Pan-cancer analysis implicates novel insights of lactate metabolism into immunotherapy response prediction and survival prognostication.

BACKGROUND: Immunotherapy has emerged as a potent clinical approach for cancer treatment, but only subsets of cancer patients can benefit from it. Targeting lactate metabolism (LM) in tumor cells as a method to potentiate anti-tumor immune responses represents a promising therapeutic strategy. METHODS: Public single-cell RNA-Seq (scRNA-seq) cohorts collected from patients who received immunotherapy were systematically gathered and scrutinized to delineate the association between LM and the immunotherapy response. A novel LM-related signature (LM.SIG) was formulated through an extensive examination of 40 pan-cancer scRNA-seq cohorts. Then, multiple machine learning (ML) algorithms were employed to validate the capacity of LM.SIG for immunotherapy response prediction and survival prognostication based on 8 immunotherapy transcriptomic cohorts and 30 The Cancer Genome Atlas (TCGA) pan-cancer datasets. Moreover, potential targets for immunotherapy were identified based on 17 CRISPR datasets and validated via in vivo and in vitro experiments. RESULTS: The assessment of LM was confirmed to possess a substantial relationship with immunotherapy resistance in 2 immunotherapy scRNA-seq cohorts. Based on large-scale pan-cancer data, there exists a notably adverse correlation between LM.SIG and anti-tumor immunity as well as imbalance infiltration of immune cells, whereas a positive association was observed between LM.SIG and pro-tumorigenic signaling. Utilizing this signature, the ML model predicted immunotherapy response and prognosis with an AUC of 0.73/0.80 in validation sets and 0.70/0.87 in testing sets respectively. Notably, LM.SIG exhibited superior predictive performance across various cancers compared to published signatures. Subsequently, CRISPR screening identified LDHA as a pan-cancer biomarker for estimating immunotherapy response and survival probability which was further validated using immunohistochemistry (IHC) and spatial transcriptomics (ST) datasets. Furthermore, experiments demonstrated that LDHA deficiency in pancreatic cancer elevated the CD8+ T cell antitumor immunity and improved macrophage antitumoral polarization, which in turn enhanced the efficacy of immunotherapy. CONCLUSIONS: We unveiled the tight correlation between LM and resistance to immunotherapy and further established the pan-cancer LM.SIG, holds the potential to emerge as a competitive instrument for the selection of patients suitable for immunotherapy.

Characterization of Pancreatic Fistula after Post-pancreatectomy Acute Pancreatitis.

OBJECTIVE: This study aimed to investigate the clinical significance and risk factors of postoperative pancreatic fistula (POPF) after post-pancreatectomy acute pancreatitis (PPAP) in patients who underwent pancreaticoduodenectomy (PD). SUMMARY BACKGROUND DATA: PPAP has been recognized as a critical factor in the pathophysiology of POPF after PD. METHODS: A total of 817 consecutive patients who underwent elective PD between January 2020 and June 2022 were included. PPAP and POPF were defined in accordance with the International Study Group for Pancreatic Surgery (ISGPS) definitions. Multivariate logistic analyses were performed to investigate the risk factors for POPF. Comparisons between PPAP-associated POPF and non-PPAP-associated POPF were made to further characterize this intriguing complication. RESULTS: Overall, 159 (19.5%) patients developed POPF after PD, of which 73 (45.9%) occurred following PPAP, and the remaining 86 (54.1%) had non-PPAP-associated POPF. Patients with PPAP-associated POPF experienced significantly higher morbidity than patients without POPF. Multivariate analyses revealed distinct risk factors for each POPF type. For PPAP-associated POPF, independent risk factors included estimated blood loss >200 mL (OR 1.93), MPD ≤3 cm (OR 2.88), and soft pancreatic texture (OR 2.01), largely overlapping with FRS (Fistula Risk Score) elements. On the other hand, non-PPAP-associated POPF was associated with age >65 years (OR 1.95), male (OR 2.10), and MPD ≤3 cm (OR 2.57). Notably, among patients with PPAP, the incidence of POPF consistently hovered around 50% regardless of the FRS stratification. CONCLUSIONS: PPAP-associated POPF presents as a distinct pathophysiology in the development of POPF after PD, potentially opening doors for future prevention strategies targeting the early postoperative period.

