens. If a pathologic complete response is possible, the surgical site should be marked with metallic clips at the time of biopsy for future identification at the time of surgery. A disadvantage of neoadjuvant therapy is the possible delay in undergoing standard curative therapy. Infrequently, a patient may have disease progression on neoadjuvant therapy, to the point where curative surgical resection is no longer possible. However, this subset of patients may have biologically aggressive disease that would have been unlikely to respond to adjuvant therapy after resection, thus increasing the risk of recurrence after surgery. Therefore, it is possible that this process selects for patients who would not have benefited from surgical resection, in terms of survival or disease-free survival.

 Preoperative radiation therapy may be used alone or in combination with chemotherapy to reduce tumor size before resection. In some cancers, such as rectal cancer, it also provides the benefit of decreased local recurrence after resection, even when given preoperatively. Advantages of preoperative radiation therapy are potentially smaller treatment fields and reduced potential seeding of the tumor during surgery. Disadvantages of preoperative radiotherapy include the resulting fibrosis, which may obscure resection margins and increase the difficulty and morbidity of the surgery. Preoperative radiation therapy renders the wound edges functionally ischemic, which may affect the type of reconstruction performed and tissue resected or result in increased wound complications. Although neoadjuvant therapy may decrease the size of the lesion, there is generally little benefit in overall survival.

1. Extent of resection. Extent of resection depends on the organ involved and method of local spread. Adequate margins range from 1 mm to 5 cm for cutaneous and hollow organ tumors. Resections for solid organ tumors are usually guided by the blood supply, and usually resection of a lobe (liver, lung) or the entire organ (kidney) or a partial resection (pancreas) is performed. The most efficacious method for local control and prevention of local recurrence is wide excision. This may require encompassing any biopsy incision or needle tract into the en bloc excision. If the malignancy is adherent to a contiguous organ, then a partial resection of the latter organ may be performed to obtain negative margins. Most solid tumors have a propensity for dissemination through local lymphatics to regional lymph nodes. If a lymph node in the draining area exceeds 3 cm in size, the tumor is likely extranodal and involves the perinodal fat. Local excision is then inadequate and en bloc resection of the organ, regional lymph nodes, and adjacent involved regions should be performed. To prevent seeding of tumor, the no-touch technique can be used, which includes minimal palpation of the tumor and early ligation of the blood supply to limit dislodgement of the tumor cells into the venous circulation. Although the ability of these techniques to reduce local recurrence is controversial, their theoretic value has led to widespread acceptance. If a second area of the body requires surgery at the time of tumor excision, gloves, gowns, sheets, and instruments must be changed. This further prevents transplantation of tumor to a distant site.

 If margins are positive after resection, options include further surgery, adjuvant therapy, or careful follow-up. If microscopic tumor is found at the resection margin, adjuvant postoperative radiation may be given. However, this may be associated with a higher risk of tumor recurrence, poorer cosmetic results, and more radiation complications due to the higher radiation doses required (breast, sarcoma, and head/neck cancers). These patients may benefit from re-excision of the tumor bed to achieve microscopically clear margins if this is technically feasible. In these cases, the potential morbidity and mortality of repeat surgery should be assessed.

