Infection evaluation in the early period after liver transplantation: A single-center exploration.

BACKGROUND: Infection is a significant risk factor that impacts for perioperative morbidity and mortality in liver transplantation (LTx) patients and is difficult to evaluate quantitatively in the early posttransplantation period. Thus, a biomarker to assess the risk of infection and the prognosis of the recipient is highly desirable. METHODS: A total of 128 consecutive patients with end-stage liver diseases undergoing LTx between January 1, 2020 and December 31, 2021, at the First Affiliated Hospital of Zhejiang University School of Medicine, were screened retrospectively. Graft preservation fluid and blood samples were collected for culture, and other perioperative laboratory examination results were recorded, for assessment of infection status. RESULTS: After a follow-up period of 30 days, the survival rate among the 128 LTx recipients was 94.5%. Multivariable regression analysis showed that the logarithmically transformed neutrophil-to-lymphocyte ratio (NLR) (HR = 3.548, 95% CI: ; p = .041) on post-LTx day 1 and graft preservation fluid culture positivity (HR = 12.032, 95% CI: ; p = .006) were independent predictive factors for early prognosis after LTx. CONCLUSIONS: Positive graft preservation fluid culture and the logarithmically transformed NLR on post-LTx day 1 were independent predictive factors for early prognosis after LTx. The logarithmically transformed NLR could provide an earlier indication than culture results in clinical practice.

Prognostic value of APTT combined with fibrinogen and creatinine in predicting 28-Day mortality in patients with septic shock caused by acute enteric perforation.

BACKGROUND: Septic shock is one of the leading causes of mortality in intensive care units. This retrospective study was carried out to evaluate the association of clinical available factors with 28-day mortality. PATIENTS AND METHOD: In this observational study, patients with perioperative septic shocks secondary to intra-abdominal infection caused by enteric perforation were included. A total of 328 sepsis patients were admitted to the surgical intensive care units from January 2012 to December 2016. A total of 138 patients met the enrolment criteria and were included in the study. The data of demographic, clinical and laboratory were all recorded. RESULT: All these 138 patients received abdominal surgery prior to surgical intensive care units caused by acute enteric perforation. These patients were all met the diagnostic criteria of septic shock according to Sepsis-3. Statistical analysis showed that lactic acid, blood platelet, fibrinogen, creatinine and activated partial thromboplastin time were found to be associated with 28-day mortality. A combination of serum activated partial thromboplastin time combined with fibrinogen and creatinine could predict in-hospital 28-day mortality. The area under the curve of serum activated partial thromboplastin time combined with fibrinogen and creatinine is 0.875 (0.806-0.944). CONCLUSION: In conclusion, this pilot study demonstrated that these factors can predict the prognosis of septic shock caused by enteric perforation. In order to reduce the mortality, surgeons and intensive care units physician may consider these data in perioperative period.

lncRNA-POIR promotes epithelial-mesenchymal transition and suppresses sorafenib sensitivity simultaneously in hepatocellular carcinoma by sponging miR-182-5p.

Sorafenib (SOR) resistance remains a major obstacle in the effective treatment of hepatocellular carcinoma (HCC). A number of long noncoding RNAs (lncRNAs) are responsible for this chemoresistance. This study aimed to reveal the essential function of a recently defined lncRNA, lncRNA-POIR, in the epithelial-mesenchymal transition (EMT) and SOR sensitivity of HCC cells. SOR-induced cytotoxicity was analyzed via cell counting kit-8 and ethynyl-2'-deoxyuridine incorporation assays, whereas immunoblotting and confocal immunofluorescence were used to determine the expression levels of EMT markers. Furthermore, loss- or gain-of-function approaches were used to demonstrate the role of lncRNA-POIR/miR-182-5p on EMT and SOR sensitivity in HCC. The direct interaction between lncRNA-POIR and miR-182-5p was verified using a luciferase reporter assay. We found that knockdown of lncRNA-POIR sensitized HCC cells to SOR and simultaneously reversed EMT. As expected, miR-182-5p was confirmed as the downstream target of lncRNA-POIR. Moreover, miR-182-5p overexpression clearly reversed EMT and promoted SOR-induced cytotoxicity in representative HCC cells, whereas miR-182-5p downregulation played a contrasting role; miR-182-5p knockdown abolished the modulatory effects of lncRNA-POIR siRNA on EMT and SOR sensitivity. Together, these pieces of data suggest that lncRNA-POIR promotes EMT progression and suppresses SOR sensitivity simultaneously by sponging miR-182-5p. Thus, we proposed a compelling rationale for the use of lncRNA-POIR as a promising predictor of SOR response and as a potential therapeutic target for HCC treatment in the future.

