MiR-200b-3p elevates 5-FU sensitivity in cholangiocarcinoma cells via autophagy inhibition by targeting KLF4.

Cholangiocarcinoma is one of the most lethal human cancers, and chemotherapy failure is a major cause of recurrence and poor prognosis. We previously demonstrated that miR-200 family members are downregulated in clinical samples of cholangiocarcinoma and inhibit cholangiocarcinoma tumorigenesis and metastasis. However, the role of differentially expressed miR-200b-3p in 5-fluorouracil chemosensitivity remains unclear. Here, we examined how miR-200b-3p modulates 5-fluorouracil chemosensitivity in cholangiocarcinoma. We observed that miR-200b-3p was associated with 5-fluorouracil sensitivity in cholangiocarcinoma and increased 5-fluorouracil-induced mitochondrial apoptosis in cholangiocarcinoma cells. Mechanistically, miR-200b-3p suppressed autophagy in cholangiocarcinoma cells to mediate 5-fluorouracil sensitivity. Further, we identified KLF4 as an essential target of miR-200b-3p in cholangiocarcinoma. Notably, the miR-200b-3p/KLF4/autophagy pathway augmented the chemosensitivity of cholangiocarcinoma cells to 5-fluorouracil. Our findings underscore the key role of miR-200b-3p in chemosensitivity to 5-fluorouracil and highlight the miR-200b-3p/KLF4/autophagy axis as a potential therapeutic target for cholangiocarcinoma.

Resistance to gemcitabine is mediated by the circ_0036627/miR-145/S100A16 axis in pancreatic cancer.

The development of gemcitabine (GEM) resistance severely limits the treatment efficacy in pancreatic cancer (PC) and increasing evidence highlights the vital roles of circular RNAs (circRNAs) in the tumorigenesis, progression and drug resistance of PC. However, the circRNAs underlying GEM resistance development of PC remains to be clarified. The current research aims to unveil the roles of circ_0036627 in dictating the aggressiveness and GEM sensitivity in PC. We reported the increased expression of circ_0036627 in PC tissues and PC cell lines. Elevated circ_0036627 expression level was correlated with advanced tumour grade and poor overall survival in PC patients. Functional assays and in vivo experiments demonstrated that circ_0036627 overexpression was required for the proliferation, migration invasion and GEM resistance in PC cells. circ_0036627 knockdown suppressed tumour development in vivo. The molecular analysis further showed that circ_0036627 increased S100A16 expression by sponging microRNA-145 (miR-145), a tumour-suppressive miRNA that could significantly attenuate PC cell proliferation, migration, invasion and GEM resistance. Furthermore, our findings suggested that S100A16 acted as an oncogenic factor to promote aggressiveness and GEM resistance in PC cells. In conclusion, the current findings provide new mechanistic insights into PC aggressiveness and GEM resistance, suggesting the critical role of circ_0036627/miR-145/S100A16 axis in PC progression and drug resistance development and offering novel therapeutic targets for PC therapy.

MicroRNA miR-20a-5p targets CYCS to inhibit apoptosis in hepatocellular carcinoma.

Hepatocellular carcinoma is a primary liver cancer, characterised by diverse etiology, late diagnoses, and poor prognosis. Hepatocellular carcinoma is mostly resistant to current treatment options, therefore, identification of more effective druggable therapeutic targets is needed. We found microRNA miR-20a-5p is upregulated during mouse liver tumor progression and in human hepatocellular carcinoma patients. In this study, we elucidated the therapeutic potential of targeting oncogenic miR-20a-5p, in vivo, in a xenograft model and in two transgenic hepatocellular carcinoma mouse models via adeno-associated virus-mediated miR-20a-Tough-Decoy treatment. In vivo knockdown of miR-20a-5p attenuates tumor burden and prolongs survival in the two independent hepatocellular carcinoma mouse models. We identified and validated cytochrome c as a novel target of miR-20a-5p. Cytochrome c plays a key role in initiation of the apoptotic cascade and in the electron transport chain. We show for the first time, that miR-20a modulation affects both these key functions of cytochrome c during HCC development. Our study thus demonstrates the promising 'two birds with one stone' approach of therapeutic in vivo targeting of an oncogenic miRNA, whereby more than one key deregulated cellular process is affected, and unequivocally leads to more effective attenuation of HCC progression and significantly longer overall survival.

