Update on the Diagnosis and Treatment of Combined Hepatocellular Cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a unique type of liver tumor that contains both hepatocellular carcinoma and cholangiocarcinoma components within a single tumor. The fifth edition of the World Health Organization classification provides a definition and diagnostic criteria for cHCC-CCA. However, the heterogeneous histomorphology and presentation resulting from variation of the proportion of each component poses challenges for clinical diagnosis and treatment. A diagnosis of cHCC-CCA may be suggested by the synchronous elevation of serum tumor markers for hepatocellular carcinoma and cholangiocarcinoma, a mixed enhancement pattern on imaging, and a discrepancy between the elevation of tumor marker and the imaging enhancement pattern. Histopathological examination using hematoxylin and eosin staining is considered the gold standard for diagnosing cHCC-CCA, and comprehensive examination of resection or biopsy specimens is crucial for an accurate diagnosis. Currently, there is no standard treatment for cHCC-CCA, and surgery is the mainstay. Anatomic hepatectomy with lymphadenectomy is among the recommended surgical procedures. The role of liver transplantation in the management of cHCC-CCA is still uncertain. Transarterial chemoembolization may be effective for unresectable cHCC-CCA, particularly for hypervascular tumors. However, the available evidence does not support systemic therapy for advanced cHCC-CCA. The prognosis of cHCC-CCA is generally poor, and there is no established staging system. Further research is needed to better understand the histogenesis and clinical management of cHCC-CCA. This review provides an overview of the current literature on cHCC-CCA with a focus on its clinical characteristics, pathological diagnosis, and management.

Influences of dexmedetomidine on stress responses and postoperative cognitive and coagulation functions in patients undergoing radical gastrectomy under general anesthesia.

BACKGROUND: Radical gastrectomy (RG) is commonly used in the treatment of patients with gastric cancer (GC), but this procedure may lead to stress responses, postoperative cognitive dysfunction, and blood coagulation abnormalities in patients. AIM: To investigate the influences of dexmedetomidine (DEX) on stress responses and postoperative cognitive and coagulation functions in patients undergoing RG under general anesthesia (GA). METHODS: One hundred and two patients undergoing RG for GC under GA from February 2020 to February 2022 were retrospectively reviewed. Of these, 50 patients had received conventional anesthesia intervention [control group (CG)] and 52 patients had received DEX in addition to routine anesthesia intervention [observation group (OG)]. Inflammatory factor (IFs; tumor necrosis factor-α, TNF-α; interleukin-6, IL-6), stress responses (cortisol, Cor; adrenocorticotropic hormone, ACTH), cognitive function (CF; Mini-Mental State Examination, MMSE), neurological function (neuron-specific enolase, NSE; S100 calcium-binding protein B, S100B), and coagulation function (prothrombin time, PT; thromboxane B2, TXB2; fibrinogen, FIB) were compared between the two groups before surgery (T0), as well as at 6 h (T1) and 24 h (T2) after surgery. RESULTS: Compared with T0, TNF-α, IL-6, Cor, ACTH, NSE, S100B, PT, TXB2, and FIB showed a significant increase in both groups at T1 and T2, but with even lower levels in OG vs CG. Both groups showed a significant reduction in the MMSE score at T1 and T2 compared with T0, but the MMSE score was notably higher in OG compared with CG. CONCLUSION: In addition to a potent inhibitory effect on postoperative IFs and stress responses in GC patients undergoing RG under GA, DEX may also alleviate the coagulation dysfunction and improve the postoperative CF of these patients.

Mechanistic insights into the allosteric inactivation mechanism of ZAP-70 induced by the hot spot W165C mutation.