Liver Enzyme Elevation in Coronavirus Disease 2019: A Multicenter, Retrospective, Cross-Sectional Study.

INTRODUCTION: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized. METHODS: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared. RESULTS: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0-55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups. DISCUSSION: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.

Development of a Novel Multiparametric MRI Radiomic Nomogram for Preoperative Evaluation of Early Recurrence in Resectable Pancreatic Cancer.

BACKGROUND: In pancreatic cancer, methods to predict early recurrence (ER) and identify patients at increased risk of relapse are urgently required. PURPOSE: To develop a radiomic nomogram based on MR radiomics to stratify patients preoperatively and potentially improve clinical practice. STUDY TYPE: Retrospective. POPULATION: We enrolled 303 patients from two medical centers. Patients with a disease-free survival ≤12 months were assigned as the ER group (n = 130). Patients from the first medical center were divided into a training cohort (n = 123) and an internal validation cohort (n = 54). Patients from the second medical center were used as the external independent validation cohort (n = 126). FIELD STRENGTH/SEQUENCE: 3.0T axial T1 -weighted (T1 -w), T2 -weighted (T2 -w), contrast-enhanced T1 -weighted (CET1 -w). ASSESSMENT: ER was confirmed via imaging studies as MRI or CT. Risk factors, including clinical stage, CA19-9, and radiomic-related features of ER were assessed. In addition, to determine the intra- and interobserver reproducibility of radiomic features extraction, the intra- and interclass correlation coefficients (ICC) were calculated. STATISTICAL TESTS: The area under the receiver-operator characteristic (ROC) curve (AUC) was used to evaluate the predictive accuracy of the radiomic signature in both the training and test groups. The results of decision curve analysis (DCA) indicated that the radiomic nomogram achieved the most net benefit. RESULTS: The AUC values of ER evaluation for the radiomics signature were 0.80 (training cohort), 0.81 (internal validation cohort), and 0.78 (external validation cohort). Multivariate logistic analysis identified the radiomic signature, CA19-9 level, and clinical stage as independent parameters of ER. A radiomic nomogram was then developed incorporating the CA19-9 level and clinical stage. The AUC values for ER risk evaluation using the radiomic nomogram were 0.87 (training cohort), 0.88 (internal validation cohort), and 0.85 (external validation cohort). DATA CONCLUSION: The radiomic nomogram can effectively evaluate ER risks in patients with resectable pancreatic cancer preoperatively, which could potentially improve treatment strategies and facilitate personalized therapy in pancreatic cancer. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2020;52:231-245.

The efficacy and toxicity of chemotherapy in the elderly with advanced pancreatic cancer.

OBJECTIVES: FOLFIRINOX (FFX) or abraxane plus gemcitabine (AG)-based chemotherapy is used widely as firstline treatment for patients with pancreatic cancer. However, their use in the elderly is discouraged because of adverse events. More clinical data about the therapeutic response and tolerability to FFX or AG in elderly patents (over 70 years old) are required. METHODS: Patients with advanced pancreatic cancer (n = 203; 131 metastatic pancreatic cancer patients (MPC) and 72 locally advanced pancreatic cancer patients (LAPC)) were treated using modified-FFX (mFFX) or AG and mFFX sequentially. The patients were grouped according to their age, patients below 70 years old and patients above 70 years old. The objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and adverse events were compared between the groups. RESULTS: The ORRs in the elderly and in patients below 70 were similar (30.0% versus 32.3%). The median OS and PFS were also similar between the groups (mOS 13.3 m vs 12.7 m, p = 0.729, HR 0.874 (95% CI 0.5310 to 1.438); mPFS mPFS 10.6 m vs 10.3 m, p = 0.363, HR 0.800 (95% CI 0.4954 to 1.293)). However, the elderly patients suffered a higher incidence of severe adverse events (50% vs. 28.3%). CONCLUSIONS: These data could provide guidance for chemotherapy use in elderly patients with advanced pancreatic cancer. Age did not affect treatment outcome; however, supportive treatment is very important for elderly patients receiving chemotherapy.