The ratio of skeletal muscle mass to body mass index combined with inflammatory immune markers to stratify survival of pancreatic cancer after pancreatoduodenectomy.

BACKGROUND: We sought to combine skeletal muscle index and inflammatory immune markers to stratify long-term survival in patients with pancreatic cancer after pancreatoduodenectomy (PD). METHODS: A total of 581 patients with pancreatic cancer underwent PD were included, and divided into the training and validation cohort. Image analysis of computed tomography scans was used to calculate the ratio of skeletal muscle (SM) area to body mass index (BMI). Naples prognostic score (NPS) was calculated from blood-test inflammatory immune markers. Propensity score matching (PSM) analysis was performed to minimize biases of clinicopathological characteristics. To estimate the overall survival (OS), a nomogram was developed using the training cohort. The predictive accuracy of nomogram was estimated by concordance index (C-index), calibration curve, and receiver operating characteristics (ROC) curve. RESULTS: After PSM analysis, SM/BMI ratio, NPS, lymph node metastasis, TNM stage, surgical margin, tumor grade and adjuvant therapy were independent predictors of OS, which were all assembled into nomogram. The SM/BMI ratio was the best single-predictor for 3- and 5-year OS, with an AUC of 0.805 (95% CI: 0.755-0.855) and 0.812 (95% CI: 0.736-0.888), respectively. Harrell's c-index of the nomogram in the training cohort was 0.786 (95% CI: 0.770-0.802), and the area under ROC curve of 1-year, 3- and 5-year OS prediction were 0.869 (95%CI: 0.837-0.901), 0.846 (95%CI: 0.810-0.882) and 0.849 (95%CI: 0.801-0.896). CONCLUSIONS: The nomogram based on SM/BMI ratio and NPS had excellent predictive performance, which should be incorporated to conventional risk scores to stratify survival of patients with PDAC after PD.

METTL3 Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Activating the MAPK Signaling Pathway.

Background: Inflammatory responses, apoptosis, and oxidative stress, are key factors that contribute to hepatic ischemia/reperfusion (I/R) injury, which may lead to the failure of liver surgeries, such as hepatectomy and liver transplantation. The N6-methyladenosine (m6A) modification has been implicated in multiple biological processes, and its specific role and mechanism in hepatic I/R injury require further investigation. Methods: Dot blotting analysis was used to profile m6A levels in liver tissues at different reperfusion time points in hepatic I/R mouse models. Hepatocyte-specific METTL3 knockdown (HKD) mice were used to determine the function of METTL3 during hepatic I/R. RNA sequencing and western blotting were performed to assess the potential signaling pathways involved with the deficiency of METTL3. Finally, AAV8-TBG-METTL3 was injected through the tail vein to further elucidate the role of METTL3 in hepatic I/R injury. Results: The m6A modification levels and the expression of METTL3 were upregulated in mouse livers during hepatic I/R injury. METTL3 deficiency led to an exacerbated inflammatory response and increased cell death during hepatic I/R, whereas overexpression of METTL3 reduced the extent of liver injury. Bioinformatic analysis revealed that the MAPK pathway was significantly enriched in the livers of METTL3-deficient mice. METTL3 protected the liver from I/R injury, possibly by inhibiting the phosphorylation of JNK and ERK, but not P38. Conclusions: METTL3 deficiency aggravates hepatic I/R injury in mice by activating the MAPK signaling pathway. METTL3 may be a potential therapeutic target in hepatic I/R injury.

Quality of life after pancreatic surgery.

