Causal roles of gut microbiota in cholangiocarcinoma etiology suggested by genetic study.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with poor prognosis. Previous studies have implicated the gut microbiota in CCA, but evidence for causal mechanisms is lacking. AIM: To investigate the causal relationship between gut microbiota and CCA risk. METHODS: We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA. Genetic variants were used as instrumental variables. Multiple sensitivity analyses assessed result robustness. RESULTS: Fifteen gut microbial taxa showed significant causal associations with CCA risk. Higher genetically predicted abundance of genus Eubacteriumnodatum group, genus Ruminococcustorques group, genus Coprococcus, genus Dorea, and phylum Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA. Increased intrahepatic CCA risk was associated with higher abundance of family Veillonellaceae, genus Alistipes, order Enterobacteriales, and phylum Firmicutes. Protective effects against CCA were suggested for genus Collinsella, genus Eisenbergiella, genus Anaerostipes, genus Paraprevotella, genus Parasutterella, and phylum Verrucomicrobia. Sensitivity analyses indicated these findings were reliable without pleiotropy. CONCLUSION: This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk. Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.

The dysregulation of biliary tract microflora is closely related to primary choledocholithiasis: a multicenter study.

Bile microecology changes play an important role in the occurrence and development of choledocholithiasis. At present, there is no clear report on the difference of bile microecology between asymptomatic patients with gallbladder polyps and choledocholithiasis. This study compared bile microecology between gallbladder polyp patients and patients with choledocholithiasis to identify risk factors for primary choledocholithiasis. This study was conducted in 3 hospitals in different regions of China. Bile samples from 26 patients with gallbladder polyps and 31 patients with choledocholithiasis were collected by laparoscopic cholecystectomy and endoscopic retrograde choledocholithiasis cholangiography (ERCP), respectively. The collected samples were used for 16S ribosomal RNA sequencing and liquid chromatography mass spectrometry analysis. The α-diversity of bile microecological colonies was similar between gallbladder polyp and choledocholithiasis, but the ß-diversity was different. Firmicutes, Proteobacteri, Bacteroidota and Actinobacteriota are the most common phyla in the gallbladder polyp group and choledocholithiasis group. However, compared with the gallbladder polyp patients, the abundance of Actinobacteriota has significantly lower in the choledocholithiasis group. At the genera level, the abundance of a variety of bacteria varies between the two groups, and Enterococcus was significantly elevated in choledocholithiasis group. In addition, bile biofilm formation-Pseudomonas aeruginosa was more metabolically active in the choledocholithiasis group, which was closely related to stone formation. The analysis of metabolites showed that a variety of metabolites decreased in the choledocholithiasis group, and the concentration of beta-muricholic acid decreased most significantly. For the first time, our study compared the bile of gallbladder polyp patients with patients with choledocholithiasis, and suggested that the change in the abundance of Actinobacteriota and Enterococcus were closely related to choledocholithiasis. The role of Pseudomonas aeruginosa biofilm in the formation of choledocholithiasis was discovered for the first time, and some prevention schemes for choledocholithiasis were discussed, which has important biological and medical significance.

Pan-cancer analysis revealing the multidimensional expression and prognostic and immunologic roles of TGFB1 in cancer.

OBJECTIVE: This study aimed to perform an integrated pan-cancer analysis to characterize the expression patterns, prognostic value, genetic alterations, and immunologic roles of transforming growth factor beta 1 (TGFB1) across diverse human cancer types. METHODS: Bioinformatics analyses were conducted using multiple public databases including The Cancer Genome Atlas, Genotype-Tissue Expression, Clinical Proteomic Tumor Analysis Consortium, TIMER2, GEPIA2, cBioPortal, StringDB, and others. Differential expression, survival, immune correlation, and protein interaction network analyses were performed. RESULTS: TGFB1 was overexpressed in several tumor types compared with that in normal tissues. High TGFB1 expression was associated with an advanced stage and poorer prognosis in certain cancers. TGFB1 mutations occurred in 1.3% of 10,967 cases surveyed. TGFB1 expression correlated with tumor-infiltrating immune cells and immunotherapy-related genes. CONCLUSIONS: This comprehensive multi-omics analysis revealed the complex expression and prognostic landscape of TGFB1 across cancers. TGFB1 is emerging as a potential immunotherapeutic target in certain contexts. Further research should elucidate its multifaceted tumor-promoting and tumor-suppressive mechanisms. Our pan-cancer analysis provides new insights into TGFB1 as a prognostic biomarker and immunotherapeutic target in human cancers, and our findings may guide future preclinical and clinical investigations of TGFB1-directed therapies.

Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis.

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver cancer with poor prognosis. The gut microbiota has been linked to ICC, but evidence for causality is lacking. Elucidating causal gut microbiota-ICC links could inform prevention and treatment strategies. Materials and methods: We performed a bidirectional two-sample Mendelian randomization (MR) study to investigate causal associations between gut microbiota and ICC risk. Genome-wide significant single nucleotide polymorphisms (SNPs) associated with gut microbiota abundances were utilized as instrumental variables (IVs). Multiple methods assessed causality and sensitivity analyses evaluated result robustness. Bioinformatics analysis of genetic loci linked to gut microbiota and ICC examined potential mechanisms. Results: Genetically predicted increases in Veillonellaceae, Alistipes, Enterobacteriales, and Firmicutes were suggestively associated with higher ICC risk, while increases in Anaerostipes, Paraprevotella, Parasutterella, and Verrucomicrobia appeared protective. Bioinformatics analysis revealed differentially expressed genes near gut microbiota-associated loci may influence ICC through regulating pathways and tumor immune microenvironment. Conclusion: Our findings provide suggestive evidence for causal links between specific gut microbiota and ICC risk.

Nanosecond pulsed electric field stimulates CD103+ DC accumulation in tumor microenvironment via NK-CD103+ DC crosstalk.

CD103+ DC is crucial for antitumor immune response. As a promising local therapy on cancers, nanosecond pulsed electric field (nsPEF) has been widely reported to stimulate anti-tumor immune response, but the underlying relationship between intratumoral CD103+ DC and nsPEF treatment remains enigmatic. Here, we focused on the behavior of CD103+ DC in response to nsPEF treatment and explored the underlying mechanism. We found that the nsPEF treatment led to the activation and accumulation of CD103+ DC in tumor. Depletion of CD103+ DC via Batf3-/- mice demonstrated CD103+ DC was necessary for intratumoral CD8+ T cell infiltration and activation in response to nsPEF treatment. Notably, NK cells recruited CD103+ DC into nsPEF-treated tumor through CCL5. Inflammatory array revealed CD103+ DC-derived IL-12 mediated the CCL5 secretion in NK cells. In addition, the boosted activation and infiltration of intratumoral CD103+ DC were abolished by cGAS-STING pathway inhibition, following IL-12 and CCL5 decreasing. Furthermore, nsPEF treatment promoting CD103+ DC-mediated antitumor response enhanced the effects of CD47 blockade strategy. Together, this study uncovers an unprecedented role for CD103+ DC in nsPEF treatment-elicited antitumor immune response and elucidates the underlying mechanisms.

Safety and Efficacy Analysis of PD-1 Inhibitors in Combination with Gemcitabine Plus Nab-Paclitaxel for Advanced Pancreatic Cancer: A Real-World, Single-Center Study.

