The prognostic value of age-adjusted Charlson comorbidity index in laparoscopic resection for hilar cholangiocarcinoma.

The prognostic role of the Age-Adjusted Charlson Comorbidity Index (ACCI) in hilar cholangiocarcinoma patients undergoing laparoscopic resection is unclear. To evaluate ACCI's effect on overall survival (OS) and recurrence-free survival (RFS), we gathered data from 136 patients who underwent laparoscopic resection for hilar cholangiocarcinoma at Zhengzhou University People's Hospital between 1 June 2018 and 1 June 2022. ACCI scores were categorized into high ACCI (ACCI > 4.0) and low ACCI (ACCI ≤ 4.0) groups. We examined ACCI's association with OS and RFS using Cox regression analyses and developed an ACCI-based nomogram for survival prediction. Our analysis revealed that higher ACCI scores (ACCI > 4.0) (HR = 2.14, 95%CI: 1.37-3.34) were identified as an independent risk factor significantly affecting both OS and RFS in postoperative patients with hilar cholangiocarcinoma (p < 0.05). TNM stage III-IV (HR = 7.42, 95%CI: 3.11-17.68), not undergoing R0 resection (HR = 1.58, 95%CI: 1.01-2.46), hemorrhage quantity > 350 mL (HR = 1.92, 95%CI: 1.24-2.97), and not receiving chemotherapy (HR = 1.89, 95%CI: 1.21-2.95) were also independent risk factors for OS. The ACCI-based nomogram accurately predicted the 1-, 2-, and 3-year OS rates, with Area Under the Curve (AUC) values of 0.818, 0.844, and 0.924, respectively. Calibration curves confirmed the nomogram's accuracy, and decision curve analysis highlighted its superior predictive performance. These findings suggest that a higher ACCI is associated with a worse prognosis in patients undergoing laparoscopic resection for hilar cholangiocarcinoma. The ACCI-based nomogram could aid clinicians in making accurate predictions about patient survival and facilitate individualized treatment planning.

LncRNA MAPKAPK5_AS1 facilitates cell proliferation in hepatitis B virus -related hepatocellular carcinoma.

We explored the biological role of long non-coding RNA (lncRNA) MAPKAPK5_AS1 (MAAS) and the mechanism of its differential expression in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Differentially expressed lncRNAs in HBV-related HCC were determined using bioinformatics analysis. Gain-of-function experiments were conducted to evaluate the effect of MAAS on cell proliferation. A xenograft model was established for in vivo experiments. Dual-luciferase reporter assays, chromatin immunoprecipitation, co-immunoprecipitation, and methylated RNA immunoprecipitation were performed to elucidate the underlying molecular mechanisms. MAAS was upregulated in HBV-related HCC cancerous tissues and its high expression was closely related to the poor survival probability of patients. Functional assays revealed that MAAS overexpression facilitated the proliferation of HBV+HCC cells in vitro and in vivo. Mechanistically, MAAS promoted the MYC proto-oncogene (c-Myc)-induced transcriptional activation of cyclin-dependent kinase 4 (CDK4), CDK6, and S-phase kinase associated protein 2 via stabilizing c-Myc protein, thereby facilitating G1/S transition. The latter contributed to the paradoxical proliferation of HBV+HCC cells. Although MAAS was upregulated in HBV-related HCC cancerous tissues, it was highly expressed in M2 macrophages, a major phenotype of tumor-associated macrophages in HBV-related HCC, instead of in HBV+HCC cells. HBeAg, an HBV-associated antigen, further elevated the MAAS level in M2 macrophages by enhancing the methyltransferase-like 3-mediated N6-methyladenosine modification of MAAS. The increased MAAS in the M2 macrophages was then transferred to HBV+HCC cells through the M2 macrophage-derived exosomes, promoting cell proliferation. Our findings show that HBV+HCC cell-secreted HBeAg upregulates MAAS expression in M2 macrophages by affecting its m6A modification. The upregulated MAAS is then transferred to HBV+HCC cells via exosomes, facilitating the proliferation of HBV+HCC cells by targeting c-Myc.

The prognostic value of stromal tumor-infiltrating lymphocytes in intrahepatic cholangiocarcinoma: a population-based study.