The Effect of Perioperative Dexamethasone on Postoperative Complications after Pancreaticoduodenectomy: A Multicenter Randomized Controlled Trial.

OBJECTIVE: This study aimed to evaluate the effect of perioperative dexamethasone on postoperative complications after pancreaticoduodenectomy. BACKGROUND: The glucocorticoid dexamethasone has been shown to improve postoperative outcomes in surgical patients, but its effects on postoperative complications after pancreaticoduodenectomy are unclear. METHODS: This multicenter, double-blind, randomized controlled trial was conducted in four Chinese high-volume pancreatic centers. Adults undergoing elective pancreaticoduodenectomy were randomized to receive either 0.2 mg/kg dexamethasone or a saline placebo as an intravenous bolus within 5 minutes after anesthesia induction. The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days after the operation, analyzed using the modified intention-to-treat principle. RESULTS: Among 428 patients for eligibility, 300 participants were randomized and 265 were included in the modified intention-to-treat analyses. 134 patients received dexamethasone and 131 patients received a placebo. The mean (SD) CCI score was 14.0 (17.5) in the dexamethasone group and 17.9 (20.3) in the placebo group (mean difference, -3.8; 95% CI, -8.4 to 0.7; P=0.100). The incidence of major complications (Clavien-Dindo grade ≥III) (12.7% vs. 16.0%, risk ratio 0.79; 95% CI, 0.44 to 1.43; P=0.439) and postoperative pancreatic fistula (25.4% vs. 31.3%, risk ratio 0.81; 95% CI, 0.55 to 1.19; P=0.286) were not significantly different between the two groups. In the stratum of participants with a main pancreatic duct ≤3 mm (n=202), the CCI score was significantly lower in the dexamethasone group (mean difference, -6.4; 95% CI, -11.2 to -1.6; P=0.009). CONCLUSION: Perioperative dexamethasone did not significantly reduce postoperative complications within 30 days after pancreaticoduodenectomy.

Short-term and Long-term Outcomes of Robotic Enucleation of Tumors Located in the Pancreatic Head and Uncinate Process.

OBJECTIVE: To assess short-term and long-term outcomes following robotic enucleation (REn) of tumors in the proximal pancreas. BACKGROUND: Despite the advantages of preserving function via pancreatic enucleation, controversies persist, since this can be associated with severe complications, such as clinically relevant postoperative pancreatic fistula, especially when performed near the main pancreatic duct. The safety and efficacy of REn in this context remain largely unknown. METHODS: A retrospective analysis was performed of all patients who underwent REn for benign and low-grade malignant neoplasms in the pancreatic head and uncinate process between January 2005 and December 2021. Clinicopathologic, perioperative, and long-term outcomes were compared with a similar open enucleation (OEn) group. RESULTS: Of 146 patients, 92 underwent REn with a zero conversion-to-open rate. REn was superior to OEn in terms of shorter operative time (90.0 minutes vs 120.0 minutes, P<0.001), decreased blood loss (20.0 mL vs 100.0 min, P=0.001), and lower clinically relevant postoperative pancreatic fistula rate (43.5% vs 61.1%, P=0.040). Bile leakage rate, major morbidity, 90-day mortality, and length of hospital stay were comparable between groups. No post-REn grade C POPF or grade IV/V complication was identified. Subgroup analyses for uncinate process tumors and proximity to the main pancreatic duct did not demonstrate inferior postoperative outcomes. In a median follow-up period of 50 months, REn outcomes were comparable to OEn regarding recurrence rate and pancreatic endocrine or exocrine function. CONCLUSIONS: REn for pancreatic head and uncinate process tumors improved clinically relevant outcomes without increased major complications compared to OEn, while demonstrating comparable long-term oncological and functional outcomes.

Robotic versus open pancreatoduodenectomy in patients with pancreatic duct adenocarcinoma after the learning curve: a propensity score-matched analysis.

