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III-12. The answer is B. (Chap. 84) Epigenetics is a term that refers to changes in the chromatin structure of the cell that lead to alterations in gene expression without underlying changes in the DNA code. As such, these changes are potentially reversible and may be targets for cancer therapy. An example of an important epigenetic change is hypermethylation of promoter regions (so-called CpG islands) in tumor suppressor genes that lead to the inactivation of one allele of the gene.

III-13. The answer is A. (Chap. 85) Generally, when metastatic disease is observed, surgical interventions do not change the outcome of a particular cancer. However, in a few instances, one should consider surgery as potentially curative. One example is metastatic osteosarcoma to the lung, which can be cured by resection of the lung lesion. There are other instances in which surgery may be effective in patients with metastatic disease. In non–small cell lung cancer, individual with a solitary brain metastasis at the time of diagnosis may also be treated with resection of the brain and lung lesions in a staged fashion. In colon cancer with liver metastases, hepatic lobectomy may produce long-term disease-free survival in as many as 25% of individuals if fewer than five lesions are observed in a single hepatic lobe. Another role for surgical resection in metastatic disease is to remove the source of hormone production that can stimulate cancer growth. This is occasionally recommended in prostate cancer, although antiandrogen therapy is most commonly used.

III-14. The answer is D. (Chap. 85) Clinical trials in cancer drug discovery follows a stepwise process before the drug is determined to be safe and effective for treatment of a specific cancer. Before proceeding to trials in human, cancer drugs must demonstrate antitumor activity with a specific dose and interval in animal trials. After this, drugs enter phase I trials to establish safe dosage range and side effects in humans. Clinical antitumor effect is observed, but phase II trials enroll a larger group of people to more rigorously quantify antitumor effects in humans. Further side effect data is collected as well. The dose given in phase II trials is the maximal tolerated dose determined in phase I trials. Although phase I trials often given escalating doses of an agent, phase II trials use a fixed dose, and the drug is given to only a very select and homogeneous group of patients. An agent is determined to be “active” and may proceed to a phase III trial if there is a partial regression rate of at least 20% to 25% with reversible non–life-threatening side effects. Phase III trials enroll the largest numbers of patients and often compare the drug with standard therapies for the particular cancer. Phase IV trials occur after release of the drug and are called postmarketing studies. These trials provide important information about risks, benefits, and optimal use in the general population of patients with a particular cancer, which can often be quite different than those patients enrolled in a clinical trial.

III-15. The answers are 1—D, 2—C, 3—A, 4—E, and 5—B. (Chap. 85) Cancer chemotherapy typically requires actively dividing cells to exert their actions to kill the cancer cells. The mechanism of action of the majority of chemotherapeutic agents can be broadly categorized as those affecting DNA, those affecting microtubules, and molecularly targeted agents. Within each of these broad categories, several common families of drugs operating have distinct mechanisms of action. DNA alkylating agents are cell cycle phase nonspecific agents that covalently modify DNA bases and lead to cross-linkage of DNA strands. These cells become unable to complete normal cell division. Examples of common DNA alkylating agents are cyclophosphamide, chlorambucil, dacarbazine, and the platinum agents (carboplatin, cisplatin, and oxaliplatin). Antitumor antibiotics are naturally occurring substances typically produced by bacteria that bind to DNA directly and cause free radical damage that leads to

DNA breakage. Included in this group are topoisomerase poisons that are derived from plants that prevent DNA unwinding and replication. Examples of agents in this category are bleomycin, etoposide, topotecan, irinotecan, doxorubicin, daunorubicin, and mitoxantrone. Other drugs that are common anticancer agents affect DNA indirectly, especially through interference in the synthesis of purines or pyrimidines. This category of agents is known as antimetabolites and includes methotrexate, azathioprine, 5-fluorouracil, cytosine arabinoside, gemcitabine, fludarabine, asparaginase, and pemetrexed, among others.

Chemotherapeutics agents that target the microtubules interfere with cell division by inhibiting the mitotic spindle. These antimitotic agents include vincristine, vinblastine, vinorelbine, paclitaxel, and docetaxel, among others.