1. Laparoscopic and laparoscopy-assisted surgeries. Laparoscopic or laparoscopy-assisted tumor resections are increasingly being performed worldwide, and are now standard options for curative resection in many cancers. The most common laparoscopic cancer surgery performed is colectomy. Laparoscopy-assisted distal pancreatectomies, hepatectomies, adrenalectomies, gastrectomies, esophagectomies, nephrectomies, prostatectomies, and video-assisted thoracic (VAT) lobectomies are now performed routinely for cancer surgery in appropriately selected patients. In general, laparoscopic procedures result in shorter hospital stay, less intraoperative blood loss, decreased requirement for analgesics, and earlier return to normal activities. Concerns have been raised regarding margin width and en bloc resection of draining nodal basins; however, studies examining these issues for colectomy have reported no significant difference. Indeed, data suggests that this holds true for other laparoscopic resection options.
2. METASTASES AND RECURRENT DISEASE
3. Distant metastasis. With many types of cancer, death is often the result of metastatic disease. It is often assumed that the patient with disseminated disease is not a candidate for surgical procedures. However, subsets of patients with isolated metastases are amenable to a complete surgical resection (hepatic and pulmonary) with resulting increased survival. Excisions of symptomatic metastases that cannot be treated by other means are appropriate for resection to improve quality of life (melanoma, breast, thyroid, and other endocrine cancers). This includes patients with subcutaneous metastases that present cosmetic problems and bowel metastases that cause obstruction or bleeding. Patients with multiple metastases to the lung or liver should be considered for resection if the metastases are present in only one organ system, if there is adequate normal parenchyma remaining after resection, and if the operative risk is minimal. The longer the time interval between initial diagnosis and the appearance of metastatic disease, the more likely it is that surgery will be beneficial and result in increased overall survival. Resection of a small number of pulmonary metastases from sarcoma or localized lung and liver metastases from colorectal cancers will result in increased survival for approximately 25% of patients. In breast cancer, there is emerging evidence that surgery of the breast improves overall survival in patients with metastatic disease.
4. Resection for recurrent locoregional disease. Local recurrence of cancer can result from incomplete excision at the initial surgery, the presence of residual cancer cells distant from the primary lesion, or second primary tumors that develop in residual normal tissue. Intensive follow-up is used to detect recurrent or persistent tumors before distant dissemination occurs. With some cancers, the presence of local recurrence may signal the presence of distant disease in a proportion of patients (approximately 50% for breast cancer). Similar surgical principles apply to resection of recurrent disease.
5. Palliative surgery. Significant improvement in quality of life and alleviation of symptoms can be achieved with palliative surgery, which allows patients to resume as many of their normal daily activities as possible (Table 3-4). This includes resection for obstruction, pain, bleeding, or perforation of a hollow viscus or for hormonal effects of endocrine tumors (insulinomas, gastrinomas, and medullary thyroid cancers). As laparoscopic techniques become more common, these minimally invasive approaches may provide invaluable tools for allowing patients the ability to maximize their quality of life without the morbidity associated with open surgery.

 VI. RECONSTRUCTION: FUNCTIONAL AND COSMETIC. Advances in the understanding of the tissue blood supply have allowed improvements in the coverage of surgical defects after cancer resections. Rarely are disfiguring primary closures or skin grafts the only option. Two advances have led to major changes in plastic reconstructions of cancer resections. The first was the anatomic elucidation of muscular blood supply, which allowed tissue associated with a defined vascular network to be moved to a defect within reach of its pedicle. The second advance was in the field of microsurgery, which allowed muscle flaps with the overlying subcutaneous fat and skin to be detached from their original blood supply and reanastomosed to vessels in a different anatomic area. These advances meant that multiple-stage reconstructions were no longer required to bring well-vascularized tissue into a surgical defect. This decreases the risk of postoperative wound complications and avoids delays in commencing adjuvant therapy. Currently, immediate reconstruction is frequently performed during the same surgery as an oncologic resection. With these techniques, large amounts of tissue can be reliably transplanted to fill dead spaces, pad and cover susceptible organs or structures, and provide restoration of form, function, and contour. Free and pedicled tissue transfers are used for reconstruction after surgery for the breast, mandibular area, and perineum. Commonly used donor myocutaneous flaps include the latissimus dorsi, rectus abdominis, and gracilis muscles. If bone is required, fibula-based flaps are commonly used. Flap success rate is 95%, and multiple studies have demonstrated improved quality of life with reconstruction procedures and no decrement in the ability to detect recurrence. In those patients requiring adjuvant therapy, reconstruction does not delay the time to initiation of treatment. Disadvantages of reconstruction are secondary problems at the donor site and increased operative time.

 VII. ABLATIVE MODALITIES. Some patients with liver tumors, who are not candidates for surgical resection, may be able to undergo ablation treatment. Patients may not be able to tolerate surgical resection owing to their overall health status, or when the extent of surgical resection required would leave inadequate functional liver tissue remaining. This is especially a consideration in the presence of cirrhosis or chemotherapy-induced liver injury. Ablative therapies have been best studied for primary hepatocellular carcinoma, and for colorectal cancer metastases to the liver. However, limited data exists for ablation of other malignancies metastatic to the liver, including breast cancer, gynecologic malignancies, and neuroendocrine tumors. Ablation also has been studied in the treatment of primary lung and renal cancers. Generally, the evidence suggests that ablation confers a survival benefit over untreated disease or chemotherapy alone in patients ineligible for resection. In some studies, the overall survival rate may approach that of surgical resection. However, the local recurrence rate is generally inferior to surgical resection, and multiple treatments may be needed to achieve local control.

