Variation Among Japanese Miso Breweries in Indoor Microbiomes is Mainly Ascribed to Variation in Type of Indoor Surface.

Miso is a microbially-fermented soybean food. The miso brewery indoor microbiome contributes to miso fermentation. Japanese breweries are not climate-controlled, so indoor spaces are strongly affected by the prevailing climate. Because climate influences microorganism distribution, our first hypothesis is that latitude, as a proxy for climate, is a major determinant of brewery indoor microbiome structure. Breweries vary in interior surface materials and in the way operations (steaming, processing, fermenting) are apportioned among rooms. Therefore, our second hypothesis is that more variability in indoor microbiomes exists among breweries than can be ascribed to a latitudinal gradient. Most miso produced today is inoculated with commercial microbial strains to standardize fermentation. If commercial strains outcompete indigenous microbes for membership in the indoor microbiome, this practice may homogenize indoor microbiomes among regions or breweries. Therefore, our third hypothesis is that inoculant fungal species dominate indoor fungal communities and make it impossible to distinguish communities among breweries or across their latitudinal gradient. We tested these hypotheses by sampling indoor surfaces in several breweries across a latitudinal gradient in Japan. We found that latitude had a significant but relatively small impact on indoor fungal and bacterial communities, that the effect of brewery was large relative to latitude, and that inoculant fungi made such small contributions to the indoor microbiome that distinctions among breweries and along the latitudinal gradient remained apparent. Recently, the Japanese Ministry of Agriculture, Forestry and Fisheries specified fungal inoculants to standardize miso production. However, this may not be possible so long as the indoor microbiome remains uncontrolled.

Survival impact of distal pancreatectomy with en bloc celiac axis resection combined with neoadjuvant chemotherapy for borderline resectable or locally advanced pancreatic body carcinoma.

BACKGROUND: The survival benefit associated with distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for patients with borderline resectable or locally advanced pancreatic body carcinoma is controversial. The aim of this study was to evaluate the impact of DP-CAR following neoadjuvant chemotherapy on survival in patients with borderline resectable or locally advanced pancreatic body carcinoma. METHODS: Medical records of patients with pancreatic ductal adenocarcinoma who underwent distal pancreatectomy (DP, n = 102) and DP-CAR following neoadjuvant chemotherapy (n = 32) between 2008 and 2019 were analyzed retrospectively. Short- and long-term outcomes were compared between the two groups. RESULTS: All patients who underwent DP-CAR had tumor contact with the celiac axis. Of these, 30 patients underwent preoperative embolization of the common hepatic artery. The pretreatment tumor size of patients who underwent DP-CAR was larger (P < 0.001), and rates of blood transfusion (P = 0.003) and postoperative complications (P = 0.016) were higher in patients who underwent DP-CAR compared with patients who underwent DP. The 5-year survival rate of patients who underwent DP and DP-CAR were 50.6% and 41.1%, respectively (median survival time, 65.9 vs 37.0 months). For all 134 patients, pretreatment serum CA19-9 levels (P < 0.001), adjuvant chemotherapy (P < 0.001), and lymph node status (P = 0.035) were independent prognostic factors of overall survival by multivariate analysis. CONCLUSIONS: DP-CAR following neoadjuvant chemotherapy for patients with borderline resectable or locally advanced pancreatic body carcinoma may bring the same survival impact as DP, despite increased morbidity.

Nitrogen and phosphorus concentrations in growth media affect the relationship between root endophytic fungi and host plant.

Endophytic fungi (EPF) colonize plant roots and enhance their growth. The relationship between host plant and EPF can be affected by several factors, such as growth media, host species, and fungal species. The objective of this study was to clarify the effect of nutrient concentration in growth media on the relationship between host plant and root EPF. Brassica campestris was grown in 1/100 Murashige and Skoog (MS), 1/10 MS, 1/100 MS and 1/10 nitrogen (high N), and 1/100 MS and 1/10 phosphorus (high P) media. B. campestris was inoculated with four root EPFs isolated from forest soils in Indonesia and harvested 28 days after transplant. Shoot dry weight (SDW) and colonization in roots were measured. All the isolates colonized roots of B. campestris. Two isolates increased the SDW of B. campestris grown on 1/100 MS media. The shoot growth response of B. campestris to EPF colonization on 1/100 MS was higher than that on 1/100 high N and 1/100 high P MS media. These results suggest that concentration of nitrogen and phosphorus in growth media determine the relationship between B. campestris and root EPF.

