Histologic Diagnosis

A pathologic diagnosis should be secured before the definitive surgical procedure in some patients. The goal of the diagnostic biopsy is to obtain sufficient tissue for complete analysis with minimal risk for complication. Whenever possible, to avoid leaving tumor seeding in the biopsy tract, the biopsy site should be positioned within the proposed surgical resection specimen. Either cytologic or histologic samples are adequate for most cancers, but a histologic diagnosis is usually preferable. A false-negative cytologic result occurs in 10% to 20% of cancer patients, and rare false-positive cytologic diagnoses have been reported. Biopsies that sample a tumor may underestimate the aggressiveness of a lesion (e.g., atypia or carcinoma in situ instead of invasive cancer) due to sampling error. A diagnostic tissue specimen may be obtained by aspiration cytology, core-needle biopsy, incisional biopsy, or excisional biopsy. A separate biopsy procedure is unnecessary unless it affects preoperative treatment planning. Endoscopically or laparoscopically directed biopsies allow more accurate staging of intra-abdominal malignancies than noninvasive procedures and provide tissue for diagnosis.

Fine-needle aspiration cytology (FNAC) is widely used to evaluate solitary thyroid nodules. Using a 21-gauge needle and syringe, an aspirate of cellular material or fluid is obtained, differentiating between solid and cystic masses. If a cyst does not completely disappear with aspiration, FNAC examination of any residual solid component is necessary. The success of FNAC depends on the experience of the clinician performing the aspiration and on the interpretation of a skilled cytologist. FNAC of the thyroid enables the pathologist to differentiate most benign from malignant tumors. Papillary, medullary, and anaplastic carcinomas have a typical cytologic appearance. Cytology cannot differentiate benign from malignant follicular and Hürthle cell neoplasms. A definitive diagnosis for these thyroid neoplasms depends on histologic examination of the entire excised tumor. The introduction of routine FNAC has dramatically reduced the number of diagnostic surgical operations for benign thyroid masses.

Percutaneous radiograph-directed FNAC has gained great popularity over the past 25 years.¹ Ultrasonography or CT scanning is routinely used to obtain hepatic, renal, pancreatic, and retroperitoneal biopsies. Percutaneous biopsy techniques are particularly useful to confirm the presence of metastases in a patient with a prior malignant tumor. Adrenal FNAC should be avoided if a pheochromocytoma has not been excluded. If potentially curable metastases (e.g., limited hepatic metastases from colorectal cancer) are present, this diagnostic test is unwarranted and potentially dangerous because it rarely results in tumor seeding. If unresectable cancer is present at exploratory laparotomy, a confirmatory biopsy should be obtained.

The choice of ultrasonographic or CT guidance depends on several factors. In general, ultrasonography is used for superficial lesions. Ultrasonography possesses other advantages, including real-time imaging, which allows constant monitoring of the needle position, and lower costs compared with CT scanning. Ultrasonographic examination is limited by overlying bone and gas. CT guidance is more beneficial for deeper tumors, particularly in the retroperitoneum. Advantages of CT-guided biopsy include better spatial resolution and lack of interference from air or bone. Intravenous contrast provides an estimate of tumor vascularity.

Core-needle biopsy can be performed by hand if the mass is easily palpable and can be stabilized by the operator. Radiographically directed core biopsies, particularly of solid breast masses, are commonly performed preoperatively. Unlike an FNAC, a core biopsy provides sufficient tissue for histologic analysis. Using local anesthesia, a small (3-mm) incision is made in the skin through which a coring biopsy needle is directed into the center of the lesion. Typically, a 1- × 10- to 20-mm tissue sample is obtained. Core-needle biopsy may also be performed with stereotactic imaging or ultrasonography for nonpalpable breast lesions.

Core-needle biopsies of intra-abdominal and thoracic tumors offer the advantages of a histologic diagnosis and greater accuracy than the FNAC. Larger-bore needles can cause complications, most commonly hemorrhage. Some tumors, including many adjacent to major blood vessels, are not safely accessible percutaneously. Core-needle biopsy should not be used for potentially resectable malignancies because of a higher risk of needle track seeding than with FNAC. Intraoperative diagnostic core biopsies are preferable to incisional biopsies when a diagnosis is needed for an unresectable tumor. The decision to resect or not, as in a pancreaticoduodenectomy for painless jaundice, should be based on the clinical and operative findings; a histologic diagnosis is not mandatory before resection.

