Learning curve of robotic-assisted splenic vessel-preserving spleen-preserving distal pancreatectomy by one single surgeon: a retrospective cohort study.

AIM: Splenic vessel-preserving spleen-preserving distal pancreatectomy (SVP-SPDP) has a lower risk of splenic infarction than the splenicvessel-sacrificing SPDP, but it is more technically demanding. Learning curve of robotic-assisted SVP-SPDP (RSVP-SPDP) remains unreported. This study sought to analyze the perioperative outcomes and learning curve of RSVP-SPDP by one single surgeon. METHODS: Seventy-four patients who were intended to receive RSVP-SPDP at the First Affiliated Hospital of Sun Yat-sen University between May 2015 and January 2023 were included. The learning curve were retrospectively analyzed by using cumulative sum (CUSUM) analyses. RESULTS: Sixty-two patients underwent RSVP-SPDP (spleen preservation rate: 83.8%). According to CUSUM curve, the operation time (median, 318 vs. 220 min; P < 0.001) and intraoperative blood loss (median, 50 vs. 50 mL; P = 0.012) was improved significantly after 16 cases. Blood transfusion rate (12.5% vs. 3.4%; P = 0.202), postoperative major morbidity rate (6.3% vs. 3.4%; P = 0.524), and postoperative length-of-stay (median, 10 vs. 8 days; P = 0.120) improved after 16 cases but did not reach statistical difference. None of the patients had splenic infarction or abscess postoperatively. CONCLUSION: RSVP-SPDP was a safe and feasible approach for selected patients after learning curve. The improvement of operation time and intraoperative blood loss was achieved after 16 cases.

Development and Validation of a New Nomogram for Predicting Clinically Relevant Postoperative Pancreatic Fistula After Pancreatoduodenectomy.

BACKGROUND: There lacks an ideal model for accurately predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD). This study aimed at developing a nomogram with high accuracy in predicting CR-POPF after PD. METHODS: A total of 1182 patients undergoing PD in the First Affiliated Hospital of Sun Yat-sen University (FAHSYSU, n = 762) and Fudan University Shanghai Cancer Center (FUSCC, n = 420) between January 2010 and May 2018 were enrolled. The patients from FAHSYSU were assigned as testing cohort, and those from FUSCC were used as external validation cohort. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors for CR-POPF. Nomogram was developed on the basis of significant predictors. The performance of nomogram was evaluated by area under receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis. RESULTS: In testing cohort, 87 out of 762 patients developed CR-POPF. Three predictors were significantly associated with CR-POPF, including body mass index ≥24.0 kg/m2, pancreatic duct diameter <3 mm, and drainage fluid amylase on postoperative day 1 ≥2484 units/L (all p ≤ 0.001). Prediction of nomogram was accurate with AUC of 0.934 (95% confidence interval [CI]: 0.914-0.950) in testing cohort and 0.744 (95% CI: 0.699-0.785) in external validation cohort. The predictive accuracy of nomogram was better than that of previously proposed fistula risk scores both in testing and external validation cohort (all p < 0.05). CONCLUSIONS: The novel nomogram based on three easily available parameters could accurately predict CR-POPF after PD. It would have high clinical value due to its accuracy and convenience.

Development and validation of a nomogram for predicting overall survival of node-negative ampullary carcinoma.

BACKGROUND: The accuracy of the current staging system for predicting the overall survival (OS) of patients with ampullary carcinoma (AC) is still unsatisfactory, especially in node-negative (N0) patients. We aimed at establishing a nomogram to accurately predict OS in N0 AC. METHODS: This study enrolled 697 N0 AC patients from the Surveillance, Epidemiology, and End Results database (design cohort [DC], n = 697) and the First Affiliated Hospital of Sun Yat-sen University (validation cohort [VC], n = 112), who underwent surgical resection. The nomogram was established by using prognostic factors determined by univariate and multivariate regression analyses. RESULTS: The nomogram for OS was developed by using four independent prognostic factors, including age, grade, T stage, and a number of examined lymph nodes. The C-index of a nomogram for OS in DC and VC was 0.665 and 0.731, respectively. Calibration curves showed good consistency of the nomogram. The nomogram had a better accuracy in predicting OS compared with conventional staging system (P < .05). On the basis of nomogram-predicted scores, the patients were stratified into groups with different risk. The OS of low-risk patients was significantly longer than high-risk ones (P ≤ .010). CONCLUSIONS: The nomogram could be used to predict the OS of N0 AC. It could help guide further treatment in clinical practice.

