Risk factor analysis of conversion in laparoscopic liver resection for intrahepatic cholangiocarcinoma.

BACKGROUND: The risk factors of patients with intrahepatic cholangiocarcinoma (ICC) requiring conversion to open surgery have not been adequately studied. This study aimed to determine the risk factors and postoperative outcomes of conversion in patients with ICC. METHODS: From May 2014 to September 2022, Unplanned conversions were compared with successful LLRs. RESULTS: 153 patients with ICC initially underwent LLR, of which 41 (26.8%) required conversion to open surgery. Multivariate analysis for those factors that were statistically significant or confirmed by clinical studies, tumor proximity to the major vessels (OR 6.643, P < 0.001), and previous upper abdominal surgery (OR 3.140, P = 0.040) were independent predictors of unplanned conversions. Compared to successful LLRs, unplanned conversions showed longer operative times (300.0 vs. 225.0 min, P < 0.001), more blood loss (500.0 vs. 200.0 mL, P < 0.001), higher transfusion rates (46.3% vs. 11.6%, P < 0.001), longer length of stays (13.0 vs. 8.0 days, P < 0.001), and higher rates of major morbidity (39.0% vs. 11.6%, P < 0.001). However, there was no statistically significant difference in 30-day or 90-day mortality between the conversion group and the laparoscopic group. CONCLUSION: Conversion during LLR should be anticipated in ICC patients with prior upper abdominal surgery or tumor proximity to major vessels as features.

Safety and feasibility of laparoscopic liver resection for intrahepatic cholangiocarcinoma: a propensity score-matched study.

BACKGROUND: Laparoscopic liver resection (LLR) is controversial in treating intrahepatic cholangiocarcinoma (ICC). Therefore, this study aimed to evaluate the safety and feasibility of LLR for the treatment of ICC and explored the independent factors affecting the long-term prognosis of ICC. METHODS: We included 170 patients undergoing hepatectomy for ICC from December 2010 to December 2021 and divided them into LLR group and open liver resection (OLR) group. We used propensity score matching (PSM) analysis to reduce the impact of data bias and confounding variables and then compared the short-term and long-term prognosis of LLR and OLR in treating ICC; Cox proportional hazards regression model was adopted to explore the independent factors affecting the long-term prognosis of ICC. RESULTS: A total of 105 patients (70 in the LLR group and 35 in the OLR group) were included after 2:1 PSM analysis. There was no difference in demographic characteristics and preoperative indexes between the two groups. The perioperative results of the OLR group were worse than those of the LLR group, that is, the intraoperative blood transfusion rate (24 (68.6) vs 21 (30.0)), blood loss (500 (200-1500) vs 200 (100-525)), and the morbidity of major postoperative complications (9 (25.7) vs 6 (8.5)) in the OLR group were worse than those in LLR group. LLR could enable patients to obtain an equivalent long-term prognosis compared to OLR. The Cox proportional hazards regression model exhibited that no matter before or after PSM, preoperative serum CA12-5 and postoperative hospital stay were independent factors affecting overall survival, while only lymph node metastasis independently influenced recurrence-free survival. CONCLUSIONS: Compared with ICC treated by OLR, the LLR group obtained superior perioperative period outcomes. In the long run, LLR could enable ICC patients to receive an equivalent long-term prognosis compared to OLR. In addition, ICC patients with preoperative abnormal CA12-5, lymph node metastasis, and more extended postoperative hospital stay might suffer from a worse long-term prognosis. However, these conclusions still need multicenter extensive sample prospective research to demonstrate.

Global research trends and foci of artificial intelligence-based tumor pathology: a scientometric study.

