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Abstract Background Ascertaining the origin of large tumors located in the region of the pancreas head and adjacent mesocolon can pose a challenge preoperatively. En bloc pancreatoduodenectomy with hemicolectomy is often required towards curative tumor resection (R0) of malignant tumors in this region. Case presentation Herein we report a case of a 48-year-old man with two contiguous masses each 5 cm in size, located in the pancreatic head. The masses were detected incidentally by abdominal ultrasonography at an annual health check. Endoscopic biopsies revealed inflammation with no malignancy. Cross-sectional imaging showed the tumor direct invasion of the uncinate process of the pancreas, and the third portion of the duodenum. Based on imaging, a malignant submucosal tumor originating from mesenchymal cells in the mesentery of the transverse colon was made preoperatively. The mass required en bloc pancreatoduodenectomy, right hemicolectomy, and resection of the superior mesenteric vein. The final pathology was carcinosarcoma of the transverse colon. The patient survived 18 years after surgery without recurrence. Conclusions Malignant tumors located in the region of the pancreas head should be considered for an en bloc curative tumor resection and adjuvant chemotherapy treatments offered that might be beneficial for carcinosarcoma.

Introduction: Urologic complications are thought to be the most common surgical complication of renal transplantation. Ureteral pathology, including stenosis, urine leak, and vesicoureteral reflux, predominates. Although endourologic and interventional radiological management may be utilized, failure rates remain relatively high and surgical reconstruction remains the definitive management. Robotic ureteral reconstruction has been demonstrated to provide patient benefit in nontransplant populations, but the literature on transplant reconstruction is very limited. This study reports an additional series of patients with a focus on surgical technique, as well as reviews the available evidence for robotic reconstruction for post-transplant ureteral complications. Methods: All institutional patients undergoing robotic-assisted reconstruction for post-transplant ureteral complications for the years 2019–2022 were included. Intra- and postoperative variables, patient demographics, and follow-up data were obtained retrospectively from parsing of patient records. Statistics were tabulated descriptively. Results: Eleven patients underwent ureteral reconstruction. Of the 11, 9 (81%) were male with a mean age of 51.9 years (16–70) and BMI of 33.8 (24.3–49.1). The most common (10/11) indication for reconstruction was stricture; the most common (10/11) technique used was Lich-Gregoir reimplantation. Mean operative time was 288 minutes (143–500). There were no intra- or immediate postoperative complications. Median length of stay was 2 days (1–22). There were two incidences of mortality at 2 and 5 months postoperatively unrelated to surgery. There were four readmissions within 30 days, three for urinary tract infection (UTI) and one for a pelvic abscess which required washout. The remainder of the cohort has been followed for a mean of 14.6 months (6–41) without any incidences of graft loss or recurrence of ureteral pathology. Conclusions: Robotic-assisted ureteral reconstruction is a technically challenging but highly feasible technique that may provide the benefits of minimally invasive surgery while still allowing definitive reconstruction. Centers with extensive robotic capabilities should consider the technique. [ABSTRACT FROM AUTHOR]

Background: Outcomes of intestinal transplantation with colon allograft (ICTx) remain controversial. We aimed to assess the outcomes of ICTx in comparison to intestinal transplantation without colon (ITx) using the UNOS/OPTN registry database. Methods: We retrospectively reviewed 2612 patients who received primary intestinal transplants from 1998 to 2020. The rates of acute rejection (AR) within 6 months after transplant were compared between ICTx and ITx. Risk factors of 6‐month AR were examined using logistic regression model by era. Furthermore, conditional graft survival was analyzed to determine long‐term outcomes of ICTx. Results: Of 2612 recipients, 506 (19.4%) received ICTx. Graft and patient survival in ICTx recipients were comparable to those in ITx recipients. White ICTx recipients had a higher incidence of AR within 6 months compared to ITx during the entire study period (p =.002), colonic inclusion did not increase the risk of 6‐month AR in the past decade. ICTx recipients who experienced 6‐month AR had worse graft and patient survival compared to those who did not (p <.001 and p =.004, respectively). Among patients who did not develop 6‐month AR, Cox proportional hazard model analysis revealed that colonic inclusion was independently associated with improved conditional graft survival. Conclusions: In the recent transplant era, colonic inclusion is no longer associated with a heightened risk of 6‐month AR and may provide better long‐term survival compared to ITx when AR is absent. Risk adjustment for rejection and proper immunosuppressive therapy are crucial to maximize the benefits of colonic inclusion. [ABSTRACT FROM AUTHOR]

