Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway.

BACKGROUND: Abnormal angiogenesis is crucial for gallbladder cancer (GBC) tumor growth and invasion, highlighting the importance of elucidating the mechanisms underlying this process. LncRNA (long non-coding RNA) is widely involved in the malignancy of GBC. However, conclusive evidence confirming the correlation between lncRNAs and angiogenesis in GBC is lacking. METHODS: LncRNA sequencing was performed to identify the differentially expressed lncRNAs. RT-qPCR, western blot, FISH, and immunofluorescence were used to measure TRPM2-AS and NOTCH1 signaling pathway expression in vitro. Mouse xenograft and lung metastasis models were used to evaluate the biological function of TRPM2-AS during angiogenesis in vivo. EDU, transwell, and tube formation assays were used to detect the angiogenic ability of HUVECs. RIP, RAP, RNA pull-down, dual-luciferase reporter system, and mass spectrometry were used to confirm the interaction between TRPM2-AS, IGF2BP2, NUMB, and PABPC1. RESULTS: TRPM2-AS was upregulated in GBC tissues and was closely related to angiogenesis and poor prognosis in patients with GBC. The high expression level and stability of TRPM2-AS benefited from m6A modification, which is recognized by IGF2BP2. In terms of exerting pro-angiogenic effects, TRPM2-AS loaded with exosomes transported from GBC cells to HUVECs enhanced PABPC1-mediated NUMB expression inhibition, ultimately promoting the activation of the NOTCH1 signaling pathway. PABPC1 inhibited NUMB mRNA expression through interacting with AGO2 and promoted miR-31-5p and miR-146a-5p-mediated the degradation of NUMB mRNA. The NOTCH signaling pathway inhibitor DAPT inhibited GBC tumor angiogenesis, and TRPM2-AS knockdown enhanced this effect. CONCLUSIONS: TRPM2-AS is a novel and promising biomarker for GBC angiogenesis that promotes angiogenesis by facilitating the activation of the NOTCH1 signaling pathway. Targeting TRPM2-AS opens further opportunities for future GBC treatments.

Injectable, Drug-Eluting Nanocrystals Prevent Fibrosis and Stricture Formation In Vivo.

BACKGROUND & AIMS: Tissue fibrosis results from uncontrolled healing responses leading to excessive mesenchymal cell activation and collagen and other extracellular matrix deposition. In the gastrointestinal tract, fibrosis leads to narrowing of the lumen and stricture formation. A drug treatment to prevent fibrosis and strictures in the gastrointestinal tract would be transformational for patient care. We aimed to develop a stricture treatment with the following characteristics and components: a small molecule with strong antifibrotic effects that is delivered locally at the site of the stricture to ensure correct lesional targeting while protecting the systemic circulation, and that is formulated with sustained-release properties to act throughout the wound healing processes. METHODS: A high-throughput drug screening was performed to identify small molecules with antifibrotic properties. Next, we formulated an antifibrotic small molecule for sustained release and tested its antifibrotic potential in 3 animal models of fibrosis. RESULTS: Sulconazole, a US Food and Drug Administration-approved drug for fungal infections, was found to have strong antifibrotic properties. Sulconazole was formulated as sulconazole nanocrystals for sustained release. We found that sulconazole nanocrystals provided superior or equivalent fibrosis prevention with less frequent dosing in mouse models of skin and intestinal tissue fibrosis. In a patient-like swine model of bowel stricture, a single injection of sulconazole nanocrystals prevented stricture formation. CONCLUSIONS: The current data lay the foundation for further studies to improve the management of a range of diseases and conditions characterized by tissue fibrosis.

Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood. METHODS: To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue. RESULTS: Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs. CONCLUSIONS: This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.

Laparoscopic Left Hepatectomy for Intrahepatic Cholangiocarcinoma.

BACKGROUND: Minimally invasive surgery for intrahepatic cholangiocarcinoma (ICC) remains challenging, especially in advanced patients. PATIENT AND METHOD: A 66-year-old male was diagnosed with stage II ICC after a comprehensive evaluation and was scheduled for laparoscopic exploration and left hepatectomy. RESULTS: The pure laparoscopic left hepatectomy was completed in 240 min, employing a no-touch en bloc technique and lymphadenectomy skeletonization. The patient was discharged 6 days after the operation without any complications and received gemcitabine and cisplatin treatment postoperatively. There was no recurrence during 14 months of follow-up. CONCLUSIONS: Our experience demonstrates that when utilizing the no-touch en bloc technique, standardized lymphadenectomy through skeletonization, and effective control of bleeding, surgeons with extensive expertise in laparoscopic hepatectomy can achieve results comparable to open surgery.