BACKGROUND: With the development of digital pathology and the renewal of deep learning algorithm, artificial intelligence (AI) is widely applied in tumor pathology. Previous researches have demonstrated that AI-based tumor pathology may help to solve the challenges faced by traditional pathology. This technology has attracted the attention of scholars in many fields and a large amount of articles have been published. This study mainly summarizes the knowledge structure of AI-based tumor pathology through bibliometric analysis, and discusses the potential research trends and foci. METHODS: Publications related to AI-based tumor pathology from 1999 to 2021 were selected from Web of Science Core Collection. VOSviewer and Citespace were mainly used to perform and visualize co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references and keywords in this field. RESULTS: A total of 2753 papers were included. The papers on AI-based tumor pathology research had been continuously increased since 1999. The United States made the largest contribution in this field, in terms of publications (1138, 41.34%), H-index (85) and total citations (35,539 times). We identified the most productive institution and author were Harvard Medical School and Madabhushi Anant, while Jemal Ahmedin was the most co-cited author. Scientific Reports was the most prominent journal and after analysis, Lecture Notes in Computer Science was the journal with highest total link strength. According to the result of references and keywords analysis, "breast cancer histopathology" "convolutional neural network" and "histopathological image" were identified as the major future research foci. CONCLUSIONS: AI-based tumor pathology is in the stage of vigorous development and has a bright prospect. International transboundary cooperation among countries and institutions should be strengthened in the future. It is foreseeable that more research foci will be lied in the interpretability of deep learning-based model and the development of multi-modal fusion model.

High-intensity focused ultrasound alone or combined with transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with unsuitable indications for hepatectomy and radiofrequency ablation: a phase II clinical trial.

OBJECTIVES: This study aims to evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) alone or combined with transcatheter arterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) but were contraindicated for hepatectomy and radiofrequency ablation (RFA). METHODS: Patients between 20 and 80 years of age with 1-3 foci of HCC were selected. Included patients have had primary or recurrent liver lesions with no evidence of extra-hepatic metastasis prior to the study. Patients were treated with ultrasound-guided HIFU alone or HIFU combined with TACE (treated with TACE once within 4 weeks prior to receiving HIFU). RESULTS: Thirty-seven patients were enrolled, for a total of 45 lesions. The 2-year local control (LC) rate was 73.0% and the median LC time was 22 months. The 2-year progression-free survival (PFS) was 29.7% and the median PFS time was 9 months. Finally, the 2-year overall survival (OS) was 70.3%, and the median OS time was 24 months. The most common adverse events (AEs) were elevated liver enzymes, followed by fatigue, and pain, no grade 4 AEs or death occurred. Multivariate analysis showed that age, Child-Pugh class, and the number of tumors were independent prognostic factors for PFS and that the AFP levels and the number of tumors were significantly correlated with the OS. CONCLUSIONS: This study indicates that the HIFU/HIFU combined with TACE treatment is safe, and is capable of achieving both a good LC rate and a considerably good prognosis. The procedure should be considered for patients who were deemed unsuitable for other local treatments.

Efficacy of laparoscopic repeat hepatectomy compared with open repeat hepatectomy: a single-center, propensity score matching study.

INTRODUCTION: Laparoscopic repeat hepatectomy (LRH) is considered to be a technically challenging procedure which has not been widely applied. This study aimed to assess the accessibility and security of LRH for patients with hepatic tumor recurrence. METHODS: Between January 2010 and October 2020, we performed 48 LRHs and 31 open repeat hepatectomies (ORHs) for recurrent liver cancer. LRHs were matched to ORHs (1:1) using propensity score matching (PSM) created by comparing preoperative factors. The perioperative data of patients were retrospectively analyzed, including baseline data, operative time, intraoperative blood loss, pathology, days of postoperative stay, complication morbidity, and mortality within 30 days. Overall survival and recurrence-free survival rates with appropriate follow-up were obtained to evaluate the long-term outcomes. RESULTS: Compared with the ORH, LRH was related with shorter operative duration (169.9 versus 232.9 ml, p < 0.01), less intraoperative bleeding (100.0 versus 500.0 ml, p < 0.01), lower rate of blood transfusion (8.3% versus 58.1%, p < 0.01), and shorter hospitalization (5.0 versus 11.0 days, p < 0.01). The median follow-up was 31 months. The LRH 1-, 3-, and 5-year overall survival were 77.1%, 61.6%, and 46.2% versus 82.3%, 66.5%, and 29.5% for ORH (p = 0.77). The 1-, 3-, and 5-year disease-free survival rates of the two groups were 73.4%, 62.0%, and 44.3% versus 66.1%, 44.1%, and 14.7%, respectively (p = 0.22). CONCLUSIONS: Laparoscopic repeated hepatectomy is safe and practicable with great short-term results for selected patients.

