Novel choledochojejunostomy technique "T-shaped anastomosis" for preventing the development of postoperative cholangitis in pancreatoduodenectomy: A propensity score matching analysis.

Background: There have been few studies of countermeasures against postoperative cholangitis, a serious complication after pancreaticoduodenectomy (PD) that impairs quality of life. Objective: To evaluate our recently developed, novel method of choledochojejunostomy with a larger anastomotic diameter, the "T-shaped anastomosis." Methods: The study included 261 cases of PD. The T-shaped choledochojejunostomy technique was performed with an additional incision for a distance greater than half the diameter of the bile duct at the anterior wall of the bile duct and the anterior wall of the elevated jejunum. To compensate for potential confounding biases between the standard anastomosis group (n = 206) and the T-shaped anastomosis group (n = 55), we performed propensity score matching (PSM). The primary endpoint was the incidence of medium-term postoperative cholangitis adjusted for PSM. Results: In the PSM analysis, 54 patients in each group were matched, and the median bile duct diameter measured by preoperative CT was 8.8 mm versus 9.3 mm, the rate of preoperative biliary drainage was 31% versus 37%, the incidence of cholangitis within 1 month before surgery was 9% versus 13%, and the incidence of postoperative bile leakage was 2% versus 2%, with no significant differences. The incidence of medium-term postoperative cholangitis was 15% versus 4%, and multivariate logistic regression revealed that T-shaped choledochojejunostomy was an independent predictor of a reduced incidence of cholangitis (odds ratio, 0.17, 95% CI 0.02-0.81; p = 0.024). Conclusions: The T-shaped choledochojejunostomy technique was shown to be effective with a significant reduction in the incidence of medium-term postoperative cholangitis. Clinical trial identification: UMIN000050990.

Evaluating staging laparoscopy indications for pancreatic cancer based on resectability classification and treatment strategies for patients with positive peritoneal washing cytology.

Introduction: The prognosis of pancreatic ductal adenocarcinoma (PDAC) in patients with positive peritoneal washing cytology (CY1) is poor. We aimed to evaluate the results of staging laparoscopy (SL) and treatment efficacy in CY1 patients based on a resectability classification. Methods: We retrospectively reviewed 250 patients with PDAC who underwent SL before the initial treatment between 2017 and 2023 at the University of Toyama. Results: The breakdown of cases by resectability classification was resectable (R):borderline resectable (BR):unresectable locally advanced (UR-LA) = 131:48:71 cases. The frequency of CY1 increased in proportion to the degree of local progression (R:BR:UR-LA = 20:23:34%), but the frequencies of liver metastasis or peritoneal dissemination were comparable (R:BR:UR-LA = 6.9:6.3:8.5%). Most CY1 patients received gemcitabine along with nab-paclitaxel therapy. The CY-negative conversion rates (R:BR:UR-LA = 70:64:52%) and conversion surgery rates (R:BR:UR-LA = 40:27:9%) were inversely proportional to the degree of local progression.Comparing H0P0CY1 factors for each classification, patients with H0P0CY1 had significantly more pancreatic body or tail carcinoma and tumor size ≥32 mm in R patients, whereas in BR patients, duke pancreatic monoclonal antigen type 2 (DUPAN-2) ≥ 230 U/mL was a significant factor. In contrast, no significant factors were observed in UR-LA patients. Conclusion: The CY1 rates, CY-negative conversion rates, and conversion surgery rates varied according to local progression. In the case of R and BR, SL could be considered in patients with pancreatic body or tail carcinoma, large tumor size, or high DUPAN-2 level. In UR-LA, SL might be considered for all patients.

Various Organ Damages in Rats with Fetal Growth Restriction and Their Slight Attenuation by Bifidobacterium breve Supplementation.

Children with fetal growth restriction (FGR) and its resultant low birthweight (LBW) are at a higher risk of developing various health problems later in life, including renal diseases, metabolic syndrome, and sarcopenia. The mechanism through which LBW caused by intrauterine hypoperfusion leads to these health problems has not been properly investigated. Oral supplementation with probiotics is expected to reduce these risks in children. In the present study, rat pups born with FGR-LBW after mild intrauterine hypoperfusion were supplemented with either Bifidobacterium breve (B. breve) or a vehicle from postnatal day 1 (P1) to P21. Splanchnic organs and skeletal muscles were evaluated at six weeks of age. Compared with the sham group, the LBW-vehicle group presented significant changes as follows: overgrowth from infancy to childhood; lighter weight of the liver, kidneys, and gastrocnemius and plantaris muscles; reduced height of villi in the ileum; and increased depth of crypts in the jejunum. Some of these changes were milder in the LBW-B.breve group. In conclusion, this rat model could be useful for investigating the mechanisms of how FGR-LBW leads to future health problems and for developing interventions for these problems. Supplementation with B. breve in early life may modestly attenuate these problems.

