Cholangiocarcinoma combined with biliary obstruction: an exosomal circRNA signature for diagnosis and early recurrence monitoring.

Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic approaches. We present a novel system to monitor CCA using exosomal circular RNA (circRNA) via serum and biliary liquid biopsies. A pilot cohort consisting of patients with CCA-induced biliary obstruction (CCA-BO, n = 5) and benign biliary obstruction (BBO, n = 5) was used to identify CCA-derived exosomal circRNAs through microarray analysis. This was followed by a discovery cohort (n = 20) to further reveal a CCA-specific circRNA complex (hsa-circ-0000367, hsa-circ-0021647, and hsa-circ-0000288) in both bile and serum exosomes. In vitro and in vivo studies revealed the three circRNAs as promoters of CCA invasiveness. Diagnostic and prognostic models were established and verified by two independent cohorts (training cohort, n = 184; validation cohort, n = 105). An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature (Bile-DS, AUROC = 0.947, RR = 6.05) and serum exosomal circRNA signature (Serum-DS, AUROC = 0.861, RR = 4.04) compared with conventional CA19-9 (AUROC = 0.759, RR = 2.08). A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score, verified with bile samples (Bile-ERS, C-index=0.783) and serum samples (Serum-ERS, C-index = 0.782). These models, combined with other prognostic factors revealed by COX-PH model, enabled the establishment of nomograms for recurrence monitoring of CCA. Our study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.

METTL3-mediated m6A modification of lncRNA TSPAN12 promotes metastasis of hepatocellular carcinoma through SENP1-depentent deSUMOylation of EIF3I.

In a previous study, we discovered that the level of lnc-TSPAN12 was significantly elevated in hepatocellular carcinoma (HCC) and correlated with a low survival rate. However, the function and mechanism of lnc-TSPAN12 in modulating epithelial-mesenchymal transition (EMT) and metastasis in HCC remains poorly understood. This study demonstrates that lnc-TSPAN12 positively influences migration, invasion, and EMT of HCC cells in vitro and promotes hepatic metastasis in vivo. The modification of N6-methyladenosine, driven by METTL3, is essential for the stability of lnc-TSPAN12, which may partially contribute to the upregulation of lnc-TSPAN12. Mechanistically, lnc-TSPAN12 exhibits direct interactions with EIF3I and SENP1, acting as a scaffold to enhance the SENP1-EIF3I interaction. As a result, the SUMOylation of EIF3I is inhibited, preventing its ubiquitin-mediated degradation. Ultimately, this activates the Wnt/ß-catenin signaling pathway, stimulating EMT and metastasis in HCC. Our findings shed light on the regulatory mechanism of lnc-TSPAN12 in HCC metastasis and identify the lnc-TSPAN12-EIF3I/SENP1 axis as a novel therapeutic target for HCC.

Epidemiology, risk factors, diagnosis, and treatment of intra-abdominal traumatic neuromas - a narrative review.

Traumatic neuroma (TN) is a disorganized proliferation of injured nerves arising from the axons and Schwann cells. Although TN rarely occurs in the abdominal cavity, the incidence of TN may be underestimated because of the large number of asymptomatic patients. TN can cause persistent pain, which seriously affects quality of life. TN of the biliary system can cause bile duct obstruction, leading to acute cholangitis. It is difficult to differentiate TN from malignancies or recurrence of malignancy, which results in a number of patients receiving aggressive treatment. We collected cases reports of intra-abdominal TN over the past 30 years form PubMed and cases diagnosed in our medical center over the past 20 years, which is the largest case series of intra-abdominal TN to the best of our knowledge. In this review, we discuss the epidemiology, pathophysiology, risk factors, classification, diagnosis, and management of intra-abdominal TN.

Timing of surgery in patients with synchronous colorectal cancer liver metastases undergoing neoadjuvant chemotherapy: a propensity score analysis.

