In order to evaluate prediction of therapeutic efficacy by intracellular enzyme activity in gastric cancer, we investigated the role of thymidilate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) activ-ity in tumor sensitivity to 5-fluorouracil (5-FU). We measured TS and DPD activities in 8 human gastric cancer cell lines, 4 human gastric cancer xenografts and 40 clincal samples from gastric cancer. TS and DPD activities were determined by [³H]-FdUMP binding assay and thin-layer chromatography protocol, respectively. Sensitivity to 5-FU was determined by MTT assay in cell lines and by in vitro ATP assay in clinical samples. In cell lines and tumor xenografts, strong correlations between TS activity or DPD activity and 5-FU sensitivity were found. In clinical samples, a statistically significant correlation between DPD activity and in vitro senstivity to 5-FU also was found. These results suggest that senstivity to 5-FU is predictable by measurement of both TS activity and DPD activit.

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This study evaluated the significance of the number of positive second regional lymph nodes and No.8a metastasis for prognostic factors in 41 n₂ gastric cancer patients who underwent curative resection. They were classified into two groups according to the number of metastatic nodes; 1-2, 3 or more. In all n₂ cases, there were no significant differences in survival rates according to the number of positive lymph nodes and No.8a metastasis. The five-year survival rate in t1+t2 cases was significantly higher than that in t₃+t₄ cases, at 54.3% and 12.2%, respectively. In t₁+t₂ cases, there were significant differences in survival depending on the number of positive lymph nodes and the presence of No.8a metastasis. Patients with 1-2 positive nodes had a significantly higher survival rate than those with 3 or more. The five-year survival rates were 67.3%(1-2) and 20.0%(3 or more), respectively. In t₃+t₄ cases, there were no significant differences in survival rates according to the number of positive lymph nodes and No.8a metastasis. Depth of invasion is therefore the most impor-tant factor in all n₂ cases. In negative serosal invasion cases only, however, the number of positive nodes and No.8a metastasis may provide a prognostic indicator.

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The postoperative function of pylorus-preserving distal gastrectomy (PPDG) was analyzed by gastroin-testinal and biliary scintigraphy in 8 patients and compared with that of pre-operative control and conven-tional distal gastrectomy with Billroth-1 reconstruction (B-1) groups. The mean evacuation times of bile to duo-denum of three groups had no significant differences and in the PPDG group, there was no difference in bile evacuation between the pre-and postoperative periods. The regurgitation of bile to the rest stomach was ob-served in more than 40% of the B-1 group, but was seldom observed in the PPDG group and control group. Gastric emptying after pylorus-preserving distal gastrectomy assessed by gastrointestinal scintigraphy was significantly slower than the control at 6 months after surgery, however, this difference was no longer ob-served 1 year after surgery. Therefore, pyloric function after PPDG was observed to improve gradually after the surgery.

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Thirty-six patients with ampullary carcinoma who underwent surgical resection were examined. Thirty patients underwent pancreatoduodenectomy, and 5 patients underwent pylorus preserving pancreatoduodenectomy (PpPD). The over all five year survival rate was 66.6%. Histopathological factors influencing survival were lymph node involvement, invasion to the pancreas, invasion to the lymphatic vessels and macroscopic appearance of tumor (ulcerative or non-ulcerative type). Among these factors, invasion to the pancreas and its macroscopic appearance can be diagnosed precisely by preoperative endoscopy and endoscopic ultrasonography. There were 17 patients without invasion to the pancreas and with non-ulcerative type tumor. All of these patients showed no lymph node involvement and no recurrence of disease. These data suggest that PpPD with D1 lymph node dissection may be applied in patients with non-ulcerative type tumors and without invasion to the pancreas. However, ampullary resection should not be applied in these patients, because 21% of them were not the early ampullary cancer. Reprint requests: Takashi Tsuchiya Department of Surgery, Sendai City Medical Center