Factors associated with failure of enhanced recovery after surgery program in patients undergoing pancreaticoduodenectomy.

BACKGROUND: The enhanced recovery after surgery (ERAS) protocol is an evidence-based perioperative care program aimed at reducing surgical stress response and accelerating recovery. However, a small proportion of patients fail to benefit from the ERAS program following pancreaticoduodenectomy. This study aimed to identify the risk factors associated with failure of ERAS program in pancreaticoduodenectomy. METHODS: Between May 2014 and December 2017, 176 patients were managed with ERAS program following pancreaticoduodenectomy. ERAS failure was indicated by prolonged hospital stay, unplanned readmission or unplanned reoperation. Demographics, postoperative recovery and compliance were compared of those ERAS failure groups to the ERAS success group. RESULTS: ERAS failure occurred in 59 patients, 33 of whom had prolonged hospital stay, 18 were readmitted to hospital within 30 days after discharge, and 8 accepted reoperation. Preoperative American Society of Anesthesiologists (ASA) score of ≥III (OR = 2.736; 95% CI: 1.276-6.939; P = 0.028) and albumin (ALB) level of <35 g/L (OR = 3.589; 95% CI: 1.403-9.181; P = 0.008) were independent risk factors associated with prolonged hospital stay. Elderly patients (>70 years) were on a high risk of unplanned reoperation (62.5% vs. 23.1%, P = 0.026). Patients with prolonged hospital stay and unplanned reoperation had delayed intake and increased intolerance of oral foods. Prolonged stay patients got off bed later than ERAS success patients did (65 h vs. 46 h, P = 0.012). Unplanned reoperation patients tended to experience severer pain than ERAS success patients did (3 score vs. 2 score, P = 0.035). CONCLUSIONS: Patients with high ASA score, low ALB level or age >70 years were at high risk of ERAS failure in pancreaticoduodenectomy. These preoperative demographic and clinical characteristics are important determinants to obtain successful postoperative recovery in ERAS program.

A preoperative nomogram predicts prognosis of up front resectable patients with pancreatic head cancer and suspected venous invasion.

BACKGROUND: Pancreatic head adenocarcinoma is commonly diagnosed at an advanced stage when adjacent vascular invasion is present. This study aimed to establish a preoperative prognostic nomogram for patients who underwent attempted curative resectional surgery for pancreatic head cancer with suspected peripancreatic venous invasion. METHODS: Data on all consecutive patients were retrospectively collected from 2012 to 2016 at four academic institutions. The demographic and radiological parameters were analyzed using univariate and multivariate Cox regression analyses. The final nomogram was established using the concordance Harrell's C-indices and calibration curves from data obtained in three institutions and validated in the cohort of patients coming from the fourth institution. RESULTS: The nomogram was constructed using data from 178 patients while the validation cohort consisted of 61 patients. Age, length of tumor contact, peripancreatic venous abnormalities and lymph node staging were independent factors of overall survival. The nomogram showed good probabilities of survival on calibration curves. The C-index of the model in predicting overall survival (OS) was 0.824 for the validation cohort. CONCLUSIONS: The nomogram accurately predicted OS in patients with pancreatic head cancer with suspected peripancreatic venous invasion after attempted curative pancreatic resectional surgery.

Hook1 inhibits malignancy and epithelial-mesenchymal transition in hepatocellular carcinoma.