1. Cryotherapy. Intraoperative cryoablation is regarded as an effective form of palliative therapy and may cure some patients with small tumors. Intraoperative ultrasonography is used to monitor hepatic cryosurgery for nonresectable disease. Hepatic cryotherapy involves the freezing and thawing of liver tumors by means of a cryoprobe inserted into the tumors. During freeze/thaw cycles, ice forms within the intracellular and extracellular spaces, leading to tumor destruction. Tumors are then left in situ to be absorbed. Postoperative complications include hemorrhage, biliary fistula, myoglobinuria, and acute renal failure. Hepatic cryoablation is also associated with a rare syndrome of multiorgan failure, coagulopathy, and disseminated intravascular coagulation. Overall morbidity rates range from 6% to 50%. Mortality rates range from 0% to 8%. Hepatic cryosurgery is an option for patients with isolated liver metastases from colorectal cancer that are not surgically resectable but are limited enough to allow cryoablation of all lesions. However, owing to the rare systemic complications, other ablation techniques are favored in patients who are not candidates for formal resection of their solid tumors.
2. Radiofrequency ablation. The radiofrequency ablation (RFA) technique involves percutaneous or intraoperative insertion of a radiofrequency (RF) probe into the center of a hepatic tumor under ultrasonography or CT guidance. RF energy is then emitted from the electrode and absorbed by the surrounding tissue. This process generates heat, leading to coagulation necrosis of the treated tissue. It relies on the ability of the tissue to conduct current, so it is less reliable for desiccated tissue or tissue with high impedance, such as lung or bone. Also, large blood vessels adjacent to the tumor can result in a “heat sink” effect, preferentially conducting current away from the lesion. The initial limitation of this therapy was the small (1.5 cm) diameter of necrosis achievable with a single RF probe. Newer probes allow treatment of larger volumes. The primary advantage of RF ablation over cryosurgery lies in the low incidence of complications and the ease of performance under CT or ultrasonography guidance. RF ablation can be performed percutaneously in many cases, thereby avoiding laparotomy or laparoscopy. It has been best studied in the treatment of cancers localized to the liver, particularly metastatic colorectal cancer and primary hepatocellular carcinomas. Radiofrequency ablation is currently the most widely used ablative therapy, and it has been the most extensively studied.
3. Microwave ablation. Microwave ablation is similar to RFA in that it generates an electromagnetic field, resulting in the production of heat within the target tissue. An antenna probe is placed into the tumor to deliver the energy, which can heat tissue up to 2 cm from the antenna. Multiple antennas can also be used simultaneously, allowing the treatment of large or multifocal lesions. Unlike RFA, microwave ablation is not as influenced by the ability of the tissue to conduct electricity, making it a better choice for tissues with higher impedance. It is also less vulnerable to “heat sink” effect and can treat large tumor volumes more reliably than RFA. A disadvantage of microwave ablation is the tendency of the antenna to overheat and potentially damage other tissues along the track of the probe.
4. Irreversible electroporation. The irreversible electroporation (IRE) technique differs from the others in that it does not induce a thermal injury to the treated tissues. IRE uses a pulsed direct current that causes irreversible cell damage, leading to apoptosis. It is thought to do so by disrupting the cell membrane and inducing the formation of pores within the lipid bilayer. Because of this, it is not subject to “heat sink” effect and does not exhibit thermal spread to nearby tissues. It is theorized that this will make IRE safer and more reliable to use for lesions close to critical anatomic structures or large blood vessels. Irreversible electroporation is a new technology, and it is still under active investigation for the treatment of multiple cancer types.

