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Gastroenterological Malignancies may be resected by a transanal approach, decreasing postop- these patients. CEA assessment should be done at approxi- erative morbidity. Unless more extensive disease is found dur- mately 6-month intervals. Contrast-enhanced CT scans of the ing surgery, no further treatment is warranted. chest, abdomen, and pelvis are recommended annually for up Full-thickness tumors (stage II) and/or those with to 5 years postoperatively. PET scanning should not be used for involved lymph nodes (stage III) routinely require irradiation, routine surveillance. Colonoscopy is recommended1 year after chemotherapy, and surgery. Evidence is insufficient to define resection (or 3 to 6 months after resection if a complete an optimal sequencing of the three treatment modalities, colonoscopy was not done preoperatively) and then in 3 years, although total neoadjuvant therapy (TNT), in which all followed by every 5 years, unless abnormalities are found. planned chemotherapy and irradiation is given before surgery, is becoming a more widespread practice. If a complete clinical e PET scans should not be used for preoperative staging HVC response to TNT is achieved, nonoperative management with or postoperative surveillance in colorectal cancer. close surveillance may be considered. Attempts are made to preserve anal sphincter function, but if distal rectal cancer is e Standard treatment of stages II and III rectal cancer not fully eradicated by TNT, an abdominal-perineal resection involves chemotherapy, irradiation and surgery, with resultant permanent colostomy is required. Surgery for although the optimal sequence is uncertain.

may be resected by a transanal approach, decreasing postop- these patients. CEA assessment should be done at approxi- erative morbidity. Unless more extensive disease is found dur- mately 6-month intervals. Contrast-enhanced CT scans of the ing surgery, no further treatment is warranted. chest, abdomen, and pelvis are recommended annually for up Full-thickness tumors (stage II) and/or those with to 5 years postoperatively. PET scanning should not be used for involved lymph nodes (stage III) routinely require irradiation, routine surveillance. Colonoscopy is recommended1 year after chemotherapy, and surgery. Evidence is insufficient to define resection (or 3 to 6 months after resection if a complete an optimal sequencing of the three treatment modalities, colonoscopy was not done preoperatively) and then in 3 years, although total neoadjuvant therapy (TNT), in which all followed by every 5 years, unless abnormalities are found. planned chemotherapy and irradiation is given before surgery, is becoming a more widespread practice. If a complete clinical e PET scans should not be used for preoperative staging HVC response to TNT is achieved, nonoperative management with or postoperative surveillance in colorectal cancer. close surveillance may be considered. Attempts are made to preserve anal sphincter function, but if distal rectal cancer is e Standard treatment of stages II and III rectal cancer not fully eradicated by TNT, an abdominal-perineal resection involves chemotherapy, irradiation and surgery, with resultant permanent colostomy is required. Surgery for although the optimal sequence is uncertain. tumors of the mid rectum and above rarely require a perma- e Patients with rectal cancer who achieve a complete nent colostomy. clinical response to chemoradiotherapy may be consid- Capecitabine, an oral prodrug that is converted into ered for nonoperative “watch and wait” management. 5-fluorouracil (5-FU), or, less commonly, intravenous 5-FU, is e Patients with stage II colon cancer that is microsatellite HVC given concurrently with radiation therapy. Both drugs may be stable or that lacks high-risk features are unlikely to associated with erythema of the palms and soles that may benefit from adjuvant chemotherapy. progress to blistering (hand-foot syndrome). Mucositis, diar- e Posttreatment surveillance for patients with colorectal rhea, and neutropenia may also occur. Leucovorin, 5-FU, and cancer includes periodic history; physical examination; oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX) serum carcinoembryonic antigen level testing; and CT regimens are typically used for the chemotherapy-only por- of the chest, abdomen, and pelvis, as early detection tion of the treatment. Oxaliplatin often causes a peripheral and resection of isolated metastatic disease can still neuropathy, which may not resolve fully. result in cure. Following therapy, patients with rectal cancer should be evaluated at approximately 6-month intervals for up to 5 years with a history, physical examination, and serum CEA level Metastatic Disease assessment. Contrast-enhanced CT scans of the chest, abdo- All metastatic CRCs require molecular analysis for KRAS,

