Association of education with cholelithiasis and mediating effects of cardiometabolic factors: A Mendelian randomization study.

BACKGROUND: Education, cognition, and intelligence are associated with cholelithiasis occurrence, yet which one has a prominent effect on cholelithiasis and which cardiometabolic risk factors mediate the causal relationship remain unelucidated. AIM: To explore the causal associations between education, cognition, and intelligence and cholelithiasis, and the cardiometabolic risk factors that mediate the associations. METHODS: Applying genome-wide association study summary statistics of primarily European individuals, we utilized two-sample multivariable Mendelian randomization to estimate the independent effects of education, intelligence, and cognition on cholelithiasis and cholecystitis (FinnGen study, 37041 and 11632 patients, respectively; n = 486484 participants) and performed two-step Mendelian randomization to evaluate 21 potential mediators and their mediating effects on the relationships between each exposure and cholelithiasis. RESULTS: Inverse variance weighted Mendelian randomization results from the FinnGen consortium showed that genetically higher education, cognition, or intelligence were not independently associated with cholelithiasis and cholecystitis; when adjusted for cholelithiasis, higher education still presented an inverse effect on cholecystitis [odds ratio: 0.292 (95%CI: 0.171-0.501)], which could not be induced by cognition or intelligence. Five out of 21 cardiometabolic risk factors were perceived as mediators of the association between education and cholelithiasis, including body mass index (20.84%), body fat percentage (40.3%), waist circumference (44.4%), waist-to-hip ratio (32.9%), and time spent watching television (41.6%), while time spent watching television was also a mediator from cognition (20.4%) and intelligence to cholelithiasis (28.4%). All results were robust to sensitivity analyses. CONCLUSION: Education, cognition, and intelligence all play crucial roles in the development of cholelithiasis, and several cardiometabolic mediators have been identified for prevention of cholelithiasis due to defects in each exposure.

Chinese expert recommendations on management of hepatocellular carcinoma during COVID-19 pandemic: a nationwide multicenter survey.

BACKGROUND: This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic. METHODS: A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic. RESULTS: 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the "face-to-face" visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC. DISCUSSION: During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery.

Mutation profile and its correlation with clinicopathology in Chinese hepatocellular carcinoma patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer worldwide. Although many studies have focused on oncogene characteristics, the genomic landscape of Chinese HCC patients has not been fully clarified. METHODS: A total of 165 HCC patients, including 146 males and 19 females, were enrolled. The median age was 55 years (range, 27-78 years). Corresponding clinical and pathological information was collected for further analysis. A total of 168 tumor tissues from these patients were selected for next-generation sequencing (NGS)-based 450 panel gene sequencing. Genomic alterations including single nucleotide variations (SNV), short and long insertions and deletions (InDels), copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. The top quartile of HCC was classified as TMB high. RESULTS: A total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues. TMB values were identified in 160 HCC specimens, with a median TMB of 5.4 Muts/Mb (range, 0-28.4 Muts/Mb) and a 75% TMB of 7.7 Muts/Mb. The most commonly mutated genes were TP53, TERT, CTNNB1, AXIN1, RB1, TSC2, CCND1, ARID1A, and FGF19. SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs. Compared to wild-type patients, the proportion of Edmondson grade III-IV and microvascular invasion was significantly higher in TP53 mutated patients (P<0.05). The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients (P<0.05). The proportion of Edmondson grade I-II, alpha fetoprotein (AFP) <25 µmg/L, and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients (P<0.05). CTNNB1 mutations were associated with TMB high in HCC patients (P<0.05). Based on correlation analysis, the mutation of TP53 was independently correlated with microvascular invasion (P=0.002, OR =3.096) and Edmondson grade III-IV (P=0.008, OR =2.613). The mutation of TERT was independently correlated with tumor invasion of the liver capsule (P=0.001, OR =3.030), and the mutation of CTNNB1 was independently correlated with AFP (<25 µmg/L) (P=0.009, OR =3.414). CONCLUSIONS: The most frequently mutated genes of HCC patients in China were TP53, TERT, and CTNNB1, which mainly lead to the occurrence and development of HCC by regulating the P53 pathway, Wnt pathway, and telomere repair pathway. There were more patients with microvascular invasion and Edmondson III-IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients, while in CTNNB1 mutated patients, there were more patients with Edmondson I-II grade, AFP <25 µmg/L, and a non-hepatitis B background. Also, the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.

