Assessing the long-term priorities of pancreaticoduodenectomy survivors.

BACKGROUND: This study assessed the long-term quality of life (QOL) and priorities of pancreaticoduodenectomy (PD) survivors. METHODS: Survivors were surveyed via internet-based support groups. The relative importance of longevity, experience, costs, and QOL were assessed. RESULTS: The PD cohort (n = 247, 35%) was 60 ± 12 years, 71% female, and 93% white. With moderate agreement, patients ranked survival most important, followed by functional and emotional well-being; costs and experience were least important (W = 35.7%, p < 0.001). Well-being improved throughout survivorship (P-QOL: 39 ± 12 at ≤3 mo vs 43 ± 12 at >10 y, p = 0.170; M-QOL: 38 ± 13 at ≤3 mo vs 44 ± 16 at >10 y; p = 0.015) but remained below the general population (p < 0.001). PD patients with benign diagnoses ranked functional independence as most important (2.00 ± 1.13 vs 2.63 ± 1.19, p < 0.001, W = 41.1%); PD patients with malignant diagnoses regarded overall survival most important (2.10 ± 1.20 vs 1.82 ± 1.22, p < 0.16, W = 35.1%). The mean rank order of priorities remained concordant between short-term (<1 year) and long-term (>5 years) survivors. CONCLUSION: PD survivors experience long-term mental and physical health impairments, underscoring the importance of functional and emotional support. Survivors place paramount importance on overall survival, functional independence, and emotional well-being. Cancer survivors prioritize longevity, while survivors of chronic benign conditions prioritize functional independence.

Navigating Precision Oncology: Insights from an Integrated Clinical Data and Biobank Repository Initiative across a Network Cancer Program.

Advancing cancer treatment relies on the rapid translation of new scientific discoveries to patient care. To facilitate this, an oncology biobank and data repository program, also referred to as the "Moonshot" program, was launched in 2021 within the Integrated Network Cancer Program of the Allegheny Health Network. A clinical data program (CDP) and biospecimen repository were established, and patient data and blood and tissue samples have been collected prospectively. To date, the study has accrued 2920 patients, predominantly female (61%) and Caucasian (90%), with a mean age of 64 ± 13 years. The most common cancer sites were the endometrium/uterus (12%), lung/bronchus (12%), breast (11%), and colon/rectum (11%). Of patients diagnosed with cancer, 34% were diagnosed at stage I, 25% at stage II, 26% at stage III, and 15% at stage IV. The CDP is designed to support our initiative in advancing personalized cancer research by providing a comprehensive array of patient data, encompassing demographic characteristics, diagnostic details, and treatment responses. The "Moonshot" initiative aims to predict therapy responses and clinical outcomes through cancer-related biomarkers. The CDP facilitates this initiative by fostering data sharing, enabling comparative analyses, and informing the development of novel diagnostic and therapeutic methods.

An LRR receptor kinase controls ABC transporter substrate preferences during plant growth-defense decisions.

The exporter of the auxin precursor indole-3-butyric acid (IBA), ABCG36/PDR8/PEN3, from the model plant Arabidopsis has recently been proposed to also function in the transport of the phytoalexin camalexin. Based on these bonafide substrates, it has been suggested that ABCG36 functions at the interface between growth and defense. Here, we provide evidence that ABCG36 catalyzes the direct, ATP-dependent export of camalexin across the plasma membrane. We identify the leucine-rich repeat receptor kinase, QIAN SHOU KINASE1 (QSK1), as a functional kinase that physically interacts with and phosphorylates ABCG36. Phosphorylation of ABCG36 by QSK1 unilaterally represses IBA export, allowing camalexin export by ABCG36 conferring pathogen resistance. As a consequence, phospho-dead mutants of ABCG36, as well as qsk1 and abcg36 alleles, are hypersensitive to infection with the root pathogen Fusarium oxysporum, caused by elevated fungal progression. Our findings indicate a direct regulatory circuit between a receptor kinase and an ABC transporter that functions to control transporter substrate preference during plant growth and defense balance decisions.

Endoreplication mediates cell size control via mechanochemical signaling from cell wall.