tumors of the mid rectum and above rarely require a perma- e Patients with rectal cancer who achieve a complete nent colostomy. clinical response to chemoradiotherapy may be consid- Capecitabine, an oral prodrug that is converted into ered for nonoperative “watch and wait” management. 5-fluorouracil (5-FU), or, less commonly, intravenous 5-FU, is e Patients with stage II colon cancer that is microsatellite HVC given concurrently with radiation therapy. Both drugs may be stable or that lacks high-risk features are unlikely to associated with erythema of the palms and soles that may benefit from adjuvant chemotherapy. progress to blistering (hand-foot syndrome). Mucositis, diar- e Posttreatment surveillance for patients with colorectal rhea, and neutropenia may also occur. Leucovorin, 5-FU, and cancer includes periodic history; physical examination; oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX) serum carcinoembryonic antigen level testing; and CT regimens are typically used for the chemotherapy-only por- of the chest, abdomen, and pelvis, as early detection tion of the treatment. Oxaliplatin often causes a peripheral and resection of isolated metastatic disease can still neuropathy, which may not resolve fully. result in cure. Following therapy, patients with rectal cancer should be evaluated at approximately 6-month intervals for up to 5 years with a history, physical examination, and serum CEA level Metastatic Disease assessment. Contrast-enhanced CT scans of the chest, abdo- All metastatic CRCs require molecular analysis for KRAS, men, and pelvis are typically obtained annually for 5 years. NRAS, and BRAF gene mutation status as well as (MMR deter- mination. This step rarely affects the choice of first-line ther- Colon Cancer apy but will define subsequent treatment options. These tests Nonmetastatic colon cancers are initially treated with surgical can be done on either the primary tumor or a metastasis; resection. Pathologic evaluation then determines further rebiopsy of late-appearing metastases for the purpose of these treatment. studies is rarely needed. When sufficient tumor tissue is una- Patients with microsatellite stable stage II cancer lacking vailable, circulating tumor DNA may be assayed in a blood high-risk features, such as poorly differentiated histology, T4 sample (liquid biopsy) for tumor genotyping. primary tumor, lymphovascular invasion, inadequate lymph Patients with metastatic disease limited to the liver or node sampling (less than 12), elevated postoperative CEA level, lung should be evaluated for surgical resection with curative or perforation or obstruction, are at low risk for recurrence intent. Unresectable metastatic CRC is treatable but not cura- and are unlikely to benefit from adjuvant treatment. Patients ble. Although chemotherapy may prolong survival and relieve with one or more of these risk factors may be considered for cancer-related symptoms, patients who have a poor perfor- adjuvant 5-FU or capecitabine. Data are equivocal on the use mance status may not benefit or may have unacceptable of FOLFOX or CAPOX. toxicity. All patients with stage III (node-positive) colon cancer 5-FU is at the center of most treatment regimens, with should receive FOLFOX or CAPOX postoperatively. In those longer infusions preferable to bolus administration. Leucovorin with favorable characteristics (T1-3, N1), 3 months of treat- is often combined with 5-FU. Capecitabine can be an alterna- ment is noninferior to 6. Patients with T4 and/or N2 disease tive to 5-FU. Other cytotoxic agents used in metastatic CRC (four or more positive nodes) are typically treated for 6 months. include irinotecan and oxaliplatin. The anti-vascular Postoperative surveillance after curative resection is used endothelial growth factor (VEGF) monoclonal antibody beva- to identify oligometastatic disease in the liver or lung that may cizumab is often given concurrently with first-line cytotoxic be resectable. Complete resection of oligometastatic foci con- chemotherapy regimens. This agent potentiates other chemo- fined to a single organ can be curative in approximately 25% of therapies, resulting in a modestly increased duration of