BACKGROUND: The optimal timing of surgery after neoadjuvant chemotherapy (NAC) in patients with synchronous colorectal cancer liver metastases (SLM) remains controversial. We plan to analyze whether the choice of different surgical timings will have different effects on the perioperative and oncologic outcomes of patients. METHOD: We retrospectively collected all patients who met the inclusion and exclusion criteria from 2010 to 2020 in West China Hospital. Patients were grouped according to time interval (TI) after NAC to surgery. The perioperative and oncologic outcomes of the two groups were compared after propensity score matching. Univariate and multivariate analyzes were used to screen factors associated with prognosis. RESULT: Among 255 enrolled patients, 188 were matched with comparable baseline (94 each group). Patients in the 6≦TI≦8 group had longer operation time, less intraoperative blood loss, and less postoperative complications than those in the 4≦TI < 6 group. However, the overall survival (OS) (p = 0.012) and disease-free survival (DFS) (p = 0.013) of the patients in the 4≦TI < 6 group were better than those in the 6≦TI≦8 group. Subgroup analysis found that the above conclusions still apply in age ≥ 60, non-anemic patients, and patients who underwent R0 resection. OS was inversely correlated with TI in patients without preoperative jaundice. DFS was negatively correlated with TI in patients with preoperative jaundice. Multivariate analysis showed that the prolongation of TI after NAC to surgery was an independent prognostic risk factor for OS and DFS. CONCLUSIONS: Patients with SLM may be a better choice for surgery within 4-6 weeks after receiving NAC. Although patients with SLM undergoing surgery 4-6 weeks after NAC has a higher rate of postoperative complications, radical surgery is still recommended for a better survival benefit.

Fabrication of 3D printed PCL/PEG artificial bile ducts as supportive scaffolds to promote regeneration of extrahepatic bile ducts in a canine biliary defect model.

In this study, a 3D porous poly(ε-caprolactone)/polyethylene glycol (PCL/PEG) composite artificial tubular bile duct was fabricated for extrahepatic bile duct regeneration. PCL/PEG composite scaffolds were fabricated by 3D printing, and the molecular structure, mechanical properties, thermal properties, morphology, and in vitro biocompatibility were characterized for further application as artificial bile ducts. A bile duct defect model was established in beagle dogs for in vivo implantation. The results demonstrated that the implanted PE1 ABD, serving as a supportive scaffold, effectively stimulated the regeneration of a new bile duct comprising CK19-positive and CK7-positive epithelial cells within 30 days. Remarkably, after 8 months, the newly formed bile duct exhibited an epithelial layer resembling the normal structure. Furthermore, the study revealed collagen deposition, biliary muscular formation, and the involvement of microvessels and fibroblasts in the regenerative process. In contrast, the anastomotic area without ABD implantation displayed only partial restoration of the epithelial layer, accompanied by fibroblast proliferation and subsequent bile duct fibrosis. These findings underscore the limited inherent repair capacity of the bile duct and underscore the beneficial role of the PE1 ABD artificial tubular bile duct in promoting biliary regeneration.

Biliary drainage in malignant biliary obstruction: an umbrella review of randomized controlled trials.