Hook1 is a member of the hook family of coiled-coil proteins, which is recently found to be associated with malignant tumors. However, its biological function in hepatocellular carcinoma is yet unknown. Here, we evaluated the Hook1 levels in human hepatocellular carcinoma samples and matched peritumoral tissues by real-time polymerase chain reaction. Small interfering RNA knockdown and a transforming growth factor-ß-induced epithelial-mesenchymal transition model were employed to investigate the biological effects of Hook1 in hepatocellular carcinoma. Our results indicated that Hook1 levels were significantly lower in hepatocellular carcinoma tissues than in the peritumoral tissues. In addition, Hook1 expression was significantly associated with hepatocellular carcinoma malignancy. Hook1 was downregulated after transforming growth factor-ß-induced epithelial-mesenchymal transition. Moreover, Hook1 knockdown promoted epithelial-mesenchymal transition and attenuated the sensitivity of hepatocellular carcinoma cells to doxorubicin. In summary, our results indicate that downregulation of Hook1 plays a pivotal role in hepatocellular carcinoma progression via epithelial-mesenchymal transition. Hook1 may be used as a novel marker and therapeutic molecular target in hepatocellular carcinoma.

LB-100 sensitizes hepatocellular carcinoma cells to the effects of sorafenib during hypoxia by activation of Smad3 phosphorylation.

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. The multikinase inhibitor sorafenib is the only clinically proved systematic treatment for HCC. However, few patients respond to sorafenib. Hypoxic microenvironments contribute to sorafenib resistance. LB-100, a serine/threonine protein phosphatase 2A (PP2A) inhibitor was previously found to be a chemosensitizer in HCC. Here, we tested whether LB-100 could sensitize HCC to the effects of sorafenib. Intriguingly, LB-100 enhanced the effects of sorafenib in HCC cells only during hypoxic environments. LB-100 dramatically increased intracellular p-Smad3 level, which was responsible for the effect of LB-100 as a sensitizer. LB-100 downregulated Bcl-2 expression and enhanced sorafenib-induced apoptosis in HCC cells. We further proved that PP2A mediated LB-100-induced p-Smad3 overexpression. In addition, p38 mitogen-activated protein kinase pathway was activated in hypoxic conditions, and enhanced p-Smad3-dependent Bcl-2 inhibition and consequent apoptosis. In conclusion, LB-100 sensitized HCC cells to sorafenib in hypoxic environments. This effect was mediated by inactivation of PP2A, resulting in enhanced level of p-Smad3. Increased p-Smad3 downregulated Bcl-2, causing increased apoptosis of HCC cells.

Management strategy for spontaneous isolated dissection of the superior mesenteric artery based on morphologic classification.

OBJECTIVE: To explore a therapy strategy for the spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) based on morphologic classification. METHODS: Forty-two symptomatic patients with SIDSMA presenting with abdominal pain between January 2007 and December 2012 were enrolled in this retrospective study. We proposed a new morphologic classification with subtypes depending on the patency of the true lumen and reviewed the patients' clinical features, risk factors, computed tomography images (morphologic classification, location of entry site, dissection length, and true lumen residual diameter), treatment modalities, and follow-up results. RESULTS: Twenty-four patients received only observation treatment, seven received open surgery, and 11 received endovascular therapy. True lumen residual diameter in the observation group (46.6%) was statistically better than that in the surgery group (0%) and the endovascular group (18.3%) (P < .05). There was clinical progression in three and imaging progression in seven of the observation group, of which two patients received endovascular treatment and one patient died of bowel infarction. There were two clinical progressions and one imaging progression in the surgery group, of which two patients received additional surgery and one patient died of bowel infarction. The endovascular group obtained encouraging results with no progressions or complications. CONCLUSIONS: Symptomatic patients with SIDSMA are at risk of progression. We suggested a morphologic classification to guide the treatment. We recommend observation treatment with close follow-up for patients with patent true lumen flow and endovascular intervention for high-risk patients with true lumen stenosis or occlusion. Surgery is indicated for patients with suspected bowel infarction or arterial rupture.

Hypoxia-inducible factor 1α expression and its clinical significance in pancreatic cancer: a meta-analysis.