Endoreplication is an evolutionarily conserved mechanism for increasing nuclear DNA content (ploidy). Ploidy frequently scales with final cell and organ size, suggesting a key role for endoreplication in these processes. However, exceptions exist, and, consequently, the endoreplication-size nexus remains enigmatic. Here, we show that prolonged tissue folding at the apical hook in Arabidopsis requires endoreplication asymmetry under the control of an auxin gradient. We identify a molecular pathway linking endoreplication levels to cell size through cell wall remodeling and stiffness modulation. We find that endoreplication is not only permissive for growth: Endoreplication reduction enhances wall stiffening, actively reducing cell size. The cell wall integrity kinase THESEUS plays a key role in this feedback loop. Our data thus explain the nonlinearity between ploidy levels and size while also providing a molecular mechanism linking mechanochemical signaling with endoreplication-mediated dynamic control of cell growth.

Xyloglucan Remodeling Defines Auxin-Dependent Differential Tissue Expansion in Plants.

Size control is a fundamental question in biology, showing incremental complexity in plants, whose cells possess a rigid cell wall. The phytohormone auxin is a vital growth regulator with central importance for differential growth control. Our results indicate that auxin-reliant growth programs affect the molecular complexity of xyloglucans, the major type of cell wall hemicellulose in eudicots. Auxin-dependent induction and repression of growth coincide with reduced and enhanced molecular complexity of xyloglucans, respectively. In agreement with a proposed function in growth control, genetic interference with xyloglucan side decorations distinctly modulates auxin-dependent differential growth rates. Our work proposes that auxin-dependent growth programs have a spatially defined effect on xyloglucan's molecular structure, which in turn affects cell wall mechanics and specifies differential, gravitropic hypocotyl growth.

Inspiration amidst crisis: e-learning in a medical school of Nepal during COVID-19 pandemic.

The Coronavirus disease (COVID-19) pandemic continues to shut down colleges and universities including medical schools all over the world, thus pushing medical schools to seek e-learning to maintain continuity of curriculum. Although developed countries are comfortable learning through the internet, low-income countries like Nepal with limited experience in e-learning have used this lockdown as an opportunity to develop online classes. This crisis has clearly revealed the importance of e-learning in for medical educators in Nepal to disseminate knowledge beyond the restrictions of geography and other barriers.

La pandémie de la maladie à coronavirus (COVID-19) continue de provoquer la fermeture des collèges et des universités partout dans le monde, incitant les facultés de médecine à recourir à l'enseignement en ligne pour maintenir la continuité des programmes d'études. Tandis que les pays développés s'adaptent bien à l'enseignement en ligne, les pays à faible revenu comme le Népal, qui ont une expérience limitée de cette technologie, ont profité du confinement pour mettre au point des cours en ligne. La crise a mis en évidence l'importance de cette modalité d'enseignement pour les enseignants en médecine au Népal dans la mesure où elle leur permet de surmonter les contraintes géographiques et d'autres barrières à la diffusion des connaissances.

An invaginated pancreaticogastrostomy following subtotal stomach-preserving pancreaticoduodenectomy: A prospective observational study.

BACKGROUND/OBJECTIVE: Postoperative pancreatic fistula (POPF) leads to life-threatening complications after pancreaticoduodenectomy (PD). Pancreaticogastrostomy (PG) often adopted as a reconstruction technique after PD to prevent POPF. Delayed gastric emptying (DGE) following PD is the most common complication that compromises the quality of life. Subtotal stomach-preserving PD (SSPPD) preserves the pooling ability of the stomach and minimize the occurrence of DGE. This study aimed to describe our PG technique following SSPPD and evaluate the perioperative outcomes. METHODS: The study included patients who underwent PG following SSPPD from August 2013 to July 2020 at our institution. An invaginated PG was performed by one-layer eight interrupted sutures with a lost stent. Patients' demographics and perioperative outcomes were documented. RESULTS: This technique was applied in 72 patients with a median age of 75 years. The median operative time was 342 min. The clinically relevant POPF, DGE and post-pancreatectomy hemorrhage was 4 (5.6%), 5 (6.9%), and 10 (13.9%), respectively. Although the drain fluid amylase concentration on postoperative day 3 was significantly higher in clinically relevant POPF (CR-POPF) positive group (median, 2006 U/L vs. 74 U/L in CR-POPF negative group, p = 0.002), none of the risk factors including disease pathology, pancreatic duct diameter, texture of pancreas and excessive blood loss were significantly associated with CR-POPF. Other morbidity ≥ Clavien-Dindo classification II occurred in 29 patients (40.3%). The 90-days operative mortality was two (2.8%). CONCLUSIONS: This novel method of one-layer invaginated PG following SSPPD is safe and dependable procedure with acceptable morbidity and mortality.