Gastric plexiform fibromyxoma: A case report.

BACKGROUND: Plexiform fibromyxoma (PF) is a rare mesenchymal tumor of the stomach. The clinical features of PF frequently include upper abdominal pain, abdominal discomfort, hematemesis, melena, pyloric obstruction and an upper abdominal mass. We herein report a case of PF resected by laparoscopic radical distal gastrectomy plus Roux-en-Y gastrojejunostomy. CASE SUMMARY: The patient was admitted to hospital, due to a 1-wk history of an abdominal space-occupying lesion identified during a health examination. He underwent complete resection by laparoscopic radical distal gastrectomy plus Roux-en-Y gastrojejunostomy. During the operation, the tumor was located in the anterior wall of the gastric antrum (approximately 7 cm × 6 cm × 5.5 cm) and did not show evidence of invasion of the serosa. Histology showed that the tumor cells were oval fibroblast-like and spindle-shaped cells, with numerous thin-walled blood vessels and abundant myxoid stroma. Cellular atypia and mitosis were both rare. Immunohistochemistry showed that the tumor cells were immunoreactive for smooth muscle actin, S-100 and CD-10, but were negative for CD-117, CD-34, DOG-1, and ALK. In this case, S-100 was positive and no significant disease was observed during the follow-up period. CONCLUSION: The fact that PF is a rare tumor with only a few cases in this region can lead to misdiagnosis of this entity and pose a real diagnostic challenge for general surgeons and pathologists when encountering such patients and differentiating PF from other primary tumors of gastric mesenchymal origin. Our report may help increase awareness of this rare, but important new disease entity.

SMAD4 Y353C promotes the progression of PDAC.

BACKGROUND: SMAD4 is frequently inactivated and associated with a poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Abnormal SMAD4 expression also plays an important role in the malignant progression of PDAC. METHODS: We investigated SMAD4 status in PDAC by immunohistochemical methods to explore the relationships between SMAD4 expression and clinicopathological features and then detected SMAD4 mutations by Sanger sequencing in 95 patients with PDAC to identify new mutation sites in PDAC. We further evaluated the effects of a missense mutation, Y353C, in the SMAD4 MH2 domain, on cell proliferation and migration in vitro. RESULTS: Immunohistochemistry showed that the expression of SMAD4 in PDAC carcinoma tissue was significantly lower than that in normal pancreatic tissue, and negative SMAD4 expression was closely related to tumour diameter, staging, lymph node metastasis and differentiation. Sanger sequencing analysis showed that the rate of SMAD4 mutation was 11.8% in 85 PDAC cases, and the novel SMAD4 Y353C missense mutation identified in this study promoted cell migration and invasion without affecting cell proliferation in vitro. Furthermore, SMAD4 Y353C resulted in reduced expression of E-cadherin and increased expression of Vimentin compared with wild-type SMAD4 overexpression. CONCLUSION: This study supports the key role of SMAD4 as a tumour suppressor gene in PDAC and shows that SMAD4 Y353C is associated with poor progression of PDAC.

Elevated Preoperative Serum CA125 Predicts Larger Tumor Diameter in Patients with Hepatocellular Carcinoma and Low AFP Levels.

AIM: Little is known about the association between cancer antigen 125 (MUC16/CA125) concentrations and tumor diameter of patients with hepatocellular carcinoma (HCC) and low AFP levels. To fill this gap in our knowledge, we conducted a retrospective study of 427 patients with HCC with AFP ≤200 ng/mL who underwent R0 resection at our center. METHODS: The associations between CA125 concentrations and patients' clinicopathological characteristics were analyzed. Survival vs CA125 levels was also evaluated between patient groups with CA125 ≤30 U/mL or CA125 >30 U/mL. Independent risk factors of disease-free survival (DFS) and overall survival (OS) were analyzed with Cox hazard regression model. RESULTS: Elevated preoperative serum CA125 was significantly associated with maximal tumor diameter (MTD) >5 cm and female sex (P < 0.001 and P=0.044, respectively). The DFS and OS of patients with CA125 ≤30 U/mL (n = 392) were significantly higher compared with those with CA125 >30 U/mL (n = 35) (P=0.003 and P=0.001 respectively). Multivariate analysis revealed that MTD >5 cm was an independent risk factor of DFS (HR = 1.891, 95% CI: 1.379-2.592, P < 0.001) and OS (2.709, 1.848-3.972, P < 0.001). CONCLUSIONS: In conclusion, elevated preoperative serum CA125 predicted larger tumor diameter and poor prognosis after patients with HCC with AFP ≤200 ng/mL underwent R0 resection, which may be explained by the elevation of the preoperative serum CA125 level significantly associated with MTD>5 cm.