BACKGROUND AND AIMS: Pancreatic cancer is characterized by inadequate vascularization and considerable tumor hypoxia is prevalent. However, whether hypoxia-inducible factor 1α (HIF-1α) is significantly correlated with clinical prognosis in pancreatic cancer remains unclear. We aimed to determine the value of HIF-1α as a predictor of survival in pancreatic cancer through a meta-analysis of available cohort studies. METHODS: We performed a literature search of the MEDLINE, Embase, and Cochrane Library databases to identify cohort studies on the prognostic value of HIF-1α in pancreatic cancer. We conducted a meta-analysis to examine the clinical status and overall survival of patients with high HIF-1α expression compared to those with low expression. RESULTS: We analyzed eight studies involving 557 patients. HIF-1α was associated with higher rate of lymph node metastasis (odd ratio [OR] = 3.16; 95% confidence interval [CI] = 1.95-5.11; p < 0.05) and advanced tumor stage (OR = 3.66; 95% CI = 2.01-6.69; p < 0.05), while no significant difference was detected for tumor diameter (OR = 1.58; 95% CI = 0.46-5.47; p > 0.05). Notably, HIF-1α overexpression was significantly correlated with poor overall survival (hazard ratio [HR] = 1.88; 95% CI = 1.39-2.56; p < 0.05). CONCLUSIONS: We believe that HIF-1α overexpression is significantly associated with poor prognosis in pancreatic cancer, and may serve as an important parameter for evaluating the biological behavior and prognosis of pancreatic cancer.

Incidence, management and outcomes in hepatic artery complications after paediatric liver transplantation: protocol of the retrospective, international, multicentre HEPATIC Registry.

INTRODUCTION: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications. METHODS AND ANALYSIS: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC. ETHICS AND DISSEMINATION: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.

Copy number variation in CCL3L1 gene is associated with susceptibility to acute rejection in patients after liver transplantation.

Copy number variation (CNV) in gene was a novel type of genetic diversity in human that affect the pathogenesis, progress, and prognosis of disease. The aim of this study was to determine the associations between CNV in CCL3L1 gene and the rejection risk in liver-transplant recipients. The 266 Han-Chinese patients and 135 volunteers were enrolled in this study. Genomic DNA and mRNA samples were obtained from the whole peripheral blood; a quantitative real-time PCR-based assay was carried out to determine the copy number of CCL3L1, and real-time PCR was carried out to calculate the CCL3L1/CCL3 mRNA ratio. The CNV distributions in patients and health controls had no significant differences. Copy number in acute rejection group (AR) shifted to higher number compared with non-acute rejection group (4.74±1.87 vs. 3.88±2.13, p=0.017). Moreover, patients with higher CCL3L1 copies (≥3 copies) had a significantly higher rejection risk than patients lower copies CCL3L1 (OR=3.85, 95% CI, 1.14-13.04; p=0.021). No association was found between CNV and rejection grades. In conclusion, liver transplant recipients with high copy number of CCL3L1 gene had a significant higher risk of AR. CNV might be a novel genetic diversity that correlated with allograft rejection.

mRNA vaccine development for cholangiocarcinoma: a precise pipeline.

Cholangiocarcinoma (CHOL) is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments, including immune checkpoint blockade therapy. The mRNA vaccine-based immunotherapeutic strategy has attracted much attention for various diseases, however, its application in CHOL is limited due to the thoughtlessness in the integration of vaccine design and patient selection. A recent study established an integrated path for identifying potent CHOL antigens for mRNA vaccine development and a precise stratification for identifying CHOL patients who can benefit from the mRNA vaccines. In spite of a promising prospect, further investigations should identify immunogenic antigens and onco-immunological characteristics of CHOL to guide the clinical application of CHOL mRNA vaccines in the future.

Personalized pancreatic cancer therapy: from the perspective of mRNA vaccine.

Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity, especially in genetic alteration and microenvironment. Conventional therapeutic strategies for pancreatic cancer usually suffer resistance, highlighting the necessity for personalized precise treatment. Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting, minimal nonspecific effects, broad therapeutic window, low toxicity, and induction of persistent immunological memory. Multiple conventional vaccines based on the cells, microorganisms, exosomes, proteins, peptides, or DNA against pancreatic cancer have been developed; however, their overall efficacy remains unsatisfactory. Compared with these vaccine modalities, messager RNA (mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment, and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer. This review summarizes the current progress on pancreatic cancer vaccines, highlights the superiority of mRNA vaccines over other conventional vaccines, and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.

