Association of Concurrent Metabolic Syndrome with Long-term Oncological Prognosis Following Liver Resection for Hepatocellular Carcinoma Among Patients with Chronic Hepatitis B Virus Infection: A Multicenter Study of 1753 Patients.

BACKGROUND: Although hepatitis B virus (HBV) infection remains the main cause of hepatocellular carcinoma (HCC) worldwide, metabolic syndrome, with its increase in prevalence, has become an important and significant risk factor for HCC. This study was designed to investigate the association of concurrent metabolic syndrome with long-term prognosis following liver resection for patients with HBV-related HCC. METHODS: From a Chinese, multicenter database, HBV-infected patients who underwent curative resection for HCC between 2010 and 2020 were identified. Long-term oncological prognosis, including overall survival (OS), recurrence-free survival (RFS), and early (≤2 years of surgery) and late (>2 years) recurrences were compared between patients with versus those without concurrent metabolic syndrome. RESULTS: Of 1753 patients, 163 (9.3%) patients had concurrent metabolic syndrome. Compared with patients without metabolic syndrome, patients with metabolic syndrome had poorer 5-year OS (47.5% vs. 61.0%; P = 0.010) and RFS (28.3% vs. 44.2%; P = 0.003) rates and a higher 5-year overall recurrence rate (67.3% vs. 53.3%; P = 0.024). Multivariate analysis revealed that concurrent metabolic syndrome was independently associated with poorer OS (hazard ratio: 1.300; 95% confidence interval: 1.018-1.660; P = 0.036) and RFS (1.314; 1.062-1.627; P = 0.012) rates, and increased rates of late recurrence (hazard ratio: 1.470; 95% confidence interval: 1.004-2.151; P = 0.047). CONCLUSIONS: In HBV-infected patients with HCC, concurrent metabolic syndrome was associated with poorer postoperative long-term oncologic survival outcomes. These results suggested that patients with metabolic syndrome should undergo enhanced surveillance for tumor recurrence even after 2 years of surgery to early detect late HCC recurrence. Whether improving metabolic syndrome can reduce postoperative recurrence of HCC deserves further exploration.

Oncological prognosis and morbidity of hepatectomy in elderly patients with hepatocellular carcinoma: a propensity score matching and multicentre study.

PURPOSE: With increasing life expectancy, the number of elderly patients (≥ 65 years) with hepatocellular carcinoma (HCC) has steadily increased. Hepatectomy remains the first-line treatment for HCC patients. However, the prognosis of hepatectomy for elderly patients with HCC remains unclear. METHODS: Clinical and follow-up data from 1331 HCC patients who underwent surgery between 2008 and 2020 were retrospectively retrieved from a multicentre database. Patients were divided into elderly (≥ 65 years) and non-elderly (< 65 years) groups, and PSM was used to balance differences in the baseline characteristics. The postoperative major morbidity and cancer-specific survival (CSS) of the two groups were compared and the independent factors that were associated with the two study endpoints were identified by multivariable regression analysis. RESULTS: Of the 1331 HCC patients enrolled in this study, 363 (27.27%) were elderly, while 968 (72.73%) were not. After PSM, 334 matched samples were obtained. In the propensity score matching (PSM) cohort, a higher rate of major morbidity was found in elderly patients (P = 0.040) but the CSS was similar in the two groups (P = 0.087). Multivariate analysis revealed that elderly age was not an independent risk factor associated with high rates of major morbidity (P = 0.117) or poor CSS (P = 0.873). The 1-, 3- and 5-year CSS rates in the elderly and non-elderly groups were 91.0% versus 86.2%, 71.3% versus 68.8% and 55.9% versus 58.0%, respectively. Preoperative alpha fetoprotein (AFP) level, Child‒Pugh grade, intraoperative blood transfusion, extended hemi hepatectomy, and tumour diameter could affect the postoperative major morbidity and preoperative AFP level, cirrhosis, Child‒Pugh grade, macrovascular invasion, microvascular invasion (MVI), satellite nodules, and tumor diameter were independently and significantly associated with CSS. CONCLUSION: Age itself had no significant effect on the prognosis of elderly patients with HCC after hepatectomy. Hepatectomy can be safely performed in elderly patients after cautious perioperative management.

Outcomes of surgery for giant hepatic hemangioma.

