Clinical characteristics and mortality of mucormycosis in hematological malignancies: a retrospective study in Eastern China.

BACKGROUND: Mucormycosis is a significant cause of morbidity and mortality in patients with hematological malignancies, but its characteristics are not fully understood. This study aimed to gain a better understanding of the clinical features of mucormycosis in patients with hematological malignancies in eastern China. METHODS: A single-center retrospective analysis was conducted on the demographic profile, microbiology, management, and 90-day mortality of mucormycosis patients with hematological malignancies between 2018 and 2023. RESULTS: A total of 50 cases were included in the study, consisting of 11 proven and 39 probable cases of mucormycosis. The median age of the patients was 39.98 ± 18.52 years, with 52% being male. Among the cases, 46% had acute myeloid leukemia (AML), 16% had acute lymphoblastic leukemia (ALL), and 16% had myelodysplastic syndrome. The most common manifestations of mucormycosis were pulmonary (80%), disseminated (16%), and rhinocerebral (4%). The diagnosis was confirmed through histology, culture, microscopy, and molecular diagnostic techniques. The most commonly identified fungal species were Cunninghamella (40%), Rhizopus (26%), and Rhizomucor (22%). Treatment involved antifungals in 84% of cases and surgery in 10% of cases. The 90-day mortality rate was 76%. Logistic regression analysis revealed that treatment with amphotericin B and surgery was associated with improved survival, while neutropenia and administration of voriconazole prior to diagnosis was associated with higher mortality. CONCLUSIONS: Mucormycosis continues to have a high mortality rate in patients with hematological malignancies. Early diagnosis using various techniques, including molecular biology, along with the appropriate use of amphotericin B and surgery when possible, is vital for the successful treatment of mucormycosis.

Inhibition of 14-3-3ε by K50 acetylation activates YAP1 to promote cholangiocarcinoma growth.

14-3-3 proteins are ubiquitous adapters combining with phosphorylated serine/threonine motifs to regulate multiple cellular processes. As a negative regulator, 14-3-3 proteins could sequester the phosphorylated YAP1 in cytoplasm to inhibit its activity. In this study, we identified the K50 acetylation (K50ac) of 14-3-3ε protein and investigated its roles and mechanism in cholangiocarcinoma progression. The NAD (+)-dependent protein deacetylases inhibitor, NAM treatment significantly up-regulated the K50ac of 14-3-3ε. K50R mutation resulted in the decrease of K50ac of 14-3-3ε. The K50ac of 14-3-3ε was reversibly mediated by PCAF acetyltransferase and sirt1 deacetylases. K50ac had no obvious effect on the protein stability of 14-3-3ε, but inhibited the combination of 14-3-3ε with phosphorylated YAP1, which resulted in the activation of YAP1 in cholangiocarcinoma. K50R significantly decreased cholangiocarcinoma cell proliferation in vitro and the growth of tumor xenograft in vivo compared with WT (wild type) 14-3-3ε. The level of K50ac were higher in cholangiocarcinoma tissues accompanied by the accumulation of YAP1 in nuclear than para-carcinoma tissues. Our study revealed the underlying mechanism of K50ac of 14-3-3ε and its roles in cholangiocarcinoma, providing a potential targeting for cholangiocarcinoma therapy.

Risk-taking in the human brain: An activation likelihood estimation meta-analysis of the balloon analog risk task (BART).

The Balloon Analog Risk Task (BART) is increasingly used to assess risk-taking behavior and brain function. However, the brain networks underlying risk-taking during the BART and its reliability remain controversial. Here, we combined the activation likelihood estimation (ALE) meta-analysis with both task-based and task-free functional connectivity (FC) analysis to quantitatively synthesize brain networks involved in risk-taking during the BART, and compared the differences between adults and adolescents studies. Based on 22 pooled publications, the ALE meta-analysis revealed multiple brain regions in the reward network, salience network, and executive control network underlying risk-taking during the BART. Compared with adult risk-taking, adolescent risk-taking showed greater activation in the insula, putamen, and prefrontal regions. The combination of meta-analytic connectivity modeling with task-free FC analysis further confirmed the involvement of the reward, salience, and cognitive control networks in the BART. These findings demonstrate the core brain networks for risk-taking during the BART and support the utility of the BART for future neuroimaging and developmental research.

