Hand-sewn gastrojejunal anastomosis reduces delayed gastric emptying after pancreaticoduodenectomy: A single-center retrospective clinical study of 1,077 consecutive patients.

BACKGROUND: Hand-sewn anastomosis and stapled anastomosis are the 2 main types of gastrojejunal anastomotic methods in pancreaticoduodenectomy. There is ongoing debate regarding the most effective anastomotic method for reducing delayed gastric emptying after pancreaticoduodenectomy. This study aims to identify factors that influence delayed gastric emptying after pancreaticoduodenectomy and assess the impact of different anastomotic methods on delayed gastric emptying. METHODS: The study included 1,077 patients who had undergone either hand-sewn anastomosis (n = 734) or stapled anastomosis (n = 343) during pancreaticoduodenectomy between December 2016 and November 2021 at our department. We retrospectively analyzed the clinical data, and a 1:1 propensity score matching was performed to balance confounding variables. RESULTS: After propensity score matching, 320 patients were included in each group. Compared with the stapled anastomosis group, the hand-sewn anastomosis group had a significantly lower incidence of delayed gastric emptying (28 [8.8%] vs 55 [17.2%], P = .001) and upper gastrointestinal tract bleeding (6 [1.9%] vs 17 [5.3%], P = .02). Additionally, the hand-sewn anastomosis group had a significantly reduced postoperative length of stay and lower hospitalization expenses. However, the hand-sewn anastomosis group had a significantly longer operative time, which was consistent with the analysis before propensity score matching. Logistic regression analysis showed that stapled anastomosis, intra-abdominal infection, and clinically relevant postoperative pancreatic fistula were independent prognostic factors for delayed gastric emptying. CONCLUSION: Hand-sewn anastomosis was associated with a lower incidence rate of clinically relevant delayed gastric emptying after pancreaticoduodenectomy. Stapled anastomosis, intra-abdominal infection, and clinically relevant postoperative pancreatic fistula could increase the incidence of postoperative clinically relevant delayed gastric emptying. Hand-sewn anastomosis should be considered by surgeons to reduce the occurrence of postoperative delayed gastric emptying and improve patient outcomes.

Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma.

Adjuvant chemotherapy benefits patients with resected pancreatic ductal adenocarcinoma (PDAC), but the compromised physical state of post-operative patients can hinder compliance. Biomarkers that identify candidates for prompt adjuvant therapy are needed. In this prospective observational study, 1,171 patients with PDAC who underwent pancreatectomy were enrolled and extensively followed-up. Proteomic profiling of 191 patient samples unveiled clinically relevant functional protein modules. A proteomics-level prognostic risk model was established for PDAC, with its utility further validated using a publicly available external cohort. More importantly, through an interaction effect regression analysis leveraging both clinical and proteomic datasets, we discovered two biomarkers (NDUFB8 and CEMIP2), indicative of the overall sensitivity of patients with PDAC to adjuvant chemotherapy. The biomarkers were validated through immunohistochemistry on an internal cohort of 386 patients. Rigorous validation extended to two external multicentic cohorts-a French multicentric cohort (230 patients) and a cohort from two grade-A tertiary hospitals in China (466 patients)-enhancing the robustness and generalizability of our findings. Moreover, experimental validation through functional assays was conducted on PDAC cell lines and patient-derived organoids. In summary, our cohort-scale integration of clinical and proteomic data demonstrates the potential of proteomics-guided prognosis and biomarker-aided adjuvant chemotherapy for PDAC.

Early oral feeding versus nasojejunal early enteral nutrition in patients following pancreaticoduodenectomy: a propensity score-weighted analysis of 428 consecutive patients.