Pancreaticoduodenectomy after transcatheter aortic valve implantation in an elderly patient with severe aortic stenosis and pancreas cancer: A case report.

INTRODUCTION AND IMPORTANCE: Not only pancreatic cancer but also aortic stenosis (AS) is increasing with the aging population. There is no optimal strategy for elderly patients with both pancreatic cancer and AS. We report a case of pancreatic head cancer with severe AS undergoing pancreaticoduodenectomy (PD) after transcatheter aortic valve implantation (TAVI). CASE PRESENTATION: An 88-year-old woman was referred to our hospital because of severe AS with symptoms of heart failure. Preoperative examination revealed resectable pancreatic head cancer, so TAVI was performed before PD to reduce the perioperative risk. The patient underwent PD 34 days after TAVI, with no significant postoperative complications, and was transferred to the other hospital for rehabilitation on postoperative day 45. No recurrence was observed at more than 7 months without adjuvant therapy. CLINICAL DISCUSSION: Aortic valve replacement (AVR) is recommended before non-cardiac surgery in patients with symptomatic severe AS. Surgical aortic valve replacement (SAVR) is the standard treatment. However, owing to the highly invasive procedure and increased perioperative risk, SAVR is usually avoided in elderly patients with malignancy and severe AS. We demonstrated that TAVI followed by PD could be safely performed in high-risk elderly patients presenting with both severe AS and pancreatic head cancer. To our knowledge, this is the first case report of PD after TAVI in a patient with severe AS. CONCLUSION: We demonstrated that TAVI followed by PD could be safely performed in high-risk elderly patients presenting with severe AS and co-existing malignancy.

External Mechanical Cues Reveal a Katanin-Independent Mechanism behind Auxin-Mediated Tissue Bending in Plants.

Tissue folding is a central building block of plant and animal morphogenesis. In dicotyledonous plants, hypocotyl folds to form hooks after seedling germination that protects their aerial stem cell niche during emergence from soil. Auxin response factors and auxin transport are reported to play a key role in this process. Here, we show that the microtubule-severing enzyme katanin contributes to hook formation. However, by exposing hypocotyls to external mechanical cues mimicking the natural soil environment, we reveal that auxin response factors ARF7/ARF19, auxin influx carriers, and katanin are dispensable for apical hook formation, indicating that these factors primarily play the role of catalyzers of tissue bending in the absence of external mechanical cues. Instead, our results reveal the key roles of the non-canonical TMK-mediated auxin pathway, PIN efflux carriers, and cellulose microfibrils as components of the core pathway behind hook formation in the presence or absence of external mechanical cues.

Central hepatectomy for hepatocellular carcinoma in a patient with anti-Gerbich antibody.

BACKGROUND: Anti-Gerbich (Ge) alloantibody against high-frequency erythrocyte antigen is extremely rare. Owing to incomplete evidence regarding the degree and severity of adverse events induced by hemolytic transfusion reactions, the transfusion management often remains cumbersome in these patients. We report an anti-Ge alloantibody positive patient with hepatocellular carcinoma (HCC) who underwent central hepatectomy (CH) without the need for an allogeneic blood transfusion. CASE PRESENTATION: A 76-year-old Japanese woman was diagnosed with HCC measuring 9.5 × 8.0 cm in segments 4, 5, and 8 of the liver. This patient with anti-Ge alloantibody had a history of two pregnancies without transfusion. CH was planned, and based on the suggestion from the multidisciplinary team meeting, preoperative autologous donation (PAD) and acute normovolemic hemodilution (ANH) were performed. CH was successfully performed by using CUSA and Thunderbeat® with Pringle maneuver and infra-hepatic inferior vena cava clamping without perioperative need for an allogeneic blood transfusion. She has been alive without recurrence after a follow-up period of 45 months. CONCLUSION: To our knowledge, this is the first case report of hepatectomy in a patient with anti-Ge alloantibody. A multidisciplinary team approach, PAD and ANH, and bloodless liver surgical techniques appear to be useful for major hepatectomy in patients with extremely rare blood type.