men, and pelvis are typically obtained annually for 5 years. NRAS, and BRAF gene mutation status as well as (MMR deter- mination. This step rarely affects the choice of first-line ther- Colon Cancer apy but will define subsequent treatment options. These tests Nonmetastatic colon cancers are initially treated with surgical can be done on either the primary tumor or a metastasis; resection. Pathologic evaluation then determines further rebiopsy of late-appearing metastases for the purpose of these treatment. studies is rarely needed. When sufficient tumor tissue is una- Patients with microsatellite stable stage II cancer lacking vailable, circulating tumor DNA may be assayed in a blood high-risk features, such as poorly differentiated histology, T4 sample (liquid biopsy) for tumor genotyping. primary tumor, lymphovascular invasion, inadequate lymph Patients with metastatic disease limited to the liver or node sampling (less than 12), elevated postoperative CEA level, lung should be evaluated for surgical resection with curative or perforation or obstruction, are at low risk for recurrence intent. Unresectable metastatic CRC is treatable but not cura- and are unlikely to benefit from adjuvant treatment. Patients ble. Although chemotherapy may prolong survival and relieve with one or more of these risk factors may be considered for cancer-related symptoms, patients who have a poor perfor- adjuvant 5-FU or capecitabine. Data are equivocal on the use mance status may not benefit or may have unacceptable of FOLFOX or CAPOX. toxicity. All patients with stage III (node-positive) colon cancer 5-FU is at the center of most treatment regimens, with should receive FOLFOX or CAPOX postoperatively. In those longer infusions preferable to bolus administration. Leucovorin with favorable characteristics (T1-3, N1), 3 months of treat- is often combined with 5-FU. Capecitabine can be an alterna- ment is noninferior to 6. Patients with T4 and/or N2 disease tive to 5-FU. Other cytotoxic agents used in metastatic CRC (four or more positive nodes) are typically treated for 6 months. include irinotecan and oxaliplatin. The anti-vascular Postoperative surveillance after curative resection is used endothelial growth factor (VEGF) monoclonal antibody beva- to identify oligometastatic disease in the liver or lung that may cizumab is often given concurrently with first-line cytotoxic be resectable. Complete resection of oligometastatic foci con- chemotherapy regimens. This agent potentiates other chemo- fined to a single organ can be curative in approximately 25% of therapies, resulting in a modestly increased duration of 18

Gastroenterological Malignancies progression-free survival, and in some studies, in increased checkpoint inhibitors such as nivolumab or pembrolizumab duration of overall survival. Continuing an anti-VEGF agent have shown activity in metastatic disease. with second-line chemotherapy also modestly improves over- Although HPV vaccination would be expected to be as all survival. Anti-VEGF agents commonly cause hypertension, effective at cancer prevention as it is with other HPV-related sometimes requiring therapy. They also impair wound healing malignancies, there is no evidence that HPV vaccination plays and need to be discontinued perioperatively. Very rare but a role in treatment or posttreatment management of patients potentially life-threatening adverse effects include arterial with anal cancer. See General Internal Medicine 2 for further thrombotic events such as myocardial infarction, cerebrovas- discussion of HPV vaccination. cular accidents, and gastrointestinal perforations. Panitumumab and cetuximab are monoclonal antibodies that bind to and block activation of the epidermal growth fac- e Anal cancer, a squamous cell carcinoma linked to human papillomavirus, is often cured by combination tor receptor. They are potentially active only in tumors that harbor nonmutated (wild-type) KRAS, NRAS, and BRAF irradiation and chemotherapy, sparing the need for sur- genes. More recent data suggest that these agents may only gical resection and colostomy. have activity in tumors derived from the left side of the large intestine. The major adverse effect of these agents is a painful and socially debilitating acneiform rash. There is a high cor- Pancreatic Cancer relation between rash and antitumor activity, and patients There are approximately 57,000 patients diagnosed with exo- who have only a mild skin rash are unlikely to benefit from crine pancreatic cancer per year in the United States. Mortality these agents. Anti-epidermal growth factor receptor agents is high, with approximately 46,000 deaths expected annually.

have activity in tumors derived from the left side of the large intestine. The major adverse effect of these agents is a painful and socially debilitating acneiform rash. There is a high cor- Pancreatic Cancer relation between rash and antitumor activity, and patients There are approximately 57,000 patients diagnosed with exo- who have only a mild skin rash are unlikely to benefit from crine pancreatic cancer per year in the United States. Mortality these agents. Anti-epidermal growth factor receptor agents is high, with approximately 46,000 deaths expected annually. should not be used concurrently with anti-VEGF agents, as Only patients who can undergo a complete resection have a outcomes are worse. Thus far, immune checkpoint inhibitors chance of cure. When disease is unresectable because of inva- have been inactive in metastatic CRC, with the exception of sion into critical vascular structures, median survival is rare metastatic tumors that are (MMR (2% to 4% of all patients approximately 1 year. For those with metastatic disease, with metastases). The programmed death 1 receptor inhibitors median survival is typically less than half that. pembrolizumab and nivolumab have both shown activity in Most pancreatic cancers lack a genetic predisposition, such patients. although 5% to 10% of patients have either a strong family his- Presently, multigene sequencing beyond KRAS, NRAS, tory of pancreatic cancer, or an identifiable mutation, includ- and BRAF offers no clinically useful information and is not ing BRCA gene mutations and dMMR (Lynch syndrome).

