The influence of familial pancreatic cancer on postoperative outcome in pancreatic cancer: relevance to adjuvant chemotherapy

Background

Familial pancreatic cancer (FPC) is defined as a family in which at least two first-degree relatives have pancreatic cancer (PC). The prognostic significance of PC in an FPC family after surgery is not fully understood.

Methods

This was a retrospective study of 427 patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma between January 2008 and December 2016. PC patients who also had at least one first-degree relative with PC were defined as FPC patients. The associations between recurrence and clinicopathological characteristics were analyzed for both FPC and non-FPC patients.

Results

FPC patients accounted for 31 of the 427 (7.3%) patients. Recurrence occurred in 72.1% of the total cohort and in 87.1% of the 31 FPC patients. Multivariate analysis showed that being an FPC patient was an independent predictor for relapse-free survival (RFS) (hazard ratio [HR] 1.52, P = 0.038). Although univariate analysis revealed that being an FPC patient was significantly associated with poorer overall survival (OS) (P < 0.001), multivariate analysis showed that being an FPC patient was not an independent predictor for OS (P = 0.164). Dichotomization of the 427 patients into those who received (n = 317: 17 FPC and 300 non-FPC patients) and did not receive (n = 110: 14 FPC and 96 non-FPC patients) adjuvant chemotherapy revealed that being an FPC patient was an independent predictor for RFS (HR 2.50, P < 0.001) and OS (HR 2.30, P = 0.003) only for patients who received adjuvant chemotherapy.

Conclusions

This study has shown that being an FPC patient is a significant prognostic indicator for PC patients who undergo resection and receive adjuvant chemotherapy.

     

Association of <Emphasis Type="Italic">SLC22A4/5</Emphasis> Polymorphisms with Steroid Responsiveness of Inflammatory Bowel Disease in Japan

Purpose We investigated the association between steroid responsiveness and single nucleotide polymorphisms of SLC22A4/A5 located within inflammatory bowel disease 5 locus. Our goal is personalized steroid therapy adjusted to match individual variations in drug responsiveness in each inflammatory bowel disease patient. Methods Unrelated Japanese cohorts of 94 patients with Crohn’s, 94 patients with ulcerative colitis, and 257 healthy control subjects were consecutively enrolled in this study. Genotyping and haplotype analysis focusing on steroid responsiveness was performed by using 15 single nucleotide polymorphisms. Results The G allele of −368T > G in SLC22A5, in which strong linkage disequilibrium was observed and the limited diversity of three haplotypes was estimated, was significantly associated with steroid resistance in Japanese patients with Crohn’s disease (P = 0.016). Haplotype analysis between −446C > T and −368T > G in the SLC22A5 promoter region showed that the CG allele appeared to be a risk haplotype for steroid resistance (CG: odds ratio, 4.13; 95 percent confidence interval, 1.41–12.1; P = 0.016). Conclusions This extensive linkage disequilibrium may form a general risk haplotype for steroid resistance in Crohn’s disease in Japanese. Further analyses of the pharmacogenomics of steroid responsiveness are warranted to achieve the goal of individualized steroid therapy against inflammatory bowel disease. Supported by a grant-in-aid from the Ministry of Health, Labour and Welfare (K.I.), Japan. Address of correspondence: Yoshiaki Arimura, M.D., First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan. E-mail: arimura@sapmed.ac.jp     

Impact of reflux esophagitis on the esophageal function before and after laparoscopic fundoplication

Background

High-resolution manometry (HRM), which is breakthrough testing equipment to evaluate esophageal motor function, was developed in Europe and United State and has garnered attention. Moreover, multichannel intraluminal impedance pH (MII-pH) testing has allowed us to grasp all liquid/gas reflux including not only acid but also non-acid reflux. We examined the impact of the presence of reflux esophagitis (RE) on esophageal motor function before and after laparoscopic fundoplication.