Background: There are still many controversies about biliary drainage in MBO, and we aimed to summarize and evaluate the evidence associated with biliary drainage. Methods: We conducted an umbrella review of SRoMAs based on RCTs. Through July 28, 2022, Embase, PubMed, WOS, and Cochrane Database were searched. Two reviewers independently screened the studies, extracted the data, and appraised the methodological quality of the included studies. GRADE was used to evaluate the quality of the evidence. Results: 36 SRoMAs were identified. After excluding 24 overlapping studies, 12 SRoMAs, including 76 RCTs, and 124 clinical outcomes for biliary drainage in MBO were included. Of the 124 pieces of evidence evaluated, 13 were rated "High" quality, 38 were rated "Moderate", and the rest were rated "Low" or "Very low". For patients with MBO, 125I seeds+stent can reduce the risk of stent occlusion, RFA+stent can improve the prognosis; compared with PC, SEMS can increase the risk of tumor ingrowth and reduce the occurrence of sludge formation, and the incidence of tumor ingrowth in C-SEMS/PC-SEMS was significantly lower than that in U-SEMS. There was no difference in the success rate of drainage between EUS-BD and ERCP-BD, but the use of EUS-BD can reduce the incidence of stent dysfunction. For patients with obstructive jaundice, PBD does not affect postoperative mortality compared to direct surgery. The use of MS in patients with periampullary cancer during PBD can reduce the risk of re-intervention and stent occlusion compared to PC. In addition, we included four RCTs that showed that when performing EUS-BD on MBO, hepaticogastrostomy has higher technical success rates than choledochoduodenostomy. Patients who received Bilateral-ENBD had a lower additional drainage rate than those who received Unilateral-ENBD. Conclusions: Our study summarizes a large amount of evidence related to biliary drainage, which helps to reduce the uncertainty in the selection of biliary drainage strategies for MBO patients under different circumstances.

Risk factors for recurrent common bile duct stones: a systematic review and meta-analysis.

BACKGROUND: Common bile duct stones (CBDS) have a reported recurrence rate of 4%-24% after stone extraction. The most commonly applied stone extraction method is endoscopic cholangiopancreatography (ERCP). We conducted a systematic review and meta-analysis to identify all available risk factors for recurrent CBDS following stone retraction. RESEARCH DESIGN AND METHODS: A literature search of studies with case-control design was performed to identify potential risk factors for recurrent CBDS. The impact of different risk factors on stone recurrence was analyzed. Pooled odds ratios (ORs) with 95% CIs and heterogeneity were calculated. Identified risk factors were graded as 'strong,' 'moderate,' or 'weak' after quality assessment. RESULTS: A total of 46 studies discussing stone recurrence following ERCP treatment were included. CBD diameter≥1.5 cm, sharp CBD angulation, multiple ERCP sessions, postoperative pneumobilia, history of CBD incision, and biliary stent placement were identified as strong risk factors; larger CBD diameter, periampullary diverticulum, mechanical lithotripsy, and history of cholecystectomy were identified as moderate. Other weak risk factors were also listed. CONCLUSIONS: In this comprehensive study, we identified 14 risk/protective factors for recurrent CBDS following ERCP. Pooled odds ratios were calculated and evaluated the quality of evidence. These findings may shed light on the assessment and management of CBDS.

Durable response to the combination of pembrolizumab and nab-paclitaxel in a metastatic extrahepatic cholangiocarcinoma: A case report and literature review.

Background: Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor with poor overall survival. Although the first-line standard chemotherapy (gemcitabine plus cisplatin) combined with immunotherapy has yielded positive results with survival prolongation, the efficacy remains unsatisfactory, and new treatment modalities need to be explored. Case presentation: We report the case of a patient with metastatic extrahepatic CCA who achieved a durable response and good tolerance to the combination treatment of pembrolizumab and nab-paclitaxel following progression on gemcitabine plus capecitabine chemotherapy. The tumor samples of the patient revealed low TMB, MSS, negative PD-L1 expression, and negative CD8+ TIL expression. This patient was treated with 3 cycles of pembrolizumab plus nab-paclitaxel and cisplatin, followed by 5 cycles of pembrolizumab plus nab-paclitaxel. Finally, 10 cycles of pembrolizumab monotherapy were administered. The patient survived for over 27 months after the initiation of combined therapy and was still in continuous remission at the last follow-up. Conclusion: As far as we know, this is the first report that pembrolizumab plus nab-paclitaxel successfully treated a patient with advanced CCA. This combination therapy might be a potential treatment option for patients with cholangiocarcinoma, and further clinical trials are needed to explore the outcomes.

Comparison of current guidelines and consensus on the management of patients with cholangiocarcinoma: 2022 update.