such patients. although 5% to 10% of patients have either a strong family his- Presently, multigene sequencing beyond KRAS, NRAS, tory of pancreatic cancer, or an identifiable mutation, includ- and BRAF offers no clinically useful information and is not ing BRCA gene mutations and dMMR (Lynch syndrome). warranted outside of a research setting. Genetic counseling and germline testing for BRCA and mis- match repair deficiency is now recommended for patients with pancreatic cancer. Chronic pancreatitis, obesity, type 2 e 5-fluorouracil (5-FU) is first-line therapy for metastatic diabetes mellitus, high red meat consumption, alcohol abuse, colorectal cancer and is often combined with leuco- and tobacco use are implicated risk factors. vorin; capecitabine is an alternative to 5-FU. Painless jaundice, abdominal pain, weight loss, persistent ¢ All metastatic colorectal cancers require molecular fevers, or protracted nausea and vomiting may be presenting analysis for KRAS, NRAS, and BRAF gene mutation sta- symptoms. Manifestations of hypercoagulability, including tus as well as mismatch repair gene deficiency, which Trousseau syndrome (a migratory superficial thrombophlebi- will determine treatment after first-line therapy. tis), chronic disseminated intravascular coagulation, deep venous thrombosis, or pulmonary embolism, may be the ini- tial manifestations of underlying pancreatic cancer. Anal Cancer A contrast-enhanced CT of the chest and abdomen (or Anal cancer is a human papillomavirus (HPV)-associated noncontrast chest CT and abdominal MRI) are appropriate for malignancy. Unlike rectal cancer, which is an adenocarci- staging and treatment planning. PET scans do not add value in noma, anal cancer is a squamous cell carcinoma. Anal cancer pancreatic cancer management. Endoscopic ultrasonography is often curable with combined irradiation and chemotherapy; may help in staging and is used to more precisely guide diag- surgery is typically not indicated. Mitomycin plus 5-FU or nostic needle biopsy. Some patients with clinical features that capecitabine is the standard chemotherapy regimen. Although strongly suggest malignancy may not require such preopera- complete regression may be observed as soon as 8 weeks after tive biopsy, as false-negative results would not obviate the need irradiation, responding tumors may continue to regress for up for surgical resection. Magnetic resonance cholangiopancrea- to 6 months after irradiation. If tumor growth is seen after tography may also be useful in delineating resectability in irradiation, then salvage surgery with a permanent colostomy borderline patients. Conversion therapy—using irradiation or is indicated. Distant metastases are rare. When they do chemotherapy to convert locally unresectable disease to develop, chemotherapy with a platinum-containing regimen resectable—may be considered in patients in whom a response (oxaliplatin, cisplatin, or carboplatin) is often active. Immune might create a plane of resection.

