Ume (Japanese Apricot)-Induced Small Bowel Obstruction with Chronic Radiation Enteritis

Stricture formation is recognized as one of the complications of chronic radiation enteritis. Here, we present a case of a 73-year-old woman who presented with small bowel obstruction 16 years after pelvic irradiation for uterine cancer. Computed tomographic (CT) scan of the abdomen demonstrated a 1-cm foreign body in the terminal ileum. Laparotomy revealed a stone of ume (Japanese apricot) stuck in an ileal stricture, leading to complete impaction and perforation. She was successfully treated with ileocecal resection and ileocolic anastomosis without any complication. Pathological study revealed that the low compliance caused by fibrosis of the bowel wall prevented the small ume stone from passing through the irradiated ileum. Our case implies the specific risk of food-induced small bowel obstruction in patients with a history of pelvic irradiation

Multicenter Phase II Study of Intravenous and Intraperitoneal Paclitaxel With S-1 for Pancreatic Ductal Adenocarcinoma Patients With Peritoneal Metastasis

OBJECTIVE:To evaluate the clinical efficacy and tolerability of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel combined with S-1, "an oral fluoropyrimidine derivative containing tegafur, gimestat, and otastat potassium" in chemotherapy-naive pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis.BACKGROUND:PDAC patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis. An effective treatment strategy remains elusive.METHODS:Paclitaxel was administered i.v. at 50 mg/m and i.p. at 20 mg/m on days 1 and 8. S-1 was administered at 80 mg/m/d for 14 consecutive days, followed by 7 days of rest. The primary endpoint was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect and safety (UMIN000009446).RESULTS:Thirty-three patients who were pathologically diagnosed with the presence of peritoneal dissemination (n = 22) and/or positive peritoneal cytology (n = 11) without other organ metastasis were enrolled. The tumor was located at the pancreatic head in 7 patients and the body/tail in 26 patients. The median survival time was 16.3 (11.47-22.57) months, and the 1-year survival rate was 62%. The response rate and disease control rate in assessable patients were 36% and 82%, respectively. OS in 8 patients who underwent conversion surgery was significantly higher than that of nonsurgical patients (n = 25, P = 0.0062). Grade 3/4 hematologic toxicities occurred in 42% of the patients and nonhematologic adverse events in 18%. One patient died of thrombosis in the superior mesenteric artery.CONCLUSIONS:This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis

Complete chemical structures of human mitochondrial tRNAs

Mitochondria generate most cellular energy via oxidative phosphorylation. Twenty-two species of mitochondrial (mt-)tRNAs encoded in mtDNA translate essential subunits of the respiratory chain complexes. mt-tRNAs contain post-transcriptional modifications introduced by nuclear-encoded tRNA-modifying enzymes. They are required for deciphering genetic code accurately, as well as stabilizing tRNA. Loss of tRNA modifications frequently results in severe pathological consequences. Here, we perform a comprehensive analysis of post-transcriptional modifications of all human mt-tRNAs, including 14 previously-uncharacterized species. In total, we find 18 kinds of RNA modifications at 137 positions (8.7% in 1575 nucleobases) in 22 species of human mt-tRNAs. An up-to-date list of 34 genes responsible for mt-tRNA modifications are provided. We identify two genes required for queuosine (Q) formation in mt-tRNAs. Our results provide insight into the molecular mechanisms underlying the decoding system and could help to elucidate the molecular pathogenesis of human mitochondrial diseases caused by aberrant tRNA modifications

Intraperitoneal Paclitaxel Is Useful as Adjuvant Chemotherapy for Advanced Gastric Cancer with Serosal Exposure

Background: Intraperitoneal administration of paclitaxel (PTX) can elicit a marked clinical response in peritoneal metastases of gastric cancer. Methods: In this study, we retrospectively analyzed the clinical outcome of 17 patients who underwent R0 resection with D2 dissection for advanced gastric cancer with macroscopic serosal exposure and received intraperitoneal PTX as adjuvant therapy. Results: A pathological study revealed that the depth of invasion of the primary tumor was pT4a or pT4b in 10 cases, and that the pN stage was more than pN2 in 8 cases. Genetic analysis of peritoneal lavage fluid was performed in 14 cases, all of which were positive for carcinoembryonic antigen mRNA. In these patients, PTX was intraperitoneally administered at 20-60 mg/m2 with oral S-1 for 3-36 months after surgery. In a median follow-up period of 66 months, recurrence occurred in the liver and peritoneum in 2 (11.7%) and 1 (5.9%) patients, respectively, and no nodal recurrence was observed. Five-year overall survival and disease-free survival were 88.2 and 82.3%, respectively. Conclusion: Since these patients are considered to be a high-risk group for peritoneal recurrence, this result strongly suggests that adjuvant chemotherapy including intraperitoneal PTX is a promising protocol to improve the outcome of patients with advanced gastric cancer with serosal exposure

CD90+ mesothelial-like cells in peritoneal fluid promote peritoneal metastasis by forming a tumor permissive microenvironment.

The peritoneal cavity is a common target of metastatic gastrointestinal and ovarian cancer cells, but the mechanisms leading to peritoneal metastasis have not been fully elucidated. In this study, we examined the roles of cells in peritoneal fluids on the development of peritoneal metastasis. We found that a minor subset of human intraperitoneal cells with CD90(+)/CD45(-) phenotype vigorously grew in culture with mesothelial-like appearance. The mesothelial-like cells (MLC) displayed the characteristics of mesenchymal stem cell, such as differentiating into adipocytes, osteocytes, and chondrocytes, and suppressing T cell proliferation. These cells highly expressed type I collagen, vimentin, α-smooth muscle actin and fibroblast activated protein-α by the stimulation with TGF-β, which is characteristic of activated myofibroblasts. Intraperitoneal co-injection of MLCs with the human gastric cancer cell line, MKN45, significantly enhanced the rate of metastatic formation in the peritoneum of nude mice. Histological examination revealed that many MLCs were engrafted in metastatic nodules and were mainly located at the fibrous area. Dasatinib, a potent tyrosine kinase inhibitor, strongly inhibited the proliferation of MLCs but not MKN45 in vitro. Nevertheless, oral administration of Dasatinib significantly inhibited the development of peritoneal metastasis of MKN45, and resulted in reduced fibrillar formation of metastatic nodules. These results suggest floating MLCs in the peritoneal fluids support the development of peritoneal metastasis possibly through the production of the permissive microenvironment, and thus the functional blockade of MLCs is a reasonable strategy to treat recurrent abdominal malignancies