2Gastrointestinal Neoplasm Dr Vahid SebghatollahiAssistant professor of gastroentrology and hepatologyIsfahan university of medical science
3Case 1آقای 65ساله ساکن گنبد سیگاری با دیسفاژی پیشرونده نسبت به جامدات واخیرا نسبت به مایعات و کاهش وزن 10کیلو طی 3 ماه به علاوه بی اشتهایی شدید مراجعه کرده است.سوالات:نکات مهم شرح حال؟تشخیص؟علائم بالینی این بیماری؟روش تشخیصی پیشنهادی شما؟Staging؟درمان؟
5INCIDENCE AND EPIDEMIOLOGY The incidence of SCC varies dramatically throughout the world.The highest rates are found in developing countries such as northern China, Iran, India, and parts of southern Africa. SCC is relatively uncommon in the United States, with an annual incidence of less than 5 cases per 100,000 population.Esophageal cancer is rare among individuals younger than 40 years, but thereafter increases in incidence with each subsequent decade.Men are affected more often than women
6ETIOLOGIC FACTORS(SCC) The major risk factors for SCC of the esophagus in the United States are smoking and alcohol consumptionThe major risk factors for SCC in the “esophageal cancer belt” of Iran and Asia are not well understood, but are thought to include poor nutritional status, low intake of fruits and vegetables, and drinking beverages at high temperatures
7ETIOLOGIC FACTORS(Adeno-ca) The major risk factors for adenocarcinoma of the esophagus are:Barrett's esophagusgastroesophageal reflux diseaseSmokinghigh body mass index
8Clinical Presentation Dysphagia is the most common symptom of esophageal carcinoma.It occurs when the esophageal lumen has been compromised by about 75% of its normal diameter.Difficulty swallowing solid foods precedes dysphagia to liquids.With complete obstruction, regurgitation, aspiration, and cough or pneumonia may occur.
9Clinical Presentation Pulmonary symptoms may also occur if a tracheoesophageal fistula is present.Patients uniformly have weight loss and anorexia.Chest pain, hiccups, or hoarseness indicates involvement of adjacent structures such as the mediastinum, diaphragm, and recurrent laryngeal nerve, respectively.If gastrointestinal bleeding occurs, it is often occult or associated with iron deficiency anemia.
10DIAGNOSISPatients with dysphagia or other suggestive symptoms should be evaluated by upper endoscopy or an esophageal barium study.The advantage of endoscopy includes the opportunity to obtain tissue of the cancer, either by biopsy or brush cytologic study.Esophageal carcinoma may appear as a plaque, an ulcer, a stricture, or a mass. Nearly 90% of adenocarcinomas develop in the distal esophagus, whereas 50% of SCCs occur in the middle third of the esophagus, and the other 50% are evenly distributed in the proximal and distal esophagus
14StagingComputed tomography (CT) scanning of the chest and abdomen is performed to detect invasion of local structures and metastases to the lung and liver.Endoscopic ultrasonography (EUS), with its ability to image the esophageal wall as a five-layer structure that correlates with histologic layers, is more accurate than CT for staging tumor depth, local invasion, and regional node involvement.
17THERAPYOnly localized tumors confined to the wall of the esophagus are potentially curable by surgery.Overall 5-year survival rates for patients undergoing curative resection, however, are just 5% to 20%.Preoperative chemotherapy with multidrug regimens combined with radiation therapy may reduce local recurrence rates and improve survival.Chemotherapy plus radiation therapy is also recommended for patients with locally unresectable disease, medical conditions that preclude surgery, and those who refuse surgery.Patients with metastatic disease should be considered for palliative treatment of dysphagia.
18THERAPYLocal treatment with endoscopic methods (such as malignant stricture dilation), placement of an endoprosthesis (stent), and tumor ablation by laser or photodynamic therapy are often the methods of choice for rapid palliation.More sustained palliation can be achieved using combined chemotherapy and radiation therapy.