OBJECTIVE: We assess the predictive value impacted by tumor-infiltrating lymphocytes (TILs) for overall survival (OS) and progression-free survival (PFS) in patients with intrahepatic cholangiocarcinoma (ICC) undergoing complete resection. METHODS: Sixty-eight patients with resectable ICC were included in this study. We studied stromal TIL density and scored it by staining sections from surgically resected ICC patients with hematoxylin and eosin (HE). The clinical data and prognosis of patients with ICC were obtained by searching clinical and follow-up records. RESULTS: A stromal TIL negative status was a predictor of poor OS (HR = 0.41, 95% CI 0.20-0.83, p = .01) and poor PFS (HR = 0.47, 95% CI 0.23-0.97, p = .04) independently. Low stromal TIL density was associated with high levels of CA125 (p = .03) and CA19-9 (p < .01). The high level of CA19-9 (p = .05), high differentiation (p = .02), a large diameter (p = .05), a positive bile duct/vascular cancer embolus (p = .03) and positive satellite nodules (p = .02) were tendencies to develop tumors for patients with a negative status of stromal TIL. CONCLUSION: Our data prompt for the prediction of the PFS and OS of patients with ICC after complete resection, stromal TILs play an important role.

Predictive significance of tumor budding in postoperative liver metastasis of pancreatic neuroendocrine tumors.

BACKGROUND: Although pancreatic neuroendocrine tumors (PNETs) are considered indolent tumors, nearly half of cases metastasize to the liver, which can be lethal. However, effective indicators to predict aggressive behavior have not been well-established. METHODS: In the current study, we explored the prognostic significance of tumor budding in Grade 1-2 PNETs. Hematoxylin-eosin and immunohistochemically stained slides of surgically removed Grade 1-2 PNETs were evaluated. RESULTS: Tumor budding, a histomorphological parameter that corresponds to single cells or small cell clusters (<5 cells), was classified as low (0-10 buds) and high (>10 buds) grade. We observed that tumor budding was correlated with aggressive histopathological parameters, such as T stage, lymph node status, metastasis, and vascular invasion (p < .05). Univariate and multivariate analyses showed that high-grade budding was an independent predictive factor for postoperative liver metastasis (p = .012). Moreover, Grade 1-2 PNETs with high-grade budding was associated with worse overall survival and disease-free survival (p = .0015 and p = .0041, respectively). CONCLUSIONS: We conclude that tumor budding may serve as a valuable parameter in the risk stratification of postoperative liver metastasis and that incorporating tumor budding into histopathological reports may aid in appropriate clinical management.

Carcinoembryonic antigen, α-fetoprotein, and Ki67 as biomarkers and prognostic factors in intrahepatic cholangiocarcinoma: A retrospective cohort study.

INTRODUCTION AND OBJECTIVE: The purpose of this study was to investigate the expression levels and prognostic roles of α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and Ki67 in tumor tissues of intrahepatic cholangiocarcinoma (ICC) patients. PATIENTS OR MATERIALS AND METHODS: The study involved ninety-two ICC patients with complete clinicopathological data and follow-up information, who had previously undergone radical surgery. AFP, CEA, CD10, CD34, and Ki67 were detected in tumor tissues using immunohistochemistry. Statistical tests were used to identify independent risk factors and their associations with overall survival (OS) and disease-free survival (DFS). RESULTS: AFP, CEA and Ki67 were strongly correlated with prognosis. Univariate analysis indicated that higher AFP (P = 0.002), CEA (P < 0.0001), Ki67 (P < 0.0001), CA19-9 (P = 0.039), and CA12-5 (P = 0.002), and larger tumor size (P = 0.001), as well as more advanced tumor node metastasis (TNM) staging (P < 0.0001) were all associated with worse OS. Meanwhile, higher AFP (P = 0.002), CEA (P = 0.001), and Ki67 (P < 0.0001), as well as more advanced TNM staging (P = 0.005) were associated with worse DFS. Multivariate analysis showed that higher AFP (HR = 2.004, 95%CI: 1.146-3.504 P = 0.015), CEA (HR = 2.226, 95%CI: 1.283-3.861 P = 0.004), and Ki67 (HR = 3.785, 95%CI: 2.073-6.909 P < 0.0001), as well as more advanced TNM staging (HR = 2.900, 95%CI: 1.498-5.757 P = 0.002) had associations with worse OS. Furthermore, higher AFP (HR = 2.172, 95%Cl: 1.291-3.654 P = 0.003), CEA (HR = 1.934, 95%Cl: 1.180-3.169 P = 0.009), and Ki67 (HR = 2.203, 95%Cl: 1.291-3.761 P = 0.004) had associations with worse DFS. CONCLUSION: High AFP, CEA, and Ki67 are significant prognostic indicators in ICC patients, and can be used to evaluate ICC biological behavior and prognosis.