BACKGROUND: Pancreatic surgery is challenging owing to the anatomical characteristics of the pancreas. Increasing attention has been paid to changes in quality of life (QOL) after pancreatic surgery. AIM: To summarize and analyze current research results on QOL after pancreatic surgery. METHODS: A systematic search of the literature available on PubMed and EMBASE was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant studies were identified by screening the references of retrieved articles. Studies on patients' QOL after pancreatic surgery published after January 1, 2012, were included. These included prospective and retrospective studies on patients' QOL after several types of pancreatic surgeries. The results of these primary studies were summarized inductively. RESULTS: A total of 45 articles were included in the study, of which 13 were related to pancreaticoduodenectomy (PD), seven to duodenum-preserving pancreatic head resection (DPPHR), nine to distal pancreatectomy (DP), two to central pancreatectomy (CP), and 14 to total pancreatectomy (TP). Some studies showed that 3-6 months were needed for QOL recovery after PD, whereas others showed that 6-12 months was more accurate. Although TP and PD had similar influences on QOL, patients needed longer to recover to preoperative or baseline levels after TP. The QOL was better after DPPHR than PD. However, the superiority of the QOL between patients who underwent CP and PD remains controversial. The decrease in exocrine and endocrine functions postoperatively was the main factor affecting the QOL. Minimally invasive surgery could improve patients' QOL in the early stages after PD and DP; however, the long-term effect remains unclear. CONCLUSION: The procedure among PD, DP, CP, and TP with a superior postoperative QOL is controversial. The long-term benefits of minimally invasive versus open surgeries remain unclear. Further prospective trials are warranted.

Effect of Laparoscopic and Open Pancreaticoduodenectomy for Pancreatic or Periampullary Tumors: Three-year Follow-up of a Randomized Clinical Trial.

OBJECTIVE: This study aimed to estimate whether the potential short-term advantages of laparoscopic pancreaticoduodenectomy (LPD) could allow patients to recover in a more timely manner and achieve better long-term survival than with open pancreaticoduodenectomy (OPD) in patients with pancreatic or periampullary tumors. BACKGROUND: LPD has been demonstrated to be feasible and may have several potential advantages over OPD in terms of shorter hospital stay and accelerated recovery than OPD. METHODS: This noninferiority, open-label, randomized clinical trial was conducted in 14 centers in China. The initial trial included 656 eligible patients with pancreatic or periampullary tumors enrolled from May 18, 2018, to December 19, 2019. The participants were randomized preoperatively in a 1:1 ratio to undergo either LPD (n=328) or OPD (n=328). The 3-year overall survival (OS), quality of life, which was assessed using the 3-level version of the European Quality of Life-5 Dimensions, depression, and other outcomes were evaluated. RESULTS: Data from 656 patients [328 men (69.9%); mean (SD) age: 56.2 (10.7) years] who underwent pancreaticoduodenectomy were analyzed. For malignancies, the 3-year OS rates were 59.1% and 54.3% in the LPD and OPD groups, respectively ( P =0.33, hazard ratio: 1.16, 95% CI: 0.86-1.56). The 3-year OS rates for others were 81.3% and 85.6% in the LPD and OPD groups, respectively ( P =0.40, hazard ratio: 0.70, 95% CI: 0.30-1.63). No significant differences were observed in quality of life, depression and other outcomes between the 2 groups. CONCLUSION: In patients with pancreatic or periampullary tumors, LPD performed by experienced surgeons resulted in a similar 3-year OS compared with OPD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03138213.

Long-term quality of life between duodenum-preserving pancreatic head resection and pancreatoduodenectomy: a systematic review and meta-analysis.

