Proton pump inhibitors and risk of bloodstream infection without an identifiable source: a hospital-based case-control study.

The association between proton-pump inhibitor (PPI) use and systemic infections caused by bacterial translocation is unclear. This study aims to investigate whether patients receiving PPI therapy have a higher risk for bloodstream infections (BSI) without an identifiable source of infection, as an alternative indicator of BSI secondary to bacterial translocation. We conducted a hospital-based case-control study which enrolled all patients aged 20 years and older who developed BSI confirmed by two sets of positive blood culture and had inpatient care in Ichinomiya-Nishi Hospital in 2019. Patients' data were collected from medical records, and bacterial translocation type (BT-type) BSI group were defined as those who had BSI without an identifiable source of infection, whereas the others were classified control group based on the diagnostic criteria for each infectious disease. We analyzed data from 309 patients, including 66 cases and 243 controls. PPI users had a 2.4-fold higher risk of developing BT-type BSI compared to non-PPI-users after controlling for potential confounders (OR: 2.41, 95% CI: 1.29-4.51, p=0.006). In conclusion, PPI use is associated with higher risk of BSI without an identifiable source and therefore, PPI use may increase the risk of septic morbidity secondary to bacterial translocation.

Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy.

PURPOSE: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. METHODS: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. RESULTS: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). CONCLUSIONS: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.

Type of Combined Endoscopic Biliary and Gastroduodenal Stenting Is Significant for Biliary Route Maintenance.

Objective Some patients with malignant gastric outlet obstruction require combined biliary and gastroduodenal stenting (double stenting). However, biliary stent dysfunction can often disturb biliary route maintenance, thus making the optimal biliary stenting for these patients unclear. The present study was designed to assess the factors associated with the long-term maintenance of biliary drainage routes. Methods The clinical features and long-term outcomes were assessed in patients who underwent double stenting. Patients The outcomes were reviewed in 43 consecutive patients who successfully underwent endoscopic double stenting with metallic stents. Results An univariate analysis of all patients with biliary stent dysfunction showed the separate type of double stenting (two stents placed in a non-crossed position) to be the only predictive factor related to successful biliary re-intervention for stent dysfunction (odds ratio 73.67, p=0.001). A comparison of the clinical features in patients who underwent separate and cross (two stents placed in a crossed position) stenting showed the functional success rate to be higher for the separate (93.3%) than for the cross (61.5%) stent type, with the median times to biliary stent dysfunction differing significantly (330 vs. 298 days, respectively; p=0.048). The success rates of re-intervention in patients with separate and cross type stents were 88.9% and 0.0%, respectively (p=0.001), and the initial biliary route maintenance rates were 96.7% and 53.8%, respectively (p=0.002). Conclusion The separate type of double stenting may enhance successful biliary re-intervention for stent dysfunction and also maintain the initial drainage route longer. The biliary drainage outcomes should therefore be considered when choosing the type of double stenting.

Evaluation of Modified Glasgow Prognostic Score for Pancreatic Cancer: A Retrospective Cohort Study.

OBJECTIVES: The modified Glasgow prognostic score (mGPS) is known to be useful in determining the prognosis of cancers. However, the utility of mGPS for pancreatic cancer (PC) has been examined based primarily on a surgical series of early-stage cancers. The purpose of this study was to examine the utility of mGPS for PC of all stages using a retrospective cohort design. METHODS: We conducted a retrospective cohort study using data from a computerized database. A total of 807 patients with pathologically confirmed PC were analyzed (mGPS-0, n = 620; mGPS-1, n = 153; mGPS-2, n = 34). RESULTS: Median overall survival (OS) was significantly worse for the mGPS-1 group than for the mGPS-0 group (5.8 vs 15.8 months, respectively) but was comparable between the mGPS-2 and mGPS-1 groups (4.8 vs 5.8 months, respectively). After adjustment, both mGPS-1 and mGPS-2 were independent predictive factors of OS (mGPS-1: hazard ratio, 1.772; 95% confidence interval, 1.417-2.215; mGPS-2: hazard ratio, 2.033; 95% confidence interval, 1.284-3.219). Subgroup analysis showed that OS was significantly worse in the mGPS-1 and mGPS-2 groups than in the mGPS-0 group for all except the following 2 subgroups: localized disease and curative resection. CONCLUSIONS: The present results show that the mGPS is an independent prognostic factor in patients with PC, especially for advanced-stage disease.

A Randomized Controlled Trial Evaluating a Low-Volume PEG Solution Plus Ascorbic Acid versus Standard PEG Solution in Bowel Preparation for Colonoscopy.