Materials and methods

The subjects included 100 patients (male: 63 patients, mean age: 54.1?±?15.8) among 145 patients who underwent laparoscopic fundoplication for GERD associated diseases during a 4-year period from October 2012 to September 2016, excluding 6 patients who underwent further surgery, 32 patients on whom HRM was not performed, 3 patients who had technical errors during testing, and 4 patients for whom the status of RE was unknown. Regarding HRM, Mano Scan from Given Imaging Ltd. was used, and for the analysis, Mano View version 3.0 from the same company was used, after which data was calculated based on the Chicago Classification advocated by Pandolfino et al. Moreover, for the MII-pH testing, Sleuth manufactured by Sandhill Scientific. Inc. was used and automatic analysis was conducted by a computer. Postoperative assessments were conducted 3 months following surgery for all. Data was described in the median value and inter-quartile range, with a statistically significant difference defined as p?<?0.05 by Chi square, Mann–Whitney, and Wilcoxon tests.

Results

RE+?group (Los Angeles classification A:B:C:D?=?7:9:16:12 patients) included 44 patients (44%), of older age compared to the RE? group (62 vs. 50 years, p?=?0.012) and a higher Body Mass Index value (24.0 vs. 22.5, p?=?0.045); however, no differences were observed in terms of gender and duration of symptoms. In the preoperative findings on MII-pH, the RE+?group demonstrated significantly longer acid reflux time (4.7 vs. 1.3%, p?=?0.005), while in the HRM findings, the RE? group demonstrated a significantly longer abdominal esophagus (0 vs. 0.4 cm, p?=?0.049) and maintained esophageal body motor function (DCI: 1054 vs. 1407 mmHg s cm, p?=?0.021, Intact peristalsis ratio: 90 vs. 100%, p?=?0.037). As to the comparison of the treatment effect before and after laparoscopic fundoplication (Toupet fundoplication for all), significant improvements were observed in both groups in various parameters regarding reflux including acid reflux time, total number of liquid reflux episodes and total number of reflux episodes. Moreover, for both groups, the total length of the lower esophageal sphincter (LES) (RE+?group: 2.7 vs. 3.2 cm, p?=?0.001, RE? group: 3.0 vs. 3.4 cm, p?=?0.003) and the total length of the abdominal esophagus (RE+?group: 0 vs. 1.6 cm, p?<?0.001, RE? group: 0 vs. 1.8 cm, p?=?0.001) were significantly extended following surgery; however, no change was observed in DCI before and after surgery.

Conclusions

Regardless of the presence of RE, cardiac function and LES function were improved following laparoscopic Toupet fundoplication, but no changes were observed in esophageal body motor function.

     

Multicystic aneurysmal dilatation of bilateral coronary artery fistula

Bilateral coronary artery fistula constitutes an uncommon subgroup of coronary artery fistulas that may have a distinct embryologic origin. Coronary artery fistulas usually show a tortuous arrangement upon coronary angiography, but aneurysmal dilatation is rare. We report here an extremely rare case of coronary artery fistula originating from both coronary arteries, which showed multicystic aneurysmal dilatation.     

A case of Farmer's lung accompaign with caseous granuloma, monitored with serum KL-6 and SP-D]

A 65-year-old man was admitted to our hospital with a productive cough, fever, and dyspnea; his chest radiographs revealed diffuse nodular and ground-glass opacities. He had worked on a farm for 11 years. Six months earlier, he had presented with similar symptoms at another hospital, and was admitted with suspected atypical pneumonia. After treatment with antibiotics, his condition improved and he was discharged. Examination on admission to our hospital revealed markedly elevated serum KL-6 levels. Histological findings from specimens obtained by video-assisted thoracic surgical lung biopsy showed caseating and non-caseating epitheloid cell granuloma, lymphocyte infiltration, and alveolitis. Bacteriological tests for mycobacteria and fungi were all negative. Farmer's lung was diagnosed in accordance with the criteria for hypersensitive pneumonia. It is generally accepted that the distinguishing histological finding for Farmer's lung disease is non-caseating epitheloid cell granuloma, but in this case, caseous granuloma was also present.     