warranted outside of a research setting. Genetic counseling and germline testing for BRCA and mis- match repair deficiency is now recommended for patients with pancreatic cancer. Chronic pancreatitis, obesity, type 2 e 5-fluorouracil (5-FU) is first-line therapy for metastatic diabetes mellitus, high red meat consumption, alcohol abuse, colorectal cancer and is often combined with leuco- and tobacco use are implicated risk factors. vorin; capecitabine is an alternative to 5-FU. Painless jaundice, abdominal pain, weight loss, persistent ¢ All metastatic colorectal cancers require molecular fevers, or protracted nausea and vomiting may be presenting analysis for KRAS, NRAS, and BRAF gene mutation sta- symptoms. Manifestations of hypercoagulability, including tus as well as mismatch repair gene deficiency, which Trousseau syndrome (a migratory superficial thrombophlebi- will determine treatment after first-line therapy. tis), chronic disseminated intravascular coagulation, deep venous thrombosis, or pulmonary embolism, may be the ini- tial manifestations of underlying pancreatic cancer. Anal Cancer A contrast-enhanced CT of the chest and abdomen (or Anal cancer is a human papillomavirus (HPV)-associated noncontrast chest CT and abdominal MRI) are appropriate for malignancy. Unlike rectal cancer, which is an adenocarci- staging and treatment planning. PET scans do not add value in noma, anal cancer is a squamous cell carcinoma. Anal cancer pancreatic cancer management. Endoscopic ultrasonography is often curable with combined irradiation and chemotherapy; may help in staging and is used to more precisely guide diag- surgery is typically not indicated. Mitomycin plus 5-FU or nostic needle biopsy. Some patients with clinical features that capecitabine is the standard chemotherapy regimen. Although strongly suggest malignancy may not require such preopera- complete regression may be observed as soon as 8 weeks after tive biopsy, as false-negative results would not obviate the need irradiation, responding tumors may continue to regress for up for surgical resection. Magnetic resonance cholangiopancrea- to 6 months after irradiation. If tumor growth is seen after tography may also be useful in delineating resectability in irradiation, then salvage surgery with a permanent colostomy borderline patients. Conversion therapy—using irradiation or is indicated. Distant metastases are rare. When they do chemotherapy to convert locally unresectable disease to develop, chemotherapy with a platinum-containing regimen resectable—may be considered in patients in whom a response (oxaliplatin, cisplatin, or carboplatin) is often active. Immune might create a plane of resection. 19

Gastroenterological Malignancies Patients without evidence of metastatic disease who Hepatology for more detailed information on Barrett esopha- appear to have technically resectable disease should undergo gus and GERD. resection. Upper endoscopy and biopsy establishes the diagnosis. Gemcitabine plus capecitabine or the modified combina- Endoscopic ultrasonography is routinely used to assess the tion regimen of oxaliplatin, irinotecan, 5-FU, and leucovorin depth of tumor penetration and presence of involved lymph are preferred rather than single-agent therapy for patients who nodes. In contrast to the evaluation of other gastrointestinal have a good performance status and can tolerate aggressive tumors, PET/CT is widely used as part of standard preoperative chemotherapy after their surgery. The routine use of postop- staging. erative irradiation is not advised. Surgery is the primary treatment of locoregional disease, After pancreatic cancer resection, most patients require found in approximately one third of patients. Data have shown pancreatic enzyme replacement therapy, and those with the a survival benefit for preoperative therapy with either neoad- most extensive pancreatic resection need lifelong insulin juvant chemotherapy or combined neoadjuvant chemotherapy therapy. and radiation therapy. Adjuvant chemotherapy is warranted For metastatic disease, the combination regimen oxali- for patients with cancer who undergo surgery first and whose platin, irinotecan, 5-FU, and leucovorin or the combination of cancer is more advanced than stage I. nab-paclitaxel and gemcitabine have each shown better anti- Unfortunately, recurrence rates after surgical resection tumor activity and modest survival benefits over single-agent remain high, even with the use of adjuvant therapy. Treatment gemcitabine, albeit with higher toxicity. In second-line ther- of recurrent or metastatic disease is only modestly effective

erative irradiation is not advised. Surgery is the primary treatment of locoregional disease, After pancreatic cancer resection, most patients require found in approximately one third of patients. Data have shown pancreatic enzyme replacement therapy, and those with the a survival benefit for preoperative therapy with either neoad- most extensive pancreatic resection need lifelong insulin juvant chemotherapy or combined neoadjuvant chemotherapy therapy. and radiation therapy. Adjuvant chemotherapy is warranted For metastatic disease, the combination regimen oxali- for patients with cancer who undergo surgery first and whose platin, irinotecan, 5-FU, and leucovorin or the combination of cancer is more advanced than stage I. nab-paclitaxel and gemcitabine have each shown better anti- Unfortunately, recurrence rates after surgical resection tumor activity and modest survival benefits over single-agent remain high, even with the use of adjuvant therapy. Treatment gemcitabine, albeit with higher toxicity. In second-line ther- of recurrent or metastatic disease is only modestly effective apy, liposome-encapsulated irinotecan added to 5-FU has and is not curative. shown very modest activity in patients with a good perfor- Approximately 25% of gastroesophageal cancers overex- mance status not previously treated with irinotecan. press the human epidermal growth factor receptor 2 (HER2). For patients with metastatic HER2-positive gastroesophageal cancer, the addition of the anti- HER2 monoclonal antibody e Patients without metastatic disease who have clinical trastuzumab to chemotherapy provides a modest but statisti- staging suggesting resectable or borderline resectable cally significant survival benefit. The anti-VEGF receptor mon- pancreatic cancer should undergo resection. oclonal antibody ramucirumab has shown modest activity as HVC e PET scans do not add value in the staging of pancreatic a non-first-line treatment, either alone or in combination cancer and are not part of standard management. with a taxane. Immune checkpoint inhibitors have shown

