S-1 and CPT-11 Plus Ramucirumab (IRIS+Rmab) as Second-Line Chemotherapy for Patients with Oxaliplatin-Refractory Metastatic Colorectal Cancer (mCRC): A Multicenter Phase II Study in Japan (N-DOCC-F-C-1701).

This multicenter phase II N-DOCC-F-C-1701 trial is being planned in order to investigate the efficacy and safety of CPT-11+S-1 +Ramucirumab (IRIS+Rmab), which is anticipated to have a stronger anti-tumor effect than IRIS+Bmab in patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin (L-OHP) containing regimen, in consideration of the result of RAISE, FIRIS and some phase II trials of IRIS+Bevacicizumab (Bmab). The number of patients is set at 38 for the statistical analysis, assuming an expected median PFS of 5.0 months (threshold: 3.0 months). The primary endpoint of the study is the progression free survival (PFS), and the secondary endpoints are the overall response rate (ORR), overall survival (OS), adverse events (AE), quality of life (QOL) and review of nausea and vomiting. This trial is registered in the UMIN Clinical Trials Registry as UMIN000028170. We intend to start conducting the trial in September 1, 2017. If this trial meets the endpoint, IRIS+Rmab might be supported as a new optional standard regimen for mCRC.

Effects of intermittent 5-fluorouracil and low-dose cisplatin therapy on advanced and recurrent gastric cancer.

BACKGROUND: Although combination therapy consisting of 5-fluorouracil (5-FU) and cisplatin for the treatment of gastric cancer has been reported, no consistent regimen has been established. Our aim was to determine the optimal treatment schedule of this therapy, for patients with advanced or recurrent gastric cancer. PATIENTS AND METHODS: We conducted a phase II study to evaluate the efficacy and safety of combination therapy consisting of intermittent 5-FU and low-dose cisplatin in 26 patients with advanced or recurrent gastric cancer. The treatment cycle consisted of intravenous cisplatin at 3.3 mg/m(2)/day for 5 consecutive days. 5-FU was administered as a continuous intravenous infusion at 300-500 mg/body every other day (days 1, 3, 5) for 4 weeks. RESULTS: The partial response rate was 34.6%. The median survival duration was 12.8 months and the one-year survival was 53.1%. There were a few adverse effects. CONCLUSION: Our results suggest that this mode of combination therapy led to a fairly favorable outcome for patients with advanced or recurrent gastric cancer.

Presence of GABA(B) receptors forming heterodimers with GABA(B1) and GABA(B2) subunits in human lower esophageal sphincter.

Baclofen, a GABA(B)-receptor (GABA(B)R) agonist has been proposed to be useful as therapeutic agent for the management of gastro-esophageal reflux disease, but whether the compound acts directly at the lower esophageal sphincter (LES) remains to be elucidated. We performed the present study to assess the presence of GABA(B)R in human LES. Western blot analysis showed that both proteins of GABA(B1(a))/GABA(B1(b)) and GABA(B2) subunits were present in the muscle layer of LES. Immunohistochemical findings showed that both GABA(B1)- and GABA(B2)-subunit proteins were located on the neurons within the myenteric plexus, and furthermore, both proteins were observed in the same neurons. Reverse transcriptase-polymerase chain reaction analysis also revealed the presence of mRNAs for both subunits of GABA(B)R and also mRNAs for 6 isoforms of GABA(B1) subunits, from GABA(B1(a)) to GABA(B1(g)), except GABA(B1(d)), in human LES. Thus, the functional GABA(B)R-forming heterodimers with subunits of GABA(B1) and GABA(B2) are located on the myenteric neurons in human LES, suggesting that GABA(B)R agonists and antagonists act at least, at the level of the peripheral nervous system.

Experience of gastric cancer in a patient who had received a living-donor liver transplantation.

A 57-year-old woman had previously undergone a living-donor liver transplantation (LDLT) for end-stage liver disease related to hepatitis B virus. The liver graft had been donated by her husband. Her postoperative course had been uneventful. In the course of postoperative surveillance, she was incidentally found to have gastric cancer by an endoscopic examination 2 years after the liver transplantation. A gastric resection was the treatment choice, and the results were successful. The tumor, which was moderately differentiated adenocarcinoma, was limited to the mucosal layer, with no metastasis. In addition, a Helicobacter pylori infection was observed. This is the first reported case of a gastric cancer after LDLT. We report this case because of its importance regarding the need to carry out close surveillance in transplant recipients who are treated with immunosuppressive drugs, in order to make a timely identification of the occurrence of common malignancies.

Situs ambiguous with gastric cancer: report of a case.