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A 59-yr-old male underwent treatment with antitubercular durg against pulmonary tuberculosis and ra-diation therapy against esophageal carcinoma from November, 1995. An esophagogastroscopy confirmed re-current lesion formed 0-IIc+IIa type esophageal carcinoma on March 26, 1997. Subtotal esohagectomy was performed on May 7, 1997. On microscopic findings of surgical specimen, the depth was detected to muscu-laris mucosae, and no lymph node metastasis were shown (0/40). Detecting slight anastomotic stenosis but good passage on esophagogram, oral intake was started from May 20. Oral potassium therapy was started from June 13, and antitubercular drug (INH, REP, EB) therapy from June 17. He complained of dysphagia from June 20. An esophagogastroscopy showed anastomotic stricture, ulcer and stases of tablets. As diagnosis of drug-induced esophageal ulcer and anastomotic stricture was made from clinical and endoscopic findings, we applied balloon dilation to the stricture. Since discontinuation oral potassium therapy, there has been no recur-rence of anastomotic stricture. Because drug-induced eophageal injury can easily occur after surgery for esophageal carcinoma, careful selection of the treatment drug, its size and shape for oral administration should be considered.

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Recent advanced treatments for esophageal cancer may contribute to prolonging survival of esophagealcancer patients. On the other hand, a second cancer occasionally has been found in the gastric tube used as a reconstructive organ. A 75-year-old man, who had undergone curative subtotal esophagectomy with recon-struction by retrosternal gastric tube substitution for an esophageal cancer about 2 years before, was admit-ted to our hospital because of vomiting and sever anemia. Upon examination, carcinoma of the gastric tube was discovered. The tumor was type-1 by Borrmann's classification. A biopsy was done and pathological find-ings showed poorly differentiated adenocarcinoma (solid type). Consequently, total resection of the gastric tube with reconstruction by retrosternal ascending colon substitution was performed. The pathological find-ings revealed that the tumor was undifferentiated carcinoma. Subsequent to surgery, lung and liver meta-stases had developed, and these were treated with chemotherapy.

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A case of gastric cancer that arose in the section of stomach, used for posterior mediastinal reconstruc-tion after radical operation for esophageal cancer is reported. The patient was a 69-year-old man, who had un-dergone thoracoscopic esophagectomy and posterior mediastinal reconstruction using stomach for moder-ately differentiated squamous cell carcinoma, with submucosal invasion, but without lymph node metastasis, in the middle thoracic esophagus, in our department, in September 1995. In October 1997, endoscopy revealed a lesion at the curvature of the gastric antrum. No malignant cells were detected in the biopsy specimen. However, in January 1998, the lesion had changed to 0-II a+II c in appearance and proved to be moderately differenciated adenocarcinoma by endoscopic biopsy. Endoscopic ultrasonography revealed submucosal layer invasion with metastasis to the subpyloric lymph node. In April 1998, the stomach was resected totally by right thoracotomy with D2 lymph node dissection followed by reconstruction using a long section of pedicled jejunum through the posterior mediastinum. The lesion was diagnosed histologically as moderately differenti-ated adenocarcinoma, m, n0, ly0, v0, stage Ia. The postoperative course was uneventful except for transient palsy of the recurrent laryngeal nerve. Although resection of the stomach for use in posterior mediastinal re-construction seemed to be a complicated approach because of possible severe adhesion developing, complete resection with lymph node dissection is essential to obtain a good out come for cancer originating in the stom-ach. Also the thoracoscopic procedure for the previous esophagectomy contributed to reduced pleural adhe-sion.

