Case Discussion <Brief History> A 77-year-old man was hospitalized because of exertional dyspnea for 10 days. Two years before this admission, the patient had subtotal gastrectomy for gastric cancer at a local hospital with initial presentation as epigastralgia. Postoperative course was quite smooth. One month before this admission, epigastralgia recurred to him. Tarry stool for three times within one day was also noted. He consulted the local hospital for fear of cancer recurrence. No active bleeder was told after upper endoscopy examination except erosion on remnant stomach. The symptoms improved after medication and transfusion. Ten days before this admission, progressive dyspnea on exertion developed. There was no history of chronic cough, fever, chills, chest pain, orthopnea or paroxysmal nocturnal dyspnea. On admission, the temperature was 36.8°C, the pulse was 123, and the respirations were 22. The blood pressure was 130/ 85 mmHg. Physical examination revealed pale conjunctivae. The jugular veins were not engorged. Regular heart beat with tachycardia was noticed on auscultation. Breath sounds were clear bilaterally. Bowel sounds were hypoactive, and no mass was palpated. There was no active lesion over bilateral lung fields in chest radiograph. The urine was normal. The hemoglobin level was 6.0 g/dl with MCV of 85.7 fl. Stool occult blood test showed (4+). He accepted to have upper endoscopy examination again, and a longitudinal submucosal tumor with ulcerated surface near the end of afferent loop was found (Fig. 1). Besides, abdominal ultrasonogram showed a 10 x 8 cm heteroechoic tumor with air trapped inside (Fig. 2). Abdominal CT scan also revealed a 10 cm well-defined hypovascular tumor with spotty calcification in the pancreatic region (Fig. 3). There was no dilatation of main pancreatic duct. As the A-loop biopsy showed spindle cell tumor, the patient accepted to have operation. Pathology of the surgical specimen also proved to be a c-kit positive gastrointestinal stromal tumor (GIST) (Fig. 4 ). The postoperative course was smooth, and the patient received regular follow-up at outpatient clinic. <Laboratory Results> 1. CBC: WBC RBC Hb Hct MCV Plt   K/μl M/μl g/dl %  fl K/μl 11/25 8.28 2.23 6.0 19.1 85.7 334 11/26 7.95 2.81 7.7 24.4 86.8 324 12/2 7.18 3.58 9.6 29.9 83.5 219 2. Biochemistry:    Alb Bil-T  Bil-D AST ALT gGT BUN Cre Na K   g/dl mg/dl mg/dl U/l U/l U/l mg/dl mg/dl mmol/l mmol/l 11/27 3.6 0.6 0.2 28 11 23 15.9 1.1 139 4.7 3. Iron Profile:   Ferritin Iron TIBC 11/25 9.92 (ng/ml)  4 (μg/dl) 336 (μg/dl) 4. Tumor markers:   CA19-9 CEA   U/ml ng/ml 12/3  9.77 1.0 <案例分析> 此為一個胃癌經亞全胃切除的病患，於門診追蹤第三年發現有上腹痛及黑便的表現。因為之前的胃癌病史，第一線的醫師安排了胃鏡以確認是否有上消化道病灶的存在。但在初次胃鏡檢查時並無發現明確之出血點，僅見胃糜爛 (erosion)於殘胃黏膜。之後發生的用力時呼吸困難，可考慮為原發性心肺疾病或是系統性疾病造成續發性心衰竭的表現。病史上並無發燒、其他相關心衰竭的病程變化或是慢性阻塞性肺病，理學檢查上有頻脈但是沒有頸靜脈脹大、心雜音、不整心律、肺囉音等等。然而結膜檢查較蒼白，加上解黑便的病史，為了代償失血引起的心輸出量提高，應該是造成這個病患呼吸不適的合理解釋。解黑便一般可視為上消化道出血的同義詞，但是需要排除使用鐵劑或其他藥物或色素的影響。不明確性消化道出血(obscure GI bleeding)係指在第一次內視鏡檢查沒發現出血點，但是臨床上仍然有反覆或是持續的出血表現，如缺鐵性貧血或黑便等等。有不少學者建議在進行腸道其他部位內視鏡檢查﹝如小腸鏡﹞之前，先重覆第二次的胃鏡檢視，因為仍有高達三成的病灶可被找出來。本病患在進行第二次的胃鏡檢視後，發現之前手術後的腸道盲端(afferent loop)內有一黏膜下腫瘤，經病理切片暨免疫染色證實為胃腸基質瘤(GIST)。病患接受手術切除的治療後，由於腫瘤大於十公分以上，分類上為高危險度的惡性傾向，所以建議仍需長期在門診追蹤。 