Nitric oxide plays an insignificant role in direct vasodilator effects of calcium channel blockers in healthy humans

Several experimental studies have suggested that the vasodilatory effects of calcium channel blockers (CCBs) are due in part to an endothelium-dependent mechanism. However, it remains unknown whether CCBs directly augment liberation of endothelium-derived dilator substances such as nitric oxide (NO) in the human vasculature. The aim of this study was to examine whether CCBs of several kinds directly increase the bioavailability of NO in forearm resistance vessels. Twenty-four healthy men (mean age 30 ± 2 years) were randomly assigned to three study groups (n = 8 in each), and each group was assigned one of three first-generation CCBs (nifedipine, nicardipine, diltiazem). Subdepressor doses of CCBs [4, 8, 16, 24, and 36 (diltiazem only) nmol/min; for 2 min in each dose] were infused intra-arterially, and forearm blood flow (FBF) was determined plethysmographically. After control FBF responses to CCBs had been measured, a NO synthase inhibitor (N ^G-monomethyl-l-arginine: l-NMMA) was infused intra-arterially, and the FBF response to CCBs was again determined. Further, as a positive control for NO stimulation, acetylcholine (ACh) was also examined before and after l-NMMA in each group. Systemic blood pressure and heart rate did not change significantly during the study protocol. The FBF responses to these CCBs did not differ before and after NO synthase inhibition by l-NMMA (FBF at maximum doses: nifedipine, 8.0 ± 0.8 vs 7.3 ± 0.7; nicardipine, 7.3 ± 1.5 vs 6.5 ± 1.3; diltiazem, 5.7 ± 0.7 vs 4.2 ± 0.7 ml/min per 100 ml: all not significant), although FBF responses to ACh were significantly reduced by l-NMMA. In conclusion, direct NO liberation does not make a significant contribution to the vasodilation associated with first-generation CCBs in healthy human resistance vessels. Received: July 12, 2001 / Accepted: October 19, 2001     

Delayed esophageal perforation after laparoscopic fundoplication in a patient with diabetes mellitus: a case report

A 55-year-old man on hemodialysis for diabetic nephropathy suffered from vomiting and hematoemesis. He was diagnosed to have reflux esophagitis with Los Angeles classification grade D, which was accompanied by a shortened esophagus and stricture. His reflux esophagitis was proton pump inhibitor resistant. Therefore, we performed laparoscopic Toupet fundoplication. Delayed esophageal perforation occurred on the ninth day postoperatively, for which he had to be reoperated. To our knowledge, there is no previous report of delayed esophageal perforation after laparoscopic fundoplication. Esophageal perforation might have been caused by denudation or attenuation of the abdominal esophagus.     

Left ventricular filling measured by Doppler echocar diography during dynamic exercise in patients with myocardial infarction

Summary To assess left ventricular diastolic properties in response to dynamic exercise, mitral inflow velocity integrals were measured by pulsed-wave Doppler echocardiography in ten patients with myocardial infarction and in ten normal subjects, and simultaneous left ventricular pressure was obtained with micromanometry in the patients. Early filling velocity integrals were maintained in the patients during exercise. Late filling velocity integrals were not augmented during exercise in the patients, but were increased in the normal subjects. In the patients, there was an increase in mitral valve opening pressure, left ventricular end-diastolic pressure, and the time constant of left ventricular isovolumic pressure decay. The lowest diastolic pressure and the number of time constants that had elapsed before the lowest diastolic pressure remained unchanged. These results show that in patients with myocardial infarction, early filling is maintained by an increase in driving pressure during exercise, despite incomplete relaxation. Augmentation of late filling, seen in normal subjects, is impaired in patients with myocardial infarction, probably due to an increase in left ventricular stiffness.