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GASTRIC CANCERS (Lecture 4) (gastric carcinoma, lymphoma and stromal tumor) Introduction: Gastric cancer is the second most common cause of cancerrelated death in the world. Geographic variation exists in the incidence of this disease around the world. Many Asian countries, including Korea, China, Taiwan, and Japan, have very high rates of gastric cancer. Adenocarcinoma of the stomach constitutes between 90% and 95% of all gastric malignancies. The second most common gastric malignancies are lymphomas. Leiomyosarcomas (2%), carcinoids (1%), adenoacanthomas (1%), and squamous cell carcinomas (1%) are the remaining tumor histologic types. Anatomical distribution of adenocarcinoma: 1. Lower part (Antrum): 40-50% 2. Middle part (Body): 30-40% 3. Proximal part (Fundus and cardia): 15-20% But recently the incidence of distal part carcinoma is reducing due to HP eradication, in contrast the incidence of proximal tumor (including fundus and cardia) probably due to increase incidence of Barrett’s oesophagus. Regarding the gross appearance of the tumor there are different types: a. Ulcerative: malignant gastric ulcer so biopsy and follow up endoscopy is indicated in gastric ulcer to exclude malignancy. b. Polypoidal or Fungating tumor c. Scirrhous (linitis plastic): diffuse submucosal type uncommon tumor and superficial mucosal biopsy may be negative. 1. Most cases of adenocarcinoma (distal) are arised as a result of atrophic gastritis with intestinal metaplasia. 2. The diffuse type which is localized at proximal stomach (fundus and cardia), and originated from normal gastric mucosa (no intestinal metaplasia and dysplasia and no role for HP infection), usually aggressive in nature and occurs in relatively young patients المقاطع اعاله لالطالع فقط Risk factors: 1 Many risk factors have been associated with the development of gastric cancer, and the pathogenesis is most likely multifactorial, but significant, genetic abnormalities are not known till now. 1. HP infection: This may lead to atrophic gastritis, achlorhydria, intestinal metaplasia, dysplasia and carcinoma. 2. Diet: Salted, smoked pickled, and nitrate containing diet (Carcinogenic compounds formed). Lack of fresh vegetable and fruits from the diet and also lack of vit C and A. 3. Others: Like adenomatous polyp, smoking, alcohol, pernicious anaemia, familial adenomatous polyposis, partial gastrectomy for more than 15 years,…..etc. also may play a role. *-These risk factors are most commonly related to the development of adenocarcinoma. Etiologies other than Helicobacter pylori infection or chronic gastritis have been difficult to elucidate for mucosa-associated lymphoid tissue tumors. Because of the indolent nature of gastric stromal tumors, the term malignancy rarely is valid or applicable. One study6 involving postmortem autopsy found gastrointestinal stromal tumors in up to 50 percent of the general Clinical picture: The initial diagnosis of gastric carcinoma often is delayed because up to 80 percent of patients are asymptomatic during the early stages of stomach cancer. In Japan, a higher incidence of adenocarcinoma and regular screening processes have led to a greater number of cases of gastric cancer being detected in an early stage cancer (i.e., when limited to the mucosa and submucosa, with or without lymph node involvement). . Late-stage gastric cancer. 1. Symptoms: Weight loss (most patient in advanced tumor), anaemia, abdominal pain, nausea and vomiting, early satiety, and peptic ulcer symptoms, dysphagia (proximal tumor) 2. Signs may include a palpably enlarged stomach, a primary mass (rare), an enlarged liver (secondaries), Virchow's node (i.e., left supraclavicular), Sister Mary Joseph's nodule (periumbilical), Krukenberg tumer (spread to ovary) or Blumer's shelf (metastatic tumor felt on rectal examination, with growth in the rectouterine/rectovesical space), ascites (peritoneal metastasis), thrombophlebitis (trousseau’s sign) . Diagnosis: In countries where the incidence of adenocarcinoma is high, a screening tests including regular screening endoscopy are done to detect early cancer. In most of other countries the diagnosis is delayed. In general the diagnosis of carcinoma is done by the following steps: 1. suspicious