Zeta chain-associated protein kinase 70 (ZAP-70) is a non-receptor tyrosine kinase that interacts with the activated T-cell receptor to transduce downstream signals, and thus plays an important role in the adaptive immune system. The biphosphorylated immunotyrosine-based activation motifs (ITAM-Y2P) binds to the N-SH2 and C-SH2 domains of ZAP-70 to promote the activation of ZAP-70. The present study explores molecular mechanisms of allosteric inactivation of ZAP-70 induced by the hot spot W165C mutation through atomically detailed molecular dynamics simulation approaches. We report microsecond-length simulations of two states of the tandem SH2 domains of ZAP-70 in complex with the ITAM-Y2P motif, including the wild-type and W165C mutant. Extensive analysis of local flexibility and dynamical correlated motions show that W165C mutation changes coupled motions of protein domains and community networks. The binding affinities of the ITAM-Y2P motif to the wild-type and W165C mutant of ZAP-70 are predicted using binding free energy calculations. The results suggest that the driving force to decrease the binding affinity in the W165C mutant derives from the difference in the protein-protein electrostatic interactions. Moreover, the per-residue free energy decomposition unravels that the contributions from residues in the phosphorylated Tyr315 (pY315) binding site, in particular pY315 of ITAM-Y2P, and Arg43, Tyr240 of ZAP-70, are the key determinants for the loss of binding affinity. This study may insights into our understanding of the pathological mechanism of ZAP-70.Communicated by Ramaswamy H. Sarma.

Expert Consensus on Pathological Diagnosis of Intrahepatic Cholangiocarcinoma (2022 version).

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

Retraction Notice to: Long Noncoding RNA OIP5-AS1 Promotes the Progression of Liver Hepatocellular Carcinoma via Regulating the hsa-miR-26a-3p/EPHA2 Axis.

[This retracts the article DOI: 10.1016/j.omtn.2020.05.032.].

Development and validation of a nomogram to predict overall survival in patients with incidental gallbladder cancer: A retrospective cohort study.

Objective: The aim of this study was to develop and validate a nomogram to predict the overall survival of incidental gallbladder cancer. Methods: A total of 383 eligible patients with incidental gallbladder cancer diagnosed in Shanghai Eastern Hepatobiliary Surgery Hospital from 2011 to 2021 were retrospectively included. They were randomly divided into a training cohort (70%) and a validation cohort (30%). Univariate and multivariate analyses and the Akaike information criterion were used to identify variables independently associated with overall survival. A Cox proportional hazards model was used to construct the nomogram. The C-index, area under time-dependent receiver operating characteristic curves and calibration curves were used to evaluate the discrimination and calibration of the nomogram. Results: T stage, N metastasis, peritoneal metastasis, reresection and histology were independent prognostic factors for overall survival. Based on these predictors, a nomogram was successfully established. The C-index of the nomogram in the training cohort and validation cohort was 0.76 and 0.814, respectively. The AUCs of the nomogram in the training cohort were 0.8, 0.819 and 0.815 for predicting OS at 1, 3 and 5 years, respectively, while the AUCs of the nomogram in the validation cohort were 0.846, 0.845 and 0.902 for predicting OS at 1, 3 and 5 years, respectively. Compared with the 8th AJCC staging system, the AUCs of the nomogram in the present study showed a better discriminative ability. Calibration curves for the training and validation cohorts showed excellent agreement between the predicted and observed outcomes at 1, 3 and 5 years. Conclusions: The nomogram in this study showed excellent discrimination and calibration in predicting overall survival in patients with incidental gallbladder cancer. It is useful for physicians to obtain accurate long-term survival information and to help them make optimal treatment and follow-up decisions.

[Molecular mechanism of geniposide in regulating GLUT2 glycosylation in pancreatic ß cells].

Type 2 diabetes mellitus( T2 DM) is a common chronic metabolic disease characterized by persistent hyperglycemia and insulin resistance. In pancreatic ß-cells,glucose-stimulated insulin secretion( GSIS) plays a pivotal role in maintaining the balance of blood glucose level. Previous studies have shown that geniposide,one of the active components of Gardenia jasminoides,could quickly regulate the absorption and metabolism of glucose,and affect glucose-stimulated insulin secretion in pancreatic ß cells,but the specific mechanism needs to be further explored. Emerging evidence indicated that glycosylation of glucose transporter( GLUT) has played a key role in sensing cell microenvironmental changes and regulating glucose homeostasis in eucaryotic cells. In this study,we studied the effects of geniposide on the key molecules of GLUT2 glycosylation in pancreatic ß cells. The results showed that geniposide could significantly up-regulate the mRNA and protein levels of Glc NAc T-Ⅳa glycosyltransferase( Gn T-Ⅳa) and galectin-9 but had no signi-ficant effect on the expression of clathrin,and geniposide could distinctively regulate the protein level of Gn T-Ⅳa in a short time( 1 h) under the conditions of low and medium glucose concentrations,but had no significant effect on the protein level of galectin-9. In addition,geniposide could also remarkably affect the protein level of glycosylated GLUT2 in a short-time treatment. The above results suggested that geniposide could quickly regulate the protein level of Gn T-Ⅳa,a key molecule of protein glycosylation in INS-1 rat pancreatic ßcells and affect the glycosylation of GLUT2. These findings suggested that the regulation of geniposide on glucose absorption,metabolism and glucose-stimulated insulin secretion might be associated with its efficacy in regulating GLUT2 glycosylation and affecting its distribution on the cell membrane and cytoplasm in pancreatic ß cells.

