Tailored Polypyrrole Nanofibers as Ion-to-Electron Transduction Membranes for Wearable K+ Sensors.

Conductive polymers are recognized as ideal candidates for the development of noninvasive and wearable sensors for real-time monitoring of potassium ions (K+) in sweat to ensure the health of life. However, the low ion-to-electron transduction efficiency and limited active surface area hamper the development of high-performance sensors for low-concentration K+ detection in the sweat. Herein, a wearable K+ sensor is developed by tailoring the nanostructure of polypyrrole (PPy), serving as an ion-to-electron transduction layer, for accurately and stably tracing the K+ fluctuation in human sweat. The PPy nanostructures can be tailored from nanospheres to nanofibers by controlling the supramolecular assembly process during PPy polymerization. Resultantly, the ion-to-electron transduction efficiency (17-fold increase in conductivity) and active surface area (1.3-fold enhancement) are significantly enhanced, accompanied by minimized water layer formation. The optimal PPy nanofibers-based K+ sensor achieved a high sensitivity of 62 mV decade-1, good selectivity, and solid stability. After being integrated with a temperature sensor, the manufactured wearable sensor realized accurate monitoring of K+ fluctuation in the human sweat.

PEDOT:PSS Nanoparticle Membranes for Organic Solvent Nanofiltration.

Recycling of valuable solutes and recovery of organic solvents via organic solvent nanofiltration (OSN) are important for sustainable development. However, the trade-off between solvent permeability and solute rejection hampers the application of OSN membranes. To address this issue, the poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) nanoparticle membrane with hierarchical pores is constructed for OSN via vacuum filtration. The small pores (the free volume of the polymer chain) charge for the solute rejection (high rejection efficiency for low molecule weight solute) and allow solvent passing while the large pores (the void between two PEDOT:PSS nanoparticles) promote the solvent transport. Owing to the lack of connectivity among the large pores, the fabricated PEDOT:PSS nanoparticle membrane enhanced solvent permeance while maintaining a high solute rejection efficiency. The optimized PEDOT:PSS membrane affords a MeOH permeance of 7.2 L m-2 h-1 bar-1 with over 90% rejection of organic dyes, food additives, and photocatalysts. Moreover, the rigidity of PEDOT endows the membrane with distinctive stability under high-pressure conditions. The membrane is used to recycle the valuable catalysts in a methanol solution for 150 h, maintaining good separation performance. Considering its high separation performance and stability, the proposed PEDOT:PSS membrane has great potential for industrial applications.

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.

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.

Micro/Nano-Fabrication of Flexible Poly(3,4-Ethylenedioxythiophene)-Based Conductive Films for High-Performance Microdevices.

With the increasing demands for novel flexible organic electronic devices, conductive polymers are now becoming the rising star for reaching such targets, which has witnessed significant breakthroughs in the fields of thermoelectric devices, solar cells, sensors, and hydrogels during the past decade due to their outstanding conductivity, solution-processing ability, as well as tailorability. However, the commercialization of those devices still lags markedly behind the corresponding research advances, arising from the not high enough performance and limited manufacturing techniques. The conductivity and micro/nano-structure of conductive polymer films are two critical factors for achieving high-performance microdevices. In this review, the state-of-the-art technologies for developing organic devices by using conductive polymers are comprehensively summarized, which will begin with a description of the commonly used synthesis methods and mechanisms for conductive polymers. Next, the current techniques for the fabrication of conductive polymer films will be proffered and discussed. Subsequently, approaches for tailoring the nanostructures and microstructures of conductive polymer films are summarized and discussed. Then, the applications of micro/nano-fabricated conductive films-based devices in various fields are given and the role of the micro/nano-structures on the device performances is highlighted. Finally, the perspectives on future directions in this exciting field are presented.

Comparative analyses between radically re-resected incidental gallbladder carcinoma and primary radically resected gallbladder carcinoma: a single-center experience in China.