[A Case of Unresectable Pancreatic Cancer with Massive Cancerous Ascites Responsive to KM-CART].

A 79-year-old woman visited our hospital complaining of bloating. An abdominal enhanced CT scan revealed pancreatic body cancer with cancerous ascites and multiple liver metastases. We started gemcitabine(GEM)plus nab-paclitaxel chemotherapy. Chemotherapy was not continued because she was unable to take oral medication owing to increased cancerous ascites. We conducted modified KM-cell-free and concentrated ascites reinfusion therapy(KM-CART). Her symptoms improved, and she began having oral intake after KM-CART. Chemotherapy was then re-initiated. Seven months have now passed since we started chemotherapy, and we can continue chemotherapy while conducting KM-CART repeatedly. KM- CART is useful for treating unresectable pancreatic cancer with massive cancerous ascites in terms of continuing chemotherapy.

Communities of mycorrhizal fungi in different trophic types of Asiatic Pyrola japonica sensu lato (Ericaceae).

Mixotrophic plants obtain carbon by their own photosynthetic activity and from their root-associated mycorrhizal fungi. Mixotrophy is deemed a pre-adaptation for evolution of mycoheterotrophic nutrition, where plants fully depend on fungi and lose their photosynthetic activity. The aim of this study was to clarify mycorrhizal dependency and heterotrophy level in various phenotypes of mixotrophic Pyrola japonica (Ericaceae), encompassing green individuals, rare achlorophyllous variants (albinos) and a form with minute leaves, P. japonica f. subaphylla. These three phenotypes were collected in two Japanese forests. Phylogenetic analysis of both plants and mycorrhizal fungi was conducted based on DNA barcoding. Enrichment in 13C among organs (leaves, stems and roots) of the phenotypes with reference plants and fungal fruitbodies were compared by measuring stable carbon isotopic ratio. All plants were placed in the same clade, with f. subaphylla as a separate subclade. Leaf 13C abundances of albinos were congruent with a fully mycoheterotrophic nutrition, suggesting that green P. japonica leaves are 36.8% heterotrophic, while rhizomes are 74.0% heterotrophic. There were no significant differences in δ13C values among organs in both albino P. japonica and P. japonica f. subaphylla, suggesting full and high mycoheterotrophic nutrition, respectively. Among 55 molecular operational taxonomic units (OTUs) detected as symbionts, the genus Russula was the most abundant in each phenotype and its dominance was significantly higher in albino P. japonica and P. japonica f. subaphylla. Russula spp. detected in P. japonica f. subaphylla showed higher dissimilarity with other phenotypes. These results suggest that P. japonica sensu lato is prone to evolve mycoheterotrophic variants, in a process that changes its mycorrhizal preferences, especially towards the genus Russula for which this species has a marked preference.

A Multicenter, Randomized, Controlled Trial Comparing Reinforced Staplers with Bare Staplers During Distal Pancreatectomy (HiSCO-07 Trial).