BACKGROUND: Notwithstanding that significant medical progress has been achieved in recent years, the optimal nutritional support method following pancreaticoduodenectomy (PD) remains uncertain. This study compared the safety and feasibility of early oral feeding (EOF) with nasojejunal early enteral nutrition (NJEEN) after PD. METHODS: A retrospective cohort study was conducted on 428 consecutive patients who underwent PD between August 2018 and December 2020. During the first study phase, the routine postoperative feeding strategy was NJEEN, later replaced by EOF during the second study phase. The primary outcome was the incidence of delayed gastric emptying (DGE) following PD. Propensity score weighting was used to control for confounding factors. RESULTS: Four hundred forty patients underwent PD during the overall study period, with 438 patients aged 18 years and older. Ten patients experienced accidental tube dislodgement or migration and were excluded from the study based on the exclusion criteria. Finally, 211 patients and 217 patients underwent EOF and NJEEN, respectively. After propensity score weighting, it was observed that patients who underwent postoperative EOF experienced a significantly lower DGE (B/C) rate compared to those who underwent postoperative NJEEN [7.38% (31/424) vs. 14.97% (62/413), P =0.0005]. Subgroup analyses according to the presence of soft pancreatic texture yielded consistent results. The EOF group exhibited lower DGE grade, DGE (B/C) rate [5.90% (11/194) vs. 22.07% (43/193), P <0.0001], postoperative gastrointestinal endoscopic intervention rate, and Clavien-Dindo Grade III or higher rate. CONCLUSIONS: EOF is superior to NJEEN in reducing the incidence of grade B/C DGE after PD. The EOF procedure is safe and feasible and should be recommended as the optimal postoperative feeding method following PD.

A novel staging system derived from natural language processing of pathology reports to predict prognostic outcomes of pancreatic cancer: a retrospective cohort study.

OBJECTIVE: To construct a novel tumor-node-morphology (TNMor) staging system derived from natural language processing (NLP) of pathology reports to predict outcomes of pancreatic ductal adenocarcinoma. METHOD: This retrospective study with 1657 participants was based on a large referral center and The Cancer Genome Atlas Program (TCGA) dataset. In the training cohort, NLP was used to extract and screen prognostic predictors from pathology reports to develop the TNMor system, which was further evaluated with the tumor-node-metastasis (TNM) system in the internal and external validation cohort, respectively. Main outcomes were evaluated by the log-rank test of Kaplan-Meier curves, the concordance index (C-index), and the area under the receiver operating curve (AUC). RESULTS: The precision, recall, and F1 scores of the NLP model were 88.83, 89.89, and 89.21%, respectively. In Kaplan-Meier analysis, survival differences between stages in the TNMor system were more significant than that in the TNM system. In addition, our system provided an improved C-index (internal validation, 0.58 vs. 0.54, P <0.001; external validation, 0.64 vs. 0.63, P <0.001), and higher AUCs for 1, 2, and 3-year survival (internal validation: 0.62 vs. 0.54, P <0.001; 0.64 vs. 0.60, P= 0.017; 0.69 vs. 0.62, P= 0.001; external validation: 0.69 vs. 0.65, P= 0.098; 0.68 vs. 0.64, P= 0.154; 0.64 vs. 0.55, P= 0.032, respectively). Finally, our system was particularly beneficial for precise stratification of patients receiving adjuvant therapy, with an improved C-index (0.61 vs. 0.57, P <0.001), and higher AUCs for 1-year, 2-year, and 3-year survival (0.64 vs. 0.57, P <0.001; 0.64 vs. 0.58, P <0.001; 0.67 vs. 0.61, P <0.001; respectively) compared with the TNM system. CONCLUSION: These findings suggest that the TNMor system performed better than the TNM system in predicting pancreatic ductal adenocarcinoma prognosis. It is a promising system to screen risk-adjusted strategies for precision medicine.

Modified artery-first approach for distal pancreatectomy with celiac axis resection.