BACKGROUND: The surgical indications for liver hemangioma remain unclear. METHODS: Data from 152 patients with hepatic hemangioma who underwent hepatectomy between 2004 and 2019 were retrospectively reviewed. We analyzed characteristics including tumor size, surgical parameters, and variables associated with Kasabach-Merritt syndrome and compared the outcomes of laparoscopic and open hepatectomy. Here, we describe surgical techniques for giant hepatic hemangioma and report on two meaningful cases. RESULTS: Most (63.8%) patients with hepatic hemangioma were asymptomatic. Most (86.4%) tumors from patients with Kasabach-Merritt syndrome were larger than 15 cm. Enucleation (30.9%), sectionectomy (28.9%), hemihepatectomy (25.7%), and the removal of more than half of the liver (14.5%) were performed through open (87.5%) and laparoscopic (12.5%) approaches. Laparoscopic hepatectomy is associated with an operative time, estimated blood loss, and major morbidity and mortality rate similar to those of open hepatectomy, but a shorter length of stay. 3D image reconstruction is an alternative for diagnosis and surgical planning for partial hepatectomy. CONCLUSION: The main indication for surgery is giant (> 10 cm) liver hemangioma, with or without symptoms. Laparoscopic hepatectomy was an effective option for hepatic hemangioma treatment. For extremely giant hemangiomas, 3D image reconstruction was indispensable. Hepatectomy should be performed by experienced hepatic surgeons.

Circular RNA ciRS-7 promotes the proliferation and metastasis of pancreatic cancer by regulating miR-7-mediated EGFR/STAT3 signaling pathway.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the most deadly type of tumor, and its pathogenesis remains unknown. Circular RNAs (circRNAs) may be functional and bind to microRNAs and consequently, influence the activity of targeted mRNAs. Recent researches indicate that one circRNA, ciRS-7, acts as a sponge of miR-7 and thus, inhibits its activity. It is well known that miR-7 is a cancer suppressor in many cancers. However, the relationship between ciRS-7 and miR-7, and the role of ciRS-7 in PDAC, remains to be elucidated. METHODS: miR-7 and ciRS-7 expression in 41 pairs of PDAC tumors and their paracancerous tissues were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationships between their expression levels and clinicopathological features in PDAC tissues were assessed. The relationship between miR-7 and ciRS-7 was also assessed by Spearman's correlation. We also used cell lines to evaluate the role of ciRS-7 in cell line behavior. The ciRS-7 interfere RNA (siRNA) and its empty vector were transfected into PDAC cells. PDAC cells proliferation and invasion abilities were detected by MTT assay and invasion analysis. The expression of proteins was assessed by Western blotting. RESULTS: ciRS-7 expression was significantly higher in PDAC tissues than paracancerous tissues (P = 0.002). However, miR-7 expression showed the opposite trend (P = 0.048). Moreover, ciRS-7 expression was inversely correlated with miR-7 in PDAC (rs = -0.353, P = 0.023). ciRS-7 expression was also significantly elevated in venous invasion (3.72 ± 2.93 vs. 2.14 ± 1.26; P = 0.028) and lymph node metastasis (4.19 ± 2.75 vs. 2.32 ± 1.90; P = 0.016) in PDAC patients. Furthermore, ciRS-7 knockdown suppressed cell proliferation and invasion of PDAC cells (P < 0.05), and the downregulation of ciRS-7 resulted in miR-7 overexpression and subsequent inhibition of epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3). CONCLUSIONS: Circular RNA ciRS-7 plays an oncogene role in PDAC, partly by targeting miR-7 and regulating the EGFR/STAT3 signaling pathway.

Long-term outcomes after hepatectomy of huge hepatocellular carcinoma: A single-center experience in China.

BACKGROUND: Currently, hepatectomy remains the first-line therapy for hepatocellular carcinoma (HCC). However, surgery for patients with huge (>10 cm) HCCs is controversial. This retrospective study aimed to explore long-term survival after hepatectomy for patients with huge HCC. METHODS: The records of 188 patients with pathologically confirmed HCC who underwent curative hepatectomy between 2007 and 2017 were reviewed; patients were divided into three groups according to tumor size: huge (>10 cm; n = 84), large (5-10 cm; n = 51) and small (<5 cm; n = 53) HCC. Kaplan-Meier analysis was used to assess overall survival (OS) and disease-free survival (DFS), and log-rank analysis was performed for pairwise comparisons among the three groups. Risk factors for survival and recurrence were analyzed using the Cox proportional hazard model. RESULTS: The median follow-up period was 20 months. Although the prognosis of small HCC was better than that of huge and large HCC, OS and DFS were not significantly different between huge and large HCC (P = 0.099 and P = 0.831, respectively). A family history of HCC, poor Child-Pugh class, vascular invasion, diolame, pathologically positive margins, and operative time ≥240 min were identified as independent risk factors for OS and DFS in a multivariate model. Tumor size (>10 cm) had significant effect on OS, and postoperative antiviral therapy and postoperative complications also had significant effects on DFS. CONCLUSIONS: Huge HCC is not a contraindication of hepatectomy. Although most of these patients experienced recurrence after surgery, OS and DFS were not significantly different from those of patients with large HCC after resection.