Does splenectomy significantly improve the prognosis of hepatocellular carcinoma patients with hypersplenism? A systematic review and meta-analysis.

BACKGROUND: Whether hepatocellular carcinoma (HCC) patients with hypersplenism can benefit from splenectomy is unclear. This study aimed at exploring the efficacy and safety of concurrent splenectomy for HCC patients with hypersplenism. METHODS: PubMed, EMBASE and Web of Science databases were systematically searched to compare data on the combination of hepatectomy or transhepatic arterial infusion (TAI) with splenectomy (the splenectomy group) with data on hepatectomy or TAI alone (the non-splenectomy group) for the treatment of HCC with hypersplenism. Prospective clinical trials or retrospective cohort studies from inception to May 10, 2020 were considered eligible for this analysis. The relevant outcomes, including patients' demographics, clinicopathologic characteristics, perioperative indices and long-term outcomes, were independently extracted by two investigators. Publication bias for overall survival (OS) and disease-free survival (DFS) was qualitatively assessed by funnel plots and quantitatively evaluated by Begg's and Egger's tests. RESULTS: Nine retrospective studies including 1,650 patients were analyzed. Short-term outcomes suggested that the incidence rate of postoperative complications, including portal or splenic vein thrombosis [odds ratio (OR) =26.28, P<0.001] and pancreatic injury (OR =14.89, P=0.001), was significantly higher in the splenectomy group, whereas the perioperative mortality rate was similar between the splenectomy and non-splenectomy groups (P=0.541). Long-term outcomes indicated that the occurrence of variceal re-hemorrhage (OR =0.31, P<0.001) and tumor progress or recurrence (OR =0.62, P=0.001) was markedly reduced for patients who underwent splenectomy, while the long-term mortality rates were not statistically different between the two groups (P=0.087). The prognostic evaluation revealed that the OS and DFS were comparable between the splenectomy and non-splenectomy groups [for OS: hazard ratio (HR) =0.77, 95% confidence interval (CI): 0.53-1.13; for DFS: HR =0.87, 95% CI: 0.63-1.19]. Funnel plots suggested an HRs symmetric distribution for OS and DFS. Begg's and Egger's tests confirmed that there was no significant HR publication bias for OS and DFS. CONCLUSIONS: Due to the significant progress in surgical techniques and perioperative care, concomitant splenectomy should be considered as an optional treatment for some HCC patients with hypersplenism.

Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer: Results from 24 hospitals in China.

BACKGROUND: Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate. AIM: To investigate whether RL can improve the prognosis of patients with T1b GBC. METHODS: We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China. The log-rank test and Cox proportional hazards model were used to compare the overall survival (OS) of patients who underwent cholecystectomy (Ch) + RL and those who underwent Ch only. To investigate whether combined hepatectomy (Hep) improved OS in T1b patients, we studied patients who underwent Ch + RL to compare the OS of patients who underwent combined Hep and patients who did not. RESULTS: Of the 121 patients (aged 61.9 ± 10.1 years), 77 (63.6%) underwent Ch + RL, and 44 (36.4%) underwent Ch only. Seven (9.1%) patients in the Ch + RL group had lymph node metastasis. The 5-year OS rate was significantly higher in the Ch + RL group than in the Ch group (76.3% vs 56.8%, P = 0.036). Multivariate analysis showed that Ch + RL was significantly associated with improved OS (hazard ratio: 0.51; 95% confidence interval: 0.26-0.99). Among the 77 patients who underwent Ch + RL, no survival improvement was found in patients who underwent combined Hep (5-year OS rate: 79.5% for combined Hep and 76.1% for no Hep; P = 0.50). CONCLUSION: T1b GBC patients who underwent Ch + RL had a better prognosis than those who underwent Ch. Hep + Ch showed no improvement in prognosis in T1b GBC patients. Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines, RL was only performed in 63.6% of T1b GBC patients. Routine Ch + RL should be advised in T1b GBC.