Efficacy of staging laparoscopy for resectable pancreatic cancer on imaging and the therapeutic effect of systemic chemotherapy for positive peritoneal cytology.

BACKGROUND: The frequency and prognosis of positive peritoneal washing cytology (CY1) in resectable pancreatic ductal adenocarcinoma (R-PDAC) remains unclear. The objective of this study was to identify the clinical implications of CY1 in R-PDAC and staging laparoscopy (SL). METHODS: We retrospectively analyzed 115 consecutive patients with R-PDAC who underwent SL between 2018 and 2022. Patients with negative cytology (CY0) received radical surgery after neoadjuvant chemotherapy, while CY1 patients received systemic chemotherapy and were continuously evaluated for cytology. RESULTS: Of the 115 patients, 84 had no distant metastatic factors, 22 had only CY1, and nine had distant metastasis. Multivariate logistic regression revealed that larger tumor size was an independent predictor of the presence of any distant metastatic factor (OR: 6.30, p = .002). Patients with CY1 showed a significantly better prognosis than patients with distant metastasis (MST: 24.6 vs. 18.9 months, p = .040). A total of 11 CY1 patients were successfully converted to CY-negative, and seven underwent conversion surgery. There was no significant difference in overall survival between patients with CY0 and those converted to CY-negative. CONCLUSION: SL is effective even for R-PDAC. The prognosis of CY1 patients converted to CY-negative is expected to be similar to that of CY0 patients.

Bifidobacterium breve during infancy attenuates mobility in low birthweight rats.

BACKGROUND: Children with low birthweight (LBW) have a higher risk for developing attention-deficit/hyperactivity disorder, for which no prophylactic measure exists. The gut microbiota in infants with LBW is different from that in infants with normal birthweight and is associated with attention-deficit/hyperactivity disorder. Oral supplementation with Bifidobacterium has several health benefits, such as suppressing inflammation. METHODS: We examined the effect of gavage supplementation with Bifidobacterium breve M-16V from postnatal days 1-21 in a rat model of intrauterine hypoperfusion. RESULTS: The open-field test at 5 weeks of age (equivalent to human pubertal age) showed that rats in the LBW-vehicle group were marginally hyperactive compared with rats in the sham group, while rats in the LBW-B.breve group were significantly hypoactive compared with rats in the LBW-vehicle group. The gut microbiota in the LBW-vehicle group exhibited a profile significantly different from that in the sham group, whereas the gut microbiota in the LBW-B.breve group did not exhibit a significant difference from that in the sham group. Anatomical/histological evaluation at 6 weeks of age demonstrated that the brain weight and the cerebral areas on coronal sections were reduced in the LBW groups compared with the sham group. Probiotic supplementation did not ameliorate these morphological brain anomalies in LBW animals. The percentage of Iba-1+ cells in the brain was not different among the LBW-B.breve, LBW-vehicle, and sham groups. CONCLUSION: Bifidobacterium breve supplementation during early life is suggested to have the potential to help children with LBW attenuate hypermobility in adolescence.

Starch synthases SSIIa and GBSSI control starch structure but do not determine starch granule morphology in the absence of SSIIIa and SSIVb.

KEY MESSAGE: High levels of two major starch synthases, SSIIa and GBSSI, in ss3a ss4b double mutant rice alter the starch structure but fail to recover the polygonal starch granule morphology. The endosperm starch granule is polygonal in wild-type rice but spherical in double mutant japonica rice lacking genes encoding two of the five major Starch synthase (SS) isozymes expressed in endosperm, SSIIIa and SSIVb. Japonica rice naturally has low levels of SSIIa and Granule-bound SSI (GBSSI). Therefore, introduction of active SSIIa allele and/or high-expressing GBSSI allele from indica rice into the japonica rice mutant lacking SS isozymes can help elucidate the compensatory roles of SS isozymes in starch biosynthesis. In this study, we crossed the ss3a ss4a double mutant japonica rice with the indica rice to generate three new rice lines with high and/or low SSIIa and GBSSI levels, and examined their starch structure, physicochemical properties, and levels of other starch biosynthetic enzymes. Lines with high SSIIa levels showed more SSI and SSIIa bound to starch granule, reduced levels of short amylopectin chains (7 ≤ DP ≤ 12), increased levels of amylopectin chains with DP > 13, and consequently higher gelatinization temperature. Lines with high GBSSI levels showed an increase in amylose content. The ADP-glucose content of the crude extract was high in lines with low or high SSIIa and low GBSSI levels, but was low in lines with high GBSSI. Addition of high SSIIa and GBSSI altered the starch structure and physicochemical properties but did not affect the starch granule morphology, confirming that SSIIIa and SSIVb are key enzymes affecting starch granule morphology in rice. The relationship among SS isozymes and its effect on the amount of substrate (ADP-glucose) is discussed.