clinical picture: patients with dyspepsia especially in a middle aged male with “Alarm Features” which include the following: a. weight loss b. Anaemia c. Hematemesis and/or melaena d. Dysphagia e. Palpable abdominal mass. The diagnosis then confirmed by next steps 2. OGD (upper endoscopy): is a highly sensitive and specific diagnostic test, especially when combined with endoscopic biopsy. Multiple biopsy specimens should be obtained from any visually suspicious areas; this step involves repeated sampling at the same tissue site, so that each subsequent biopsy reaches deeper into the gastric wall. 3. However, good double-contrast barium swallow, a, noninvasive, and readily available study, may be used as the initial step if performed by expert radiologist. This radiographic study provides preliminary information that may help the physician determine if a gastric lesion is present and whether the lesion has benign or malignant features. 4. For Staging and distal metastasis lesions: After the initial diagnosis of gastric cancer is established, further evaluation for metastases is necessary to determine treatment options. US: of the abdomen Computed tomographic (CT) scanning: Endoscopic ultrasonography (EUS): Laparoscopy of abdomen also may be needed All important biochemical and hematological tests are also indicated. AJCC (American Joint Committee on Cancer) Staging System for Gastric Cancer هذا المقطع لالطالع فقط وليس مطلوبا ً في االمتحان Primary tumor (T) TX: Primary tumor cannot be assessed T0: No evidence of primary tumor Tis: Carcinoma in situ: intraepithelial tumor without invasion of the lamina propria T1: Tumor invades lamina propria or submucosa T2: Tumor invades the muscularis propria or the subserosa TNM Stage classification 0 Tis, N0, M0 IA T1, N0,M0 IB T1, T2, M0 T2a, N0, M0 T2b, N0, M0 T2a: Tumor invades muscularis propria T2b: Tumor invades subserosa T2a, N1, M0 T3: Tumor penetrates the serosa (visceral peritoneum) without invading adjacent structures T2b, N1, M0 T4: T2a, N2, M0 II Tumor invades adjacent structures IIIA Regional lymph nodes (N) NX: Regional lymph node(s) cannot be assessed N0: No regional lymph node metastasis§ T1, N2, M0 T3, N0, M0 T2b, N2, M0 T3, N1, M0 N1: Metastasis in 1 to 6 regional lymph nodes T4, N0, M0 N2: Metastasis in 7 to 15 regional lymph nodes IIIB N3: IV Metastasis in more than 15 regional lymph nodes T3, N2, M0 Distant metastasis (M) T4, N1, M0 MX: Distant metastasis can not be assessed T4, N2, M0 M0: No distant metastasis T4, N3, M0 M1: Distant metastasis T1, N3, M0 T2, N3, M0 T3, N3, M0 Any T, any N, M1 Gastric lymphoma (NH) 4 تكملة محاضرة رقم Contribute to only 5% of stomach tumers. However the stomach is the comment site for extra-nodal lymphoma. May be asymptomatic or presents with features just like carcinoma. The tumor may be polypoidal or ulcerative. Endoscopy is a diagnostic tool of choice for diagnosis. A rare, Low-grade, T-cell-lymphoma (MALT- oma) may follow HP infection. treatment with anti-H. Pylorus is needed in addition. Treatment of high grade lymphoma by combination of chemotherapy, surgery and /or radiotherapy. Prognosis: Depended on stage, histology, respectability and age of the patient. Other tumours 1. Leiomyoma (and rarely leiomyosarcoma) can occur and usually are asymptomatic but may ulcerate and cause bleeding ore may be presented with epigastric mass. 2. Gastric Polyps like hyperplastic polyp and adenoma. 3. Carcinoid-tumer: Often multiple. Occur at fundus and body originate from enterochromaffin-like (ECL). It may follow long-standing pernicious anaemia. Unlike carcinoid in othewr parts of GIt, the gastric type is usually benign, but large one should be removed. TREATMENT OF GASTRIC CARCINOMA 1. Surgery for resectable tumors: A. Curable resection in early carcinoma B. Surgery as palliative treatment In distal carcinoma: Partial gastrectomy and end to end anastaomosis. In proximal carcinoma: Oesophageogastrectomy. Pre-operative chemotherapy may be of benefit but post-operative is useless. Radiotherapy is also useless 2. Unresectable tumors: 1. Chemotherapy: FAM (5 Fluro, Adriamycin, Mitomycin C). 2. Endoscopic Laser ablation of tumor tissue for control of dysphagia or bleeding 3. Endoscopic dilatation, laser therapy, or insertion of expandable metalic stents .