Risk factors and prognosis of patients with recurrent hepatocellular carcinoma who undergo liver re-resections.

BACKGROUND: Management of recurrent hepatocellular cancer (HCC) after liver resection is challenging, with unsatisfactory long-term patient outcomes. Liver re-resection, in theory, is a good treatment option. We therefore studied prognosis and risk factors of patients who undergo re-hepatectomy. METHODS: We retrospectively analyzed 103 patients who underwent re-hepatectomy. RESULTS: The re-resection postoperative complication rate was 31.1% (32/103). Patients with gross vascular invasion (GVI), cirrhosis, or hepatitis B (HBV) infections not treated with antiviral therapy had higher morbidity than patients without these diseases (per chi-square tests). In bivariate regression analysis, cirrhosis (odds ratio [OR]: 10.308, P = 0.031) and HBV not treated with antiviral therapy (OR: 3.982, P = 0.011) were associated with immediate postoperative morbidity. Median overall survival (OS) after re-resection was 65.0 months (range: 2.1-119.3 months); cumulative OS rates were 1-year: 92.1%, 2-year: 78.2%, and 5-year: 54.4%. Independent risk factors for worse survival were serum AFP level > 20 ng/mL at first resection, portal hypertension (PH) and GVI at recurrence. In the non-PH group, microvascular invasion (micro-VI), GVI and pTNM III-IV disease were associated with poor prognosis; patients with pTNM I-II disease had significantly less micro-VI and GVI than did patients with advanced disease. CONCLUSION: Repeat hepatectomy has favorable long-term outcomes. Cirrhosis and HBV not treated with antiviral therapy were associated with immediate postoperative morbidity. Serum AFP > 20 ng/mL at first resection, PH, and GVI at recurrence are independent prognostic factors. For patients without PH, TNM staging can predict prognosis.

Treatment of primary hepatic neuroendocrine tumors with associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): A case report and literature review.

RATIONALE: Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare and are difficult to diagnose preoperatively.We report a case of PHNET diagnosed preoperatively and successfully resected using associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). PATIENT CONCERNS: A 72-year-old woman was admitted to our hospital for a hepatic mass, which was incidentally identified during a routine health checkup. The patient has no other obvious symptoms of discomfort. DIAGNOSES: Physical examination revealed a palpable mass in the right upper quadrant of her abdomen. Dynamic contrast-enhanced abdominal computed tomography (CT) showed a low-density mass measuring 13 × 7 × 6 cm in both, the right and left hepatic lobes. F-fluorodesoxyglucose positron emission tomography (F-FDG PET) and fused PET/CT showed increased uptake by the mass, which was indicative of a hepatic tumor. INTERVENTIONS: We use a novel ALPPS surgical procedure to safely and radically remove primary neuroendocrine tumors. OUTCOMES: No postoperative bleeding and bile leakage were reported, and the patient recovered uneventfully.The patient was followed-up for a year without recurrence. LESSONS: PHNETs are rare tumors, and confirming the diagnosis using the best possible preoperative examination is important. An optimal treatment plan is selected based on the patient's condition to ensure a favorable prognosis. Tumors too large to undergo surgical removal can be resected using the ALPPS procedure, as described in this case report.

Recurrence of Barcelona Clinic Liver Cancer Stage A Hepatocellular Carcinoma After Hepatectomy.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) staging system is widely used to classify hepatocellular carcinoma (HCC). This study was performed to investigate the prognostic factors for patients with BCLC stage A HCC after R0 hepatectomy. METHODS: A total of 592 patients with BCLC stage A HCC following R0 hepatectomy from 1997-2012 were enrolled in this study. Kaplan-Meier analysis and Cox regression were used to analyze the risk factors associated with recurrence. Receiver operating characteristic curves were used to establish a new scoring system to evaluate the independent risk factors for recurrence. Furthermore, subgroup analyses were performed to evaluate surgical margins on tumor recurrence between the anatomic and nonanatomic resection group. RESULTS: Independent risk factors for BCLC stage A HCC recurrence were preoperative alanine transaminase >40U/L, liver cirrhosis, surgical margin <5mm, nonanatomic resection and maximum tumor diameter >5cm. Based on these 5 risk factors, we established a new scoring system, named "HCC recurrence scoring system." Patients with a high score (≥3 points, 1 point for each factor) composed the high recurrence risk group. Moreover, the subgroup analyses demonstrated that different surgical margins had no significant effect on tumor recurrence in the anatomic resection group (P = 0.408), while it had a significant effect in the nonanatomic resection group (P = 0.000). CONCLUSIONS: For patients with BCLC stage A with scores ≥3 points, close postoperative follow-up and positive measures to prevent recurrence are particularly important. Anatomic resection is preferred for patients with BCLC stage A. Adequate surgical margins are necessary for patients with poor liver function.