Impact of enhanced recovery after surgery protocol on pancreaticoduodenectomy: a meta-analysis of non-randomized and randomized controlled trials.

BACKGROUND: Enhanced recovery after surgery (ERAS) has been widely applied in many surgical specialties. However, with respect to the impact of ERAS on pancreaticoduodenectomy (PD), there still exist some controversies. METHODS: Literature search was performed in PubMed, Web of Science and the Cochrane Library from January, 1990 to July, 2019. A meta-analysis was performed using fixed-effects or random-effects models. RESULTS: Twenty-two studies containing 4147 patients were identified. The entire pooled data showed that ERAS significantly reduced overall and minor morbidity (RR: 0.80, 95% CI: 0.72-0.88, p < 0.001; RR: 0.78, 95% CI: 0.69-0.88, p < 0.001, respectively), but didn't affect major morbidity (RR: 0.97, 95% CI: 0.84-1.13, p = 0.72). ERAS markedly reduced the incidences of delayed gastric emptying (DGE) (RR: 0.69, 95% CI: 0.55-0.88, p = 0.002), incisional infection (RR: 0.75, 95% CI: 0.60-0.94, p = 0.01) and intra-abdominal infection (RR: 0.79, 95% CI: 0.63-1.00, p = 0.05), but didn't influence clinically-relevant postoperative pancreatic fistula (CR-POPF) (RR: 0.86, 95% CI: 0.73-1.01, p = 0.07). Shorter length of stay (LOS) (WMD: -5.07, 95% CI: -6.71 to -3.43, p < 0.001) was noted in ERAS group, without increasing 30-day readmission (RR: 1.03, 95% CI: 0.86-1.24, p = 0.71) and mortality (RR: 0.70, 95% CI: 0.41-1.21, p = 0.20). CONCLUSION: ERAS significantly reduced overall and minor morbidity, incidences of DGE, incisional and intra-abdominal infections, and shortened LOS in PD, without increasing 30-day readmission and mortality. However, more large-scale randomized controlled trials are still needed to confirm the findings.

EYA4 inhibits hepatocellular carcinoma by repressing MYCBP by dephosphorylating ß-catenin at Ser552.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the fourth leading cause of cancer-related death worldwide. Our previous study showed that EYA4 functioned by suppressing growth of HCC tumor cells, but its molecular mechanism is still not elucidated. Based on the results of gene microassay, EYA4 was inversely correlated with MYCBP and was verified in human HCC tissues by immunohistochemistry and western blot. Overexpressed and KO EYA4 in human HCC cell lines confirmed the negative correlation between EYA4 and MYCBP by qRT-PCR and western blot. Transfected siRNA of MYCBP in EYA4 overexpressed cells and overexpressed MYCBP in EYA4 KO cells could efficiently rescue the proliferation and G2/M arrest effects of EYA4 on HCC cells. Mechanistically, armed with serine/threonine-specific protein phosphatase activity, EYA4 reduced nuclear translocation of ß-catenin by dephosphorylating ß-catenin at Ser552, thereby suppressing the transcription of MYCBP which was induced by ß-catenin/LEF1 binding to the promoter of MYCBP. Clinically, HCC patients with highly expressed EYA4 and poorly expressed MYCBP had significantly longer disease-free survival and overall survival than HCC patients with poorly expressed EYA4 and highly expressed MYCBP. In conclusion, EYA4 suppressed HCC tumor cell growth by repressing MYCBP by dephosphorylating ß-catenin S552. EYA4 combined with MYCBP could be potential prognostic biomarkers in HCC.

Establishment of a Nomogram by Integrating Molecular Markers and Tumor-Node-Metastasis Staging System for Predicting the Prognosis of Hepatocellular Carcinoma.