The prognostic value of arginase-1 and glypican-3 expression levels in patients after surgical intrahepatic cholangiocarcinoma resection.

BACKGROUND: The aim of this study was to investigate the prognostic value of arginase-1 (Arg-1) and glypican-3 (GPC-3) in patients with intrahepatic cholangiocarcinoma (ICC). METHODS: Two hundred and thirty-seven patients with ICC were included in this study. All patients had undergone radical surgery and had complete clinical information. Immunohistochemistry was used to assess the levels of Arg-1 and GPC-3 in ICC tissues. Univariate and multivariate analyses were conducted to identify independent risk factors in ICC. The relationship between Arg-1 and GPC-3 levels and patient survival was determined using the Kaplan-Meier method. RESULTS: High Arg-1 and GPC-3 expression levels were associated with poor prognosis in patients with ICC, and they could be as new prognostic biomarkers in ICC. CONCLUSION: Arg-1 and GPC-3 can serve as independent prognostic biomarkers in ICC.

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.

Prognostic significance of K-ras mutations in pancreatic cancer: a meta-analysis.

BACKGROUND: K-ras gene mutations are common in patients with pancreatic cancer (PC); however, their prognostic value for PC remains inconclusive. This meta-analysis was performed to quantitatively evaluate the association between K-ras mutations and survival in patients with pancreatic cancer. METHODS: We performed a comprehensive search of electronic sources including MEDLINE (via PubMed), Web of Science, and the Cochrane Library. The search covered a publication period from inception to November 2015. RESULTS: Seventeen studies with a total of 2249 patients with pancreatic cancer were included in the tissue detection of this study. The meta-analysis indicated a significant association between mutant K-ras genes and overall survival (OS) (HR = 1.51, 95% CI 1.32-1.72, P < 0.001). Moreover, further subgroup analyses by ethnicity, publication year, therapy method, cancer resectability, and gene detection method all revealed that pancreatic cancer patients with the K-ras mutation had significantly poorer OS (P < 0.05). And results from four studies with 225 patients focused on plasma K-ras mutations enhanced such association (HR = 2.23, 95% CI 1.69-2.95, P < 0.001). CONCLUSIONS: As a prediction of poor prognosis, the detection of K-ras mutations may be a useful prognostic factor for pancreatic cancer patients.

New HCC Subtypes Based on CD8 Tex-Related lncRNA Signature Could Predict Prognosis, Immunological and Drug Sensitivity Characteristics of Hepatocellular Carcinoma.

Purpose: Hepatocellular carcinoma has become one of the severe diseases threatening human health. T cell exhaustion is deemed as a reason for immunotherapy resistance. However, little is known about the roles of CD8 Tex-related lncRNAs in HCC. Materials and Methods: We processed single-cell RNA sequencing to identify CD8 Tex-related genes. CD8 Tex-related lncRNAs were identified based on their correlations with mRNAs. Unsupervised clustering approach was used to identify molecular clusters of CD8 Tex-related lncRNAs. Differences in prognosis and immune infiltration between the clusters were explored. Machine learning algorithms were used to construct a prognostic signature. Samples were classified as low- and high-risk groups based on their risk scores. We identified prognosis-related lncRNAs and constructed a ceRNA network. In vitro experiments were conducted to investigate the impacts of CD8 Tex-related lncRNAs on proliferation and apoptosis of HCC cells. Results: We clarified cell types within two HCC single-cell datasets. We identified specific markers of CD8 Tex cells and analyzed their potential functions. Twenty-eight lncRNAs were identified as CD8 Tex-related. Based on CD8 Tex-related lncRNAs, samples were categorized into two distinct clusters, which exhibited significant differences in survival rates and immune infiltration. Ninety-six algorithm combinations were employed to establish a prognostic signature. RSF emerged as the one with the highest C-index. Patients in high- and low-risk groups exhibited marked differences in prognosis, enriched pathways, mutations and drug sensitivities. MCM3AP-AS1, MAPKAPK5-AS1 and PART1 were regarded as prognosis-related lncRNAs. A ceRNA network was constructed based on CD8 Tex-related lncRNAs and mRNAs. Experiments on cell lines and organoids indicated that downregulation of MCM3AP-AS1, MAPKAPK5-AS1 and PART1 suppressed cell proliferation and induced apoptosis. Conclusion: CD8 Tex-related lncRNAs played crucial roles in HCC progression. Our findings provided new insights into the regulatory mechanisms of CD8 Tex-related lncRNAs in HCC.