VIII. SURGICAL INTERVENTION FOR ONCOLOGIC EMERGENCIES. Although true oncologic emergencies are rare, surgeons are often consulted regarding the management of complications that are a result of tumor progression or cytotoxic therapy. In cases of widespread metastasis or unresectable disease, it is essential that part of the discussion about prognosis should include the patient’s wishes for surgical intervention in the event that such a complication occurs. Ideally, this would occur when the patient is relatively well and able to express their wishes and ask appropriate questions. Frequently, these discussions take place only in the context of the emergency itself, when the patient and family are unable to have a well-considered discussion about goals of care. Emergent surgery carries a higher risk of complications than elective surgery, and generally delays palliative chemotherapy during the recovery.

1. Bowel perforation. Perforation of the gastrointestinal (GI) tract in patients with cancer carries a high morbidity and mortality. Although most perforations are from benign causes (diverticulitis, appendicitis, and peptic ulcer disease), they can also occur as a result of chemotherapy or radiation therapy or as a primary presentation of a malignancy. Undiagnosed colorectal cancers can present with perforation as a result of full-thickness colonic involvement or proximal perforation from a distal obstructing mass. The response of some malignancies, such as GI lymphomas, is so great to chemotherapy that full-thickness necrosis of the bowel wall occurs. Patients undergoing cancer therapy are often immunosuppressed and malnourished, which masks the traditional signs of a perforation (peritonitis, leukocytosis, fever, and tachycardia). Immunosuppression and poor nutrition are associated with an increase in the operative mortality and morbidity of these patients. Mortality rates as high as 80% have been reported in patients who undergo an emergency laparotomy and in those who have metastatic disease and are undergoing chemotherapy. Comfort care and nonsurgical treatments should be discussed in patients with an overall poor prognosis. In patients who undergo abdominal exploration, ostomies, gastrostomy, and feeding jejunostomy tubes should be considered.
2. Bowel obstruction. Intestinal obstruction is commonly found in cancer patients presenting with nausea, vomiting, abdominal distention, and obstipation. Benign sources of obstruction such as adhesions from previous surgery and radiation enteritis account for approximately one-third of cases in these patients. Primary (ovarian, colonic, and stomach) malignancies or metastatic disease (lung, breast, and melanoma) are the cause of intestinal obstruction in two-thirds of cases. In a small percentage of cancer patients, functional obstruction can also occur without a mechanical cause from electrolyte abnormalities, radiation therapy, malnutrition, narcotic analgesics, and prolonged immobility. In these patients, correction of the underlying cause and bowel decompression are the cornerstones of treatment.

 The approach to the diagnosis and treatment of obstruction in patients with cancer should be similar to that for patients with benign disease. Diagnosis is most frequently made by CT scan, though additional studies using oral or rectal contrast may be diagnostic and/or therapeutic in some cases. CT scans of the abdomen with oral and rectal contrast can be helpful for determining the presence of a transition point, bowel wall thickening, or the presence of recurrent disease.

 All patients should be initially resuscitated with IV fluids, have electrolyte abnormalities corrected, be decompressed with a nasogastric tube, and have urine output monitored. Patients who have signs of compromised bowel viability or perforation (abdominal tenderness, leukocytosis, fever, persistent tachycardia, and free intra-abdominal air) should undergo immediate exploratory laparotomy. Patients with a complete bowel obstruction rarely respond to medical management and require surgical exploration. Between 25% and 50% of patients with a partial small bowel obstruction will resolve their obstruction with conservative measures. Those patients who do not demonstrate resolution after a finite period or progress to complete obstruction should undergo laparotomy. Cancer patients with benign obstructions from adhesions or internal herniation benefit from surgery. If malignant obstruction is present, resection or bypass of the obstructed segment may be performed; however, only 35% of patients will have durable relief of symptoms after surgical treatment. These patients should be strongly considered for gastrostomy tube placement at the time of surgery, which provides significant palliation by relieving emesis and obviating the need for nasogastric suction. Radiation-induced enteritis may be clinically indistinguishable from adhesive small bowel obstruction. In cases of radiation enteritis, short segments of narrowed bowel may be resected; however, long segments should be treated with bypass. Surgical intervention for a malignant bowel obstruction is associated with a significant morbidity (30%) and mortality (10%), and patients have a mean survival of approximately 6 months only following laparotomy for a malignant bowel obstruction.