Evaluation of polyethylene glycol electrolyte lavage solution containing ascorbic acid (PEG-ASC) has been controversial in the point of its hyperosmolarity, especially in old population. So we therefore designed the present study to compare the efficacy, acceptability, tolerability, and safety of 1.5 L PEG+ASC and 2 L standard PEG electrolyte solution (PEG-ELS), not only in the general population, but also in patients of advanced age. Randomization was stratified by age (<70 years or 70> years), and hematological and biochemical parameters were compared in each age group, especially with respect to the safety profile of each regimen. As a result, the 1.5-L PEG-ASC regimen had higher patient acceptability than the 2-L PEG-ELS regimen. Tolerability, bowel cleansing, and safety were similar between regimens. However, we demonstrated significant statistical changes in the hematological and biochemical parameters after taking bowel preparation solutions, not only in the PEG+ASC group, but also in the PEG-ELS group. No significant differences in the safety profile were found between subjects aged less than 70 years and those aged 70 years or more; nevertheless, regardless of age, proper hydration is needed throughout the bowel preparation process.

Risk factors for postoperative recurrence of intraductal papillary mucinous neoplasms of the pancreas based on a long-term follow-up study: proposals for follow-up strategies.

BACKGROUND: The aim of this study was to examine the associations between postoperative clinicopathological features of intraductal papillary mucinous neoplasm (IPMN) and recurrence over a long follow-up period. METHODS: We retrospectively assessed 153 IPMN patients who underwent resection. RESULTS: The resected tumors showed low/intermediate-grade dysplasia (LGD/IGD), high-grade dysplasia (HGD), T1a (stromal invasion ≤5 mm), and invasive intraductal papillary mucinous carcinoma (IPMC), in 54.9%, 22.2%, 4.6%, and 18.3% of patients, respectively. The median follow-up period after surgery was 46.4 (6.0-216.3) months, with an overall recurrence rate of 17.0%; the recurrence rates by histological type were 6.0%, 5.9%, 42.9%, and 57.1% for LGD/IGD, HGD, T1a, and invasive IPMC, respectively. Multivariate analysis revealed that recurrences related with tumor location, mural nodule size, presence of invasive cancer, lymph node metastasis, IPMN in the remnant pancreas, and main pancreatic duct dilatation after surgery. Recurrence occurred within the remnant pancreas in all LGD-T1a patients and as extrapancreatic metastasis in all patients with invasive IPMC. Of the total recurrences, 15.4% occurred over 5 years postoperatively. CONCLUSIONS: The postoperative follow-up protocol for patients with LGD-T1a should be similar to non-resected IPMN, and that for invasive IPMC should be the same as for pancreatic ductal adenocarcinoma patients.

Does the WHO 2010 classification of pancreatic neuroendocrine neoplasms accurately characterize pancreatic neuroendocrine carcinomas?

BACKGROUND: The WHO classified pancreatic neuroendocrine neoplasms in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to the Ki67 labeling index (LI). However, the clinical behavior of NEC is still not fully studied. We aimed to clarify the clinicopathological and molecular characteristics of NECs. METHODS: We retrospectively evaluated the clinicopathological characteristics, KRAS mutation status, treatment response, and the overall survival of eleven pNEC patients diagnosed between 2001 and 2014 according to the WHO 2010. We subclassified WHO-NECs into well-differentiated NEC (WDNEC) and poorly differentiated NEC (PDNEC). The latter was further subdivided into large-cell and small-cell subtypes. RESULTS: The median Ki67 LI was 69.1% (range 40-95%). Eleven WHO-NECs were subclassified into 4 WDNECs and 7 PDNECs. The latter was further separated into 3 large-cell and 4 small-cell subtypes. Comparisons of WDNEC vs. PDNEC revealed the following traits: hypervascularity on CT, 50% (2/4) vs. 0% (0/7) (P = 0.109); median Ki67 LI, 46.3% (40-53%) vs. 85% (54-95%) (P = 0.001); Rb immunopositivity, 100% (4/4) vs. 14% (1/7) (P = 0.015); KRAS mutations, 0% (0/4) vs. 86% (6/7) (P = 0.015); response rates to platinum-based chemotherapy, 0% (0/2) vs. 100% (4/4) (P = 0.067), and median survival, 227 vs. 186 days (P = 0.227). CONCLUSIONS: The WHO-NEC category may be composed of heterogeneous disease entities, namely WDNEC and PDNEC. These subgroups tended to exhibit differing profiles of Ki67 LI, Rb immunopositivity and KRAS mutation, and distinct response to chemotherapy. Further studies for the reevaluation of the current WHO 2010 classification are warranted.

Whipple's disease: the first Japanese case diagnosed by electron microscopy and polymerase chain reaction.

A 52-year-old man presented with diarrhea and 20 kg weight loss in one year. Enteroscopy showed diffuse yellow-white shaggy mucosa in the duodenum and jejunum. Biopsies of the duodenal mucosa revealed massive infiltration within the lamina propria by foamy macrophages strongly positive for periodic acid-Schiff stain. Electron microscopy demonstrated numerous bacilli within macrophages of the lamina propria. Tropheryma whipplei DNA was detected by polymerase chain reaction. The definitive diagnosis of Whipple's disease was made. Antibiotic therapy dramatically improved his clinical picture. This is the first Japanese case with Whipple's disease diagnosed by electron microscopy and polymerase chain reaction.