BiClamp® vessel-sealing device for open hepatic resection of malignant and benign liver tumours: a single-institution experience.

BACKGROUND: Intraoperative blood loss during hepatectomy worsens prognosis, and various tools have been used to improve perioperative safety and feasibility. We aimed to retrospectively evaluate the feasibility and safety of the BiClamp® device for open liver resection. METHODS: We included 84 patients undergoing liver resection from a single centre, with all patients operated by the same surgical group. All hepatectomies were performed using BiClamp® (Erbe Elektromedizin GmbH, Tubingen, Germany), an electrosurgical device that simultaneously transects liver parenchyma and seals vessels <7 mm in diameter. We collected data on intraoperative blood loss, resection time, and perioperative complications, comparing cirrhotic and non-cirrhotic patients. RESULTS: The 84 patients enrolled in this study included 56 cirrhotic and 28 non-cirrhotic patients. All patients underwent hepatectomy (30 major and 54 minor hepatectomies) using the BiClamp®, exclusively, and 54 patients required inflow occlusion (Pringle manoeuvre). Overall intraoperative blood loss (mean ± standard deviation) was 523.5 ± 558.6 ml, liver parenchymal transection time was 36.3 ± 16.5 min (range, 13-80 min), and the mean parenchymal transection speed was 3.0 ± 1.9 cm2/min. Twelve patients received perioperative blood transfusion. The cost of BiClamp® for each patient was 800 RMB (approximately 109€). There were no deaths, and the morbidity rate was 25%. The mean (standard deviation) hospital stay was 9.3 (2.3) days. Comparisons between cirrhotic and non-cirrhotic patients revealed no difference in blood loss (491.0 ± 535.7 ml vs 588.8 ± 617.5 ml, P = 0.598), liver parenchymal transection time (34.1 ± 14.8 min vs 40.9 ± 19.2 min, P = 0.208), mean parenchymal transection speed (3.3 ± 2.1 cm2/min vs 2.5 ± 1.3 cm2/min, P = 0.217), and operative morbidity (28.6% vs 14.3%, P = 0.147). CONCLUSIONS: The reusable BiClamp® vessel-sealing device allows for safe and feasible major and minor hepatectomy, even in patients with cirrhotic liver. TRIAL REGISTRATION: This trial was retrospectively registered and the detail information was as followed. Registration number: ChiCTR-ORC-17011873 (Chinese Clinical Trial Registry). Registration Date: 2017-07-05.

A retrospective analysis of long term outcomes in patients undergoing hepatic resection for large (>5 cm) hepatocellular carcinoma.

AIM: The treatment of large (>5 cm) hepatocellular carcinoma (HCC) remains controversial. The aim of this study was to report short and long term outcomes and analyze the factors associated with long term survival for patients who underwent hepatic resection for large HCC. METHODS: All patients who underwent hepatic resection for large HCC at the department of Hepato-Pancreato-Biliary Surgery of the First Affiliated Hospital of Anhui Medical University between August 2005 and December 2011 were identified and included for analysis. Demographic and operative data, pathological findings and post-operative outcomes were entered into a computer database. Prognostic factors were analyzed by univariate and multivariate analysis. RESULTS: Ninety-nine patients were included for analysis. Two patients died within 30 days of surgery secondary to hepatic failure. The 1-, 3-, 5-year disease-free survival and overall survival rates following hepatic resection were 67%, 49%, 37% and 77%, 56%, 43%, respectively. Poor histological grade was the only independent predictor of a reduced 5-year disease-free survival. Spontaneous tumor rupture and tumor recurrence were independent predictors of a reduced 5-year overall survival. CONCLUSIONS: For selected patients with large HCC, hepatic resection can be performed safely and effectively with moderate expectation of long term survival. True cure however remains rare.

Pancreaticogastrostomy is associated with significantly less pancreatic fistula than pancreaticojejunostomy reconstruction after pancreaticoduodenectomy: a meta-analysis of seven randomized controlled trials.

