Establishment of a cholangiocarcinoma risk evaluation model based on mucin expression levels.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant cancer, characterized by frequent mucin overexpression. MUC1 has been identified as a critical oncogene in the progression of CCA. However, the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still incomplete. AIM: To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA patients. METHODS: Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins, complemented by bioinformatic analyses. Subsequent validations were conducted through spatial transcriptomics and immunohistochemistry. The construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm, which was further confirmed by independent cohorts and diverse data types. RESULTS: CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased invasiveness. MUC5AC-high cells were found to promote CCA progression through WNT signaling. MUC5B-high cells exhibited robust cellular oxidation activities, leading to resistance against antitumoral treatments. MUC13-high cells were observed to secret chemokines, recruiting and transforming macrophages into the M2-polarized state, thereby suppressing antitumor immunity. MUC16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with neutrophils. Utilizing the expression levels of these mucins, a risk factor evaluation formula for CCA was developed and validated across multiple cohorts. CCA samples with higher risk factors exhibited stronger metastatic potential, chemotherapy resistance, and poorer prognosis. CONCLUSION: Our study elucidates the functional mechanisms through which mucins contribute to CCA development, and provides tools for risk stratification in CCA.

SPINK1 Overexpression Correlates with Hepatocellular Carcinoma Treatment Resistance Revealed by Single Cell RNA-Sequencing and Spatial Transcriptomics.

Low efficacy of treatments and chemoresistance are challenges in addressing refractory hepatocellular carcinoma (HCC). SPINK1, an oncogenic protein, is frequently overexpressed in many HCC cases. However, the impact of SPINK1 on HCC treatment resistance remains poorly understood. Here, we elucidate the functions of SPINK1 on HCC therapy resistance. Analysis of SPINK1 protein level reveals a correlation between elevated SPINK1 expression and unfavorable prognosis. Furthermore, intercellular variations in SPINK1 expression levels are observed. Subsequent examination of single cell RNA-sequencing data from two HCC cohorts further suggest that SPINK1-high cells exhibit heightened activity in drug metabolic pathways compared to SPINK1-low HCC cells. High SPINK1 expression is associated with reduced sensitivities to both chemotherapy drugs and targeted therapies. Moreover, spatial transcriptomics data indicate that elevated SPINK1 expression correlates with non-responsive phenotype during treatment with targeted therapy and immune checkpoint inhibitors. This is attributed to increased levels of drug metabolic regulators, especially CES2 and CYP3A5, in SPINK1-high cells. Experimental evidence further demonstrates that SPINK1 overexpression induces the expression of CES2 and CYP3A5, consequently promoting chemoresistance to sorafenib and oxaliplatin. In summary, our study unveils the predictive role of SPINK1 on HCC treatment resistance, identifying it as a potential therapeutic target for refractory HCC.

Preoperative Multiparametric Quantitative Magnetic Resonance Imaging Correlates with Prognosis and Recurrence Patterns in Pancreatic Ductal Adenocarcinoma.

Magnetic resonance imaging (MRI) has been shown to be associated with prognosis in some tumors; however, the correlation in pancreatic ductal adenocarcinoma (PDAC) remains inconclusive. In this retrospective study, we ultimately included 136 patients and analyzed quantitative MRI parameters that are associated with prognosis and recurrence patterns in PDAC using survival analysis and competing risks models; all the patients have been operated on with histopathology and immunohistochemical staining for further evaluation. In intravoxel incoherent motion diffusion-weighted imaging (DWI), we found that pure-diffusion coefficient D value was an independent risk factor for overall survival (OS) (HR: 1.696, 95% CI: 1.003-2.869, p = 0.049) and recurrence-free survival (RFS) (HR: 2.066, 95% CI: 1.252-3.409, p = 0.005). A low D value (≤1.08 × 10-3 mm2/s) was significantly associated with a higher risk of local recurrence (SHR: 5.905, 95% CI: 2.107-16.458, p = 0.001). Subgroup analysis revealed that patients with high D and f values had significantly better outcomes with adjuvant chemotherapy. Distant recurrence patients in the high-D value group who received chemotherapy may significantly improve their OS and RFS. It was found that preoperative multiparametric quantitative MRI correlates with prognosis and recurrence patterns in PDAC. Diffusion coefficient D value can be used as a noninvasive biomarker for predicting prognosis and recurrence patterns in PDAC.

