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Advancements in regenerative medicine, particularly through the use of induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), are garnering substantial attention as potential solutions to the limited availability of donors, leading to prolonged waiting periods for people with type 1 diabetes who require transplantation of pancreatic islets from deceased donors. The promising outcomes from recent clinical trials suggest that transplantation of iPSC- or ESC-derived islet cells could pave the way for more effective and broadly accessible treatment options. This progress holds potential not only for individuals with type 1 diabetes but may also extend to type 2 diabetes treatment in the future., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Introduction: The only treatment for non-resectable colorectal liver metastasis (CRLM) is medical therapy, and the overall survival (OS) rate at 3 and 5 years is approximately 30%-40% and less than 10%, respectively. In 2020, a group in Norway reported that liver transplantation for non-resectable CRLM improved the 5-year OS rate to up to 83%. Clinical trials have been launched since that report was published, but most have involved deceased-donor liver transplantation rather than living-donor liver transplantation. Our study will assess the efficacy and safety of living-donor liver transplantation for patients with non-resectable CRLM., Methods and Analysis: This is an investigator-driven, multicentre, prospective, single-arm study involving 11 university hospitals in Japan. Patients with non-resectable CRLM and resected primary cancers will be enrolled in the study. Any patients with histopathological or genetic mutations, such as those of RAS and BRAF, are eligible. Furthermore, patients who underwent lung treatment for three or fewer pulmonary metastases and experienced no recurrence for more than 6 months are eligible. The eligibility of the candidates will be reviewed by the Central Eligibility Review Committee. The primary endpoint is the 3-year OS rate. Assuming an OS rate of 70% and a threshold of 45%, the number of required patients is 23, with an alpha error of 5% (one-sided), power of 80% and a 10% dropout rate., Ethics and Dissemination: Ethical approval was obtained from the ethical review board of Kyoto University (R-1591). All participants are required to provide written informed consent. The results will be submitted for publication in a peer-reviewed journal., Trial Registration Number: jRCT1050230053 and UMIN000049785., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Gastroenteropancreatic neuroendocrine tumors (NET) often metastasize to the liver. Although curative liver resection provides a favorable prognosis for patients with neuroendocrine liver metastasis (NELM), with a 5-year survival rate of 70-80%, recurrence is almost inevitable, mainly in the remnant liver. In Western countries, liver transplantation (LT) has been performed in patients with NELM, with the objective of complete removal of macro- and micro-NELMs. However, prognosis had been unsatisfactory, with 5-year overall survival and recurrence-free survival rates of approximately 50 and 30%, respectively. In 2007, the Milan criteria were proposed as indications for LT for NELM. The criteria included: (1) confirmed histology of NET-G1 or G2; (2) a primary tumor drained by the portal system and all extrahepatic diseases removed with curative resection before LT; (3) liver involvement ≤50%; (4) good response or stable disease for at least 6 months before LT; (5) age ≤ 55 years. A subsequent report demonstrated outstanding LT outcomes for NELM within the Milan criteria, with 5-year overall survival and recurrence rates of 97 and 13%, respectively. In Japan, living donor LT (LDLT) for NELM has been performed sporadically in only 16 patients by 2021 in Japan; however, no consensus has been reached on the indications or perioperative management of LDLT. This article presents the outcomes of these 16 patients who underwent LDLT in Japan and reviews the literature to clarify optimal indications and perioperative management of LDLT for NELM in the era of novel multimodal treatments., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest., (© 2024. The Author(s).)

Background: The incidence of pancreatic cancer is on the rise, and its prognosis remains poor. Recent reports have established a link between the gut and oral microbiome and pancreatic cancer. However, the intricacies of this association within the Japanese population remain unclear. In this study, we investigated the gut and oral microbiomes of Japanese patients with pancreatic cancer, comparing them with those of healthy individuals., Methods: We recruited 30 patients with untreated pancreatic cancer and 18 healthy controls at Kyoto University Hospital (2018-2022). We performed a comprehensive 16S rRNA gene sequencing to analyze their gut and oral microbiomes., Results: Analysis revealed that the diversity of the gut and oral microbiomes of patients with pancreatic cancer was reduced compared to that of the healthy controls. Specifically, we observed an increase in the genus Streptococcus in both the gut and oral microbiomes and a significant decrease in several butyrate-producing bacteria in fecal samples. Moreover, bacteria such as Streptococcus mitis and Holdemanella biformis were present in pancreatic cancer tissues, suggesting that they might influence the carcinogenesis and progression of pancreatic cancer., Conclusions: The gut and oral microbiome differed between patients with pancreatic cancer and healthy controls, with a notable decrease in butyrate-producing bacteria in the gut microbiome of the patients. This suggests that there may be a distinct microbial signature associated with pancreatic cancer in the Japanese population. Further studies are required to elucidate the microbiome's causal role in this cancer and help develop prognostic markers or targeted therapies., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