OBJECTIVES: This study aimed to compare pancreaticojejunostomy (PJ) with pancreaticogastrostomy (PG) after pancreaticoduodenectomy (PD). METHODS: A literature search of PubMed and the Cochrane Central Register of Controlled Trials for studies comparing PJ with PG after PD was conducted. The primary outcome for meta-analysis was pancreatic fistula. Secondary outcomes were morbidity, mortality, biliary fistula, intra-abdominal fluid collection, hospital length of stay (LoS), postoperative haemorrhage and reoperation. Outcome measures were odds ratios (ORs) and mean differences with 95% confidence intervals (CIs). RESULTS: Seven recent RCTs encompassing 1121 patients (559 PJ and 562 PG cases) were involved in this meta-analysis. Incidences of pancreatic fistula (10.6% versus 18.5%; OR 0.52, 95% CI 0.37-0.74; P = 0.0002), biliary fistula (2.3% versus 5.7%; OR 0.42, 95% CI 0.03-3.15; P = 0.03) and intra-abdominal fluid collection (8.0% versus 14.7%; OR 0.50, 95% CI 0.34-0.74; P = 0.0005) were significantly lower in the PG than the PJ group, as was hospital LoS (weighted mean difference: -1.85, 95% CI -3.23 to -0.47; P = 0.008). Subgroup analysis indicated that severe pancreatic fistula (grades B or C) occurred less frequently in the PG than the PJ group (8.3% versus 20.5%; OR 0.37, 95% CI 0.23-0.59; P < 0.00001). However, there was no significant difference in morbidity (48.9% versus 51.0%; OR 0.90, 95% CI 0.70-1.16; P = 0.41), mortality (3.2% versus 3.5%; OR 0.82, 95% CI 0.43-1.58; P = 0.56), delayed gastric emptying (16.6% versus 14.7%; relative risk: 1.02, 95% CI 0.62-1.68; P = 0.94), postoperative haemorrhage (9.6% versus 11.1%; OR 0.82, 95% CI 0.54-1.24; P = 0.35) or reoperation (9.9% versus 9.8%; OR 0.93, 95% CI 0.60-1.43; P = 0.73). CONCLUSIONS: Pancreaticogastrostomy provides benefits over PJ after PD, including in the incidences of pancreatic fistula, biliary fistula and intra-abdominal fluid collection and in hospital LoS. Therefore, PG is recommended as a safer and more reasonable alternative to PJ reconstruction after PD.

Single-incision versus conventional three-port laparoscopic appendectomy: A meta-analysis of randomized controlled trials.

PURPOSE: The aim of this article was to compare the advantages and disadvantages of single-incision laparoscopic appendectomy (SILA) and conventional three-port laparoscopic appendectomy (CTLA). MATERIAL AND METHODS: A meta-analysis was performed by analyzing all randomized controlled trials (RCTs) published in English that compared SILA and CTLA for appendicitis in adults and children. These studies compared these two methods from different angles including outcomes of interest, patient characteristics, operative time, pain visual analogue scales scores (VAS scores), length of hospital stay, time to return to full activity, resumption of diet, postoperative complications and cosmetic results The risk ratios (RR) and mean difference (MD) with 95% confidence intervals (CIs) were employed to assess the outcome. RESULTS: Seven recent RCTs encompassing 1170 patients (586 SILA and 584 CTLA cases) were included in this meta-analysis. The pooled results demonstrated that conversion rate, drain inserted, reoperation, length of hospital stay, resumption of normal diet and postoperative complications were statistically comparable between the two groups. The postoperative abdominal pain within 24 h was -0.57 in favor of the SILA technique (p = 0.05). Compared with CTLA, SILA showed a better cosmetic satisfaction score (SMD, 0.58; 95% CI, 0.32-0.83; p < 0.0001) and shorter time to recover normal activity (WMD, -0.69; 95% CI, -1.11-0.26; p = 0.001). However, SILA has a longer operative time (WMD, 5.38; 95% CI, 2.94-7.83; p < 0.0001). CONCLUSIONS: In selected patients, SILA was confirmed to be as safe and effective as CTLA. Despite the longer operative time, SILA has higher cosmetic satisfaction and shorter recovery time to normal activity. Due to the limitations of the available data, further research is needed.

Association of Pringle maneuver with postoperative recurrence and survival following hepatectomy for hepatocellular carcinoma: a multicenter propensity score and competing-risks regression analysis.