Molecularly targeted agents are relatively new agents for the treatment of malignancy. When compared with traditional cancer chemotherapy, these agents are directed against specific proteins within cells that are important in cell signal processing. There are many different types of molecularly targeted agents with the largest class being tyrosine kinase inhibitors. Commonly used tyrosine kinase inhibitors include imatinib, gefitinib, erlotinib, sorafenib, and sunitinib. All-trans retinoic acid is another example of a molecularly targeted agent that attaches to the promyelocytic leukemia–retinoic acid receptor fusion protein to stimulate differentiation of the promyelocytes to mature granulocytes. Other categories of targeted agents include histone deacetylase inhibitors and mTOR (mammalian target of rapamycin) inhibitors.

III-16. The answer is E. (Chap. 85) Myelosuppression predictably occurs after administration of a variety of chemotherapeutic agents. Antimetabolites and anthracyclines (including doxorubicin) typically cause neutropenia between 6 and 14 days after administration of the agent. Febrile neutropenia is diagnosed based on a single temperature greater than 38.5°C or three temperatures greater than 38.0°C. Treatment of febrile neutropenia conventionally includes initiation of treatment with broad-spectrum antibiotics. If there is no obvious site of infection, then coverage for Pseudomonas aeruginosa is recommended. Active antibiotics include third- or fourth-generation cephalosporins (including ceftazidime), antipseudomonal penicillins, carbapenems, and aminoglycosides. Vancomycin should be considered in this patient because of her tunneled intravenous catheter despite the apparent lack of cutaneous infection and would be continued until culture demonstrated the absence of a resistant organism. There is no need for an antifungal agent because this patient has not had prolonged neutropenia, and this is the first fever recorded. Moreover, given the chemotherapy given, the expected duration of neutropenia is expected to be relatively brief. In many instances such as this, oral antibiotics such as ciprofloxacin can be given.

There is no role for granulocyte transfusions in the treatment. However, the use of colony-stimulating factors often is considered. These agents have historically been overused, and the American Society of Clinical Oncology has developed practice guidelines to assist in determining which patients should receive colony-stimulating factors. Briefly, there is no evidence for benefit in either febrile or afebrile neutropenic patients, and they should not routinely be used in acute myeloid leukemia or myelodysplastic syndromes. The only therapeutic use is in individuals who have undergone bone marrow or stem cell transplantation to speed myeloid recovery. The primary use of colony-stimulating factors is in the setting of prevention. Because this patient has now experienced an episode of febrile neutropenia, she should be given colony-stimulating factors beginning 24 to 72 hours after chemotherapy administration, and the medication should continue until the neutrophil count is 10,000/μL or greater. Colony-stimulating factors may be given after the first cycle of chemotherapy if

the likelihood of febrile neutropenia is greater than 20%, if the patient has preexisting neutropenia or active infection, if the patient is older than 65 years of age and is being treated for lymphoma, or if the patient has a poor performance status or has had extensive prior chemotherapy.

III-17. The answer is E. (Chap. 85) Nausea with or without vomiting is the most common side effect of chemotherapy. It can be anticipatory in nature, acute, or occur more than 24 hours after administration. Patients at increased risk of nausea include younger patients, women, and those with a history of motion or morning sickness. The chemotherapeutic agents used also alter the risk of nausea and vomiting. Highly emetogenic drugs include high-dose cyclophosphamide and cisplatin. Low-risk drugs include fluorouracil, taxanes, and etoposide. In patients receiving high-risk regimens, prophylactic treatment with a combination of medications acting at different sites is recommended. Typically, the regimen would include a serotonin antagonist such as dolasetron, a neurokine receptor antagonist such are aprepitant, and potent corticosteroids such as dexamethasone.

III-18. The answer is C. (Chap. 86) Patients who have undergone allogeneic stem cell transplant remain at risk for infectious complications for an extended period despite engraftment and apparent return of normal hematopoietic capacity. Individuals with graft-versus-host disease (GVHD) often require immunosuppressive treatment that further increases their infectious risk. Prevention of infection is the goal in these individuals, and the clinician should ensure appropriate vaccinations for all patients who have undergone intensive chemotherapy, have been treated for Hodgkin’s disease, or have undergone hematopoietic stem cell transplant. No vaccines except influenza should be given before 12 months after transplant. Then the only vaccines that should be given are inactivated vaccines. Therefore, oral vaccine for poliomyelitis and the varicella zoster vaccine are contraindicated. The measles, mump, and rubella vaccine is also a live virus vaccine, but can be safely given after 24 months if the patient does not have GVHD. Other recommended vaccines include diphtheria–tetanus, inactivated poliomyelitis (by injection), Haemophilus influenzae type B, hepatitis B, and 23-valent pneumococcal polysaccharide vaccine. Meningococcal vaccination is recommended in splenectomized patients and in those living in endemic areas, including college dormitories.