Epicatechin increases the persistence of long-term memory formed by conditioned taste aversion in Lymnaea.

We examined the effects of epicatechin (Epi), a flavonoid abundant in green tea and cocoa, on long-term memory (LTM) formed following conditioned taste aversion (CTA) training in Lymnaeastagnalis In CTA training, the snails learnt to avoid a food that initially they liked (i.e. sucrose). Twenty-four hours after CTA training, 67% of the trained snails showed a significant decrease in the feeding behaviour elicited by sucrose. Placing snails in the Epi solution in CTA training did not alter the percentage of snails exhibiting LTM, but it significantly increased LTM persistence. We also examined changes following Epi exposure in spontaneous activity of the cerebral giant cells (CGCs) that modulate feeding behaviour and are necessary for CTA-LTM. Our data suggest that Epi causes a decrease in CGC activity and increases LTM persistence, possibly via a GABAergic mechanism.

Three Major Nucleotide Polymorphisms in the Waxy Gene Correlated with the Amounts of Extra-long Chains of Amylopectin in Rice Cultivars with S or L-type Amylopectin.

Extra-long chains (ELC) of amylopectin in rice endosperm are synthesized by granule-bound starch synthase I encoded by the Waxy (Wx) gene, which primarily synthesizes amylose. Previous studies showed that single nucleotide polymorphisms (SNP) in intron 1 and exon 6 of the Wx gene influences ELC amount. However, whether these SNPs are conserved among rice cultivars and if any other SNPs are present in the Wx gene remained unknown. Here, we sequenced the Wx gene from 17 rice cultivars with S or L-type amylopectin, including those with known ELC content and those originating in China with unique starch properties, as well as typical japonica and indica cultivars. In addition to the two SNPs described above, an additional SNP correlating with ELC content was found in exon 10. Low ELC cultivars (<3.0 %) had thymine at the splicing donor site of intron 1, Tyr224 in exon 6, and Pro415 in exon 10. Cultivars with moderate ELC content (4.1-6.9 %) had guanine at the splicing donor site of intron 1, Ser224 in exon 6, and Pro415 in exon 10. Cultivars with high ELC content (7.7-13.9 %) had guanine at the splicing donor site of intron 1, Tyr224 in exon 6, and Ser415 in exon 10. The chain length distribution pattern of amylopectin was correlated with the amounts of SSIIa found in starch granules and gelatinization temperature, but not with ELC content. The combinations of SNPs in the Wx gene found in this study may provide useful information for screening specific cultivars with different ELC content.

Incidence of and risk factors associated with nedaplatin-related hypersensitivity reactions.

BACKGROUND: Nedaplatin (NDP)-related hypersensitivity reactions (HSRs) trigger adverse clinical events. Prediction and prevention of NDP-HSRs are thus essential to minimize the risk and maximize the benefit of NDP therapy. However, the incidence of NDP-HSRs and the associated risk factors remain unclear. METHODS: We retrospectively examined patients who received NDP monotherapy between April 2011 and July 2015 in Nagoya University Hospital. HSRs severity was defined according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE ver.4). Risk factors for NDP-HSRs were determined using multivariate logistic regression. RESULTS: Of 111 patients who received NDP monotherapy, 90 (81%) were female; median age was 59 years (range, 29-78 years). Eighty-eight patients had gynecological cancer and 20 suffered from head and neck cancer. Eight of 111 patients (7.2%) experienced NDP-HSRs, six of which developed in the second NDP cycle. However, all patients with NDP-HSRs were treated with carboplatin (CBDCA) for more than three cycles. Grade 3 and 4 HSRs developed in 2 patients. NDP-HSRs were significantly associated with a history of CBDCA-HSRs (odds ratio 37.5, 95% confidence interval 5.38-262, p < 0.001) and with the interval between NDP administration and the previous platinum treatment (odds ratio 13.9, 95% confidence interval 1.23-158, p = 0.034). CONCLUSION: The risk of NDP-HSRs increases in patients with a history of CBDCA-HSRs and in those administered NDP for more than 6 months after previous platinum treatment. Such individuals must be closely monitored if given NDP, even if they are expected to benefit from the treatment.