BACKGROUND: Studies have demonstrated that the learning curve plays an important role in robotic pancreatoduodenectomy (RPD). Although improved short-term outcomes of RPD after the learning curve have been reported compared to open pancreatoduodenectomy (OPD), there is a lack of long-term survival analyses. METHODS: Patients who underwent curative intended RPD and OPD for pancreatic duct adenocarcinoma (PDAC) between January 2017 and June 2020 were retrospectively reviewed. A 1:2 propensity score matching (PSM) analysis was performed to balance the baseline characteristics between the RPD and OPD groups. RESULTS: Of the 548 patients (108 RPD and 440 OPD), 103 RPD patients were matched with 206 OPD patients after PSM. There were 194 (62.8%) men and 115 (37.2%) women, with a median age of 64 (58-69) years. The median overall survival (OS) in the RPD group was 33.2 months compared with 25.7 months in the OPD group (p = 0.058, log-rank). The median disease-free survival (DFS) following RPD was longer than the OPD (18.5 vs. 14.0 months, p = 0.011, log-rank). The RPD group has a lower incidence of local recurrence compared the OPD group (36.9% vs. 51.2%, p = 0.071). Multivariate Cox analysis demonstrated that RPD was independently associated with improved OS (HR 0.70, 95% CI 0.52-0.94, p = 0.019) and DFS (HR 0.66, 95% CI 0.50-0.88, p = 0.005). CONCLUSION: After the learning curve, RPD had improved oncologic outcomes in PDAC patients compared to OPD. Future prospective randomized clinical trials will be required to validate these findings.

Enhancement pattern of the pancreatic parenchyma predicts postpancreatectomy acute pancreatitis after pancreaticoduodenectomy.

OBJECTIVES: To assess the association between the enhancement pattern of the pancreatic parenchyma on preoperative multiphasic contrast-enhanced computed tomography (CECT) and the occurrence of postpancreatectomy acute pancreatitis (PPAP) after pancreaticoduodenectomy (PD). METHODS: A total of 513 patients who underwent PD were retrospective enrolled. The CT attenuation values of the nonenhanced (N), arterial (A), portal venous (P), and late (L) phases in the pancreatic parenchyma were measured on preoperative multiphasic CECT. The enhancement pattern was quantized by the CT attenuation value ratios in each phase. Receiver operating characteristic (ROC) curve analyses were computed to evaluate predictive performance. Regression analyses were used to identify independent risk factors for PPAP. RESULTS: PPAP developed in 102 patients (19.9%) and was associated with increased morbidity and a worse postoperative course. The A/P ratio, P/L ratio, and A/L ratio were significantly higher in the PPAP group. On the ROC analysis, the A/L ratio and A/P ratio both performed well in predicting PPAP (A/L: AUC = 0.7579; A/P: AUC = 0.7497). On multivariate analyses, the A/L ratio > 1.29 (OR 4.30 95% CI: 2.62-7.06, p < 0.001) and A/P ratio > 1.13 (OR 5.02 95% CI: 2.98-8.45, p < 0.001) were both independent risk factors of PPAP in each model. CONCLUSIONS: The enhancement pattern of the pancreatic parenchyma on multiphasic preoperative CECT is a good predictor of the occurrence of PPAP after PD, which could help clinicians identify high-risk patients or enable selective enhance recovery protocols. CLINICAL RELEVANCE STATEMENT: Preoperative identification of patients at high risk for postpancreatectomy acute pancreatitis by enhancement patterns of the pancreatic parenchyma allows surgeons to tailor their perioperative management and take precautions. KEY POINTS: PPAP is associated with increased risk of postoperative complications and a worse postoperative course. A rapid-decrease enhancement pattern of the pancreatic parenchyma is related to the occurrence of PPAP. The A/L and A/P ratios were both independent risk factors of PPAP in each multivariate model.

Random matrix-based laser speckle contrast imaging enables quasi-3D blood flow imaging in laparoscopic surgery.