KRAS G12D mutation eliminates reactive oxygen species through the Nrf2/CSE/H 2S axis and contributes to pancreatic cancer growth.

In pancreatic cancer, KRAS G12D can trigger pancreatic cancer initiation and development. Rapid tumor growth is often accompanied by excess intracellular reactive oxygen species (ROS) production, which is unfavorable to tumor. However, the regulation of intracellular ROS levels in KRAS mutant pancreatic cancer remains unclear. In this study, we establish BxPC3 stable cell strains expressing KRAS wild type (WT) and G12D mutation and find unchanged ROS levels despite higher glycolysis and proliferation viability in KRAS mutant cells than KRAS WT cells. The key hydrogen sulfide (H 2S)-generating enzyme cystathionine-γ-lyase (CSE) is upregulated in KRAS mutant BxPC3 cells, and its knockdown significantly increases intracellular ROS levels and decreases cell glycolysis and proliferation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is activated by KRAS mutation to promote CSE transcription. An Nrf2 binding site (‒47/‒39 bp) in the CSE promoter is verified. CSE overexpression and the addition of NaHS after Nrf2 knockdown or inhibition by brusatol decreases ROS levels and rescues cell proliferation. Our study reveals the regulatory mechanism of intracellular ROS levels in KRAS mutant pancreatic cancer cells, which provides a potential target for pancreatic cancer therapy.

The impact of preoperative biliary drainage on postoperative outcomes in patients with malignant obstructive jaundice: a retrospective analysis of 290 consecutive cases at a single medical center.

BACKGROUND: The efficacy of preoperative biliary drainage (PBD) has been debated for several decades, and yet indications for PBD remain controversial. The aim of this study was to compare the postoperative morbidity and mortality in patients with malignant obstructive jaundice undergoing direct surgery versus surgery with PBD. METHODS: All consecutive patients with malignant obstructive jaundice who underwent radical resection between June 2017 and December 2019 at Zhongshan Hospital were analyzed retrospectively. The study population was divided into two groups: PBD group (PG) and direct surgery group (DG). The subgroups were chosen based on the site of obstruction. Perioperative indicators and postoperative complications were compared and analyzed. RESULTS: A total of 290 patients were analyzed. Postoperative complications occurred in 134 patients (46.4%). Patients in the PG group had a lower overall rate of postoperative complications compared with the DG group, with perioperative total bilirubin (TB) identified as an independent risk factor in multivariate analysis (hazard ratio = 1.004; 95% confidence interval 1.001-1.007; P = 0.017). Subgroup analysis showed that PBD reduced the complication rate in patients with proximal obstruction. In the proximal-obstruction subgroup, a preoperative TB level > 162 µmol/L predicted postoperative complications. CONCLUSIONS: PBD may reduce the overall rate of postoperative complications among patients with proximal malignant obstructive jaundice. TRIAL REGISTRATION: ClinicalTrials.gov, 2018ZSLC 24 . Registered May 17, 2018, https://clinicaltrials.gov/ .

The clinical and prognostic factors for biliary neuroendocrine neoplasm: a study based on the SEER database.

BACKGROUND: In this study, we aimed at elucidating the postoperative survival and prognostic factors in patients with biliary neuroendocrine neoplasm (NEN). METHODS: Cases of biliary system NEN and adenocarcinoma from 1975 to 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. A propensity score matching (PSM) method was used to adjust baseline differences in clinicopathological characteristics in our analysis. The Kaplan-Meier analysis was carried out for survival analysis. RESULTS: A total of 233 patients with biliary system NEN were enrolled in this study, of which 119 patients' lesions located in gallbladder, while the others' located in bile duct. The postoperative overall survival of bile duct NEN is significantly longer than that of gallbladder NEN (P < 0.001). For gallbladder NENs, surgery method (P = 0.020) and lymph node metastasis (P = 0.018) were identified as independent prognostic factors. In terms of ampulla of vater (AOV) NENs, age (P = 0.017) and lymph node metastasis (P = 0.006) were identified as independent prognostic factors, while grade (P = 0.002) and lymph node metastasis (P = 0.036) were identified as independent prognostic factors for extrahepatic bile duct (EBD) NENs. PSM analysis indicated that patients with biliary duct NENs have a better postoperative prognosis than biliary duct adenocarcinoma. CONCLUSIONS: Patients with NEN have better overall survival than patients with adenocarcinoma. Gallbladder NEN has an adverse prognosis than that of biliary tract NEN. The pathological subtype, differentiation, lymph node metastasis, surgery method, and lymph node resection could affect the postoperative prognosis of the gallbladder and biliary tract NEN.