PURPOSES: The current study was performed to comparatively evaluate the similarities and differences between cases with radically re-resected incidental gallbladder carcinoma (RRIGBC) and those with primary radically resected gallbladder carcinoma (PRGBC). METHODS: Comparative analysis between patients with RRIGBC and those with PRGBC were performed in terms of clinic-pathological features and long-terms survival. RESULTS: A total of 330 surgically treated GBC patients with 110 patients with IGBC were identified. PRGBCs were generally in a more advanced tumor stage, sharing more aggressive tumor biological features and worse prognosis than those with RRIGBC. Subgroup analyses indicated a comparable prognosis among T1-2 patients between RRIGBC and PRGBC groups. However, among T3-4 patients, patients in the PRGBC group shared a much worse prognosis. Moreover, IGBC itself can be regarded as a prognostic factor but cannot be regarded as an independent prognostic factor. It is the tumor stage which really determined the overall prognosis. CONCLUSION: Patients with RRIGBC were generally in a much earlier tumor stage and shared a much better prognosis than those with PRGBC. IGBC itself can be regarded as a prognostic factor but cannot be regarded as the independent prognostic factors. It is the tumor stage which really determine the overall prognosis.

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.

The effectiveness of combined extrahepatic bile duct resection in radically resected cases with intrahepatic cholangiocarcinoma: a SEER-based retrospective cohort study and an external validation.

OBJECTIVE: To evaluate the effectiveness of the combined extrahepatic bile duct resection (EHBDR) in cases with intrahepatic cholangiocarcinoma (IHCC) in terms of clinicopathological features and long-term survival. METHODS: Radically resected cases with IHCC from 2000 to 2020 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Comparative analyses were performed between resected IHCC patients who received EHBDR and those without EHBDR. Moreover, an external validation was further performed based on a single-center cohort. RESULTS: A total of 1521 radically resected cases with IHCC (EHBDR: 189) were identified from the SEER database. Comparable age, sex, race, marital status, liver cirrhosis, differentiation status, and adjuvant chemotherapy were acquired between the two groups. EHBDR was associated with a higher incidence of adequate lymphadenectomy ( P <0.001). The incidence of cases with T3-4 or N+ disease was significantly higher in EHBDR group ( P <0.001). Adjuvant radiotherapy was more frequently performed in cases with EHBDR ( P <0.001). EHBDR failed to bring any survival benefit and was associated with a worse prognosis even after matching. Similar findings have also been revealed in the external validation cohort ( n =522, EHBDR: 117). EHBDR was associated with more extended resections, more aggressive tumor biological features, and worse prognosis. In the matched validation cohort, EHBDR was still associated with a higher incidence of early recurrence. CONCLUSION: EHBDR was an indicator of the advanced stage and failed to bring any survival benefit. It is the tumor stage that really determines the prognosis. More in-depth analyses focusing on different situations of EHBDR with more detailed clinical data are required.

Prognostic factors for resected cases with gallbladder carcinoma: a systematic review and meta-analysis.