YY1 promotes HDAC1 expression and decreases sensitivity of hepatocellular carcinoma cells to HDAC inhibitor.

YY1 is a DNA-binding transcription factor and reported to be involved in cancer progression. Histone deacetylase inhibitor (HDACi) could inhibit proliferation and promote apoptosis of Hepatocellular carcinoma (HCC) cells. However, it is unclear about the roles of YY1 in the sensitivity of HCC cells to HDACi. In this study, firstly, we identified two drug-response profiles to HDACi in HCC cell lines, while our results showed that HDAC1 expression was positively correlated with YY1 in HCC cell lines and primary tumor tissues. Secondly, YY1 decreased the sensitivity of HCC cells to HDACi in vitro and in vivo. Furthermore, we found that YY1 promoted HDAC1 expression by binding to its promoter, while HDAC1 in turn up-regulated the expression of YY1. In conclusion, our results showed that YY1 could reduce the sensitivity of HCC cells to HDACi and might be a potential therapeutic target in HCC.

MicroRNA-23b functions as an oncogene and activates AKT/GSK3ß/ß-catenin signaling by targeting ST7L in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor and threatens human life worldwide, whereas the etiology and pathogenesis of HCC have not been fully determined. In the past few years, many microRNAs (miRNAs) have been proved to have important roles in tumorigenesis of HCC. In this study, we found that miR-23b was significantly upregulated in tumor tissues of HCC patients. Functional tests showed that miR-23b could promote HCC cell proliferation and metastasis in vitro and in vivo. Then, mechanistic investigations suggested that ST7L was a direct target of miR-23b and involved in the promotion effects of miR-23b on HCC tumorigenesis and metastasis. Furthermore, our study indicated that ST7L could interact with the carboxyl terminal region of AKT and suppress AKT/GSK3ß/ß-catenin pathway in HCC cells. In conclusion, our study revealed important roles of miR-23b and ST7L in progression of HCC.

Polymorphisms in the IL-17 Gene (rs2275913 and rs763780) Are Associated with Hepatitis B Virus Infection in the Han Chinese Population.

AIM: Interleukin-17 (IL-17) can accelerate the release of many pro-inflammatory cytokines. The purpose of our study was to investigate the potential association between polymorphisms in the IL-17 gene and susceptibility to hepatitis B virus (HBV) infection in the Han Chinese population. METHODS: We recruited 596 HBV-infected patients and 612 ethnically matched controls, who were then genotyped for the IL-17A and IL-17F polymorphisms, rs2275913 and rs763780, respectively, by using TaqMan probe-based real-time polymerase chain reaction. The frequencies of the alleles and genotypes in patients and controls were compared by the χ2 test. RESULTS: Statistically significant differences in genotypic and allelic frequencies were revealed at both polymorphic sites between HBV-positive patients and controls (rs2275913: genotype χ2 = 37.74, p < 0.001 and allele χ2 = 22.17, p < 0.001, odds ratio [OR] = 0.654, 95% confidence interval [CI] = 0.548-0.781. rs763780: genotype χ2 = 19.80, p < 0.001 and allele χ2 = 18.78, p < 0.001, OR = 0.507, 95% CI = 0.371-0.692). CONCLUSIONS: These results indicate that the IL-17A rs2275913 and IL-17F rs763780 polymorphisms are associated with HBV infection in the Han Chinese population. We conclude that possession of the GG genotype and the G allele at rs2275913, and the TT genotype and the T allele at rs763780 might increase the risk of HBV infection. Larger-scale, multiracial studies are necessary to evaluate the role of IL-17 polymorphisms in relation to an enhanced risk of HBV infection.