BACKGROUND: The authors aimed to compare the differences in quality of life (QOL) and overall survival (OS) between duodenum-preserving pancreatic head resection (DPPHR) and pancreatoduodenectomy (PD) during long-term follow-up. DPPHR and PD have been shown to be effective in alleviating symptoms and controlling malignancies, but there is ongoing debate over whether DPPHR has an advantage over PD in terms of long-term benefits. METHOD: The authors searched the PubMed, Cochrane, Embase, and Web of Science databases for relevant studies comparing DPPHR and PD published before 1 May 2023. This study was registered with PROSPERO. Randomised controlled trials and non-randomised studies were included. The Mantel-Haenszel model and inverse variance method were used as statistical approaches for data synthesis. Subgroup analyses were conducted to evaluate the heterogeneity of the results. The primary outcome was the global QOL score, measured using the QLQ-C30 system. RESULTS: The authors analysed ten studies involving 976 patients (456 DPPHR and 520 PD). The global QOL score did not differ significantly between the DPPHR and PD groups [standard mean difference (SMD) 0.21, 95% CI (-0.05, 0.46), P =0.109, I2 =70%]; however, the OS time of patients with DPPHR was significantly improved [hazard ratio 0.59, 95% CI (0.44, 0.77), P <0.001, I2 =0%]. The follow-up length may be an important source of heterogeneity. Studies with follow-up length between two to seven years showed better global QOL for DPPHR than for PD [SMD 0.43, 95% CI (0.23, 0.64), P <0.001, I2 =0%]. There were no significant differences between the two groups in any of the functional scales of the QLQ-C30 system (all P >0.05). On the symptom scale, patients in the DPPHR group had lower scores for fatigue, nausea and vomiting, loss of appetite, insomnia, and diarrhoea than those in the PD group (all P <0.05). CONCLUSIONS: There were no significant differences in global QOL scores between the two surgeries; however, DPPHR had advantages over PD in terms of safer perioperative outcomes, lower long-term symptom scores, and longer OS times. Therefore, DPPHR should be recommended over PD for the treatment of benign pancreatic diseases and low-grade malignant tumours.

Retroperitonealization of the pancreatic stump in distal pancreatectomy: a novel technique to reduce postoperative pancreatic fistula.

PURPOSE: To evaluate the efficacy and safety of retroperitonealization of the pancreatic stump in distal pancreatectomy. METHODS: Clinical data from the Tongji Hospital pancreatic database were retrospectively reviewed in this study. The data of 68 patients who underwent retroperitonealized distal pancreatectomy from January, 2019, to April, 2021, were collected and analyzed. Sixty-four patients who underwent conventional distal pancreatectomy during the same period were matched. We compared and analyzed the operative outcomes and postoperative complications between the patients in the two groups before and after propensity score matching (PSM). RESULTS: Before PSM, the operative outcomes and postoperative complications were comparable between the two groups. After PSM, the retroperitonealized group had a lower incidence of postoperative pancreatic fistula (POPF) (10.53% vs 31.58%, P = 0.047) and shorter time until drainage removal (10.00, 8.00-13.00 days vs 13.00, 10.00-18.00 days, P = 0.005). In the univariate and multivariate regression analyses, non-retroperitonealization and intra-abdominal infection were found to be independent risk factors for postoperative pancreatic fistula (POPF). CONCLUSION: Retroperitonealization of the pancreatic stump can reduce the incidence of POPF after distal pancreatectomy.

Short-Term Outcomes Following Laparoscopic vs Open Pancreaticoduodenectomy in Patients With Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial.