OBJECTIVE: Current meta-analysis was performed to systematically evaluate the potential prognostic factors for overall survival among resected cases with gallbladder carcinoma. METHODS: PubMed, EMBASE, and the Cochrane Library were systematically retrieved and hazard ratio (HR) and its 95% confidence interval were directly extracted from the original study or roughly estimated via Tierney's method. Standard Parmar modifications were used to determine pooled HRs. RESULTS: A total of 36 studies with 11 502 cases were identified. Pooled results of univariate analyses indicated that advanced age (HR=1.02, P =0.00020), concurrent gallstone disease (HR=1.22, P =0.00200), elevated preoperative CA199 level (HR=1.93, P <0.00001), advanced T stage (HR=3.09, P <0.00001), lymph node metastasis (HR=2.78, P <0.00001), peri-neural invasion (HR=2.20, P <0.00001), lymph-vascular invasion (HR=2.37, P <0.00001), vascular invasion (HR=2.28, P <0.00001), poorly differentiated tumor (HR=3.22, P <0.00001), hepatic side tumor (HR=1.85, P <0.00001), proximal tumor (neck/cystic duct) (HR=1.78, P <0.00001), combined bile duct resection (HR=1.45, P <0.00001), and positive surgical margin (HR=2.90, P <0.00001) were well-established prognostic factors. Pathological subtypes ( P =0.53000) and postoperative adjuvant chemotherapy ( P =0.70000) were not prognostic factors. Pooled results of multivariate analyses indicated that age, gallstone disease, preoperative CA199, T stage, lymph node metastasis, peri-neural invasion, lymph-vascular invasion, tumor differentiation status, tumor location (peritoneal side vs hepatic side), surgical margin, combined bile duct resection, and postoperative adjuvant chemotherapy were independent prognostic factors. CONCLUSION: Various prognostic factors have been identified beyond the 8th AJCC staging system. By incorporating these factors into a prognostic model, a more individualized prognostication and treatment regime would be developed. Upcoming multinational studies are required for the further refine and validation.

The significance of peri-neural invasion in patients with resected hilar cholangiocarcinoma: A single-center experience in China.

BACKGROUND: The significance of peri-neural invasion (PNI) in resected patients with hilar cholangiocarcinoma (HCCA) has been rarely explored. Our study was performed to evaluate the significance of PNI in resected HCCA patients in terms of tumor biological features and long-term survival. METHODS: We retrospectively reviewed surgically-treated HCCA patients between June, 2000 and June 2018. SPSS 25.0 software was used for statistical analysis. RESULTS: A total of 239 resected HCCA patients were included (No. PNI: 138). PNI indicated more aggressive tumor biological features. Major vascular reconstruction was more frequently performed in patients with PNI (34.8% vs 24.8%, P = 0.064). Patients with PNI shared a significantly higher percentage of surgical margin width <5 mm (29.0% vs 16.8%, P = 0.02). The proportion of patients with T1-2 disease (31.2% vs 40.6%, P = 0.085) or I-II disease (21% vs 34.7%, P = 0.014) was significantly lower in patients with PNI. The overall morbidity rate was significantly higher in patients with PNI (P = 0.042). A much worse overall survival (OS) (P = 0.0003) or disease-free survival (DFS) (P = 0.0011) in patients with PNI. Even after matching vital prognostic factors, a significantly worse OS (P = 0.0003) or DFS (P = 0.0002) was still observed in patients with PNI. PNI was an independent prognostic factor in both OS (P = 0.011) and DFS (P = 0.024). CONCLUSION: PNI indicated more aggressive tumor biological features and more advanced tumor stage in patients with resected HCCA. PNI can be an independent prognostic factor in both OS and DFS. Future multi-center studies covering various races or populations are required for further validation.

Meta-analysis of prognostic factors for overall survival and disease-free survival among resected patients with combined hepatocellular carcinoma and cholangiocarcinoma.

BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (CHCC-CC) is a rare subtype of primary liver malignancy and has been treated equally as intra-hepatic cholangiocarcinoma (IHCC) according to the 8th AJCC staging system. Owing to its rarity, its prognostic factors have been rarely explored and defined. METHODS: PubMed, EMBASE, the Cochrane Library and Web of Science were searched up till January 1st, 2023 and eligible studies were restricted to studies reported prognostic factors of resected CHCC-CC. Standard Parmar modifications were used to determine pooled univariable hazard ratios (HRs). RESULTS: A total of eleven studies with 1286 patients with resected classical CHCC-CC were finally included. Pooled results indicated that serum tumor biomarkers, including AFP, CA199, and CEA, were prognostic factors for postoperative overall survival (OS) and disease-free survival (DFS). Moreover, liver cirrhosis (P = 0.010), HBV infection (P = 0.030), and HCV infection (P < 0.001) were prognostic factors for OS. Age (HR = 1.03, P = 0.005) was a prognostic factor for DFS. Tumor size (OS: HR = 2, P < 0.001, DFS: HR = 2.15, P < 0.001), tumor number (OS: HR = 2.05, P < 0.001; DFS: HR = 1.96, P = 0.006), surgical margin (OS: HR = 2.33, <0.001001; DFS: HR = 2.35, P < 0.001), node metastasis (OS: HR = 2.96, P < 0.001; DFS: HR = 2.1, P < 0.001), vascular invasion (OS: HR = 2.17, P < 0.001; DFS: HR = 2.64, P < 0.001), and postoperative prophylactic trans-arterial chemotherapy embolization (PPTACE) (OS: HR = 1.67, P = 0.04; DFS: HR = 2.31, P < 0.001) were common prognostic factors for OS and DFS. CONCLUSION: Various risk factors unmentioned in the 8th AJCC staging system were identified. These promising findings would facilitate a more personalized predictive model and help clinicians to stratify patients with different survival outcomes.