III-19. The answer is B. (Chap. 86) Specific malignancies are associated with underlying immune dysfunction and infection with specific organisms. Chronic lymphocytic leukemia and multiple myeloma may have an associated hypogammaglobulinemia. Individuals with these disorders are at risk of infections with Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. Although immunoglobulin therapy is effective, it is more cost effective to give prophylactic antibiotics in these patients. Acute myeloid or lymphocytic leukemias often have an associated neutropenia and may present with overwhelming infection from extracellular bacteria and fungi, especially if the duration of neutropenia is prolonged. Patients with lymphomatous disorders often have abnormal T-cell function despite normal numbers of T cells. Moreover, most patients also receive treatment with high doses of glucocorticoids that further impair T-cell function. These individuals have an increased risk of infection with intracellular pathogens and may contract pneumonia with Pneumocystis jiroveci.

III-20. The answer is D. (Chap. 86) Clinicians are often faced with treatment decisions regarding catheter-related infections in patients who are immunocompromised from cancer and chemotherapy. Because many patients require several weeks of chemotherapy, tunneled catheters are often placed, and determining the need for catheter removal is an important consideration. When blood culture results are positive or there is evidence of infection along the track of the tunnel, catheter removal is

recommended. When the erythema is limited to the exit site only, then it is not necessary to remove the catheter unless the erythema fails to respond to treatment. The recommended treatment for an exit site infection should be directed against coagulase-negative staphylococci. In the options presented, vancomycin alone is the best option for treatment. There is no need to add therapy for gram-negative organisms because the patient does not have neutropenia and has negative culture results.

III-21. The answer is A. (Chap. 87) The staging criteria for melanoma include the thickness of the lesion, the presence of ulceration, and the presence and number of involved lymph nodes. Of these, the single best predictor of metastatic risk is the Breslow thickness, particularly greater than 4 mm, although the other factors also provide additional predictive value. Other factors that predict survival in melanoma are younger age, gender with female sex predicting a better survival, and anatomic site with favorable sites being the forearm and leg. The Clark level defined melanoma based on the layer of skin to which a melanoma had invaded, but this has been found to be not predictive of metastatic risk.

III-22. The answer is E. (Chap. 87, Chapman PB et al: N Engl J Med 2011; 364: 2507-2516) Treatment of metastatic melanoma has largely shown very little improvements on mortality in this disease. The median survival after diagnosis of metastatic disease is typically 6 to 15 months. Until August 2011, the only Food and Drug Administration (FDA)–approved chemotherapy for the treatment of metastatic disease was dacarbazine, although response rates are about 20% or less. Interleukin-2 therapy has also been attempted alone or in combination with interferon-α. This therapy has lead to long-term disease-free survival in about 5% of treated patients but is associated with significant toxicity that limits its usefulness. Interleukin-2 should only be administered to patients with good performance status and at centers experienced in the treatment of IL-2 toxicity. Most recently in August 2011, the FDA approved the drug vemurafenib (PLX4032) for the treatment of metastatic melanoma. This drug targets BRAF, which is a common mutation in melanoma that results in constitutive activation of the mitogen-activated protein (MAP) kinase pathway. Vemurafenib has specifically demonstrated to have the best activity against the BRAF V600E mutation, the most common kinase mutation in metastatic melanoma. Data published in 2011 demonstrated that individuals with this specific mutation have response rates of 48% to the drug compared with only 5% for dacarbazine. Furthermore, the 6-month survival was 84% in the vemurafenib group compared with only 64% in the dacarbazine group. Ipilimumab is another promising new therapy for the treatment of metastatic melanoma. This treatment is a monoclonal antibody that blocks cytotoxic T-cell antigen 4 (CTLA-4), and a recent clinical trial demonstrated improved overall survival rates in patients treated with ipilimumab plus dacarbazine compared with dacarbazine alone (Robert C et al: N Engl J Med 2011; 364: 2517-25).