A Meta-Analysis of Prognostic Factors in Patients with Posterior Circulation Stroke after Mechanical Thrombectomy.

BACKGROUND: Posterior circulation stroke is characterized by poor prognosis because its optimal thrombolysis "time window" is always missed. After mechanical thrombectomy (MT), the recanalization rate of posterior circulation obstruction is significantly increased, but prognosis remains poor. To best manage patients, prognostic factors are needed to inform MT triaging after posterior circulation stroke. METHODS: A systematic literature search was done for the period through April 2020. Studies included those with posterior circulation stroke cases that underwent MT. The primary outcome measure in this study was the modified Rankin Scale on day 90. RESULTS: No outcome differences were found in gender, atrial fibrillation, smoking, and coronary artery disease (OR = 1.07, 95% CI: 0.90-1.28; OR = 1.02, 95% CI: 0.82-1.26; OR = 1.26, 95% CI: 0.94-1.68; and OR = 0.84, 95% CI: 0.58-1.22, respectively). Hypertension, diabetes mellitus, and previous stroke correlated with poorer prognosis (OR = 0.61, 95% CI: 0.48-0.77; OR = 0.60, 95% CI: 0.50-0.73; and OR = 0.74, 95% CI: 0.55-0.99, respectively). However, hyperlipidemia correlated with better prognosis (OR = 1.28, 95% CI: 1.04-1.58). CONCLUSION: Our analysis indicates that hypertension, diabetes mellitus, or previous stroke correlate with poorer outcomes. Intriguingly, hyperlipidemia correlates with better prognosis. These factors may help inform triage decisions when considering MT for posterior circulation stroke patients. However, large, multicenter, randomized controlled trials are needed to validate these observations.

Comparison of Quality of Life and Nutritional Status of Between Roux-en-Y and Billroth-I Reconstruction After Distal Gastrectomy: A Systematic Review and Meta-Analysis.

Background: This paper purports to use a meta-analysis to compare the postoperative quality of life (QoL) and nutritional status of between Roux-en-Y (R-Y) and Billroth-I (B-I) reconstruction after distal gastrectomy.Methods: For this study, the following databases were searched for articles published from inception until December 2018: PubMed, Web of Science, EBSCO, and Cochrane library.Results: A total of 13 eligible studies, covering 3645 patients, were selected for a meta-analysis. The analysis showed that compared with B-I group in term of short-term outcomes, patients undergoing R-Y reconstruction did not only have significantly better physiological function (P = 0.02), but had significantly less pain (P = 0.04). In the long-term outcomes, the dyspnea and constipation in the B-I group were worse than that in the R-Y group (P = 0.004; P = 0.04, respectively). Patients in the B-I group had higher cholesterol than those in the R-Y group at 5 years postoperatively (P = 0.003). There were no significant differences in termof other nutritional indicators including total protein, cholesterol, albumin, hemoglobin and weight in short-term outcomes.Conclusions: The final conclusion was that R-Y may be superior to the B-I reconstruction in some aspects of QoL. Besides, R-Y reconstruction could reduce the patient's cholesterol level for a long time. For the short-term outcomes, there were no significant differences in other common nutritional indicators.

Comparison of tenofovir versus entecavir on reducing incidence of hepatocellular carcinoma in chronic hepatitis B patients: A systematic review and meta-analysis.