繼續教育考題 1. (D) Which of the following items is NOT a risk factor for gastric cancer? A Cigarette smoking B Helicobacter pylori infection C Gastric adenoma larger than 1cm D Diet high in fruits and low in salted foods E 20 years after gastrectomy 2. (C) Which of the following items is NOT a cause of high-output heart failure? A Anemia B Pregnancy C Constrictive pericarditis D Hyperthyroidism E Arteriovenous fistulas 3. (E) Which of the following items is NOT a common cause for iron deficiency anemia? A Post-gastrectomy B Pregnancy C Hypermenorrhagia D Peptic ulcer with bleeding E Chonic renal insufficiency 4. (E) Which of the following study could be used as a diagnostic tool for evaluating obscure GI bleedng? A Push enteroscopy B Capsule endoscopy C Nuclear scans D Angiography E All of the above 5. (A) At which bleeding rate could angiography be useful in detecting overt obscure GI bleeding? A > 0.5 mL/min. B 0.1 to 0.4 mL/min. C > 0.5 mL/Hr. D 0.1 to 0.4 mL/Hr. E None of the above 6. (B) Which are the most common immunohistological markers for GIST? A CD45 + CD8 B c-kit + CD34 C S-100 + NSE D TTF-1 + CK-20 E Vimentin + desmin 7. (B) Which is the most common site for GIST to develop? A Esophagus B Stomach C Small intestine D colon E rectum 8. (A) Which of the following condition is associated with a relatively better prognosis? A Size < 2 cm + mitotic count < 5 / 50 HPF B Size < 2 cm + mitotic count > 10 / 50 HPF C Size > 10 cm + mitotic count < 5 / 50 HPF D Size >10 cm + mitotic count > 10 / 50 HPF E Small intestine GIST 9. (C) The following items could be the target for Imatinib (GlivecR ) EXCEPT A c-kit (KIT) B PDGFR-a C Protein kinase C D BCR-ABL E PDGFR-b 10. (E) Which of the following description about GIST is WRONG? A GISTs are generally thought to be malignant but with different degrees of aggressiveness B Surgical resection is the treatment of choice for GISTs C GISTs are usually unresponsive to chemotherapy D GISTs are usually unresponsive to radiotherapy E Imatinib should be given to all cases of GISTs to prevent metastasis 答案解說 (D) Diets high in fresh fruits and vegetables may offer protective effect for gastric cancer. (C) High-output heart failure is seen in patients with heart failure and hyperthyroidism, anemia, pregnancy, arteriovenous fistulas, beriberi, and Paget's disease. But constrictive pericarditis is related to low-output heart failure. (E ) Conditions that increase demand for iron, increase iron loss, or decrease iron intake, absorption, or use can produce iron deficiency. But anemia of chronic renal insufficiency is attributed primarily to decreased endogenous Epo production. (E ) (A ) Angiography may localize site of GI bleeding only when bleeding rate exceeds 0.5 ml/min. (B ) The immunohistochemical markers for GIST cells are c-kit and CD-34. (B ) Approximately 70% of GISTs occur in the stomach, 20-30% in the small intestine and less than 10% elsewhere in the GI tract. (A ) The mitotic index (fewer than 2 mitoses per 50 high-power fields) and size of the tumor (less than 5 cm versus 5 cm or more) are generally accepted as independent prognostic factors. Esophageal tumors as a group have the most favorable long-term survival while small intestine tumors have the worst. (C) Imatinib is a relatively selective and competitive inhibitor of all ABL tyrosine kinases (including c-ABL, BCR-ABL), platelet-derived growth factor receptor (PDGFR) and c-kit. It binds to the ATP-binding site of the target kinase and so inhibits phosphate transferring with subsequent downstream signaling. (E ) Surgical resection is the treatment of choice for GISTs. Resistance to single-agent therapy is common in cancer management; whether those GIST responsers will remain responsive to imatinib over time is uncertain. It is approved by US FDA only for c-kit positive unresectable (inoperable) and/or metastatic GISTs currently.