Whole-Transcriptome Sequencing Identifies Key Differentially Expressed mRNAs, miRNAs, lncRNAs, and circRNAs Associated with CHOL.

To systematically evaluate the whole-transcriptome sequencing data of cholangiocarcinoma (CHOL) to gain more insights into the transcriptomic landscape and molecular mechanism of this cancer, we performed whole-transcriptome sequencing based on the tumorous (C) and their corresponding non-tumorous adjacent to the tumors (CP) from eight CHOL patients. Subsequently, differential expression analysis was performed on the C and CP groups, followed by functional interaction prediction analysis to investigate gene-regulatory circuits in CHOL. In addition, The Cancer Genome Atlas (TCGA) for CHOL data was used to validate the results. In total, 2,895 differentially expressed messenger RNAs (dif-mRNAs), 56 differentially expressed microRNAs (dif-miRNAs), 151 differentially expressed long non-coding RNAs (dif-lncRNAs), and 110 differentially expressed circular RNAs (dif-circRNAs) were found in CHOL samples compared with controls. Enrichment analysis on those differentially expressed genes (DEGs) related to miRNA, lncRNA, and circRNA also identified the function of spliceosome. The downregulated hsa-miR-144-3p were significantly enriched in the competing endogenous RNA (ceRNA) complex network, which also included 7 upregulated and 13 downregulated circRNAs, 7 upregulated lncRNAs, and 90 upregulated and 40 downregulated mRNAs. Moreover, most of the DEGs and a few of the miRNAs (such as hsa-miR-144-3p) were successfully validated by TCGA data. The genes involved in RNA splicing and protein degradation processes and miR-144-3p may play fundamental roles in the pathogenesis of CHOL.

Prognosis for intrahepatic cholangiocarcinoma patients treated with postoperative adjuvant transcatheter hepatic artery chemoembolization.

OBJECTIVE: We used meta-analysis to evaluate the efficacy of transcatheter hepatic arterial chemoembolization (TACE) for the treatment of intrahepatic cholangiocarcinoma (ICC). METHODS: We performed the meta-analysis using the R 3.12 software and the quality evaluation of data using the Newcastle-Ottawa Scale. The main outcomes were recorded as 1-year overall survival (OS), 3-year OS, 5-year OS, and hazard ratio (HR) of TACE treatment or non-TACE treatment. The heterogeneity test was performed using the Q-test based on chi-square and I2 statistics. Egger's test was used to test the publication bias. The odds ratio or HR and 95% confidence interval (CI) were used to represent the effect index. RESULTS: Nine controlled clinical trials involving 1724 participants were included in this study; patients came mainly from China, Italy, South Korea, and Germany. In the OS meta-analysis, the 1-year and 3-year OS showed significant heterogeneity, but not the 5-year OS. TACE increased the 1-year OS (odds ratio = 2.66, 95% CI: 1.10-6.46) of the patients with ICC, but the 3- and 5-year OS rates were not significantly increased. The results had no publication bias, but the stability was weak. The HR had significant heterogeneity (I2 = 0%, P= 0.54). TACE significantly decreased the HR of ICC patients (HR = 0.59, 95% CI: 0.48-0.73). The results had no publication bias, and the stability was good. CONCLUSIONS: Treatment with TACE is effective for patients with ICC. Regular updating and further research and analysis still need to be carried out.

Long Noncoding RNA OIP5-AS1 Promotes the Progression of Liver Hepatocellular Carcinoma via Regulating the hsa-miR-26a-3p/EPHA2 Axis.