Background: The application of Pringle maneuver (PM) during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion, but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma (HCC) remains controversial. We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC. Methods: Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified. Using two propensity score methods [propensity score matching (PSM) and inverse probability of treatment weight (IPTW)], cumulative recurrence rate and cancer-specific mortality (CSM) were compared between the patients in the PM and non-PM groups. Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors. Results: Of the 2,798 included patients, 2,404 and 394 did and did not adopt PM (the PM and non-PM groups), respectively. The rates of intraoperative blood transfusion, postoperative 30-day mortality and morbidity were comparable between the two groups (all P>0.05). In the PSM cohort by the 1:3 ratio, compared to 382 patients in the non-PM group, 1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM (63.9% and 39.1% vs. 55.3% and 31.6%, both P<0.05). Similar results were also yielded in the entire cohort and the IPTW cohort. Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts [hazard ratio (HR), 0.82 and 0.77 in the adjusted entire cohort, HR 0.80 and 0.73 in the PSM cohort, and HR 0.80 and 0.76 in the IPTW cohort, respectively]. Conclusions: The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20-25%.

[Endoscopic papillary balloon dilatation vs. endoscopic sphincteropapillotomy for common bile duct stones: a meta analysis].

OBJECTIVE: To evaluate the safety and efficacy between endoscopic papillary balloon dilatation (EPBD) and endoscopic sphincteropapillotomy ( EST) for common bile duct stones using meta-analysis method. METHODS: Randomizd controlled trials comparing EPBD with EST for common bile duct stones and published from January 1990 to July 2012 were recruited. This meta-analysis was conducted to estimate short-term and long-term complications. Fixed random effect model or random effect model was established to analyze the data. RESULTS: Twelve randomizd controlled trials were included in this analysis. These studies included 1865 patients, 925 of them were treated with EPBD and 940 were treated with EST. The analysis of basic characteristics of these included studies showed that: compared to EST, patients in the EPBD group were younger (OR = -1.16, 95% CI: -1.49 to -0.84, P = 0.00), while in two groups, there were no significant difference (P > 0.05) in gender proportion, average size of stones, number of gallstones, previous cholecystectomy, the number of merged duodenal diverticulum, common bile duct diameter, the total follow-up time. Also, compared to EST, the overall stone clearance in the EPBD group was lower (OR = 0.64, 95% CI: 0.42 to 0.96, P = 0.03), pancreatitis incidence was higher (OR = 2.67, 95% CI: 1.61 to 4.43, P = 0.00), incidence of bleeding (OR = 0.12, 95% CI: 0.04 to 0.34, P = 0.00), acute cholecystitis (OR= 0.39, 95% CI: 0.18 to 0.84, P = 0.02), total long-term complication rate (OR = 0.53, 95% CI: 0.36 to 0.77, P = 0.01), stone recurrence rate more than a year were lower (OR= 0.48, 95% CI: 0.26 to 0.90, P = 0.02). While in two groups, there were no significant difference (P > 0.05) in the stone removal on 1 '' attempt, the total near-term complications and acute cholangitis. CONCLUSIONS: On the basis of lower rates of bleeding, EPBD seems to be preferred strategy over EST for endoscopic remove of common bile duct stones in patients who have coagulopathy. Although stone recurrence rate more than a year of EPBD is lower, but the overall stone clearance rate is lower and the risk of pancreatitis is higher than that of EST.

Adjuvant immunotherapy improves recurrence-free and overall survival following surgical resection for intermediate/advanced hepatocellular carcinoma a multicenter propensity matching analysis.

Background & aims: The effectiveness of adjuvant immunotherapy to diminish recurrence and improve long-term prognosis following curative-intent surgical resection for hepatocellular carcinoma (HCC) is of increased interest, especially among individuals at high risk of recurrence. The objective of the current study was to investigate the impact of adjuvant immunotherapy on long-term recurrence and survival after curative resection among patients with intermediate/advanced HCC. Methods: Using a prospectively-collected multicenter database, patients who underwent curative-intent resection for Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC were identified. Propensity score matching (PSM) analysis was used to compare recurrence-free survival (RFS) and overall survival (OS) between patients treated with and without adjuvant immune checkpoint inhibitors (ICIs). Multivariate Cox-regression analysis further identified independent factors of RFS and OS. Results: Among the 627 enrolled patients, 109 patients (23.3%) received adjuvant immunotherapy. Most ICI-related adverse reactions were grading I-II. PSM analysis created 99 matched pairs of patients with comparable baseline characteristics between patients treated with and without adjuvant immunotherapy. In the PSM cohort, the median RFS (29.6 vs. 19.3 months, P=0.031) and OS (35.1 vs. 27.8 months, P=0.036) were better among patients who received adjuvant immunotherapy versus patients who did not. After adjustment for other confounding factors on multivariable analyzes, adjuvant immunotherapy remained independently associated with favorable RFS (HR: 0.630; 95% CI: 0.435-0.914; P=0.015) and OS (HR: 0.601; 95% CI: 0.401-0.898; P=0.013). Subgroup analyzes identified potentially prognostic benefits of adjuvant immunotherapy among patients with intermediate-stage and advanced-stage HCC. Conclusion: This real-world observational study demonstrated that adjuvant immunotherapy was associated with improved RFS and OS following curative-intent resection of intermediate/advanced HCC. Future randomized controlled trials are warranted to establish definitive evidence for this specific population at high risks of recurrence.