BACKGROUND: Although distal pancreatectomy (DP) using a reinforced stapler is expected to reduce PF, no multicenter RCT has been performed. To investigate whether reinforced staplers reduce the incidence of clinically relevant pancreatic fistula (PF) after DP compared with staplers without reinforcement. METHODS: Between July 2016 and December 2017, patients scheduled for DP were enrolled in a multicenter, randomized, controlled trial (RCT) at nine hospitals in Hiroshima Japan. Patients were randomized either to reinforced stapler or bare stapler. The primary endpoint was incidence of clinically relevant PF. This RCT was registered with UMIN Clinical Trial Registry (UMIN000022341). RESULTS: A total of 122 patients were assigned to reinforced stapler (n = 61) or bare stapler (n = 61), and 119 patients (61 reinforced stapler and 59 bare stapler) were analyzed. There was no significant difference in the incidence of clinically relevant PF between the reinforced stapler and bare stapler groups (16.3% vs. 27.1%, p = 0.15). Furthermore, the rates of major complication (16.3% vs. 18.6%, p = 0.74), postpancreatectomy hemorrhage (0% vs. 3.4%, p = 0.08), and median postoperative in-hospital days (19 days vs. 20 days, p = 0.78) did not differ between the two groups. Within a subset of 82 patients in whom the thickness of pancreatic transection line was less than 14 mm, a significant difference was found in the incidence of clinically relevant PF (4.5% vs. 21.0% in the reinforced stapler vs. bare stapler groups, respectively, p = 0.01). CONCLUSIONS: Reinforced stapler for pancreatic transection during DP does not reduce the incidence of clinically relevant PF compared to stapler without reinforcement.

Proposed Nomogram Predicting the Individual Risk of Malignancy in the Patients With Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas.

OBJECTIVES: This study evaluated individual risks of malignancy and proposed a nomogram for predicting malignancy of branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) using the large database for IPMN. BACKGROUND: Although consensus guidelines list several malignancy predicting factors in patients with BD-IPMN, those variables have different predictability and individual quantitative prediction of malignancy risk is limited. METHODS: Clinicopathological factors predictive of malignancy were retrospectively analyzed in 2525 patients with biopsy proven BD-IPMN at 22 tertiary hospitals in Korea and Japan. The patients with main duct dilatation >10 mm and inaccurate information were excluded. RESULTS: The study cohort consisted of 2258 patients. Malignant IPMNs were defined as those with high grade dysplasia and associated invasive carcinoma. Of 2258 patients, 986 (43.7%) had low, 443 (19.6%) had intermediate, 398 (17.6%) had high grade dysplasia, and 431 (19.1%) had invasive carcinoma. To construct and validate the nomogram, patients were randomly allocated into training and validation sets, with fixed ratios of benign and malignant lesions. Multiple logistic regression analysis resulted in five variables (cyst size, duct dilatation, mural nodule, serum CA19-9, and CEA) being selected to construct the nomogram. In the validation set, this nomogram showed excellent discrimination power through a 1000 times bootstrapped calibration test. CONCLUSION: A nomogram predicting malignancy in patients with BD-IPMN was constructed using a logistic regression model. This nomogram may be useful in identifying patients at risk of malignancy and for selecting optimal treatment methods. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.

Prognostic Impact of Para-Aortic Lymph Node Micrometastasis in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: It is still unclear whether micrometastasis of para-aortic lymph nodes (PALNs) in pancreatic ductal adenocarcinoma (PDAC) is tantamount to PALN metastasis detected by hematoxylin and eosin (HE) staining. METHODS: A total of 242 patients with PDAC who underwent radical pancreatectomy with PALN dissection were eligible for this study. Micrometastasis in PALNs was evaluated by CAM 5.2 immunohistochemistry. The relationship between PALN status and overall survival (OS) was analyzed. RESULTS: Of the 242 enrolled patients, 25 (10 %) had PALN metastasis detected by HE (PALN HE-positive), and 21 (9 %) had PALN micrometastasis not detected by HE but identified by CAM 5.2 immunohistochemistry. Univariate analysis revealed that patients with PALN micrometastasis (p = .004) and PALN HE positivity (p = .003) had a significantly shorter OS than those without PALN metastasis, whereas no significant difference was observed between the two former groups (p = .874). In multivariate analysis, lack of adjuvant chemotherapy (hazard ratio [HR] 2.43, p < .001), PALN micrometastasis (HR 1.89; p = .046), and PALN HE-positivity (HR 1.89, p = .023) were identified as independent risk factors for poor prognosis. Within a subset of 46 patients with PALN HE-positivity or micrometastasis, lack of adjuvant chemotherapy was independently associated with poor OS (HR 2.58. p = .029). CONCLUSIONS: The prognosis of patients with PALN micrometastasis was extremely poor as well as HE-positive PALNs. However, postoperative adjuvant chemotherapy may contribute to improving the prognosis of PDAC patients with PALN metastasis.