Prediction Efficacy for Clinical Outcome of Prognostic Nutritional Index in Patients with Resectable Biliary Tract Cancer Depends on Sex and Obstructive Jaundice Status.

BACKGROUND: The Prognostic Nutritional Index (PNI), a marker of nutritional status and systemic inflammation, is a proven prognostic biomarker in some cancers. The predictive value of PNI in biliary tract cancer (BTC) has not been established. OBJECTIVE: The aim of this study was to determine the relationship between the PNI and outcomes of resectable BTC. METHODS: In total, 430 patients with stage I-III resectable BTC [gallbladder cancer (GBC), n = 212; cholangiocarcinoma (CHO), n = 218] who had attended Fudan University Zhongshan Hospital were enrolled. The relationship between the PNI and clinical outcomes was evaluated both in the whole cohort and in selected subgroups. RESULTS: Eligible patients were classified into PNI-low (PNI < 45) and PNI-high (PNI ≥ 45) groups. The PNI-low group had significantly worse overall survival (OS) in both the whole cohort (p = 0.002) and in the GBC subgroup (p = 0.001), but had similar OS as the PNI-high group in the CHO subgroup (p = 0.328). Multivariate analysis revealed that low PNI is an independent risk factor for worse survival in GBC (hazard ratio 1.623, 95% confidence interval 1.063-2.480, p = 0.026). PNI was found to predict clinical outcome in women (p < 0.001) and patients without obstructive jaundice (p = 0.017) with GBC, but was not a prognostic factor in any subgroup with CHO. The estimated area under the time-dependent receiver operating characteristic curve was significantly greater when TNM stage was combined with PNI in women with GBC. CONCLUSIONS: PNI is an independent predictor of OS in GBC, but not in CHO. It has no prognostic value in men with GBC or patients with obstructive jaundice.

Clinical correlation of cadherin-17 marker with advanced tumor stages and poor prognosis of cholangiocarcinoma.

BACKGROUND AND OBJECTIVES: In this retrospective study, we examined the CA17 tissue expression and analyzed its clinical significance in cholangiocarcinoma (CCA). MATERIALS AND METHODS: Immunohistochemistry was performed to assess CA17 expression on tissue microarrays in a training cohort enrolling 120 CCA patients and a validation cohort comprising 60 CCA patients. Image pro plus was applied to score the staining intensity and expression level of CA17 marker. Kaplan-Meier analysis, Cox's proportional hazards regression, and nomogram were applied to evaluate the prognostic significance of CA17. RESULTS: CA17 cancer biomarker over-expression was significantly observed in CCA compared to their non-tumor counterparts, and positively correlated with aggressive tumor phenotypes, like lymph node metastasis. Meanwhile, patients with high expression of CA17 correlated with worse postoperative overall survival (OS) and recurrence-free survival. Besides, multivariate analysis identified that CA17 expression was an independent prognostic factor for cholangiocarcinoma patients, which indicated that the CA17 could be more efficient than serum CA19-9 in predicting the OS of CCA patients. Notably, the nomogram integrating CA17 expression had better prognostic performance as compared with current TNM staging systems. CONCLUSION: CA17 was an independent adverse prognostic factor for CCA patients' survival, which may serve as a promising prognostic biomarker for CCA patients.

MUC16 C-terminal binding with ALDOC disrupts the ability of ALDOC to sense glucose and promotes gallbladder carcinoma growth.