1. Neutropenic enterocolitis (typhlitis). Neutropenic enterocolitis most often occurs in patients who are undergoing chemotherapy and are neutropenic for more than 7 days. Symptoms include febrile neutropenia, diarrhea, abdominal distention, and right lower quadrant pain. Initially, the presentation can be very similar to appendicitis. Radiologic findings are often nonspecific or may demonstrate thickening of the cecum. Serial abdominal examinations are critical for proper diagnosis and treatment. Most episodes will resolve with conservative management with bowel rest, IV fluid resuscitation, nasogastric decompression, and broad-spectrum antibiotics. However, if patients develop perforation, uncontrolled hemorrhage, become septic, or symptoms continue to worsen despite medical therapy, a laparotomy should be performed. A right hemicolectomy with ileostomy and mucous fistula is the surgery of choice and may be reversed after several months.
2. Biliary obstruction. In addition to pancreatic and bile duct carcinomas, lymphomas, melanomas, and breast, colon, stomach, lung, and ovarian cancers can cause biliary obstruction due to metastasis to the portal lymph nodes or hilum of the liver. The prognosis for patients with biliary obstruction from metastatic disease is poor. Two-month mortality rates approaching 70% have been reported. Treatment should be aimed at preventing cholangitis and palliating jaundice. Endoscopic retrograde cholangiopancreatography (ERCP) with stent placement or percutaneous transhepatic drainage should be the initial treatment strategy.
3. Hemorrhage. Patients with malignancies who develop GI bleeding should undergo the same workup as those without malignant disease. Resuscitation, correction of coagulopathies, and a workup to define the bleeding site should be initiated immediately. Bright blood per rectum or hematemesis can give clues to a lower or upper GI source. Malignant tumors are rarely the source of significant intra-abdominal hemorrhage. If the bleeding is not at a life-threatening rate, tagged red blood cell scan, angiography, embolization, and endoscopic interventions can all be used to diagnose and treat the hemorrhage. The timing of surgical intervention is based on the rate and volume of blood loss, the underlying pathology, and the overall prognosis of the patient.
4. Pericardial tamponade. Metastatic disease to the pericardium leading to malignant obstruction of the pericardial lymphatics is the most common cause of pericardial tamponade in cancer patients. Lung cancer, breast cancer, lymphoma, leukemia, melanoma, and primary neoplasms of the heart are most commonly implicated in tamponade. The development of symptoms in a patient depends on the rate of accumulation of the volume of the pericardial fluid and compliance of the sac. If the accumulation is gradual, more than 2 L can be found in the pericardial sac. Patients often present with vague symptoms of chest pain, dyspnea, and anxiety. On examination, decreased heart sounds, tachycardia, pulsus paradoxus, and jugular venous distention can be found. Echocardiography is the best test to determine whether there is excess pericardial fluid. Pericardiocentesis with placement of a drainage catheter can be life-saving in a patient in tamponade and shock. Additional options in more stable patients include tetracycline sclerosis, radiation therapy, subxiphoid pericardiotomy, window pericardectomy, and complete pericardectomy. A subxiphoid approach avoids the need for a thoracotomy.
5. Superior vena cava syndrome. Superior vena cava syndrome (SVCS) results from an impedance to outflow from the superior vena cava (SVC) due to external compression by malignancy, fibrosis, or thrombosis. In more than 95% of patients, SVCS results from a malignancy. The SVC is a thin-walled vessel in the middle mediastinum, and any enlargement of the perihilar or paratracheal lymph nodes or abnormalities of the aorta, pulmonary artery, or mainstem bronchus could lead to impingement on the SVC. The SVC is responsible for venous drainage of the head, neck, upper extremities, and upper thorax. Small cell lung cancer and other pulmonary malignancies are the most common etiology of SVCS, although lymphomas, germ cell tumors, and metastatic lesions to the supraclavicular nodal basins are also responsible. In most cases, SVCS develops gradually. The most common symptoms are dyspnea and facial fullness. Other symptoms associated with SVCS are venous engorgement of the neck and chest wall, cyanosis, and upper extremity edema. Symptoms are worse when the patient bends forward or reclines. Unless SVCS causes impedance of the airway from laryngeal edema (an emergency treated with intubation, tracheostomy, or emergent radiation therapy), a thorough workup can be conducted. Chest radiography, CT, and biopsy can be useful in determining the etiology of SVC obstruction. Treatment includes diuretics, elevation of the head, and steroids, and chemotherapy and/or radiation therapy directed at treating the underlying cause. SVCS can be secondary to indwelling central venous catheters causing thrombosis. This can often be successfully treated with thrombolytic agents followed by systemic anticoagulation. Balloon angioplasty and vascular stenting can be used if initial therapies fail. Surgical innominate vein–right atrial bypass is the last option.
6. Spinal cord compression. Spinal cord compression is an acute emergency. The severity of neurologic impairment at presentation dictates the potential reversibility of symptoms. Early recognition is essential in preventing progressive or irreversible neurologic deterioration that can lead to paralysis and loss of sphincter control. Extradural metastatic lesions of the vertebral body or neural arch are the most common cause of spinal cord compression in patients with malignancies. As tumors expand, they often impinge on the anterior aspect of the spinal cord. Metastatic lesions from lung, breast, prostate cancers, and multiple myeloma are the most common lesions responsible for spinal cord compression. Of these, 10% occur in the cervical vertebrae, 70% in the thoracic vertebrae, and 20% in the lumbosacral vertebrae. 90% of patients will present with localized back pain. The pain usually precedes the onset of neurologic deterioration by weeks to months. Patients will develop motor loss and weakness followed by sensory loss. Patients often describe an ascending tingling sensation beginning in the distal extremities. The onset of urinary retention, constipation, and/or loss of bowel or bladder control is a late and ominous manifestation. In addition to plain radiographs, MRI is the study of choice for evaluating patients with suspected spinal cord compression. Gadolinium contrast provides optimal imaging of extramedullary and intramedullary lesions. In cases of rapid compression of the spinal cord, therapeutic intervention must be performed immediately to avoid irreversible neurologic deficits. The patient should be immediately started on steroids, and treatment options include radiation therapy, surgery, chemotherapy, or a combination of all three. Laminectomy is effective in managing patients with epidural masses, and in select cases, surgical resection of the mass may be possible. As mentioned earlier, the functional status at the time of presentation clearly correlates with the posttreatment outcome; early diagnosis and recognition is crucial.