Survival effects of adjuvant gemcitabine plus S-1 chemotherapy on pancreatic carcinoma stratified by preoperative resectability status.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the efficacy of adjuvant gemcitabine plus S-1(GS) chemotherapy for pancreatic carcinoma patients, stratified by the National Comprehensive Cancer Network (NCCN) preoperative resectability definition. METHODS: A total of 141 consecutive patients with resected pancreatic carcinoma who received adjuvant GS chemotherapy were evaluated retrospectively. According to the NCCN preoperative resectability definition, tumors were divided into resectable tumors (R group), borderline resectable tumors with portal vein contact (BR-PV group), and borderline resectable tumors with arterial contact (BR-A group). Overall survival and prognostic factors were analyzed. RESULTS: Overall 1-, 2-, and 5-year survival rates for the 141 patients were 89.6%, 69.9%, and 41.1%, respectively. Overall survival of the R group was significantly better than that of the BR-PV group and the BR-A group (P < 0.05). Overall 5-year survival rates of the R group, the BR-PV group, and the BR-A group were 49.0%, 25.0%, and 11.3%, respectively. Arterial contact (P = 0.020), preoperative CA 19-9 level ≥150 U/ml (P < 0.001), and positive nodal involvement (P = 0.025) were independent prognostic factors for poor overall survival. CONCLUSIONS: Adjuvant GS chemotherapy may provide a survival benefit especially for patients with resectable pancreatic carcinoma. J. Surg. Oncol. 2016;113:405-412. © 2016 Wiley Periodicals, Inc.

Nerve Growth Factor Expression Is Not Associated with Perineural Invasion in Extrahepatic Cholangiocarcinoma.

BACKGROUND: Although the presence of perineural invasion has been recognized as a poor prognostic factor in extrahepatic cholangiocarcinoma, the molecular mechanisms of perineural invasion in extrahepatic cholangiocarcinoma remain unclear. Nerve growth factor has been reported to be a candidate predictive biomarker of perineural invasion in some cancers. AIM: To investigate the impact of intratumoral nerve growth factor expression in resected extrahepatic cholangiocarcinoma on survival. METHODS: Intratumoral nerve growth factor expression was investigated immunohistochemically in 112 patients with resected extrahepatic cholangiocarcinoma. Associations between nerve growth factor expression and clinicopathological factors were statistically evaluated, and risk factors for poor survival were analyzed using univariate and multivariate analyses. RESULTS: High and low nerve growth factor expression was observed in 62 (55%) and 50 (45%) patients, respectively. For all 112 patients, no significant correlation was found between nerve growth factor expression and presence of perineural invasion (P = 0.942). Moreover, nerve growth factor expression was not associated with recurrence-free survival (P = 0.861) and overall survival (P = 0.973). In multivariate analysis, lymph node metastasis (P = 0.004) was identified as an independent risk factor for early recurrence and the presence of perineural invasion (P = 0.002) and lymph node metastasis (P < 0.001) was identified as independent risk factors for poor survival. CONCLUSIONS: Intratumoral nerve growth factor expression is not associated with perineural invasion or recurrence-free and overall survival in patients with resected extrahepatic cholangiocarcinoma.

The Selective Arterial Calcium Injection Test is a Valid Diagnostic Method for Invisible Gastrinoma with Duodenal Ulcer Stenosis: A Case Report.