The MUC16 C-terminal (MUC16c) level is associated with tumor serum CA-125 levels, however, the roles remain unclear in gallbladder carcinoma (GBC). In this study, we found that MUC16c promoted glucose uptake and glycolysis for GBC cell proliferation. Mass spectrometry analysis suggested that MUC16c could combine with aldolase. The ALDOC mRNA and protein are overexpressed in GBC tumors. The IHC results also showed the consistent up-regulation of. ALDOC and MUC16c level in GBC tumor tissues than in peritumor tissues. We determined that MUC16c combining with ALDOC promoted ALDOC protein stability and disrupted the ability of ALDOC sensing glucose deficiency, which activated AMPK pathway and increased GBC cell proliferation. ALDOC knockdown significantly inhibited the glucose uptake and glycolysis induced by MUC16c. Our study established important roles of MUC16c promoting GBC cell glycolysis and proliferation and revealed the underlying mechanism of CA-125-related heavy tumor metabolic burden in GBC.

3D laparoscopic common bile duct exploration versus 2D in choledocholithiasis patients: a propensity score analysis.

BACKGROUND: This study was designed to investigate whether 3D laparoscopic common bile duct (LCBDE) could improve surgical outcomes in choledocholithiasis patients compared with 2D LCBDE. METHOD: Propensity score-matched analysis was performed to balance the bias in baseline characteristic between two groups. RESULTS: 213 patients underwent 3D LCBDE and 212 patients receiving 2D LCBDE were enrolled in this study. The operation time and blood loss in 3D group were significantly less than that in 2D group. After propensity score matching, a total of 114 paired cases were selected from the two groups. The operation time and blood loss in 3D group remain significantly lower than in 2D group. In the end, the subgroup analysis based on abdominal adhesion level was performed and it was observed that for patients with adhesion level 1 and level 2, 3D surgery could obviously decrease the operation time and intraoperative blood loss. CONCLUSIONS: 3D LCBDE would significantly reduce operation time, blood loss, and conversion rate to laparotomy in choledocholithiasis patients versus 2D LCBDE. For patients with abdominal adhesions level 1 and level 2, 3D LCBDE could provide better surgical outcomes than 2D LCBDE.

A Novel Method for the Complex Tube System Reconstruction and Measurement.

Pipe structures are at the base of the entire industry. In the industry structure, heat and vibration are transmitted in each pipe. The minimum distance between each pipe is significant to the security. The assembly error and the deformation of the pipeline positions after multiple runs are significant problems. The reconstruction of the multi-pipe system is a critical technical difficulty in the complex tube system. In this paper, a new method for the multi-pipes structure inspection is presented. Images of the tube system are acquired from several positions. The photogrammetry technology calculates positions, and the necessary coordination of the structure is reconstructed. A convolution neural network is utilized to detect edges of tube-features. The new algorithm for tube identification and reconstruction is presented to extract the tube feature in the image and reconstruct the 3D parameters of all tubes in a multi-pipes structure. The accuracy of the algorithm is verified by simulation experiments. An actual engine of the aircraft is measured to verify the proposed method.

A Novel Concentric Circular Coded Target, and Its Positioning and Identifying Method for Vision Measurement under Challenging Conditions.

Coded targets have been demarcated as control points in various vision measurement tasks such as camera calibration, 3D reconstruction, pose estimation, etc. By employing coded targets, matching corresponding image points in multi images can be automatically realized which greatly improves the efficiency and accuracy of the measurement. Although the coded targets are well applied, particularly in the industrial vision system, the design of coded targets and its detection algorithms have encountered difficulties, especially under the conditions of poor illumination and flat viewing angle. This paper presents a novel concentric circular coded target (CCCT), and its positioning and identifying algorithms. The eccentricity error has been corrected based on a practical error-compensation model. Adaptive brightness adjustment has been employed to address the problems of poor illumination such as overexposure and underexposure. The robust recognition is realized by perspective correction based on four vertices of the background area in the CCCT local image. The simulation results indicate that the eccentricity errors of the larger and smaller circles at a large viewing angle of 70° are reduced by 95% and 77% after correction by the proposed method. The result of the wing deformation experiment demonstrates that the error of the vision method based on the corrected center is reduced by up to 18.54% compared with the vision method based on only the ellipse center when the wing is loaded with a weight of 6 kg. The proposed design is highly applicable, and its detection algorithms can achieve accurate positioning and robust identification even in challenging environments.