As a consequence of breakthroughs in the area of guidelines research, the therapy for cholangiocarcinoma has significantly improved the efficacy rate of diagnosis and survival outcomes. We compared the most recently updated clinical practice guidelines and consensus to provide recommendations based on the diagnostic and therapeutic equipment available in various countries. Following a systematic review, we discovered that these guidelines and consensus had both similarities and differences in terms of what organizations or groups drafted the guidelines and the approach, applicability, content and recent updates of the guidelines as well as in terms of diagnostic and treatment algorithms. The disparities could be attributable to a variety of etiological factors, high risk patients, health resources, medical technology, treatment options, and income levels. Additionally, while complete adoption of guidelines may benefit physicians, patients, and authorities, there remains a disconnect between expected goals and implementation.

A composite scaffold fabricated with an acellular matrix and biodegradable polyurethane for the in vivo regeneration of pig bile duct defects.

Bile duct regeneration is urgently needed to restore the normal function of the damaged biliary system. In this study, an artificial bile duct (ABD) was fabricated for extrahepatic bile duct regeneration based on biodegradable polyurethane (BPU) and ureter acellular matrix (UAM) to endow it with favorable biocompatibility and eliminate bile leakage during in vivo bile duct regeneration. The mechanical properties, in vitro simulation of bile flow and cytocompatibility of BPU-UAM ABD were evaluated in vitro, and surgical implantation in the biliary defect site in minipigs was implemented to reveal the in vivo degradation of BPU-UAM and regeneration of the new bile duct. The results indicated that BPU-UAM ABD with a mechanical strength of 11.9 MPa has excellent cytocompatibility to support 3T3 fibroblast survival and proliferation in extraction medium and on the scaffolds. The in vivo implantation of BPU-UAM ABD revealed the change of collagen content throughout the new bile duct regeneration. Biliary epithelial cells were observed at day 70, and continuous biliary epithelial layer formation was observed after 100 days of implantation. Altogether, the BPU-UAM ABD fabricated in this study possesses excellent properties for application study in the regeneration of bile duct. STATEMENT OF SIGNIFICANCE: Extrahepatic bile duct defects carry considerable morbidity and mortality because they are the only pathway for bile to go down into the intestinal tract. At present, no artificial bile duct can promote biliary regeneration. In this study, BPU-UAM ABD was built based on biodegradable polyurethane and ureter acellular matrix to form a continuous compact layer of polyurethane in the internal wall of UAM and avoid bile leakage and experimental failure during in vivo implantation. Our work verified the effectiveness of the synthesized biodegradable polyurethane emulsion-modified urethral acellular matrix in bile regeneration and continuous biliary epithelial layer formation. This study provided a new approach for the curing of bile duct defects and inducing new bile tissue formation.

The role of diet and nutrition related indicators in biliary diseases: an umbrella review of systematic review and meta-analysis.

BACKGROUND: Diet and nutrition, as a modifiable risk factor, have been demonstrated to play a significant role in the etiology of biliary diseases, whereas few comprehensive studies have been able to evaluate the strength and quality of these evidence. This umbrella review aims to evaluate the evidence pertaining risk factors for biliary diseases in terms of diet and nutrition-related indicators. METHODS: An umbrella review method was adopted: evidence from observational studies up to 22 November 2021 were identified using PubMed, Web of Science, the Cochrane database, as well as manual screening. Eligible systematic reviews and meta-analyses were screened according to inclusion and exclusion criteria. The inclusion criteria were: (1) meta analysis or systematic review; (2) The theme of the study is the relationship between diet or nutrition and biliary tract diseases; (3) Summarized and reported OR, RR or HR values and corresponding 95% CI; (4) No restrictions on the use of participants and languages; (5) Only extract the data of biliary tract diseases from multiple health outcomes; (6) Only the most recent studies on the same subject were included. This study had been registered at PROSPERO (CRD42021293908). For each eligible systematic review and meta-analysis, we extracted the data of general characteristics and the main findings. The methodological quality of the meta-analyses included in our study were assessed by AMSTAR2 and the quality of evidence was evaluated by the GRADE. RESULTS: A total of 323 articles were searched, among which 24 articles with 83 unique outcomes were identified as eligible. 35 of these outcomes were downgraded in GRADE evaluation as they reported heterogeneity. In short, among 83 unique outcomes, 5 were rated as moderate, 16 as low, and the rest as very low. For the prevention of biliary tract diseases, emphasis should be placed on appropriately increasing the intake of fruits, vegetables, coffee and tea, and reducing the intake of alcohol, raw fish and foods with high nitrate. Meanwhile, weight, blood sugar and lipid levels should be controlled, and diabetes should be actively prevented and treated. Drinking is not recommended to prevent gallstones, although studies have shown that it may reduce the risk of cholecystolithiasis. CONCLUSIONS: Our study summarizes the current multifaceted evidence on the relationship between dietary and nutritional indicators and biliary diseases, but the quality of all evidence was not high. Evidence from additional high-quality prospective studies are needed in the future.