Incisional biopsy excises more of a tumor mass than needle biopsy. A full-thickness biopsy using a scalpel or punch biopsy tool of a larger skin tumor is a commonly performed incisional biopsy. A full-thickness sampling of the thickest portion of the lesion should be removed to allow accurate tumor staging. Sometimes an incisional biopsy of a sarcoma is performed to provide the diagnosis before proceeding with definitive treatment (e.g., amputation, preoperative chemotherapy or radiation), but core-needle biopsies are another option. An incisional biopsy of an extremity tumor is preferably obtained through a longitudinal rather than a transverse incision because the longitudinal incision can be more readily incorporated with a wide local excision.² Intraoperative incisional biopsies during thoracotomy and laparotomy are rarely indicated; tumor spillage is more likely than with FNAC or core-needle biopsies.

Excisional biopsy of a breast mass illustrates the key principles of a diagnostic surgical biopsy. This procedure can be used for small, palpable lesions amenable to easy complete excision. A diagnostic excisional breast biopsy is now rarely performed. Almost all breast cancers are diagnosed with FNAC or core biopsy preoperatively. If possible, the skin incision should be circumareolar or situated within the elliptical incision that would be used for a mastectomy (Fig. 7-1). If the breast mass is believed to be malignant, it should be excised with a 1-cm margin of normal tissue, centering the suspicious lesion in the specimen (Fig. 7-2A). The biopsy specimen should be oriented to permit the pathologist to specify which of the resection margins, if any, are histologically involved by tumor. Specimen orientation can be denoted with two sutures (see Fig. 7-2B) or by painting the specimen with multiple colored stains. If frozen-section evaluation of the resection margins is available, re-excisions can be performed immediately when necessary. When frozen-section evaluation is unavailable, separate, individually labeled margins may be sent in addition to the primary tumor specimen. Selective re-excision can be performed at a later date if the main specimen has been appropriately orientated with sutures, clips, multicolored inks, or separate margins. Surgical clips left at the base of the biopsy cavity facilitate accurate partial breast or boost-field radiation therapy after breast-conservation surgery. Small titanium clips provide accurate localization for the radiation oncologist with minimal interference on future images, including MRI.

Figure 7-1 Excisional breast biopsy performed within the confines of a mastectomy incision.

Courtesy the Mayo Foundation.

Figure 7-2 A, Excisional breast biopsy. B, Specimen orientation.

Courtesy the Mayo Foundation.

Staging

The stage of a malignant tumor usually determines the goal of intervention. Symptoms or physical signs frequently alert the clinician to metastatic disease, but diagnostic studies are usually required to confirm distant disease spread. Accurate preoperative staging results in the best treatment because the extent of tumor spread remains the single most important determinant of patient prognosis.

Clinical and pathologic stages of disease for most cancers have been standardized in the American Joint Committee for Cancer (AJCC) TNM system.³ In this nomenclature, T refers to the primary tumor, N indicates the status of regional lymph nodes, and M denotes the presence or absence of metastatic disease. For most cancers, the size (e.g., in lung, liver, or breast cancers) or the degree of invasion (e.g., in melanoma or stomach or colorectal cancers) of the primary tumor correlates with the probability of metastases.

Clinical tumor staging is normally determined using combined data from physical examination, a variety of radiologic tests (including plain radiographs, ultrasonography, CT, and MRI), and endoscopic examination. Positron emission tomography (PET)-CT imaging provides more sensitive staging compared with other imaging studies in a number of disease sites. PET-CT can be especially helpful in the diagnosis of unsuspected metastatic disease (e.g., esophageal cancer; melanoma) and in evaluating patients with possible recurrent cancer (e.g., locally recurrent rectal cancer). In symptomatic patients, skeletal metastases can also be diagnosed with a radioisotope bone scan or correlative plain radiographs.