Crack Length Measurement Using Convolutional Neural Networks and Image Processing.

Fatigue failure is a significant problem in the structural safety of engineering structures. Human inspection is the most widely used approach for fatigue failure detection, which is time consuming and subjective. Traditional vision-based methods are insufficient in distinguishing cracks from noises and detecting crack tips. In this paper, a new framework based on convolutional neural networks (CNN) and digital image processing is proposed to monitor crack propagation length. Convolutional neural networks were first applied to robustly detect the location of cracks with the interference of scratch and edges. Then, a crack tip-detection algorithm was established to accurately locate the crack tip and was used to calculate the length of the crack. The effectiveness and precision of the proposed approach were validated through conducting fatigue experiments. The results demonstrated that the proposed approach could robustly identify a fatigue crack surrounded by crack-like noises and locate the crack tip accurately. Furthermore, crack length could be measured with submillimeter accuracy.

Low immune index correlates with favorable prognosis but with reduced benefit from chemotherapy in gallbladder cancer.

Use of immune index is a new potential approach for cancer classification and prediction. To investigate the status and clinical effect of immune index in gallbladder cancer (GBC), 238 GBC patients from Zhongshan Hospital affiliated to Fudan University were involved in the present study, including 113 patients in a training set and 125 patients in a validation set. Five immune cells (macrophages, neutrophils, regulatory T cells, cytotoxic T cells and mast cells) were selected based on a literature review and the immune index for each patient was calculated using the LASSO regression. A low immune index (<1) was defined as immunotype A and a high immune index (≥1) was defined as immunotype B. The 5-year overall survival rate for immunotype A was higher than that for immunotype B in the training set and the validation set (70.0% vs 37.0%, P < 0.001; 68.9% vs 47.5%, P = 0.002; respectively). Moreover, the immune index showed higher prediction efficiency compared with all the single immune cells which we selected. When combined with the immune index, the areas under the curve (AUC) of the TNM staging system in both sets were elevated from 0.677 to 0.787 and from 0.631 to 0.694, respectively. Interestingly, gemcitabine-based chemotherapy only benefits stage II patients of immunotype B and stage III patients of both immunotype A and immunotype B (P = 0.015, P = 0.030, P = 0.011, respectively) but does not work in stage II patients of immunotype A (P = .307). Taken together, the immune index could effectively predict prognosis and the benefits of gemcitabine-based chemotherapy and might improve on the TNM staging system.

High infiltration of mast cells is associated with improved response to adjuvant chemotherapy in gallbladder cancer.

Recent studies have reported that tumor-infiltrating mast cells (TIM) play an important role in tumor regression, but the effect of TIM in gallbladder cancer (GBC) remains unclear. The present study aims to investigate the prognostic value of TIM in GBC patients and its responsiveness to gemcitabine-based adjuvant chemotherapy (ACT). A total of 298 GBC patients from Zhongshan Hospital were recruited for this study. TIM infiltration was measured by immunohistochemical staining. Accumulation of TIM is significantly associated with prolonged overall survival in GBC patients. The benefit from gemcitabine-based ACT was superior among patients with high infiltration of TIM with GBC. Multivariate analysis identified TIM infiltration as an independent prognostic factor for overall survival. A heatmap showed that TIM-activated gene signatures were positively correlated with CD8+ T cells' gene signatures. Gene set enrichment analysis (GSEA) suggested that TIM was related to multiple T cell-related processes and signaling pathways, including the interferon gamma signaling pathway and the leukocyte migration signaling pathway. It was confirmed that CD8+ T cell infiltration was positively correlated with high TIM infiltration in tissue microarray (TMA), suggesting that TIM infiltration was linked to the immune surveillance in GBC. TIM can be used as an independent prognostic factor and a predictor of therapeutic response of gemcitabine-based ACT in GBC patients, which may mediate immune surveillance by recruiting and activating CD8+ T cells in GBC.