Is conventional functional liver remnant volume higher than 40% still sufficient to prevent post-hepatectomy liver failure in jaundiced patients with hilar cholangiocarcinoma? A single-center experience in China.

OBJECTIVE: Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post-hepatectomy liver failure (PHLF) among surgically-treated jaundiced patients with hilar cholangiocarcinoma (HCCA). METHODS: We retrospectively reviewed surgically-treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated. RESULTS: A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic-pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly-acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p < 0.05). Moreover, patients with FLRV lower than 53.5% also shared a significantly higher major morbidity rate as well as a worse prognosis, which were not detected for FLRV of 40%. CONCLUSION: For jaundiced patients with HCCA, a modified FLRV of 53.5% is recommended due to its great impact on PHLF, as well as its correlation with postoperative major morbidities as well as overall prognosis, which might help clinicians to stratify patients with different therapeutic regimes and outcomes. Future multi-center studies for training and validation are required for further validation.

A meta-analysis between robotic hepatectomy and conventional open hepatectomy.

Current meta-analysis was performed to compare robotic hepatectomy (RH) with conventional open hepatectomy (OH) in terms of peri-operative and postoperative outcomes. PubMed, EMBASE, and the Cochrane Library were all searched up for comparative studies between RH and OH. RevMan5.3 software and Stata 13.0 software were used for statistical analysis. Nineteen studies with 1747 patients who received RH and 23,633 patients who received OH were included. Pooled results indicated that patients who received RH were generally younger than those received OH (P < 0.00001). Moreover, RH was associated with longer operative time (P = 0.0002), less intraoperative hemorrhage (P < 0.0001), lower incidence of intraoperative transfusion (P = 0.003), lower incidence of postoperative any morbidity (P < 0.00001), postoperative major morbidity (P = 0.0001), mortalities with 90 days after surgery (P < 0.0001), and shorter length of postoperative hospital stay (P < 0.00001). Comparable total hospital costs were acquired between RH and OH groups (P = 0.46). However, even at the premise of comparable R0 rate (P = 0.86), RH was associated with smaller resected tumor size (P < 0.00001). Major hepatectomy (P = 0.02) and right posterior hepatectomy (P = 0.0003) were less frequently performed in RH group. Finally, we concluded that RH was superior to OH in terms of peri-operative and postoperative outcomes. RH could lead to less intraoperative hemorrhage, less postoperative complications and an enhanced postoperative recovery. However, major hepatectomy and right posterior hepatectomy were still less frequently performed via robotic approach. Future more powerful well-designed studies are required for further exploration.

The prognostic value of combined preoperative PLR and CA19-9 in patients with resectable gallbladder cancer.