BACKGROUND AND AIM: Studies had shown that tenofovir (TDF) and entecavir (ETV) are widely used as the first-line therapy to inhibit hepatitis B virus replication, which can reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients, but it was unclear which nucleos(t)ide analogue was most effective. Therefore, we performed a meta-analysis and a systematic review to compare the incidence of HCC in CHB patients who are either on TDF or ETV. METHODS: For this study, the following databases were searched for clinical trials published from its inception until November 2019: PubMed, Web of Science, MEDLINE, Embase, and Cochrane Library. RESULTS: A total of 11 eligible studies were selected, including 70 864 patients. The meta-analysis showed that TDF was superior to ETV with regard to the incidence of HCC, the incidence of death or transplantation, and virologic response. There were no significant differences in terms of biochemical response and loss of seroconversion response among the entire cohort. CONCLUSIONS: The conclusion was that CHB patients treated with TDF had a reduced incidence of HCC compared with patients treated with ETV.

Smokers or non-smokers: who benefits more from immune checkpoint inhibitors in treatment of malignancies? An up-to-date meta-analysis.

BACKGROUND: Immune checkpoint inhibitors, which are a milestone in anti-cancer therapy, have been applied in the treatment of multiple malignancies. Real-world data have suggested that smoking status may be associated with the efficacy of anti-PD-1/PD-L1 therapy. Hereby, to evaluate "smoking benefit or not", we included numerous high-quality randomized controlled clinical trials (RCTs) without any restriction on category. METHODS: A systematic search of online database was performed from July 2010 to July 2019. Eligible studies included phase II/III RCTs comparing PD-1/PD-L1 inhibitors with chemotherapy in the treatment of multiple carcinomas and contained subgroup analysis of smoking status. Then, related hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) were pooled. RESULTS: In the initial meta-analysis, compared with chemotherapy, the OS of non-smokers (HR, 0.81; 95% CI, 0.67-0.98) and smokers (HR, 0.77; 95% CI, 0.71-0.83) were significantly prolonged with PD-1/PD-L1 inhibitors. Outcomes from subgroup analysis showed that in anti-PD-1/PD-L1 monotherapy groups, non-smokers showed no significant improvement in OS (HR, 0.94; 95% CI, 0.83-1.06), while the OS of smokers was significantly prolonged (HR, 0.79; 95% CI, 0.74-0.85); in groups of PD-1/PD-L1 inhibitors combined with chemotherapy, the OS of non-smokers (HR, 0.45; 95% CI, 0.28-0.71) and smokers (HR, 0.72; 95% CI, 0.61-0.85) were significantly prolonged. Combined ipilimumab and chemotherapy showed no significance in both groups. CONCLUSION: Smokers benefit from either anti-PD-1/PD-L1 monotherapy or the combined regimen compared with chemotherapy. Considering cost-effectiveness, monotherapy was recommended to smokers. For non-smokers, only the combined regimen was feasible in non-small cell lung cancer.

The relationship between the number of examined lymph nodes and the efficacy of chemotherapy for gastric cancer.

BACKGROUND: The purpose of this research was to investigate the relationship between the number of examined lymph nodes (eLNs) and the prognosis. METHODS: A retrospective examination of reports and studies carried out at two institutions was conducted. According to TNM stages, the relationship between the number of eLNs and the prognosis was analyzed. RESULTS: The 5-year disease-specific survival (DSS) of all enrolled patients was 66.3%. A multivariate analysis showed the type of gastrectomy, histologic type, perineural invasion, pT stage, pN stage, chemotherapy and eLNs to be independent prognostic markers. Additionally, with the exception of patients with stage I disease, the 5-year DSS of patients who had < 25 eLNs removed had a higher risk of having a worst prognosis compared to patients who had ≥ 25 eLNs removed. Through this study, a hypothetical TNM staging system was obtained for predicting the prognosis according to the number of eLNs. Chemotherapy was able to improve the prognosis of patients with stage III and < 25 eLNs in stage II. CONCLUSIONS: Extended lymphadenectomy with a new goal of dissecting 25 LNs for the evaluation of stage II-III cancer cases is recommended. Our hypothetical TNM staging system may be able to stratify the risk more accurately compared to the current AJCC 8th system. Chemotherapy can improve the prognosis in advanced gastric cancer, but its benefit may be affected by the surgical quality.