apy, liposome-encapsulated irinotecan added to 5-FU has and is not curative. shown very modest activity in patients with a good perfor- Approximately 25% of gastroesophageal cancers overex- mance status not previously treated with irinotecan. press the human epidermal growth factor receptor 2 (HER2). For patients with metastatic HER2-positive gastroesophageal cancer, the addition of the anti- HER2 monoclonal antibody e Patients without metastatic disease who have clinical trastuzumab to chemotherapy provides a modest but statisti- staging suggesting resectable or borderline resectable cally significant survival benefit. The anti-VEGF receptor mon- pancreatic cancer should undergo resection. oclonal antibody ramucirumab has shown modest activity as HVC e PET scans do not add value in the staging of pancreatic a non-first-line treatment, either alone or in combination cancer and are not part of standard management. with a taxane. Immune checkpoint inhibitors have shown e The use of adjuvant chemotherapy with modified activity in the non-first-line setting in gastroesophageal oxaliplatin, irinotecan, 5-FU, and leucovorin or gem- tumors with MSI, or, to a lesser degree, in those that are micro- citabine plus capecitabine has been shown to increase satellite stable but express programmed death 1, the target for survival in patients with good postoperative perfor- programmed death 1 inhibitors such as nivolumab or mance status. pembrolizumab. Gastroesophageal Cancer e Upper endoscopy and biopsy establishes the diagnosis Epidemiology, risk factors, and clinical manifestations of of gastroesophageal cancer, and endoscopic ultrasonog-

mance status. pembrolizumab. Gastroesophageal Cancer e Upper endoscopy and biopsy establishes the diagnosis Epidemiology, risk factors, and clinical manifestations of of gastroesophageal cancer, and endoscopic ultrasonog- esophageal and gastric cancer are discussed in Gastroenterology raphy is routinely used to assess the depth of tumor and Hepatology. penetration and presence of involved lymph nodes.

Epidemiology, risk factors, and clinical manifestations of of gastroesophageal cancer, and endoscopic ultrasonog- esophageal and gastric cancer are discussed in Gastroenterology raphy is routinely used to assess the depth of tumor and Hepatology. penetration and presence of involved lymph nodes. Upper gastrointestinal tract cancers are a major cause of e In contrast to other gastrointestinal tumors, PET/CT is cancer deaths worldwide, particularly in Asia and Africa. The widely used as part of standard preoperative staging of incidence has been increasing steadily in North America and gastroesophageal cancer. other Western countries, albeit with changing histology. With e Upper gastrointestinal tumors should be evaluated for the dramatic rise in the incidence of adenocarcinoma of the HER2 overexpression; adding trastuzumab to chemo- distal esophagus and proximal stomach, gastroesophageal therapy regimens for patients with HER2 overexpres- cancer is now considereda single entity. sion and metastatic disease provides a modest survival Smoking and alcohol use remain the major risk factors for benefit. squamous cell carcinoma of the esophagus. Risk factors for the more common adenocarcinoma also include smoking along with gastroesophageal reflux disease (GERD) and obesity. The development of Barrett esophagus as a result of GERD, espe- Gastric Lymphoma cially with dysplastic features, is a further risk for developing The stomach may be the primary site for extranodal lym- adenocarcinoma of the esophagus. Surveillance and treatment phoma, a heterogeneous group of B-cell and T-cell neoplasms, recommendations are based on grade of Barrett esophagus generally treated with combination chemotherapy. A specific and the presence of dysplasia. See Gastroenterology and variant, mucosa-associated lymphoid tissue lymphomas, are

