Evaluation of neoadjuvant chemotherapy with paclitaxel, 5-fluorouracil and cisplatin for advanced gastric cancer with pyloric stenosis

S-1 is currently recognized as one of the standard treatments for advanced and recurrent gastric cancer in Japan. However, there are some patients who can not take oral medication due to pyloric stenosis. We performed a critical evaluation of neoadjuvant chemotherapy (NAC) with paclitaxel (PTX), 5-fluorouracil (5-FU) and cisplatin (CDDP); (PTX+FP) for patients with advanced gastric cancer with pyloric stenosis. Since September 2001, 13 patients with far advanced or non-curative respectable gastric cancer with pyloric stenosis received NAC. These patients were treated with paclitaxel 40 mg/m(2) infusions on days 1 and 8, combined with CDDP (6.5 mg/m(2)) and 5-FU (350 mg/m(2)) on days 1 through 8 followed by 2 weeks rest as one course. After at least 2 courses of treatment, the patients underwent gastrectomy with lymphadectomy. The overall response rate was 38.5% (CR: 0, PR: 5), 7 patients had SD and 1 patient had PD. Seven patients had received staging laparoscopy before NAC and 6 patients had free cancer cells in the peritoneal cavity. Of 6 patients with positive cytology at laparoscopy, 4 had no free cancer cells at operation. The MST was 405 days and one-year survival rate was 55.6%. Toxicities were generally mild, and no serious adverse reactions were observed. There were only 2 cases of grade 3 neutropenia. In conclusion, combination of PTX+FP for NAC appears to be an effective treatment for patients with advanced gastric cancer with pyloric stenosis.     

Identification of transforming activity of free fatty acid receptor 2 by retroviral expression screening

Gallbladder cancer (GBC) is a highly fatal malignancy in humans. Genetic alterations in KRAS or TP53 as well as overexpression of ERBB2 have been shown to contribute to the development of certain types of GBC. However, many cases of GBC do not harbor such genetic changes, with other transforming events awaiting discovery. We here tried to identify novel cancer-promoting genes in GBC, with the use of a retroviral cDNA expression library. A retroviral cDNA expression library was constructed from a surgically resected clinical specimen of GBC, and was used to infect 3T3 fibroblasts in a focus formation assay. cDNA incorporated into the transformed foci was rescued by PCR. One such cDNA was found to encode free fatty acid receptor 2 (FFAR2), a G protein-coupled receptor for short-chain fatty acids. The oncogenic potential of FFAR2 was confirmed both in vitro with the focus formation assay and by evaluation of cell growth in soft agar as well as in vivo with a tumorigenicity assay in nude mice. The isolated FFAR2 cDNA had no sequence alterations, suggesting that upregulation of FFAR2 expression may contribute to malignant transformation. Indeed, all of quantitative RT-PCR, in situ hybridization, and immunohistochemical analyses showed that the amount of FFAR2 mRNA and its protein product was increased in digestive tract cancer specimens. Furthermore, short-chain fatty acids potentiated the mitogenic action of FFAR2 in 3T3 cells. Our data thus, for the first time, implicate FFAR2 in carcinogenesis of the digestive tract. ( Cancer Sci 2009)     

Characteristics and Prognosis of Stroke in Living Donor Renal Transplant Recipients

Aims: We aimed to determine the characteristics and vascular outcomes of stroke in renal transplant (RT) recipients and compare them with those in patients on hemodialysis (HD) and those with no renal replacement therapy (RRT). Methods: In this prospective observational study, 717 patients (mean age, 70.8 years; male, 60.5%) with acute ischemic stroke within one week of onset were consecutively enrolled and followed for one year. The patients were classified into three groups: (1) living donor RT recipients (n=27); (2) patients on maintenance HD before the index stroke (n=39); and (3) those with no history of RRT (n=651). The primary outcome was a composite of major adverse cardiovascular events (MACE). Results: Diabetic nephropathy was the most common reason for RRT in both RT and HD patients. RT patients were more likely to have embolic stroke of undetermined source (33.3%) than others, whereas HD patients more often had cardioembolism (51.3%). No difference was observed in the MACE risk between the patients in RT and non-RRT groups (annual rate, 11.3% vs. 13.1%; log-rankP=0.82; hazard ratio [95% confidence interval], 0.92 [0.29-2.98]). In contrast, HD patients had a greater risk of MACE than those with no RRT (annual rate, 28.2% vs. 13.1%; log-rankP=0.019; hazard ratio [95% confidence interval], 2.24 [1.16-4.3]). Conclusions: The underlying etiologies of stroke differed in RT and HD patients. The one-year risk of MACE for stroke patients who had received an RT was lower than that for patients undergoing HD and comparable with that of patients with no RRT.     

Addition of Two Substantial Side-Branch Silencers to the Interference Silencer by Incorporating a Zero-Mass Metamaterial

Zero-mass metamaterials comprise an orifice and a thin film. The resonance between the film and the air mass of the orifice hole is caused by sound waves, which significantly decreases the transmission loss at a specific frequency. The study novelly incorporates acoustic metamaterials in the delay tube of an interference silencer. In this case, it is determined that an interference silencer and a “side-branch silencer with two different branch pipe lengths” can be realized in a single silencer. At certain frequencies, the acoustic mass of the acoustic metamaterial approaches zero, which results in an interference silencer with the full length of the delay tube applied. At other frequencies, the acoustic metamaterial acts as a rigid wall with high transmission loss, thereby reflecting sound waves at the zero-mass metamaterial location. In this case, it is a side-branch silencer with two different tube lengths, corresponding to the tube lengths from the entrance and exit of the delay tube to the zero-mass metamaterial, respectively. The incorporation of zero-mass metamaterial into an interference-type silencer can introduce the silencing effect of a side-branch silencer with two different branch tube lengths without increasing the volume of the interference-type silencer. Theoretical values were obtained using the transfer matrix. Consequently, the theoretical and experimental values were close, enabling us to predict the transmission loss of the proposed silencer.     

Exacerbation of Secondary Pulmonary Hypertension by Flat Chest after Lung Transplantation

A 40-year-old woman with idiopathic pleuroparenchymal fibroelastosis (IPPFE) and flat chest underwent left single lung transplantation (SLT). Although she had developed over-systemic pulmonary arterial pressure (PAP) at transplantation, it was alleviated. However, her PAP gradually increased again. Her transplanted lung was well-inflated, but progression of fibrosis in her right native lung appeared to have caused a mediastinal shift, and her flat chest caused obstruction of the outflow tract of the pulmonary vein. She died of heart failure and associated infection 1.5 years after transplantation. An autopsy confirmed irreversible pulmonary arterial and venous changes in the transplanted lung, suggestive of chronic pressure overload. The flat chest associated with IPPFE can affect pulmonary circulation after SLT.