X-inactive-specific transcript of peripheral blood cells is regulated by exosomal Jpx and acts as a biomarker for female patients with hepatocellular carcinoma.

BACKGROUND: Long noncoding ribonucleic acid (lncRNA) X-inactive-specific transcript (Xist) was reported to affect cell proliferation and metastasis in hepatocellular carcinoma (HCC). However, there are rare reports focusing on the diagnostic evaluation and regulatory mechanism of Xist expression from peripheral blood cells of patients with HCC. METHODS: In this study, a cohort of 206 female participants including healthy volunteers (HVs) and patients with chronic hepatitis B (CHB), cirrhosis and HCC was recruited. Coculture system was used to evaluate the effects of exosomal JPX transcript, XIST activator (Jpx) on Xist expression of blood cells. RESULTS: First, Xist expressions of both peripheral blood mononuclear cells and granulocytes were upregulated in female patients with HCC, and showed significantly increased discriminatory power when differentiating female patients with early-stage HCC from controls or differentiating female patients with HCC from patients with CHB and cirrhosis, compared with alpha fetoprotein (AFP). Then, another lncRNA Jpx that was an activator of Xist was upregulated in exosomes, mononuclear cells and granulocytes of female patients with HCC. Furthermore, our results showed that Jpx could be delivered from HCC cells to blood cells via exosomes and activate Xist expression of blood cells by repressing the transregulatory effects of CCCTC-binding factor (CTCF). CONCLUSIONS: This study revealed an exosome-mediated regulation of Xist expression in blood cells and suggested that Xist expressions of mononuclear cells and granulocytes would be promising biomarkers for diagnosis of female patients with HCC.

Prognosis of hepatocellular carcinoma with bile duct tumor thrombus after R0 resection: a matched study.

BACKGROUND: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare. The present study aimed to determine post-surgical prognoses in HCC patients with BDTT, as outcomes are currently unclear. METHODS: We compared the prognoses of 110 HCC patients without BDTT (group A) to 22 cases with BDTT (group B). The two groups were matched in age, gender, tumor etiology, size, number, portal vascular invasion, and TNM stage. Additionally, 28 HCC patients with BDTT were analyzed to identify prognostic risk factors. RESULTS: The 1-, 3-, and 5-year overall survival rates were 90.9%, 66.9%, and 55.9% for group A and 81.8%, 50.0%, and 37.5% for group B, respectively. The median survival time in groups A and B was 68.8 and 31.4 months, respectively (P=0.043). The patients for group B showed higher levels of serum total bilirubin, alanine aminotransferase and gamma-glutamyl transferase, a larger hepatectomy range, and a higher rate of anatomical resection. In subgroup analyses of patients with BDTT who underwent R0 resection, TNM stage III-IV was an independent risk factor for overall survival; these patients had worse prognoses than those with TNM stage I-II after R0 resection (hazard ratio=6.056, P=0.014). Besides, univariate and multivariate analyses revealed that non-R0 resection and TNM stage III-IV were independent risk factors for both disease-free survival and overall survival of 28 HCC patients with BDTT. The median overall survival time of patients with BDTT who underwent R0 resection was longer than that of patients who did not undergo R0 resection (31.0 vs 4.0 months, P=0.007). CONCLUSIONS: R0 resection prolonged survival time in HCC patients with BDTT, although prognosis remains poor. For such patients, R0 resection is an important treatment that determines long-term survival.

DANCR Acts as a Diagnostic Biomarker and Promotes Tumor Growth and Metastasis in Hepatocellular Carcinoma.

BACKGROUND: Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) is considered to be an oncogene in many cancer types. However, the role of DANCR in diagnosis and progression of hepatocellular carcinoma (HCC) is still unknown. PATIENTS AND METHODS: In this study, 146 participants including healthy volunteers (HVs) and patients with chronic hepatitis B (CHB), cirrhosis and HCC were recruited. RESULTS: Firstly, quantitative reverse transcription-PCR analysis showed that DANCR was up-regulated in tumor tissues and plasma of patients with HCC, and its expression was highly correlated with microvascular and liver capsule invasion of HCC. Receiver operating characteristic analysis showed that plasma DANCR exhibited significantly increased discriminatory power for differentiating patients with HCC from HVs and non-HCC patients compared to alpha fetoprotein, which has been used as a biomarker for HCC diagnosis. Furthermore, knockdown of DANCR repressed the ß-catenin pathway and inhibited HCC cell proliferation and metastasis both in vitro and in vivo. CONCLUSION: This study revealed, for the first time, the importance of DANCR in clinical diagnosis and disease progression of HCC.