We introduce a novel notation system for pancreatectomy designed to provide a clear and concise representation of surgical procedures. As surgical techniques and the scope of pancreatic surgeries continue to diversify, existing communication methods among medical professionals regarding the specifics of the surgeries have proven inadequate. Our proposed notation system clearly indicates the approach (open, laparoscopic, or robot-assisted), type of surgery (e.g., pancreatoduodenectomy, distal pancreatectomy), and extent of resection and accompanying resected organs or vasculature. These elements are all recorded in this order by using abbreviations. For example, a pancreatoduodenectomy with pancreatic transection just above the SMA and combined resection of the SMV would be noted as "OPD(hb')-SMV". This new notation system allows for concise expression of the essential information on performed procedures of pancreatic resection, leading to smooth information sharing. This initiative is an essential step towards standardizing pancreatic surgery documentation on a global scale. Here, we present the development and application of this system, highlighting its potential to transform surgical communication and documentation., (© 2024 The Author(s). Journal of Hepato‐Biliary‐Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Background: The indication of living donor liver retransplantation (re-LDLT) for retransplant candidates with chronic allograft failure (CAF) is increasing because of the high mortality rate of patients on the waiting list. However, evidence supporting re-LDLT for CAF remains scarce because of technical difficulties. We aimed to examine the feasibility based on our significant case experience., Methods: A total of 95 retransplant cases (adult: 53, pediatric: 42) between 2000 and 2020 were retrospectively reviewed. Graft survival after re-LDLT and deceased donor liver retransplantation (re-DDLT) was compared among recipients with CAF and acute allograft failure (AAF)., Results: Re-LDLTs for CAF were performed in 58 (61.1%) cases, re-DDLTs for CAF in 16 (16.8%) cases, re-LDLTs for AAF in 13 (13.7%) cases, and re-DDLTs for AAF in 8 (8.4%) cases. Re-DDLTs have become increasingly prevalent over time. Retransplantation for AAF results in lower graft survival than that for CAF in both adult and pediatric cases. All adult recipients who underwent re-LDLT for AAF died within 1 y after retransplantation. The 5-y graft survival between re-LDLT and re-DDLT for CAF was not significantly different (73.8% versus 75.0%, P  = 0.84). Operation time and blood loss were not significantly different., Conclusions: The survival rate of re-LDLT for recipients with CAF is permissible. Re-LDLT may be another treatment option for recipients with CAF., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Dogs with retroperitoneal hemangiosarcoma (HSA) exhibit variable postoperative median survival times (MST)., Objective: To retrospectively evaluate the prognostic value of selected tumour-related factors, such as tumour size, rupture, invasion into adjacent tissue, involvement of lymph node and distant metastasis, they were analysed in dogs with retroperitoneal HSA., Methods: Ten dogs with retroperitoneal HSA managed solely with surgical excision were reviewed and compared with spleen (71) and liver (9) HSA. The Kaplan-Meier method and log-rank analysis were used compare MSTs between factors. Multivariable Cox proportional-hazard analysis was used to compare differences between arising sites., Results: Retroperitoneal HSA showed comparatively longer postoperative MST compared with that of spleen and liver HSA and demonstrated significantly longer MST (p = 0.003) for tumours ≥5 cm (195 days) than <5 cm (70 days). Spleen HSA revealed significantly shorter MSTs in involvement of distant lymph nodes (23 days) and distant metastasis (39 days) than those in negative (83 days, p = 0.002 and 110 days, p < 0.001, respectively). Liver HSA also revealed significantly shorter MST (16.5 days compared with 98 days, p = 0.003) for distant metastasis. Additionally, hazard ratios (HRs) and their forest plot for overall HSA revealed as poor prognostic factors, arising sites (spleen; HR 2.78, p = 0.016 and liver; HR 3.62, p = 0.019), involvement of distant lymph nodes (HR 2.43, p = 0.014), and distant metastasis (HR 2.86, p < 0.001), and as better prognostic factor of tumour size ≥5 cm (HR 0.53, p = 0.037)., Conclusion: In combination with overall HSA, retroperitoneal HSA shows comparatively longer postoperative MST compared to spleen and liver HSA, associated with tumour size ≥5 cm suggesting better prognostic factor., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Background: The utilization of islet-like cells derived from pluripotent stem cells may resolve the scarcity of islet transplantation donors. The subcutaneous space is a promising transplantation site because of its capacity for graft observation and removal, thereby ensuring safety. To guarantee subcutaneous islet transplantation, physicians should ensure ample blood supply. Numerous methodologies, including prevascularization, have been investigated to augment blood flow, but the optimal approach remains undetermined., Methods: From C57BL/6 mice, 500 syngeneic islets were transplanted into the prevascularized subcutaneous site of recipient mice by implanting agarose rods with basic fibroblast growth factor at 1 and 2 wk. Before transplantation, the blood glucose levels, cell infiltration, and cytokine levels at the transplant site were evaluated. Furthermore, we examined the impact of the extracellular matrix capsule on graft function and the inflammatory response., Results: Compared with the 1-wk group, the 2-wk group exhibited improved glycemic control, indicating that longer prevascularization enhanced transplant success. Flow cytometry analysis detected immune cells, such as neutrophils and macrophages, in the extracellular matrix capsules, whereas cytometric bead array analysis indicated the release of inflammatory and proinflammatory cytokines. Treatment with antitumor necrosis factor and anti-interleukin-6R antibodies in the 1-wk group improved graft survival, similar to the 2-wk group., Conclusions: In early prevascularization before subcutaneous transplantation, neutrophil and macrophage accumulation prevented early engraftment owing to inflammatory cytokine production., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

One of the challenges in liquid biopsy for early cancer detection is ascribed to the fact that mutation DNA often represents an extremely small ratio of less than 1% compared to wild-type genes in blood. However, in conventional fragment analysis with capillary electrophoresis (CE), the detectable allele frequency could be about 5%. In this work, we developed an original reagent-based fragment analysis with single base extension (SBE) reactions for cancer-associated mutation assay using a commercially available CE device, and investigated on a possibility of improvement of limit of detection (LOD) for genetic mutation. First, after adjustment of reagent conditions for the SBE reactions, the linear relationship between gene template concentration and fluorescence intensity was obtained from 1 to 100 fmol of target genes. Next, from the results of an experiment to detect mutation EGFR L858R at abundance ratios of mutant type to wild type (100-fmol template) of 0, 1, 5, and 10%, it was shown that the target gene can be detected with LOD of 0.33%. This high sensitivity was realized in part by separating fluorescently labeled substrates into an individual tube for an each-colored SBE reaction. Moreover, mutations EGFR L858R and KRAS G12V were simultaneously detected at sensitivities equivalent to LODs of 0.57 and 0.47%, respectively. These results indicate that < 1% of mutations in multiplex gene mutations can be simultaneously detected, and that possibility suggests that the developed method can be used in clinical practice for detecting cancers., (© 2024. The Author(s).)

