A LASSO Cox Regression Predictive Model for Patients Undergoing Surgery for Pancreatic Body and Tail Adenocarcinoma Patients: Comparative Long-Term Survival Analysis of Radical Antegrade Modular Pancreatosplenectomy (RAMPS) and Standard Retrograde Pancreatosplenectomy (SPRS).

PURPOSE: This study was designed to assess the advantages of radical antegrade modular pancreatosplenectomy (RAMPS) over standard retrograde pancreatosplenectomy (SPRS) in terms of disease-free survival (DFS) by comparing clinical outcomes. METHODS: Clinical data from 154 patients who underwent distal pancreatectomy at Tianjin Medical University Cancer Institute and Hospital between January 2015 and August 2018 were collected. We compared the preoperative conditions, postoperative complications, and survival outcomes of patients who underwent two different surgical procedures. By creating a LASSO-Cox model, we determined the parameters affecting DFS and the risk ratios of the two surgical procedures on DFS. RESULTS: The R0 resection rate (85.23% vs. 68.18%, P = 0.003), negative posterior margin rate (96.59% vs. 75.76%, P < 0.001), and tumor bed recurrence rate (15.29% vs. 40.00%, P = 0.001) significantly differed between the RAMPS and SPRS groups. The 1-, 3-, and 5-year survival and DFS rates of the RAMPS group were significantly better than those of the SPRS group (P < 0.05). Disease-free survival analysis based on Kaplan-Meier curves revealed that RAMPS was superior to SPRS (P < 0.001). CONCLUSIONS: We recommend RAMPS as the preferred procedure for treating ductal adenocarcinoma of the pancreatic body and tail due to its enhanced lymph node repair capacity and visualization of posterior pancreatic sections, which can increase DFS in patients.

Identification of PANoptosis-relevant subgroups and predicting signature to evaluate the prognosis and immune landscape of patients with biliary tract cancer.

BACKGROUND: This study conducted molecular subtyping of biliary tract cancer patients based on 19 PANoptosis-related gene signatures. METHODS: Through consensus clustering, patients were categorized into two subtypes, A and B. By integrating multi-omics data and clinical information from different cohorts, we elucidated the association between different subtypes of biliary tract cancer and patient prognosis, which correlated with the immune infiltration characteristics of patients. RESULTS: LASSO regression analysis was performed on the 19 gene signatures, and we constructed and validated a 9-gene risk score prognostic model that accurately predicts the overall survival rate of different biliary tract cancer patients. Additionally, we developed a predictive nomogram demonstrating the clinical utility and robustness of our model. Further analysis of the risk score-based immune landscape highlighted potential associations with immune cell infiltration, chemotherapy, and immune therapy response. CONCLUSION: Our study provides valuable insights into personalized treatment strategies for biliary tract cancer, which are crucial for improving patient prognosis and guiding treatment decisions in clinical practice.

Bowel function, quality of life, and mental health of patients with high-grade intraepithelial neoplasia or T1 colorectal cancer after organ-preserving versus organ-resection surgeries: a cross-sectional study at a Chinese tertiary care center.

BACKGROUND: This study aimed to determine the postoperative intestinal functioning, quality of life (QoL), and psychological well-being of patients treated either with organ-preserving surgery (OPS) or organ-resection surgery (ORS) for high-grade intraepithelial neoplasia (HIN) or T1 colorectal cancer (CRC). METHODS: This cross-sectional study was conducted at a single tertiary care center. In total, 175 eligible individuals with T1 CRC or HIN were divided into the OPS (n = 103) or ORS (n = 72) group based on whether the relevant segment of the intestine was preserved or resected. Intestinal function was evaluated using low anterior resection syndrome (LARS) scores. QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30 and EORTC-QLQ-CR29. Psychological status was evaluated using the Fear of Progression Questionnaire-Short Form and the Self-rating Anxiety and Depression scales. Propensity score matching (PSM) was used to minimize the influence of potential confounders. RESULTS: Overall, 130 of 175 patients (74.29%) responded to the questionnaires; 56 and 74 were in the ORS and OPS groups, respectively. Thirty-five patient pairs were successfully matched through PSM. The mild and severe LARS rates were significantly higher in the ORS group than in the OPS group (P < 0.001). The EORTC-QLQ-C30 and EORTC-QLQ-CR29 scores revealed significantly better physical, role, and emotional functioning and an overall improved state of health (with multiple reduced symptom scores) in the OPS group than in the ORS group (P < 0.05). Significantly more patients were depressed in the ORS group than in the OPS group (P = 0.034), whereas anxiety or fear of disease progression did not differ significantly between the groups. CONCLUSIONS: OPS for the treatment of HIN or T1 CRC was found to be more advantageous for patients in terms of improved intestinal function, QoL, and psychological status than was ORS.