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Gastric leiomyosarcoma account for about 0.5-2% of primary gastric malignant neoplasms. The most common signs and symptoms are abdominal pain, gastrointestinal bleeding, and abdominal mass. Cases of in-traperitoneal hemorrhage are rare. The patient was a 25-year-old man with epigastric pain. He was admitted to our hospital with a diagnosis of acute generalized peritonitis. We detected an 8 cm gastric leiomyosarcoma with intraperitoneal hemorrhage by gastrofiberscopy, endoscopic ultrasonography, and abdominal CT exami-nations. At operation, massive bleeding of about 600 ml was found in the abdomen with a hematomous tumor 2.3×2.0cm in diameter growing from the antrum of the stomach. Histopathological diagnosis revealed a small low grade malignant leiomyosarcoma of the stomach. Postoperatively, he has remained healthy for 54 months. Reprint requests: Takafumi Oshiro Second Department of Surgery, Hiroshima University School of Medi-cine

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We present a very rare case of malignant schwannoma with gastric metastasis. A 54-year-old woman was admitted to the Department of Orthopedics due to local recurrence of malignant schwannoma in the left upper arm associated with lung metastasis. She underwent amputation of the left upper arm at 44 years of age. Examination of the severe anemia (Hb 4.5g/ml), as well as upper gastrointestinal fiberscopy (GIF) and upper gastrointestinal tract series (UGIS) were performed in our department. The findings showed a large tu-mor with ulceration in the stomach, but pathological findings from the biopsy specimen suspected poorly dif-ferentiated adenocarcinoma. Surgery was performed with a pre-operative diagnosis of gastric cancer and ma-lignant schwannoma in the left upper arm. The tumor arose from the submucosal layer of the stomach, and occupied the antrum. Microscopic findings confirmed the diagnosis of malignant schwannoma in the left up-per arm. The results of immunohistochemical staining of the specimens from the left upper arm and the stom-ach were also the same: S-100 protein (-), NSE (+). The final diagnosis was malignant schwannoma with gastric metastasis.

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The clinical feature of hepatic caudate lobe metastasis originating from colorectal carcinoma remains un-clear. We recently experienced two cases of this disease. The first patient is a 69 year-old woman who under-went extended left lobectomy and total caudate lobectomy with partial resection of the inferior vena cava (IVC) for a large tumor that occupied the entire caudate lobe with infiltration to the IVC. Although the post-operative course was uneventful, she had recurrent disease in liver, lung and bone, and is now undergoing chemoradiotherapy 13 months after the operation. The second case is a 56 year-old man, who underwent par-tial resection of the caudate lobe for a metastatic lesion limited to the Spiegel lobe. He is disease free 7months after operation. There have been only 8 reported cases of metastatic caudate lobe cancer from colorectal pri-maries until the present in Japanese literatures. We analyzed the clinical feature of this disease and concluded as follows: 1) Precise diagnosis of the caudate lobe lesion in an early stage is difficult. 2) Median survival time is 25 months, suggesting that aggressive surgical treatment may prolong survival. 3) The majority of postop-erative recurrence sites is the residual liver, which is similar to postoperative findings of liver metastasis in other than tha caudate lobe.

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A 49-year-old woman was admitted because of nausea and epigastralgia. Esophagogastrointestinal fiberscopy revealed a gastric varix located in the fundus and a moderate amount of coagulum in the stomach without evidence of active bleeding. On the 2nd hospital day, she went into hypovolemic shock due to rupture of the gastric varix. CT scanning demonstrated a pancreatic body tumor involving the splenic vein, which resulted in left-sided portal hypertension causing the gastric varix, along with multiple liver metastases. An emergency proximal partial gastrectomy was performed. A wedge biopsy of the pancreatic tumor suggested the diagnosis of a solid and papillary epithelial neoplasm. After her recovery, distal pancreatectomy with splenectomy was performed for debulking of the tumor. Intraarterial infusion of anti-cancer drugs including doxorubicin and cisplatin failed to improve the liver metastases. A preoperative biochemical study revealed an elevated serum level of gastrin (1, 560pg/ml), which increased markedly with growth of the metastatic liver tumors (>10, 000pg/ml). She frequently experienced hypoglycemic attacks due to hyperinsulinemia (150μU/ml). On histological review of surgical specimens, a final diagnosis of an islet cell tumor was established. The hyperinsulinemia could not be controlled by the administration of either Ca blockers or somatostatin analogs. Intraarterial infusion of streptozotocin was initiated, with marked improvement in hormone levels and her clinical condition. We report this case focusing on 3 major topics including the specific symptoms found at the onset of the disease, the process to the final pathological diagnosis and the treatment strategies for liver metastasis of neuroendocrine tumors.