A meta-analysis of the medium- and long-term effects of laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are two representative bariatric surgeries. This study aimed to compare the effects of the LSG and LRYGB based on high-quality analysis and massive amount of data. METHODS: For this study databases of PubMed, Web of Science, EBSCO, Medline, and Cochrane Library were searched for articles published until January 2019 comparing the outcomes of LSG and LRYGB. RESULTS: This study included 28 articles. Overall, 9038 patients (4597, LSG group; 4441, LRYGB group) were included. The remission rate of type 2 diabetes mellitus (T2DM) in the LRYGB group was superior to that in the LSG group at the 3-years follow-up. Five-year follow-up results showed that LRYGB had an advantage over LSG for the percentage of excess weight loss and remission of T2DM, hypertension, dyslipidemia, and abnormally low-density lipoprotein. CONCLUSIONS: In terms of the long-term effects of bariatric surgery, the effect of LRYGB was better than of LSG.

Clinicopathological and prognostic significance of PD-L1 expression in colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: To analyze the prognostic value of programmed death factor ligand 1 (PD-L1) in colorectal cancer. METHODS: Electronic databases, such as PubMed, Web of Science, Embase, and Cochrane library, were searched to identify studies evaluating the PD-L1 expression and overall survival (OS) in these patients. Afterwards, the relevant data were extracted to perform the meta-analysis. RESULTS: A total of 3481 patients were included in 10 studies. The combined hazard ratio (HR) was 1.22 (95%CI = 1.01-1.48, P = 0.04), indicating that high expression of PD-L1 was significantly correlated with poor prognosis of colorectal cancer. Apropos of clinicopathological features, the merged odds ratio (OR) exhibited that highly expressed PD-L1 was firmly related to lymphatic invasion (OR = 3.49, 95%CI = 1.54-7.90, P = 0.003) and advanced stage (OR = 1.77, 95%CI = 1.41-2.23, P < 0.00001), but not correlative with patients' gender, microsatellite instability, or tumor location. CONCLUSION: The expression of PD-L1 can be utilized as an independent factor in judging the prognosis of colorectal cancer, and patients with advanced cancer or lymphatic invasion are more likely to express PD-L1. This conclusion may lay a theoretical foundation for the application of PD-1/PD-L1 immunoassay point inhibitors but still needs verifying by sizeable well-designed cohort studies.

Pancreaticoduodenectomy versus limited resection for duodenal gastrointestinal stromal tumors: a systematic review and meta-analysis.

BACKGROUND: By comparing the long-term prognostic outcomes after pancreaticoduodenectomy (PD) and limited resection (LR), this study aimed to investigate the optimal surgical modality for duodenal gastrointestinal stromal tumors (GISTs). METHODS: Two authors independently searched PubMed, Web of Science, Embase, and the Cochrane Library for published articles comparing the long-term prognostic and clinicopathological factors of duodenal GIST patients undergoing PD versus LR. Relevant information was extracted and analyzed. RESULTS: After screening, 10 items comprising 623 cases were eventually included. This meta-analysis explicitly indicated that PD treatment was associated with worse long-term prognosis (hazard ratio = 1.93; 95% confidence interval [CI], 1.39-2.69; p < 0.001; I2 = 0) and more complications (odds ratio [OR] = 2.90; 95% CI, 1.90-4.42; p < 0.001; I2 = 10%) than LR treatment. Nevertheless, for duodenal GISTs, PD was related to the following clinicopathological features: invasion of the second part of the duodenum (OR = 3.39; 95% CI, 1.69-6.79; p < 0.001; I2 = 50%), high-degree tumor mitosis (> 5/50 high-power fields; OR = 2.24; 95% CI, 1.42-3.52; p < 0.001; I2 = 0), and high-risk classification (OR = 3.17; 95% CI; 2.13-4.71; p < 0.001; I2 = 0). CONCLUSIONS: Since PD is associated with worse long-term prognosis and more complications, its safety and efficacy should be ascertained. Our findings recommend the use of LR to obtain negative incision margins when conditions permit it.