Impact of antithrombotic therapy on the outcomes with focus on bleeding and thromboembolic events in patients undergoing pancreticoduodenectomy.

BACKGROUND: We investigated perioperative outcomes of pancreaticoduodenectomy (PD) in patients receiving antithrombotic therapy (ATT) with a focus on the incidence of perioperative bleeding and thromboembolic complications. METHODS: A total of 77 patients who underwent PD at our institution between 2013 and 2019 were retrospectively reviewed. Clinical findings and surgical outcomes including bleeding and thromboembolic complications were compared in patients with or without ATT. Interruption of ATT and perioperative heparin bridging were based on our hospital protocol. RESULTS: Among ATT (30) and non-ATT (47) groups, ATT group had a significantly higher age and history of cardiocerebrovascular diseases. No significant difference was observed in intraoperative and post-pancreatectomy haemorrhage (PPH) between the groups. ATT group was associated with a significantly higher rate of post-operative complications, Clavien-Dindo classification ≥II and thromboembolic events. Operative mortality in ATT and non-ATT groups was 2 (6.7%) and 1 (2.1%), respectively. There was no significant association between ATT and excessive intraoperative blood loss (≥1000 mL), PPH (≥grade B) and thromboembolic complications (Clavien-Dindo classification ≥II). CONCLUSION: In patients with ATT, PD is a feasible procedure with no major impact on intraoperative bleeding or PPH.

Interplay between Cell Wall and Auxin Mediates the Control of Differential Cell Elongation during Apical Hook Development.

Differential growth plays a crucial role during morphogenesis [1-3]. In plants, development occurs within mechanically connected tissues, and local differences in cell expansion lead to deformations at the organ level, such as buckling or bending [4, 5]. During early seedling development, bending of hypocotyl by differential cell elongation results in apical hook structure that protects the shoot apical meristem from being damaged during emergence from the soil [6, 7]. Plant hormones participate in apical hook development, but not how they mechanistically drive differential growth [8]. Here, we present evidence of interplay between hormonal signals and cell wall in auxin-mediated differential cell elongation using apical hook development as an experimental model. Using genetic and cell biological approaches, we show that xyloglucan (a major primary cell wall component) mediates asymmetric mechanical properties of epidermal cells required for hook development. The xxt1 xxt2 mutant, deficient in xyloglucan [9], displays severe defects in differential cell elongation and hook development. Analysis of xxt1 xxt2 mutant reveals a link between cell wall and transcriptional control of auxin transporters PINFORMEDs (PINs) and AUX1 crucial for establishing the auxin response maxima required for preferential repression of elongation of the cells on the inner side of the hook. Genetic evidence identifies auxin response factor ARF2 as a negative regulator acting downstream of xyloglucan-dependent control of hook development and transcriptional control of polar auxin transport. Our results reveal a crucial feedback process between the cell wall and transcriptional control of polar auxin transport, underlying auxin-dependent control of differential cell elongation in plants.

ABCG36/PEN3/PDR8 Is an Exporter of the Auxin Precursor, Indole-3-Butyric Acid, and Involved in Auxin-Controlled Development.