Systematic analysis of levels of evidence supporting Chinese clinical practice guidelines for gastrointestinal disease.

BACKGROUND: Clinical practice guidelines (CPGs) inform healthcare decisions and improve patient care. However, an evaluation of guidelines on gastrointestinal diseases (GIDs) is lacking. This study aimed to systematically analyze the level of evidence (LOE) supporting Chinese CPGs for GIDs. METHODS: CPGs for GIDs were identified by systematically searching major databases. Data on LOEs and classes of recommendations (CORs) were extracted. According to the Grades of Recommendation, Assessment, Development, and Evaluation system, LOEs were categorized as high, moderate, low, or very low, whereas CORs were classified as strong or weak. Statistical analyses were conducted to determine the distribution of LOEs and CORs across different subtopics and assess changes in evidence quality over time. FINDINGS: Only 27.9% of these recommendations were supported by a high LOE, whereas approximately 70% were strong recommendations. There was a significant disparity among different subtopics in the proportion of strong recommendations supported by a high LOE. The number of guidelines has increased in the past 5 years, but there has been a concomitant decline in the proportion of recommendations supported by a high LOE. CONCLUSIONS: There is a general lack of high-quality evidence supporting Chinese CPGs for GIDs, and there are inconsistencies in strong recommendations that have not improved. This study identified areas requiring further research, emphasizing the need to bridge these gaps and promote the conduct of high-quality clinical trials. FUNDING: This study was supported by the National Key R&D Program of China (2022YFC2503604 and 2022YFC2503605) and Special Topics in Military Health Care (22BJZ25).

Macrophage-coated tumor cluster aggravates hepatoma invasion and immunotherapy resistance via generating local immune deprivation.

Immune checkpoint inhibitors (ICIs) represent a promising treatment for hepatocellular carcinoma (HCC) due to their capacity for abundant lymphocyte infiltration. However, some patients with HCC respond poorly to ICI therapy due to the presence of various immunosuppressive factors in the tumor microenvironment. Our research reveals that a macrophage-coated tumor cluster (MCTC) signifies a unique spatial structural organization in HCC correlating with diminished recurrence-free survival and overall survival in a total of 572 HCC cases from 3 internal cohorts and 2 independent external validation cohorts. Mechanistically, tumor-derived macrophage-associated lectin Mac-2 binding protein (M2BP) induces MCTC formation and traps immunocompetent cells at the edge of MCTCs to induce intratumoral cytotoxic T cell exclusion and local immune deprivation. Blocking M2BP with a Mac-2 antagonist might provide an effective approach to prevent MCTC formation, enhance T cell infiltration, and thereby improve the efficacy of ICI therapy in HCC.

Cystic tumor ablation with different concentrations of lauromacrogol solution in an animal model.