Effect of surgical margin in R0 hepatectomy on recurrence-free survival of patients with solitary hepatocellular carcinomas without macroscopic vascular invasion.

The study aimed to investigate the impact of different surgical margins on recurrence-free survival (RFS) of patients with solitary hepatocellular carcinoma (HCC) without macroscopic vascular invasion.The data of 586 selected patients who underwent curative hepatectomy for HCC between 2001 and 2012 were analyzed. The patients were divided into the anatomic resection and the nonanatomic resection groups according to the surgical approaches. Each group was further divided into group A (surgical margin <5 mm), group B (5 mm ≤ surgical margin < 10 mm), and group C (surgical margin ≥10 mm). Relationship between surgical margins and RFS in different groups was established by receiver operating characteristic curve and Kaplan-Meier analyses.The RFS of the anatomic resection group was significantly longer than that of the nonanatomic resection group (P = 0.026). There were no statistical differences in RFS between groups A, B, and C (PA VS B = 0.512, PA VS C = 0.272, PB VS C = 0.822, nA = 38, nB = 43, nC = 80) in the anatomic resection group while in the nonanatomic resection group, RFSs of groups B and C were longer than that of group A (PA VS B = 0.009, PA VS C = 0.000, PB VS C = 0.505, nA = 151, nB = 119, nC = 155).The analytic results suggest that if the patients with solitary HCC without macroscopic vascular invasion fall in the anatomic resection group, a minimal surgical margin (≥0 mm) is probably appropriate for hepatectomy; however, in cases of the nonanatomic resection, a surgical margin ≥5 mm should be regarded suitable for surgery of HCC.

Combined measurements of tumor number and size helps estimate the outcome of resection of Barcelona clinic liver cancer stage B hepatocellular carcinoma.

BACKGROUND: Although the Barcelona Clinic Liver Cancer (BCLC) staging system suggests that patients with stage B hepatocellular carcinoma (HCC) should be treated with transcatheter arterial chemoembolization instead of surgical treatment, recent studies indicated that the prognosis of surgical resection for patients with BCLC stage B HCC was better than that of TACE. However, the portion of patients with stage B that will achieve better outcomes from surgical treatment remains unclear. In this study, we identified risk factors that influence the prognosis of BCLC stage B HCC after R0 surgical resection to determine whether some patients with stage B HCC may benefit more from R0 resection than other patients and to provide a guideline to estimate the tendency. METHODS: The clinical data of 78 patients with BCLC stage B HCC after R0 surgical treatment within 11 years were analyzed retrospectively, using relapse or death as the endpoint. Kaplan-Meier survival and Cox regression analyses were used to study prognosis (disease-free survival, DFS and overall survival, OS) and independent risk factors. RESULTS: For all stage B patients, 1-, 2-, and 5-year DFS rates were 62.5, 36.4, and 16.6%, respectively. Cumulative tumor size >5.0 cm and tumor number ≥4 were independent prognostic risk factors for DFS. The 1-, 2-, and 5- year DFS rates and OS rates of patients with at least one of these two factors were 49.0, 17.2, and 7.4% (for DFS), and 78.6, 54.8, and 13.4% (for OS), respectively, which were significantly lower than patients without these two factors (77.8, 58.3, and 27.2% for DFS, and 94.4, 83.3,and 51.8% for OS, respectively, P < 0.01). CONCLUSIONS: The analyses indicated that the outcomes of R0 resection were much better for patients with BCLC stage B HCC with two or three tumors and cumulative tumor sizes of ≤5.0 but >3.0 cm than other patients with stage B.

Hepatic falciform ligament clear cell myomelanocytic tumor: A case report and a comprehensive review of the literature on perivascular epithelioid cell tumors.