III-23. The answer is C. (Chap. 88) Head and neck cancers account for about 3% of all malignancies in the United States and comprise a varied site of tumors, including those of the nasopharynx, oropharynx, hypopharynx, and larynx. Squamous cell history is the predominant cell type at all sites, but there are different risk factors by site. Nasopharyngeal cancers are rare in the United States but are endemic in the Mediterranean and Far East, where they are associated with Epstein-Barr virus infection. Oropharyngeal cancers are associated with tobacco use, especially smokeless tobacco, and increasing numbers of oropharyngeal cancers are found to be associated with human papilloma virus (HPV). The association with HPV virus infection, particularly serotypes 16 and 18, characterizes these oropharyngeal cancers as a form of sexually transmitted disease and is associated with oral sexual practices and an increased number of sexual partners. However, the predominant risk factors for head

and neck cancers, particularly those of the hypopharynx and larynx, are alcohol and tobacco use. Cancers of the larynx often present with the subacute onset of hoarseness that does not resolve over time, but symptoms of head and neck cancer can be rather nonspecific. In more advanced cases, pain, stridor, dysphagia, odynophagia, and cranial neuropathies can occur. Diagnosis of head and neck cancer should include computed tomography of the head and neck and endoscopic examination under anesthesia to perform biopsies. Positron emission tomography scans may be used as adjunctive therapy. The staging of head and neck cancers follows a TNM staging guideline. This patient would be staged as T2N0M0 based on a tumor size without evidence of lymph node involvement or distant metastatic disease. With this designation, the patient’s overall stage would be stage II and classified as localized disease. The intent of therapy at this stage of disease is cure of cancer, and the overall 5-year survival is 60% to 90%. The choice of therapy for laryngeal cancer is radiation therapy to preserve the voice. Surgical therapy could be chosen by the patient as well but is less desirable. In locally or regionally advanced disease, patients can still be approached with curative intent, but this requires multimodality therapy with surgery followed by concomitant chemotherapy and radiation treatment.

III-24. The answer is A. (Chap. 89) Solitary pulmonary nodules are frequent causes of referral to a pulmonologist, but most solitary pulmonary nodules are benign. In fact, more than 90% of incidentally identified nodules are of benign origin. Features that are more likely to be present in a malignant lesion are size larger than 3 cm, eccentric calcification, rapid doubling time, and lobulated and irregular contour. Ground-glass appearance on computed tomography can be either malignant or benign. Among malignant lesions, it is seen more commonly in bronchoalveolar cell carcinoma. When multiple pulmonary nodules are identified, it most commonly represents prior granulomatous disease from healed infections. If multiple nodules are malignant in origin, it usually indicates disease metastatic to the lung but can be simultaneous lung primary lesions or lesions metastatic from a primary lung cancer. Many incidentally identified nodules are too small to be diagnosed by biopsy and are nonspecific in nature. In this situation, it is prudent to follow the lesions for 2 years, especially in a patient who is high risk for lung cancer to allow for a proper doubling time to occur. If the lesion remains stable for 2 years, it is most likely benign, although some slow-growing tumors such bronchoalveolar cell carcinoma can have a slower growth rate.

III-25. The answer is E. (Chap. 89) The evaluation and treatment of solitary pulmonary nodules is important to understand. This patient has a long smoking history with a new nodule that was not apparent by chest radiography 3 years previously. This should be assumed to be a malignant nodule, and definitive diagnosis and treatment should be attempted. The option for diagnostic and staging procedures include positron emission tomography (PET) and computed tomography (CT), bronchoscopic biopsy, percutaneous needle biopsy, and surgical biopsy with concomitant resection if positive. PET and CT would be low yield in this patient given the small size of the primary lesion (<1 cm) and the lack of enlarged mediastinal lymph nodes. Likewise, bronchoscopy would not provide a good yield because the lesion is very peripheral in origin, and a negative biopsy for malignancy would not be definitive. Appropriate approaches would be to either perform a percutaneous needle biopsy with CT guidance or perform a surgical biopsy with definitive resection if positive. Because this patient has preserved lung function, surgical biopsy and resection is a good treatment option. A repeat CT scan assessing for interval growth would only be appropriate if the patient declined further workup at this time. Referral for treatment with radiation therapy is not appropriate in the absence of tissue diagnosis of malignancy, and surgical resection is the preferred primary treatment because the patient

has no contraindications to surgical intervention.

III-26. The answer is E. (Chap. 89) Pancoast syndrome results from apical extension of a lung mass into the brachial plexus with frequent involvement of the eighth cervical and first and second thoracic nerves. As the tumor continues to grow, it will also involve the sympathetic ganglia of the thoracic chain. The clinical manifestations of a Pancoast tumor include shoulder and arm pain and Horner’s syndrome (ipsilateral ptosis, miosis, and anhidrosis). Often, the shoulder and arm pain presents several months before diagnosis. The most common cause of Pancoast syndrome is an apical lung tumor, usually non–small cell lung cancer. Other causes include mesothelioma and infection, among others. Although midbrain lesions can cause Horner’s syndrome, other cranial nerve abnormalities would be expected.

