[Dihydropyrimidine dehydrogenase deficiency causes severe adverse effects of capecitabine].

We report the case of a 61-year-old man who experienced severe adverse effects of capecitabine because of dihydropyrimidine dehydrogenase (DPD) deficiency. In 2016, he visited our hospital for adenocarcinoma of the gastroesophageal junction and was prescribed neoadjuvant chemotherapy with capecitabine, cisplatin, and trastuzumab. On day 14 of chemotherapy, he developed severe diarrhea, canker sores, enterocolitis, febrile neutropenia, and thrombocytopenia. He was then urgently hospitalized, and anticancer treatment was stopped. We administered antibiotics and G-CSF, and he gradually recovered. However, he complained of severe bloody stools due to hemorrhagic enteritis;hence, we performed a bowel resection. The level of DPD protein, which metabolizes 5-fluorouracil (FU), was very low (2.83U/mg). Therefore, he was diagnosed with DPD deficiency, based on DPD protein or urinary pyrimidine levels, which caused serious adverse effects of capecitabine. It is a rare condition, and 5-FU administration should be avoided in DPD deficiency cases.

[A case of pseudo-Meigs' syndrome caused by metastatic ovarian tumors from gastric cancer].

A 54-year-old woman brought by ambulance had a lower abdominal mass and cough. Bilateral pleural effusion was revealed by X-ray and CT. An abdominal CT and MRI disclosed bilateral ovarian tumors which were considered to be metastatic tumors. GI endoscopy disclosed IIc-like advanced gastric cancer on the posterior wall of the stomach. Distal gastrectomy, total hysterectomy and bilateral adnexectomy were carried out. Gastric cancer was pathologically diagnosed as signet-ring cell carcinoma. Ovarian tumors had a similar histology, which suggested metastasis from gastric cancer. Since bilateral pleural effusion completely vanished after the ovarian resection, we concluded that this case coincided with pseudo-Meigs' syndrome. Pseudo-Meigs' syndrome of metastatic ovarian tumor from gastric cancer is very rare, only 3 cases having been reported in Japan.

[A case of advanced gastric cancer with pulmonary carcinomatous lymphangiosis responding remarkably to combination chemotherapy of docetaxel (TXT) and TS-1].

A 51-old-female patient was admitted because of dyspnea. This case was diagnosed inoperable advanced gastric cancer and pulmonary carcinomatous lymphangiosis. She was treated by combination of docetaxel (TXT) and TS-1. TXT (40 mg/m2) was administered on day 1, and TS-1 (80 mg/body/day) was then administered for 14 days followed by a 7-day interval as one course. After two courses of chemotherapy, carcinomatous lymphangiosis declined, tumor markers decreased, and dyspnea improved. Administration of oxygen was thus discontinued. No side effects appeared (hematological or non-hematological).

The cytotoxicity of hydrophobic bile acids is ameliorated by more hydrophilic bile acids in intestinal cell lines IEC-6 and Caco-2.

Bile acids, especially those with hydrophobic properties, are known to possess cytotoxicity. However, the mechanisms responsible for the cytotoxicity of bile acids are still under investigation. On the other hand, the hydrophilic bile acid, ursodeoxycholic acid has been reported to exhibit therapeutic effects against cytotoxic hydrophobic bile acids. The aim of the present study was to investigate the cytotoxicity of individual bile acids and combinations of bile acids using the intestinal cell lines IEC-6 and Caco-2 cells. The cytotoxicities of individual bile acids and the effects of various bile acid combinations were evaluated using the MTS [3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. The bile acids induced cytotoxic effects depending on their hydrophobicity except for hyodeoxycholic acid. In the study for the effects of combined bile acids, not only ursodeoxycholic acid but other hydrophilic bile salts such as cholic acid and hyocholic acid exhibited cytoprotection against deoxycholic acid-induced cytotoxicity. Moreover, even some hydrophobic bile acids, such as chenodeoxycholic acid also exhibited cytoprotection. It is possible that the cytotoxicity of hydrophobic bile acids is ameliorated by more hydrophilic bile acids under certain conditions. The understanding of the precise mechanism of this phenomenon remains to be determined.

Mast cells may not play a crucial role in the pathogenesis of experimental closed duodenal loop-induced pancreatitis in rats.

INTRODUCTION: Ws/Ws rats have a small deletion of the c-kit gene and are deficient in both mucosal-type mast cells and connective tissue-type mast cells. AIM: To investigate the role of pancreatic mast cells in the development of experimental closed duodenal loop (CDL)-induced pancreatitis using Ws/Ws rats. METHODOLOGY: Pancreatitis was induced by the CDL technique for 5 and 12 hours, and the subsequent ascites volume, wet pancreatic weight, pancreatic myeloperoxidase activities, and serum amylase levels were evaluated. The pancreatic tissue damage was also evaluated histologically. RESULTS: The CDL technique induced equally severe ascites, pancreatic edema and hyperemia, and hyperamylasemia in the Ws/Ws versus the control (+/+) rats. The microscopic mucosal damage score was also equivalent in the Ws/Ws and control (+/+) rats, and there were no significant differences in mucosal myeloperoxidase activity between the Ws/Ws and control (+/+) rats. CONCLUSION: These results indicate that mast cells may not be crucial for the development of CDL-induced pancreatitis.