Situs ambiguous is an unpredictable anomaly characterized by disorder of the organ arrangement in the chest and abdomen. We report a case of situs ambiguous found incidentally in a 73-year-old man with gastric cancer. Preoperative imaging showed polysplenia, a bridging liver, a midline gall bladder, and pancreatic divisum. The vessels around the stomach were clearly shown by computed tomography with multiplanar reconstruction (MPR). Computed tomography with MPR proved a good diagnostic tool for identifying both the abdominal vessels and the location of the organs. Based on a precise evaluation of this unusual anatomy, we performed distal gastrectomy with dissection of the regional lymph nodes.

Characterization of GABA(B) receptors involved in inhibition of motility associated with acetylcholine release in the dog small intestine: possible existence of a heterodimer of GABA(B1) and GABA(B2) subunits.

Characterization of the gamma-aminobutyric acid (GABA)(B) receptor involved in the motility of dog small intestine was analyzed by application of the microdialysis method to the small intestine of the whole body of the dog. The reverse transcription-polymerase chain reaction (RT-PCR) was used. Intraarterial administration of muscimol induced acceleration of motility associated with acetylcholine (ACh) release, these responses being antagonized by bicuculline. Intraarterial administration of baclofen induced inhibition of motility associated with ACh release, these responses being antagonized by CGP62349. GABA induced inhibition of motility associated with decrease in ACh release. CGP62349 alone induced acceleration of motility associated with increase in ACh release. RT-PCR revealed the presence of mRNAs for both subunits of GABA(B) receptor, GABA(B1) and GABA(B2), in the dog small intestine, although GABA(B1) subunits were 6 isoforms of GABA(B1) (GABA(B1(a)) - GABA(B1(g))), except GABA(B1(d)). Thus, the GABA(B) receptor located at cholinergic neurons as a heterodimer with subunits of GABA(B1) and GABA(B2) in the dog small intestine operates predominantly relative to the GABA(A) receptor in physiological motility.

Characterization of GABAB receptor in the human colon.

Characterization of the GABA(B) receptor in the human colon was performed by the reverse transcription-polymerase chain reaction (RT-PCR). mRNAs for both subunits of the GABA(B) receptor, GABA(B1) and GABA(B2), were detected in the human colon. The GABA(B1(e)) isoform was detected in the human colon, but not in the brain, and the other isoforms, except GABA(B1(d)), were detected in both tissues. Thus, the GABA(B) receptor may be present as a heterodimer with subunits of GABA(B1) and GABA(B2) in the human colon.

In vivo assessment of acceleration of motor activity associated with acetylcholine release via 5-hydroxytryptamine4 receptor in dog intestine.

Effect of mosapride, a benzamide, on the motor activity associated with the release of endogenous acetylcholine (ACh) from enteric neurons was examined in the ileum of anesthetized dogs using an in vivo microdialysis method and compared with the effect of 5-hydroxytryptamine (5-HT). Intraarterial administration of 5-HT accelerated intestinal motor activity and increased the concentration of dialysate ACh, and the responses were inhibited by SB204070, a specific 5-HT4-receptor antagonist, but were apparently not affected by methiothepin, ketanserin and granisetron. Intraarterial administration of mosapride, a prokinetic benzamide, accelerated intestinal motor activity and the concentration of dialysate ACh increased. The effects of mosapride were antagonized by SB204070. Specific [125I]SB207710 binding was observed in the myenteric and submucosal plexuses and muscle layers of dog ileum by in vitro receptor autoradiography. High densities of [125I]SB207710 binding sites were detected in the myenteric and submucosal plexuses. Mosapride as well as SB204070 inhibited [125I]SB207710 binding. Thus, in the whole body of dogs, 5-HT and mosapride accelerated the intestinal motor activity due to the increases in ACh release mediated by stimulation of the 5-HT4 receptor.

Combination chemotherapy of 5-fluorouracil and low-dose cisplatin in advanced and recurrent gastric cancer: a multicenter retrospective study in Nagasaki, Japan.

BACKGROUND: Combination therapy consisting of 5-fluorouracil (5-FU) and cisplatin (CDDP) has been shown to be effective in the treatment of gastric cancer. PATIENTS AND METHODS: The efficacy and safety of the combination therapy consisting of 5-FU and low-dose CDDP were assessed in 37 patients with advanced or recurrent gastric cancer. One course consisted of continuous drip infusion of 5-FU (330 mg/m2/day) on days 1-5 (7) + 5-day drip infusion of CDDP (5 mg/m2/day) for 4 weeks. The patients were treated with at least one course. RESULTS: The complete response (CR) + partial response (PR) rate was 35.1% and median survival-time (MST) was 7.1 months. There were no grade 3 or more adverse effects. CONCLUSION: Our results suggest that this mode of combination therapy leads to a fairly favorable outcome with few adverse effects in patients with advanced and recurrent gastric cancer.