Importance: The safety and efficacy of laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma remain controversial. Objective: To compare laparoscopic and open pancreaticoduodenectomy performed by experienced surgeons in patients with pancreatic ductal adenocarcinoma. Design, Setting, and Participants: This was a noninferiority, open-label randomized clinical trial between September 20, 2019 and March 20, 2022, at 10 hospitals in China. A total of 412 adult patients were assessed for eligibility; 200 patients with histologically confirmed or clinically diagnosed pancreatic ductal adenocarcinoma who were eligible to undergo pancreaticoduodenectomy were enrolled. Study recruitment is complete, and follow-up is ongoing. This article reports prespecified early safety results from the trial. Interventions: Participants were randomized in a 1:1 ratio to undergo either laparoscopic or open pancreaticoduodenectomy, to be performed by experienced surgeons who had already performed at least 104 laparoscopic pancreaticoduodenectomy operations. Main Outcomes and Measures: The primary end point is 5-year overall survival, but the data for this end point are not yet mature; thus, secondary short-term outcomes, including operative findings, complications, mortality, and oncological results are reported here. The outcomes were analyzed according to a modified intention-to-treat and per-protocol principle. Results: Among 412 patients for eligibility, 200 patients were enrolled and randomly assigned 1:1 to have laparoscopic pancreaticoduodenectomy or open pancreaticoduodenectomy. The mean (SD) age was 61.3 (9.3) years, and 78 participants (39%) were female. Laparoscopic procedures had longer operative times (median [IQR], 330.0 [287.5-405.0] minutes vs 297.0 [245.0-340.0] minutes; P < .001). Patients in the laparoscopic group lost less blood than those in the open group (median [IQR], 145.0 [100.0-200.0] mL vs 200.0 [100.0-425.0] mL; P = .02). Ninety-day mortality occurred in 2 of 100 patients in the laparoscopic group and 0 of 100 patients in the open group. There was no difference in the rates of complications of the Clavien-Dindo grades III-IV (n = 17 [17.0%] vs n = 23 [23.0%]; P = .29), comprehensive complication index (median [IQR], 0.0 [0.0-22.6] vs 8.7 [0.0-26.2]; P = .79) or median (IQR) postoperative length of stay (14.0 [11.0-17.0] days vs 14.0 [12.0-18.5] days; P = .37) between the 2 groups. Conclusions and Relevance: Laparoscopic pancreaticoduodenectomy performed by experienced surgeons in high-volume specialized institutions resulted in similar short-term outcomes compared with open pancreaticoduodenectomy among patients with pancreatic ductal adenocarcinoma. Trial Registration: ClinicalTrials.gov Identifier: NCT03785743.

A comparative study of the "superior mesenteric artery first" approach versus the conventional approach in short-term and long-term outcomes in patients with pancreatic ductal adenocarcinoma undergoing laparoscopic pancreaticoduodenectomy.

BACKGROUND: The use of laparoscopic pancreaticoduodenectomy (LPD) in pancreatic head cancer remains controversial, and an appropriate surgical approach can help improve perioperative safety and oncological outcomes. This study aimed to assess the short-term outcomes and long-term survival of the superior mesenteric artery first (SMA-first) approach in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing LPD. METHODS: The data of 91 consecutive PDAC patients who underwent LPD from June 2014 to June 2021 were retrospectively analyzed. Patients were divided into two groups, the modified SMA-first approach group, using a combined posterior and anterior approach, and the conventional approach group. Perioperative outcomes, pathologic results, and overall survival (OS) were compared between groups, and propensity score-matched (PSM) analysis was performed. RESULTS: The number of lymph nodes harvested was greater in the SMA-first approach group (19 vs. 15, P = 0.021), as did the results in the matched cohort (21 vs. 15, P = 0.046). No significant difference was observed in the R0 resection rate (93.3% vs. 82.6%, P = 0.197), but the involvement of the SMA margin was indeed lower in the SMA-first approach group (0 vs. 13%). There were no obvious variances between the two groups in terms of intraoperative bleeding, operative time, overall and major postoperative complication rates, and mortality in either the original cohort or matched cohort. The median OS was 21.8 months in the SMA-first group, whereas it was 19.8 months in the conventional group (P = 0.900). Survival also did not differ in the matched cohort (P = 0.558). TNM stage, resection margin, overall complications, and adjuvant therapy were independent risk factors affecting OS. CONCLUSION: The modified SMA-first approach is safe and feasible for PDAC patients undergoing LPD. It had a slight advantage in specimen quality, but OS was not significantly prolonged.

TRIM21-Promoted FSP1 Plasma Membrane Translocation Confers Ferroptosis Resistance in Human Cancers.