Laser speckle contrast imaging (LSCI) provides full-field and label-free imaging of blood flow and tissue perfusion. It has emerged in the clinical environment, including the surgical microscope and endoscope. Although traditional LSCI has been improved in resolution and SNR, there are still challenges in clinical translations. In this study, we applied a random matrix description for the statistical separation of single and multiple scattering components in LSCI using a dual-sensor laparoscopy. Both in-vitro tissue phantom and in-vivo rat experiments were performed to test the new laparoscopy in the laboratory environment. This random matrix-based LSCI (rmLSCI) provides the blood flow and tissue perfusion in superficial and deeper tissue respectively, which is particularly useful in intraoperative laparoscopic surgery. The new laparoscopy provides the rmLSCI contrast images and white light video monitoring simultaneously. Pre-clinical swine experiment was also performed to demonstrate the quasi-3D reconstruction of the rmLSCI method. The quasi-3D ability of the rmLSCI method shows more potential in other clinical diagnostics and therapies using gastroscopy, colonoscopy, surgical microscope, etc.

The Impact of Additional Para-aortic Dissection During Pancreaticoduodenectomy for Resectable Pancreatic Cancer.

BACKGROUND: The short-term outcome and long-term survival of pancreaticoduodenectomy with additional para-aortic dissection (PAD) for patients with resectable pancreatic cancer remain obscure. PATIENTS AND METHODS: Consecutive patients who underwent radical pancreaticoduodenectomy for resectable pancreatic cancer in a single high-volume center during a 7-year period were included retrospectively. Both short- and long-term effects of PAD were compared between the PAD group and the no PAD group. Then, the PAD group was divided into the non-metastatic para-aortic lymph node (PALN-) group and the metastatic PALN (PALN+) group to further analyze the prognosis of PALN+. RESULTS: Of the 909 included patients, 280 (30.8%) underwent PAD during pancreaticoduodenectomy. The PAD group had a higher rate of intra-abdominal infection compared with the no PAD group (28.6% vs. 20.7%, P = 0.009) but no differences were found in the incidence of other complications. The overall survival (OS) and recurrence-free survival (RFS) were also comparable between the two groups. Subgroup analysis showed that patients with PALN+ had a worse OS than patients in the PALN- group (median of 14 vs. 20 months, P = 0.048). Multivariate Cox regression analysis further revealed that PALN+ was an independent adverse predictor of OS (hazard ratio: 1.70, P = 0.007). CONCLUSIONS: This study suggests that the addition of PAD during pancreaticoduodenectomy does not improve the prognosis of patients with resectable pancreatic cancer and may lead to an increased risk of infection. However, the accurate preoperative assessment and appropriate treatment strategy for patients with PALN+ need further investigation due to the poor prognosis.

Postpancreatectomy Acute Pancreatitis After Pancreaticoduodenectomy: A Distinct Clinical Entity.

OBJECTIVE: This study aimed to characterize postpancreatectomy acute pancreatitis (PPAP) after pancreaticoduodenectomy (PD) in a high-volume center. BACKGROUND: The International Study Group for Pancreatic Surgery (ISGPS) has recently proposed a new definition and grading scale of PPAP, but specific studies are lacking. METHODS: Patients who underwent PD from 2020 to 2021 were retrospectively reviewed. PPAP was defined based on the International Study Group for Pancreatic Surgery definition: sustained elevation of serum amylase levels for least the first 48 hours postoperatively and radiologic alterations consistent with PPAP. RESULTS: Among a total of 716 patients who were finally analyzed, PPAP occurred in 152 (21.2%) patients. Patients with PPAP were associated with significantly higher incidences of postoperative pancreatic fistula (POPF) (40.8% vs 11.7%, P <0.001), major complications (13.8% vs 6.6%, P =0.004), and biliary leak (11.8% vs 4.6%, P =0.001). Among them, 8 patients developed grade C PPAP leading to organ failure, reoperation, or death. Patients developing PPAP alone also demonstrated a statistically significantly increased rate of major complications than those without PPAP or POPF. In contrast, no differences were found in postoperative outcomes in patients with POPF in terms of whether they were associated with PPAP. CONCLUSION: PPAP is a distinct complication after PD with distinctive clinical outcomes. A part of PPAP presents as an inflammatory process in the early postoperative period but sometimes could lead to necrotizing pancreatitis or other severe clinical scenarios, and another part of PPAP would lead to anastomotic failure that accounts for a great proportion of POPF occurrence.