We have developed a simple, compact, and robust eight-channel ultraviolet (UV) absorption detection setup featuring two eight-fiber arrays (an irradiation fiber array and a detection fiber array) whose ends face each other across eight capillaries. UV light of a 220-nm wavelength from a single deuterium lamp is stably and evenly split into eight lights by using a thick homogenizing fiber connected to a fiber bundle with eight thin fibers, which make up the irradiation fiber array. Each capillary is directly irradiated with each UV light emitted from the irradiation fiber array and then each of the UV lights transmitted through the capillaries is collected by each fiber of the detection fiber array without using any other optical devices (e.g., a lens) and is detected by each of the eight photodetectors. This setup achieves simultaneous UV absorption measurement for all eight capillaries with the detection limit of 54 μAU, linear dynamic range of four logs or more, and negligible crosstalk of 0.01% or less. We also implemented an eight-capillary electrophoresis system and simultaneously analyzed eight immunoglobulin G samples, separated by capillary electrophoresis sodium dodecyl sulfate., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ryo Imai reports a relationship with Hitachi Ltd that includes: employment. Kentaro Osawa reports a relationship with Hitachi Ltd that includes: employment. Takashi Anazawa reports a relationship with Hitachi Ltd that includes: employment. Kentaro Osawa and Takashi Anazawa are inventors of a patent PCT/JP2020/030789 whose rights are owned by Hitachi High-Tech Corp., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Total pancreatectomy with islet autotransplantation (TPIAT) is an established and effective treatment modality for patients diagnosed with intractable chronic pancreatitis (CP) and recurrent acute pancreatitis (RAP). TPIAT primarily aims to manage debilitating pain leading to impaired quality of life among patients with CP or RAP, which can be successfully managed with medical, endoscopic, or surgical interventions. TPIAT is significantly successful in relieving pain associated with CP and improving health-related quality of life outcomes. Furthermore, the complete loss of pancreatic endocrine function attributed to total pancreatectomy (TP) can be compensated by autologous islet transplantation (IAT). Patients receiving IAT can achieve insulin independence or can be less dependent on exogenous insulin compared with those receiving TP alone. Historically, TPIAT has been mainly used in the United States, and its outcomes have been improving due to technological advancements. Despite some challenges, TPIAT can be a promising treatment for patients with CP-related intractable pain. Thus far, TPIAT is not commonly performed in Japan. Nevertheless, it may improve health-related quality of life in Japanese patients with CP, similar to Western patients. This review article aimed to provide an overview of the indications, related procedures, and outcomes of TPIAT and to discuss future prospects in Japan., Competing Interests: The authors declare no conflicts of interest for this article., (© 2023 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Pancreatic acinar cystic transformation (ACT) is a rare non-neoplastic cystic lesion that is predominantly located at the pancreatic head in females. Preoperative definitive diagnosis of ACT remains challenging despite advances in radiologic imaging methods. A 25-year-old male patient presented with abdominal discomfort and a 50-mm cystic lesion in the pancreatic tail. The patient underwent laparoscopic distal pancreatectomy, because branch duct intraductal papillary mucinous neoplasm cannot be ruled out and the presence of abdominal symptoms. The resected specimen revealed a collection of small and large cysts lined by a single cuboidal epithelium layer with scattered pancreatic tissue exhibiting fibrosis in the septal wall. The cystic lesion was epithelial, trypsin-positive, B cell lymphoma 10-positive, cytokeratin 19-positive, mucin 1-positive, and MUC6-negative with a differentiated lobular central conduit causing to an adeno-cystic cell, thereby supporting the ACT diagnosis. Distinguishing ACT from other pancreatic cystic tumors remains a diagnostic challenge despite improvements in radiologic imaging methods. Surgical resection may be justified when other cystic neoplasms cannot be excluded because of its heterogeneous nature, although the ACT is a non-neoplastic lesion, and cases of malignant transformation have never been reported to date., (© 2023. Japanese Society of Gastroenterology.)

Background: Pancreas divisum (PD) is a congenital anomaly that occurs due to failure of fusion of the dorsal and ventral pancreatic ductal systems. 1-3 In PD, pancreatic juice drains mainly through the minor papilla via the dorsal duct, leading to high intraductal pressure, which can cause pancreatitis. 1-3 We report a case of PD that underwent preoperative decompression using endoscopic minor papilla sphincterotomy (EMPS) before laparoscopic distal pancreatectomy (LDP) for pancreatic cancer. 3 METHODS: The patient was a 74-year-old woman with pancreatic tail cancer, measuring 35 mm in size, in PD with an entirely dilated dorsal duct, implying high, intraductal pressure caused by minor papillary dysfunction. We performed EMPS to prevent postoperative pancreatitis and pancreatic fistula before LDP using a left-posterior approach, as previously described. 4 As the pancreatic transection margin was positive for high-grade pancreatic intraepithelial neoplasia on intraoperative pathology, an additional resection of the pancreatic head to the right side of the portal vein was performed after the liberation of the gastroduodenal artery with both the dorsal and ventral pancreatic ducts ligated and divided., Results: The operative time was 421 min, and blood loss was 70 mL. The postoperative course was uneventful, with no evidence of pancreatitis or pancreatic fistula. The patient was discharged on postoperative Day 10. Postoperative computed tomography revealed reduced dilatation of the dorsal duct., Conclusions: Preoperative EMPS may be effective in preventing pancreatic fistula after LDP in patients with PD., (© 2023. Society of Surgical Oncology.)