Ferroptosis, an iron-dependent form of regulated cell death driven by excessive accumulation of lipid peroxides, has become a promising strategy in cancer treatment. Cancer cells exploit antioxidant proteins, including Ferroptosis Suppressor Protein 1 (FSP1), to prevent ferroptosis. In this study, it is found that the E3 ubiquitin ligase TRIM21 bound to FSP1 and mediated its ubiquitination on K322 and K366 residues via K63 linkage, which is essential for its membrane translocation and ferroptosis suppression ability. It is further verified the protective role of the TRIM21-FSP1 axis in RSL3-induced ferroptosis in cancer cells and a subcutaneous tumor model. Moreover, TRIM21 is highly expressed in multiple gastrointestinal (GI) tumors, and its expression is further stimulated upon ferroptosis induction in cancer cells and the KPC mouse model. In summary, This study identifies TRIM21 as a negative regulator of ferroptosis through K63 ubiquitination of FSP1, which can serve as a therapeutic target to enhance the chemosensitivity of tumors based on ferroptosis induction.

The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis.

BACKGROUND: Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC). METHODS: A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS). RESULTS: Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately. PROTOCOL REGISTRATION: PROSPERO (CRD42021277495) on the 25th of October 2021.

Laparoscopic versus open surgery for perihilar cholangiocarcinoma: a multicenter propensity score analysis of short- term outcomes.

BACKGROUND: Laparoscopic surgery (LS) has been increasingly applied in perihilar cholangiocarcinoma (pCCA). In this study, we intend to compare the short-term outcomes of LS versus open operation (OP) for pCCA in a multicentric practice in China. METHODS: This real-world analysis included 645 pCCA patients receiving LS and OP at 11 participating centers in China between January 2013 and January 2019. A comparative analysis was performed before and after propensity score matching (PSM) in LS and OP groups, and within Bismuth subgroups. Univariate and multivariate models were performed to identify significant prognostic factors of adverse surgical outcomes and postoperative length of stay (LOS). RESULTS: Among 645 pCCAs, 256 received LS and 389 received OP. Reduced hepaticojejunostomy (30.89% vs 51.40%, P = 0.006), biliary plasty requirement (19.51% vs 40.16%, P = 0.001), shorter LOS (mean 14.32 vs 17.95 d, P < 0.001), and lower severe complication (CD ≥ III) (12.11% vs. 22.88%, P = 0.006) were observed in the LS group compared with the OP group. Major postoperative complications such as hemorrhage, biliary fistula, abdominal abscess, and hepatic insufficiency were similar between LS and OP (P > 0.05 for all). After PSM, the short-term outcomes of two surgical methods were similar, except for shorter LOS in LS compared with OP (mean 15.19 vs 18.48 d, P = 0.0007). A series subgroup analysis demonstrated that LS was safe and had advantages in shorting LOS. CONCLUSION: Although the complex surgical procedures, LS generally seems to be safe and feasible for experienced surgeons. TRIAL REGISTRATION: NCT05402618 (date of first registration: 02/06/2022).

Benchmarking: a novel measuring tool for outcome comparisons in surgery.

INTRODUCTION: Benchmarking, a novel measuring tool for outcome comparisons, is a recent concept in surgery. The objectives of this review are to examine the concept, definition, and evolution of benchmarking and its application in surgery. METHODS: The literature about benchmarking was reviewed through an ever-narrowing search strategy, commencing from the concept, definition, and evolution of benchmarking to the application of benchmarking and experiences of benchmarking in surgery. PubMed, Web of Science, Embase, and Science Direct databases were searched until 20 September 2022, in the English language according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. RESULTS: In the first phase of the literature search, the development of benchmarking was identified. The definitions of benchmarking evolved from a surveying term to a novel quality-improvement tool to assess the best achievable results in surgery. In the second phase, a total of 23 studies were identified about benchmarking in surgery, including esophagectomy, hepatic surgery, pancreatic surgery, rectum resection, and bariatric surgery. All studies were multicenter analyses from national, international, or global expert centers. Most studies (87.0%) adopted the definition that benchmark was the 75th percentile of the median values of centers. Performance metrics to define benchmarks were clinically relevant intraoperative and postoperative outcome indicators. CONCLUSION: Benchmarking in surgery is a novel quality-improvement tool to define and measure the best achievable results, establishing a meaningful reference to evaluate surgical performance.