[Family survey and clinical analysis of von Hippel-Lindau syndrome].

OBJECTIVE: To study the clinical characteristics and summary diagnostic and therapeutical experience of von Hippel-Lindau syndrome. METHODS: von Hippel-Lindau syndrome genealogy and clinical characteristics was investigated. Then a dendrogram was drawn and a genetic analysis was performed. Last the diagnostic and therapeutical experience of von Hippel-Lindau syndrome was investigated according to literatures. RESULTS: There are 6 members attacked by the von Hippel-Lindau syndrome of 5 generations which includes 42 members. Three patients underwent operation. Two of the three patients who suffered operation had been removed of right lobe of liver tumor and one cerebellar hemangioblastomas independently. The third patient sustained three operations for removal of three cerebellar hemangioblastomas and left renal clear cell carcinoma. Three patients died of this syndrome. CONCLUSIONS: The characteristic of this kindred is according with that of autosomal dominant inheritance disease. Until now, von Hippel-Lindau syndrome involves in multisystem, the prognosis of this syndrome is not very well. However, patients and their family members may get much benefit from genetic testing, periodic surveillance, early diagnosis and prompt treatment.

Prognostic Value of Drug Targets Predicted Using Deep Bioinformatic Analysis of m6A-Associated lncRNA-Based Pancreatic Cancer Model Characteristics and Its Tumour Microenvironment.

The role of N6-methyladenosine (m6A)-associated long-stranded non-coding RNA (lncRNA) in pancreatic cancer is unclear. Therefore, we analysed the characteristics and tumour microenvironment in pancreatic cancer and determined the value of m6A-related lncRNAs for prognosis and drug target prediction. An m6A-lncRNA co-expression network was constructed using The Cancer Genome Atlas database to screen m6A-related lncRNAs. Prognosis-related lncRNAs were screened using univariate Cox regression; patients were divided into high- and low-risk groups and randomised into training and test groups. In the training group, least absolute shrinkage and selection operator (LASSO) was used for regression analysis and to construct a prognostic model, which was validated in the test group. Tumor mutational burden (TMB), immune evasion, and immune function of risk genes were analysed using R; drug sensitivity and potential drugs were examined using the Genomics of Drug Sensitivity in Cancer database. We screened 129 m6A-related lncRNAs; 17 prognosis-related m6A-related lncRNAs were obtained using multivariate analysis and three m6A-related lncRNAs (AC092171.5, MEG9, and AC002091.1) were screened using LASSO regression. Survival rates were significantly higher (p < 0.05) in the low-risk than in the high-risk group. Risk score was an independent predictor affecting survival (p < 0.001), with the highest risk score being obtained by calculating the c-index. The TMB significantly differed between the high- and low-risk groups (p < 0.05). In the high- and low-risk groups, mutations were detected in 61 of 70 samples and 49 of 71 samples, respectively, with KRAS, TP53, and SMAD4 showing the highest mutation frequencies in both groups. A lower survival rate was observed in patients with a high versus low TMB. Immune function HLA, Cytolytic activity, and Inflammation-promoting, T cell co-inhibition, Check-point, and T cell co-stimulation significantly differed in different subgroups (p < 0.05). Immune evasion scores were significantly higher in the high-risk group than in the low-risk group. Eight sensitive drugs were screened: ABT.888, ATRA, AP.24534, AG.014699, ABT.263, axitinib, A.443654, and A.770041. We screened m6A-related lncRNAs using bioinformatics, constructed a prognosis-related model, explored TMB and immune function differences in pancreatic cancer, and identified potential therapeutic agents, providing a foundation for further studies of pancreatic cancer diagnosis and treatment.

Online calculator for predicting the risk of malignancy in patients with pancreatic cystic neoplasms: A multicenter, retrospective study.