BACKGROUND: Lauromacrogol, as a sclerosing agent, can induce aseptic inflammation and fibrous tissue proliferation to achieve sclerotherapy. Lauromacrogol is widely used not only for vascular sclerotherapy but also for the treatment of different cystic tumors. To evaluate the efficacy and safety of cystic tumor ablation with different concentrations of lauromacrogol solution in a rat endometriosis model, and explore the advantages and disadvantages of this model in simulating pancreatic cystic neoplasm. METHODS: An endometriotic cyst model was established in 50 mature female Sprague-Dawley rats. After 4 weeks, successfully modeled cysts were randomly divided into four groups: group A, in which cyst were injected with normal saline; and groups B to D, in which cyst were injected with 1%, 2%, and 3% lauromacrogol solution, respectively. The rats were then fed for 4 more weeks. The abdominal cavity was opened to observe the morphology of the cyst and the degree of damage to surrounding organs. If the ablation procedure failed, the whole cyst was collected; if the ablation procedure was successful, residual scar tissue was collected. The ratio of ablated epithelial cells to the epithelial layer and the intactness of the lamina propria were observed by low- and high-power microscopy. RESULTS: After ablation, the cysts in normal saline group showed a maintained hemispherical structure, whereas those in three different concentrations of lauromacrogol solution groups showed a flat scar. The effective rate of each group was statistically different. Pairwise comparison of corrected significance levels using the Bonferroni method showed statistically a significant difference between normal saline group and 1% lauromacrogol solution group, 2% lauromacrogol solution group and 3% lauromacrogol solution group. CONCLUSIONS: According to the morphology and pathology of rat endometriotic cysts after ablation, it can be preliminarily concluded that ablation with 1%, 2%, or 3% lauromacrogol solution is an effective and safe therapeutic option. Rat endometriotic cyst model can simulate pancreatic cystic neoplasms to a certain extent.

Lenvatinib plus sintilimab with or without transarterial chemoembolization for intermediate or advanced stage hepatocellular carcinoma: a propensity score-matching cohort study.

In this retrospective study, we compared the efficacy and safety of lenvatinib plus sintilimab, with or without transarterial chemoembolization (TLS vs. LS), in patients with intermediate or advanced stage hepatocellular carcinoma (HCC). Eligible patients who received combination therapy with TLS or LS at Tianjin Medical University Cancer Institute & Hospital from December 2018 to October 2020 were propensity score matched (PSM) to correct for potential confounding biases between the two groups. The primary endpoint was progression-free survival (PFS) and secondary endpoints were overall survival (OS), overall response rate (ORR) and treatment-related adverse events (TRAEs). Cox proportional hazards models were used to identify prognostic factors. The study included 152 patients (LS group, n=54, TLS group, n=98). After PSM, patients in the TLS group had significantly longer PFS (11.1 versus 5.1 months, P=0.033), OS (not reached versus 14.0 months, P=0.0039) and ORR (modified Response Evaluation Criteria in Solid Tumors: 44.0% versus 23.1%; P=0.028) than those in the LS group. In the multivariate Cox regression analysis, the treatment regimen (TLS versus LS) was an independent predictor for both PFS (HR=0.551; 95% CI: 0.334-0.912; P=0.020) and OS (HR=0.349; 95% CI: 0.176-0.692; P=0.003) and CA19-9 level was an independent predictor for OS (HR=1.005; 95% CI: 1.002-1.008; P=0.000). No significant differences in the incidence of grade ≥3 TRAEs were reported between the two treatment groups. In conclusion, triple combination therapy with TLS improved survival with an acceptable safety profile compared with LS in patients with intermediate or advanced stage HCC.

Cholangioscopy-assisted basket extraction of choledocholithiasis through papillary support without endoscopic sphincterotomy: a pilot exploration for super minimally invasive surgery.

Video 1The procedure of cholangioscopy-assisted basket extraction of choledocholithiasis through papillary support.

Hepatic arterial infusion chemotherapy combined with anti-PD-1/PD-L1 immunotherapy and molecularly targeted agents for advanced hepatocellular carcinoma: a real world study.