It is crucial to develop practical and noninvasive methods to assess the functional beta-cell mass in a donor pancreas, in which monitoring and precise evaluation is challenging. A patient with type 1 diabetes underwent noninvasive imaging following simultaneous kidney-pancreas transplantation with positron emission tomography/computed tomography (PET/CT) using an exendin-based probe, [ 18 F]FB(ePEG12)12-exendin-4. Following transplantation, PET imaging with [ 18 F]FB(ePEG12)12-exendin-4 revealed simultaneous and distinct accumulations in the donor and native pancreases. The pancreases were outlined at a reasonable distance from the surrounding organs using [ 18 F]FB(ePEG12)12-exendin-4 whole-body maximum intensity projection and axial PET images. At 1 and 2 h after [ 18 F]FB(ePEG12)12-exendin-4 administration, the mean standardized uptake values were 2.96 and 3.08, respectively, in the donor pancreas and 1.97 and 2.25, respectively, in the native pancreas. [ 18 F]FB(ePEG12)12-exendin-4 positron emission tomography imaging allowed repeatable and quantitative assessment of beta-cell mass following simultaneous kidney-pancreas transplantation., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Resectable pancreatic cancer (RPC) is potentially resectable on admission, and the impact of neoadjuvant therapy on these tumors is controversial. Moreover, the safety and efficacy of neoadjuvant chemoradiotherapy with moderately hypofractionated intensity-modulated radiation therapy (NACIMRT) for RPC have not been studied. Here, we conducted a phase II study to evaluate the safety and efficacy of hypofractionated NACIMRT for RPC., Methods: A total of 54 RPC patients were enrolled and treated according to the study protocol. We used moderately hypofractionated (45 Gy in 15 fractions) IMRT with gemcitabine to shorten the duration of radiotherapy and reduce gastrointestinal toxicity. The primary endpoint was overall survival (OS), and we subsequently analyzed the microscopically margin-negative resection (R0) rate, disease-free survival (DFS), and histologic effects and safety of NACIMRT., Results: Median OS for the cohort was 40.0 months. Forty-two patients (77.8%) underwent pancreatectomy after NACIMRT. Median DFS was 20.3 months. The R0 resection rate was 95.2% (40/42) per protocol and 85.2% (46/54) for the cohort. There were no intervention-related deaths during the study period. Local treatment response, as assessed by the CAP classification, showed no residual tumor in 4.8% of patients. Overall, 23.9% of patients experienced CTCAE grade 3 or 4 during NACIMRT. Adjuvant therapy was initiated in 88% of patients undergoing resection. Postoperative complications grade ≥3b on the Clavien-Dindo scale occurred in 4.8% of patients. CA19-9 level at enrollment was an independent prognostic factor for OS and DFS., Conclusions: This is the first prospective study of hypofractionated IMRT as neoadjuvant therapy for RPC. Hypofractionated NACIMRT for RPC could be safely introduced with a high induction rate of adjuvant chemotherapy, with an overall survival of 40.0 months., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

BACKGROUND ＆ AIMS: Optimizing treatments balancing prognosis and therapeutic invasiveness is important in the management of pancreatic cancer (PC) owing to global ageing. This study aimed to verify the different utility of biomarkers by patients' age. MATERIALS ＆ METHODS: This is a single-center, retrospective cohort analysis involving 160 patients who undertook pancreaticoduodenectomy (PD) for PC. After comparing clinicopathological factors and survival after PD between aged (≥70 y/o) and young (＜70 y/o) patients, we compared neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), controlling nutrition (CONUT) score, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 as well as clinicopathological factors between long and short survivors in each group. We also performed Kaplan-Meyer analysis between patients stratified by biomarkers. RESULTS: Overall survival (OS) was significantly worse in aged patients (p = 0.002). In aged patients, CEA was significantly higher in short survivors. In young patients, CONUT score and CA19-9 were higher in short survivors. Kaplan-Meyer analysis showed that NLR and CEA stratified OS in aged patients, whereas CONUT score and CA19-9 could stratify OS in young patients. CONCLUSION: Our current results suggest that these biomarkers had different impact on survivals according to the patients' age., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: The safety and feasibility of completion total pancreatectomy (TP) for remnant pancreatic neoplasms remain controversial and are rarely compared with that of initial TP. Thus, we aimed to compare the safety of these two procedures inducing a pancreatic state., Methods: Patients who underwent TP for pancreatic neoplasms between 2006 and 2018 at our institution were included in this study. Tumor pathologies were classified into three subgroups according to survival curves. We used 1:1 propensity score matching (PSM) to analyze age, sex, Charlson Comorbidity Index, and tumor stage. Finally, we analyzed the primary outcome Clavien-Dindo classification (CDC) grade, risks of other safety-related outcomes, and the survival rate of patients with invasive cancer., Results: Of 54 patients, 16 underwent completion TP (29.6%) and 38 (70.4%) underwent initial TP. Before PSM analysis, age and Charlson Comorbidity Index were significantly higher, and T category and stage were significantly lower for the completion TP group. Upon PSM analysis, these two groups were equivalent in CDC grade [initial TP vs. completion TP: 71.4% (10/14) vs. 78.6% (11/14); p = 0.678] and other safety-related outcomes. Additionally, while the overall survival and recurrence-free survival of patients with invasive cancer were not significantly different between these two groups, the T category and stage tended to be remarkably severe in the initial TP group., Conclusions: PSM analysis for prognostic factors showed that completion TP and initial TP have similar safety-related outcomes that can be used as a decision-making reference in the surgery of pancreatic tumors., (© 2023. Society of Surgical Oncology.)