Prognostic Significance of Tumor Necrosis in Patients with Gallbladder Carcinoma Undergoing Curative-Intent Resection.

BACKGROUND: Tumor necrosis has been indicated to correlate with dismal survival outcomes of a variety of solid tumors. However, the significance and prognostic value of tumor necrosis remain unclear in gallbladder carcinoma. The aim of this research is to explore the relationships between necrosis with long-term survival and tumor-related biological characteristics of patients with gallbladder carcinoma. PATIENTS AND METHODS: Patients with gallbladder carcinoma who accepted curative-intent resection in West China Hospital of Sichuan University (China) between January 2010 and December 2021 were retrospectively analyzed. Tumor necrosis was determined by staining the patient's original tissue sections with hematoxylin and eosin. Based on the presence of tumor necrosis, the pathologic features and survival outcomes were compared. RESULTS: This study enrolled 213 patients with gallbladder carcinoma who underwent curative-intent surgery, of whom 89 had tumor necrosis. Comparative analyses indicated that patients with tumor necrosis had more aggressive clinicopathological features, such as larger tumor size (p = 0.002), poorer tumor differentiation (p = 0.029), more frequent vascular invasion (p < 0.001), presence of lymph node metastasis (p = 0.014), and higher tumor status (p = 0.01), and experienced poorer survival. Univariate and multivariate analyses revealed that tumor necrosis was an independent prognostic factor for overall survival (multivariate: HR 1.651, p = 0.026) and disease-free survival (multivariate: HR 1.589, p = 0.040). CONCLUSIONS: Tumor necrosis can be considered as an independent predictive factor for overall survival and disease-free survival among individuals with gallbladder carcinoma, which was a valuable pathologic parameter.

Prognostic value of combined preoperative inflammatory marker neutrophil-lymphocyte ratio and platelet distribution width in patients with gallbladder carcinoma.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) and platelet distribution width (PDW) are associated with poor prognosis in various cancers. We aimed to analyze the prognostic value of the combination of preoperative NLR and PDW in patients with gallbladder carcinoma (GBC). METHODS: A total of 287 GBC patients who underwent curative-intent surgery in our institution was included. The relationship between NLR and PDW and clinicopathological features were analyzed. The receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value for NLR and PDW. Overall survival (OS) was estimated using the Kaplan-Meier method. Meanwhile, the univariate and multivariate Cox regression models were used to assess the risk factors for OS. RESULTS: The optimal cutoff value of NLR and PDW was 3.00 and 14.76, respectively. In addition, survival analysis demonstrated that patients with NLR > 3.00 and PDW > 14.76 had a worse prognosis than patients with NLR ≤ 3.00 and PDW ≤ 14.76, respectively. The multivariate analysis showed that NLR and PDW were independent prognostic factors in the patients with GBC. When we combined NLR and PDW, the area under the ROC curve increased from 0.665 (NLR) and 0.632 (PDW) to 0.676. Moreover, the 1-, 3-, and 5-year OS of group A (patients with NLR ≤ 3.00 and PDW ≤ 14.76), group B (patients with either of NLR > 3.00 or PDW > 14.76) and group C (patients with NLR > 3.00 and PDW > 14.76) were 88.7%, 62.6%, 28.1%, 65.1%, 26.9%, 13.1%, and 34.8%, 8.3%, 0%, respectively. CONCLUSION: The combination of NLR and PDW may serve as a significant prognostic biomarker for GBC patients superior to either NLR or PDW alone.

A Review of Ultrasonic Treatment in Mineral Flotation: Mechanism and Recent Development.