Background: Pancreatic cancer is a deadly disease with a low five years survival rate, and chemotherapy remains the standard treatment for advanced cases. However, the efficacy of chemotherapy alone is limited, and there is a need for new treatment options. Recently, immune checkpoint inhibitors (ICIs), particularly programmed death-1 (PD-1) inhibitors, have shown promising results in various cancers, including pancreatic cancer. In this study, we explore the safety and efficacy of PD-1 inhibitors in combination with chemotherapy for advanced pancreatic cancer. Materials and Methods: A retrospective analysis was conducted on clinical data from 27 patients with advanced pancreatic cancer who were administered a combination of anti-PD-1 antibody and gemcitabine plus nab-paclitaxel (GnP) regimen. The study evaluated the safety of the treatment as well as the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: In this study, treatment with a combination of anti-PD-1 antibody and GnP regimen for pancreatic cancer resulted in partial response (PR) for 10 out of 27 (37.04%) patients, stable disease (SD) for 10 (37.04%) patients, and progressive disease (PD) for 7 (25.92%) patients. The study found that the median OS (mOS) for these patients was 16.4 months [standard error (SE) = 1.117, 95% confidence interval (CI) 14.211-18.589], while the median PFS (mPFS) was 6.4 months (SE = 1.217, 95% CI 3.981-8.752). Subgroup analysis revealed that pancreatic cancer patients' Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0 vs 1) and treatment cycles (≤6 cycles vs >6 cycles) significantly affected OS and PFS. Patients experienced mostly grade 1-2 adverse events (AEs), which were relieved through clinical treatment. Conclusion: The combination of GnP with anti-PD-1 antibodies shows promise as a potential treatment option for advanced pancreatic cancer.

Advanced hepatocellular carcinoma with MET-amplified contained excellent response to crizotinib: a case report.

Introduction: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Several novel therapeutic strategies have been developed to prolong the survival of patients with advanced HCC. However, therapeutic decision-making biomarkers owing to the extensive heterogeneity of HCC. Next-generation sequencing (NGS) is generally used in treatment decisions to help patients benefit from genome-directed targeting. Case presentation: A 56 year-old male with type-B hepatitis for more than 20 years was admitted to our department and underwent laparoscopic left lateral hepatic lobectomy for hepatocellular carcinoma. Unfortunately, the tumor recurred 1 year later. Despite multiple treatments, the tumor continued to progress and invaded the patient's 5th thoracic vertebras, leading to hypoesthesia and hypokinesia below the nipple line plane 2 years later. NGS revealed MET amplification, and crizotinib, an inhibitor of MET, was recommended. After administration for a month, tumor marker levels decreased, and the tumor shrunk. The patient has remained in remission since that time. Conclusions: We report that a patient with high MET amplification benefited from its inhibitor, which was recommended by NGS. This indicates the potential clinical decision support value of NGS and the satisfactory effect of MET inhibitors.

Isolated pancreatic tuberculosis masquerading as malignancy in an immunocompetent host: a case report and review of the literature.

A 41-year-old man was admitted to our department with a 7-day history of jaundice of the skin. He was misdiagnosed with carcinoma because imaging tests showed a space-occupying lesion in the pancreatic head, and laboratory examinations showed elevated liver enzymes, and elevated serum bilirubin, alpha-fetoprotein, carbohydrate antigen 19-9, and ferroprotein levels. However, there was slight calcification in the lesion and a subsequent T-Spot test result was positive. The patient then underwent endoscopic retrograde cholangiopancreatography for biopsy and bile drainage. Histologically, the pancreatic mass showed granulomatosis, and the pathologic diagnosis of the isolated pancreatic neoplasm was tuberculosis. The patient accordingly received anti-tuberculosis agents, resulting in a significant decrease in the size of the pancreatic mass. The patient recovered well. Pancreatic tuberculosis can masquerade as malignancy; however, careful attention to a differential diagnosis can prevent the need for laparotomy.

Surgical treatment for recurrent hepatocellular carcinoma: Current status and challenges.

Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020. It includes hepatocellular carcinoma (HCC) (representing 75%-85% of cases), intrahepatic cholangiocarcinoma (representing 10%-15% of cases), and other rare types. The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years; however, high tumor recurrence rates continue to limit long-term survival, even after radical surgical resection (exceeding 50% recurrence). For resectable recurrent liver cancer, surgical removal [either salvage liver transplantation (SLT) or repeat hepatic resection] remains the most effective therapy that is potentially curative for recurrent HCC. Thus, here, we introduce surgical treatment for recurrent HCC. Areas Covered: A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022. Expert commentary: In general, long-term survival after the re-resection of recurrent liver cancer is usually beneficial. SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients; however, SLT is constrained by the supply of liver grafts. SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival. When considering the similar overall survival rate and the current situation of donor shortages, repeat liver resection remains an important option for recurrent HCC.