Development of a difficulty scoring system for laparoscopic pancreatoduodenectomy in the initial stage of the learning curve: a retrospective cohort study.

BACKGROUND: It remains uncertain how surgeons can safely pass the learning curve of laparoscopic pancreatoduodenectomy (LPD) without potentially harming patients. We aimed to develop a difficulty scoring system (DSS) to select an appropriate patient for surgeons. MATERIALS AND METHODS: A total of 773 elective pancreatoduodenectomy surgeries between July 2014 and December 2019, including 346 LPD and 427 open pancreatoduodenectomy cases, were included. A 10-level DSS for LPD was developed, and an additional 77 consecutive LPD surgeries which could provide information of the learning stage I of LPD externally validated its performance between December 2019 and December 2021. RESULTS: The incidences of postoperative complications (Clavien-Dindo≥III) gradually decreased from the learning curve stage I-III (20.00, 10.94, 5.79%, P =0.008, respectively). The DSS consisted of the following independent risk factors: (1) tumor location, (2) vascular resection and reconstruction, (3) learning curve stage, (4) prognostic nutritional index, (5) tumor size, and (6) benign or malignant tumor. The weighted Cohen's κ statistic of concordance between the reviewer's and calculated difficulty score index was 0.873. The C -statistics of DSS for postoperative complication (Clavien-Dindo≥III) were 0.818 in the learning curve stage I. The patients with DSS<5 had lower postoperative complications (Clavien-Dindo≥III) than those with DSS≥5 (4.35-41.18%, P =0.004) in the training cohort and had a lower postoperative pancreatic fistula (19.23-57.14%, P =0.0352), delayed gastric emptying (19.23-71.43%, P =0.001), and bile leakage rate (0.00-21.43%, P =0.0368) in validation cohort in the learning curve stage I. CONCLUSION: We developed and validated a difficulty score model for patient selection, which could facilitate the stepwise adoption of LPD for surgeons at different stages of the learning curve.

Minimally invasive versus open pancreatoduodenectomy for pancreatic ductal adenocarcinoma: Individual patient data meta-analysis of randomized trials.

OBJECTIVE: Assessment of minimally invasive pancreatoduodenectomy (MIPD) in patients with pancreatic ductal adenocarcinoma (PDAC) is scarce and limited to non-randomized studies. This study aimed to compare oncological and surgical outcomes after MIPD compared to open pancreatoduodenectomy (OPD) for patients after resectable PDAC from published randomized controlled trials (RCTs). METHODS: A systematic review was performed to identify RCTs comparing MIPD and OPD including PDAC (Jan 2015-July 2021). Individual data of patients with PDAC were requested. Primary outcomes were R0 rate and lymph node yield. Secondary outcomes were blood-loss, operation time, major complications, hospital stay and 90-day mortality. RESULTS: Overall, 4 RCTs (all addressed laparoscopic MIPD) with 275 patients with PDAC were included. In total, 128 patients underwent laparoscopic MIPD and 147 patients underwent OPD. The R0 rate (risk difference(RD) -1%, P = 0.740) and lymph node yield (mean difference(MD) +1.55, P = 0.305) were comparable between laparoscopic MIPD and OPD. Laparoscopic MIPD was associated with less perioperative blood-loss (MD -91ml, P = 0.026), shorter length of hospital stay (MD -3.8 days, P = 0.044), while operation time was longer (MD +98.5 min, P = 0.003). Major complications (RD -11%, P = 0.302) and 90-day mortality (RD -2%, P = 0.328) were comparable between laparoscopic MIPD and OPD. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with resectable PDAC suggests that laparoscopic MIPD is non-inferior regarding radicality, lymph node yield, major complications and 90-day mortality and is associated with less blood loss, shorter hospital stay, and longer operation time. The impact on long-term survival and recurrence should be studied in RCTs including robotic MIPD.

Textbook outcome as a composite outcome measure in laparoscopic pancreaticoduodenectomy: a multicenter retrospective cohort study.