Upper gastrointestinal tract cancers are a major cause of e In contrast to other gastrointestinal tumors, PET/CT is cancer deaths worldwide, particularly in Asia and Africa. The widely used as part of standard preoperative staging of incidence has been increasing steadily in North America and gastroesophageal cancer. other Western countries, albeit with changing histology. With e Upper gastrointestinal tumors should be evaluated for the dramatic rise in the incidence of adenocarcinoma of the HER2 overexpression; adding trastuzumab to chemo- distal esophagus and proximal stomach, gastroesophageal therapy regimens for patients with HER2 overexpres- cancer is now considereda single entity. sion and metastatic disease provides a modest survival Smoking and alcohol use remain the major risk factors for benefit. squamous cell carcinoma of the esophagus. Risk factors for the more common adenocarcinoma also include smoking along with gastroesophageal reflux disease (GERD) and obesity. The development of Barrett esophagus as a result of GERD, espe- Gastric Lymphoma cially with dysplastic features, is a further risk for developing The stomach may be the primary site for extranodal lym- adenocarcinoma of the esophagus. Surveillance and treatment phoma, a heterogeneous group of B-cell and T-cell neoplasms, recommendations are based on grade of Barrett esophagus generally treated with combination chemotherapy. A specific and the presence of dysplasia. See Gastroenterology and variant, mucosa-associated lymphoid tissue lymphomas, are 20

Lung Cancer indolent tumors; patients often present with localized disease radiotherapy with lutetium 177-labeled somatostatin analogue and concomitant Helicobacter pylori infection. In that setting, is a newer approach that is active in well-differentiated NETs standard treatment to eradicate the H. pylori infection results and is an appropriate consideration in progressing and/or in sustained complete remission in the majority of patients symptomatic disease. without the need for additional chemotherapy or radiation therapy. Mucosa-associated lymphoid tissue is discussed fur- ther in Lymphoid Malignancies. e Although histologically similar, gastrointestinal and pancreatic neuroendocrine tumors (NETs) behave dif- ferently, with several drugs showing activity against Neuroendocrine Tumors pancreatic NETs but not gastrointestinal NETs. Gastrointestinal neuroendocrine tumors (NETs) (formerly e Well-differentiated neuroendocrine tumors are indolent HVC called carcinoid tumors) arise from the endocrine cells of the and often initially only require observation and serial digestive tract. Pancreatic NETs arise from the islets of imaging. Langerhans cells and were previously called islet cell tumors. Although histologically similar, gastrointestinal and pancre- atic NETs behave differently, with several drugs showing activ- Gastrointestinal Stromal Tumors ity against pancreatic NETs but not gastrointestinal NETs. The clinical features of pancreatic NETs are discussed in Gastrointestinal stromal tumors (GISTs) are sarcomas charac- Gastroenterology & Hepatology. terized by an activating mutation in the c-kit proto-oncogene, Most NETs do not produce hormones and are termed which leads to constitutive activation of the receptor tyrosine “nonfunctional.” These tumors are often found incidentally or Kinase. Histologically, GISTs are identified by overexpression of during the evaluation of metastatic cancer, most commonly to the KIT gene, the immunohistochemical marker for KIT pro-

Most NETs do not produce hormones and are termed which leads to constitutive activation of the receptor tyrosine “nonfunctional.” These tumors are often found incidentally or Kinase. Histologically, GISTs are identified by overexpression of during the evaluation of metastatic cancer, most commonly to the KIT gene, the immunohistochemical marker for KIT pro- the liver. Up to 25% of NETs may produce hormones that cause tein. Although these tumors may be asymptomatic or inciden- symptoms suggesting a diagnosis. tally discovered during an endoscopic or imaging procedure, ; Multiphasic contrast-enhanced CT is used for staging in most are associated with nonspecific gastrointestinal symp- most patients with NETs except those with low potential to toms, and some may cause overt bleeding, pain, or signs of spread. Surgical resection is recommended for localized NETs, obstruction. They are most commonly located in the stomach, and resection may be considered in selected patients with which confers a better prognosis, and in the proximal intes- metastatic disease in order to palliate pain or reduce hormone tine. Other prognostic factors include tumor size and mitotic production. Well-differentiated gastrointestinal NETs exhibit rate. indolent growth. Intermediate-grade tumors are generally, but For patients undergoing a potentially curative resection of not always, more aggressive, whereas poorly differentiated, a localized GIST, low-risk tumors do not benefit from further high-grade NETs are highly aggressive tumors that are treated treatment. Higher-risk tumors are treated for 3 years with the with platinum-based cytotoxic regimens used for small cell adjuvant tyrosine kinase inhibitor imatinib. Imatinib is also lung cancer. used to treat patients who present with unresectable or meta- Given the indolent nature of metastatic or unresectable static disease.