Long-term outcomes of surgical approaches for bilateral hepatolithiasis: A real-world six-decade experience at a single center.

BACKGROUND: Bilateral hepatolithiasis is an intractable disease and repeated attacks of acute cholangitis seriously threaten patient health. The surgical approaches evolve along with gradually greater understanding of its pathophysiology. METHODS: This is a retrospective cohort study for bilateral hepatolithiasis from January 1958 to December 2018. Before May 1993 (Group A, n = 70), three surgical approaches were adopted: 37 patients with common bile duct exploration (CBDE), 29 with choledochoenterostomy (CE) and four with partial hepatectomy (PH). After June 1993 (Group B, n = 150), 101 patients underwent Oddi sphincter-preserved cholangioplasty with hepatico-subcutaneous stoma (OSPCHS), and 16 with CBDE, 21 with CE, 12 with PH. The perioperative and long-term outcomes were compared. RESULTS: After 1993, the cholangitis recurrence rate significantly decreased from 49.2% to 20.9%, and the stone recurrence rate from 76.3% to 37.1% (both P < .001). Also, the stone-/cholangitis-free durations were prolonged significantly (median: 50.8 vs 26.4/49.6 vs 16.2 months, both P < .001). Preoperative cholangitis was an independent risk factor for stone recurrence (hazard ratio [HR] = 1.863, P = .018), and residual stone for cholangitis recurrence (HR = 2.838, P < .001). OSPCHS and PH were protective surgical approaches for recurrent stone (CBDE: reference; OSPCHS: HR = .469, P = .016, PH: HR = .219, P = .018) and cholangitis (CBDE: reference; OSPCHS: HR = .421, P = .010, PH: HR = .283, P = .093). CONCLUSIONS: For bilateral hepatolithiasis, the management should focus on hepatobiliary lesion eradication and Oddi sphincter function preservation.

Tumour radiological appearance evaluated by enhanced CT correlates with tumour progression and survival in curable gallbladder cancer.

BACKGROUND: Surgical resection has been proposed for curable gallbladder cancer (GBCA); however, optimal preoperative evaluation and resection planning methods remain unestablished. The aim of this study was to establish the types of CT tumour radiological appearances in GBCA with a focus on its association with clinicopathologic features and its prognostic impact in curable GBCA. METHODS: In all, 118 patients surgically treated for GBCA were identified and CT tumour radiological appearances were reviewed. Models were established and internally validated. Clinicopathologic variables and prognostic impact were analysed for correlation with tumour radiological appearance. RESULTS: The classification and distribution of tumour radiological appearance in these patients was Type 1 (n = 14), Type 2 (n = 60), Type 3 (n = 21), Type 4 (n = 18), and undetermined (n = 5). Among the 113 patients, a higher tendency of T stage and incidence of lymph node metastasis was observed from Type 1 to Type 4. Most Type 1 patients were T1 stage, they have no lymph node involvement or recurrence. With a median follow-up of 25 months (range, 1-135 months), a clear prognostic difference was observed among the 4 types after surgical treatment (p < 0.001). Type 1 patients showed 100% 5-year survival rate. Among the 66 T2 tumours, both tumour location and tumour radiological appearance effectively stratified patient prognosis (p < 0.001, p = 0.007). Introducing tumour radiological appearance into tumour location enabled further prognostic stratification of the 35 T2h tumours (p < 0.001). CONCLUSIONS: Type of CT tumour radiological appearance is a predictor of tumour biology. It may improve preoperative evaluation and resection planning.

Serum Derived Exosomes From Pancreatic Cancer Patients Promoted Metastasis: An iTRAQ-Based Proteomic Analysis.