The localization and diagnosis of microgastrinomas in a patient with multiple endocrine neoplasia type 1 is difficult preoperatively. The selective arterial calcium injection (SACI) test is a valid diagnostic method for the preoperative diagnosis of these invisible microgastrinomas. We report a rare case of multiple invisible duodenal microgastrinomas with severe duodenal stenosis diagnosed preoperatively by using the SACI test. A 50-year-old man was admitted to our hospital with recurrent duodenal ulcers. His serum gastrin level was elevated to 730 pg/ml. It was impossible for gastrointestinal endoscopy to pass through to visualize the inferior part of the duodenum, because recurrent duodenal ulcers had resulted in severe duodenal stenosis. The duodenal stenosis also prevented additional endoscopic examinations such as endoscopic ultrasonography. Computed tomography did not show any tumors in the duodenum and pancreas. The SACI test provided the evidence for a gastrinoma in the vascular territory of the inferior pancreatic-duodenal artery. We diagnosed a gastrinoma in the peri- ampullary lesion, so we performed Subtotal Stomach-Preserving Pancreatico- duodenectomy with regional lymphadenectomy. Histopathological findings showed multiple duodenal gastrinomas with lymph node metastasis and nonfunctioning pancreatic neuroendocrine tumors. Twenty months after surgery, the patient is alive with no evidence of recurrence and a normal gastrin level. In conclusion, the SACI test can enhance the accuracy of preoperative localization and diagnosis of invisible microgastrinomas, especially in the setting of severe duodenal stenosis.

Does preoperative biliary drainage compromise the long-term survival of patients with pancreatic head carcinoma?

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the impact of preoperative biliary drainage (PBD) on long-term survival in patients with pancreatic head carcinoma after surgical resection. METHODS: Medical records of 160 patients with pancreatic head carcinoma who underwent surgical resection were reviewed retrospectively. Clinicopathological parameters including long-term survival were compared between patients who did and did not undergo PBD. RESULTS: Overall survival of patients who underwent PBD (n = 93) was significantly worse than that of patients who did not (n = 67) by univariate analysis (P = 0.030). However, multivariate analysis revealed that PBD was not an independent prognostic factor for overall survival (P = 0.227). Patients who underwent percutaneous transhepatic biliary drainage (PTBD) had significantly worse survival than patients who underwent endoscopic retrograde biliary drainage (ERBD, P = 0.038) and patients who did not undergo PBD (P = 0.001). The rate of peritoneal recurrence in patients who underwent PTBD was significantly higher than that of patients who underwent ERBD (P = 0.033) or patients who did not undergo PBD (P = 0.034). CONCLUSIONS: PBD may not affect the long-term survival of patients with pancreatic head carcinoma if ERBD is used.

Is pancreatic fistula associated with worse overall survival in patients with pancreatic carcinoma?

BACKGROUND: Pancreatic fistula (PF) is one of the leading complications after pancreatic resection for pancreatic carcinoma. The aim of this study was to determine whether PF was associated with deterioration of long-term outcomes in patients with pancreatic carcinoma after surgical resection. METHODS: Medical records of 210 patients with pancreatic carcinoma who underwent tumor resection were reviewed retrospectively. PF was defined as grade B or C PF according to the criteria of the International Study Group on Pancreatic Fistula. Clinicopathological factors including overall survival were compared between patients with and without PF by univariate and multivariate analyses. RESULTS: Thirty-one patients (15 %) developed postoperative PF, and 179 (85 %) did not. The 31 cases of PF consisted of 27 grade B PF and 4 grade C PF. There were no differences in the use of adjuvant chemotherapy, tumor differentiation, lymph node status, surgical margin status, or UICC stage between groups. Overall 5-year survival rates for patients with and without PF were 25 and 27 %, respectively. There was no significant difference in overall survival between the two groups (P = 0.743). Multivariate analysis demonstrated that the use of postoperative adjuvant chemotherapy (P < 0.001), tumor differentiation (P = 0.005), and lymph node metastasis (p < 0.001) were factors independently associated with overall survival. CONCLUSIONS: These results suggested that PF was not associated with deterioration of long-term outcomes in patients with pancreatic carcinoma. However, further analyses on larger number of patients are needed to determine a negative effect of grade C PF on long-term survival.

Identification of risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy using a 13C-labeled mixed triglyceride breath test.