A meta-analysis of comparison of proximal gastrectomy with double-tract reconstruction and total gastrectomy for proximal early gastric cancer.

BACKGROUND: In theory, proximal gastrectomy with double-tract reconstruction (PG-DT) was superior to total gastrectomy (TG) in hematologic and nutritional outcomes. However, its clinical effects in proximal early gastric cancer (EGC) have been controversial. METHODS: The purpose of this study was to investigate the outcomes of laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DT) for proximal EGC. For this systematic review and meta-analysis, we searched for articles published before December of 2018 in the following databases: PubMed, Web of Science, EBSCO, Medline, and Cochrane Library. RESULTS: The results showed no significant difference in the anastomotic stenosis (OR = 0.91, 95%CI = 0.33-2.50, p = 0.85) and reflux esophagitis (OR = 1.87, 95%CI = 0.62-5.65, p = 0.27) between LPG-DT and laparoscopic total gastrectomy (LTG). The vitamin B12 supplementation rate in the LPG-DT group was lower than the LTG group (OR = 0.06, 95%Cl = 0.01-0.59, p = 0.02). CONCLUSIONS: Due to comparable clinical effect, PG-DT is comparable to TG for patients with proximal EGC. In addition, LPG-DT not only appears superior to TG in terms of preventing vitamin B12 deficiency, but also does not increase the risk of anastomotic stricture and reflux esophagitis.

A bibliometric insight into neoadjuvant chemotherapy in bladder cancer: trends, collaborations, and future avenues.

Background: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) remains the cornerstone of treatment for muscle-invasive bladder cancer (MIBC). While platinum-based regimens have demonstrated benefits in tumor downstaging and improved long-term survival for selected patients, they may pose risks for those who are ineligible or unresponsive to chemotherapy. Objective: We undertook a bibliometric analysis to elucidate the breadth of literature on NAC in bladder cancer, discern research trajectories, and underscore emerging avenues of investigation. Methods: A systematic search of the Web of Science Core Collection (WoSCC) was conducted to identify articles pertaining to NAC in bladder cancer from 1999 to 2022. Advanced bibliometric tools, such as VOSviewer, CiteSpace, and SCImago Graphica, facilitated the examination and depicted the publication trends, geographic contributions, institutional affiliations, journal prominence, author collaborations, and salient keywords, emphasizing the top 25 citation bursts. Results: Our analysis included 1836 publications spanning 1999 to 2022, indicating a growing trend in both annual publications and citations related to NAC in bladder cancer. The United States emerged as the predominant contributor in terms of publications, citations, and international collaborations. The University of Texas was the leading institution in publication output. "Urologic Oncology Seminars and Original Investigations" was the primary publishing journal, while "European Urology" boasted the highest impact factor. Shariat, Shahrokh F., and Grossman, H.B., were identified as the most prolific and co-cited authors, respectively. Keyword analysis revealed both frequency of occurrence and citation bursts, highlighting areas of concentrated study. Notably, the integration of immunochemotherapy is projected to experience substantial growth in forthcoming research. Conclusions: Our bibliometric assessment provides a panoramic view of the research milieu surrounding neoadjuvant chemotherapy for bladder cancer, encapsulating the present state, evolving trends, and potential future directions, with a particular emphasis on the promise of immunochemotherapy.

Estimation of the tumor size at cure threshold among adult patients with adrenocortical carcinoma: A populational-based study.