The platelet to lymphocyte ratio (PLR) is the marker of host inflammation and it is a potential significant prognostic indicator in various different tumors. The serum carbohydrate antigen 19-9 (CA19-9) is a tumor-associated antigen and it is associated with poor prognosis of gallbladder cancer (GBC). We aimed to analyze the prognostic value of the combination of preoperative PLR and CA19-9 in patients with GBC. A total of 287 GBC patients who underwent curative surgery in our institution was included. To analyze the relationship between PLR and CA19-9 and clinicopathological features. A receiver operating characteristic (ROC) curve was used to identify the optimal cutoff value for PLR and CA19-9. The Kaplan-Meier method was used to estimate the overall survival (OS). Meanwhile, the univariate and multivariate Cox regression models were used to assess the risk factors for OS. The cutoff values of 146.82 and 36.32U/ml defined as high PLR and high CA19-9, respectively. Furthermore, survival analysis showed that patients with PLR > 146.82 and CA19-9 > 36.32 U/ml had a worse prognosis than patients with PLR ≤ 146.82 and CA19-9 ≤ 36.32 U/ml, respectively. The multivariate analysis demonstrated that PLR (hazard ratio (HR) = 1.863, 95% CI: 1.366-2.542, P < 0.001) and CA19-9 (HR = 1.412, 95% CI: 1.021-1.952, P = 0.037) were independent prognostic factors in the GBC patients. When we combined these two parameters, the area under the ROC curve increased from 0.624 (PLR) and 0.661 (CA19-9) to 0.711. In addition, the 1-, 3-, and 5-year OS of group A (patients with PLR ≤ 146.82 and CA19-9 ≤ 36.32 U/ml), group B (patients with either of PLR > 146.82 or CA19-9 > 36.32 U/ml) and group C (patients with PLR > 146.82 and CA19-9 > 36.32 U/ml) were 83.6%, 58.6%, 22.5%, 52.4%, 19.5%, 11.5%, and 42.3%, 11.9%, 0%, respectively. The preoperative PLR and serum CA19-9 are associated with prognosis of patients with GBC. The combination of PLR and CA19-9 may serve as a significant prognostic biomarker for GBC patients superior to either PLR or CA19-9 alone.

Does the size of the neuroendocrine-carcinoma component determine the prognosis of gallbladder cancer?

Background: Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass. Methods: Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses. Demographic features, surgical variables, and tumor characteristics were evaluated for association with patients' overall and recurrence-free survival (OS and RFS). Results: The study included 26 GBNEC, 11 GBMANEC, 4 gallbladder squamous-cell carcinoma (GBSCC), and 7 gallbladder adenocarcinoma (GBADC) mixed with a small fraction of GBNEC. All patients had stage III or higher tumors (AJCC8th edition). The majority of included patients (79.17%) underwent curative surgical resection (R0), with only ten patients having tumoral resection margins. In the analysis comparing patients with GBNEC percentage (GBNEC≥30% vs. GBNEC<30%), the basic demographics and tumor characteristics of most patients were comparable. The prognosis of these patients was also comparable, with a median OS of 23.65 months versus 20.40 months (P=0.13) and a median RFS of 17.1 months versus 12.3 months (P=0.24). However, patients with GBADC or GBSCC mixed with GBNEC <30% had a statistically significant decreased OS and RFS (both P<0.0001)) compared with GBNEC and GBMANEC. Patients with GBNEC who exhibited advanced tumor stages and lymphovascular invasion had a higher risk of experiencing worse overall survival (OS) and recurrence-free survival (RFS). However, a 30% GBNEC component was not identified as an independent risk factor. Conclusion: Patients with GBNEC were frequently diagnosed at advanced stages and their prognosis is poor. The 30% percentage of the GBNEC component is not related to the patient's survival.

Neuroendocrine Component in Extrahepatic Cholangiocarcinoma is Associated with Better Survival: Data from the SEER Study.