Association between gut microbiota and hepatocellular carcinoma from 2011 to 2022: Bibliometric analysis and global trends.

Background: Hepatocellular carcinoma (HCC) is a primary malignant tumor responsible for approximately 90% of all liver cancers in humans, making it one of the leading public health problems worldwide. The gut microbiota is a complex microbial ecosystem that can influence tumor formation, metastasis, and resistance to treatment. Therefore, understanding the potential mechanisms of gut microbiota pathogenesis is critical for the prevention and treatment of HCC. Materials and methods: A search was conducted in the Web of Science Core Collection (WoSCC) database for English literature studies on the relationship between gut microbiota and HCC from 2011 to 2022. Bibliometric analysis tools such as VOSviewer, CiteSpace, and R Studio were used to analyze global trends and research hotspots in this field. Results: A total of 739 eligible publications, comprising of 383 articles and 356 reviews, were analyzed. Over the past 11 years, there has been a rapid increase in the annual number of publications and average citation levels, especially in the last five years. The majority of published articles on this topic originated from China (n=257, 34.78%), followed by the United States of America (n=203, 27.47%), and Italy (n=85, 11.50%). American scholars demonstrated high productivity, prominence, and academic environment influence in the research of this subject. Furthermore, the University of California, San Diego published the most papers (n=24) and had the highest average citation value (value=152.17) in the study of the relationship between gut microbiota and HCC. Schnabl B from the USA and Ohtani N from Japan were the authors with the highest number of publications and average citation value, respectively. Conclusion: In recent years, research on the gut microbiota's role in HCC has made rapid progress. Through a review of published literature, it has been found that the gut microbiota is crucial in the pathogenesis of HCC and in oncotherapy.

The "No-touch" technique improves the survival of patients with advanced hepatocellular carcinomas treated by liver transplantation: A single-center prospective randomized controlled trial.

BACKGROUND: Liver transplantation (LT) is the best treatment for patients with hepatocellular carcinoma (HCC). However, the surgical technique needs to be improved. The present study aimed to evaluate the "no-touch" technique in LT. METHODS: From January 2018 to December 2019, we performed a prospective randomized controlled trial on HCC patients who underwent LT. The patients were randomized into two groups: a no-touch technique LT group (NT group, n = 38) and a conventional LT technique group (CT group, n = 46). Operative outcomes and survival in the two groups were analyzed. RESULTS: The perioperative parameters were comparable between the two groups (P > 0.05). There was no significant difference between the two groups in disease-free survival (DFS) (P = 0.732) or overall survival (OS) (P = 0.891). Of 36 patients who were beyond the Hangzhou criteria for LT, the DFS of the patients in the NT group was significantly longer than that in the CT group (median 402 vs. 126 days, P = 0.025). In 31 patients who had portal vein tumor thrombosis (PVTT), DFS and OS in the NT group were significantly better than those in the CT group (median DFS 420 vs. 167 days, P = 0.022; 2-year OS rate 93.8% vs. 66.7%, P = 0.043). In 14 patients who had diffuse-type HCCs, DFS and OS were significantly better in the NT group than those in the CT group (median DFS 141 vs. 56 days, P = 0.008; 2-year OS rate 75.0% vs. 33.3%, P = 0.034). Multivariate analysis showed that for patients with PVTT and diffuse-type HCCs, the no-touch technique was an independent favorable factor for OS (PVTT: HR = 0.018, 95% CI: 0.001-0.408, P = 0.012; diffuse-type HCCs: HR = 0.034, 95% CI: 0.002-0.634, P = 0.024). CONCLUSIONS: The no-touch technique improved the survival of patients with advanced HCC compared with the conventional technique. The no-touch technique may provide a new and effective LT technique for advanced HCCs.

Safely Modified Laparoscopic Liver Resection for Segment VI and/or VII Hepatic Lesions Using the Left Lateral Decubitus Position.