Oncological outcomes of robotic pancreatectomy in patients with pancreatic cancer who receive adjuvant chemotherapy: A propensity score-matched retrospective cohort study.

BACKGROUND: Limited data are available regarding long-term oncological outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo robotic pancreatectomy (RP). METHOD: All patients who underwent RP and open pancreatectomy (OP) for resectable PDAC between January 2011 and December 2019 were included. The RP group was matched 1:1 with OP group by propensity score matching (PSM). The oncological outcomes were collected and analyzed. RESULTS: Overall, 1606 patients were included in this study. After PSM, a well-balanced cohort of 335 patients in each group was selected for further analysis. The RP group had shorter operative time (210 min vs. 240 min, P < 0.001), lower estimated blood loss (200 ml vs. 300 ml, P = 0.011), lower wound infection rates (4.5% vs. 10.1%, P = 0.005) and shorter length of postoperative hospital stay (15 days vs. 17 days, P = 0.001) compared to the OP group, with no significant differences in other perioperative outcomes. OS was comparable between the two groups (31 months vs. 28 months, P = 0.077); however, RFS was improved in the RP group (17 months vs. 14 months, P = 0.015). Subgroup analysis showed that patients who received adjuvant chemotherapy (AC) in the RP group had better RFS than the similar patient cohort in the OP group (17 months vs. 14 months, P = 0.024). CONCLUSION: Robotic pancreatectomy is safe and oncologically effective for resectable PDAC. OS was comparable between RP and OP, and RFS was improved in the RP group, especially in patients who receive AC.

Serum lipase on postoperative day one is a strong predictor of clinically relevant pancreatic fistula after pancreaticoduodenectomy: A retrospective cohort.

BACKGROUND: Increased postoperative serum amylase has been recently reported to be associated with increased postoperative morbidity, but studies on postoperative serum lipase are limited. The aim of this study was to evaluate the value of postoperative serum lipase in predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). METHOD: A retrospective analysis was performed on 212 patients who underwent PD from September 2018 and March 2021, focusing on the association between postoperative day (POD) 1 serum lipase and CR-POPF. RESULTS: Overall, 108 (50.9%) patients had elevated serum lipase levels (>68 U/L) on POD 1. Patients with elevated serum lipase exhibited a significantly higher incidence of CR-POPF (37.0% vs. 6.7%, p < 0.001). Receiver operating characteristic (ROC) analyses showed improved diagnostic accuracy for POD 1 serum lipase compared with POD 1 serum amylase in predicting CR-POPF (AUC: 0.801 vs. 0.745, p = 0.029). Elevated serum lipase on POD 1 and elevated serum CRP on POD 3 were identified as independent predictors of CR-POPF. A simple early postoperative model, consisting of POD 1 serum lipase levels and POD 3 serum CRP levels, showed good discrimination (AUC 0.76, 95% CI 0.69-0.83) to identify the onset of CR-POPF. CONCLUSION: Serum lipase on POD 1 outperformed serum amylase on POD 1 in predicting CR-POPF after PD. The combination of POD 1 serum lipase and POD 3 serum CRP provides a reliable predicting model for CR-POPF.

Machine learning algorithms as early diagnostic tools for pancreatic fistula following pancreaticoduodenectomy and guide drain removal: A retrospective cohort study.