BACKGROUND: There are only a few reports concerning long-term exocrine function after pancreaticoduodenectomy (PD), although the number of long-term survivors has increased. We assessed pancreatic exocrine function after PD in 189 patients to identify risk factors for pancreatic exocrine insufficiency. METHODS: We evaluated patients' exocrine function by using the (13)C-labeled mixed triglyceride breath test, a noninvasive test feasible in outpatient service units. The present study included 99 patients that underwent pancreaticojejunostomy (PJ) at Wakayama Medical University Hospital and 90 patients that underwent pancreaticogastrostomy (PG) at Hiroshima University Hospital, the standard reconstruction techniques during PD at the respective hospitals. We also analyzed long-term morphological changes of remnant pancreas by computed tomography (main pancreatic duct dilation and parenchymal atrophy), nutritional status, and endocrine function. RESULTS: Independent risk factors for exocrine insufficiency after PD include hard pancreas (P = 0.003, odds ratio; 3.157) and PG reconstruction (P = 0.040, odds ratio; 2.321). Breath test results correlated significantly with post-operative morphological changes, nutritional status, and endocrine function. Atrophic changes of the remnant pancreas in the PG group were more severe than those in the PJ group. Furthermore, for patients with a soft pancreas, postoperative body weight changes, prognostic nutritional index, serum total protein levels as well as exocrine test were worse in the PG group, compared with the PJ group. CONCLUSIONS: Our results showed that PJ reconstruction might be superior to PG during PD, from the viewpoint of long-term pancreatic exocrine function, although further prospective studies are needed.

Mirizzi Syndrome with a Biliobiliary Fistula: a case report.

Mirizzi syndrome is a rare complication of cholelithiasis, which is defined as a common bile duct obstruction due to stones impacted in Hartman's pouch or the cystic duct of the gallbladder. The impacted stones and surrounding inflammation can lead to a biliobiliary fistula. We herein present the case of a 73-year-old Japanese man with a biliobiliary fistula that was diagnosed by peroral cholangiography (POCS). We performed partial cholecystectomy and choledochoplasty as the stone had eroded almost the entire circumference of the bile duct. Postoperative complications included a minor bile leak from the repaired common bile duct apparent on postoperative day 1, which was managed conservatively. The patient was discharged on postoperative day 9. Based on this experience, POCS is useful for detecting the existence of a biliobiliary fistula in cases of Mirizzi syndrome. Once a biliobiliary fistula is confirmed, it is important to select an appropriate surgical procedure based on the extent of common bile duct involvement in the inflammatory process.

[A case of synchronous sigmoid cancer and ureter cancer].

A 78-year-old-man visited a nearby doctor for treatment of hepatitis C and high blood pressure.He was diagnosed with right hydronephrosis by abdominal echography conducted in follow-up of hepatitis C treatment in November 2011; he was then introduced to our hospital for close inspection and medical treatment.We observed wall hyperplasia and narrowing of the lumen in the central sigmoid part by contrast-enhanced computed tomography (CT).The right ureter at the L4/5 level showed wall hyperplasia and a deep color, and the right ureter, renal pelvis, and calix were expanded on the head side. By examination for CF, we observed a type 2 lesion in the sigmoid colon, and a biopsy showed well-differentiated adenocarcinoma. Based upon these findings, he was diagnosed with synchronous sigmoid colon cancer (cT4aN0M0, cStage II) and ureter cancer (cT2N0M0, cStage II); we performed laparotomy sigmoidectomy(D3 dissection)and full extraction of the right kidney urinary tract (lymph node dissection in front of the vena cava, the latter outside and between the aorta and vena cava). The postoperative course was particularly uneventful, and the patient was discharged from the hospital on day 38 after the operation. More than 2 years after the surgery, the patient exhibits no sign of sigmoid colon cancer or ureter cancer recurrence.

Clinical pharmacokinetics of meropenem in pancreatic juice and site-specific pharmacodynamic target attainment against Gram-negative bacteria: dosing considerations.