Purpose: To explore the feasibility and safety of using the left lateral decubitus position (LLDP) to perform laparoscopic liver resection (LLR) for the treatment of hepatic lesions in segment VI and/or VII. Patients and Methods: Clinical data concerning 50 patients underwent LLR including 25 patients in the LLDP and the other 25 patients in the routine operative position (ROP) at Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College (Hangzhou, China) and Shulan (Quzhou) Hospital between March 2019 and May 2022 were retrospectively analyzed. All of the patients underwent LLR while in the LLDP or the ROP for the treatment of hepatic lesions located in segment VI and/or VII. Results: The preoperative clinical and laboratory parameters were comparable between the two groups (P > 0.05). All patients completed the surgery successfully. There were two patients required conversion to open resection in the ROP comparing with zero in the LLDP. The mean operative time was 256.9 ± 132.7 minutes in LLDP and 255.7 ± 92.1 minutes in ROP, while the median perioperative blood loss was 100 mL (range: 50-300 mL) in LLDP and 200 mL (range: 50-425 mL), respectively. The postoperative pathological examination showed that margin-negative resection was achieved all of the cases. The important postoperative parameters all returned to normal within five days after the LLR. The mean postoperative hospital stay (15.6 vs 19.3 days; p < 0.05) and the extraction of the drainage tube time (7.8 vs 10.4 days; p < 0.05) were shorter for patients in LLDP. Conclusion: The LLDP represents a safe and feasible position for performing LLR in selected patients with lesions in segment VI and/or VII. LLR in the LLDP is helpful in terms of the exposure of the surgical field and the recovery of the patient.

Sevoflurane Inhibits lncRNA HOTAIR-Modulated Stability of HK2 mRNA in a m6A-Dependent Manner to Dampen Aerobic Glycolysis and Proliferation in Lung Cancer.

Previous studies have shown that sevoflurane has an inhibitory effect on tumor cells. So far, the effect of sevoflurane on hepatocellular carcinoma needs to be confirmed by more studies. HOX transcript antisense intergenic RNA (HOTAIR), a long noncoding RNA (lncRNA), has been shown to enhance cancer cell proliferation and medication resistance. The inherent importance and biological function of HOTAIR in the course of lung cancer (LC) is, however, poorly unclear. HOTAIR was shown to be highly elevated in LC cells in this investigation. Impairment of function trials with sevoflurane indicated that it has anticancer effects on LC cell growth, apoptosis, and aerobic glycolysis. In a mechanistic manner, HOTAIR was related to HK2 mRNA and promoted expression and constancy. Additional research revealed that HOTAIR coupled with hexokinase 2 (HK2) mRNA and favorably controlled its stabilization in a traditional-component way. By HK2, the LC enhancement role was mediated. In summary, our data show that HOTAIR promotes the synthesis and proliferation of LC glycogen by increasing the transcription of HK2, and HOTAIR is likely to be a potential treatment for LC patients.

Pancancer Analyses Reveal Genomics and Clinical Characteristics of the SETDB1 in Human Tumors.

Background: Malignant tumor is one of the most common diseases that seriously affect human health. The prior literature has reported the biological function and potential therapeutic targets of SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) as an oncogene. However, SETDB1 has rarely been analyzed from a pan-cancer perspective. Methods: Bioinformatics analysis tools and databases, including GeneCards, National Center for Biotechnology Information (NCBI), UniProt, Illustrator for Biological Sequences (IBS), Human Protein Atlas (HPA), GEPIA, TIMER2, Sangerbox 3.0, UALCAN, Kaplan-Meier (K-M) plotter, cBioPortal, Catalogue Of Somatic Mutations In Cancer (COSMIC), PhosphoSitePlus, TISIDB, STRING, and GeneMANIA, were utilized to clarify the biological functions and clinical significance of SETDB1 from a pan-cancer perspective. Results: In this study, the pan-cancer analysis demonstrated that SETDB1 showed significantly differential expression in most tumor tissues and paracancerous tissues, and SETDB1 expression was associated with clinicopathological features and clinical prognosis. We also found that SETDB1 mutations occurred in most tumors and were related to tumorigenesis. In addition, DNA methylation of SETDB1 primarily occurred at the cg10444928 site and was associated with prognosis in several human tumors. The predicted phosphorylation site of SETDB1 was Ser1006. We found that SETDB1 was significantly related to the specific tumor-infiltrating immune cell populations and expression of clinically targetable immune checkpoints and may be a promising immunotherapy target. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses also indicated that SETDB1 may function as crucial regulator in carcinogenesis of human cancers. Conclusions: SETDB1 is an important oncogene involved in tumorigenesis and tumor progression through different biological mechanisms. Furthermore, SETDB1 may be a potential therapeutic target for cancer treatment.