Laparoscopic common bile duct exploration in patients with previous abdominal biliary tract operations.

BACKGROUND: A history of abdominal biliary tract surgery has been identified as a relative contraindication for laparoscopic common bile duct exploration (LCBDE), and there are very few reports about laparoscopic procedures in patients with a history of abdominal biliary tract surgery. METHODS: We retrospectively reviewed the clinical outcomes of 227 consecutive patients with previous abdominal biliary tract operations at our institution between December 2013 and June 2019. A total of 110 consecutive patients underwent LCBDE, and 117 consecutive patients underwent open common bile duct exploration (OCBDE). Patient demographics and perioperative variables were compared between the two groups. RESULTS: The LCBDE group performed significantly better than the OCBDE group with respect to estimated blood loss [30 (5-700) vs. 50 (10-1800) ml; p = 0.041], remnant common bile duct (CBD) stones (17 vs. 28%; p = 0.050), postoperative hospital stay [7 (3-78) vs. 8.5 (4.5-74) days; p = 0.041], and time to oral intake [2.5 (1-7) vs. 3 (2-24) days; p = 0.015]. There were no significant differences in the operation time [170 (60-480) vs. 180 (41-330) minutes; p = 0.067]. A total of 19 patients (17%) in the LCBDE group were converted to open surgery. According to Clavien's classification of complications, the LCBDE group had significantly fewer postoperative complications than the OCBDE group (40 vs. 57; p = 0.045). There was no mortality in either group. Multiple previous operations (≥ 2 times), a history of open surgery, and previous biliary tract surgery (including bile duct or gallbladder + bile duct other than cholecystectomy alone) were risk factors for postoperative adhesion (p = 0.000, p = 0.000, and p = 0.000, respectively). CONCLUSION: LCBDE is ultimately the least invasive, safest, and the most effective treatment option for patients with previous abdominal biliary tract operations and is especially suitable for those with a history of cholecystectomy, few previous operations (< 2 times), or a history of laparoscopic surgery.

Serum lipid levels are the risk factors of gallbladder stones: a population-based study in China.

BACKGROUND: Gallstones are the cause of a majority of biliary tract discomfort. Although many community-based studies have addressed the risk factors for gallstone disease (GSD), little is known about GSD prevalence and risk factors in Chinese populations. METHODS: From January 2014 to January 2015, participants (N = 2,068,523) were recruited by Meinian Onehealth Healthcare Co., Ltd. They received a physical examination, and GSD was determined by ultrasound. RESULTS: The prevalence of GSD was 8.1%. Risks of GSD were similar between males and females in all age groups. Risk factors for gallstones include body mass index, waist circumference, waist-to-hip ratio, and physical activity, as well as biological factors such as age, sex, and elevated blood lipid levels. Serum lipid levels of GSD were statistically different from controls in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (H-DL), low-density lipoprotein cholesterol (LDL), and apolipoprotein B (APOB). Furthermore, TC > 5.00 mmol/L, TG > 1.39 mmol/L, HDL < 1.19 mmol/L, LDL > 3.04 mmol/L, and APOB > 0.97 mmol/L were risk factors for gallstones. CONCLUSIONS: Serum lipid levels are associated with GSD. TC, TG, LDL, and APOB are risk factors, while HDL is a protective factor.

PLAC8 overexpression correlates with PD-L1 upregulation and acquired resistance to chemotherapies in gallbladder carcinoma.