BACKGROUND: Pancreatic cancer (PC) is one of the most aggressive malignancies and has a poor prognosis despite being extensively researched. The role of serum-derived exosomes in tumorigenesis and the development of PC is still unclear. METHOD: The present study employed iTRAQ-based proteomic analysis to search for differences between the serum exosomes of PC patients and those from control patients. Then, bioinformatics methods were used to analyze the functions of the identified proteins, and the possible functions were verified through cell culture experiments. RESULTS: A total of 611 proteins were identified from exosomes, and 141 proteins were differentially expressed, with 91 up- and 50 down regulated proteins in PC cancer compared to healthy controls. Further analysis indicated that APOE serves as an important hub in the network. In addition, CRP, VWF, APOA2, NIN, and GSK3B potentially interact with many other proteins. We then tested the effect of patient serum-derived exosomes on pancreatic cancer cells and found that patient serum-derived exosomes, but not those from healthy controls, induced cell proliferation, migration, and EMT, supporting the role of exosomes in metastasis. CONCLUSION: Our data suggest that exosomes derived from PC patients may promote PC metastasis.

Postoperative metastasis prediction based on portal vein circulating tumor cells detected by flow cytometry in periampullary or pancreatic cancer.

PURPOSE: The aim of this study was to evaluate the value of flow cytometry (FCM) detection of portal vein circulating tumor cells (CTCs) in predicting postoperative metastasis. METHODS: Samples of portal venous blood and peripheral blood were collected from 39 patients during surgery, and CTCs were detected by FCM, with confirmation by laser confocal microscopy and single-cell sequencing. RESULTS: Among all patients, a portal EpCAM+CD45- percentage ≥24.5×10-4 (P=0.06), peripheral EpCAM+CD45- count ≥97/5 mL (P=0.034), peripheral EpCAM+CD45- percentage ≥4.4×10-4 (P=0.042), and CA242≥3.5 U/mL (P=0.027) were significant predictors of metastasis. Further analysis showed that the portal EpCAM+CD45- ratio ≥24.5×10-4 is a predictor of metastasis (P=0.025) in pancreatic cancer after curative resection. CONCLUSION: CTCs detected by FCM in portal venous blood are of significant value for the prediction of postoperative metastasis in pancreatic or periampullary tumors.

Usefulness of Ultrasound in Differentiating Xanthogranulomatous Cholecystitis from Gallbladder Carcinoma.

Our study was aimed at finding the ultrasound (US) features of xanthogranulomatous cholecystitis (XGC) and evaluating the usefulness of US in differentiating XGC from gallbladder carcinoma (GBC). Through use of an electronic medical record system and the picture archiving and communication system, 31 cases of XGC and 52 cases of GBC with both sonograms and pathologic results were identified. Sonographic features of the abnormal gallbladder were evaluated. The smooth and intact interface between gallbladder lumen and mucosa was observed in most XGC cases (23/31, 74.2%) but in no GBC cases. XGC featured hyper-echoic foci, small hypo-echoic nodules and a layered appearance in the lesion, which were more frequently seen in the XGC group than in the GBC group. In conclusion, US may prove useful in the differential diagnosis of XGC and GBC, but more studies are required.

Pathological analysis of the superior mesenteric artery boundary in preoperative computed tomography of resectable pancreatic head adenocarcinoma.

The aim of the present study was to evaluate the biological and prognostic implications of the superior mesenteric artery (SMA) boundary on preoperative abdominal contrast-enhanced computed tomography (CE-CT) for resectable adenocarcinoma of the pancreatic head. A total of 121 patients treated over a 6-year period at Peking University Third Hospital (Beijing, China) were included in the present study. The pattern of the SMA boundary was investigated on preoperative CE-CT and detailed pathological analysis of the extrapancreatic plexus [the pancreatic head plexus II (PLX-II) located on the right edge of the SMA] was performed. The results revealed that the radiological SMA boundary was associated with the grade of parasympathetic neurogenesis (P=0.014) in PLX-II, and was predictive of postoperative disease-free survival (P=0.014) and liver metastasis (P=0.013). Therefore, it was proposed that extrapancreatic parasympathetic neurogenesis may account for the different patterns of the SMA boundary on preoperative abdominal CE-CT, and affect the prognosis, particularly for liver metastasis in resectable pancreatic head adenocarcinoma.