[Comparison of bowel function pre and post-sigmoid augmentation cystoplasty in spinal cord injury patients].

OBJECTIVE: To explore the changes of bowel function in spinal cord injury (SCI) patients undergoing sigmoid augmentation cystoplasty. METHODS: From September 2005 to January 2011, 30 SCI patients undergoing sigmoid augmentation cystoplasty were surveyed by follow-up questionnaires at Beijing Charity hospital and Affiliated Hospital of Nantong University. RESULTS: Among them, 18 cases (60.0%) believed their defecation became softer and 18 cases (60.0%) thought their defecation time became shorter. The postoperative profiles of patient defecation traits and defecation time were better (P < 0.05), especially traumatic SCI patients (P < 0.05). CONCLUSION: The subtotal resection of sigmoid colon improves the defecation of spinal cord injury patients. The SCI patients undergoing sigmoid augmentation cystoplasty may avoid urinary tract dysfunctions and improve bowel dysfunction.

Prevalences of and risk factors for biliary stones and gallbladder polyps in a large Chinese population.

OBJECTIVES: This study aimed to identify the prevalences of and risk factors associated with the development of gallbladder stones and polyps in a large Chinese population. METHODS: Prevalences of and risk factors for biliary stones and gallbladder polyps were retrospectively investigated among subjects who underwent a general check-up at the Health Screening Centres of Peking Union Medical College Hospital and Beijing Charity Hospital between January 2007 and June 2010. RESULTS: A total of 60,064 people were enrolled in the study. Overall prevalences of biliary stones and gallbladder polyps were 4.2% (n= 2527) and 6.9% (n= 4119), respectively. Risk factors associated with increased odds ratios (ORs) for the development of biliary stones were female gender (OR = 1.51), age ≥ 50 years (OR = 2.09), history of hypertension (OR = 1.37), thickened gallbladder wall (cholecystitis) (OR = 1.98), fasting blood glucose ≥ 6.10 mmol/l (OR = 1.27), body mass index ≥ 25 kg/m(2) (OR = 1.25), systolic blood pressure ≥ 140 mmHg (OR = 1.31) and diastolic blood pressure ≥ 90 mmHg (OR = 1.44). Factors associated with gallbladder polyps were female gender (OR = 0.66), thickened gallbladder wall (OR = 2.09), negativity for hepatitis B surface antigen (HBsAg) and positivity for hepatitis B core antibody (anti-HBc) (OR = 2.61), and positivity for both HBsAg and anti-HBc (OR = 3.21). CONCLUSIONS: Prevalences of biliary stones and gallbladder polyps among Chinese people are similar to those reported for other populations. Biliary stones appear to be associated with female gender, age, obesity, blood glucose, blood pressure and cholecystitis. Male gender, hepatitis B virus infection and cholecystitis were strong risk factors for the formation of gallbladder polyps.

[Metabolism-related risk factors of cholelithiasis among Beijing residents: a case-control study].

OBJECTIVE: To explore the metabolism-related risk factors of cholelithiasis among residents in Beijing. METHODS: The clinical data including previous disease history, findings of physical examination, and results of cholecystosonography of 2270 patients with cholelithiasis identified in the Health Screening Center of Peking Union Medical College Hospital between August 2007 and August 2010 were retrospectively reviewed (the case group). Meanwhile, 4336 healthy individuals during the same period were randomly chosen as the control group. RESULTS: Total cholesterol, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, body mass index, and systolic blood pressure were positively correlated with the incidence of cholelithiasis (P < 0.05), while high-density lipoprotein cholesterol was negatively correlated (P < 0.05). Diastolic blood pressure showed no association with cholelithiasis (P > 0.05). CONCLUSION: Cholelithiasis is resulted from multiple factors including elevated blood lipids, blood glucose, and systolic blood pressure among residents in Beijing.