Numerous studies have suggested that dysregulated long noncoding RNAs (lncRNAs) contributed to the development and progression of many cancers. lncRNA OIP5 antisense RNA 1 (OIP5-AS1) has been reported to be increased in several cancers. However, the roles of OIP5-AS1 in liver hepatocellular carcinoma (LIHC) remain to be investigated. In this study, we demonstrated that OIP5-AS1 was upregulated in LIHC tissue specimens and its overexpression was associated with the poor survival of patients with LIHC. Furthermore, loss-of function experiments indicated that OIP5-AS1 promoted cell proliferation and inhibited cell apoptosis both in vitro and in vivo. Moreover, binding sites between OIP5-AS1 and hsa-miR-26a-3p as well as between hsa-miR-26a-3p and EPHA2 were confirmed by luciferase assays. Finally, a rescue assay was performed to prove the effect of the OIP5-AS1/hsa-miR-26a-3p/EPHA2 axis on LIHC cell biological behaviors. Based on all of the above findings, our results suggested that OIP5-AS1 promoted LIHC cell proliferation and invasion via regulating the hsa-miR-26a-3p/EPHA2 axis.

Tumor suppressor LKB1 inhibits the progression of gallbladder carcinoma and predicts the prognosis of patients with this malignancy.

Gallbladder carcinoma (GBC) represents the most common fatal tumors of the biliary tract. The 3-year or 5-year survival rate for patients with this disease are 30 and 5%, respectively. Liver kinase B1 (LKB1), a primary upstream kinase of adenosine monophosphate-activated protein kinase (AMPK) necessary for maintaining cell metabolism and energy homeostasis, has been found to be an important tumor suppressor gene in recent years, and its inactivation has also found to be closely associated with tumor growth, metastasis and cancer stem cell (CSC) proliferation. Nevertheless, the function of LKB1 in GBC remains unclear. In this study, we found that the expression of LKB1 in GBC tissues was decreased compared with that in non-cancerous tissues. LKB1 overexpression suppressed the proliferation, metastasis and expansion of GBC CSCs. Mechanically, LKB1 suppressed GBC cell progression via the JAK/signal transducer and activator of transcription 3 (STAT3) pathway. The use of the JAK2 inhibitor, AZD­1480, attenuated the suppressive effects of LKB1 overexpression on the growth, metastasis and self-renewal ability of the GBC cells, which further demonstrated that JAK/STAT3 was involved in the LKB1-induced suppression of GBC cell growth, metastasis and self-renewal ability. More importantly, the decreased expression of LKB1 was a predictor of a poor prognosis of patients with GBC. On the whole, our data indicate that LKB1 inhibits GBC cell growth, metastasis and self-renewal ability by disrupting JAK/STAT3 signaling, and may thus prove to be a novel prognostic biomarker for patients with GBC.

An end-to-side suspender pancreaticojejunostomy: A new invagination pancreaticojejunostomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a severe complication of the pancreaticoduodenectomy (PD). Recently, we introduced a method of suspender pancreaticojejunostomy (PJ) to the PD. In this study, we retrospectively analyzed various risk factors for complications after PD. We also introduced and assessed the suspender PJ to demonstrate its advantages. METHODS: Data from 335 patients with various periampullary lesions, who underwent the Whipple procedure (classic Whipple procedure or pylorus-preserving) PD by either traditional end-to-side invagination PJ or suspender PJ, were analyzed. The correlation between either perioperative or postoperative complications and corresponding PD approaches was evaluated by univariate analysis. RESULTS: A total of 147 patients received the traditional end-to-side invagination PJ, and 188 patients were given the suspender PJ. Overall, 51.9% patients had various complications after PD. The mortality rate was 2.4%. The POPF incidence in patients who received the suspender PJ was 5.3%, which was significantly lower than those who received the traditional end-to-side invagination PJ (18.4%) (P < 0.001). Univariate analysis showed that PJ approach and the pancreas texture were significantly associated with the POPF incidence rate (P < 0.01). POPF was a risk factor for both postoperative abdominal cavity infection (OR = 8.34, 95% CI: 3.99-17.42, P < 0.001) and abdominal cavity hemorrhage (OR = 4.86, 95% CI: 1.92-12.33, P = 0.001). CONCLUSIONS: Our study showed that the impact of the pancreas texture was a major risk factor for pancreatic leakage after a PD. The suspender PJ can be easily accomplished and widely applied and can effectively decrease the impact of the pancreas texture on pancreatic fistula after a PD and leads to a lower POPF incidence rate.