BACKGROUND: The superior mesenteric artery-first approach has been proved superior in pancreatoduodenectomy compared with the standard procedure. It is unclear whether similar benefits could be obtained in distal pancreatectomy with celiac axis resection. METHODS: Perioperative and survival outcomes of patients who underwent distal pancreatectomy with celiac axis resection with the modified artery-first approach or traditional approach between January 2012 and September 2021 were compared. RESULTS: The entire cohort comprised 106 patients (modified artery-first approach, n = 35; traditional approach, n = 71). The most common complication was postoperative pancreatic fistula (n = 18, 17.0 per cent), followed by ischaemic complications (n = 17, 16.0 per cent) and surgical site infection (n = 15, 14.0 per cent). Intraoperative blood loss (400 versus 600 ml, P = 0.017) and intraoperative transfusion rate (8.6 versus 29.6 per cent, P = 0.015) were lower in the modified artery-first approach group compared with the traditional approach group. A higher number of harvested lymph nodes (18 versus 13, P = 0.030) and R0 resection rate (88.6 versus 70.4 per cent, P = 0.038) and a lower incidence of ischaemic complications (5.7 versus 21.1 per cent, P = 0.042) was observed in the modified artery-first approach group compared with the traditional approach group. In multivariable analysis, the modified artery-first approach (OR 0.006, 95 per cent c.i., 0 to 0.447; P = 0.020) was protective against ischaemic complications. CONCLUSIONS: Compared with the traditional approach, the modified artery-first approach was associated with lower blood loss and fewer ischaemic complications, and a higher number of harvested lymph nodes and R0 resection rate. Thus, it might improve the safety, staging and prognosis of distal pancreatectomy with celiac axis resection for pancreatic cancer.

PI3K/ c-Myc/AFF4 axis promotes pancreatic tumorigenesis through fueling nucleotide metabolism.

MLL-AFF4 fusion gene has been discovered in acute leukemia, whether AFF4 alone plays a role in tumor, especially pancreatic tumorigenesis, is still elusive. Increasing evidence suggests that cancer cells altered nucleotide metabolism during tumorigenesis. In present study, we observed AFF4 overexpression promoted cell proliferation, colony formation and cell cycle progression while loss of AFF4 impairs above phenotypes of pancreatic ductal carcinoma (PDAC) cells. Using RNA-profiling, we revealed that HPRT1 and IMPDH2, two enzymes in the nucleotide metabolism pathway, were upregulated following AFF4 overexpression. Simultaneous expression of HPRT1 and IMPDH2 would mainly rescue the phenotypes of cells lacking AFF4. Additionally, xenograft study proved HPRT1 and IMPDH2 genetically function in the downstream of AFF4, which was recruited by PAX2 when CDK9 mediated AFF4 phosphorylation at S388 and drove HPRT1 and IMPDH2 expression. We further discovered PI3K/c-Myc axis is required for AFF4 expression in PDAC cells. Finally, we obtained the positive correlation between c-Myc and AFF4 or AFF4 and HPRT1/IMPDH2 in clinical PDAC samples. Otherwise, we conducted data-mining and found that the expression levels of AFF4 and HPRT1/IMPDH2 are correlated with patients' prognosis, establishing AFF4 as a potential biomarker and therapeutic target for PDAC.

Incidence of bifid pancreatic duct in pancreaticoduodenectomy and its impact on clinically relevant postoperative pancreatic fistula.