21Case 2آقای 73 ساله ساکن اردبیل با درد مبهم اپی گاستر و بی اشتهایی و کاهش وزن بارز و استفراغ بعد از غذا خوردن مراجعه کرده است.سوالات:تشخیص؟علایم بالینی؟روش تشخیصی پیشنهادی؟درمان؟
22Gastric cancer INCIDENCE AND EPIDEMIOLOGY More than 90% of gastric cancers are adenocarcinomas.The disease is more common in developing countries than industrialized nations and shows a predilection for urban and lower socioeconomic groups.Gastric cancer rarely occurs before age 40 years; thereafter, the incidence rises steadily, peaking in the seventh decade.Men are afflicted at a rate nearly twice that of women.
23Gastric cancer Risk factors Dietary factors include deficiencies in fats, protein, and vitamins A and C and excesses in salted meat and fish, smoked foods, pickled vegetables, and nitrates.Predisposing conditions including atrophic gastritis, postgastrectomy states, achlorhydria, pernicious anemia, adenomatous polyps, and Ménétrier disease are also associated with an increased incidence.The World Health Organization has classified Helicobacter pylori as a carcinogen and epidemiologically linked to gastric adenocarcinoma
24CLINICAL PRESENTATION Abdominal discomfort is the most frequent symptom; however, early satiety, nausea, and vomiting may occur, especially with gastric outlet obstruction.Gastrointestinal bleeding may manifest as iron deficiency anemia, occult bleeding, or frank upper gastrointestinal hemorrhage.Anorexia and often accompany other symptoms.
25The signs of metastatic disease: Virchow (left supraclavicular) nodeBlumer shelf (mass in the perirectal pouch, found on digital rectal examination)Krukenberg tumor (metastasis to the ovaries).Paraneoplastic syndromes:Trousseau syndrome (thrombosis),acanthosis nigricans (pigmented dermal lesions),membranous nephropathy,microangiopathic hemolytic anemia,Leser-Trélat sign (seborrheic keratoses),dermatomyositis.
29DIAGNOSISThe diagnostic tests for gastric malignancies include double contrast (barium) upper gastrointestinal radiography or endoscopy.Lesions detected on barium study require endoscopic biopsy and cytologic study for histologic evaluation.Gastric carcinomas may appear as ulcers, masses, enlarged gastric folds, or an infiltrative process with a nondistensible stomach wall (linitis plastica).
36StagingThe accuracy of endoscopic ultrasonography is in the range of 77% to 93% for determining the depth of invasion and 65% to 90% for predicting regional node involvement.CT scanning of the chest and abdomen may detect metastases in the lung and liver but is otherwise poor for staging.
39THERAPYThe standard treatment of gastric cancer is complete surgical resection with removal of all gross and microscopic disease.The postoperative local-regional recurrence rate remains 80%.A postoperative combination of chemotherapy plus radiation therapy reduces local recurrence rates and improves survival in patients undergoing curative resection.In the United States, nearly two thirds of patients present with advanced disease (stages III to IV), with a survival rate of less than 20%. Chemotherapy is the mainstay of treatment for such patients, but long-term survival is rare.Palliative resection may be performed to prevent obstruction or treat bleeding;
40Case 3بیمار خانم 63 ساله با آنمی فقر آهن و کاهش وزن و هماتوشزی مراجعه نموده است. سابقه کولون کانسر در خواهرش در سن 54 سالگی را متذکر است.سوالات:تشخیص احتمالی؟روش تشخیصی پیشنهادی؟درمان؟پیشگیری؟
41Colon cancerCarcinoma of the colon and rectum is the third most common cancer and the second most common cause of cancer deaths in American men and women
46EpidemiologyAbout 6% of Americans will develop colorectal cancer during their lifetime.Age is an important determinant of risk.Although extremely uncommon in individuals younger than 35 years (except those with rare predisposing genetic syndromes), the incidence of colorectal cancer increases steadily with age, beginning at about 40 years of age, with an approximate doubling with each successive decade thereafter to about 80 years of age.Cancer of the colon affects men and women at similar rates, whereas cancer of the rectum is more common in men.