AIMS: This study aimed to develop a valuable nomogram by integrating molecular markers and tumor-node-metastasis (TNM) staging system for predicting the long-term outcome of patients with hepatocellular carcinoma (HCC). METHODS: The gene expression profiles of HCC patients undergoing liver resection were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. One hundred and ninety-nine patients from TCGA and 94 patients from GEO were selected to be part of the training cohort and validation cohort respectively. Univariate and multivariate cox analyses were performed to identify genes with independent prognostic values for overall survival (OS) of HCC patients in training cohort. Risk score was calculated based on the coefficients and Z-score of 3 genes for each patient. The nomogram was developed based on the risk score and TNM staging system. Discrimination and predictive accuracy of the nomogram were measured by using the concordance index (C-index) and calibration curve. The efficacy of the nomogram was tested in the external validation cohort. RESULTS: Univariate and multivariate cox analyses revealed that EXT2 (p = 0.035, hazard ratio 13.412), ETV5 (p = 0.010, hazard ratio 4.325), and CHODL (p < 0.001, hazard ratio 6.286) were independent prognostic factors and chosen for further nomogram establishment. The C-index of the nomogram for predicting the OS in the training cohort was superior to that of the TNM staging system (0.77 vs. 0.64, p < 0.01). The calibration curve of predicted 1-, 3-, and 5-year OS showed satisfactory accuracy. The external validation cohort showed good performance of comprehensive nomogram as well. CONCLUSION: The novel nomogram by integrating the molecular markers and TNM staging system has better performance in predicting long-term prognosis in HCC patients than the TNM staging system alone.

Prognostic significance of neutrophil/prealbumin ratio for intrahepatic cholangiocarcinoma undergoing curative resection.

BACKGROUND: This study aimed to clarify the prognostic significance of neutrophil/prealbumin ratio index (NPRI) for overall survival (OS) and recurrence free survival (RFS) of ICC after curative surgery. METHODS: Two-hundred and seventy-six ICC patients who underwent curative resection from December 2006 to April 2017 were recruited and analyzed retrospectively. The correlations between clinicopathological features and NPRI were analyzed. OS and RFS were calculated using Kaplan-Meier curve, and cox univariate and multivariate analyses were used to identify the prognostic factors. RESULTS: The optimal cut-off value of NPRI determined by ROC curve was 1.74 and the patients were divided into high-value and low-value groups. High-value NPRI was associated with higher risk of postoperative complications (p = 0.035) and longer hospitalization (p = 0.004).Univariate and multivariate cox analyses demonstrated that NPRI was an independent predictor for OS (p = 0.015) and RFS (p = 0.004) in ICC after curative resection. Furthermore, NPRI was also a significant predictor for OS and RFS in different subgroups of ICC, including CA19-9<35U/mL, single tumor, no vascular invasion, no local invasion and AJCC stages I + II. CONCLUSIONS: NPRI was an independent prognostic predictor for ICC after curative resection. It would have high clinical values due to its convenience.

BTG2 Is Down-Regulated and Inhibits Cancer Stem Cell-Like Features of Side Population Cells in Hepatocellular Carcinoma.

BACKGROUND: Our previous study found that B cell translocation gene 2 (BTG2) was hyper-methylated and down-regulated in side population (SP) cells of hepatocellular carcinoma (HCC) cell line. However, its clinical significances and biological impacts on HCC SP cells remained unclear. AIMS: To investigate the prognostic value of BTG2 gene in HCC and its influences on cancer stem cells (CSCs)-like traits of HCC cell line SP cells. METHODS: BTG2 expression in human HCC and adjacent non-cancerous tissues was detected by immunohistochemical staining and quantitative real-time PCR, and also obtained from GEO and TCGA data. Its prognostic values were assessed. Its biological influences on HCC cell line SP cells were evaluated using cell viability, cell cycle, plate clone-forming assay, and chemoresistance in vitro and tumorigenicity in vivo. RESULTS: BTG2 expression was significantly suppressed in human HCC compared to adjacent non-cancerous tissues. BTG2 expression was correlated with TNM stage, tumor size and vascular invasion. Lower expression of BTG2 was associated with poorer overall survival and disease-free survival. In vitro, overexpression of BTG2 substantially suppressed cell proliferation and accumulation of HCC cell line SP cells in G0/G1 phase. Colony formation ability was markedly suppressed by BTG2 overexpression. Moreover, sensitivity of HCC cell line SP cells to 5-fluorouracil was substantially increased by overexpression of BTG2. Furthermore, tumorigenicity of HCC cell line SP cells transfected with BTG2 plasmids was significantly reduced in vivo. CONCLUSIONS: BTG2 gene could regulate the CSC-like traits of HCC cell line SP cells, and it represented as a molecular prognostic marker for HCC.