BACKGROUND: Efficient and practical methods for predicting the risk of malignancy in patients with pancreatic cystic neoplasms (PCNs) are lacking. AIM: To establish a nomogram-based online calculator for predicting the risk of malignancy in patients with PCNs. METHODS: In this study, the clinicopathological data of target patients in three medical centers were analyzed. The independent sample t-test, Mann-Whitney U test or chi-squared test were used as appropriate for statistical analysis. After univariable and multivariable logistic regression analysis, five independent factors were screened and incorporated to develop a calculator for predicting the risk of malignancy. Finally, the concordance index (C-index), calibration, area under the curve, decision curve analysis and clinical impact curves were used to evaluate the performance of the calculator. RESULTS: Enhanced mural nodules [odds ratio (OR): 4.314; 95% confidence interval (CI): 1.618-11.503, P = 0.003], tumor diameter ≥ 40 mm (OR: 3.514; 95%CI: 1.138-10.849, P = 0.029), main pancreatic duct dilatation (OR: 3.267; 95%CI: 1.230-8.678, P = 0.018), preoperative neutrophil-to-lymphocyte ratio ≥ 2.288 (OR: 2.702; 95%CI: 1.008-7.244, P = 0.048], and preoperative serum CA19-9 concentration ≥ 34 U/mL (OR: 3.267; 95%CI: 1.274-13.007, P = 0.018) were independent risk factors for a high risk of malignancy in patients with PCNs. In the training cohort, the nomogram achieved a C-index of 0.824 for predicting the risk of malignancy. The predictive ability of the model was then validated in an external cohort (C-index: 0.893). Compared with the risk factors identified in the relevant guidelines, the current model showed better predictive performance and clinical utility. CONCLUSION: The calculator demonstrates optimal predictive performance for identifying the risk of malignancy, potentially yielding a personalized method for patient selection and decision-making in clinical practice.

Clinical online nomogram for predicting prognosis in recurrent hepatolithiasis after biliary surgery: A multicenter, retrospective study.

BACKGROUND: Methods for predicting the prognosis of patients undergoing surgery for recurrent hepatolithiasis after biliary surgery are currently lacking. AIM: To establish a nomogram to predict the prognosis of patients with recurrent hepatolithiasis after biliary surgery. METHODS: In this multicenter, retrospective study, data of consecutive patients in four large medical centers who underwent surgery for recurrent hepatolithiasis after biliary surgery were retrospectively analyzed. We constructed a nomogram to predict the prognosis of recurrent hepatolithiasis in a training cohort of 299 patients, following which we independently tested the nomogram in an external validation cohort of 142 patients. Finally, we used the concordance index (C-index), calibra-tion, area under curve, decision curve analysis, clinical impact curves, and visual fit indices to evaluate the accuracy of the nomogram. RESULTS: Multiple previous surgeries [2 surgeries: Odds ratio (95% confidence interval), 1.451 (0.719-2.932); 3 surgeries: 4.573 (2.015-10.378); ≥ 4 surgeries: 5.741 (1.347-24.470)], bilateral hepatolithiasis [1.965 (1.039-3.717)], absence of immediate clearance [2.398 (1.304-4.409)], neutrophil-to-lymphocyte ratio ≥ 2.462 [1.915 (1.099-3.337)], and albumin-to-globulin ratio ≤ 1.5 [1.949 (1.056-3.595)] were found to be independent factors influencing the prognosis. The nomogram constructed on the basis of these variables showed good reliability in the training (C-index: 0.748) and validation (C-index: 0.743) cohorts. Compared with predictions using traditional classification models, those using our nomogram showed better agreement with actual observations in the calibration curve for the probability of endpoints and the receiver operating characteristic curve. Dichloroacetate and clinical impact curves showed a larger net benefit of the nomogram. CONCLUSION: The nomogram developed in this study demonstrated superior performance and discriminative power compared to the three traditional classifications. It is easy to use, highly accurate, and shows excellent calibration.

Development and validation of safety and efficacy-associated risk calculator for hepatocellular carcinoma in the elderly after resection (SEARCHER): A multi-institutional observational study.