Prediction of Early Recurrence After R0 Resection for Gallbladder Carcinoma of Stage T1b-T3.

PURPOSE: The time-to-tumor recurrence can predict the prognosis of hepatobiliary cancers following curative-intent resection. Therefore, for patients with gallbladder carcinoma (GBC) of stage T1b-T3 who had undergone R0 resection, we investigated the risk factors for early recurrence of GBC and their prognosis. PATIENTS AND METHODS: A total of 260 patients with GBC with T1b-T3 disease and an R0 margin were identified. Their clinicopathologic characteristics, perioperative details and prognostic data were reviewed. Survival analyses were carried out using the Kaplan-Meier method. Logistic regression models were used to identify the risk factors for early recurrence. RESULTS: The optimal cutoff for early recurrence was 29 months. Early recurrence tended to result in relapse far from the primary tumor, and such patients tended to have significantly worse overall survival. Multivariate analysis revealed that T3 disease, N1/N2 stage, poor differentiation of tumor, and lymphovascular invasion (LI) were associated with a greater risk of early recurrence. Patients diagnosed as having GBC incidentally and who had the risk factors of early recurrence were more likely to benefit from re-resection 2-4 weeks after a cholecystectomy. CONCLUSION: T3 stage, N1-N2 stage, poor differentiation, and LI were independent risk factors associated with early recurrence for patients with GBC with stage T1b-T3 disease after R0 resection.

Diagnostic Accuracy of Serum/Plasma Circular RNAs and the Combination of Circular RNAs and α-Fetoprotein for Detecting Hepatocellular Carcinoma: A Meta-Analysis.

The lack of an accurate biomarker in hepatocellular carcinoma (HCC) has hindered early detection, diagnosis, and treatment. Circular RNAs (circRNAs), which can be used as novel biomarkers in liquid biopsies, have been brought to light as a result of the advances in research on molecular biomarkers and the progression of genomic medicine. We conducted a meta-analysis of the diagnostic accuracy of serum/plasma circRNAs or the combination of circRNAs and α-fetoprotein (AFP) in HCC. We identified eight studies that met the inclusion/exclusion criteria from PubMed, Web of Science, EMBASE, and Cochrane Library databases. The data were pooled, and the sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) with 95% confidence intervals (CIs) were calculated. The areas under the summary receiver operator characteristic (SROC) curves (AUCs) were also calculated. The sensitivity of circRNAs was 0.82 (95% CI: 0.78-0.85), and the specificity was 0.82 (95% CI: 0.78-0.86). The sensitivity of AFP was 0.65 (95% CI: 0.61-0.68), and the specificity was 0.90 (95% CI: 0.85-0.93). The AUC was 0.89 (95% CI: 0.86-0.91) for circRNAs and 0.77 (95% CI: 0.74-0.81) for AFP. The sensitivity of the combination of circRNAs and AFP was 0.88 (95% CI: 0.84-0.92), specificity was 0.86 (95% CI: 0.80-0.91), and AUC was 0.94 (95% CI: 0.91-0.96). Additionally, a subgroup analysis was conducted based on the control groups used; the diagnostic accuracy was particularly high in the comparison of HCC vs. healthy controls. In summary, serum/plasma circRNAs are accurate biomarkers suitable for clinical use for detecting HCC, and the combination of circRNAs and AFP improved the diagnostic accuracy.