BACKGROUND: Textbook outcome (TO) is a composite outcome measure for surgical quality assessment. The aim of this study was to assess TO following laparoscopic pancreaticoduodenectomy (LPD), identify factors independently associated with achieving TO, and analyze hospital variations regarding the TO after case-mix adjustment. METHODS: This multicenter cohort study retrospectively analyzed 1029 consecutive patients undergoing LPD at 16 high-volume pancreatic centers in China from January 2010 to August 2016. The percentage of patients achieving TO was calculated. Preoperative and intraoperative variables were compared between the TO and non-TO groups. Multivariate logistic regression was performed to identify factors independently associated with achieving TO. Hospital variations regarding the TO were analyzed by the observed/expected TO ratio after case-mix adjustment. Differences in expected TO rates between different types of hospitals were analyzed using the one-way analysis of variance test. RESULTS: TO was achieved in 68.9% ( n =709) of 1029 patients undergoing LPD, ranging from 46.4 to 85.0% between different hospitals. Dilated pancreatic duct (>3 mm) was associated with the increased probability of achieving TO [odds ratio (OR): 1.564; P =0.001], whereas advanced age (≥75 years) and concomitant cardiovascular disease were associated with a lower likelihood of achieving TO (OR: 0.545; P =0.037 and OR: 0.614; P =0.006, respectively). The observed/expected TO ratio varied from 0.62 to 1.22 after case-mix adjustment between different hospitals, but no significant hospital variations were observed. Hospital volume, the surgeon's experience with open pancreaticoduodenectomy and minimally invasive surgery, and surpassing the LPD learning curve were significantly correlated with expected TO rates. CONCLUSION: TO was achieved by less than 70% of patients following LPD. Dilated pancreatic ducts, advanced age, and concomitant cardiovascular disease were independently associated with achieving TO. No significant hospital variations were observed after case-mix adjustment.

Risk factors for achieving textbook outcome after laparoscopic duodenum-preserving total pancreatic head resection: a retrospective cohort study.

INTRODUCTION: The risk factors for achieving textbook outcome (TO) after laparoscopic duodenum-preserving total pancreatic head resection (LDPPHR-t) are unknown, and no relevant articles have been reported so far. The aim of this study was to identify the risk factors for achieving TO after LDPPHR-t. METHODS: The risk factors for achieving TO after LDPPHR-t were retrospectively evaluated by logistic regression analysis in 31 consecutive patients from May 2020 to December 2021. RESULTS: All LDPPHR-t procedures were successfully performed without conversion. There was no death within 90 days after surgery and no readmission within 30 days after discharge. The percentage of achieving TO after LDPPHR-t was 61.3% (19/31). Among the six TO items, the postoperative complication of grade B/C postoperative pancreatic fistula (POPF) occurred most frequently with 22.6%, followed by grade B/C bile leakage with 19.4%, Clavien-Dindo≥III complications with 19.4%, and grade B/C postpancreatectomy hemorrhage with 16.1%. POPF was the major obstacle to achieve TO after LDPPHR-t. Placing an endoscopic nasobiliary drainage (ENBD) catheter and prolonged operation time (>311 min) were significantly associated with the decreased probability of achieving TO after LDPPHR-t (odd ratio (OR), 25.775; P =0.012 and OR, 16.378; P =0.020, respectively). Placing an ENBD catheter was the only significant independent risk factor for POPF after LDPPHR-t (OR, 19.580; P =0.017). Bile leakage was the independent risk factor for postpancreatectomy hemorrhage after LDPPHR-t (OR, 15.754; P =0.040). The prolonged operation time was significantly correlated with Clavien-Dindo grade≥III complications after LDPPHR-t (OR, 19.126; P =0.024). CONCLUSION: Placing the ENBD catheter was the independent risk factor for POPF and achieving TO after LDPPHR-t. In order to reduce POPF and increase the probability of achieving TO, placing an ENBD catheter should be avoided prior to LDPPHR-t.