DNA methylation profiling identifies EYA4 gene as a prognostic molecular marker in hepatocellular carcinoma.

BACKGROUND: DNA hypermethylation plays important roles in carcinogenesis by silencing key genes. This study aims to identify pivotal genes in hepatocellular carcinoma (HCC) by DNA methylation microarray and to assess their prognostic values. MATERIALS AND METHODS: DNA methylation microarray was performed in 45 pairs of HCC and adjacent nontumorous tissues and six normal liver tissues to identify hypermethylated genes in HCC. Potential prognosis-related genes were selected among hypermethylated genes by analyzing influences of methylation levels on disease-free survival (DFS) and overall survival (OS) in 45 patients. Their prognostic values were validated in 154 patients with HCC (including the initial 45 patients) to determine the independent prognostic gene. RESULTS: Altogether, 54 CpG islands in 44 genes were hypermethylated in HCC compared with liver tissues. Among them, methylation levels of ERG and HOXA11 were inversely associated with DFS (both P < 0.050), and methylation levels of EYA4 were inversely related to DFS and OS (both P < 0.050). EYA4 expression was inversely related to tumor size (P < 0.050). Lower EYA4 expression and larger tumor size were independent predictors of both shorter DFS and OS, and higher Barcelona Clinic Liver Cancer (BCLC) staging was an independent predictor of shorter OS (all P < 0.050). CONCLUSIONS: EYA4 functions as a prognostic molecular marker in HCC. Its aberrant hypermethylation and subsequent down-regulation may promote tumor progression.

Robotic-assisted organ-preserving or parenchymal-sparing pancreatectomy in pancreatic benign or low-grade malignant tumors: a single institute's experience.

AIM: Robotic-assisted pancreatectomy has been widely used. Organ-preserving pancreatectomy (OPP) and parenchymal-sparing pancreatectomy (PSP) has been gradually adopted for pancreatic benign or low-grade malignant tumors. This study aimed to evaluate the safety and efficacy of robotic-assisted OPP/PSP in our institute. METHODS: Patients undergoing robotic-assisted OPS/PSP at First Affiliated Hospital of Sun Yat-sen University between July 2015 and October 2021 were included in this study. The short-term and long-term outcomes of patients were retrospectively analyzed. RESULTS: Seventy-two patients were enrolled, including spleen-preserving distal pancreatectomy, central pancreatectomy, duodenum-preserving pancreatic head resection, and enucleation. Patients included were more likely to be young female (female: 46/72, median age: 47 years old). The median intraoperative blood loss and operation time was 50 ml and 255 min, respectively. Clinically relevant postoperative pancreatic fistula was 20.8% (grade B: 15/72, 20.8%; no grade C). The overall complication rate was 22.2% with the median postoperative length-of-stay of 8 days. At a median follow-up time of 28.5 months, the 5-year overall survival and recurrence-free survival rate were 100.0% and 100.0%, respectively. CONCLUSION: The short-term and long-term outcomes of patients receiving robotic-assisted OPP/PSP were acceptable. Robotic-assisted OPP/PSP was a feasible and safe technique for pancreatic benign or low-grade malignant lesions.

Simvastatin enhances the chemotherapeutic efficacy of S-1 against bile duct cancer: E2F-1/TS downregulation might be the mechanism.