Mixed adenoneuroendocrine carcinomas of stomach and ampulla of vater after curative-intent resection: a single center cases series.

BACKGROUND: Mixed adenoneuroendocrine carcinoma is a rare clinical manifestation, especially in the gastric and ampullary. The purpose of this study was to investigate the clinicopathological features and prognosis of mixed adenoneuroendocrine carcinoma in the gastric and ampullary and summarize related treatment suggestions. METHODS: In all, 32 cases of mixed adenoneuroendocrine carcinoma in the gastric and ampullary that were diagnosed from resected specimens were analyzed from 2009 to 2015. The corresponding demographic, clinicopathological and survival data were retrospectively reviewed. RESULTS: The 1-year, 3-year and 5-year survival rates were 78.1%, 28.1 and 9.4%, respectively, and the median overall survival was 28.0 months. In all, 75.0% (24/32) had lymph node metastasis at the time of initial diagnosis. A multivariate analysis revealed that TNM stage (HR 6.444 95%CI 1.477-28.121 P = 0.013), lymph nodes metastasis (HR10.617 95%CI 1.409-79.997 P = 0.022), vascular invasion (HR 5.855 95%CI 1.719-19.940 P = 0.005), grade of the adenocarcinoma component (HR 3.876 95%CI 1.451-10.357 P = 0.007) and CD56 positivity (HR 0.265 95%CI 0.100-0.705 P = 0.008) were independent predictors of overall survival. CONCLUSIONS: Mixed adenoneuroendocrine carcinoma is an aggressive clinical entity with a poor prognosis. Taking both the neuroendocrine component and the adenocarcinoma component into consideration of optimal treatment is strongly recommended.

Rare DNA Mismatch Repair-Related Protein Loss in Patients with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma and Their Response to Immunotherapy.

PURPOSE: The patients with advanced mismatch repair deficiency (dMMR) cancers can benefit from programmed cell death 1 (PD-1) pathway blockade, regardless of the tumor type. Little is known about the prevalence of dMMR in intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (cHCC-CC). This study aimed to assess the mismatch repair (MMR)-related protein expression in patients with ICC and cHCC-CC. PATIENTS AND METHODS: Formalin-fixed, paraffin-embedded tumor specimens were obtained from patients undergoing surgery at the West china Hospital between 2009 and 2017. The immunoreactions for MLH1, MSH2, MSH6, and PMS2 were investigated to determine the MMR status. RESULTS: A total of 97 patients were evaluated, including 73 ICC patients and 24 cHCC-CC patients. The prevalence of dMMR was only found in two cases of 97 patients (2.06%). Both patients are ICC. In 24 cHCC-CC patients, no dMMR was observed. They did not receive an adjuvant chemotherapy after surgery. At the end of the follow-up, one patient was in a tumor-free state, and the other patient had local recurrence and metastasis. After receiving sintilimumab (an immune checkpoint inhibitor [ICI] for PD- 1), the patient had a partial response. CONCLUSION: DMMR was detected in few patients with ICC and cHCC-CC. Thus, it is not recommended to routinely evaluate the MMR status of patients with ICC or cHCC-CC after surgery, but that of patients with advanced ICC or cHCC-CC should be assessed.

The preoperative elevated plasma fibrinogen level is associated with the prognosis of hilar cholangiocarcinoma.