BACKGROUND: Increased life expectancy and improved perioperative management have resulted in increased utilization of hepatectomy for hepatocellular carcinoma (HCC) among elderly patients. However, individualized model for predicting the surgical safety and efficacy is lacking. The present study aimed to develop a safety and efficacy-associated risk calculator for HCC in the elderly after resection (SEARCHER). METHODS: From an international multicenter database, elderly patients who underwent curative-intent hepatectomy for HCC were stratified by patient age: 65-69 years, 70-74 years, 75-79 years, and ≥80 years. Short- and long-term outcomes among the 4 groups were compared. Univariate and multivariate analyses of risk factors of postoperative major morbidity, cancer-specific survival (CSS) and overall survival (OS) were performed in the training cohort. A nomogram-based online calculator was then constructed and validated in the validation cohort. RESULTS: With increasing age, the risk of postoperative major morbidity and worse OS increased (P = 0.001 and 0.020), but not postoperative mortality and CSS (P = 0.577 and 0.890) among patients across the 4 groups. Based on three nomograms to predict major morbidity, CSS and OS, the SEARCHER model was constructed and made available at https://elderlyhcc.shinyapps.io/SEARCHER. The model demonstrated excellent calibration and optimal performance in both the training and validation cohorts, and performed better than the several commonly-used conventional scoring and staging systems of HCC. CONCLUSIONS: With higher potential postoperative major morbidity and worse OS as patients age, the decision of whether to perform a hepatectomy for HCC needs to be comprehensively considered in the elderly. The proposed SEARCHER model demonstrated good performance to individually predict safety and efficacy of hepatectomy in elderly patients with HCC.

[Percutaneous radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma: a meta analysis].

OBJECTIVE: To evaluate the curative effect of percutaneous radiofrequency ablation (RFA) and hepatic resection (RES) for small hepatocarcinoma eligible for Milan criterion using meta analysis method. METHODS: Retrieved clinical trials comparing percutaneous radiofrequency ablation with RES for small hepatocarcinoma published from 1990 to 2010. A meta-analysis was conducted to estimate overall survival and disease free survival. A fixed random effect model or random effect model was established to collect the data. RESULTS: Four randomized controlled trials were included in this analysis. These studies included a total of 539 patients: 252 treated with percutaneous RFA and 287 treated with RES. The differences in overall survival were not statistically significant between RFA and RES (P > 0.05). In the patients treated with RES group, the 2-, 3- and 4-years disease free survival rates were significantly better than that in the patients treated with percutaneous RFA (P < 0.05). The postoperative morbidity rate was significant lower in patients treated with percutaneous RFA (OR: 0.14, 95%CI: 0.09 - 0.22, P = 0.000). But percutaneous RFA had a higher rate of tumor recurrence compared to RES (OR: 2.63, 95%CI: 1.67 - 4.15, P = 0.000). CONCLUSIONS: For small hepatocarcinoma eligible for Milan criterion, percutaneous RFA had a similar overall survival to RES. Percutaneous RFA was the invasive lesser and had a lower postoperative morbidity rate than RES, but RES may had a better prevention of the tumor recurrence than percutaneous RFA. For those patients who don't want to be treated by RES, percutaneous RFA may be a recommendable choice.

Systematic review of outcomes and meta-analysis of risk factors for prognosis after liver resection for hepatocellular carcinoma without cirrhosis.

Long-term overall survival (OS) after liver resection for non-cirrhotic hepatocellular carcinoma (NCHCC) has been reported recently. The aim of this study was to review outcomes systematically and analyze risk factors for survival after surgical resection for HCC without cirrhosis. A literature search was performed of the PubMed and Embase databases for papers published between January 1995 and October 2012, which focused on hepatic resection for HCC without underlying cirrhosis. Cochrane systematic review methodology was used for this review. Outcomes were OS, operative mortality and disease-free survival (DFS). Pooled hazard ratios (HR) were calculated using the random effects model for parameters considered as potential prognostic factors. Totally, 26 retrospective case series were eligible for inclusion. The 1-, 3- and 5-year OS rate after surgical resection of NCHCC ranged from 62% to 100%, 46.3%-78.0%, and 30%-64%, respectively. The corresponding DFS rates ranged from 48.7% to 84%, 31.0%-66.0%, and 24.0%-58.0%, respectively. Five variables were related to poor survival: multiple tumors (HR 1.68, 95%CI 1.25-2.11); larger tumor size (HR 2.66, 95%CI 1.69-3.63); non-clear resection margin (R0 resection) (HR 3.52, 95%CI 1.63-5.42); poor tumor stage (HR 2.61, 95%CI 1.64-3.58); and invasion of the lymphatic vessels (HR 4.85, 95%CI 2.67-7.02). In sum, hepatic resection provides excellent OS rates for patients with NCHCC, and results have tended to improve recently. Risk factors for poor prognosis comprise multiple tumors, lager tumor size, non-R0 resection and invasion of the lymphatic vessels.