Ultrasonic treatment has been widely used in the mineral flotation process due to its advantages in terms of operational simplicity, no secondary pollutant formation, and safety. Currently, many studies have reported the effect of ultrasonic treatment on mineral flotation and shown excellent flotation performance. In this review, the ultrasonic mechanisms are classified into three types: the transient cavitation effect, stable cavitation effect, and acoustic radiation force effect. The effect of the main ultrasonic parameters, including ultrasonic power and ultrasonic frequency, on mineral flotation are discussed. This review highlights the uses of the application of ultrasonic treatment in minerals (such as the cleaning effect, ultrasonic corrosion, and desulfuration), flotation agents (such as dispersion and emulsification and change in properties and microstructure of pharmaceutical solution), and slurry (such formation of microbubbles and coalescence). Additionally, this review discusses the challenges and prospects of using ultrasonic approaches for mineral flotation. The findings demonstrate that the application of the ultrasonic effect yields diverse impacts on flotation, thereby enabling the regulation of flotation behavior through various treatment methods to enhance flotation indices and achieve the desired objectives.

Quaternary nanoparticles enable sustained release of bortezomib for hepatocellular carcinoma.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related mortality in the world. Over the past two decades, there has been minimal improvement in therapies as well as clinical outcomes for patients with Barcelona Clinic Liver Cancer (BCLC)-B. These patients are treated with local interventions, including transarterial chemoembolization. Current methodologies only allow sustained intratumoral release measured in hours. Methodologies to allow sustained local release of the drug cargo over days to weeks are acutely needed. We hypothesize that tumor response as well as outcomes of patients with BCLC-B can be improved through utilization of a highly cytotoxic agent delivered with a sustained release platform. APPROACH AND RESULTS: High-throughput drug screening across 40 HCC patient-derived organoids identified bortezomib (BTZ) as a highly cytotoxic small molecule for HCC. We designed and manufactured sustained release BTZ nanoparticles (BTZ-NP) using a flash nanocomplexation/nanoprecipitation process. We quantified the release profile and tested the anti-tumoral effects in vivo. The BTZ-NP formulation demonstrated a sustained release of BTZ of 30 days. This BTZ-NP formulation was highly effective in controlling tumor size and improved survival in vivo in three animal models of HCC, including when delivered via the hepatic artery, as we envision its delivery in patients. In addition, the BTZ-NP formulation was superior to treatment with doxorubicin-drug eluting beads. CONCLUSIONS: The BTZ-NP formulation provides a potent and safe treatment of HCC via a localized delivery approach. These results warrant additional preclinical studies to advance this technology to human clinical trials.

Laparoscopic Resection of Perihilar Cholangiocarcinoma Type IIIb: A Video Demonstration of No-Touch En-Block Technique and Radical Lymphadenectomy.

BACKGROUND: Minimally invasive surgery for perihilar cholangiocarcinoma (pCCA) is in an exploratory phase by now and is only recommended for carefully selected patients. PATIENTS AND METHODS: Our team performed total laparoscopic hepatectomy in a 64-year-old woman with perihilar cholangiocarcinoma type IIIb. Laparoscopic left hepatectomy and caudate lobectomy were performed involving a no-touch en-block technique. Meanwhile, extrahepatic bile duct resection, radical lymphadenectomy with skeletonization, and biliary reconstruction were performed. RESULTS: Laparoscopic left hepatectomy and caudate lobectomy were successfully performed in 320 min with 100 ml of blood loss. The histological grading was T2bN0M0 (stage II). The patient was discharged on the 5th day without postoperative complications. Following the operation, the patient received single-drug capecitabine chemotherapy. There was no recurrence after 16 months of follow-up. CONCLUSION: Our experience is that, in selected patients with pCCA type IIIb or type IIIa, laparoscopic resection can reach comparable outcome to open surgery with standardized lymph node dissection by skeletonization, use of no-touch en-block technique, and proper digestive tract reconstruction.

A Novel Patient-like Swine Model of Perianal Crohn's Disease.