Enlarged mediastinal lymph nodes and masses in the middle mediastinum can occlude the superior vena cava (SVC), leading to SVC syndrome. Individuals with SVC syndrome typically present with dyspnea and have evidence of facial and upper extremity swelling. Eaton Lambert myasthenic syndrome is caused by antibodies to voltage-gated calcium channels and is characterized by generalized weakness of muscles that increases with repetitive nerve stimulation. Cervical ribs can cause thoracic outlet syndrome by compression of nerves or vasculature as they exit the chest. This typically presents with ischemic symptoms to the affected limb, but intrinsic wasting of the muscles of the hand can be seen because of neurologic compromise.

III-27. The answer is E. (Chap. 89) At the time of diagnosis, 70% of small cell lung cancers have metastasized. In contrast to non–small cell lung cancer, small cell lung cancer is staged as limited or extensive disease based on the spread of disease in the body rather than size of the tumor burden or extent of lymph node involvement. Common sites of metastases in small cell lung cancer are thoracic lymph nodes, brain, adrenal glands, and liver. All patients diagnosed with small cell lung cancer should undergo chest and abdominal computed tomography (CT) scans as well as CT or magnetic resonance imaging (MRI) imaging of the brain. If bone pain is present, radionuclide bone scans should be performed. Bone marrow biopsies are not typically indicated as isolated bone marrow metastases are rare. If there are signs of spinal cord compression or leptomeningeal involvement, imaging of the spine by MRI or CT and lumbar puncture are indicated, respectively.

III-28. The answer is C. (Chap. 89) Mutations of the epidermal growth factor receptor (EGFR) have recently been recognized as important mutations that affect the response of non–small cell lung cancers to treatment with EGFR tyrosine kinase inhibitors. Initial studies of erlotinib in all patients with advanced non–small cell lung cancer failed to show a treatment benefit; however, when only patients with EGFR mutations were considered, treatment with anti-EGFR therapy improved progression-free and overall survival. Patients who are more likely to have EGFR mutations are women, nonsmokers, Asians, and those with adenocarcinoma histopathology.

III-29. The answer is B. (Chap. 89, N Engl J Med 2011; 365: 395-409) Screening for lung cancer in high-risk individuals has been investigated for many years. Screening trials require large numbers of participants that can be followed for long periods of time and are expensive to conduct. Until 2011, no screening trial had been able to demonstrate any decrease in lung cancer mortality. Previous screening modalities have been primarily chest radiographs with or without sputum cytology. In June 2011, the main results of the National Lung Cancer Screening Trial (NLST) were published in the New England Journal of Medicine. The trial enrolled more than 50,000 individuals with a greater than 30 pack-year

history of cigarette smoking and randomized the individuals to yearly chest radiographs or low-dose computed tomography (CT) scans for a period of 3 years. Outcomes in the individuals continued to be followed for a total of almost 8 years, when the trial was stopped early. Individuals receiving low-dose CT scans demonstrated a 20% mortality reduction from lung cancer compared with those receiving chest radiographs alone, and more individuals receiving CT scans were diagnosed at early stages of disease. A caveat in broadly applying these results in clinical practice is that more than 90% of positive scans proved to be false positives. At this point, more research on the cost effectiveness of CT scans and the appropriate population to which to offer scans needs to be done before widespread screening is recommended.

III-30. The answer is C. (Chap. 90) The patient has a breast cyst. This has a benign feel on examination, and aspiration of the mass showed nonbloody fluid with resolution of the mass. If there were residual mass or bloody fluid, mammography and biopsy would be the next step. In patients such as this with nonbloody fluid in whom aspiration clears the mass, reexamination in 1 month is indicated. If the mass recurs, then aspiration should be repeated. If fluid recurs, mammography and biopsy would be indicated at that point. There is no indication at this point to refer for advanced imaging or surgical evaluation. Breastfeeding is not affected by the presence of a breast cyst.