Evaluating the Response and Safety of Inactivated COVID-19 Vaccines in Liver Transplant Recipients.

Purpose: To evaluate the response and safety of an inactivated vaccine (Sinovac Life Sciences Co., Ltd., Beijing, China) for coronavirus disease 2019 (COVID-19) in liver transplant (LTx) recipients from China. Patients and Methods: Thirty-five recipients post LTx from the First Affiliated Hospital of Zhejiang University School of Medicine who received inactivated vaccine from June to October 2021 were screened. Information regarding vaccine side effects and clinical data were collected. Results: Thirty-five LTx recipients were enrolled, with a mean age of 46 years, and most patients were male (30, 85.71%). All the participants had a negative history of COVID-19 infection. Predictors for negative response in the recipients were interleukin-2 receptor (IL-2R) induction during LTx, shorter time post LTx and application of a derivative from mycophenolate acid (MPA). No serious adverse events were observed during the progress of vaccination or after the vaccination. Conclusion: LTx recipients have a substantially partial immunological response to the inactivated vaccine for COVID-19. IL-2R induction during LTx, a shorter time post LTx and the application of a derivative from MPA seem to be predictors for a negative serological immunoglobulin G (IgG) antibody response in recipients. The findings require booster vaccination in these LTx recipients.

Central pancreatectomy for benign or low-grade malignant pancreatic tumors in the neck and body of the pancreas.

BACKGROUND: For tumors in the neck and body of the pancreas, distal pancreatectomy (DP) has been the standard surgical procedure for the last few decades and central pancreatectomy (CP) is an alternative surgical option. Whether CP better preserves remnant pancreatic endocrine and exocrine functions after surgery remains a subject of debate. AIM: To evaluate the safety and efficacy of CP compared with DP for benign or low-grade malignant pancreatic tumors in the neck and body of the pancreas. METHODS: This retrospective study enrolled 296 patients who underwent CP or DP for benign and low-malignant neoplasms at the same hospital between January 2016 and March 2020. Perioperative outcomes and long-term morbidity of endocrine/exocrine function were prospectively evaluated. RESULTS: No significant difference was observed in overall morbidity or clinically relevant postoperative pancreatic fistula between the two groups (P = 0.055). Delayed gastric emptying occurred more frequently in the CP group than in the DP group (29.4% vs 15.3%; P < 0.005). None of the patients in the CP group had new-onset or aggravated distal metastasis, whereas 40 patients in the DP group had endocrine function deficiency after surgery (P < 0.05). There was no significant difference in the incidence of diarrhea immediately after surgery, but at postoperative 12 mo, a significantly higher number of patients had diarrhea in the DP group than in the CP group (0% vs 9.5%; P < 0.05). CONCLUSION: CP is a generally safe procedure and is better than DP in preserving long-term pancreatic endocrine and exocrine functions. Therefore, CP might be a better option for treating benign or low-grade malignant neoplasms in suitable patients.

Meteorin links the bone marrow hypoxic state to hematopoietic stem/progenitor cell mobilization.

Hematopoietic stem/progenitor cells (HSPCs) are supported and regulated by niche cells in the bone marrow with an important characterization of physiological hypoxia. However, how hypoxia regulates HSPCs is still unclear. Here, we find that meteorin (Metrn) from hypoxic macrophages restrains HSPC mobilization. Hypoxia-induced factor 1α and Yin Yang 1 induce the high expression of Metrn in macrophages, and macrophage-specific Metrn knockout increases HSPC mobilization through modulating HSPC proliferation and migration. Mechanistically, Metrn interacts with its receptor 5-hydroxytryptamine receptor 2b (Htr2b) to regulate the reactive oxygen species levels in HSPCs through targeting phospholipase C signaling. The reactive oxygen species levels are reduced in HSPCs of macrophage-specific Metrn knockout mice with activated phospholipase C signaling. Targeting the Metrn/Htr2b axis could therefore be a potential strategy to improve HSPC mobilization for stem cell-based therapy.