The PDR-type ABCG transporter, ABCG36/PDR8/PEN3, is thought to be implicated in the export of a few structurally unrelated substrates, including the auxin precursor, indole-3-butyric acid (IBA), although a clear-cut proof of transport is lacking. An outward facing, lateral root (LR) location for ABCG36 fuelled speculations that it might secrete IBA into the rhizosphere. Here, we provide strong evidence that ABCG36 catalyzes the export of IBA - but not of indole-3-acetic acid - through the plasma membrane. ABCG36 seems to function redundantly with the closely related isoform ABCG37/PDR9/PIS1 in a negative control of rootward IBA transport in roots, which might be dampened by concerted, lateral IBA export. Analyses of single and double mutant phenotypes suggest that both ABCG36 and ABCG37 function cooperatively in auxin-controlled plant development. Both seem to possess a dual function in the control of auxin homeostasis in the root tip and long-range transport in the mature root correlating with non-polar and polar expression profiles in the LR cap and epidermis, respectively.

Bivalent property of intra-platelet VWF in liver regeneration and HCC recurrence: A prospective multicenter study.

BACKGROUND AND AIMS: A striking difference has been observed in structure and functional properties between plasma and platelet von Willebrand factor (VWF). While the existing evidence has revealed a clinical relevance of plasma VWF-Ag in liver regeneration (LR) and different cancers, this study was designed to explore the properties of intra-platelet (IP) and serum VWF-Ag in patients with hepatocellular carcinoma (HCC) undergoing partial hepatectomy. METHODS: A total of 40 patients undergoing partial hepatectomy were prospectively recruited from 3 institutions. VWF-Ag concentrations were evaluated mainly in serum and platelet extracts. Patients were followed-up for postoperative liver dysfunction and HCC recurrence. RESULTS: We observed a post-resection increase in the concentration of VWF-Ag in serum and platelet. Patients with postoperative liver dysfunction had substantially reduced serum and IP VWF-Ag concentrations. After a 2-year follow-up, patients with higher post-resection serum and IP VWF-Ag concentrations were found to develop early HCC recurrence. Likewise, IP VWF-Ag was able to independently predict post-resection early HCC recurrence. CONCLUSION: This multicenter, prospective, pilot study demonstrates a bivalent property of IP VWF in LR and oncological outcome; low preoperative VWF appeared to have a negative association on post-resection liver dysfunction, whereas, patients with higher post-resection VWF-Ag concentrations were found to have early HCC recurrence.

Simultaneous Surgery for Inferior Vena Cava Leiomyosarcoma with Multiple Hepatic Metastases: A Justified Challenge.

BACKGROUND Leiomyosarcoma of inferior vena cava (IVC), a rarely encountered malignancy originating from the smooth muscle cells of media of the IVC, frequently metastasize to the liver. The suggested treatment of choice of IVC leiomyosarcoma is radical en-bloc excision aimed to obtain a negative resection margin. There are a few reported cases of surgical management in patients with liver metastasis from IVC leiomyosarcoma. CASE REPORT This report describes a simultaneous surgical approach for a case of IVC leiomyosarcoma with multiple liver metastases followed by chemotherapy. CONCLUSIONS Tumor volume reduction surgery of metastatic lesions combined with radical resection of the primary tumor may provide better survival benefit in patients with advanced IVC leiomyosarcoma.

A substrate of the ABC transporter PEN3 stimulates bacterial flagellin (flg22)-induced callose deposition in Arabidopsis thaliana.

Nonhost resistance of Arabidopsis thaliana against Phytophthora infestans, a filamentous eukaryotic microbe and the causal agent of potato late blight, is based on a multilayered defense system. Arabidopsis thaliana controls pathogen entry through the penetration-resistance genes PEN2 and PEN3, encoding an atypical myrosinase and an ABC transporter, respectively, required for synthesis and export of unknown indole compounds. To identify pathogen-elicited leaf surface metabolites and further unravel nonhost resistance in Arabidopsis, we performed untargeted metabolite profiling by incubating a P. infestans zoospore suspension on leaves of WT or pen3 mutant Arabidopsis plants. Among the plant-secreted metabolites, 4-methoxyindol-3-yl-methanol and S-(4-methoxy-indol-3-yl-methyl) cysteine were detected in spore suspensions recollected from WT plants, but at reduced levels from the pen3 mutant plants. In both whole-cell and microsome-based assays, 4-methoxyindol-3-yl-methanol was transported in a PEN3-dependent manner, suggesting that this compound is a PEN3 substrate. The syntheses of both compounds were dependent on functional PEN2 and phytochelatin synthase 1. None of these compounds inhibited mycelial growth of P. infestans in vitro Of note, exogenous application of 4-methoxyindol-3-yl methanol slightly elevated cytosolic Ca2+ levels and enhanced callose deposition in hydathodes of seedlings treated with a bacterial pathogen-associated molecular pattern (PAMP), flagellin (flg22). Loss of flg22-induced callose deposition in leaves of pen3 seedlings was partially reverted by the addition of 4-methoxyindol-3-yl methanol. In conclusion, we have identified a specific indole compound that is a substrate for PEN3 and contributes to the plant defense response against microbial pathogens.