Objectives: This study aimed to examine the incidence of bifid pancreatic duct (BPD) in pancreaticoduodenectomy (PD) and clarify its impact on clinically relevant postoperative pancreatic fistula (CR-POPF). Background: Until now, all the literature about BPD during PD are published as case reports, and the incidence of BPD in PD and its impact on CR-POPF remain unknown. Results: A total of 438 consecutive PDs were divided into two groups: the former year group and the latter year group. The former year group included 215 consecutive PDs, while the latter year group included 223. In the latter year group, we found 16 BPDs during PD (O-BPD); the incidence of O-BPD is 7.17%. Of them, there were eight patients who had BPD in the preoperative imaging (I-BPD). All the I-BPDs are O-BPDs; which means that 50% of O-BPDs were a single pancreatic duct in the preoperative imaging (I-SPD). There were 17 I-BPDs in the 438 consecutive PDs; the incidence of I-BPD is 3.88%. In the former year group, the rate of severe complications of I-BPD and I-SPD is 77.78% and 27.18%, respectively (p = 0.003); the rate of CR-POPF of I-BPD is higher than I-SPD, 55.56% vs. 27.18%, but there were no statistically significant differences. In the latter year group, the rate of severe complications of O-BPD and O-SPD is 50% and 18.36%, and the rate of CR-POPF of O-BPD and O-SPD is 37.5% and 22.22%, respectively; both of them have statistically significant differences, and the p-value is 0.003 and 0.006, respectively. In the subgroup analysis, both the rate of severe complications and the rate of CR-POPF of I-BPD were higher than O-BPD, 77.78% vs. 50%, and 55.56% vs. 37.5%, but there were no statistically significant differences in both of them; the p-value is 0.174 and 0.434, respectively. Univariate and multivariate analyses showed that BPD was an independent risk factor of CR-POPF. Conclusions: The incidence of O-BPD in PD is 7.17%, 50% of O-BPDs were I-SPD, and the incidence of I-BPD is 3.88%. BPD is an independent risk factor of CR-POPF. The suture closure method may be a simple, safe, and effective method in dealing with BPD in PD.

Systemic therapy and perioperative management improve the prognosis of pancreatic ductal adenocarcinoma: A retrospective cohort study of 2000 consecutive cases.

OBJECTIVE: This study aimed to explore patterns of the treatment strategies of pancreatic ductal adenocarcinoma based on 2000 consecutive cases of a prospective database since 2012 to obtain new insights for future directions. METHODS: Among 2000 patients enrolled in this study, 210 patients were excluded, and 710, 521, and 559 patients were treated between 2012 and 2015 (group 1), between 2016 and 2017 (group 2), and between 2018 and 2019 (group 3), respectively. Patient clinicopathologic and biological factors, and perioperative outcomes were used to assess the prognostic factors. RESULTS: The median survival for all patients with pancreatic ductal adenocarcinoma was 21.7 months (1-year survival, 75.0%; 2-year survival, 43.7%; 5-year survival, 19.7%). Group 3 had a better survival outcome than groups 1 and 2 (median survival time: 23 versus 20.5 and 21.1 months). The proportion of patients younger than 65 gradually increased over time, as did the use of systemic chemotherapy and postoperative adjuvant radiotherapy. The tendency for early diagnosis (lower CA19-9 and CEA levels, smaller size, and earlier N stage), use of chemotherapy and radiotherapy, early recovery (lesser hospital stay and Clavien-Dindo grade <3), absence of abdominal pain, younger age, length of operation ≤3 h, and pathological factors (absence of lymphovascular invasion, peripancreatic fat infiltration and neural invasion, higher differentiation) were related to patients' survival. Multivariable analysis for prognosis revealed that tumor biological factors (increased preoperative serum CA19-9 level, tumor size, tumor differentiation, N stage, and presence of lymphovascular invasion and neural invasion), chemotherapy, radiotherapy, abdomen pain, operation period, length of stay, and length of operation correlated with patients' survival. CONCLUSIONS: Systemic therapy, including chemotherapy and radiotherapy, has gradually improved the prognosis after operative resection for pancreatic ductal adenocarcinoma. Neoadjuvant therapy is also beneficial to improve the prognosis to a certain extent. The enhanced recovery after surgery (ERAS) policies and the specific assessment of postoperative pancreatic fistula (POPF) risk may be related to reduced hospital stays and the reduction of serious complications. These advancements show that the concept of systemic therapy has been accepted and actively applied by Chinese medical institutions.

LINC00483 promotes proliferation and metastasis through the miR-19a-3p/TBK1/MAPK axis in pancreatic ductal adenocarcinoma (PDAC).