INTRODUCTION: This study was performed to evaluate the prognostic value of the neuroendocrine component in patients with extrahepatic cholangiocarcinoma (EHCC). METHODS: Cases with EHCC derived from the SEER database were retrospectively reviewed and analyzed. The clinicopathological features and long-term survival were compared between patients with neuroendocrine carcinoma (NECA) and those with pure adenocarcinoma (AC). RESULTS: A total of 3277 patients with EHCC were included (62 patients with NECA and 3215 patients with AC). T stage (P = 0.531) and M stage (P = 0.269) were comparable between the two groups. However, lymph node metastasis was more frequently detected in NECA (P = 0.022). NECA was correlated with more advanced tumor stage than pure AC (P < 0.0001). Inconsistent differentiation status was also observed between the two groups (P = 0.001). The proportion of patients who received surgery was significantly higher in the NECA group (80.6% vs 62.0%, P = 0.003) while chemotherapy was more frequently performed among patients with pure AC (45.7% vs 25.8%, P = 0.002). Comparable incidence of radiotherapy was acquired (P = 0.117). Patients with NECA shared a better overall survival than those with pure AC (P = 0.0141), even after matching (P = 0.0366). The results of univariate and multivariate analyses indicated that the neuroendocrine component was a protective factor as well as an independent prognostic factor for overall survival (HR < 1, P < 0.05). CONCLUSION: Patients with EHCC with a neuroendocrine component shared a better prognosis than those with pure AC, and NECA could serve as a favorable prognostic factor for overall survival. Considering various unprovided but potentially confounding factors, future more well-conducted research is required.

The Significance of Tumor Locations in Patients with Gallbladder Carcinoma After Curative-Intent Resection.

OBJECTIVE: To evaluate the significance of tumor locations in patients with resected gallbladder carcinoma (GBC) and to supply the indication of extra-hepatic bile duct resection (EHBDR) according to tumor locations. METHODS: Patients with resected GBC from 2010 to 2020 in our hospital were retrospectively analyzed. Comparative analyses and a meta-analysis were performed according to different tumor locations (body/fundus/neck/cystic duct). RESULTS: Article: A total of 259 patients were identified (neck: 71; cystic: 29; body: 51; fundus: 108). Patients with proximal tumors (neck/cystic duct) were often in a more advanced stage and had more aggressive tumor biological features as well as a worse prognosis compared with those with distal tumors (fundus/body). Moreover, the observation was even more obvious between cystic duct and non-cystic duct tumors. Cystic duct tumor was an independent prognostic factor for overall survival (P = 0.01). EHBDR provided no survival advantage even in those with cystic duct tumor. META-ANALYSIS: With our own cohort incorporated, five studies with 204 patients with proximal tumors and 5167 patients with distal tumors were identified. Pooled results revealed that proximal tumors indicated worse tumor biological features and prognosis versus distal tumors. CONCLUSION: Proximal GBC had more aggressive tumor biological features, and a worse prognosis versus distal GBC and cystic duct tumor can be regarded as an independent prognostic factor. EHBDR had no obvious survival advantage even in those with cystic duct tumor and was even harmful in those with distal tumors. Upcoming more powerful well-designed studies are required for further validation.

The role of extra-hepatic bile duct resection in patients with gallbladder carcinoma with peri-neural invasion: A ten-year experience in China.

BACKGROUND: Peri-neural invasion (PNI) in gallbladder carcinoma (GBC) has been demonstrated as a vital prognostic factor. However, whether PNI in patients with GBC can be regarded as a surgical indication of bile duct resection (BDR) remains controversial. METHODS: GBC patients with pathologically-confirmed PNI between September 2010 and September 2020 were retrospectively reviewed. Comparative analyses were performed in patients with PNI according to the performance of BDR. SPSS 25.0 software and Graph pad PRISMA 7.0 software were used for statistical analyses. RESULTS: A total of 70 patients GBC patients with PNI were incorporated. The results of comparative analyses indicated that patients who received BDR were generally in a more advanced stage and often required a more extended radical cholecystectomy. Higher incidences of preoperative jaundice (48.6% vs 2.9%, P < 0.0001), major hepatectomy (25.7% vs 8.6%, P = 0.055), combined multi-visceral resections (48.6% vs 5.7%, P < 0.0001), combined major vascular reconstruction (22.9% vs 2.9%, P = 0.014), and a lower R0 rate (68.6% vs 88.6%, P = 0.039) were detected in patients who received BDR. Even after propensity score matching (PSM), BDR still had no significant survival advantage but only increased the length of postoperative stay and the frequency of postoperative morbidities. CONCLUSION: BDR seemed to have no significant survival advantage in GBC patients with PNI and was only correlated with a longer postoperative hospital stay and a higher rate of morbidities. PNI should not be regarded as a surgical indication of BDR in patients with GBC.