 IX. VASCULAR ACCESS

1. Central venous catheterization. Many cancer patients require frequent venous catheterization for phlebotomy, chemotherapy, or infusions. Peripheral venous sites for catheterization can become quickly exhausted because of the venotoxic effects of the cytotoxic agents, the trauma of repeated use, and the undesirability of performing access procedures in limbs with proximal lymphadenectomies. Central venous catheters are designed for repeated venous access. Although they are generally easily placed, complications of placement include pneumothorax, hemothorax, air embolism, cardiac arrhythmia, and arterial injury. Over the long term, these catheters can cause central vein thrombosis, embolism, infection, and scarring. Infection and symptomatic catheter-associated thrombosis are indications for catheter removal. Relative contraindications to placement include uncorrected thrombocytopenia or coagulopathy and previous irradiation to the head or neck, which can result in scarring. For these latter patients or patients with a known history of central vein thrombosis, an ultrasonography before the procedure may be useful to establish the patency of their veins. Patients who are hypercoagulable from their cancers may benefit from low-dose warfarin (1 to 2 mg/day) to prevent central venous thrombosis. Catheters are available in tunneled externalized types (Hickman, Broviac) or implantable types (Portacath, Infusaport). They may be placed under local anesthesia, with or without sedation, on an outpatient basis. The choice of catheter type and placement location will depend on a number of factors, including the expected duration of therapy requiring the catheter, the anticipated infection risk to the patient, any history of prior central lines or central vein thrombosis, and the number of lumens needed. It is important to discuss these factors beforehand with the surgeon or radiologist who will be performing the procedure.
2. Arterial catheters: hepatic artery infusion catheters. Hepatic artery infusion (HAI) catheters are an option for treating hepatic metastases in patients with unresectable disease. HAI chemotherapy targets liver metastases, which derive most of their blood supply from the hepatic arterial circulation, in contrast to normal liver, which derives most of its blood supply from the portal circulation. In addition, higher levels of local therapy can be achieved without concomitant systemic toxicity owing to the clearance of many chemotherapeutic agents from first pass through the liver. HAI chemotherapy is generally reserved for patients without evidence of extrahepatic disease. Traditionally, catheters have been placed surgically by laparotomy, though percutaneous placement under radiographic guidance by interventionalists is currently under study in clinical trials. Before placement, patients undergo an angiogram to define regional arterial anatomy because of the highly variant arterial anatomy in this area. The infusion port or continuous infusion pump is placed in the abdominal subcutaneous tissues over the rectus muscle fascia, and the catheter is tunneled into the abdomen. The tip of the catheter is placed in the gastroduodenal artery at its junction with the common hepatic artery. Cholecystectomy is required to prevent chemotherapy-induced chemical cholecystitis, and complete separation of the hepatic arterial circulation from the gastroduodenal blood supply must be achieved to prevent GI toxicity. Postoperatively, radiolabeled microaggregated albumin is injected into the infusion pump, and a scintillation scan is obtained to verify hepatic infusion and exclusion of extrahepatic perfusion. Chemotherapeutic agents are injected into the port reservoir, which is designed to ensure continuous infusion of a constant amount of agent. Studies have demonstrated higher response rates with HAI than with systemic chemotherapy; however, no survival advantage has been observed. Current strategies combine liver resection, residual tumor ablation, and HAI pump placement.