III-31. The answer is C. (Chap. 90) Breast cancer risk is related to many factors, but age of menarche, age of first full-term pregnancy, and age at menopause together account for 70% to 80% of all breast cancer risk. The lowest risk patients have the shortest duration of total menses (i.e., later menarche and earlier menopause), as well as an early first full-term pregnancy. Specifically, the lowest risks are menarche at age 16 years old or older, first pregnancy by the age of 18 years, and menopause that begins 10 years before the median age of menopause of 52 years. Thus, patient C meets these criteria.

III-32. The answer is D. (Chap. 90) Pathologic staging remains the most important determinant of overall prognosis. Other prognostic factors have an impact on survival and the choice of therapy. Tumors that lack estrogen or progesterone receptors are more likely to recur. The presence of estrogen receptors, particularly in postmenopausal women, is also an important factor in determining adjuvant chemotherapy. Tumors with a high growth rate are associated with early relapse. Measurement of the proportion of cells in S-phase is a measure of the growth rate. Tumors with more than the median number of cells in S-phase have a higher risk of relapse and an improved response rate to chemotherapy. Histologically, tumors with a poor nuclear grade have a higher risk of recurrence than do tumors with a good nuclear grade. At the molecular level, tumors that overexpress erbB2 (HER-2/neu) or that have a mutated p53 gene portend a poorer prognosis for patients. The overexpression of erbB2 is also useful in designing optimal treatment regimens, and a human monoclonal antibody to erbB2 (Herceptin) has been developed.

III-33. The answer is E. (Chap. 91) Esophageal cancer is an uncommon gastrointestinal malignancy with a high mortality rate because most patients do not present until advanced disease is present. The typical presenting symptoms of esophageal cancer are dysphagia with significant weight loss. Dysphagia is typically fairly rapidly progressive over a period of weeks to months. Dysphagia initially in only to solid foods but progresses to include semisolids and liquids. For dysphagia to occur, an estimated 60% of the esophageal lumen must be occluded. Weight loss occurs because of decreased oral intake in addition to the cachexia that is common with cancer. Associated symptoms may include

pain with swallowing that can radiate to the back, regurgitation or vomiting of undigested food, and aspiration pneumonia. The two major cell types of esophageal cancer in the United States are adenocarcinoma and squamous cell carcinoma, which have different risk factors. Individuals with squamous cell carcinomas typically have a history of both tobacco and alcohol abuse, but those with adenocarcinoma more often have a history of long-standing gastroesophageal reflux disease and Barrett’s esophagitis. Among those with a history of alcohol and tobacco abuse, there is an increased risk with increased intake and interestingly is more associated with whiskey drinking compared with wine or beer. Other risk factors for squamous cell carcinoma of the esophagus include ingestion of nitrites, smoked opiates, fungal toxins in pickled vegetables, and physical insults that include long­standing ingestion of very hot tea or lye.

III-34. The answer is E. (Chap. 91) Colorectal cancer is the second most common cause of cancer death in the United States, and the mortality rate related to the disease has been decreasing in recent years. When colorectal cancer is identified, patients should be referred for surgical intervention because proper staging and prognosis cannot be determined without pathologic specimens if there is no gross evidence of metastatic disease. The preoperative workup to assess for metastatic or synchronous disease includes a complete colonoscopy if possible, chest radiography, liver function testing, carcinoembryonic antigen (CEA) testing, and computed tomography of the abdomen. Staging of colorectal cancer follows a TNM staging system. However, the T staging is not based on absolute size of the tumor rather it is based upon the extension of the tumor through the colonic wall. T1 tumors can extend into the submucosa but not beyond, T2 tumors extend into the muscularis propria, and T3 tumors involve the serosa and beyond. Nodal metastases are graded as N1 (one to three lymph nodes positive) and N2 (≥four lymph nodes positive). This patient’s stage of cancer would be T2N1M0 and would be staged as a stage III cancer. Despite the relatively advanced stage, the overall 5-year survival rate would be 50% to 70% because of improvements in overall care of the patient with colorectal cancer. Because the patient had an occluding lesion that prevents preoperative colonoscopy, the patient needs to have a complete colonoscopy performed within the first several months after surgery and every 3 years thereafter. Serial measurements of CEA every 3 months have also been advocated by some specialists. Annual CT scanning may be performed for the first 3 years after resection, although the utility of the practice is debated. Radiation therapy to the pelvis is recommended for all patients with rectal cancer because it reduces the local recurrence rate, especially in stage II and III tumors. When postoperative radiation therapy is combined with chemotherapeutic regimens containing 5-fluorouracil, the local recurrence rate is further reduced and overall survival is increased as well.