Metabolomics identifies serum and exosomes metabolite markers of pancreatic cancer.

INTRODUCTION: Pancreatic cancer (PC) is one of the most aggressive malignancies, and it's difficult to diagnosis PC at an early stage, which leads to the poor prognosis of PC. OBJECTIVES: To identifiy the possible prognosis or dignosis metabolite biomarkers in the serum exosome of PC patients. METHODS: We employed LC-DDA-MS based untargeted lipidomic analysis to search for potential candidate biomarkers in the serum exosome of PC patients. Then LC-MRM-MS based targeted lipid quantification was used to validate the trends of the candidate biomarkers in larger sample cohorts. RESULTS: About 270 lipids belonging to 20 lipid species were found significantly dysregulated between the serum exosome of PC patients and healthy controls. 61 of them were validated in larger samples size. We further analysis the correlation between these dysregulated lipids and other PC related factors, and results show that LysoPC 22:0, PC (P-14:0/22:2) and PE (16:0/18:1) are all associated with tumor stage, CA19-9, CA242 and tumor diameter. What's more, PE (16:0/18:1) is also found to be significantly correlated with the patient's overall survival. CONCLUSION: These data reveal dysregulated lipids in serum exosome of PC patients, which have potential to be biomarkers for diagnosis, or unveil pathological relationship between exosome and PC progress.

Intestinal Perforation Secondary to Pits of Jujube Ingestion: A Single-Center Experience with 18 Cases.

BACKGROUND: Ingestion of jujube pits is a common clinical problem, which can be difficult to diagnose and life-threatening if accompanied with intestinal perforation and peritonitis. In this study, 18 cases of intestinal perforation caused by ingestion of jujube pits were reviewed and summarized to discuss the clinical characteristics, diagnosis and treatments. METHODS: From 2012 to 2018, a total of 18 patients diagnosed as intestinal perforation due to ingested pits of jujube in our center were retrospectively reviewed and the manifestations, laboratory tests, imaging examinations and treatment strategies were summarized. RESULTS: The patients comprised of 11 males and 7 females with an average age of 63.5 years. The main clinical manifestation was abdominal pain. Twelve patients (67%) presented to the emergency department with signs of localized peritonitis. CT imaging revealed positive findings in 17 (94%) patients. Conservative treatments were attempted in 3 patients, and the other 15 patients received emergency surgical exploration, where 7 patients had more than one perforation identified during surgery. Five patients were admitted in the surgical intensive care unit after surgery. The average length of stay of all 18 patients was 9.8 days (range 5-24 days). CONCLUSION: Ingestion of jujube pits is a common clinical problem and potentially leads to intestinal perforation and peritonitis. CT imaging is the first imaging modality of choice. Patients with milder symptoms might be managed with cautious conservative treatment, and patients with more than one perforation can be identified during surgery.