Background: Molecular targeted therapy combined with immunotherapy significantly improves the prognosis of patients with advanced liver cancer. Additionally, hepatic arterial infusion chemotherapy (HAIC) can improve the prognosis of patients with advanced liver cancer. This real-world study aimed to evaluate the clinical efficacy and safety of HAIC combined with molecular targeted therapy and immunotherapy in the treatment of primary unresectable hepatocellular carcinoma (uHCC). Methods: A total of 135 patients with uHCC were enrolled in this study. Progression-free survival (PFS) was the primary endpoint. The efficacy of the combination therapy was assessed based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. Overall survival (OS), adverse events (AEs) and surgical conversion rate were the secondary endpoints. Univariate and multivariate Cox regression analyses were performed to examine independent prognostic factors. For sensitivity analysis, inverse probability weighting (IPW) was used to balance the influence of the tested confounding factors between groups to verify the robustness of conversion surgery for survival benefits. The E-values were estimated to assess robustness to unmeasured confounders. Results: The median number of therapies was three. Approximately 60% of the patients had portal vein tumour thrombosis (PVTT). The most common targeted drugs were lenvatinib and bevacizumab, whereas the most common immunotherapy drug was sintilimab. The overall objective response rate (ORR) was 54.1%, and the disease control rate (DCR) was 94.6%. A total of 97 (72%) patients experienced AEs of grades 3-4. Fatigue, pain and fever were the most common symptoms of grade 3-4 AEs. The median PFS was 28 months and 7 months in the successful and unsuccessful conversion groups, respectively. The median OS was 30 months and 15 months in the successful and unsuccessful conversion groups, respectively. Successful conversion surgery, sex, hapatic vein invasion, BCLC stage, baseline tumour size, AFP levels and maximum therapeutic response were independent prognostic factors for PFS. Successful conversion surgery, number of interventions, hapatic vein invasion and total bilirubin levels were independent prognostic factors for OS. After IPTW, no standardised differences exceeding 0.1 were found. IPW-adjusted Kaplan-Meier curves showed that successful conversion surgery was an independent prognostic factor for both PFS and OS. The E-values of successful conversion surgery were 7.57 and 6.53 for OS and PFS, respectively, which indicated a relatively robust impact of successful conversion surgery on the prognosis of patients. Conclusion: Patients with primary uHCC undergoing HAIC combined with immunotherapy and molecular targeted therapy have a higher tumour regression rate and the side effects are manageable. Patients undergoing surgery after combination therapy have survival benefits.

A Retrospective Analysis of Conversion Therapy with Lenvatinib, Sintilimab, and Arterially-Directed Therapy in Patients with Initially Unresectable Hepatocellular Carcinoma.

Purpose: The purpose of this study was to investigate the triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy as a conversion therapy for initially unresectable hepatocellular carcinoma (HCC). Patients and Methods: We retrospectively analyzed data from all HCC patients who underwent lenvatinib plus sintilimab plus arterially-directed therapy at Tianjin Medical University Cancer Hospital between December 2018 and October 2020. Of 98 enrolled patients, 37 patients were classified as potentially resectable. We compared the potentially resectable population (PRP) with the non-potentially resectable population (NPRP). The primary study endpoint was conversion rate, and secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: The baseline characteristics were comparable between populations except for a higher proportion of patients with extrahepatic metastases in the NPRP versus PRP (23/61 [37.7%] vs 3/37 [8.1%], respectively; p=0.003). For PRP, the ORR was 67.6% based on RECIST v1.1 (75.7% based on mRECIST), conversion rate was 40.5% (15/37). Of the 15 patients who underwent surgical resection, three achieved complete pathological remission. The median follow-up for all patients was 28 months (range: 2-47). For NPRP, the ORR was 22.9% based on RECIST v1.1 (31.1% based on mRECIST), The median PFS for PRP was significantly longer than that of NPRP (25 vs 13 months, p = 0.0025). The median OS for PRP was significantly longer than that of NPRP (not reached VS 21 months, p=0.014). Hypertension was the most common grade ≥3 adverse reaction in both PRP and NPRP. No new safety signals were observed for any of the treatments. Conclusion: The triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy can convert potentially unresectable HCC into resectable disease and improve long-term survival.

Diagnostic value of EUS-guided SF6 pancreatography for pancreatic cystic lesions on cyst communication with the pancreatic duct.