Simvastatin has inhibitory effects on cancers. The present study aimed to investigate the interactive effects between simvastatin and S-1 against bile duct cancer and its mechanisms. The effects of simvastatin and 5-fluorouracil (5-FU) alone or in combination on the growth and apoptosis of the human cholangiocarcinoma cell line EGI-1 and the gallbladder carcinoma cell line Mz-ChA-1 cells were evaluated in vitro. Real-time PCR and western blot were used to determine E2F-1 and thymidylate synthase (TS) expressions in the treated cells. Tumoricidal efficacy of simvastatin and S-1 was further investigated in a subcutaneous bile duct cancer model in NOD/SCID mice. Simvastatin enhanced the cytotoxicity of 5-FU on bile duct cancer cells in vitro. IC50 of 5-FU alone was 4.34 µmol/l for EGI-1 and 13.9 µmol/l for MZ-ChA-1, whereas it decreased markedly to 0.90 and 2.95 µmol/l, respectively, when combined with simvastatin. The Chou and Talalay combination index of 5-FU and simvastatin was 0.41 and 0.40 at IC50 for EGI-1 and MZ-ChA-1, respectively. Simvastatin alone or plus 5-FU significantly suppressed E2F-1 and TS expressions in EGI-1 and MZ-ChA-1. Simvastatin plus 5-FU induced greater proportion of apoptotic cells on both EGI-1 and MZ-ChA-1, with an increase in cleaved caspase-3 levels, compared with simvastatin or 5-FU alone (all P < 0.05). Simvastatin plus S-1 induced greater tumor inhibition than simvastatin or S-1 alone with E2F-1/TS downregulation in vivo (all P < 0.05). Simvastatin and S-1 exerted synergistic effects against bile duct cancer, which might be mediated by E2F-1/TS downregulation. The combination could be a reasonable regimen in the management of bile duct cancer.

Analysis of the genome-wide DNA methylation profile of side population cells in hepatocellular carcinoma.

BACKGROUND: DNA methylation plays an important role in maintaining pluripotency and regulating the differentiation of stem cells, but the DNA methylation profile of stem cells in hepatocellular carcinoma (HCC) remains unclear. AIMS: To investigate the genome-wide DNA methylation profile of side population (SP) cells of HCC, a special subpopulation of cells enriched with cancer stem cells, by DNA methylation microarray analysis and to analyze the functions and signal pathways of the aberrantly methylated genes in SP cells. METHODS: Side population cells were isolated from HCC cell lines Huh7 and PLC/PRF/5 using flow cytometry, and the tumorigenicity of these SP cells was assessed in NOD/SCID mice. The genome-wide DNA methylation status of SP cells and non-SP (NSP) cells was detected and compared by DNA methylation microarray analysis. Genes with differential methylation between SP and NSP cells were further analyzed for their functions and roles in related signaling pathways. RESULTS: Subcutaneous inoculation of 1 × 10(3) SP cells yielded tumors in 60 % NOD/SCID mice, whereas no tumor was developed after the inoculation of 1 × 10(6) NSP cells. Genome-wide DNA methylation microarray analysis showed that 72 and 181 genes were hypermethylated and hypomethylated, respectively, in both Huh7 and PLC/PRF/5 SP cells as compared with their corresponding NSP cells. Analyses of signaling pathways revealed that hypermethylated and hypomethylated genes were related to four and eight pathways, respectively. CONCLUSIONS: Hepatocellular carcinoma SP cells possessed a differential DNA methylation status compared with NSP cells, and the differentially methylated genes in SP cells were involved in 12 signaling pathways. Our results provide valuable clues for further investigations in elucidating the importance of epigenetic regulation in sustaining HCC SP cells and tumorigenesis.

Learning curves of resection and reconstruction procedures in robotic-assisted pancreatoduodenectomy by a single surgeon: a retrospective cohort study of 160 consecutive cases.