Role of Laparoscopy

The introduction of laparoscopy in general surgical practice has led to more precise staging of many intra-abdominal malignancies, particularly gastric,⁴ pancreatic,⁵ and hepatobiliary cancers.^6,7 Thoracoscopy allows inspection and biopsy of the pleural cavity to assess for intrathoracic tumor spread. When used for diagnosis, laparoscopy allows visualization of peritoneal surfaces; histologic evaluation of peritoneal, omental, or hepatic tumor masses; biopsy of lymph nodes; and collection of ascites or peritoneal washings for cytologic examination. Laparoscopic ultrasonography further improves the staging of pancreatic and hepatobiliary malignancies.^8–10 If the laparoscopic findings confirm metastatic malignancy, the attendant morbidity from tumor resection by traditional or minimally invasive techniques can be avoided. Laparoscopic techniques can be used for cancer therapy to palliate patients with advanced malignancy and curatively resect others.¹¹

Staging of Pancreatic Malignancy

Laparoscopy is frequently used to stage pancreatic and periampullary carcinomas because hepatic or peritoneal metastases undetectable by radiographic means occur in up to 30% of patients with tumors believed to be resectable preoperatively.^5,12,13 A complete laparoscopic inspection of the abdominal cavity is undertaken using a 5- or 10-mm port at the umbilicus (Fig. 7-3). Additional subcostal cannulae allow for retraction of the liver, omentum, and loops of intestine. Inspection of the upper abdomen, looking for small hepatic metastases or drop metastases on the parietal and visceral peritoneum or the greater omentum, is readily accomplished. Any suspicious lesions should be sampled using a biopsy forceps or core-needle biopsy tool. The remainder of the abdomen can be examined, including the peritoneal surfaces, for seeding and dependent areas for ascites. Evidence of direct spread of a pancreatic carcinoma into the transverse mesocolon and small bowel mesentery should be assessed.

Figure 7-3 Laparoscopic examination of the upper abdominal cavity.

Courtesy the Mayo Foundation.

With the patient in the reverse Trendelenburg position, limited visualization of the anterior surface of the pancreas may be obtained with a supragastric approach after division of the lesser omentum (Fig. 7-4A) or an infragastric approach, entering the lesser sac through the gastrocolic omentum (see Fig. 7-4B). Biopsy of peritoneal implants within the lesser sac should be obtained. Laparoscopic ultrasonography provides a more accurate assessment of visceral vascular involvement and deep hepatic metastases,¹⁰ although endoscopic ultrasonography (EUS) provides highly accurate staging in these sites.

Figure 7-4 Laparoscopic examination of the pancreas: supragastric (A) and infragastric (B) approaches.

Courtesy the Mayo Foundation.

Goals of Surgical Intervention

The primary intent of surgical intervention is curative resection. The surgeon must be familiar with the cancer biology, including modes of spread (i.e., hematogenous, lymphatic, intracavitary, or direct extension). En bloc excision of the tumor is performed for the highest probability of cure (complete resection or R0 resection = no residual tumor). Complete extirpation of the primary tumor with a margin of normal tissue plus a regional lymph node dissection typifies this type of resection. For cancers such as colon carcinomas or retroperitoneal sarcomas, normal adjacent structures directly invaded or adherent to the malignancy should also be resected. Lysis of adhesions between a primary cancer and an adjacent structure can result in residual cancer and tumor spillage. When the local extent of a nonmetastatic malignancy prevents a gross total resection with negative margins, the surgeon should facilitate postoperative irradiation planning by leaving titanium clips at the site of residual microscopic disease (R1 resection = microscopic residual cancer).

Certain intra-abdominal malignancies are appropriately treated by surgical debulking (R2 resection = gross residual disease) plus perioperative therapy. Examples include ovarian carcinomas and rare low-grade mucinous adenocarcinomas, known traditionally as pseudomyxoma peritonei, that are usually of appendiceal origin. The goal of operative therapy is to remove as much macroscopic intra-abdominal disease as is feasible because patient outcome is improved.

For patients with known metastatic disease who have symptoms or are at risk for complications from locally advanced disease, surgical palliation (R1 or R2 resection) should be considered. Operative procedures should be reserved for well-defined problems amenable to surgical treatment in patients with reasonable performance status and life expectancy. Intestinal obstruction can be corrected by a resection, bypass, or proximal diversion (i.e., ostomy formation). When technically feasible, laparoscopic, laparoscopically assisted (i.e., mobilization using laparoscopic technique and a portion of the procedure performed through a limited celiotomy), and endoscopic stenting techniques are suitable and preferable to a formal laparotomy. Diffuse peritoneal implantation often prevents successful palliation and increases the risk of postoperative complications, including infection and intestinal fistula formation. The surgeon may prevent life-threatening hemorrhage or improve pain by resection of some cancers. Pain can also be alleviated by nerve transection or blockade, such as celiac plexus block for pancreatic carcinoma.