Bile duct cancer (BDC) frequently invades the nerve fibers, making complete surgical resection difficult. A single tumor mass contains cells of variable malignancy and cell-differentiation states, with cancer stem cells (CSCs) considered responsible for poor clinical outcomes. This study aimed to investigate the contribution of autosynthesized dopamine to CSC-related properties in BDC. Sphere formation assays using 13 commercially available BDC cell lines demonstrated that blocking dopamine receptor D1 (DRD1) signaling promoted CSC-related anchorage-independent growth. Additionally, we newly established four new BDC patient-derived organoids (PDOs) and found that blocking DRD1 increased resistance to chemotherapy and enabled xenotransplantation in vivo. Single-cell analysis revealed that the BDC PDO cells varied in their cell-differentiation states and responses to dopamine signaling. Further, DRD1 inhibition increased WNT7B expression in cells with bile duct-like phenotype, and it induced proliferation of other cell types expressing Wnt receptors and stem cell-like signatures. Reagents that inhibited Wnt function canceled the effect of DRD1 inhibition and reduced cell proliferation in BDC PDOs. In summary, in BDCs, DRD1 is a crucial protein involved in autonomous CSC proliferation through the regulation of endogenous WNT7B. As such, inhibition of the DRD1 feedback signaling may be a potential treatment strategy for BDC., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

This study retrospectively evaluated the fentanyl-sparing effect of ultrasound-guided proximal radial, ulnar, median, and musculocutaneous nerve (RUMM) block for radial and ulnar fracture repair in dogs. Fentanyl was prepared for intraoperative analgesia in dogs, although proximal RUMM block was performed using 0.5% or 0.25% bupivacaine before surgery in the block group. Dogs without a nerve block were assigned to the control group. The fentanyl dose in the block group [0.8 (0-1.9) μg/kg/hr] [median (interquartile range)] was significantly lower than in the control group [8.4 (7.2-10) μg/kg/hr]. Surgery was performed without fentanyl in >50% of the dogs (5/7), using 0.5% bupivacaine. Ultrasound-guided proximal RUMM block can be useful as an intraoperative analgesic for radial and ulnar fracture repair in dogs.

An ultra-small (54 × 58 × 8.5 mm) and large aperture (1 × 7 mm) nine-color spectrometer-using an array of ten dichroic mirrors "biparted" as two layers-was developed and used for snapshot spectral imaging. Incident-light flux with a cross section smaller than the aperture size is split into nine color fluxes with 20-nm-width contiguous wavelength bands and central wavelengths of 530, 550, 570, 590, 610, 630, 650, 670, and 690 nm. Images of the nine color fluxes are simultaneously and efficiently measured by an image sensor. Unlike a conventional dichroic-mirror array, the developed dichroic-mirror array has a unique biparted configuration that not only increases the number of colors that can be measured simultaneously but also improves the image resolution of each color flux. The developed nine-color spectrometer was used for four-capillary-array electrophoresis. Eight dyes concurrently migrating in each capillary were simultaneously quantified by nine-color laser-induced fluorescence detection. Since the nine-color spectrometer is not only ultra-small and inexpensive but also has high light throughput and sufficient spectral resolution for most spectral-imaging applications, it has the potential to be widely used in various fields., (© 2022. The Author(s).)

We isolated a phage infecting a member of the Sphingomonadaceae family from a freshwater lake. The phage has a DNA genome of 41,771 bp, with a GC content of 61.7%. The genome harbors 50 predicted protein-coding genes and an auxiliary metabolic gene, which encodes a protein belonging to the radical S -adenosylmethionine superfamily.

Background: Portal annular pancreas (PAP), also called circumportal pancreas, is a congenital pancreatic anomaly in which the portal and/or mesenteric veins are surrounded by pancreatic parenchyma [1,2]. Joseph et al. classified PAP into three types (according to the fusion pattern of the pancreatic parenchyma and ductal system [1]), each of which they subdivided (based on the relation to the portal confluence) into the suprasplenic, infrasplenic, and mixed type [1,3]. The most common type is IIIa [1,4], where the portal vein (suprasplenic) is encased by the uncinate process with an anteportal main pancreatic duct., Methods: The patient was a 78-year-old woman who had undergone left nephrectomy for renal cell carcinoma five years prior. We performed laparoscopic pancreatoduodenectomy for a metastatic tumor of the head of a type IIIa PAP (Fig. 1). The anteportal pancreas was transected, and dissection was performed around the superior mesenteric artery using a right approach. The retroportal pancreas was transected using a linear stapler with bioabsorbable polyglycolic acid felt. We performed pancreatojejunostomy for the anteportal stump of the pancreas containing a main pancreatic duct; the retroportal stump was not reconstructed, because it had no major pancreatic ducts on preoperative imaging., Results: The operative time was 505 minutes, and the blood loss was 70 ml. The postoperative course was uneventful, and the patients was discharged on postoperative day 12., Conclusion: Laparoscopic pancreatoduodenectomy was performed successfully in a patient with a type IIIa PAP. The retroportal pancreas can be transected using a linear stapler, without reconstruction., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We isolated two bacterial strains ( Sphingomonadaceae family) from Lake Biwa, Japan. Based on whole-genome sequencing results, one strain (BSN-002) was assigned to the Sphingopyxis genus and the other (BSN-004) to Sphingomonas aquatilis.