Background: Long noncoding RNAs (lncRNAs) have been found to promote tumor progression. However, the role of lncRNAs in pancreatic ductal adenocarcinoma (PDAC) requires more investigation. Methods: In this study, microarray was used to measure lncRNA levels in 3 pairs of PDAC tissues. As the highest upregulated lncRNA, LINC00483 was selected for further investigation to determine its functions in PDAC. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to confirm LINC00483 level in PDAC. PDAC cell lines were transfected with short hairpin RNA (shRNA) or microRNA (miRNA). 5-ethynyl-2'-deoxyuridine (EdU) assay, colony formation assay, wound healing assay, transwell assay, and xenograft mouse models were used to evaluate LINC00483 inhibition in vitro and in vivo. Luciferase reporter assay was performed to confirm binding sites of LINC00483 with miR-19a-3p, and miR-19a-3p with TANK-binding kinase 1 (TBK1). Immunohistochemistry (IHC) was performed to evaluate TBK1 and c-myc expression in PDAC tissues. Western blot was used to elucidate the LINC00483/miR-19a-3p/TBK1/mitogen-activated protein kinase (MAPK) axis. Results: Our data showed that LINC00483 was significantly upregulated in PDAC compared to normal tissue. High level of LINC00483 was correlated with advanced clinical stage, tumor invasion and metastasis, and adverse prognosis in PDAC patients. LINC00483 suppression inhibited proliferation and invasion in vitro and tumor development in vivo via modulation of miR-19a-3p expression. Subsequently, we found that miR-19a-3p binds to TBK1 in PDAC and LINC00483 could regulate PDAC cell progression by regulating miR-19a-3p via the TBK1/MAPK pathway. Conclusions: The results of our study suggested that the LINC00483/miR-19a-3p/TBK1/MAPK axis contributed to PDAC progression, which provides a potential therapeutic target for PDAC treatment.

Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity.

Chromatin accessibility plays an essential role in controlling cellular identity and the therapeutic response of human cancers. However, the chromatin accessibility landscape and gene regulatory network of pancreatic cancer are largely uncharacterized. Here, we integrate the chromatin accessibility profiles of 84 pancreatic cancer organoid lines with whole-genome sequencing data, transcriptomic sequencing data and the results of drug sensitivity analysis of 283 epigenetic-related chemicals and 5 chemotherapeutic drugs. We identify distinct transcription factors that distinguish molecular subtypes of pancreatic cancer, predict numerous chromatin accessibility peaks associated with gene regulatory networks, discover regulatory noncoding mutations with potential as cancer drivers, and reveal the chromatin accessibility signatures associated with drug sensitivity. These results not only provide the chromatin accessibility atlas of pancreatic cancer but also suggest a systematic approach to comprehensively understand the gene regulatory network of pancreatic cancer in order to advance diagnosis and potential personalized medicine applications.

Impact of previous upper/lower abdominal surgery on pancreatic surgical outcomes and complications: a propensity score matching study.

PURPOSE: Pancreatic surgery is a complex operation that has been associated with severe intraoperative and postoperative complications, especially in patients with previous abdominal surgery (PAS). Our study aimed to assess the impact of PAS on pancreatic surgery. METHODS: A total of 1430 patients who underwent pancreatic surgery were included in this retrospective study and classified into the following 3 groups: previous upper abdominal surgery (PUAS) (n = 135); previous lower abdominal surgery (PLAS) (n = 161), and no history of abdominal surgery (non-PAS) (n = 1134). Using propensity score matching (PSM), patients were matched to one another at a 1:1:1 ratio with balanced baseline characteristics. Intraoperative factors, surgical complications, hospital costs, and postoperative hospitalization were collected and compared. RESULTS: A longer operative duration was observed in the PUAS group compared to the non-PAS group (187.54 vs. 150.50 min, p = 0.016). The intraoperative blood loss in the PUAS group was significantly higher (193.68 vs. 150.51 and 156.81 mL, p < 0.05), while the intraoperative plasma transfusion volume was higher in PLAS patients than in non-PAS patients (183.8 vs. 102.7 mL, p = 0.008). Intra-abdominal adhesions in PUAS patients were most severe, and non-PAS patients exhibited significantly lower intra-abdominal adhesion grading (p < 0.001). No significant differences were observed in postoperative complications, postoperative histopathology, postoperative hospitalization, or hospital cost. CONCLUSION: PAS has no significant influences on surgical outcomes, and pancreatic surgery is relatively safe in this patient population. A patient history of PAS may prolong operation duration and increase intraoperative blood loss but has no impact on postoperative complications and does not increase the economic burden.