Distinct role of nuclear receptor corepressor 1 regulated de novo fatty acids synthesis in liver regeneration and hepatocarcinogenesis in mice.

It is urgent that the means to improve liver regeneration (LR) be found, while mitigating the concurrent risk of hepatocarcinogenesis (HCG). Nuclear receptor corepressor 1 (NCoR1) is a co-repressor of nuclear receptors, which regulates the expression level of metabolic genes; however, little is known about its potential contribution for LR and HCG. Here, we found that liver-specific NCoR1 knockout in mice (NCoR1Δhep ) dramatically enhances LR after partial hepatectomy and, surprisingly, blocks the process of diethylnitrosamine (DEN)-induced HCG. Both RNA-sequencing and metabolic assay results revealed improved expression of Fasn and Acc2 in NCoR1Δhep mice, suggesting the critical role of de novo fatty acid synthesis (FAS) in LR. Continual enhanced de novo FAS in NCoR1Δhep mice resulted in overwhelmed adenosine triphosphate ATP and nicotinamide adenine dinucleotide phosphate (NADPH) consumption and increased mitochondrial reactive oxygen species production, which subsequently attenuated HCG through inducing apoptosis of hepatocytes at an early stage after DEN administration. CONCLUSION: NCoR1 functions as a negative modulator for hepatic de novo FAS and mitochondria energy adaptation, playing distinct roles in regeneration or carcinogenesis. (Hepatology 2018;67:1071-1087).

Dynamic Change of Total Bilirubin after Portal Vein Embolization is Predictive of Major Complications and Posthepatectomy Mortality in Patients with Hilar Cholangiocarcinoma.

OBJECTIVES: This study aims to evaluate the role of dynamic change in total bilirubin after portal vein embolization (PVE) in predicting major complications and 30-day mortality in patients with hilar cholangiocarcinoma (HCCA). METHODS: Retrospective analysis of prospectively maintained data of 64 HCCA patients who underwent PVE before hepatectomy in our institution was used. Total bilirubin and other parameters were measured daily in peri-PVE period. The difference between them and the baseline value from days 0-5 to day -1 (∆D1) and days 5-14 to day -1 (∆D2) were calculated. The relationship between ∆D1 and ∆D2 of total bilirubin and major complications as well as 30-day mortality was analyzed. RESULTS: Out of 64 patients, 10 developed major complications (15.6 %) and 6 patients (9.3 %) had died within 30 days after surgery. The ∆D2 of total bilirubin after PVE was most significantly associated with major complications (P < 0.001) and 30-day mortality (P = 0.002). In addition, it was found to be an independent predictor of major complications after PVE (odds ratio (OR) = 1.050; 95 % CI 1.017-1.084). ASA >3 (OR = 12.048; 95 % CI 1.019-143.321), ∆D2 of total bilirubin (OR = 1.058; 95 % CI 1.007-1.112), and ∆D2 of prealbumin (OR = 0.975; 95 % CI 0.952-0.999) were associated with higher risk of 30-day mortality after PVE. Receiver operating characteristic curves showed that ∆D2 of total bilirubin were better predictors than ∆D1 for major complications (AUC (∆D2) 0.817; P = 0.002 vs. AUC (∆D1) 0.769; P = 0.007) and 30-day mortality (ACU(∆D2) 0.868; P = 0.003 vs. AUC(∆D1) 0.721;P = 0.076). CONCLUSION: Patients with increased total bilirubin in 5-14 days after PVE may indicate a higher risk of major complications and 30-day mortality if the major hepatectomy were performed.

Nanorods of a new metal-biomolecule coordination polymer showing novel bidirectional electrocatalytic activity and excellent performance in electrochemical sensing.