BACKGROUND: Perianal Crohn's disease is associated with poor outcomes and high medical costs. It is notoriously difficult to treat despite therapeutic advancements for luminal disease. A large animal model that mimics human perianal disease is needed to test innovative therapies. OBJECTIVE: This study aimed to create a swine model that replicates the inflammatory component and therapeutic challenges found in patients with perianal Crohn's disease. DESIGN: This was an animal preclinical study. SETTINGS: The experiments were performed at the animal laboratory at the Johns Hopkins University. PATIENTS: Four sus scrufus female pigs were included in the study. INTERVENTIONS: Four female pigs underwent creation of 3 surgical perianal fistulas each, 1 rectovaginal and 2 perianal. Size 24 French setons were placed to maintain patency of the fistula tracts for 4 weeks. After removal of the setons, trinitrobenzene sulfonic acid was administered into the fistula tract to create and maintain local inflammation mimicking perianal Crohn's disease. MAIN OUTCOMES MEASURES: An MRI was obtained to assess the fistulas and the pigs were euthanized to review histopathology. RESULTS: Three inflammatory chronic fistula tracts were successfully created in each pig as confirmed by MRI and examination under anesthesia. This is the first report of maintaining patent fistulas in swine 2 weeks after removal of setons. For the first time, we reported that 2 pigs developed branching fistulas and small abscesses reminiscent of human perianal Crohn's disease. The corresponding histopathologic examination found significant chronic active inflammation on standard hematoxylin and eosin staining. LIMITATIONS: The fistulas were surgically induced and did not occur naturally. CONCLUSIONS: A chronic perianal fistula model in pigs that strongly resembles human perianal Crohn's disease was successfully created. This model can be used to test novel therapeutics and techniques to pave the path for human trials. See Video Abstract at http://links.lww.com/DCR/B969 . UN NUEVO MODELO PORCINO SIMILAR A UN PACIENTE DE LA ENFERMEDAD DE CROHN PERIANAL ANTECEDENTES: La enfermedad de Crohn perianal se asocia con malos resultados y altos costos médicos. Es notoriamente difícil de tratar a pesar de los avances terapéuticos para la enfermedad luminal. Se precisa de un modelo animal grande que imite la enfermedad perianal humana para probar terapias innovadoras.OBJETIVO:Nuestro objetivo de este estudio fue crear un modelo porcino que replique el componente inflamatorio y los desafíos terapéuticos que se encuentran en los pacientes con enfermedad de Crohn perianal.DISEÑO:Este fue un estudio preclínico en animales.AJUSTES:Los experimentos se realizaron en el laboratorio de animales de la Universidad Johns Hopkins.PACIENTES:Se incluyeron en el estudio cuatro cerdas sus scrofa.INTERVENCIONES:Cuatro cerdas fueron sometidas a la creación de 3 fístulas perianales quirúrgicas cada una: 1 recto vaginal y 2 perianales. Se colocaron sedales de 24 French para mantener la permeabilidad de los trayectos fistulosos durante 4 semanas. Tras el retiro de los sedales, se administró ácido trinitrobenceno sulfónico en el trayecto de la fístula para crear y mantener la inflamación local simulando la enfermedad de Crohn perianal.PRINCIPALES MEDIDAS DE RESULTADOS:Se obtuvo una resonancia magnética para evaluar las fístulas y los cerdos fueron sacrificados para revisar la histopatología.RESULTADOS:Se crearon de manera exitosa tres trayectos fistulosos inflamatorios crónicos en cada cerdo, confirmados por imágenes de resonancia magnética y examen bajo anestesia. Este es el primer informe de preservación de fístulas permeables en cerdos 2 semanas tras el retiro de los setones. Por primera vez, informamos que dos cerdos desarrollaron fístulas ramificadas y pequeños abscesos que recuerdan a la enfermedad de Crohn perianal humana. El examen histopatológico correspondiente encontró una significativa inflamación crónica activa en la tinción estándar de hematoxilina y eosina.LIMITACIONES:Las fístulas se indujeron quirúrgicamente y no se produjeron de forma natural.CONCLUSIONES:Se logro recrear con éxito un modelo de fístula perianal crónica en cerdos que se asemeja mucho a la enfermedad de Crohn perianal humana. Este modelo se puede utilizar para probar nuevas terapias y técnicas para allanar el camino para los ensayos en humanos. Consulte Video Resumen en http://links.lww.com/DCR/B969 . (Traducción-Dr Osvaldo Gauto).

Metastatic lymph node ratio as an important prognostic factor in advanced gallbladder carcinoma with at least 6 lymph nodes retrieved.