High Expression of EZH2 Mediated by ncRNAs Correlates with Poor Prognosis and Tumor Immune Infiltration of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and is accompanied by a complex regulatory network. Increasing evidence suggests that an abnormal gene expression of EZH2 is associated with HCC progression. However, the molecular mechanism by which non-coding RNAs (ncRNAs) regulate EZH2 remains elusive. METHODS: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to perform differential expression analysis and prognostic analysis. We used the Encyclopedia of RNA Interactomes (ENCORI) database to predict candidate miRNAs and lncRNAs that may bind to EZH2. Subsequently, the comprehensive analysis (including expression analysis, correlation analysis, and survival analysis) identified ncRNAs that contribute to EZH2 overexpression. RESULTS: EZH2 was found to be upregulated in the majority of tumor types and associated with a poor prognosis. Hsa-miR-101-3p was identified as a target miRNA of EZH2. Additionally, SNHG6 and MALAT1 were identified as upstream lncRNAs of hsa-miR-101-3p. Meanwhile, correlation analysis revealed that EZH2 expression was significantly associated with the infiltration of several immune cell types in HCC. CONCLUSION: SNHG6 or MALAT1/hsa-miR-101-3p/EZH2 axis were identified as potential regulatory pathways in the progression of HCC.

Glucocorticoids rapidly promote YAP phosphorylation via the cAMP-PKA pathway to repress mouse cardiomyocyte proliferative potential.

Adult mammalian cardiomyocytes (CMs) lose their proliferative potential due to cell-cycle withdrawal and polyploidization and fail to mount a proliferative response to regenerate new CMs after cardiac injury. The decline in the proliferative potential of mammalian CMs occurs in the neonatal period when the endocrine system undergoes drastic changes for adaptation to extra-uterine life. There is an increase in circulating glucocorticoid (GC) levels shortly after birth in mammals, and thus, we sought to determine the roles and mechanisms of GCs in regulating CM proliferation. Here, we showed that GCs suppressed CM proliferation in vitro and in vivo, decreased the total number of CMs, and increased the cross-sectional area of CMs. However, the glucocorticoid receptor antagonist had no effect on CM proliferation. Agonists of adenylate cyclase and protein kinase A (PKA) inhibited CM proliferation, while PKA antagonists or knockdown of PKA alleviated the inhibitory effect of GCs on CM proliferation. GCs and the activation of the cyclic adenosine monophosphate (cAMP)/PKA signaling pathway facilitated yes-associated protein (YAP) phosphorylation in mouse CMs and promoted YAP protein translocation from the nucleus to the cytoplasm. Meanwhile, blocking the cAMP/PKA signaling pathway partially blocked the effect of GCs on YAP protein phosphorylation and YAP protein translocation. Thus, our findings suggest that GCs suppress mouse CM proliferation in vitro and in vivo, through a mechanism that involves targeting the cAMP-PKA-YAP signaling pathway.

Accuracy of brush cytology in biliopancreatic strictures: a single-center cohort study.