Expression, oncological and immunological characterizations of BZW1/2 in pancreatic adenocarcinoma.

Background: Despite the progress in early diagnosis and treatment, prognosis of pancreatic adenocarcinoma (PAAD) is still poor. Basic leucine zipper and W2 domain-containing protein 1 (BZW1) and protein 2 (BZW2) are attached to the basic leucine zipper (bZIP) superfamily. Recently, BZW1 was identified as an important role in glycolysis of PAAD. However, the comprehensive reports about BZW1/2 in PAAD are not sufficient. Methods: RNA-seq data in the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were retrospectively analyzed. We explored the expression of BZW1/2 in PAAD tissues and the associations between BZW1/2 and prognosis. In addition, the potential roles of BZW1/2 in tumor microenvironment (TME) of PAAD were analyzed. Finally, clinicopathological data of 49 patients with PAAD in our institution were collected. Immunohistochemistry was used to determine the expression of BZW1/2 in PAAD samples. Results: BZW1 and BZW2 were upregulated in PAAD tissues compared to normal tissues (p < 0.05). The expression of BZW1/2 were not significantly correlated with gender, grade and stage of PAAD (p > 0.05). High expression of BZW2 was an independent predictor for poor prognosis of PAAD (HR 1.834, 95%CI 1.303-2.581, p = 0.001). And a nomogram to predict overall survival (OS) of PAAD was established with a C-index of 0.685. BZW1 and BZW2 expression were positively associated with T cell mediated immune response to tumor cell and Th2 cells in xCell database. Tumor Immune Single-Cell Hub (TISCH) analyses indicated that BZW1 and BZW2 were mainly expressed in B cells and malignant cells. External cohort furtherly validated that high expression of BZW1 and BZW2 were predictors for poor prognosis of PAAD. Conclusion: We found that BZW1 and BZW2 are highly expressed in malignant cells and B cells in the TME of PAAD. BZW2 is an independent predictor for OS of PAAD. BZW1 and BZW2 expression are positively associated with T cell mediated immune response to tumor cell and Th2 cells in PAAD.

Integrated proteomics and phosphoproteomics reveal perturbed regulative pathways in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to its inefficient diagnosis, rapid progress, and tenacious drug resistance. Here, we aimed to analyze the expressive patterns of proteins and phosphorylation in PDAC tissue samples and compare them to normal pancreatic tissue to investigate the underlying mechanisms and to reveal potential protein targets for diagnosis and drug development. Liquid chromatography coupled to mass spectrometry (LC-MS) based proteomics and phosphoproteomics analyses were performed using 20 pairs of patient-derived PDAC tissue and normal pancreatic tissue samples. Protein identification and quantification were conducted using MaxQuant software. Bioinformatics analysis was used to retrieve PDAC-relevant pathways and gene ontology (GO) terms. 4985 proteins and 3643 phosphoproteins were identified with high confidence; of these, 322 proteins and 235 phosphoproteins were dysregulated in PDAC. Several pathways, including several extracellular matrix-related pathways, were found to be strongly associated with PDAC. Further, the expression levels of filamin A (FLNA), integrin alpha-V (ITGAV), thymidine phosphorylase (TYMP), medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM), short-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADS), and acetyl-CoA acetyltransferase, mitochondrial (ACAT1) were examined through western blot and immunohistochemistry analysis, and the results confirmed the validity of the proteomics analysis results. These findings provide comprehensive insight into the dysregulated regulative networks in PDAC tissue samples at the protein and phosphorylation levels, and they provide clues for further pathological studies and drug-target development.

Significance of circulating tumor cells in the portal vein regarding metastases and vascular invasion in hepatocellular carcinoma patients.