Extrapancreatic Neuropathy Correlates with Early Liver Metastasis in Pancreatic Head Adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma has a devastatingly poor prognosis, and most prognostic factors reflected the tumor stage more than the tumors' biology. The peripheral nerve plexus is densely distributed in the tumor micro-environment, and there are interactions between tumor cells and these nerves. Perineural invasion is an important risk factor for tumor recurrence and metastasis in pancreatic head adenocarcinoma, but the concrete types of extrapancreatic neuropathy and its role in predicting prognosis are still not clear. OBJECTIVE: To clarify the role of extrapancreatic neuropathy in the early postoperative liver metastasis and tumor-related mortality in pancreatic head adenocarcinoma and to study the mechanism of tumor recurrence and liver metastasis in pancreatic head adenocarcinoma. METHODS: We reported a retrospective study of 60 patients with resectable pancreatic head adenocarcinoma, all of whom accepted radical pancreaticoduodenectomy. Plexus pancreaticus capitalis II (PLX-II) was the representation of extrapancreatic plexus in our study, and all of these plexus had immunohistochemical staining. We defined the postoperative tumor recurrence and tumor-related mortality within 6 months as the early prognostic indicators and analyzed the pathological alterations in PLX-II among different prognosis groups. RESULTS: There were 18 patients suffering early postoperative liver metastasis; these two groups differed significantly in the average number of nerve trunks (P<0.001), the proportion of neuritis (P=0.003), the content of sympathetic nerve fibers (P=0.004) and parasympathetic nerve fibers (P<0.001) per unit area of PLX-II. There were 15 patients suffering early postoperative mortality, and there were significant differences between these two groups in the average number of nerve trunks (P<0.001), the proportion of neuritis (P=0.009), the content of sympathetic nerve fibers (P=0.023) and parasympathetic nerve fibers (P<0.001) per unit area of PLX-II. CONCLUSION: The patterns of extrapancreatic neuropathy could reflect the biological behavior of resectable pancreatic head adenocarcinoma, and the pathological features of PLX-II were closely related to early liver metastasis and mortality.

G-CSF associates with neurogenesis and predicts prognosis and sensitivity to chemotherapy in pancreatic ductal adenocarcinoma.

BACKGROUND: Recent studies demonstrated that granulocyte colony-stimulating factor (G-CSF), regularly used for the prevention of neutropenia, is engaged in cancer progression. However, the role of G-CSF in pancreatic ductal adenocarcinoma (PDAC) is not clear. The aim of the present study was to investigate the expression and prognostic value of G-CSF in patients with PDAC. MATERIALS AND METHODS: The localization and expression of G-CSF in PDAC were examined by immunohistochemistry (IHC). The analysis of the levels of G-CSF in plasma was evaluated using ELISA kit. The correlation between G-CSF expression and patients' survival was assessed by Kaplan-Meier analysis. RESULTS: In IHC specimens, G-CSF was discovered predominantly in the cell cytoplasm and expressed in most of PDAC, while in plasma, the systemic level of G-CSF is no different between normal patients and pancreatic cancer patients. In 100 PDAC cases with IHC, patients with grades 2 and 3 were defined as the high expression group (41 patients, 41%), and those with grades 0 and 1 as the low expression group (59 patients, 59%). Significant correlation was noted between high G-CSF expression and neural invasion (P = 0.042) or early recurrence (P < 0.001). G-CSF appeared to be an independent adverse prognostic factor (hazard ratio = 1.774, 95% confidence interval 1.150-2.737, P = 0.010) in addition to N stage (P = 0.002). Specifically, adjuvant chemotherapy consisting of gemcitabine prolongs survival of patients with high G-CSF expression (median survival time 14 months vs 7.5 months). Morphologically, high G-CSF expression cells demonstrate the association with neurogenesis. CONCLUSION: High expression of G-CSF is a prognostic marker and an indicator to chemotherapy response in PDAC.

Pancreatic duct obstruction after pancreaticojejunostomy: implications for early prediction and prevention of long-term pancreatic complications.

BACKGROUND: Pancreatic duct obstructions are common in patients with pancreaticoduodenectomy. However, it is often neglected in follow up. This study was to review the outcomes of pancreatic duct obstruction and explore the prevention of pancreatic duct obstruction. METHODS: A retrospective analysis of 78 patients undergoing pancreaticojejunostomy without reccurence of disease within 24 months between 2004 and 2014. Pancreatic duct obstruction and long-term pancreatic complications were analysed. RESULTS: Twenty-five patients developed pancreatic duct obstruction following pancreaticojejunostomy, 13 of whom were found to have long-term pancreatic complications. The presence of pancreatic duct obstruction and early pancreatic obstruction were associated with long-term pancreatic complications, respectively (p = 0.002, p = 0.002). There are 10 patients with pancreatic duct stent more than 24 months, the postoperative median pancreatic parenchymal thickness in these 10 patients (17.1 mm, range 8.0 to 24.7 mm) was not significantly change than the median in them preoperative (16.4 mm, range 7.2 to 24.7 mm; p = 0.747). All of them have no long-term pancreatic complications, though the difference was not significantly (p = 0.068). CONCLUSIONS: Early pancreatic duct obstruction is associated with postoperative pancreatic long-term complications. Sustained internal pancreatic stent may improve pancreatic duct obstruction.