 X. ENTERAL FEEDING TUBES. Malnutrition is common in the cancer patient and may be related to inadequate voluntary intake, altered metabolism, or the effects of therapy. Enteral alimentation can be useful before or after surgery or during therapy. Early concerns that hyperalimentation would lead to rapid tumor growth have not been borne out by experience, and in severely malnourished patients (less than 80% standard weight for height), there is a measurable improvement in operative morbidity if nutritional supplementation is provided 7 to 10 days before surgery. Postoperatively, enteral or parenteral alimentation can support the cancer patient who is unable to eat because of a healing anastomosis or a postoperative ileus. During chemotherapy or radiation therapy, inflammation, infection, or strictures may lead to inadequate oral intake requiring enteral alimentation. The route of administration of nutritional support is selected on the basis of length of anticipated need, intestinal tract function, degree of malnutrition, access for administration, and potential complications. In patients with adequate GI function, enteral alimentation is preferred over the parenteral route. Enteral alimentation is less expensive, leads to fewer metabolic imbalances, preserves the GI architecture, and is thought to prevent bacterial translocation. The most common morbidities associated with enteral alimentation are abdominal distention, nausea, or diarrhea, which can occur in 10% to 20% of patients. These symptoms usually abate with a decreased rate of infusion or strength of the formula.

1. Gastrostomy tubes. Gastrostomy tubes (G-tubes) may be placed percutaneously, laparoscopically, or via laparotomy. They can serve the dual functions of conduits for feeding or intestinal decompression. Other advantages of a G-tube are bolus feeding with high-osmolar formulas because of the reservoir capacity of the stomach, and the ability to replace dislodged tubes easily through the gastrocutaneous fistula. Disadvantages include risk of aspiration in patients with lower esophageal sphincter dysfunction or without an intact gag reflex. Enteral feeds can be administered by bolus (200 to 400 mL over a 5- to 10-minute period) and is the preferred feeding method in ambulatory patients because it is less confining. Crushed pills may be administered through G-tubes.
2. Jejunostomy tubes. Jejunostomy tubes (J-tubes) are small-caliber feeding tubes placed distal to the ligament of Treitz by laparotomy or laparoscopy. The advantages of J-tubes are the minimal risk of aspiration and the ability to feed distal to the obstruction or fistula. Because there is no reservoir capacity, enteral feeds are administered continuously over 12- to 24-hour periods, and there is limited tolerance to high-osmolar loads. Once dislodged, these tubes are not easily replaced. In addition, because of the small caliber, these tubes may become clogged with inspissated material and require vigorous flushing to reestablish patency. For this reason, crushed pills should not be administered via most standard J-tubes, although medications in liquid form may be given via this route.