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Somatostatinoma is still extremely rare, though reports of this tumor have increased in number owing to development of RIA of plasma somatostatin, immunohistochemistry, and so on. We experienced a case of combined pancreas tumor of duct cell carcinoma and somatostatin-producing islet cell carcinoma. The patient was 62-year-old female who was referred to our hospital for nausea, back pain, diarrhea, and weight loss. She also had a history of cholecytectomy for the gallbladder stone. Ultrasonography and CT scanning of the abdomen showed a tumor 7cm in size, surrounded by lateral segment of the liver, the stomach, and the pancreas. The tumor was resected, because no distant metastases were found. The pathological specimen showed the combined tumor of duct cell carcinoma and islet cell carcinoma. Immunohistochemical study revealed somatostatinpositive cells in islet cell carcinoma. The level of plasma somatostatin decreased from 46pg/ml to 21pg/ml and diarrhea ceased after the resection. From these results, we concluded that the symptom was caused by hypersecretion of somatostatin produced by the tumor.

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Ehlers-Danlos syndrome (EDS) type IV, the so-called arterialecchymotic type, has a high incidence of mortality because of arterial and bowel rupture. We report an extremely rare case of EDS type IV complicated with massive intraperitoneal hemorrhage resulting from a ruptured aneurysm of the ileal artery. A 49-year-old man suffering from right lower abdominal pain and diarrhea was admitted to the hospital. Intraperitoneal hemorrhage was detected by abdominal CT and paracentesis, and an emergent laparotomy was performed. During laparotomy, a bleeding tumor 3.0cm in diameter was detected in the mesentery of the ileum. Partial resection of the ileum was performed. A total of 1, 144 ml of hematoma and hemorrhage was removed. Histological investigation revealed that the bleeding tumor was a ruptured aneurysm of the ileal artery. The patient was finally diagnosed as EDS type IV with an ileal artery aneurysm rupture causing intraperitoneal hemorrhage because of aortic insufficiency, scoliosis, hyperextensible skin and hypermobile joints. He was alive after the surgery without any further hemorrhagic complications. Thirty one cases of EDS type IV have been reported in the Japanese literature. This is the first report of a curable case having a rupture of the ileal artery and massive intraperitoneal hemorrhage.

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Gastrointestinal autonomic nerve (GAN) tumors, also known as plexosarcomas, are a rare distinct subtype of the gastrointestinal stromal tumors. We experienced a case of small bowel GAN tumor diagnosed with immunohistochemical and ultrastructural examination. A 46-year-old woman complained of abdominal pain and body weight loss. Ultrasonographic examination and computed tomography showed a solid tumor in the ileum. Superior mesenteric arteriography showed a well stained tumor at the furcation of the ileac artery. An operation was performed after a diagnosis of an ileum tumor. Immunohistochemical examination revealed positive staining for vimentin, neuron specific enolase, synaptophysin, S-100 protein and neurofilament. Ultrastructural examination revealed neurosecretory granules and rudimentary cell junctions. These findings were consistent with those of GAN tumors Four cases of GAN tumors have been described in the literature, but our case is the first one of GAN tumors of the ileum in Japan.