OBJECTIVE: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains the major cause of morbidity following pancreaticoduodenectomy (PD). Several model score systems such as the Fistula Risk Score (FRS) have been developed to predict CR-POPF using preoperative and intraoperative data. Machine learning (ML) algorithms are increasingly applied in the medical field and they could be used to assess the risk of CR-POPF, identify clinically meaningful data and guide drain removal. METHODS: Data from consecutive patients who underwent PD between January 1, 2010 and March 31, 2021 at a single high-volume center was collected retrospectively in this study. Demographics, clinical features, intraoperative parameters, and laboratory values were used to conduct the ML model. Four different ML algorithms (CatBoost, lightGBM, XGBoost and Random Forest) were used to train this model with cross-validation. RESULTS: A total of 2421 patients with 62 clinical parameters were enrolled in this ML model. The majority of patients (76.3%) underwent open PD while others underwent robot-assisted PD. CR-POPF occurred in 424 (17.5%) patients. The CatBoost algorithm outperformed other algorithms with a mean area under the receiver operating characteristic curve (AUC) of 0.81 (95% confidence interval: 0.80-0.82) from the 5-fold cross-validation procedure. In the test dataset, the CatBoost algorithm also achieved the best mean-AUC of 0.83. The most important value was mean drain fluid amylase (DFA) in the first seven postoperative days (POD). The performance of models that used only preoperative data and intraoperative data was marginally lower than that of models that used combined data. CONCLUSION: Our ML algorithms could be applied as early diagnostic tools for CR-POPF in patients who underwent PD. Such real-time clinical decision support tools can identify patients with a high risk of CR-POPF, help in developing the perioperative management plan and guide the optimal timing of drain removal.

Robotic versus open pancreaticoduodenectomy with vascular resection for pancreatic ductal adenocarcinoma: surgical and oncological outcomes from pilot experience.

PURPOSE: Venous resection and reconstruction (VR) is a feasible surgical technique to achieve optimal outcomes in selected patients with pancreatic ductal adenocarcinoma (PDAC) who undergo open pancreaticoduodenectomy (OPD). However, data regarding patient outcomes in patients who undergo VR in robotic-assisted pancreaticoduodenectomy (RPD) are scarce. METHODS: All patients with a diagnosis of PDAC who underwent upfront open or robotic pancreatoduodenectomy with VR in a high-volume institution for pancreatic surgery between 2011 and 2019 were retrospectively reviewed. Perioperative and long-term outcomes were compared between the RPD and OPD cohorts. RESULTS: A total of 84 patients were included in the final analysis, 14 patients underwent RPD with VR and 70 who had OPD with VR. Reconstructed venous patency, postoperative 30-day morbidity, and 90-day mortality were comparable; however, lymph node resection rates were lower in the RPC cohort (p = 0.029). No difference was identified in 3-year survival rates between the two groups (34.0% versus 25.7% respectively, p = 0.667). CONCLUSION: RPD with VR is a feasible approach for patients with PDAC and venous invasion. Further studies are needed to assess long-term outcomes compared to the open approach.

Clinical characteristics and surgical outcomes of resectable acinar cell carcinoma of the pancreas-propensity score matching analysis with pancreatic ductal adenocarcinoma.

BACKGROUND: Surgical resection is recommended for patients with resectable acinar cell carcinoma (ACC). The aim of this study was to investigate the clinical characteristics and surgical outcomes of resectable ACC in comparison to pancreatic ductal adenocarcinoma (PDAC). METHOD: A retrospective analysis was performed on all patients who consecutively underwent radical resection with pathologically confirmed ACC and PDAC from December 2011 to December 2018. Clinicopathologic characteristics and follow-up information were analyzed. A 1:3 propensity score matching (PSM) method was used to minimize the bias between ACC and PDAC. RESULTS: A total of 26 patients with ACC and 1351 with PDAC were included. Compared to PDAC, ACC tended to be larger (4.5 vs. 3.0 cm; p < 0.001) and more frequently located in the pancreatic body/tail (61.5% vs. 36.6%, p = 0.009), with lower total bilirubin levels, lower neutrophil lymphocyte ratio (NLR) levels and lower carbohydrate antigen 19-9 (CA19-9) levels and carcinoembryonic antigen (CEA) levels. There was no difference in postoperative morbidities in patients with ACC and PDAC. The median OS and RFS were longer in ACC when compared to PDAC (OS: 43.5 mo vs. 19.0 mo, p = 0.004; RFS: 24.5 mo vs. 11.6 mo, p = 0.023). After the 1:3 PSM, ACC remained to be a better histological type for OS (p = 0.024), but had comparable RFS with PDAC (p = 0.164). CONCLUSION: Patients with ACC after radical resection had better OS than that with PDAC. However, ACC is also an aggressive tumor with a similar trend of RFS with PDAC after the matching, necessitating the multidisciplinary treatment for resectable ACC disease.