A safe, efficacious, and clinically applicable immunosuppressive regimen is necessary for islet xenotransplantation to become a viable treatment option for diabetes. We performed intraportal transplants of wild-type adult porcine islets in 25 streptozotocin-diabetic cynomolgus monkeys. Islet engraftment was good in 21, partial in 3, and poor in 1 recipient. Median xenograft survival was 25 days with rapamycin and CTLA4Ig immunosuppression. Adding basiliximab induction and maintenance tacrolimus to the base regimen significantly extended median graft survival to 147 days (p < .0001), with three animals maintaining insulin-free xenograft survival for 265, 282, and 288 days. We demonstrate that this regimen suppresses non-Gal anti-pig antibody responses, circulating effector memory T cell expansion, effector function, and infiltration of the graft. However, a chronic systemic inflammatory state manifested in the majority of recipients with long-term graft survival indicated by increased neutrophil to lymphocyte ratio, IL-6, MCP-1, CD40, and CRP expression. This suggests that this immunosuppression regimen fails to regulate innate immunity and resulting inflammation is significantly associated with increased incidence and severity of adverse events making this regimen unacceptable for translation. Additional studies are needed to optimize a maintenance regimen for regulating the innate inflammatory response., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Borderline resectable pancreatic cancer (BRPC) is a category of pancreatic cancer that is anatomically widely spread, and curative resection is uncommon with upfront surgery. Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that delivers precise radiation to a tumor while minimizing the dose to surrounding normal tissues. Here, we conducted a phase 2 study to estimate the curability and efficacy of neoadjuvant chemoradiotherapy using IMRT (NACIMRT) for patients with BRPC with arterial abutment (BRPC-A)., Methods: A total of 49 BRPC-A patients were enrolled in this study and were treated at our hospital according to the study protocol between June 2013 and March 2021. The primary endpoint was microscopically margin-negative resection (R0) rates and we subsequently analyzed safety, histological effect of the treatment as well as survivals among patients with NACIMRT., Results: Twenty-nine patients (59.2%) received pancreatectomy after NACIMRT. The R0 rate in resection patients was 93.1% and that in the whole cohort was 55.1%. No mortality was encountered. Local therapeutic effects as assessed by Evans classification showed good therapeutic effect (Grade 1, 3.4%; Grade 2a, 31.0%; Grade 2b, 48.3%; Grade 3, 3.4%; Grade 4, 3.4%). Median disease-free survival was 15.5 months. Median overall survival in the whole cohort was 35.1 months. The only independent prognostic pre-NACIMRT factor identified was serum carbohydrate antigen 19-9 (CA19-9) > 400 U/ml before NACIMRT., Conclusions: NACIMRT showed preferable outcome without significant operative morbidity for BRPC-A patients. NACIMRT contributes to good local tumor control, but a high initial serum CA19-9 implies poor prognosis even after neoadjuvant treatment., Trial Registration: UMIN-CTR Clinical Trial: https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000011776 Registration number: UMIN000010113. Date of first registration: 01/03/2013., (© 2022. The Author(s).)

Background: /Objectives: Although the presence of lymph node metastasis (LNM) defines malignant potential, preoperative prediction of LNM has not been established for non-functional pancreatic neuroendocrine neoplasm (NF-PNEN). We sought to develop a prediction system using only preoperatively available factors that would stratify the risk of LNM for NF-PNEN., Methods: We retrospectively reviewed patients who underwent R0/1 resection of NF-PNEN at Kyoto University (2007-2019) and the University of California, San Francisco (2010-2019). Risk stratification of LNM was developed using preoperative factors by the logistic regression analysis. Long-term outcomes were compared across the risk groups., Results: A total of 131 patients were included in this study. Lymph nodes were pathologically examined in 116 patients, 23 (20%) of whom had LNM. Radiological tumor size [1.5-3.5 cm (odds ratio: 13.5, 95% confidence interval: 1.77-398) and >3.5 cm (72.4, 9.06-2257) against ≤1.5 cm], <50% cystic component (8.46 × 10^6, 1.68 × 10^106-), and dilatation of main pancreatic duct ≥5 mm (31.2, 3.94-702) were independently associated with LNM. When patients were classified as the low-risk (43 patients), intermediate-risk (44 patients), and high-risk groups (29 patients), proportions of LNM differed significantly across the groups (0%, 14%, and 59%, respectively). Recurrence-free survival (RFS) of the low- and intermediate-risk groups were significantly better than that of the high-risk group (5-year RFS rates of 92.2%, 85.4%, and 47.1%, respectively)., Conclusions: The prediction system using preoperative radiological factors stratifies the risk of LNM for NF-PNEN. This stratification helps to predict malignant potential and determine the surgical procedure and necessity of regional lymphadenectomy., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