Perioperative Care of the Oncology Patient

The cancer patient may develop unique perioperative problems. The surgeon must strive to avoid such problems and must monitor the patient for their occurrence to minimize morbidity and minimize delays in adjuvant therapy. Patients with malignancy have a higher prevalence of postoperative complications because of their neoplastic disease, coincidental co-morbidities in older patients, the major surgical procedures patients have undergone, and perioperative and adjuvant therapy-induced immunosuppression. Patients with gastrointestinal malignancies with or without obstruction frequently suffer from substantial weight loss, malnutrition, and resultant immunodeficiency. The hematologic, gastrointestinal, pulmonary, and cardiac toxicities associated with chemotherapy pose additional risks for the postoperative oncologic patient. Before adjuvant therapy is started, sufficient time must be allowed to pass for wound healing and resolution of infectious complications to occur.

The extent and type of operative management must take into account the patient’s preexisting and malignancy-induced comorbidities. Cancer cachexia resulting from anorexia is common and results in significant lean tissue loss and immunodeficiency. Because malnutrition significantly increases the risk for perioperative morbidity, the surgeon must carefully assess the degree of preoperative malnutrition. Although retrospective studies evaluating preoperative nutritional support show a reduction in postoperative complications for patients with severe malnutrition,¹⁴ a meta-analysis did not support routine preoperative nutrition for oncologic patients.¹⁵ Total parenteral nutrition should be reserved for patients unable to tolerate enteral nutrition, those unable to take sufficient calories by oral or enteric routes during therapy, and those felt to be unsuitable for operative or combined-modality therapy until their nutritional status improves. Enteral rather than parenteral nutrition should be used whenever possible. Postoperative nutritional support should always be considered, especially in patients with upper gastrointestinal malignancies such as esophageal, gastric, and pancreatic cancers. A feeding jejunostomy catheter placed intraoperatively facilitates delivery of postoperative nutrition.

The oncologic patient has a higher risk for postoperative infection. Immune compromise in cancer patients occurs due to older age, surgical stress, malnutrition, and impaired host defense mechanisms. Neutropenia combined with defective cell-mediated immune responses render malnourished patients especially prone to postoperative complications and impair the patient’s response to sepsis. Appropriate perioperative antibiotics and vigilant postoperative observation for infection are critical in reducing the morbidity of postoperative infections.

Older age, the presence of a malignancy, and undergoing operative procedures all increase the incidence of thromboembolic complications. A hypercoagulable state is especially common in patients with pancreatic, prostate, lung, breast, and gastric cancers. Increased factors I, V, VIII, IX, and XI; decreased proteins C and S; and reduced antithrombin III levels have all been implicated in higher rates of thromboembolic events in cancer patients. Perioperative subcutaneous heparin (both low-molecular-weight and unfractionated heparin are appropriate treatments), thromboembolic stockings, and sequential compression devices should be used for all oncologic surgical patients. Patients at high long-term risk for thromboembolic complications (e.g., prior history of deep venous thrombosis/pulmonary embolism (DVT/PE), inherited hypercoagulable trait, debilitated patient, or those with residual cancer) need to be considered for extended anticoagulation therapy.

Patients with malignancy are often anemic. Blood transfusions result in immunosuppression, including depression of specific cellular immunity, and nonspecific immune responses, including natural killer cell activity and macrophage phagocytosis. Some retrospective studies have shown higher cancer recurrence rates in cancer patients receiving blood transfusions, but controlled trials have not demonstrated a poorer disease-specific survival rate specifically related to perioperative transfusions.^16,17 Blood transfusion must be administered as appropriate in oncologic patients.

Radiation Therapy and Wound Healing

Tissues exposed to radiation therapy develop acute inflammatory changes in proportion to the total dose. Higher-dose fractions cause more significant changes. Acute radiation injury is manifested by vasodilation (erythema) and tissue edema. Following moderate-dose preoperative radiation (45 to 50 Gy in 1.8- to 2.0-Gy fractions), a 3- to 6-week preoperative recovery period is generally allowed for partial resolution of acute radiation changes.¹⁸ Late radiation changes include atrophy and fibrosis, which result from decreased tissue vascularity.