Laparoscopic treatment for suspected gallbladder cancer confined to the wall: a 10-year study from a single institution.

OBJECTIVE: Although laparoscopic treatment of gallbladder cancer (GBC) has been explored in the last decade, long-term results are still rare. This study evaluates long-term results of intended laparoscopic treatment for suspected GBC confined to the gallbladder wall, based on our experience over 10 years. METHODS: Between August 2006 and December 2015, 164 patients with suspected GBC confined to the wall were enrolled in the protocol for laparoscopic surgery. The process for GBC treatment was analyzed to evaluate the feasibility of computed tomography (CT) and/or magnetic resonance imaging (MRI) combined with frozen-section examination in identifying GBC confined to the wall. Of 159 patients who underwent the intended laparoscopic radical treatment, 47 with pathologically proven GBC were investigated to determine the safety and oncologic outcomes of a laparoscopic approach to GBC. RESULTS: Among the 164 patients, 5 patients avoided further radical surgery because of unresectable disease and 12 were converted to open surgery; in the remaining 147 patients, totally laparoscopic treatment was successfully accomplished. Extended cholecystectomy was performed in 37 patients and simple cholecystectomy in 10. The T stages based on final pathology were Tis (n=6), T1a (n=2), T1b (n=9), T2 (n=26), and T3 (n=4). Recurrence was detected in 11 patients over a median follow-up of 51 months. The disease-specific 5-year survival rate of these 47 patients was 68.8%, and rose to 85% for patients with a normal cancer antigen 19-9 (CA19-9) level. CONCLUSIONS: The favorable long-term outcomes demonstrate the feasibility of combined CT/MRI and frozen-section examination in the selection of patients with GBC confined to the gallbladder wall, confirm the oncologic safety of laparoscopic treatment in selected GBC patients, and favor measurement of preoperative CA19-9 in the selection of GBCs suitable for laparoscopic treatment.

TGF-ß signaling regulates DACT1 expression in intestinal epithelial cells.

DACT1, was first identified as a Dishevelled-associated antagonist of Wnt signaling pathway. It has been reported that DACT1 functions in embryonic development and tumorigenesis. However, the regulation of DACT1 still remains unclear. We found Wnt signaling has no effect on DACT1, but TGF-ß increases expression of DACT1 in intestinal epithelial cells. In addition, the minimal promoter is located in the region of -500bp to +1bp and the region between -3000bp to +1bp enhanced promoter activity. Site-directed mutation analysis was performed and indicated that potential regulatory elements was near -335bp. Our study provided the basic information for the exploration of DACT1 regulation and expression. Moreover, TGF-ß inhibits Wnt signaling to enhance the function of DACT1 inhibiting Wnt signaling.

Surgical resection of primary tumor improves survival of pancreatic neuroendocrine tumor with liver metastases.

This study investigates survival of patients diagnosed with pancreatic neuroendocrine tumor with liver metastases based on local treatment on the primary tumor. Patients diagnosed with stage IV PNET between 2010 and 2014 were identified from the Surveillance Epidemiology and End Results database. Cancer-Specific Survival and Overall Survival were examined. A total of 191 patients with pancreatic neuroendocrine tumor with liver metastases were included in this analysis. There were 47 patients (24.6%) who received surgical resection and 144 (75.4%) who did not. Patients with N1 stage was more likely to be treated with surgical resection. The results showed that surgical resection of primary tumor was associated with Cancer-Specific Survival (p = 0.028) and Overall Survival (p = 0.025) benefit. Not receiving surgery, being unmarried and N1 stage are factors associated with poor survival. This study reveals that local treatment on the primary benefits both Cancer-Specific Survival and Overall Survival in PNET patients with LM. This may be suggestive for the management on this patient population.