Background: Robotic-assisted pancreatoduodenectomy (RPD) has been routinely performed in a few of centers worldwide. This study aimed to evaluate the perioperative outcomes and the learning curves of resection and reconstruction procedures in RPD by one single surgeon. Methods: Consecutive patients undergoing RPD by a single surgeon at the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between July 2016 and October 2022 were included. The perioperative outcomes and learning curves were retrospectively analysed by using cumulative sum (CUSUM) analyses. Results: One-hundred and sixty patients were included. According to the CUSUM curve, the times of resection and reconstruction procedures were shortened significantly after 30 cases (median, 284 vs 195 min; P < 0.001) and 45 cases (median, 138 vs 120 min; P < 0.001), respectively. The estimated intraoperative blood loss (median, 100 vs 50 mL; P < 0.001) and the incidence of clinically relevant post-operative pancreatic fistula (29.2% vs 12.5%; P = 0.035) decreased significantly after 20 and 120 cases, respectively. There were no significant differences in the total number of lymph nodes examined, post-operative major complications, or post-operative length-of-stay between the two groups. Conclusions: Optimization of the resection procedure and the acquisition of visual feedback facilitated the performance of RPD. RPD was a safe and feasible procedure in the selected patients.

Values of debulking surgery for unresectable well-differentiated metastatic pancreatic neuroendocrine tumors: a comparative study.

Background and objective: The value of debulking surgery for unresectable well-differentiated metastatic pancreatic neuroendocrine tumor (m-PNET) remains poorly defined. This study aimed to evaluate the outcomes of m-PNET following debulking surgery in our institute. Methods: Patients with well-differentiated m-PNET in our hospital between February 2014 and March 2022 were collected. Clinicopathological and long-term outcomes of patients treated with radical resection, debulking surgery, and conservative therapy were compared retrospectively. Results: Fifty-three patients with well-differentiated m-PNET were reviewed, including 47 patients with unresectable m-PNET (debulking surgery, 25; conservative therapy, 22) and 6 patients with resectable m-PNET (radical resection). Patients undergoing debulking surgery had a post-operative Clavien-Dindo ≥ III complication rate of 16.0% without mortality. The 5-year overall survival (OS) rate of patients treated with debulking surgery was significantly higher than that of those treated with conservative therapy alone (87.5% vs 37.8%, log-rank P = 0.022). Besides, the 5-year OS rate of patients treated with debulking surgery was comparable to that of patients with resectable m-PNET undergoing radical resection (87.5% vs 100%, log-rank P = 0.724). Conclusions: Patients with unresectable well-differentiated m-PNET who underwent resection had better long-term outcomes than those who received conservative therapy alone. The 5-year OS of patients undergoing debulking surgery and radical resection were comparable. Debulking surgery could be considered for patients with unresectable well-differentiated m-PNET if no contraindication exists.

Evaluation of the short-term outcomes of robotic-assisted radical resection for perihilar cholangiocarcinoma: a propensity-scored matching analysis.

Background: The application of robotic-assisted radical resection in perihilar cholangiocarcinoma (pCCA) remains poorly defined. This study aimed to evaluate the safety and efficacy of robotic-assisted radical resection for pCCA in our institute. Methods: Between July 2017 and July 2022, pCCA patients undergoing robotic-assisted and open radical resection at First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were included. The short-term outcomes were compared by using propensity-scored matching (PSM) analysis. Results: Eighty-six pCCA patients were enrolled. After PSM at a ratio of 1:2, 10 and 20 patients were assigned to the robotic-assisted and open groups, respectively. There were no significant disparities in the clinicopathological features between the two groups. The robotic-assisted group had significantly longer operation time (median: 548 vs 353 min, P = 0.004) and larger total number of lymph nodes examined (median: 11 vs 5, P = 0.010) than the open group. The robotic-assisted group tended to have a lower intraoperative blood loss (median: 125 vs 350 mL, P = 0.067), blood transfusion rates (30.0% vs 70.0%, P = 0.056), and post-operative overall morbidities (30.0% vs 70.0%, P = 0.056) than the open group, even though the differences were not statistically significant. There were no significant differences in the negative resection margin, post-operative major morbidities, or post-operative length-of-stay between the robotic-assisted and open groups (all P > 0.05). Conclusions: Robotic-assisted radical resection of pCCA may get a larger total number of lymph nodes examined than open surgery. Provided robotic-assisted surgery may be a feasible and safe technique for selected pCCA patients.