BACKGROUND: The objective of the study was to explore the clinical expression, radiological and pathological features, differential diagnosis, and biological behavior of a clear cell myomelanocytic tumor. In a case involving a clear cell myomelanocytic tumor located in the hepatic falciform ligament, we evaluated clinical expression, radiological characteristics, histopathology, immunohistochemistry, and biological behavior; we also reviewed the relevant literature. CASE PRESENTATION: Clear cell myomelanocytic tumor is a benign soft-tissue neoplasm that often occurs in women, and is expressed as a painless mass. The falciform ligament is its most frequent site of occurrence. The imaging characteristics of this lesion were uneven enhancement in the arterial phase, continuing to strengthen in the venous phase, and equal density in the balance phase. Histological and immunohistochemical analysis revealed the main transparent epithelioid cells and smooth muscle spindle cells to be HMB-45(+), smooth muscle actin(+), and melan-A (+). CONCLUSION: Hepatic vascular epithelioid cell tumors are very rare mesenchymal neoplasms. Few studies have investigated this tumor in the hepatic falciform ligament; consequently, its diagnosis and the selection of an appropriate treatment and follow-up protocol are challenging. Treatment outcome remains unpredictable. Therefore, clear cell myomelanocytic tumor should be viewed as a tumor with uncertain malignant potential requiring long-term follow-up.

Use of Cytokeratin-19 Concentration to Assess Early Recurrence and Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma following Radical Resection in Patients with a Low Serum Alpha-Fetoprotein Concentration.

Cytokeratin 19 (CK-19) is a prognostic indicator of recurrence and metastasis of hepatocellular carcinoma (HCC) following radical resection. To investigate the role of CK-19 in assessment of early recurrence and prognosis in patients with hepatitis B virus (HBV)-related HCC following radical resection. In total, 235 patients with HBV-related HCC (age, 15-82 years; mean age, 54 ± 10 years) undergoing radical resection were screened for inclusion from January 2005 to December 2010. Malignant tissues and adjacent non-malignant tissues were sampled during surgery, and CK-19 and Ki-67 expression was determined by tissue microarray and immunohistochemistry. CK-19 mRNA levels in 30 randomly selected frozen HCC specimens were examined by reverse transcription polymerase chain reaction from January 2011 to June 2011. Correlations of CK-19 and Ki-67 expression with tumor recurrence, metastasis, disease-free survival (DFS), and overall survival (OS) were analyzed. Elevated CK-19 expression was correlated with early recurrence (P = 0.001), shorter DFS (P = 0.001), and reduced OS (P = 0.010). CK-19 expression was correlated with the Ki-67 index (P = 0.037), histological differentiation (P = 0.016), focal number (P = 0.044), and blood vessel tumor embolism (P = 0.002). Patients with metastasis within 1 year exhibited stronger CK-19 expression than did patients without metastasis (P < 0.05). Furthermore, early recurrence was associated with elevated CK-19 mRNA levels (χ2 = 5.761, P = 0.016).When confirmed by a low alpha-fetoprotein concentration (<400 µg/L), CK-19 expression in surgical biopsy specimens taken from patients with HCC during radical resection is an additional valuable indicator of early recurrence, distant metastasis, and poor prognosis in HBV-positive patients.

Tryptophan hydroxylase 2 gene is associated with cognition in late-onset depression in a Chinese Han population.

Accumulating evidences suggest that Tryptophan hydroxylase 2 (TPH2) gene is associated with major depressive disorder (MDD) and cognitive function. In present study, we aimed to explore the association of cognitive disturbances in patients with late-onset depression (LOD) in the Chinese Han population. One hundred and ninety unrelated LOD patients who met DSM-IV criteria for major depressive disorder were recruited for the study and 155 normal controls were recruited from local community. All subjects completed the demographic assessments. Furthermore, 97 patients and 44 controls completed a series of neuropsychological tests. Patients and normal controls were genotyped for TPH2 (rs4290270 and rs7305115) variants using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results of our analysis indicated no significant differences in the frequencies of the single alleles and genotypes of two polymorphisms in TPH2 gene between LOD patients and normal controls. Haplotype association indicated that no differences were found in the frequencies of haplotype between two groups. A significant main effect of rs4290270 genotype on Verbal Fluency Test (VFT) test performance was found (P<0.05). There was a significant interactive effect of rs7305115 polymorphisms and depression diagnosis on Symbol Digit Modalities Test (SDMT) (P<0.05). After controlling for covariates, the subjects with carriers of GG genotype in rs7305115 had more better SDMT performance compared to AG and AA carriers in LOD groups. The result suggests that there is a major effect of rs4290270 in TPH2 on cognitive function alone. Moreover, an interaction of rs7305115 polymorphisms and depression diagnosis may be associated with the cognitive function. Further studies in a large sample are needed to replicate the genetic role in the LOD patients.