BACKGROUND: The metastatic lymph node (LN) ratio (LNR) has shown to be an important prognostic factor in various gastrointestinal malignancies. Nevertheless, the prognostic significance of LNR in gallbladder carcinoma (GBC) remains to be determined. METHODS: From January 2007 to January 2018, 144 advanced GBC patients (T2-4 stages) who underwent curative surgery with at least 6 LNs retrieved were enrolled. Receiver operating characteristic (ROC) curve was performed to identify the optimal cut-off value for LNR. The clinicopathological features stratified by LNR level were analyzed. Meanwhile, univariate and multivariate Cox regression proportional hazard models were performed to identify risk factors for overall survival (OS). RESULTS: The optimal cut-off point for LNR was 0.28 according to the ROC curve. LNR>0.28 was associated with higher rate of D2 LN dissection (P=0.004) and higher tumor stages (P<0.001). Extent of liver resection, extrahepatic bile duct resection, tumor stage, LNR, margin status, tumor differentiation, and perineural invasion were associated with OS in univariate analysis (all P<0.05). GBC patients with LNR≤0.28 had a significantly longer median OS compared to those with LNR>0.28 (27.5 vs 18 months, P=0.004). Multivariate analysis indicated that tumor stage (T2 vs T3/T4; hazard ratio (HR) 1.596; 95% confidence interval (CI) 1.195-2.132), LNR (≤0.28 vs >0.28; HR 0.666; 95% CI 0.463-0.958), margin status (R0 vs R1; HR 1.828; 95% CI 1.148-2.910), and tumor differentiation (poorly vs well/moderately; HR 0.670; 95% CI 0.589-0.892) were independent prognostic factors for GBC (all P<0.05). CONCLUSIONS: LNR is correlated to advanced GBC prognosis and is a potential prognostic factor for advanced GBC with at least 6 LNs retrieved.

The influence of resection margin width in patients with intrahepatic cholangiocarcinoma: a meta-analysis.

BACKGROUND: Some studies have pointed out that a wide resection margin can improve the prognosis of intrahepatic cholangiocarcinoma, but some researchers disagree and believe that a wide margin may increase complications. The optimal margin length of intrahepatic cholangiocarcinoma is controversial. METHOD: The literature was searched in PubMed, MedLine, Embase, the Cochrane Library, and Web of Science until December 31, 2021, to evaluate the postoperative outcomes of patients with different margin width after resection. Odds ratios (ORs) with 95% confidence intervals were used to determine the effect size. RESULT: A total of 11 articles were included in this meta-analysis, including 3007 patients. The narrow group had significantly lower 1-, 3-, and 5-year overall survival rates and recurrence-free survival rates than the wide group. Postoperative morbidity and prognostic factors were also evaluated. CONCLUSION: A resection margin width of over 10 mm is recommended in intrahepatic cholangiocarcinoma patients, especially in patients with negative lymph node and early tumor stage. When the resection margin width cannot be greater than 10 mm, we should ensure that the resection margin width is greater than 5 mm.

Laparoscopic surgery for oncologic extended resection of T1b and T2 incidental gallbladder carcinoma at a high-volume center: a single-center experience in China.

BACKGROUND: Surgical treatment is still the most effective treatment for gallbladder cancer. For the patients with stage T1b and above, the current guidelines recommend the extended radical operation, and oncologic extended resection can benefit the survival of the patients. The laparoscopic approach is still in the early phase, and its safety and oncological outcomes are not well known. OBJECTIVE: To evaluate the technical feasibility and oncological outcomes of laparoscopic surgery for oncologic extended resection of early-stage incidental gallbladder carcinoma. RESULTS: This study included 18 male and 32 female patients. Twenty patients underwent laparoscopic oncologic extended resection and 30 patients underwent open oncologic extended resection. All of the patients had R0 resection. A laparoscopic approach was associated with less intraoperative blood loss (242 ± 108.5 vs 401 ± 130.3; p < 0.01) and shorter duration of postoperative hospital stay (6.2 ± 2.4 vs 8.6 ± 2.3; p < 0.01). There was no statistically significant difference between two groups for lymph nodes yield (5.4 ± 3.5 vs 5.8 ± 2.1; p > 0.05), incidence of lymphatic metastasis (15% vs 16.67%; p > 0.05), residual disease (20% vs 23.3%; p > 0.05), and postoperative morbidity (15% vs 20%; p > 0.05). During follow-up time of median 20.95 (12-29.5) months, no significant difference was found between the two groups for early tumor recurrence (10% vs 13.33%; p > 0.05) and disease-free survival (p > 0.05). CONCLUSION: Laparoscopic surgery may offer similar intraoperative, perioperative, and short-term oncological outcomes as an open oncologic extended resection for incidental gallbladder carcinoma.