PURPOSE: Elevated fibrinogen (Fbg) levels contribute to tumor progression and metastasis. However, little is known regarding the association of the clinicopathological characteristics and the prognosis of hilar cholangiocarcinoma (HC) with plasma fibrinogen. METHODS: Data on the plasma Fbg levels, clinicopathological characteristics, and overall survival were retrospectively collected. Plasma fibrinogen concentrations over 4.0 g/L were classified as hyperfibrinogen, elevated fibrinogen, or abnormal fibrinogen levels. We then analyzed the relationships among plasma fibrinogen level, clinicopathological features, and patient prognosis. RESULTS: A total of 171 HC patients were included. An elevated plasma fibrinogen level was associated with lymph-node metastasis (P < 0.001), the AJCC stage (P < 0.001), the surgical margin (P = 0.005), and vascular invasion (P = 0.027). Univariate analyses revealed that preoperative plasma fibrinogen (P < 0.001), operative blood loss (P = 0.044), vascular invasion (P < 0.001), CA19-9 (P = 0.003), surgical margin (P < 0.001), T stage (P < 0.001), histologic differentiation (P = 0.007), and lymph-node metastasis (P < 0.001) were associated with OS. The survival time of patients with high Fbg levels was shorter than that of patients with normal fibrinogen levels (P < 0.001). Furthermore, a multivariate analysis showed that fibrinogen was negatively and independently associated with the HC prognosis (P = 0.029). CONCLUSIONS: An elevated plasma Fbg level was associated with lymph-node metastasis, vascular invasion, the surgical margin, and the tumor stage, and the Fbg level might therefore be an independent factor associated with poor outcomes in HC patients.

Postsurgical radiotherapy in stage IIIB gallbladder cancer patients with one to three lymph nodes metastases: A propensity score matching analysis.

BACKGROUND: The effect of postsurgical radiotherapy (PSRT) among T1-3 gallbladder cancer (GBC) patients with one to three lymph node metastases remains controversial. The aim of this study was to assess the impact of PSRT on gallbladder cancer-specific survival (GBCSS) in patients with stage IIIB. METHODS: The data of GBC patients were obtained from the American Surveillance, Epidemiology, and End Results (SEER) Data resources between 2004 and 2015. Then, a 1:1 propensity score matching (PSM) method was performed. GBCSS was compared among all patients. Subgroup analysis was conducted to identify patients who would benefit from PSRT. RESULTS: 726 AJCC (8th edition) stage IIIB GBC patients were included. PSRT failed to improve GBCSS (p = 0.168). Male sex, tumor size ≥ 4 cm and absence of chemotherapy were independent negative prognostic factors. No significant survival benefit from PSRT was found in any subgroup. CONCLUSIONS: PSRT provides no survival benefit for IIIB GBC.

Diagnostic Accuracy of Circular RNAs in Different Types of Samples for Detecting Hepatocellular Carcinoma: A Meta-Analysis.

The lack of accurate biomarkers impeded the screening, diagnosis and early treatment of hepatocellular carcinoma (HCC). As a result of the development of high-throughput transcriptome analysis techniques, circular RNAs, a newly discovered class of noncoding RNAs, were recognized as potential novel biomarkers. This meta-analysis was performed to update the diagnostic roles of circular RNAs for HCC. We acquired 23 articles from PubMed, Web of Science, EMBASE, and Cochrane Library databases up to September 2021. The overall sensitivity was 0.80 (95% CI: 0.77-0.84), and the specificity was 0.83 (95% CI: 0.79-0.85), with an AUC of 0.88 (0.85-0.91). Considering of the significant heterogeneity, studies were divided into four groups based on the control types. The circular RNAs in exosomes had a sensitivity of 0.69 (95% CI: 0.61-0.75), and a highest specificity of 0.91 (95% CI: 0.83-0.96). The pooled sensitivity of circular RNAs in serum/plasma was 0.84 (95% CI: 0.81-0.87), and the pooled specificity was 0.83 (95% CI: 0.79-0.86). The pooled sensitivity of circular RNAs distinguishing tumor tissue from chronic hepatitis/cirrhosis tissues was 0.56 (95% CI: 0.48-0.64), and specificity was 0.76 (95% CI: 0.67-0.82). When the controls were adjacent tissues, the sensitivity was 0.78 (95% CI: 0.70-0.84), and the specificity was 0.78 (95% CI: 0.71-0.85). Hsa_circ_0001445 with a pooled sensitivity of 0.81, a specificity of 0.76 and an AUC of 0.85 in two studies, might be a suitable diagnostic blood biomarker for HCC. Relying on function in HCC, the AUC of subgroups were 0.88 (95%CI: 0.84-0.90) (function group) and 0.87 (95%CI: 0.84-0.90) (unknown function group). As for only reported in HCC or not, these circular RNAs had an AUC of 0.89 (95%CI: 0.86-0.91) (only in HCC) and 0.85 (95%CI: 0.82-0.88) (not only in HCC). In conclusion, the results suggested that circular RNAs were acceptable biomarkers for detecting HCC, especially those circular RNAs existing in exosomes or serum/plasma.