with platinum-based cytotoxic regimens used for small cell adjuvant tyrosine kinase inhibitor imatinib. Imatinib is also lung cancer. used to treat patients who present with unresectable or meta- Given the indolent nature of metastatic or unresectable static disease. NETs, observation and serial examination and imaging, at 3 months initially, then 3 to 6 months subsequently, are appro- ¢ High-risk gastrointestinal stromal tumors should be priate. Asymptomatic patients may do well, with minimal treated with surgery and 3 years of adjuvant imatinib. growth and no symptoms for years, even with metastatic disease. The somatostatin analogues octreotide or lanreotide may be used for hormonal control or to delay tumor progres- Lung Cancer sion in patients who have metastatic tumors with somatosta- This section focuses on treatment and follow-up of patients tin receptors. Hepatic arterial embolization, radiofrequency with lung cancer. See Pulmonary and Critical Care Medicine ablation, or surgical debulking are sometimes used to for discussion of epidemiology, screening, clinical manifesta- decrease hormone production or to relieve symptoms of tions, diagnosis, and staging of patients with lung cancer. tumor bulk. Initial biopsy can distinguish tumors as either non-small cell When treatment is needed for either metastatic or unre- lung cancer (NSCLC) or small cell lung cancer (SCLC). NSCLC sectable disease, pancreatic NETs can be treated with temozo- can be divided into pathologic subtypes, including large cell, lomide plus capecitabine, or sunitinib (an anti-VEGF tyrosine adenocarcinoma, and squamous cell cancer. These subtypes kinase inhibitor), or everolimus (a mammalian target of rapa- have characteristic clinical features, and there are some differ- mycin inhibitor). Everolimus has more modest activity in ences in treatment between them, notably for metastatic dis- gastrointestinal NETs, but the other agents used for pancreatic ease. The staging criteria and treatment of SCLC differ from NETs are inactive in gastrointestinal NETs. Peptide-receptor NSCLC.

NETs, observation and serial examination and imaging, at 3 months initially, then 3 to 6 months subsequently, are appro- ¢ High-risk gastrointestinal stromal tumors should be priate. Asymptomatic patients may do well, with minimal treated with surgery and 3 years of adjuvant imatinib. growth and no symptoms for years, even with metastatic disease. The somatostatin analogues octreotide or lanreotide may be used for hormonal control or to delay tumor progres- Lung Cancer sion in patients who have metastatic tumors with somatosta- This section focuses on treatment and follow-up of patients tin receptors. Hepatic arterial embolization, radiofrequency with lung cancer. See Pulmonary and Critical Care Medicine ablation, or surgical debulking are sometimes used to for discussion of epidemiology, screening, clinical manifesta- decrease hormone production or to relieve symptoms of tions, diagnosis, and staging of patients with lung cancer. tumor bulk. Initial biopsy can distinguish tumors as either non-small cell When treatment is needed for either metastatic or unre- lung cancer (NSCLC) or small cell lung cancer (SCLC). NSCLC sectable disease, pancreatic NETs can be treated with temozo- can be divided into pathologic subtypes, including large cell, lomide plus capecitabine, or sunitinib (an anti-VEGF tyrosine adenocarcinoma, and squamous cell cancer. These subtypes kinase inhibitor), or everolimus (a mammalian target of rapa- have characteristic clinical features, and there are some differ- mycin inhibitor). Everolimus has more modest activity in ences in treatment between them, notably for metastatic dis- gastrointestinal NETs, but the other agents used for pancreatic ease. The staging criteria and treatment of SCLC differ from NETs are inactive in gastrointestinal NETs. Peptide-receptor NSCLC. 21