Enhancing bile tolerance of Lactobacilli is involved in the hypolipidemic effects of liraglutide.

Liraglutide is an analog of human glucagon-like peptide-1 which play essential roles in regulation of glycolipid metabolism. To investigate role of lactic acid bacteria (LAB) in lipid-lowering effect of liraglutide, 40 mice were divided into normal food diet (NFD), high-fat food (HFD), 10.0 mg/kg/d simvastatin-treated HFD (SIM + HFD), 200 and 400 µg/kg/d liraglutide-treated HFD (LL + HFD and HL + HFD) groups for 5 weeks. We found that liraglutide could upregulate cholesterol 7α-hydroxylase (CYP7A1) and LDL-receptor (LDLR), whereas downregulate 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Besides, liraglutide enhance abundance of lactobacillaceae in gut of hyperlipidemic mice and increase bile tolerance ability of LAB by upregulating bile salt hydrolases, and the lysate of liraglutide-sensitive LAB could also directly downregulate HMGCR, the key enzyme in cholesterol synthesis, and inhibit hepatocyte steatosis. These findings might provide new theoretical guidance for clinical application of liraglutide and research and development of antiobesity, hypolipidemic, and cholesterol-lowering drugs or functional foods.

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.

Defining a minimum number of examined lymph nodes improves the prognostic value of lymphadenectomy in pancreas ductal adenocarcinoma.

BACKGROUND: Lymph node (LN) metastasis is associated with decreased survival following resection for pancreatic ductal adenocarcinoma (PDAC). In N0 disease, increasing total evaluated LN (ELN) correlates with improved outcomes suggesting patients may be understaged when LNs are undersampled. We aim to assess the optimal number of examined lymph nodes (ELN) following pancreatectomy. METHODS: Data from 1837 patients undergoing surgery were prospectively collected. The binomial probability law was utilized to analyze the minimum number of examined LNs (minELN) and accurately characterize each histopathologic stage. LN ratio (LNR) was compared to American Joint Committee on Cancer (AJCC) guidelines. RESULTS: As ELN total increased, the likelihood of finding node positive disease increased. An evaluation based upon the binomial probability law suggested an optimal minELN of 12 for accurate AJCC N staging. As the number of ELNs increased, the discriminatory capacity of alternative strategies to characterize LN disease exceeded that offered by AJCC N stage. CONCLUSION: This is the first study dedicated to optimizing histopathologic staging in PDAC using models of minELN informed by the binomial probability law. This study highlights two separate cutoffs for ELNs depending upon prognostic goal and validates that 12 LNs are adequate to determine AJCC N stage for the majority of patients.

Optimized modification of the eighth edition of AJCC TNM staging system for resected pancreatic ductal adenocarcinoma.

Aim: To reassess the prognostic performance of the American Joint Committee on Cancer (AJCC) 8th edition for pancreatic ductal adenocarcinoma (PDAC) and optimize the categorization of PDAC staging. Patients & methods: A total of 11,858 patients with resected PDAC from the Surveillance, Epidemiology and End Results database were retrospectively enrolled by sequential analyses. Results: There was no statistical significance between stage IIA and IIB tumors with hazard ratios of 2.065 and 2.184 (p = 0.620) for stages IIA and IIB, respectively. With the proposed modification, there was a significant difference between the hazard ratios of stages IIIA and IIIB which were 2.481 and 2.715, respectively (p = 0.009). The C-index of modified system was 0.609, slightly higher than AJCC 8th staging system 0.604. Conclusion: We proposed a modified eighth edition of the AJCC staging system by combining stage IIA with IIB and further subclassifying stage III patients in order to lead to better discriminative power.

Correction to: A Novel Rabbit Model for Benign Biliary Stricture Formation and the Effects of Medication Infusions on Stricture Formation.

The original version of the article unfortunately contained an error in funding information. This has been corrected with this erratum.