Establishment and validation of a nomogram for predicting overall survival of node-negative perihilar cholangiocarcinoma.

AIM: There lacks a predictive model for overall survival (OS) of node-negative perihilar cholangiocarcinoma (PHC). This study aimed at developing and validating a prognostic nomogram to predict OS of node-negative PHC after resection. METHODS: We established a nomogram via multivariate regression analysis by using the design cohort (n = 410, obtained from Surveillance, Epidemiology, and End Results database), and its external verification was done in the validation cohort (n = 100, the First Affiliated Hospital of Sun Yat-sen University). Predictive accuracy of the nomogram was assessed by concordance-index (C-index), calibration curves, and decision curve analysis (DCA). Performance of the nomogram was compared with the American Joint Committee on Cancer (AJCC) staging system. RESULTS: Multivariate regression analysis revealed that age, tumor grade, and the count of examined lymph nodes were independent prognostic factors for OS of node-negative PHC. The nomogram had a C-index of 0.603 and 0.626 in design cohort and validation cohort, respectively, which was better than that of AJCC staging system (both p < 0.05). The calibration curves showed good consistency between actual and nomogram-predicted OS probabilities. DCA showed that nomogram had better clinical usefulness. Furthermore, the nomogram-predicted scores could stratify the patients into three risk groups, and patients in higher risk group had worse prognosis than those in lower risk group (all p < 0.05). CONCLUSION: The proposed nomogram had a better prognostic accuracy than the AJCC staging system in predicting postoperative OS of node-negative PHC. It was helpful to guide the adjuvant therapeutic strategies for node-negative PHC.

Values of spleen-preserving distal pancreatectomy in well-differentiated non-functioning pancreatic neuroendocrine tumors: a comparative study.

Background: The feasibility of spleen-preserving distal pancreatectomy (SPDP) to treat well-differentiated non-functioning pancreatic neuroendocrine tumors (NF-pNETs) located at the body and/or tail of the pancreas remains controversial. Distal pancreatectomy with splenectomy (DPS) has been widely applied in the treatment of NF-pNETs; however, it may increase the post-operative morbidities. This study aimed to evaluate whether SPDP is inferior to DPS in post-operative outcomes and survivals when being used to treat patients with NF-pNETs in our institute. Methods: Clinicopathological features of patients with NF-pNETs who underwent curative SPDP or DPS at the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between January 2010 and January 2022 were collected. Short-term outcomes and 5-year survivals were compared between patients undergoing SPDP and those undergoing DPS. Results: Sixty-three patients (SPDP, 27; DPS, 36) with well-differentiated NF-pNETs were enrolled. All patients had grade 1/2 tumors. After identifying patients with T1-T2 NF-pNETs (SPDP, 27; DPS, 15), there was no disparity between the SPDP and DPS groups except for tumor size (median, 1.4 vs 2.6 cm, P = 0.001). There were no differences in operation time (median, 250 vs 295 min, P = 0.478), intraoperative blood loss (median, 50 vs 100 mL, P = 0.145), post-operative major complications (3.7% vs 13.3%, P = 0.287), clinically relevant post-operative pancreatic fistula (22.2% vs 6.7%, P = 0.390), or post-operative hospital stays (median, 9 vs 9 days, P = 0.750) between the SPDP and DPS groups. Kaplan-Meier curve showed no significant differences in the 5-year overall survival rate (100% vs 100%, log-rank P > 0.999) or recurrence-free survival (100% vs 100%, log-rank P > 0.999) between patients with T1-T2 NF-pNETs undergoing SPDP and those undergoing DPS. Conclusions: In patients with T1-T2 well-differentiated NF-pNETs, SPDP could achieve comparable post-operative outcomes and prognosis compared with DPS.

Comparison between robotic-assisted and laparoscopic left hemi-hepatectomy.