Abstract Background The development, morphology and genetics of sensory neurons have been extensively studied in Drosophila. Sensory neurons in the body wall of larval Drosophila in particular have been the subject of numerous anatomical studies, however, little is known about the intrinsic electrical properties of larval sensory cells. Findings We performed whole cell patch recordings from an identified peripheral sensory cell, the dorsal bipolar sensory neuron (dbd) and measured voltage-gated ionic currents in 1st instar larvae. Voltage clamp analysis revealed that dbds have a TEA sensitive, non-inactivating IK type potassium current as well as a 4-AP sensitive, inactivating IA type potassium current. dbds also show a voltage-gated calcium current (ICa) and a voltage-gated sodium current (INa). Conclusions This work provides a first characterization of voltage-activated ionic currents in an identified body-wall sensory neuron in larval Drosophila. Overall, we establish baseline physiology data for future studies aimed at understanding the ionic and genetic basis of sensory neuron function in fruit flies and other model organisms.

Summary: The use of livers from donation after circulatory death (DCD) is historically characterized by increased rates of biliary complications and inferior short‐term graft survival (GS) compared to donation after brain death (DBD) allografts. This study aimed to evaluate the dynamic prognostic impact of DCD livers to reveal whether they remain an adverse factor even after patients survive a certain period following liver transplant (LT). This study used 74 961 LT patients including 4065 DCD LT in the scientific registry of transplant recipients from 2002–2017. The actual, 1 and 3‐year conditional hazard ratio (HR) of 1‐year GS in DCD LT were calculated using a conditional version of Cox regression model. The actual 1‐, 3‐, and 5‐year GS of DCD LT recipients were 83.3%, 73.3%, and 66.3%, which were significantly worse than those of DBD (all P < 0.01). Actual, 1‐, and 3‐year conditional HR of 1‐year GS in DCD compared to DBD livers were 1.87, 1.49, and 1.39, respectively. Graft loss analyses showed that those lost to biliary related complications were significantly higher in the DCD group even 3 years after LT. National registry data demonstrate the protracted higher risks inherent to DCD liver grafts in comparison to their DBD counterparts, despite survival through the early period after LT. These findings underscore the importance of judicious DCD graft selection at individual center level to minimize the risk of long‐term biliary complications. [ABSTRACT FROM AUTHOR]

Multiple PIP2 dependent molecular processes including receptor activated phospholipase C activity occur at the neuronal plasma membranes, yet levels of this lipid at the plasma membrane are remarkably stable. Although the existence of unique pools of PIP2 supporting these events has been proposed, the mechanism by which they are generated is unclear. In Drosophila photoreceptors, the hydrolysis of PIP2 by G-protein coupled phospholipase C activity is essential for sensory transduction of photons. We identify dPIP5K as an enzyme essential for PIP2 re-synthesis in photoreceptors. Loss of dPIP5K causes profound defects in the electrical response to light and light-induced PIP2 dynamics at the photoreceptor membrane. Overexpression of dPIP5K was able to accelerate the rate of PIP2 synthesis following light induced PIP2 depletion. Other PIP2 dependent processes such as endocytosis and cytoskeletal function were unaffected in photoreceptors lacking dPIP5K function. These results provide evidence for the existence of a unique dPIP5K dependent pool of PIP2 required for normal Drosophila phototransduction. Our results define the existence of multiple pools of PIP2 in photoreceptors generated by distinct lipid kinases and supporting specific molecular processes at neuronal membranes. [ABSTRACT FROM AUTHOR]

During sensory transduction, Drosophila photoreceptors experience substantial increases in intracellular Ca2+ levels ([Ca2+]i). Nevertheless in a number of mutants associated with excessive Ca2+ influx through transient receptor potential (TRP) channels, Drosophila photoreceptors undergo loss of normal cellular structure manifest as a retinal degeneration. However, the molecular mechanisms that underpin this degeneration process remain unclear. The authors previously isolated a mutant, su(40), that is able to suppress the retinal degeneration seen in photoreceptors from loss-of-function alleles of rdgA that are known to have constitutively active TRP channels. Here the authors report the genetic mapping of su(40) as well the isolation of additional alleles of su(40). Studies of su(40) as well as these new alleles should facilitate the understanding of the mechanisms by which excessive Ca2+ influx results in retinal degeneration. [ABSTRACT FROM AUTHOR]