Wound healing is impaired in irradiated tissue by several factors, including diminished blood supply, impaired collagen formation, and the increased risk of infection resulting in part from decreased leukocyte function. After high-dose irradiation, slow and nonhealing wounds are commonplace. In this situation, nonirradiated tissues, such as vascularized myocutaneous flaps, need to be transferred into the radiation field to allow proper wound healing.¹⁹ This is preferably done at the time of tumor resection rather than after a nonhealing postoperative wound develops. If partial resection of an irradiated hollow organ (e.g., bowel, bile duct, trachea) is necessary, one side of the anastomosis should be nonirradiated tissue whenever possible. This precaution provides a better blood supply for healing of the anastomosis. This policy will reduce the incidence of early postoperative leak and fistula formation and late anastomotic strictures.

Surgical Treatment of Breast Cancer

The treatment of breast cancer patients should occur in a multidisciplinary setting. Ideally, patients are evaluated in a breast clinic with treatment specialists, including a surgeon, radiation oncologist, medical oncologist, nurse, and medical geneticist providing preoperative consultation. There should be a focus on patient education regarding the treatment options currently available for both operative and nonsurgical adjuvant therapies.

Most women with breast cancer can now choose breast conservation. Data from multiple mature, controlled trials have demonstrated no significant difference in disease control or survival between patients who elect breast-conservation therapy and those who choose mastectomy.20,21,22 Mastectomy is a suitable option if the woman chooses this form of treatment. Mastectomy is preferable for the management of multicentric disease and most large primary tumors (neoadjuvant chemotherapy may allow breast conservation in patients with a sufficient response) and in patients unable to receive postoperative radiation therapy. The majority of patients undergoing mastectomy can have immediate breast reconstruction, if desired. Consultation with a plastic surgeon should be obtained preoperatively to allow the patient to assess the immediate reconstruction options. The timing of breast reconstruction depends partly on patient preference. In addition, if chest wall irradiation is indicated by the breast cancer stage, the immediate reconstruction results are often cosmetically affected.

Early Breast Cancer

Most women with early-stage breast cancer (i.e., stage 0, I, or II breast cancers) are suitable candidates for breast-conservation surgery. The goals of breast-conservation surgery are optimal locoregional control of the breast cancer and preservation of the natural appearance of the breast. All known breast cancers must be excised from the breast and axilla. (It is not necessary to pathologically stage the axilla for most ductal carcinomas in situ.) Radiation therapy must be administered following breast-conservation surgery to reduce the risk of local tumor recurrence, given the high incidence of residual microscopic disease, even with pathologically clear margins. Because radiation therapy is an integral component of breast conservation, patients who are unsuitable for radiotherapy should not undergo this form of surgery. Contraindications to breast-conservation surgery include a history of certain collagen vascular diseases (e.g., scleroderma, polymyositis), the presence of diffuse indeterminate or suspicious calcifications on mammography, a history of therapeutic irradiation to the breast, and positive margins of resection despite wide excision.

Breast-conserving surgery is performed through an incision as close to the primary tumor as possible, whether the lesion is a palpable mass or a mammographic abnormality that has been localized. It is best to remove the entire abnormality with a 1-cm margin of grossly normal tissue. A curvilinear incision in Langer’s lines optimizes the cosmetic result in most locations, whereas a radial incision may be preferable in the lower quadrants. Incisions should be positioned to allow them to be included in a standard mastectomy incision wherever possible. After specimen excision, markers (e.g., sutures, clips, dyes) should be placed on the tissue to provide orientation. If frozen-section pathologic analysis is available, evaluation of margins can be obtained intraoperatively. If margin evaluation is performed later, correct specimen orientation will result in less tissue re-excision when the original specimen has tumor involvement of one or more margins. Titanium clips are placed at the base of the biopsy cavity to help target postoperative irradiation. The breast wound is usually closed without approximation of the breast parenchyma. Oncoplastic closures with mobilization of flaps can provide better cosmesis, especially with larger tumor excisions.

Sentinel lymph node biopsy or axillary lymph node dissection is best performed through a separate incision. The axillary incision should be placed between the axillary folds and not cross the lateral border of the pectoralis major muscle (Fig. 7-5). Axillary staging aids patient management in determining prognosis and systemic adjuvant treatment. Patients with positive axillary nodes are almost routinely advised to receive systemic treatment, usually combination chemotherapy. Postoperative therapy commences after sufficient wound healing has occurred, usually within 4 weeks.

Figure 7-5 Incision of axillary dissection.

Courtesy the Mayo Foundation.