In living donor liver transplantation (LDLT), anastomotic biliary stricture is a serious and refractory complication. In this study, we reviewed the transition of post-LDLT anastomotic biliary strictures and evaluated long-term outcomes of stent placement inside the bile duct, which is referred to as an "inside-stent." Of 805 consecutive adult LDLT recipients in our institution (2000-2018), we reviewed 639 patients with duct-to-duct biliary reconstruction and analyzed chronological changes of post-LDLT biliary strictures. Moreover, we focused on the year 2006 when various surgical modifications were introduced and compared the details of post-LDLT biliary strictures before and after 2006, especially focusing on the long-term outcome of inside-stent placement. The proportion of left lobe grafts had increased from 1.8% before 2005 to 39.3% after 2006 (P < 0.001) to maximize the living donor safety. Overall, post-LDLT anastomotic biliary strictures occurred in 21.3% of the patients with a median follow-up period of 106.1 months, which was decreased from 32.6% before 2005 to 12.8% after 2006 (P < 0.001). Anastomotic biliary strictures were less frequent in patients with left lobe grafts than with right lobe grafts (9.4% versus 25.4%; P < 0.001). The overall technical success rate of inside-stent placement was 82.4%, with an improvement from 75.3% before 2005 up to 95.7% after 2006 (P < 0.01). Furthermore, the stricture resolution rate remained high at approximately 90% throughout the observation period. Increased use of left lobe grafts with several surgical modifications significantly reduced post-LDLT anastomotic biliary strictures, leading to favorable long-term outcomes of inside-stent placements for this condition., (Copyright © 2021 by the American Association for the Study of Liver Diseases.)

Background: The aim of this study was to investigate the effect of pretransplant culture on the survival of pancreatic islet grafts, and to determine the biological characteristics of isolated islets during pretransplant culture., Methods: The survival of islets from Wistar rats, transplanted to diabetic C57BL/B6 mice, was compared between fresh islets and cultured islets. A comprehensive gene expression analysis was employed to investigate biological processes during pretransplant culture, and in vitro validation studies were performed., Results: Survival of cultured xenografts was significantly prolonged as compared to that of fresh islets (fresh:12.5 ± 1.9 days, 1-day cultured:16.0 ± 1.3 days (p= 0.017), 3-day cultured:17.0 ± 2.6 days (p= 0.014)). Comprehensive gene expression analysis identified significant upregulation of annotated functions associated with inflammation in cultured groups. Six proinflammatory genes, including heme oxygenase 1 (HO-1) and IL-6, were significantly upregulated during culture.　Validation studies revealed significantly higher levels of IL-6 in the supernatant of cultured islets and HO-1 in the cultured islets when compared with fresh islets., Conclusion: Transplantation of cultured islets induced significant but minimal prolongation of graft survival in xenogeneic combinations. Comprehensive analysis of gene expression in cultured islets showed biological processes associated with proinflammation during culture.

Tailored material is necessary in many industrial applications since material properties directly determine the characteristics of components. However, the conventional trial and error approach is costly and time-consuming. Therefore, materials informatics is expected to overcome these drawbacks. Here, we show a new materials informatics approach applying the Ising model for solving discrete combinatorial optimization problems. In this study, the composition of the composite, aimed at developing a heat sink with three necessary properties: high thermal dissipation, attachability to Si, and a low weight, is optimized. We formulate an energy function equation concerning three objective terms with regard to the thermal conductivity, thermal expansion and specific gravity, with the composition variable and two constrained terms with a quadratic unconstrained binary optimization style equivalent to the Ising model and calculated by a simulated annealing algorithm. The composite properties of the composition selected from ten constituents are verified by the empirical mixture rule of the composite. As a result, an optimized composition with high thermal conductivity, thermal expansion close to that of Si, and a low specific gravity is acquired.

Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel liver fibrosis biomarker, but there are few studies on M2BPGi in liver transplantation (LT) recipients. This study aimed to evaluate the utility of M2BPGi measurement in LT recipients. We collected the clinicopathological data of 233 patients who underwent a liver biopsy at Kyoto University Hospital after LT between August 2015 and June 2019. The median values of M2BPGi in patients with METAVIR fibrosis stages F0, F1, F2, and ≥F3 were 0.61, 0.76, 1.16, and 1.47, respectively, whereas those in patients with METAVIR necroinflammatory indexes A0, A1, and ≥A2 were 0.53, 1.145, and 2.24, respectively. Spearman rank correlation test suggested that the necroinflammatory index had a stronger correlation to the M2BPGi value than the fibrosis stage. The area under the receiver operating characteristic curve of M2BPGi to predict ≥A1 was 0.75, which was significantly higher than that of any other liver fibrosis and inflammation marker. Patients with a rejection activity index (RAI) of ≥3 had a higher M2BPGi value than those with RAI ≤ 2 (P = 0.001). Patients with hepatitis C virus viremia had a higher M2BPGi value than sustained virological responders or those with other etiologies. In conclusion, the present study demonstrated that M2BPGi values are more strongly influenced by necroinflammatory activity and revealed M2BPGi, which has been thought to be a so-called fibrosis marker, as a disease activity marker in transplant recipients. M2BPGi measurement may be useful to detect early stage liver inflammation that cannot be detected by routine blood examination of LT recipients., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