BACKGROUND: Vascular invasion is an important risk factor of poor prognosis in hepatocellular carcinoma (HCC) patients. The detection of circulating tumor cells (CTCs) in the blood is direct evidence of tumor presence. There are few reports on CTCs and metastasis and vascular invasion of HCC. The purpose of this study was to analyze the significance of CTCs in the portal vein regarding metastases and vascular invasion in HCC patients. METHODS: A total of 104 HCC patients diagnosed and treated in Zhengzhou University People's Hospital were enrolled. Surgery was performed in 60 individuals. Portal vein blood samples were collected before treatment for CTCs detection. We used the isolation by size of epithelial tumor cells (ISET) and fluorescence in situ hybridization (FISH) to enrich and classify CTCs from blood samples. The patients were divided into metastasis and nonmetastasis groups according to the metastasis status before treatment. Differences in clinical indicators such as alpha-fetoprotein (AFP) levels, tumor size, CTCs count, and macrovascular tumor thrombus between the two groups were analyzed as well as the associations of CTCs count with the above indicators. For individuals with postoperative pathology, the relationship between CTCs counts and microvascular invasion (MVI) was analyzed. RESULTS: The amounts of portal vein CTCs were higher in patients with metastases compared with the nonmetastases group (20 vs. 7; z=3.795; P<0.001). Multivariate logistic regression analysis showed that the CTC count was a risk factor for HCC metastasis [odds ratio (OR) =1.044; 95% CI: 1.011-1.079]. The sensitivity and specificity of CTC count in predicting HCC metastasis were 82.93% and 52.38%, respectively. CTC count was significantly correlated with tumor size (rs=0.308; P=0.001), vascular invasion (z=4.211; P<0.001), and MVI (z=12.763; P=0.002). A threshold CTC count of seven showed the most significant power for predicting metastasis. CONCLUSIONS: Vascular invasion positivity was closely related to HCC metastasis. Portal vein CTC count before treatment was correlated with vascular invasion and could be considered one of the factors affecting HCC metastasis. However, the ability of CTC count was limited in predicting HCC metastasis due to insufficient specificity.

Portal Venous Circulating Tumor Cells Undergoing Epithelial-Mesenchymal Transition Exhibit Distinct Clinical Significance in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Much importance is attached to the clinical application value of circulating tumor cells (CTCs), meanwhile tumor-proximal CTCs detection has interested researchers for its unique advantage. This research mainly discusses the correlation of portal venous (PoV) CTCs counts in different epithelial-mesenchymal transition status with clinicopathologic parameters and postoperative prognosis in resectable pancreatic ductal adenocarcinoma patients (PDAC). METHODS: PDAC patients (n=60) who received radical resection were enrolled in this research. PoV samples from all patients and peripheral venous (PV) samples from 32 patients among them were collected to verify spatial heterogeneity of CTCs distribution, and explore their correlation with clinicopathologic parameters and clinical prognosis. RESULTS: CTCs detectable rate and each phenotype count of PoV were higher than those of PV. Patients with recurrence had higher PV and PoV epithelial CTCs (E-CTCs) counts than recurrence-free patients (P<0.05). Some unfavourable clinicopathologic parameters were closely related to higher PoV CTCs counts. Multivariate regression analysis demonstrated that PoV mesenchymal CTC (M-CTC)s≥1/5 ml was an independent risk factor for metastasis free survival (MFS) (P=0.003) and overall survival (OS) (P=0.043). CONCLUSIONS: Our research demonstrated that portal venous was a preferable vessel for CTC test, and patients with PoV M-CTC≥1/5 ml had shorter MFS and OS time in resectable PDAC patients. PoV CTC phenotype detection has the potential to be a reliable and accurate tool to identify resectable PDAC patients with high tendency of postoperative metastasis for better stratified management.

Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a case-control study in China.

BACKGROUND/AIMS: The risk factors for cholangiocarcinoma are incompletely defined in China, especially for intrahepatic cholangiocarcinoma (ICC). We evaluated the risk factors for both ICC and extrahepatic cholangiocarcinoma (ECC). METHODS: A case-control study in which cases were cholangiocarcinoma patients referred to Peking Union Medical College Hospital (PUMCH) between 1998 and 2008 and controls were healthy individuals. Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of PUMCH. Data on liver disease, family history, diabetes, smoking and drinking were collected by a retrospective review of the patients' records and health examination reports or by interview. RESULTS: A total of 190 patients (61 ICC; 129 ECC) and 380 age- and sex-matched controls were enrolled. HBsAg (P<0.001) and anti-HBc without HBsAg (P=0.001) were significantly related to ICC. The adjusted odds ratios (OR) and 95% confidence intervals (CI) were 18.1 (95% CI: 7.5-44.0) and 3.6 (95% CI: 1.7-7.6) respectively. Diabetes mellitus (P=0.007), cholecystolithiasis (P=0.004) and previous cholecystectomy (P<0.001) were significantly associated with ECC. The prevalence of cirrhosis was higher in ICC than that in ECC (P<0.001). Furthermore, on excluding the ICC patients with cirrhosis, ICC patients showed significant independent associations with HBsAg (OR: 7.3; 95% CI: 3.1-17.2) and anti-HBc without HBsAg (OR: 2.4; 95% CI: 1.1-5.2). CONCLUSION: Cirrhosis and chronic hepatitis B virus infection are risk factors for ICC, while cholecystolithiasis, diabetes and previous cholecystectomy are risk factors for ECC.