Prognostic role of lymphocyte to monocyte ratio for patients with pancreatic cancer: a systematic review and meta-analysis.

BACKGROUND: Lymphocyte to monocyte ratio (LMR) was recently reported as a prognostic factor of pancreatic cancer (PC). However, the prognostic role of LMR in PC remains inconsistent and inconclusive. The aim of this study was to assess the prognostic value of LMR in patients with PC through meta-analysis. METHODS: Eligible studies inquiring into the connection between LMR and survival of patients with PC were collected and extracted by searching PubMed, Embase, Cochrane Library and Web of Science up to May 9, 2017. Pooled hazard ratios (HRs) and the 95% CIs were calculated to assess the prognostic value of LMR on overall survival (OS) and disease-free survival/recurrence-free survival/time to progression (DFS/RFS/TTP). RESULTS: A total of 1,795 patients with PC from 8 studies were included in the meta-analysis. Pooled analysis indicated that elevated LMR predicted a favorable OS (HR =0.56, 95% CI: 0.38-0.83, P=0.004) and DFS/RFS/TTP in PC patients (HR =0.38, 95% CI: 0.15-0.95, P=0.04). Prognostic values of LMR on OS were observed in subgroups with all ethnicities, treatment with surgery, American Joint Committee on Cancer (AJCC) stage of III-IV, and LMR cut-off value ≥3. In addition, low LMR was significantly connected with gender and AJCC stage. CONCLUSION: An elevated LMR is associated with favorable survival in patients with pancreatic cancer.

High expression of muscarinic acetylcholine receptor 3 predicts poor prognosis in patients with pancreatic ductal adenocarcinoma.

AIMS: Recent studies showed that muscarinic acetylcholine receptor 3 (M3), as a muscarinic acetylcholine receptor family member that plays an important role in normal physiological function, is engaged in cancer progression. However, the role of M3 in pancreatic ductal adenocarcinoma (PDAC) is not known. The aim of this study is to investigate the expression and prognostic value of M3 in patients with PDAC. MATERIALS AND METHODS: The localization and expression of M3 in PDAC were examined by immunohistochemistry. VAChT was employed to detect parasympathetic nerve fibers in the corresponding M3 PDAC tissues. The correlation between M3 expression and patients' survival was assessed by Kaplan-Meier analysis. RESULTS: M3 was discovered predominantly localized in the cell cytoplasm and expressed in all specimens of PDAC patients. Significant correlation was noted between increased M3 intensity and high grade of PDAC (P<0.01), more lymph node metastasis (P<0.01) as well as shorter patient overall survival (P<0.01). Morphologically, cells with high M3 expression were more frequently located at the invasive tumor front/tumor budding cells, metastatic lymph nodes and parasympathetic nerve fibers. CONCLUSION: High expression of M3 is a prognostic marker for PDAC.

Heart rate variability in the prediction of survival in patients with cancer: A systematic review and meta-analysis.

PURPOSE: Although the predictive value of vagal nerve activity, indexed by heart rate variability (HRV), has been confirmed in a variety of diseases, its value in the prediction of survival in cancer patients still remains controversial. The aim of this meta-analysis was to evaluate the predictive value of HRV in cancer patients in an evidence based manner. METHODS: A systematic review and meta-analysis was conducted through a comprehensive search of the PubMed, EMBASE and the Cochrane Central Library databases for all studies regarding HRV, vagal nerve activity and cancer. Pooled data of overall survival was analyzed. RESULTS: Six studies with 1286 patients were included in our meta analysis. Analysis of the pooled data revealed that overall survival was significantly longer in the higher HRV group than in the lower HRV group (HR 0.70, 95% CI [0.60, 0.82]; P<0.001, I2=27%). CONCLUSION: The current evidence indicates a predictive value of HRV in the survival of patients with cancer and higher vagal nerve activity might predict longer survival, but the results should be applied with caution considering the heterogeneity between included studies.