An ultra-small and highly efficient spectral-detection system for four emission points was developed by integrating an injection-molded-plastic four-lens array, a seven-dichroic-mirror array, and an image sensor as one device. The seven-dichroic-mirror array was further miniaturized compared to our previous four-dichroic-mirror array by measures including reduction of the thickness of each dichroic mirror from 1.0 to 0.5 mm. As a result, the system enables highly sensitive and low-crosstalk seven-color detection of laser-induced fluorescence from four emission points of a four-capillary array. This capability allows simultaneous quantification of up-to-seven fluorophores concurrently present in each capillary. Sanger DNA sequencing and STR genotyping by four-capillary-array electrophoresis were experimentally demonstrated by the system., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: /Objectives: This study aimed to elucidate the efficacy of CT findings and perioperative characteristics to predict post-pancreatectomy hemorrhage (PPH): a critical complication after pancreaticoduodenectomy., Methods: The records of 590 consecutive patients who underwent pancreaticoduodenectomy at three institutes between 2012 and 2018 were included. The presence of a vascular wall abnormality or ascites with high density (vascular abnormality) on postoperative day (POD) 5-10 contrast-enhanced CT (early CT), perioperative characteristics, and any PPH or pseudoaneurysm formation (PPH events) were analyzed through a multivariate analysis., Results: PPH events occurred in 48 out of 590 patients (8%). The vascular abnormality on early CT and the C-reactive protein (CRP) value on POD 3 were independent risk factors for PPH events after POD5 (vascular abnormality: odds ratio 6.42, p = 0.001; CRP on POD 3: odds ratio 1.17, p = 0.016). The sensitivity of vascular abnormality for PPH events was 24% (7/29), and the positive predictive value was 30% (7/23). The combination of vascular abnormality and a high CRP value (≥15.5 mg/dL) on postoperative day 3 had a higher positive predictive value of 64% (7/11) than the vascular abnormality alone. None of the seven PPH events that occurred more than one month after surgery were foreseen via early CT., Conclusion: The combination of vascular abnormality and high CRP value was associated with increasing risk of PPH events after pancreaticoduodenectomy, but the low sensitivity of early CT must be noted as an important shortcoming. The normal findings on early CT could not eliminate the risk of late PPH., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Purpose: We describe a "left-posterior approach" in which the important steps in laparoscopic distal pancreatectomy (LDP) for left-sided pancreatic cancer are accomplished in the direction caudal and dorsal to the pancreas., Methods: The patients who underwent LDP with a left-posterior approach at our hospital from January 2016 to April 2020 were reviewed to evaluate the short-term postoperative outcomes. In LDP, we first dissected retroperitoneal tissues above the left renal vein and superior mesenteric artery, yielding the mobilization of the pancreatic body widely. Then, the splenic artery was divided behind the ventrally lifted pancreas as an artery-first approach. The regional lymphadenectomy was performed in an en bloc manner consecutively in the same operative field. The neck of the pancreas was transected with a linear stapler after mobilization of the spleen., Results: In nine patients (five men and four women) aged 76 years (range: 64-82 years), the operative time was 398 min (276-482 min) with the estimated blood loss of 40 ml (0-80 ml). No patients developed grade B/C pancreatic fistula or delayed gastric emptying. Postoperative complications classified as grade III in the Clavien-Dindo classification occurred in one patient (abdominal abscess). The pathology confirmed R0 resection in all patients who had pancreatic cancer (n = 5), IPMNs (n = 3), and high-grade pancreatic intraepithelial neoplasia (PanIN) (n = 1). The number of retrieved lymph nodes was 35 (11-49)., Conclusion: The procedure with a left-posterior approach is a rational surgical technique in LDP for left-sided pancreatic cancer.

The risk factors and clinical impact of post-transplantation splenomegaly (SM) are poorly understood. We investigated the predictors and impacts of post-transplantation SM in 415 LT patients at Kyoto University Hospital from April 2006 to December 2015. First, the predictors and clinical consequences of SM three years post-transplantation were analyzed among spleen-preserved recipients. Second, the clinical data of surviving recipients three years post-transplantation were compared between splenectomized and spleen-preserved recipients. There was no difference in indication for liver transplantation between these two groups. Third, survival outcomes were compared between splenectomized and spleen-preserved recipients. SM was determined as a SV/body surface area (BSA) higher than 152 ml/m 2 . In the first analysis, preoperative SM occurred in 79.9% recipients and SM persisted three years post-transplantation in 72.6% recipients among them. Preoperative SV/BSA was the only independent predictor of three year post-transplantation SM, which was associated with lower platelet (PLT), white blood cell (WBC) counts and significant graft fibrosis (21.4% vs. 2.8%). In the second analysis, spleen-preservation was related to lower PLT, WBC counts and a higher proportion of significant graft fibrosis (26.7% vs. 7.1%) three years post-transplantation. In the third analysis, spleen-preserved recipients showed worse survival than splenectomized recipients. In conclusion, preoperative SM frequently persists more than three years post-transplantation and is associated with subclinical hypersplenism, graft fibrosis, graft loss, and even death., (© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background and Objectives: A postoperative pancreatic fistula (POPF) is a critical complication after surgery for pancreatic cancer. Whether a POPF affects the long-term prognosis of pancreatic cancer cases remains controversial. This study aimed to clarify the effect of a POPF on the long-term prognosis of pancreatic cancer patients, especially after neoadjuvant chemoradiotherapy (NACRT)., Methods: Patients who underwent curative pancreatectomy for pancreatic cancer between January 2012 and June 2019 at Kyoto University Hospital were retrospectively investigated. A fistula ≥ Grade B was considered a POPF., Results: During the study period, 148 patients underwent upfront surgery (Upfront group), and 52 patients underwent surgery after NACRT (NACRT group). A POPF developed in 16% of patients in the Upfront group and 13% in the NACRT group (p = 0.824). In the Upfront group, development of a POPF did not have a significant effect on recurrence-free survival (p = 0.766) or overall survival (p = 0.863). However, in the NACRT group, development of a POPF significantly decreased recurrence-free survival (HR 5.856, p = 0.002) and overall survival (HR 7.097, p = 0.020) on multivariate analysis., Conclusions: The development of a POPF decreases the survival of pancreatic cancer patients treated by surgery after NACRT., (Copyright © 2020 Elsevier Ltd. All rights reserved.)