Large-cohort humanized NPI mice reconstituted with CD34+ hematopoietic stem cells are feasible for evaluating preclinical cancer immunotherapy.

Cancer immunotherapy has achieved impressive therapeutic effects in many cancers, while only a small subset of patients benefit from it and some patients even have experienced severe toxicity. It is urgent to develop a feasible large-cohort humanized mouse model to evaluate the pre-clinical efficacy and safety of cancer immunotherapy. Furthermore, developing potentially effective combination therapy between cancer immunotherapy and other therapies also needs humanized mouse model to adequately mimic clinical actual setting. Herein, we established a humanized mouse model engrafted with less human CD34+ HSCs than ever before and then evaluated reconstitution efficiency and the profiles of human immune cells in this humanized mouse model. Also, this humanized mouse model was used to evaluate the preclinical efficacy and safety of cancer immunotherapy. For each batch of CD34+ HSCs humanized mouse model, a relatively-large cohort with over 25% human CD45+ cells in peripheral blood was established. This humanized mouse model could efficiently reconstitute human innate and adaptive immune cells. This humanized mouse model supported patient-derived xenograft tumor growth and tumor infiltration of PD-1+ human T cells. Furthermore, therapeutic efficacy, re-activation of tumor-infiltrated T cells, and side effects of checkpoint blockade therapy could be monitored in this humanized mouse model. Human T cells from this humanized mouse model were successfully engineered with CD19-CAR. CD19 CAR-T cells could effectively deplete B cells and suppress tumor growth of acute lymphoblastic leukemia in vivo in this humanized mouse model. This humanized mouse model also could be used to demonstrate the efficacy of bispecific antibodies, such as anti-CD19/CD3. Overall, our work provides a feasible large-cohort humanized mouse model for evaluating a variety of cancer immunotherapy approaches including checkpoint inhibitors, adoptive cell therapy, and bispecific antibody therapy, and demonstrates that human T cells from this humanized mouse model possess anti-tumor activities in vitro and in vivo.

The Landscape of Genetic Alterations Stratified Prognosis in Oriental Pancreatic Cancer Patients.

BACKGROUND: Pancreatic cancer is a life-threatening malignant disease with significant diversity among geographic regions and races leading to distinct carcinogenesis and prognosis. Previous studies mainly focused on Western patients, while the genomic landscape of Oriental patients, especially Chinese, remained less investigated. METHODS: A total of 408 pancreatic cancer patients were enrolled. A panel containing 436 cancer-related genes was used to detect genetic alterations in tumor samples. RESULTS: We profiled the genomic alteration landscape of pancreatic duct adenocarcinoma (PDAC), intraductal papillary mucinous neoplasm (IPMN), periampullary carcinoma (PVC), and solid-pseudopapillary tumor (SPT). Comparison with a public database revealed specific gene mutations in Oriental PDAC patients including higher mutation rates of DNA damage repair-related genes. Analysis of mutational signatures showed potential heterogenous carcinogenic factors caused by diabetes mellitus. KRAS mutation, especially KRAS G12D mutation, was associated with poor survival, while patients not harboring the 17 significant copy number variations (CNVs) had a better prognosis. We further identified multiple correlations between clinicopathologic variables and genetic mutations, as well as CNVs. Finally, by network-based stratification, three classes of PDAC patients were robustly clustered. Among these, class 1 (characterized by the Fanconi anemia pathway) achieved the best outcome, while class 2 (involved in the platinum drug resistance pathway) suffered from the worst prognosis. CONCLUSIONS: In this study, we reported for the first time the genetic alteration landscape of Oriental PDAC patients identifying many Oriental-specific alterations. The relationship between genetic alterations and clinicopathological factors as well as prognosis demonstrated important genomic impact on tumor biology. This study will help to optimize clinical treatment of Oriental PDAC patients and improve their survival.