BACKGROUND AND OBJECTIVE: Very few studies have revealed the dynamics of meropenem penetration into the pancreas or pancreatic juice in humans. This study of the clinical pharmacokinetics and pharmacodynamics of meropenem in human pancreatic juice was performed to establish a basis for the validation of dosing regimens for pancreatic infections. METHODS: Ten patients with endoscopic naso-pancreatic drainage received 500 mg meropenem over 0.5 h via intravenous infusion. Venous blood and pancreatic juice samples were collected post-infusion for up to 5.0 h and used to obtain measures of meropenem concentration. The probability of attaining the pharmacodynamic target (40% of the time above the minimum inhibitory concentration [MIC]) in pancreatic juice against MIC distributions for clinical isolates of Gram-negative bacteria was determined using a Monte Carlo simulation. RESULTS: The mean maximum concentration of meropenem in pancreatic juice was 2.08 ± 0.94 µg/mL at 1.025 ± 0.18 h. The pancreatic juice/plasma ratio was 0.055 ± 0.028. A 0.5-h infusion of 500 mg meropenem every 8 h achieved a 99.4% probability of target attainment against Escherichia coli, 96.4% against Klebsiella species, 94.3% against Enterobacter species and 96.2% against Proteus species, but only 41.3% against Pseudomonas aeruginosa isolates. CONCLUSION: Intravenous meropenem exhibits low penetrance into pancreatic juice. However, a dosing regimen of 500 mg meropenem (0.5-h infusion) every 8 h provides sufficient drug-exposure time in pancreatic juice against the four common Gram-negative bacteria populations.

Elevated perioperative serum CA 19-9 levels are independent predictors of poor survival in patients with resectable cholangiocarcinoma.

BACKGROUND AND OBJECTIVES: Identification of prognostic markers is important to establish a perioperative therapeutic strategy for resectable cholangiocarcinoma (CC). The aim of this study was to investigate whether perioperative serum carbohydrate antigen 19-9 (CA19-9) levels can predict survival of patients who underwent surgical resection for CC. METHODS: The study included 106 patients who underwent surgical resection for CC. Serum CA19-9 levels were measured preoperatively after biliary drainage and postoperatively about 4 weeks after surgery. The association of clinicopathological factors (including perioperative serum CA19-9 levels) with overall survival (OS) was analyzed with univariate and multivariate analyses. RESULTS: Differences in OS were significant between groups divided on the basis of two preoperative CA19-9 cutoff values (in U/ml) of 37 and 200 and three postoperative CA19-9 cutoff values (in U/ml) of 37, 100, and 200. In multivariate analysis, absence of postoperative adjuvant chemotherapy (P = 0.002), lymph node metastasis (P = 0.0002), preoperative CA19-9 (≥ 200 IU/ml) (P = 0.03), and postoperative CA19-9 (≥ 37 IU/ml) (P < 0.0001) were identified as independent predictors of poor OS. CONCLUSION: Both pre- and postoperative serum CA19-9 levels predict the survival of patients with resectable CC, and may contribute to the establishment of a new therapeutic strategy.

Nonalcoholic fatty liver disease after pancreatoduodenectomy is closely associated with postoperative pancreatic exocrine insufficiency.

BACKGROUND: In recent years, nonalcoholic fatty liver disease (NAFLD) after pancreatoduodenectomy (PD) has become increasingly problematic. Our aims were to clarify the relationship between NAFLD and postoperative pancreatic exocrine function and to identify the risk factors for NAFLD after PD. METHODS: Patients who underwent PD (n = 104) were assessed with abdominal unenhanced computed tomography (CT) to determine the fatty liver changes and were given a (13) C-labeled mixed triglyceride breath test to measure pancreatic exocrine function. The percent (13) CO2 cumulative dose at 7 hr (% dose (13) C cum 7 hr) <5% was considered diagnostic for pancreatic exocrine insufficiency (PEI). Relationships between the occurrence of NAFLD and clinical factors including postoperative pancreatic exocrine function were analyzed. RESULTS: Twenty-six of 104 patients (25%) developed postoperative NAFLD. The postoperative CT attenuation of the liver (R = 0.326, P < 0.001) and the liver-to-spleen attenuation ratio (R = 0.315, P = 0.001) significantly correlated with the postoperative values of % dose (13) C cum 7 hr. Multivariate analysis determined that postoperative PEI was the only independent risk factor for NAFLD (P = 0.025). CONCLUSIONS: NAFLD frequently occurs postoperatively after PD. NAFLD after PD may be closely associated with postoperative PEI.