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A case of adenocarcinoma arising in multiple duplication of the alimentary tract is reported. A 74-year-old woman complained of a sudden onset of abdominal pain in the right lower abdomen suddenly. Diagnostic images suggested a tumor in the same location. Laparotomy revealed a lesion growing like an extramural tumor, the size of 11×4 cm in the ileocecum. Rapid intraoperative frozen section diagnosis was adenocarcinoma. The lesion was thought to be metastatic carcinoma. Resection of the ileocecum and ascending colon was performed. Macroscopically and histopathologically, the lesion consisted of the alimentary tract had two duplicated tracts. Histopathological findings also showed that adenocarcinoma was arising in one of the duplication. It is very difficult to diagnose duplication of the alimentary tract preoperatively because of its uncharacteristic patterns in symptoms and examinations. Cases described of this disease have been increasing, but cases with multiple or malignant changes are very rare. There has been no case of neoplastic change in multiple duplication of the alimentary tract in literature to the best of our knowledge. This case is the first reported.

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Simple ulcer in the small intestine causing massive bloody stool is rarely encountered. We experienced four cases, all of which were diagnosed by intraoperative endoscopy during emergency laparotomy. A 44-year-old woman (Case 1), a 65-year-old man (Case 2), a 54-year-old man (Case 3) and a 67-year-old woman (Case 4) were each admitted to our hospital because of massive bloody stool. However, original lesions associated with massive bleeding were not detected in the stomach, duodenum, colon and rectum. All four patients underwent emergency laparotomies. In all cases, intraoperative endoscopy revealed hemorrhagic ulcers in the small intestine, and partial resections of the small intestine were performed. Histologic examination confirmed that the lesions were simple ulcer (Ul-II-III). The distinct diagnosis of small intestine ulcer is very difficult by means of routine gastrointestinal examinations. Therefore, laparotomy and intraoperative endoscopy are recommended in cases where original lesions associated with bloody stool and severe anemia cannot be identified.

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A case of intestinal tuberculosis associated with ileocutaneous fistula is reported.A 75-year-old man was hospitalized with complaints of fecal material discharge from a fistula in the right lateral abdomen. Mycobacterium tuberculosis was detected in his sputum as Gaffky 3, and chest plain radiography revealed an infiltrative shadow in the right upper lung field. Endoscopic examination dermonstrated circular stenosis just over the ileocecal valve, and the endoscope was not able to pass through this stenotic portion. The dilated small intestine was demonstrated to articulate with the cutaneous fistula, which was visualized by percutaneous fisterography. Under the diagnosis of intestinal tuberculosis, an operation was carried out. The ileocecal portion was found to be clumped due to inflammation, and the terminal ileum to be dilated, so right hemicolectomy was carried out. The resected specimen showed a fistula between the skin and one of the multiple intestinal ulcers. Histological examination did not reveal mycobacterium tuberculosis, but did show epitheloid granuloma accompanied with Langhans giant cell. Intestinal tuberculosis is most apt to spread superficially along the intestinal wall, and fistula formation is most uncommon. This case was intriguing, especially when contemplating the diversified conditions of intestinal tuberculosis.

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In case 1, a 42-year -old female had a Isp type polyp of the lower rectum with a 1.0cm in diameter. We conducted endoscopic polypectomy, and histological examination revealed carcinoid tumor, sm invasion, positive for the stump and for vascular invasion. Therefore, low anterior resection of the rectum was performed. A metastatic pararectal lymph node was diagnosed by frozen section analysis. In case 2, a 61-year-old man had a Isp type carcinoid of the lower rectum with a 0.8cm diameter. We conductedendoscopic polypectomy, and histological examination showed sm invasion, and positive findings for stump and for vascular invasion. Therefore, low anterior resection ofthe rectum was performed, and histological examination of the resected specimen revealed a metastatic pararectal lymph node. Carcinoids of the rectum with a diameter ofless than 2cm and submucosal layer invasion associated with lymph node metastasis israre. Only 18 cases, including the present two cases, have been reported in the Japanese literature. Of these, 91.7% were positive for vascular invasion, therefore, this finding appeares to be a useful predictor of lymph node involvement. Endoscopic polypectomy is indicated for rectal carcinoids which are less than 5mm in diameter, and local excision is indicated for lesions more than 5mm in diameter. Furthermore, under histological examination, radical operation with lymph node dissection is indicated for cases that are positive for vascular invasion and invasion deapth of more than sm2.

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