Mutational landscape and potential therapeutic targets for sporadic pancreatic neuroendocrine tumors based on target next-generation sequencing.

Pancreatic neuroendocrine tumor (PNET), a heterogenous type of neoplasm with limited treatment options, is relatively rare and to date, the genetic background has remained to be fully elucidated. The present study aimed to determine the mutational landscape of PNET with and without liver metastasis, as well as its clinical application value for treatment. Fresh tumor tissues were collected from 14 patients with PNET following surgery, 4 of whom had developed liver metastasis. Subsequently, targeted next-generation sequencing of 612 cancer-associated genes and comprehensive analysis were performed on the tumor tissues. The results identified 63 somatic mutations in 53 genes in the 14 patients with PNET, amongst which menin 1 was identified as the most recurrently mutated gene. The analysis also identified several novel recurrently mutated genes, including adrenoceptor alpha 2B, ARVCF delta catenin family member, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase and neuregulin 1. Among the 53 mutated genes, 11 were enriched in the PI3K/AKT signaling pathway (adjusted P=7.12x10-5). In addition, 4 patients with PNET with liver metastasis had distinctly different mutational profiles compared with those without liver metastasis; 13 genes were discovered to be exclusively mutated in the liver metastasis group of the patients with PNET, including ATRX chromatin remodeler, thioredoxin reductase 2, anus kinase 3, ARVCF delta catenin family member, integrin subunit alpha V and RAD50 double strand break repair protein. In addition, two potentially actionable alterations in BRCA2 DNA repair-associated (p.Q548Q) and neurofibromin 1 (p.Q1188X) were identified using the OncoKB database. In conclusion, the present study generated a comprehensive mutational profile of 14 patients with PNET and further described the features of patients with liver metastasis, which highlights potential targets for drug development of PNET.

ACOT4 accumulation via AKT-mediated phosphorylation promotes pancreatic tumourigenesis.

The acyl-CoA thioesterase (ACOT) family catalyses the hydrolysis of acyl-CoA thioesters to their corresponding non-esterified fatty acid and coenzyme A (CoA). Increasing evidence suggests that cancer cells generally have altered lipid metabolism in different aspects. However, the roles of the ACOT family in cancer, especially in pancreatic ductal carcinoma (PDAC), are largely unknown. In the present study, we mined data to determine the clinical significance of all eleven ACOT genes among nine major solid tumour types from TCGA database and found that the expression of ACOT4 in PDAC was negatively correlated with patient survival, establishing ACOT4 as a potential biomarker of PDAC. Depletion of ACOT4 attenuated the proliferation and tumour formation of PDAC cells. Using mass spectrometry, HSPA1A was found to associate with ACOT4. Furthermore, we found that phosphorylation of ACOT4 at S392 by AKT decreased the binding of ACOT4 to HSPA1A, resulting in ACOT4 accumulation. The ACOT4 elevation promotes pancreatic tumourigenesis by producing excessive CoA to support tumour cell metabolism. Thus, our study expands the relationship between AKT signalling and lipid metabolism and establishes a functional role of ACOT4 in PDAC.

Effect of Psychological-Behavioral Intervention on the Depression and Anxiety of COVID-19 Patients.