Background and Objectives: ERCP remains the reliable method to determine whether pancreatic cystic lesions (PCLs) and pancreatic duct communicate when other modalities (computed tomography, magnetic resonance imaging, and EUS) fail. However, complications after ERCP are still a risk that should not be ignored. In this study, we evaluated the value of EUS-guided SF6 pancreatography (ESP) for the diagnosis of PCLs focusing on pancreatic cyst communication with the pancreatic duct. Patients and Methods: We reviewed the database of medical records to retrieve the clinicopathological data of the patients with PCLs who had undergone ESP, and analyzed the diagnostic value of ESP to determine communication between the cyst and the pancreatic duct. The inclusion criteria were as follows: (1) PCLs were pathologically diagnosed by postsurgery specimen or through-the-needle biopsy and (2) ESP was performed to determine communication between the pancreatic cyst and the pancreatic duct. Results: Pathological diagnosis confirmed communication with the pancreatic duct in all eight patients with positive pancreatography, among whom seven were branch-duct-intraductal papillary mucinous neoplasm (BD-IPMN) and one was the main duct-IPMN. Pathological diagnosis confirmed noncommunication with the pancreatic duct in 20 of the 21 patients with negative pancreatography, among whom 11 were mucinous cystic neoplasm, 7 were serous cystic neoplasm, 1 was solid pseudopapillary neoplasm, 1 was pancreatic pseudocyst, and 1 was BD-IPMN. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of ESP to determine communication between the pancreatic cyst and the pancreatic duct were 96.6% (28/29), 88.9% (8/9), 100% (20/20), 100% (8/8), and 95.2% (20/21), respectively. Conclusions: ESP achieved high accuracy to determine communication between the pancreatic cyst and the pancreatic duct.

Causes of endoscopic misdiagnosis of gastrointestinal cyst as solid lesion.

BACKGROUND: To explore the causes of endoscopic misdiagnosis of gastrointestinal cyst as solid lesion and the diagnostic value and limitations of EUS, guide clinicians to develop appropriate treatment strategies and improve the ability to identify SMT. METHODS: We enrolled patients diagnosed with gastrointestinal SMT between January 2001 and December 2021 who underwent endoscopic resection with postoperative pathological diagnosis of cyst. Age, sex, maximum lesion diameter, judge the texture of lesion, origin and echo are potential factors affecting the diagnostic accuracy of cysts. RESULTS: The diagnostic accuracy of EUS assessment 39.3% higher than that without EUS assessment (6.7%). The error rate was 60.7%, lower than that without EUS assessment (93.3%), suggesting that preoperative EUS assessment improved the diagnostic accuracy of gastrointestinal cyst (Fisher's accurate test, P = 0.033). The diagnostic accuracy of "judge the texture of lesion" was higher than that of no touch (P = 0.031). When the lesion size increased by 1 cm, the diagnostic accuracy decreased by about 21%. Hypoechoic lesions were less likely to be diagnosed correctly than anechoic lesions (P = 0.003). CONCLUSIONS: The main cause of misdiagnosing gastrointestinal cyst as solid lesion is that no EUS assessment was performed before endoscopic resection or anechoic lesion was judged as hypoechoic lesion by preoperative EUS assessment.

Sintilimab, bevacizumab biosimilar, and HAIC for unresectable hepatocellular carcinoma conversion therapy: a prospective, single-arm phase II trial.

We assessed the efficacy and safety of sintilimab [an anti-programmed death (PD-1)] plus bevacizumab biosimilar (IBI305), and hepatic arterial infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC). The patients received sintilimab (200 mg) plus IBI305 (7.5 mg/kg) and HAIC (FOLFOX for 23 h) and were treated every 3 weeks. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC) per mRECIST v1.1. Twenty-nine patients were enrolled in our clinical trial (1 patient voluntarily withdrew due to adverse events after the initial treatment). Objective response was reached in 17/29 (58.6%) patients per mRECIST. A total of 19/29 (65.5%) patients became eligible for further treatment; 14 of them completed surgical resection; 1 (5.3%) achieved pathological complete response (pCR); and 5 (26.3%) reached major partial response (mPR). The 1-year OS rate was better in the PR or pCR+mPR+PR group than in the PD+SD group by either mRECIST or pathological assessment (p=0.039 and 0.006). The 1-year EFS rate was better in the PR group than in the PD+SD group by pathological assessment (p=0.007). The most common treatment-related adverse events (TEAEs) in 30 HCC patients included thrombocytopenia (40.0%), hypertension (23.3%), and leukopenia (23.3%). The grade 3-5 TEAEs that were observed were hypertension (10%), diarrhea (6.7%), asthenia (3.3%), and ascites (3.3%). Sintilimab plus IBI305 and HAIC showed promising efficacy and manageable safety in patients with unresectable HCC. It might represent a novel treatment option for these patients.