III-35. The answer is A. (Chap. 91) Most colorectal cancers arise from adenomatous polyps. Only adenomas are premalignant, and only a minority of these lesions becomes malignant. Most polyps are asymptomatic, causing occult bleeding in fewer than 5% of patients. Sessile (flat-based) polyps are more likely to become malignant than pedunculated (stalked) polyps. Histologically, villous adenomas are more likely to become malignant than tubular adenomas. The risk of containing invasive carcinoma in the polyp increases with size with less than 2% in polyps smaller than 1.5 cm, 2% to 10% in polyps 1.5 to 2.5 cm, and 10% in polyps larger than 2. 5 cm. This patient had two polyps that were high risk based on histology (villous) and appearance (sessile) but only moderate risk by size (<1.5 cm). Polyps, particularly those larger than 2.5 cm in size, sometimes contain cancer cells but usually progress to cancer quite slowly over an approximate 5-year period. Patients with adenomatous polyps should have a follow-up colonoscopy or radiographic study in 3 years. If no polyps are found on initial study, the

test (endoscopic or radiographic) should be repeated in 10 years. Computed tomography is only warranted for staging if there is a diagnosis of colon cancer, not for the presence of polyps alone.

III-36. The answer is A. (Chap. 91) A strong family history of colon cancer should prompt consideration for hereditary nonpolyposis colon cancer (HNPCC), or Lynch syndrome, particularly if diffuse polyposis is not noted on colonoscopy. HNPCC is characterized by (1) three or more relatives with histologically proven colorectal cancer, one of whom is a first-degree relative and of the other two, at least one with the diagnosis before age 50 years, and (2) colorectal cancer in at least two generations. The disease is an autosomal dominant trait and is associated with other tumors, including in the endometrium and ovary. The proximal colon is most frequently involved, and cancer occurs with a median age of 50 years, 15 years earlier than in sporadic colon cancer. Patients with HNPCC are recommended to receive biennial colonoscopy and pelvic ultrasonography beginning at age 25 years. Innumerable polyps suggest the presence of one of the autosomal dominant polyposis syndromes, many of which carry a high malignant potential. These include familial adenomatous polyposis, Gardner’s syndrome (associated with osteomas, fibromas, epidermoid cysts), or Turcot’s syndrome (associated with brain cancer). Peutz-Jeghers syndrome is associated with mucocutaneous pigmentation and hamartomas. Tumors may develop in the ovary, breast, pancreas, and endometrium; however, malignant colon cancers are not common. Ulcerative colitis is strongly associated with development of colon cancer, but it is unusual for colon cancer to be the presenting finding in ulcerative colitis. Patients are generally symptomatic from their inflammatory bowel disease long before cancer risk develops.

III-37. The answer is E. (Chap. 93) Pancreatic cancer is the fourth leading cause of cancer death in the United States despite representing only 3% of all newly diagnosed malignancies. Infiltrating ductal adenocarcinomas account for the vast majority of cases and arise most frequently in the head of pancreas. At the time of diagnosis, 85% to 90% of patients have inoperable or metastatic disease, which is reflected in the 5-year survival rate of only 5% for all stages combined. An improved 5-year survival of up to 20% may be achieved when the tumor is detected at an early stage and when complete surgical resection is accomplished. Over the past 30 years, 5-year survival rates have not improved substantially. Cigarette smoking may be the cause of up to 20% to 25% of all pancreatic cancers and is the most common environmental risk factor for this disease. Other risk factors are not well established because of inconsistent results from epidemiologic studies, but they include chronic pancreatitis and diabetes. Alcohol does not appear to be a risk factor unless excess consumption gives rise to chronic pancreatitis.

III-38. The answer is B. (Chap. 93) Dual-phase, contrast-enhanced spiral computed tomography (CT) is the imaging modality of choice to visualize suspected pancreatic masses. In addition to imaging the pancreas, it also provides accurate visualization of surrounding viscera, vessels, and lymph nodes. In most cases, this study can determine surgical resectability. There is no advantage of magnetic resonance imaging (MRI) over CT in predicting tumor resectability, but selected cases may benefit from MRI to characterize the nature of small indeterminate liver lesions and to evaluate the cause of biliary dilatation when no obvious mass is seen on CT. Preoperative confirmation of malignancy is not always necessary in patients with radiologic appearances consistent with operable pancreatic cancer. Endoscopic ultrasound-guided needle biopsy is the most effective technique to evaluate the mass for malignancy. It has an accuracy of approximately 90% and has a smaller risk of intraperitoneal dissemination compared with CT-guided percutaneous biopsy. Endoscopic retrograde