Identification of EMT-related alternative splicing event of TMC7 to promote invasion and migration of pancreatic cancer.

Objective: Epithelial-to-mesenchymal transition (EMT) is tightly associated with the invasion and metastasis of pancreatic cancer with rapid progression and poor prognosis. Notably, gene alternative splicing (AS) event plays a critical role in regulating the progression of pancreatic cancer. Therefore, this study aims to identify the EMT-related AS event in pancreatic cancer. Methods: The EMT-related gene sets, transcriptomes, and matched clinical data were obtained from the MSigDB, The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases. Key gene AS events associated with liver metastasis were identified by prognostic analysis, gene set variation analysis (GSVA), and correlation analysis in pancreatic cancer. The cell line and organoid model was constructed to evaluate these key gene AS events in regulating pancreatic cancer in vitro. Furthermore, we established an EMT-related gene set consisting of 13 genes by prognostic analysis, the role of which was validated in two other databases. Finally, the human pancreatic cancer tissue and organoid model was used to evaluate the correlation between the enrichment of this gene set and liver metastasis. Results: Prognostic analysis and correlation analysis revealed that eight AS events were closely associated with the prognosis of pancreatic cancer. Furthermore, the expression of TMC7 and CHECK1 AS events was increased in the metastatic lesions of the human tissue and organoid model. Additionally, the knockdown of exon 17 of TMC7 significantly inhibited the proliferation, invasion, and migration of pancreatic cancer cells in 2D and 3D cell experiments. Finally, the expression of exon 17 of TMC17 exhibited a significant correlation with the poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Conclusion: The AS events of TMC7 and CHECK1 were associated with liver metastasis in pancreatic cancer. Moreover, exon 17 of TMC7 could be a potential therapeutic target in pancreatic cancer.

Worth it or not? Primary tumor resection for stage IV pancreatic cancer patients: A SEER-based analysis of 15,836 cases.

BACKGROUND: Primary tumor resection (PTR) as a treatment option for patients with stage IV pancreatic cancer (PC) is controversial. PATIENTS AND METHODS: Stage IV PC patients, with treatment data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER), were screened. The main outcomes were overall survival (OS) and cancer-specific survival (CSS). RESULTS: We enrolled 15,836 stage IV PC patients in this study. Propensity score-matched analyses revealed improved OS and CSS of patients receiving chemotherapy plus PTR versus chemotherapy (median survival time [MSTOS ]: 13 vs. 9 months, p = 0.024; MSTCSS : 14 vs. 10 months, p = 0.035), and chemoradiotherapy plus PTR versus chemoradiotherapy (MSTOS : 14 vs. 7 months, p = 0.044; MSTCSS : 14 vs. 7 months, p = 0.066). Multivariate adjusted analyses further confirmed these results. Stratified with different metastatic modalities, multivariate analyses suggested that PTR significantly improved the OS and CSS among patients with ≤1 metastatic organ, and that patients with brain metastasis might not benefit from chemotherapy treatment. CONCLUSION: PTR improves the OS and CSS of stage IV PC patients on the basis of chemotherapy or chemoradiotherapy, provided that the metastases involve ≤1 organ. Chemotherapy, however, should be carefully considered in patients with metastases involving the brain.

Robotic distal pancreatectomy reduces pancreatic fistula in patients without visceral obesity as compared to open distal pancreatectomy: A propensity score matching retrospective cohort study.