Predictive Value of Diminished Serum PDGF-BB after Curative Resection of Hepatocellular Cancer.

PURPOSE: Platelet derived growth factor-BB (PDGF-BB) has emerged as one of the key cytokines in malignant transformation of different cells. PDGF-BB also exhibits a potent mitogenic effect on liver cells; studies have advocated clinical implications of monitoring serum PDGF-BB (sPDGF-BB) in patients with liver disease. We thus investigated the predictive relevance of perioperative sPDGF-BB after curative resection of hepatocellular carcinoma (HCC). METHODS: We evaluated perioperative sPDGF-BB in a prospective homogenous cohort of 40 patients diagnosed with HCC. During the first two-year follow-up, patients were evaluated every three months for postresection HCC recurrence. RESULTS: Patients who developed recurrence during two-year follow-up were found to have lower concentration of sPDGF-BB than those without recurrence in both pre- and postoperative settings (P < 0.05 and P < 0.001, resp.). We validated that the reduced postoperative sPDGF-BB (< 2133.29 pg/mL) was associated with an increased incidence of postresection HCC recurrence [area under curve (AUC) > 0.8, 95% confidence interval (CI) = 0.68 - 0.94, P < 0.001]; furthermore, we were able to demonstrate that postoperative sPDGF-BB was an independent predictor of HCC recurrence (hazard ratio = 5.64, 95% CI = 1.56 - 20.30, P < 0.01). CONCLUSIONS: These findings provide a new insight into an association between diminished perioperative sPDGF-BB and HCC recurrence. Patients with low perioperative sPDGF-BB progressed early HCC recurrence. Therefore, evaluating perioperative sPDGF-BB may provide useful clinical information to characterize patients with postresection HCC recurrence.

Evaluation of THUNDERBEAT® in open liver resection- a single-center experience.

BACKGROUND: THUNDERBEAT® (TB) (Olympus Medical Systems Corp., Tokyo, Japan) is a dynamic energy system device that simultaneously delivers ultrasonically generated frictional heat energy and electrically generated bipolar energy. TB is being routinely used in various operative procedures, however, less is known about its utility in liver resection. We, herein, report our early experience of using TB in open liver resection particularly in patients with normal or near-normal liver parenchyma. METHODS: We retrospectively reviewed the clinical characteristics, and evaluated the perioperative outcome of twenty-eight patients who underwent liver resection with TB, and twenty-four patients who underwent liver resection with basic procedure in our institution. The resection type was stratified into: major hepatectomy; resection of 3 or more than 3 Couinauds segments, and minor hepatectomy; resection of less than 3 Couinauds segments. RESULTS: Liver resection time (mean ± SD) in TB group with major hepatectomy was significantly shorter: 16.7 ± 8.8 compared to 62.8 ± 39.4 min in basic procedure group (P < 0.0001). Accordingly, the liver resection time (mean ± SD) in TB group with minor hepatectomy was also significantly shorter, 8.3 ± 2.9 min compared to 45.2 ± 23.9 min in liver resection with basic procedure (P < 0.001). No significant difference was observed between the groups in terms of intraoperative blood transfusion ratio, postoperative complication and postoperative liver dysfunction. CONCLUSION: TB as a new energy device can offer a safe, reliable and substantially rapid liver resection particularly in patients with normal or near-normal liver parenchyma.