Gallbladder carcinoma (GBC) is always diagnosed at an advanced stage, and patients often miss the opportunity for surgery. Gemcitabine (GEM) and platinum-based drugs, including oxaliplatin (OXA), are mainstays of chemotherapy. However, drug resistance causes treatment failure. Hence, salvage mechanisms are critical to improve outcomes. This study revealed the positive correlation between placenta-specific protein 8 (PLAC8) overexpression and PD-L1 overexpression in GBC. Given the roles of PLAC8 and PD-L1 in chemotherapy resistance, GEM-resistant and OXA-resistant cell lines (SGC966GR and SGC966OR, respectively) were established to test whether and how PLAC8 and PD-L1 function in chemotherapy resistance. Drug-insensitive SGC966GR and SGC966OR cells upregulated MRP and MDR1 and had high expression of PLAC8. PLAC8 blockade using siRNA reversed chemotherapy resistance and downregulated MRP and MDR1 in SGC966GR and SGC966OR cells, suggesting that PLAC8 mediates chemotherapy resistance in GBC. Consistent with the increased mRNA levels of PD-L1 after the acquisition of resistance, PLAC8 knockdown reduced PD-L1 mRNA expression in SGC966GR and SGC966OR cells. In conclusion, PLAC8 overexpression in GBC patients positively correlated with PD-L1 expression. PLAC8 conferred resistance to GEM and OXA by upregulating PD-L1 expression, and PLAC8 or PD-L1 blockade may have potential for overcoming chemotherapy resistance, providing therapeutic options for chemotherapy-refractory GBC patients.

Tumor-infiltrating neutrophils predict prognosis and adjuvant chemotherapeutic benefit in patients with biliary cancer.

Tumor-infiltrating neutrophils (TIN) carry out quite significant but opposite functions in different cancers, and their function in biliary cancer has not been fully characterized. To investigate the prognostic significance of TIN in biliary cancer, a training set (n = 118) and a validation set (n = 127) were involved in this study. TIN were evaluated by immunohistochemical staining of CD66b, and then defined as low (neutrophils <18/high-power field [HPF]) vs high (neutrophils ≥18/HPF). Kaplan-Meier curve, Cox proportional hazards models and receiver operating characteristic curve were used to assess the prognostic significance. TIN was identified as an independent prognostic factor for overall survival in the training set (HR: 4.720; 95% CI: 2.623-8.493; P < .001) which was confirmed in the validation set (HR: 4.993; 95% CI: 2.626-9.492; P < .001). Notably, among patients with stage III and IV disease, those with low TIN could benefit from adjuvant chemotherapy, with a reduced risk of compromised survival compared with those with high TIN (HR: 0.294; 95% CI: 0.099-0.873; P = .047 in the training set; and HR: 0.100; 95% CI: 0.022-0.462; P = .006 in the validation set). In addition, TIN were negatively related to biological pathways as regulation of activated T-cell proliferation and lymphocyte-mediated immunity, and showed a negative correlation with CD8 +  T cells (r = -.324, P < .001). Taken together, our results implicate TIN as an independent marker of prognosis and indicator of patients who would benefit from adjuvant chemotherapy in biliary cancer.

Tumor-infiltrating mast cells predict prognosis and gemcitabine-based adjuvant chemotherapeutic benefit in biliary tract cancer patients.

BACKGROUND: Recent studies have reported TIMs play an important role in tumors progression or regression, but the effect of TIMs in biliary tract cancer remains unclear. The aim of this study is to investigate the prognostic value of tumor infiltrating mast cells (TIMs) and its influence on gemcitabine-based adjuvant chemotherapy (ACT) benefits in biliary tract cancer patients after surgery. METHODS: TIMs were evaluated by immunohistochemical staining of tryptase in 250 patients with resected gallbladder carcinoma (GBC) or extrahepatic bile duct carcinoma (EBDC) from Zhongshan Hospital. The relationships between TIMs and clinicopathological factors and postoperative prognosis were analyzed respectively. RESULTS: High TIMs infiltration was significantly correlated with prolonged overall survival (OS). Furthermore, multivariate analysis indicated TNM stage and TIMs as independent prognostic factors for OS. Patients with high TIMs infiltration appeared to significantly benefit from Gemcitabine-based ACT in the discovery and validation cohorts. Spearman analysis identified that TIMs infiltration were positively correlated with anti-tumor CD8+ T cells. CONCLUSION: TIMs infiltration is an independent favorable prognostic factor in GBC and EBDC patients, which could better stratify patients with different prognosis and predict benefit from gemcitabine-based ACT.