Comparison of serum tumor markers for intrahepatic cholangiocarcinoma and hepatocellular carcinoma.

Serum tumor markers such as alpha-fetoprotein (AFP), carcinoembryonic antigen, carbohydrate antigen (CA) 19-9, CA242, and CA50 were analyzed to evaluate their diagnostic values in single and combined tests for distinguishing intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). Preoperative serum levels of AFP, carcinoembryonic antigen, CA19-9, CA242, and CA50 were measured in 45 ICC and 76 HCC patients. The serum levels and the positive rate of AFP, CA19-9, and CA242 were significantly different between the ICC patients and HCC patients. Although AFP (-) was the most sensitive assay for distinguishing ICC from HCC (91.1%), its specificity was significantly lower than that of CA242 (+) and CA19-9 (+). The combination of AFP (-) and CA242 (+) afforded a high specificity of 94.3 per cent and showed highest accuracy (78.5%). Evaluation of patients without liver cirrhosis also showed similar results. The diagnostic value of CA242 (+) is better than that of CA19-9 (+) and AFP (-) in distinguishing ICC from HCC. Combined detection of AFP (-) and CA242 (+) can improve the specificity and accuracy of diagnosing ICC.

Gender-specific prognostic markers of patients with gallbladder cancer after surgical resection.

The aim of this study was to elucidate gender-specific markers for postresectional long-term survival of gallbladder cancer (GBC) based on a cohort of Chinese patients. Clinicopathological records of 81 patients (27 males and 54 females) after surgical resection for GBC were reviewed retrospectively. The influence of each variable on survival was determined using the Kaplan-Meier method and log-rank test. For females, Cox regression analysis was also adopted. Univariate analysis showed that the absence of lymph node and distant metastases, differentiation grade, and curative resection were associated with prolonged survival for all males, whereas tumor size, differentiation grade, and the presence of lymph node metastases influenced the overall or disease-free survival of patients after curative resection (all P < 0.05). On the other hand, Nevin stage was an independent marker for both overall survival for all females and overall and disease-free survival for female patients who underwent curative resection. Additionally, resection type and differentiation grade were of independent prognostic significance for different subgroups of females (all P < 0.05). Our data suggested that tumor-related factors affect prognosis of both male and female patients with GBC after resection. Of these factors, tumor differentiation status might be more significant for males, but Nevin stage had a stronger predictive potential for females.

Laparoscopic splenectomy via the spleen bed in combination with selective esophagogastric devascularization for patients with cirrhotic portal hypertension: a single-institution experience.

INTRODUCTION: The safety and feasibility of laparoscopic splenectomy plus selective esophagogastric devascularization (LSSD) via the spleen bed for cirrhotic portal hypertension have not been well studied. AIM: To assess the safety and feasibility of LSSD via the spleen bed for patients with cirrhotic portal hypertension. MATERIAL AND METHODS: From June 2012 to December 2017, 423 patients suffering from portal hypertension and hypersplenism with liver cirrhosis underwent surgery in our department. One hundred and sixty-seven of these patients received totally LSSD, and the others received open splenectomy and esophagogastric devascularization (OSD). The characteristics, intraoperative and postoperative details and complications of the two groups were compared. RESULTS: The operations were successfully performed in all patients. Intraoperative blood loss volume and blood transfusion were similar between the two groups (all p-values > 0.05). Postoperative length of hospital stay and time to oral intake were significantly shorter, but operation time was longer in the LSSD group compared with the OSD group (all p < 0.05). However, postoperative portal vein diameter was significantly smaller in the LSSD group (p < 0.001). The postoperative grade of varices was significantly lower in the LSSD group (p = 0.030). No significant differences were detected between the two groups regarding postoperative liver function, but the incidences of pancreatic leakage, pleural effusion, and wound infections were higher in the OSD group (all p < 0.05). CONCLUSIONS: LSSD via the spleen bed is safe and feasible for liver cirrhosis and portal hypertension.