The COVID-19 epidemic has caused increasing public panic and mental health stress. In this study, we explore the prevalence and factors linked to anxiety and depression in hospitalized patients with COVID-19. A total of 144 patients diagnosed with COVID-19 underwent depression and anxiety assessment by using the Hospital Anxiety and Depression Scale (HADS). Social support level was also evaluated by the Perceived Social Support Scale (PSSS) at admission. Results showed that gender, age, oxygen saturation, and social support were associated with anxiety for COVID-19 patients. In addition, age, family infection with SARS-CoV-2, and social support were the risk factors associated with depression. Moreover, we designed a psychological-behavioral intervention (PBI) program that included psychological support and breathing exercises, and explored its effects on patients with COVID-19. Of the 144 participants, 26 patients with both anxiety and depression symptoms (cutoff score of ≥8 on HADS-A and HADS-D) were randomly assigned to the intervention group and the control group at a 1:1 ratio. After 10-day treatment, the HADS scores of depression and anxiety were significantly reduced in the intervention group, and PSSS scores were also significantly improved. However, no significant differences in HADS and PSSS scores between pre- and post-treatment were found in the control group. Our findings indicate that mental concern and appropriate intervention are essential parts of clinical care for COVID-19 patients.

Efficacy and safety of tocilizumab in COVID-19 patients.

In this retrospective study we assessed the efficacy and safety of tocilizumab in patients with critical or severe coronavirus disease 2019 (COVID-19). We enrolled 181 patients admitted to Huoshenshan Hospital (Wuhan, China) with confirmed COVID-19 between January 2020 and February 2020. Ninety-two patients were treated with tocilizumab, and 89 patients were treated conventionally. We analyzed the clinical manifestations, changes in CT scan images, and laboratory tests before and after tocilizumab treatment, and compared these results with the conventionally treated group. A significant reduction in the level of C-reactive protein was observed 1 week after tocilizumab administration. In some cases this meant the end of the IL-6-related cytokine storm. In addition, tocilizumab relieved fever, cough, and shortness of breath with no reported adverse drug reactions. These findings suggest tocilizumab improves clinical outcomes and is effective for treatment of patients with critical or severe COVID-19. However, future clinical trials are needed to better understand the impact of tocilizumab interference with IL-6 and provide a therapeutic strategy for treatment of COVID-19.

Robot-assisted distal pancreatectomy improves spleen preservation rate versus laparoscopic distal pancreatectomy for benign and low-grade malignant lesions of the pancreas.

BACKGROUND: The aim of this retrospective study was to compare robot-assisted distal pancreatectomy (RDP) with laparoscopic distal pancreatectomy (LDP) for patients with benign and low-grade malignant lesions of the pancreas. METHODS: This study included 166 patients who underwent RDP (n=63) or LDP (n=103) for benign or low-grade malignant lesions of the pancreas from January 2011 to October 2018 in Changhai Hospital. A retrospective analysis was performed between the two groups. The primary points were operation time, operative blood loss, hospital stay, pancreatic fistula and spleen preservation. RESULTS: There were no significant differences in patient characteristics or indications between RDP and LDP. Notably, among all patients, RDP was associated with a significantly higher rate of spleen preservation than that for LDP (30.2% vs. 6.8%, P<0.001), while other intraoperative variables were similar between the two groups. No death cases in the study group within 30 days were reported in either group. Referring to postoperative outcomes, postoperative pancreatic fistula (POPF) was 22% for the RDP group and 33% for the LDP group. In addition, the rate of clinically significant grade B/C pancreatic fistula was 5% and 7%, respectively. There were also no significant differences in hospital stay (6.0±3.0 vs. 6.4±2.5, P=0.404). Furthermore, the univariate analysis demonstrated that tumor size (P=0.001) and surgery group (RDP/LDP) (P=0.002) were associated with SP rate independent factor for spleen preservation. CONCLUSIONS: RDP is an effective and safe technique with significant advantage in spleen preservation for patients with benign and low-grade malignant lesions in the distal pancreas.