Should more aggressive surgical resection be considered in the treatment for Bismuth types I and II hilar cholangiocarcinoma? A meta-analysis.

Evidence regarding the optical surgical extent for Bismuth type I/II HCCA is lacking. we aims to evaluate the optimal surgical methods for Bismuth type I/II HCCA. Studies comparing bile duct resection (BDR) and BDR combined with liver resection (BDR + LR) for all types of HCCA patients were searched for analyses, and 14 studies were finally included. The main outcomes were the R0 resection rate and overall survival (OS). For all types of HCCA patents, BDR + LR resulted with higher R0 resection rates when comparing with BDR only (RR = 0.70, 95%CI, 0.63-0.78), and patients with R0 resections had eight times longer median survival and more long-time survival outcomes (3 and 5 year OS) comparing to those with non-R0 resections. Bismuth I/II HCCA patients also showed longer median survival and 3-year OS after R0 resections (P = 0.04). Moreover, there was no significant difference in 3-year OS between BDR and BDR + LR (P = 0.89) and we additionally found BDR resulted in less mortality or morbidity rates. In Europe and US, they resulted the R0 resection rates could be comparable between BDR and BDR + LR (P = 0.18), and Bismuth type I HCCA accounted for 75.8%, while in Asia, BDR + LR still resulted with higher R0 resection rates (P < 0.0001) and the Bismuth type I HCCA accounted for only 40.3%. The surgical approaches may not directly impact patient prognosis, patients with R0 resections are usually associated with improved survival outcomes; for selected Bismuth type I/II HCCA, BDR may be an acceptable option with regard to lower morbidity and comparable R0 resection rate comparing with BDR + LR.

The significance of peri-neural invasion in patients with gallbladder carcinoma after curative surgery: a 10 year experience in China.

The significance of peri-neural invasion (PNI) in patients with gallbladder carcinoma (GBC) after curative surgery remains unknown. Current study was performed to evaluate the significance of PNI in resected GBC patients in terms of tumor-related biological features and long-term survival. Patients with GBC between September 2010 and September 2020 were reviewed and analyzed. SPSS 25.0 software were used for statistical analysis. A total of 324 resected GBC patients were identified (No. PNI: 64). An elevated preoperative Ca19.9 level (P = 0.001), obstructive jaundice (P = 0.001), liver invasion (P < 0.0001), lymph-vascular invasion (P < 0.0001), lymph-node metastasis (P < 0.0001), and poor or moderate differentiation status (P = 0.036) were more frequently detected in patients with PNI. Major hepatectomy (P = 0.019), bile duct resection (P < 0.0001), combined multi-visceral resections (P = 0.001), and combined major vascular resections and reconstructions (P = 0.002) were also more frequently detected. However, a significantly lower R0 rate (P < 0.0001) was acquired in patients with PNI. Patients with PNI were generally more advanced disease and shared a much worse prognosis even after matching. PNI was an independent prognostic factor of disease-free survival as well as an independent predictor of early recurrence. Postoperative adjuvant chemotherapy has brought an obvious survival benefit in resected GBC patients with PNI. PNI could be regarded as an indicator of worse prognosis and could serve as an independent predictor of early recurrence. Postoperative adjuvant chemotherapy was correlated with an improved survival for resected GBC patients with PNI. Upcoming multicenter studies covering various races are warranted for further validation.