BACKGROUND: Several studies have suggested an association between visceral obesity and adverse perioperative outcomes in pancreatic surgery. However, no study has reported the impact of visceral obesity on robotic pancreatic surgery. This study aimed to assess the impact of preoperative visceral obesity on clinically relevant postoperative pancreatic fistula (CR-POPF) in pancreatic ductal adenocarcinoma (PDAC) patients following robotic distal pancreatectomy (RDP) or open distal pancreatectomy (ODP). METHODS: A retrospective analysis was performed on all patients who consecutively underwent RDP or ODP for PDAC. The visceral adipose tissue was measured on preoperative computed tomography (CT) images at the L3 vertebra level. A 1:1 propensity score matching method was used in the visceral obesity group and the nonvisceral obesity group to minimize the bias between RDP and ODP. RESULTS: Between December 2011 and December 2018, a total of 445 patients were included. Visceral obesity (n = 219) was found to be associated with higher estimated blood loss (p = 0.033), a higher CR-POPF rate (p = 0.001), delayed drain removal (p = 0.005) and a longer length of stay (p = 0.033). In multivariable analysis, visceral obesity was an independent risk factor for CR-POPF (OR: 1.69; 95% CI 1.07-2.67, p = 0.024). Among patients without visceral obesity, the incidence of CR-POPF was lower among RDP than among ODP patients (11.27% vs. 23.87%, p = 0.028), and the difference remained after propensity score matching (9.52% vs. 26.98%, p = 0.011). However, there was no significant difference in the CR-POPF rate between RDP and ODP for visceral obesity patients. CONCLUSION: In nonvisceral obesity patients, RDP had better perioperative outcomes than ODP, with a significantly lower CR-POPF rate. However, in visceral obesity patients, RDP showed equivalent CR-POPF rate when compared to ODP.

A novel nomogram for predicting the risk of major complications after pancreaticoduodenectomy in patients with obstructive jaundice.

BACKGROUND: The aim of this study was to construct and internally validate a nomogram for predicting major complications in obstructive jaundice patients planned to undergo pancreaticoduodenectomy (PD). METHODS: The clinical data of 835 obstructive jaundice patients who underwent PD in a high-volume center were collected and retrospectively analyzed during an 8-year period. Factors affecting the major complication rate were optimized by least absolute shrinkage and selection operator (LASSO) regression analysis and were incorporated in logistic regression analysis. The performance of this nomogram was evaluated by discrimination, calibration, internal validation and clinical utility. RESULTS: Predictors included in the model were sex, American Society of Anesthesiologists (ASA) score, preoperative biliary drainage (PBD), neutrophil-to-lymphocyte ratio (NLR), hemoglobin, prealbumin, total bilirubin, transfusion, and pathology category. The model had good discrimination and calibration with a C-index of 0.700. Internal validation generated an acceptable C-index of 0.701. Decision curve analysis indicated this nomogram was clinically useful for predicting the possibility of major complications at a threshold between 1% and 59%. CONCLUSION: This novel nomogram could be conveniently used and assist in decisions for PBD in clinical practice.

Learning Curve From 450 Cases of Robot-Assisted Pancreaticoduocectomy in a High-Volume Pancreatic Center: Optimization of Operative Procedure and a Retrospective Study.

OBJECTIVE: We aimed to describe our experience and the learning curve of 450 cases of robot-assisted pancreaticoduodenectomy (RPD) and optimize the surgical process so that our findings can be useful for surgeons starting to perform RPD. SUMMARY BACKGROUND DATA: Robotic surgical systems were first introduced 20 years ago. Pancreaticoduodenectomy (PD) is a challenging surgery because of its technical difficulty. RPD may overcome some of these difficulties. METHODS: The medical records of 450 patients who underwent RPD between May 2010 and December 2018 at the Shanghai Ruijin Hospital were retrospectively analyzed. Operative times and estimated blood loss (EBL) were analyzed and the learning curve was determined. A cumulative sum (CUSUM) analysis was used to identify the inflexion points. Other postoperative outcomes, postoperative complications, and long-term follow-up were also analyzed. RESULTS: Operative time improved graduallyovertimefrom405.4 ±â€Š112.9 minutes (case 1-50) to 273.6 ±â€Š70 minutes (case 301-350) (P < 0.001). EBL improved from 410 ±â€Š563.5 mL (case 1-50) to 149.0 ±â€Š103.3 mL (case 351-400) (P< 0.001). According to the CUSUM curve, there were 3 phases in the RPD learning curve. The inflexion points were around cases 100 and 250. The incidence of pancreatic leak in the last 350 cases was significantly lower than that in the first 100 cases (30.0% vs 15.1%, P = 0.003). CONCLUSIONS: RPD is safe and feasible for selected patients. Operative and oncologic outcomes were much improved after experience of 250 cases. Our optimization of the surgical process may have also contributed to this. Future prospective and randomized studies are needed to confirm our results.