Background: The development, morphology and genetics of sensory neurons have been extensively studied in Drosophila. Sensory neurons in the body wall of larval Drosophila in particular have been the subject of numerous anatomical studies, however, little is known about the intrinsic electrical properties of larval sensory cells. Findings: We performed whole cell patch recordings from an identified peripheral sensory cell, the dorsal bipolar sensory neuron (dbd) and measured voltage-gated ionic currents in 1st instar larvae. Voltage clamp analysis revealed that dbds have a TEA sensitive, non-inactivating IK type potassium current as well as a 4-AP sensitive, inactivating IA type potassium current. dbds also show a voltage-gated calcium current (ICa) and a voltage-gated sodium current (INa). Conclusions: This work provides a first characterization of voltage-activated ionic currents in an identified body-wall sensory neuron in larval Drosophila. Overall, we establish baseline physiology data for future studies aimed at understanding the ionic and genetic basis of sensory neuron function in fruit flies and other model organisms. [ABSTRACT FROM AUTHOR]

Simple Summary: Bile duct cancers are rare cancers that have poor prospects and limited treatment options. Recently, significant advances have been made in the field of nanomedicine which has allowed new approaches to the diagnosis and treatment (i.e., theranosis) of human diseases. To develop nanomedicines that could earmark or target bile duct cancer, specific proteins (or biomarkers) that are present in bile duct cancer but absent in normal tissues are required. We conducted a systematic search of the published literature for bile duct cancer biomarkers that would be suitable for theranosis. Specialist bioinformatics tools were used to help categorize the resulting data set. To select the most promising biomarkers from the search, biomarkers were ranked according to a theranosis-scoring-system and then evaluated in detail. The biomarkers identified using this approach have the potential to promote targeted nanomedicine-based systems to treat bile duct cancers. Cholangiocarcinoma (CCA) is a rare disease with poor outcomes and limited research efforts into novel treatment options. A systematic review of CCA biomarkers was undertaken to identify promising biomarkers that may be used for theranosis (therapy and diagnosis). MEDLINE/EMBASE databases (1996–2019) were systematically searched using two strategies to identify biomarker studies of CCA. The PANTHER Go-Slim classification system and STRING network version 11.0 were used to interrogate the identified biomarkers. The TArget Selection Criteria for Theranosis (TASC-T) score was used to rank identified proteins as potential targetable biomarkers for theranosis. The following proteins scored the highest, CA9, CLDN18, TNC, MMP9, and EGFR, and they were evaluated in detail. None of these biomarkers had high sensitivity or specificity for CCA but have potential for theranosis. This review is unique in that it describes the process of selecting suitable markers for theranosis, which is also applicable to other diseases. This has highlighted existing validated markers of CCA that can be used for active tumor targeting for the future development of targeted theranostic delivery systems. It also emphasizes the relevance of bioinformatics in aiding the search for validated biomarkers that could be repurposed for theranosis. [ABSTRACT FROM AUTHOR]

Cholecystectomy is the treatment of choice for acute cholecystitis but the management of high-risk surgical patients is a difficult dilemma. Percutaneous cholecystostomy (PC) could represent a safer and less invasive option. The aim of the study was to assess the outcomes of PC in high-risk patients. This is a retrospective single-center study; data were collected from our hospital electronic record system. From February 2009 to March 2014, there were 753 patients admitted with acute cholecystitis. Of these 39 were considered high risk for surgery and underwent PC during their hospital stay. The radiological approach was transperitoneal in 29 patients and transhepatic in 10 patients. Median follow-up was 19 months. There were 27 males (69.2%) and 12 females (30.8%) with a mean age of 72 years (range 41-90 years). Twenty-seven patients had PC as definitive treatment (group A) and 12 patients as a bridge to cholecystectomy (group B). There were no postprocedure complications. Five patients in group A were readmitted once with another episode of cholecystitis after PC (18.5%), one patient in group B was readmitted with cholecystitis after two years before proceeding to cholecystectomy, and two patients were readmitted after cholecystectomy (16.6%) for intra-abdominal collections treated with percutaneous radiological drainage. Seven patients died (17.9%) as a result of severe biliary sepsis during their index hospital admission. PC is a safe approach in high-risk patients with acute cholecystitis and can provide satisfactory long-term results when cholecystectomy is not a viable option. [ABSTRACT FROM AUTHOR]