47Risk factorFactors associated with an increased risk for the disease include obesity, red meat, alcohol, and tobaccoconversely, factors associated with a decreased risk include physical activity, nonsteroidal antiinflammatory agents, and multivitamins.
48Most colorectal cancers are believed to arise from benign adenomatous polyps (adenomas). The epidemiology of colorectal adenomas is similar to that of colorectal cancer.Fortunately, only a minority of adenomas progress to colorectal cancer. It is unknown how long an adenoma takes to develop into an invasive cancer, but data from multiple observational studies suggest at least 10 years.
50High risk groupsHigh-risk groups have been identified and include those with a personal or family history of colorectal cancer or adenomas, various genetic polyposis and nonpolyposis syndromes, and inflammatory bowel disease (Table 39-1).Hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) are well-defined genetic syndromes associated with the highest risk for colorectal cancer.
51HNPCC (Lynch syndromes) HNPCC (Lynch syndromes) is characterized by:inherited mutations in one of the DNA mismatch repair genes (e.g., hMLH-1 or hMSH-2)early-onset colorectal cancer (average age, 44 years)absence of polyposispredominance (60% to 70%) of tumors proximal to the splenic flexurean excess of both colorectal and extracolonic (e.g., endometrial) cancersestimated lifetime risk for colorectal cancer of 80% to 90%.
52FAPIn contrast, FAP is characterized by inherited mutations in the APC geneThe appearance of hundreds of colorectal adenomas during the second or third decade of life, and a risk for colorectal cancer that approaches 100% by the fifth decade if left untreated.FAP is also associated with benign fundic gland polyps in the stomach and duodenal adenomas and adenocarcinomas that have a predilection for the periampullary region.
54CLINICAL PRESENTATION Most colorectal neoplasms are asymptomatic until advanced.Gastrointestinal blood loss is the most common symptomand may present as occult bleeding, hematochezia, or unexplained iron deficiency anemia.Other symptoms include abdominal pain from obstruction or invasion, change in bowel habits, or unexplained anorexia or weight loss.A palpable mass may be present in patients with advanced cancers of the cecum.
56DIAGNOSISAll patients with symptoms suggestive of colorectal neoplasia should undergo an evaluation of the colon by colonoscopy, flexible sigmoidoscopy, or double contrast barium enema.About 50% of colorectal adenomas and cancers are located between the rectum and splenic flexure;however, the prevalence of cancers proximal to the splenic flexure increases with increasing age, especially among women.Colonoscopy has greater accuracy than a barium enema study in the detection of small polyps and early cancers as well as the ability to remove neoplasms or biopsy lesions at the time of the examination.
57Lesions detected on barium enema study necessitate colonoscopic evaluation. CT scanning and of the abdomen and pelvis is used preoperatively to assess the extent of metastatic disease.EUS is used for the preoperative staging of rectal cancer.Carcinoembryonic antigen level is measured preoperatively for a baseline value and, if elevated, monitored to detect tumor recurrence postoperatively.
60Colorectal cancer screening Periodic screening by colonoscopy, CT colonography (virtual colonoscopy), flexible sigmoidoscopy, or double contrast enema is recommended for asymptomatic, average risk patients beginning at age 50 years.Stool blood testing and stool DNA testing are alternative screening methods for patients who refuse one of the preferred methodsScreening recommendations for high-risk patients vary depending on the risk factor but in general rely on colonoscopy performed at a younger age and at more frequent intervals than for those at average risk.
62THERAPY Surgery alone is curative for early-stage colorectal cancers. Surgery and adjuvant chemotherapy with 5-fluorouracil and leucovorin ± oxiliplatin or capecitabine alone are recommended for stage III colon cancer.For patients with stage II and III rectal cancer, the combination of postoperative radiation and 5-fluorouracil (± leucovorin) has been found to significantly reduce the recurrence rate, cancer-related deaths, and overall mortality.Independent of nodal status, preoperative chemoradiotherapy followed adjuvant chemotherapy is recommended for patients with locally advanced rectal cancers.For patients with stage IV disease, palliative surgery, chemotherapy, and radiation therapy are the mainstays of therapy.