Background: The prognostic significance of tumor size with adrenocortical carcinoma (ACC) patients has not yet been thoroughly evaluated. Our objective was to investigate the influence of tumor size on prognostic value in adult ACC patients. Methods: The Surveillance, Epidemiology and End Results Program (SEER) was employed to identify adult ACC patients who had been diagnosed from 2004 to 2015. The "X-Tile" program determined the optimal cutoff value of tumor size. Cancer-specific survival (CSS) and overall survive (OS) were estimated. The survival outcomes and risk factors were analyzed by the Kaplan-Meier methods and the multivariable cox regression respectively. Results: A total 426 adult ACC patients were included. Univariable and multivariable cox analysis revealed age, larger tumor size and metastasis as consistent predictors of lower CSS and OS. The optimal cutoff value of tumor size was identified as 8.5 cm using X-tile software, and Kaplan-Meier method showed dramatic prognostic difference between patients with larger tumors (＞8.5 cm) and smaller tumors (≤8.5 cm) (log-rank test, P < 0.001). Subgroup analyses revealed no statistical significance and a consistent proportionate effect of tumor size on CSS and OS across all eight pre-specified subgroups. Interestingly, an additional subgroup analysis showed that ACC patients could not benefit from chemotherapy in terms of CSS and OS. Conclusion: The study suggests that tumor size is a crucial prognostic factor in ACC patients and a cutoff value 8.5 cm might indicate a poor outcome. Given the limitations of the available data, it is challenging to conclusively determine the benefit of chemotherapy in adult ACC patients across different tumor size ranges.

Assessing the predictive value of smoking history for immunotherapy outcomes in bladder cancer patients.

Background: The therapeutic effectiveness of immune checkpoint inhibitors (ICIs) in bladder cancer varies among individuals. Identifying reliable predictors of response to these therapies is crucial for optimizing patient outcomes. Methods: This retrospective study analyzed 348 bladder cancer patients treated with ICIs, with additional validation using data from 248 patients at our institution who underwent PD-L1 immunohistochemical staining. We examined patient smoking history, clinicopathological characteristics, and immune phenotypes. The main focus was the correlation between smoking history and immunotherapy outcomes. Multivariate logistic and Cox proportional hazard regressions were used to adjust for confounders. Results: The study cohort comprised 348 bladder cancer patients receiving ICIs. Among them, 116 (33.3%) were never smokers, 197 (56.6%) were former smokers (median pack-years = 28), and 35 (10.1%) were current smokers (median pack-years = 40). Analysis revealed no statistically significant difference in overall survival across different smoking statuses (objective response rates were 11.4% for current smokers, 17.2% for never smokers, and 22.3% for former smokers; P = 0.142, 0.410, and 0.281, respectively). However, a notable trend indicated a potentially better response to immunotherapy in former smokers compared to current and never smokers. In the validation cohort of 248 patients from our institution, immunohistochemical analysis showed that PD-L1 expression was significantly higher in former smokers (55%) compared to current smokers (37%) and never smokers (47%). This observation underscores the potential influence of smoking history on the tumor microenvironment and its responsiveness to ICIs. Conclusion: In conclusion, our study demonstrates the importance of incorporating smoking history in predicting the response to immunotherapy in bladder cancer patients, highlighting its role in personalized cancer treatment approaches. Further research is suggested to explore the comprehensive impact of lifestyle factors on treatment outcomes.