Metal organic coordination polymers (CPs), as most attractive multifunctional materials, have been studied extensively in many fields. However, metal-biomolecule CPs and CPs' electrochemical properties and applications were studied much less. We focus on this topic aiming at electrochemical biosensors with excellent performance and high biocompatibility. A new nanoscaled metal-biomolecule CP, Mn-tyr, containing manganese and tyrosine, was synthesized hydrothermally and characterized by various techniques, including XRD, TEM, EDS, EDX mapping, elemental analysis, XPS, and IR. Electrode modified with Mn-tyr showed novel bidirectional electrocatalytic ability toward both reduction and oxidation of H2O2, which might be due to Mn. With the assistance of CNTs, the sensing performance of Mn-tyr/CNTs/GCE was improved to a much higher level, with high sensitivity of 543 mA mol(-1) L cm(-2) in linear range of 1.00×10(-6)-1.02×10(-4) mol L(-1), and detection limit of 3.8×10(-7) mol L(-1). Mn-tyr/CNTs/GCE also showed fast response, high selectivity, high steadiness and reproducibility. The excellent performance implies that the metal-biomolecule CPs are promising candidates for using in enzyme-free electrochemical biosensing.

Applied anatomy of small branches of the portal vein in transverse groove of hepatic hilum.

PURPOSE: The objective of this study was to provide the morphological details on small branches of the portal vein in transverse groove of hepatic hilum. METHODS: According to the surgery significance, the small branches of portal vein in transverse groove of hepatic hilum were named as "Short hepatic portal veins (SHPVs)". SHPVs were minutely dissected in 30 adult cadaveric livers. The number, diameter, length, origin points, and entering liver sites of SHPVs were explored and measured. RESULTS: There were 181 SHPVs in 30 liver specimens, including 46% (83/181) from the left portal vein, 31% (56/181) from the bifurcation, and 23% (42/181) from the right portal vein. At the entering liver sites of SHPVs, 22% (40/181) supplied for segment IV, 9% (17/181) for segment V, 4% (7/181) for segment VI, 23% (41/181) for segment VII, and 42% (76/181) for segment I (caudate lobe). There were 6.0 ± 2.4 branches per liver specimen with range 3-12. The mean diameter of SHPVs was 2.25 ± 0.89 mm. The average length of SHPVs was 4.86 ± 2.12 mm. CONCLUSIONS: SHPVs widely existed in each liver specimen. The detailed anatomical study of SHPVs could be useful to avoid damaging the short portal branches during hepatic operations, such as isolated or combined caudate lobectomy.

Combined detection tumor markers for diagnosis and prognosis of gallbladder cancer.

AIM: To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis. METHODS: Serum cancer antigens (CA)199, CA242, carcinoembryonic antigen (CEA), and CA125 levels were measured in 78 patients with gallbladder cancer (GBC), 78 patients with benign gallbladder diseases, and 78 healthy controls using electrochemiluminescence. CA199, CA242, CEA, and CA125 levels and positive rates were analyzed and evaluated pre- and post-operatively. Receiver operator characteristic curves were used to determine diagnostic sensitivity and specificity of GBC. Survival time analysis, including survival curves, and multivariate survival analysis of a Cox proportional hazards model was performed to evaluate independent prognostic factors. RESULTS: Serum CA242, CA125, and CA199 levels in the GBC group were significantly higher when compared with those in the benign gallbladder disease and healthy control groups (P < 0.01). With a single tumor marker for GBC diagnosis, the sensitivity of CA199 was the highest (71.7%), with the highest specificity being in CA242 (98.7%). Diagnostic accuracy was highest with a combination of CA199, CA242, and CA125 (69.2%). CA242 could be regarded as a tumor marker of GBC infiltration in the early stage. The sensitivity of CA199 and CA242 increased with progression of GBC and advanced lymph node metastasis (P < 0.05). The 78 GBC patients were followed up for 6-12 mo (mean: 8 mo), during which time serum CA199, CA125, and CA242 levels in the recurrence group were significantly higher than in patients without recurrence (P < 0.01). The post-operative serum CA199, CA125, and CA242 levels in the non-recurrence group were significantly lower than those in the GBC group (P < 0.01). Multivariate survival analysis using a Cox proportional hazards model showed that cancer of the gallbladder neck and CA199 expression level were independent prognostic factors. CONCLUSION: CA242 is a marker of GBC infiltration in the early stage. CA199 and cancer of the gallbladder neck are therapeutic and prognostic markers.