OBJECTIVE: False positive and negative results are associated with biliary tract cell brushing cytology during endoscopic retrograde cholangiopancreatography (ERCP). The causes are uncertain. The purpose of this study was to evaluate the accuracy of diagnoses made via cell brushing in our center, and to explore the factors influencing diagnosis. METHODS: The clinical data of patients who underwent cell brushing at our center from January 2016 to August 2019 were retrospectively analyzed. These included age, gender, stricture location, thickness of the bile duct wall in the narrow segment, maximum diameter of the biliary duct above the stricture, number of cell brush smears, carbohydrate antigen 19-9, and carcinoembryonic antigen. Positive brush cytology results were compared with results of surgical histology or tumor biopsy as well as with the patient's clinical course. RESULTS: Of the 48 patients who underwent cell brushing cytology, 27 (56.3%) had positive results. The sensitivity and specificity of biliary duct cell brushing was 79.4%, and 85.7%, respectively. None of the above-mentioned factors were associated with positive cytology brushing results. CONCLUSIONS: Cell brushing cytology remains a reliable method for diagnosis of pancreaticobiliary malignancies.

Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration: A single-center analysis.

Background: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) has become an important modality for identification of intra-abdominal masses. This study analyzed the accuracy of EUS-FNAB in a single medical center and explored factors related to positive diagnosis. Materials and methods: In total, 77 patients with EUS-FNAB were retrospectively reviewed from July 2016 to February 2020. "Atypical (tends to be neoplasm/malignancy)," "suspicious (first consider neoplasm/malignancy)," and "malignant" were defined as positive cytology. The final diagnoses were based on histopathologic examination. The positive rate of EUS-FNAB for the diagnosis of neoplasm and its associations with age, sex, target puncture mass size, liver function, tumor markers, albumin, hypertension, and diabetes were examined. Results: Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNAB cytologic diagnoses in all patients were 77.9% (60/77), 76.1% (54/71), 100%, 100%, and 26.1% (6/23), respectively. Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNAB cytologic diagnoses in the pancreas were 80.0% (48/60), 79.3% (46/58), 100%, 100%, and 14.3% (2/14), respectively. The results of EUS-FNAB in pancreatic masses showed that the level of CA19-9 was higher in the true positive group than in the false-negative group (p<0.05). There were no factors associated with the true positive cytologic diagnoses (p>0.05). Conclusions: Our single-medical center study showed that EUS-FNAB is an accurate diagnostic procedure for the evaluation of intra-abdominal masses. Further follow-up is required to explore factors associated with the true positive cytology.

Impact of treatment modalities on patients with recurrent hepatocellular carcinoma after liver transplantation: Preliminary experience.

BACKGROUND: Post-liver transplantation (LT) hepatocellular carcinoma (HCC) recurrence still occurs in approximately 20% of patients and drastically affects their survival. This study aimed to evaluate the efficacy of various treatments for recurrent HCC after LT in a Chinese population. METHODS: A total of 64 HCC patients with tumor recurrence after LT were enrolled in this study. Univariate and multivariate analyses were performed to identify factors affecting post-recurrence survival. RESULTS: Of the 64 patients with recurrent HCC after LT, those who received radical resection followed by nonsurgical therapy had a median overall survival (OS) of 20.9 months after HCC recurrence, significantly superior to patients who received only nonsurgical therapy (9.4 months) or best supportive care (2.4 months). The one- and two-year OS following recurrence was favorable for patients receiving radical resection followed by nonsurgical therapy (93.8%, 52.6%), poor for patients receiving only nonsurgical therapy (30.8%, 10.8%), and dismal for patients receiving best supportive care (0%, 0%; overall P < 0.001). Median OS in sorafenib-tolerant patients treated with lenvatinib was 19.5 months, far surpassing the patients that discontinued sorafenib or were treated with regorafenib after sorafenib failure (12 months, P < 0.001). Compared with tacrolimus-based immunosuppressive therapy, OS was significantly increased with sirolimus-based therapy at one and two years after HCC recurrence (P = 0.035). Multivariate analysis showed radical resection combined with nonsurgical therapy for recurrent HCC and sorafenib-lenvatinib sequential therapy were independent favorable factors for post-recurrence survival. CONCLUSIONS: Aggressive surgical intervention in well-selected patients significantly improves OS after recurrence. A multidisciplinary treatment approach is required to slow down disease progression for patients with unresectable recurrent HCC.