Activation of IGFBP4 via unconventional mechanism of miRNA attenuates metastasis of intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy. Although its incidence is lower than that of hepatocellular carcinoma (HCC), ICC has a worse prognosis, and it is more prone to recur and metastasize, resulting in a far greater level of malignancy. METHODS: Bioinformatics analysis and qRT-PCR were applied to assess the level of miR-122-5p and IGFBP4. Western blot, transwell assays, wound-healing assays, real-time cellular invasion monitoring, in vivo study were applied to explore the function of miR-122-5p and IGFBP4. Dual luciferase reporter assays and chromatin isolation by RNA purification (ChiRP) were applied to explore the regulation of IGFBP4 by miR-122-5p. RESULTS: Using The Cancer Genome Atlas (TCGA) data set, Sir Run Run Shaw hospital data set and bioinformatics analyses, we identified miR-122-5p as a potential tumor suppressor in ICC and validated its suppressive effect in metastasis and invasion of ICC. Transcriptome sequencing, rescue and complement experiments were used to identify insulin-like growth factor binding protein 4 (IGFBP4) as a target of miR-122-5p. The mechanism by which miR-122-5p regulates IGFBP4 was clarified by chromatin separation RNA purification technology, and dual-luciferase reporter assays. We discovered a rare novel mechanism by which miR-122-5p promotes IGFBP4 mRNA transcription by binding to its promoter region. Furthermore, in mouse orthotopic metastasis model, miR-122-5p inhibited the invasion of ICC. CONCLUSION: In summary, our study revealed a novel mechanism of miR-122-5p and function of the miR-122-5p/IGFBP4 axis in the metastasis of ICC. We also highlighted the clinical value of miR-122-5p and IGFBP4 in inhibiting ICC invasion and metastasis.

Inflammatory bowel disease is causally related to irritable bowel syndrome: a bidirectional two-sample Mendelian randomization study.

Introduction: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are lifelong digestive diseases that severely impact patients' quality of life. The existence of a causal association between IBS and IBD remains unclear. This study aimed to determine the direction of causality between IBD and IBS by quantifying their genome-wide genetic associations and performing bidirectional two-sample Mendelian randomization (MR) analyses. Methods: Genome-wide association studies (GWAS) among a predominantly European patient cohort identified independent genetic variants associated with IBS and IBD. Two separate databases (a large GWAS meta-analysis and the FinnGen cohort) for both IBS and IBD were consulted to retrieve statistics on instrument-outcome associations. MR analyses included inverse-variance-weighted, weighted-median, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods, and sensitivity analyses were performed. The MR analyses were carried out for each outcome data, followed by a fixed-effect meta-analysis. Results: Genetically predicted IBD was associated with an increased risk of IBS. Odds ratios (95% confidence intervals) for samples of 211,551 (17,302 individuals with IBD), 192,789 (7,476 Crohn's disease cases), and 201,143 (10,293 ulcerative colitis cases) individuals were 1.20 (1.00, 1.04), 1.02 (1.01, 1.03), and 1.01 (0.99, 1.03), respectively. After outlier correction using MR-PRESSO, the odds ratio for ulcerative colitis was 1.03 (1.02, 1.05) (p = 0.001). However, an association between genetically influenced IBS and IBD was not identified. Discussion: This study confirms that IBD is causally related to IBS, which may interfere with the diagnosis and treatment of both diseases.

Bulk and single-cell transcriptome profiling reveal extracellular matrix mechanical regulation of lipid metabolism reprograming through YAP/TEAD4/ACADL axis in hepatocellular carcinoma.

Emerging studies have revealed matrix stiffness promotes hepatocellular carcinoma (HCC) development. We studied metabolic dysregulation in HCC using the TCGA-LIHC database (n=374) and GEO datasets (GSE14520). HCC samples were classified into three heterogeneous metabolic pathway subtypes with different metabolic profiles: Cluster 1, an ECM-producing subtype with upregulated glycan metabolism; Cluster 2, a hybrid subtype with partial pathway dysregulation. Cluster 3, a lipogenic subtype with upregulated lipid metabolism; These three subtypes have different prognosis, clinical features and genomic alterations. We identified key enzymes that respond to matrix stiffness and regulate lipid metabolism through bioinformatic analysis. We found long-chain acyl-CoA dehydrogenase (ACADL) is a mechanoreactive enzyme that reprograms HCC cell lipid metabolism in response to extracellular matrix stiffness. ACADL is also regarded as tumor suppressor in HCC. We found that increased extracellular matrix stiffness led to activation of Yes-associated protein (YAP) and the YAP/TEA Domain transcription factor 4 (TEAD4) transcriptional complex was able to directly repress ACADL at the transcriptional level. The ACADL-dependent mechanoresponsive pathway is a potential therapeutic target for HCC treatment.