RNA sequencing reveals the long noncoding RNA and mRNA profiles and identifies long non-coding RNA TSPAN12 as a potential microvascular invasion-related biomarker in hepatocellular carcinoma.

Emerging evidence demonstrates that abnormally expressed long noncoding RNAs (lncRNAs) are involved in the progression of various cancers. However, the expression profiles and functions of lncRNAs in hepatocellular carcinoma (HCC) with microvascular invasion (MVI) remain largely unknown. In this study, we revealed the differential expression profiles of lncRNA and messenger RNA in four pairs of HCC with MVI and adjacent nontumor liver tissues by using high-throughput RNA sequencing. Among these dysregulated lncRNAs, lnc-TSPAN12 was the most significantly upregulated lncRNA in HCC. The results of real time-PCR showed that lnc-TSPAN12 was highly expressed in HCC, including HCC with MVI, and its high expression was associated with unfavorable clinicopathological features and poor prognosis. Moreover, multivariate Cox regression analysis verified that lnc-TSPAN12 was an independent prognostic predictor for overall and recurrence-free survival. Receiver operating characteristic curve analysis indicated that lnc-TSPAN12 could serve as a potential diagnostic biomarker for HCC with MVI. In addition, a loss-of-function experiment demonstrated that lnc-TSPAN12 knockdown inhibited HCC cell migration and invasion in vitro. Our findings suggest that lnc-TSPAN12 may function as an oncogene in HCC progression and could serve as a novel diagnostic/prognostic biomarker and potential therapeutic target for HCC with MVI.

A simple scoring system to predict early recurrence of Bismuth-Corlette type IV perihilar cholangiocarcinoma.

BACKGROUND: Early recurrence has been reported to be predictive of a poor prognosis for patients with perihilar cholangiocarcinoma (pCCA) after resection. The objective of our study was to construct a useful scoring system to predict early recurrence for Bismuth-Corlette type IV pCCA patients in clinic and to investigate the value of early recurrence in directing post-operative surveillance and adjuvant therapy. METHODS: In total, 244 patients who underwent radical resection for type IV pCCA were included. Data on clinicopathological characteristics, perioperative details and survival outcomes were analyzed. Survival curves were generated using the Kaplan-Meier method. Univariate and multivariate logistic-regression models were used to identify factors associated with early recurrence. RESULTS: Twenty-one months was defined as the cutoff point to distinguish between early and late recurrence. Univariate and multivariate analysis revealed that CA19-9 level >200 U/mL, R1 resection margin, higher N category and positive lymphovascular invasion were independent predictors of early recurrence. The scoring system was constructed accordingly. The early-recurrence rates of patients with scores of 0, 1, 2, 3, 4, and 5 were 23.9%, 38.7%, 60.0%, 78.6%, 83.4%, and 100%, respectively. Adjuvant therapy was significantly associated with higher overall survival rate for patients with early recurrence, but not for those with late recurrence. Patients in the early-recurrence group with scores ≥2 had better prognoses after adjuvant therapy. CONCLUSIONS: A simple scoring system using CA19-9 level, N category, resection margin and lymphovascular invasion status could predict early recurrence, and thus might direct post-operative surveillance and adjuvant therapy for patients with type IV pCCA.