cholangiopancreatography (ERCP) is a useful method for obtaining ductal brushings, but the diagnostic value of pancreatic juice sampling is only 25% to 30%. CA 19-9 is elevated in approximately 70% to 80% of patients with pancreatic carcinoma, but ERCP is not recommended as a routine diagnostic or screening test because its sensitivity and specificity are inadequate for accurate diagnosis. Preoperative CA 19-9 levels correlate with tumor stage and prognosis. It is also an indicator of asymptomatic recurrence in patients with completely resected tumors. Fluorodeoxyglucose positron emission tomography (FDG-PET) should be considered before surgery for detecting distant metastases.

III-39. The answer is D. (Chap. 94) Bladder cancer is the fourth most common cancer in men and the thirteenth most common cancer in women. Cigarette smoking has a strong association with bladder cancer, particularly in men. The increased risk persists for at least 10 years after quitting. Bladder cancer is a small cause of cancer deaths because most detected cases are superficial with an excellent prognosis. Most cases of bladder cancer come to medical attention by the presence of gross hematuria emanating from exophytic lesions. Microscopic hematuria is more likely caused by prostate cancer than bladder cancer. Cystoscopy under anesthesia is indicated to evaluate for bladder cancer. In cases of superficial disease, bacille Calmette-Guérin (BCG) is an effective adjuvant to decrease recurrence or treat unresectable superficial disease. In the United States, cystectomy is generally recommended for invasive disease. Even invasive cancer with nodal involvement has a greater than 40% 10-year survival after surgery and adjuvant therapy.

III-40 and III-41. The answers are C and E, respectively. (Chap. 94) The incidence of renal cell carcinoma continues to rise and is now nearly 58,000 cases annually in the United States, resulting in 13,000 deaths. The male-to-female ratio is 2 to 1. Incidence peaks between the ages of 50 and 70 years, although this malignancy may be diagnosed at any age. Many environmental factors have been investigated as possible contributing causes; the strongest association is with cigarette smoking. Risk is also increased for patients who have acquired cystic disease of the kidney associated with end-stage renal disease and for those with tuberous sclerosis. Most renal cell carcinomas are clear cell tumors (60%) with papillary and chromophobic tumors less common. Clear cell tumors account for more than 80% of patients who develop metastases. The classic triad of hematuria, flank pain, and a palpable mass is only present in 10% to 20% of patients initially. Most cases currently are found as incidental findings on computed tomography or ultrasonography done for different reasons. The increasing number of incidentally discovered low-stage tumors has contributed to an improved 5-year survival. The paraneoplastic phenomenon of erythrocytosis caused by increased production of erythropoietin is only found in 3% of cases; anemia caused by advanced disease is far more common. Stage 1 and 2 tumors are confined to the kidney and have a greater than 80% survival after radical nephrectomy. Stage 4 tumors with distant metastases have a 50year survival of 10%. Renal cell carcinoma is notably resistant to traditional chemotherapeutic agents. Cytokine therapy with interleukin-2 or interferon-gamma produces regression in 10% to 20% of patients with metastatic disease. Recently, the advent of antiangiogenic medications has changed the treatment of advance renal cell carcinoma. Sunitinib was demonstrated to be superior to interferon-gamma, and it (or sorafenib) is now first-line therapy for patients with advanced metastatic disease.

III-42. The answer is A. (Chap. 95) The results from several large double-blind, randomized chemoprevention trials have established 5 alpha-reductase inhibitors as the predominant therapy to reduce the future risk of a prostate cancer diagnosis. Randomized placebo-controlled trials have shown

that finasteride and dutasteride reduce the period prevalence of prostate cancer. Trials of selenium, vitamin C, and vitamin E have shown no benefit versus placebo.

III-43. The answer is E. (Chap. 95) As shown in Figure III-43, transrectal ultrasound-guided biopsy is recommended for men with either an abnormal digital rectal examination (DRE) or abnormal serum prostate-specific antigen (PSA) results. Twenty-five percent of men with a PSA above 4 ng/mL and abnormal DRE results have cancer, as do 17% of men with a PSA of 2.5 to 4 ng/mL and normal DRE results.

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Date: 2016-04-22; view: 740