OBJECTIVE: To compare the safety and short-term outcomes between robotic-assisted and laparoscopic left hemi-hepatectomies in a single academic medical center. METHODS: A cohort of 52 patients, who underwent robotic-assisted or laparoscopic left hemi-hepatectomies between April 2015 and January 2020 in Department of Pancreatobiliary Surgery, the First Affiliated Hospital of Sun Yat-Sen University was recruited into the study. Their clinicopathological features and short-term outcomes were analyzed retrospectively. RESULTS: There were 25 robotic-assisted and 27 laparoscopic cases, with a median age of 55 years (34-77 years). There was one conversion to open in laparoscopic group. There were no significant differences in clinicopathological features between two groups, except robotic group had higher body mass index (23.9 vs. 22.0 kg/m2, p = 0.047). Robotic-assisted and laparoscopic groups had similar operative time (300 vs. 310 min, p = 0.515), length of hospital stay (8 vs. 8 days, p = 0.981) and complication rates (4.0% vs. 14.8%, p = 0.395), but the former had less blood loss (100 vs. 200 ml, p < 0.001) and lower incidence of blood transfusion (0% vs. 22.2%, p = 0.023) in comparison with laparoscopic group. R0 resection was achieved for all patients with malignancies. There was no perioperative mortality in both groups. The cost of robotic group was higher than laparoscopic group (105,870 vs. 64,191 RMB yuan, p = 0.02). CONCLUSION: The robotic-assisted and laparoscopic approaches had similar safety and short-term outcomes in left hemi-hepatectomy, and the former can reduce operative blood loss and blood transfusion. However, the costs were higher in robotic group.

Identification of Genomic Alterations in Sporadic Pancreatic Neurogenic Tumors.

Pancreatic neurogenic tumors, including schwannoma and neurofibroma, are rare, and their genetic aberrances have not been defined. The present study aimed at investigating the genomic alterations of pancreatic schwannoma and neurofibroma. Two patients with pancreatic schwannoma and 1 patient with neurofibroma, who underwent surgical resection at the First Affiliated Hospital, Sun Yat-sen University between June 2016 and April 2019, were recruited into the study. Their tumor tissues were analyzed by exome sequencing and genome sequencing. Exome sequencing revealed a MUTYH likely pathogenic germline variant in 1 schwannoma with somatic NF2del and NOTCH1 amplification. Pathway enrichment analysis on the other schwannoma case showed that the main abnormal function involved DNA damage repair, mitosis, and cell cycle. In addition, genome sequencing showed the inversion (INV) variant of SPIRE gene and multiple mitochondrial INV variants in both schwannoma cases. Furthermore, exome sequencing revealed NF1del, single nucleotide variation, TP53, and ERBB3 amplification in neurofibroma, whereas genomic duplication/deletion variants and mitochondrial abnormalities were much less than that in schwannoma. In conclusion, variants in NF1 and NF2 genes, amplification of key driver genes, and somatic and mitochondrial INV variants may play important roles in the development of pancreatic schwannoma and neurofibroma.

Ki-67 Index of 5% is Better Than 2% in Stratifying G1 and G2 of the World Health Organization Grading System in Pancreatic Neuroendocrine Tumors.

OBJECTIVE: The World Health Organization (WHO) grading system for the stratification of G1 and G2 pancreatic neuroendocrine tumors (pNETs) using an optimal Ki-67 index cutoff is still controversial. The present study aimed at finding one optimal Ki-67 cutoff value that distinguishes G1 and G2 tumors by analyzing the prognosis of patients with pNET in our center. METHODS: Data from 84 patients with pNET undergoing surgical resection in The First Affiliated Hospital of Sun Yat-sen University between March 2003 and October 2015 were retrospectively analyzed. RESULTS: The 5-year overall survival rate was 74.2%. Univariate analysis revealed that functional secretion, WHO grade, and TNM stage were significantly associated with long-term survival (all P < 0.05). Multivariate analysis demonstrated that WHO grade (P = 0.023) and TNM stage (P = 0.040) were independent prognostic factors. The receiver operating characteristic curve showed that the Ki-67 index of 5% had the best predictive ability (76.7%) for 5-year survival with a hazard ratio of 44.7. The hazard ratio was only 8.14 when the Ki-67 index cutoff was 2%. CONCLUSIONS: TNM stage and WHO grade were independent prognostic factors of pNETs. A Ki-67 index of 5% is better than 2% in stratifying G1 and G2 pNET tumors.