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Clinical importance of TERT overexpression in hepatocellular carcinoma treated with curative surgical resection in HBV endemic area.

ABSTRACT: This study was designed to investigate the associations between TERT overexpression and the clinicopathologic factors of hepatocellular carcinoma (HCC). A total of 291 patients with HCC were enrolled. The site of first recurrence (anywhere in the liver) was classified as intrahepatic recurrence (IHR). Recurrence was then sub classified as either early or late IHR according to whether it was discovered within 2 years of resection, or after, respectively. TERT overexpression was not significantly correlated with previously recognized prognostic factors. During follow-up, early IHR occurred in 126 (63.6%) patients, while late IHR was detected in 59 patients among 145 patients who remained free of HCC recurrence for ≥ 2 years after surgery. Multivariate analysis showed late IHR was significantly correlated with TERT overexpression (P < 0.001, hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.51-4.72). Intrahepatic metastasis (P < 0.001, HR 4.48, 95% CI 2.62-7.65) and TERT overexpression (P < 0.001, HR 1.77, 95% CI 1.28-2.45) were significant prognostic factors for IHR-free survival in both univariate and multivariate analyses. TERT overexpression was the only significant prognostic factor for late IHR in HCC treated with curative resection. And, the statistical significance of TERT overexpression on late IHR was limited to HBsAg-positive patients.

SUBMITTER: Yu JI

PROVIDER: S-EPMC5612986 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Occult HBV infection status and its impact on surgical outcomes in patients with curative resection for HCV-associated hepatocellular carcinoma.

Project description:Background:We sought to clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and to determine whether OBI affects the surgical outcomes in curatively resected Japanese patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Methods:A total of 257 patients with HCV-related HCC who underwent curative surgical resection were enrolled. All enrolled patients were serologically negative for HBV surface antigen and positive for HCV antibody. DNA was extracted from formalin-fixed paraffin-embedded liver tissue. OBI was determined by the HBV-DNA amplification of at least two different sets of primers by TaqMan real-time polymerase chain reaction. Surgical outcomes were evaluated according to overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Results:OBI was identified in 15 of the 257 (5.8%) cases. In the multivariate analyses, the factors significantly correlated with OS were BMI >25 (P=0.0416), portal vein invasion (P=0.0065), and multiple tumors (P=0.0064). The only factor significantly correlated with DSS was T-stage (P=0.0275). The factors significantly correlated with DFS were liver fibrosis (P=0.0017) and T-stage (P=0.0001). The status of OBI did not show any significant correlation with OS, DSS or DFS, but a weak association with DSS (P=0.0603) was observed. Conclusions:The prevalence of OBI was 5.8% in 257 cases of HCV-related HCC. Although a weak association between DSS and OBI was observed, and statistical analyses were limited by small number of OBI cases, no significant correlation between OBI and surgical outcomes was detected.

| S-EPMC6295390 | biostudies-other

Local recurrence after curative resection for rectal carcinoma: The role of surgical resection.

Project description:Local recurrence of rectal cancer is difficult to treat, may cause severe and disabling symptoms, and usually has a fatal outcome. The aim of this study was to document the clinical nature of locally recurrent rectal cancer and to determine the effect of surgical resection on long-term survival.A retrospective review was conducted of the prospectively collected medical records of 2485 patients with primary rectal adenocarcinoma who underwent radical resection between September 1994 and December 2008.In total, 147 (5.9%) patients exhibited local recurrence. The most common type of local recurrence was lateral recurrence, whereas anastomotic recurrence was the most common type in patients without preoperative concurrent chemoradiotherapy (CCRT). Tumor location with respect to the anal verge significantly affected the local recurrence rate (P < 0.001), whereas preoperative CCRT did not affect the local recurrence rate (P = 0.433). Predictive factors for surgical resection of recurrent rectal cancer included less advanced tumor stage (P = 0.017, RR = 3.840, 95% CI = 1.271-11.597), axial recurrence (P < 0.001, RR = 5.772, 95% CI = 2.281-14.609), and isolated local recurrence (P = 0.006, RR = 8.679, 95% CI = 1.846-40.815). Overall survival after diagnosis of local recurrence was negatively influenced by advanced pathologic tumor stage (P = 0.040, RR = 1.867, 95% CI = 1.028-3.389), positive CRM (P = 0.001, RR = 12.939, 95% CI = 2.906-57.604), combined distant metastases (P = 0.001, RR = 2.086, 95% CI = 1.352-3.218), and nonsurgical resection of recurrent tumor (P < 0.001, RR = 4.865, 95% CI = 2.586-9.153).In conclusion, the clinical outcomes of local recurrence after curative resection of rectal cancer are diverse. Surgical resection of locally recurrent rectal cancer should be considered as an initial treatment, especially in patients with less advanced tumors and axial recurrence.

| S-EPMC5058796 | biostudies-literature

Project description:BackgroundBoth persistent inflammatory activity and liver function damage contribute to a poor prognosis of hepatocellular carcinoma (HCC). This study aimed to develop nomograms that incorporate hepatitis virus B (HBV)-related peritumoral inflammation score (PIS) and liver function based on ALBI score to predict postoperative outcomes of HCC.MethodsThe prognostic roles of HBV-related preoperative PIS and ALBI scores in HCC recurrence were examined, and then two nomograms were constructed. The predictive accuracy and discriminative ability of the nomograms were compared with AJCC and BCLC staging systems of HCC.ResultsPIS (HBV-PIS) and ALBI scores (HBV-ALBI) with different HBV-DNA loads had association with overall survival (OS) and/or recurrence-free survival (RFS) of HCC. The independent predictors of OS and RFS were incorporated into the corresponding nomograms. In the training cohort, the C-indexes of OS and RFS nomograms were 0.751 and 0.736, respectively. ROC analyses showed that both OS and RFS nomograms had larger AUC (0.775 and 0.739, respectively) than AJCC and BCLC staging systems. These results were verified by the internal and external validation cohorts.ConclusionThe proposed nomograms, including HBV-DNA load-related PIS and ALBI scores, were accurate in predicting survival for HCC after curative resection.

| S-EPMC6171205 | biostudies-literature

Curative-intent pancreas resection for pancreatic metastases: surgical and oncological results.

Project description:BACKGROUND:Pancreatic metastasis is a rare cause for pancreas surgery and often a sign of advanced disease no chance of curative-intent treatment. However, surgery for metastasis might be a promising approach to improve patients' survival. The aim of this study was to analyze the surgical and oncological outcome after pancreatic resection of pancreatic metastasis. METHODS:This is a retrospective cohort analysis of a prospectively-managed database of patients undergoing pancreatic resection at the University of Freiburg Pancreatic Center from 2005 to 2017. RESULTS:In total, 29 of 1297 (2%) patients underwent pancreatic resection due to pancreatic metastasis. 20 (69%) patients showed metastasis of renal cell carcinoma (mRCC), followed by metastasis of melanoma (n?=?5, 17%), colon cancer (n?=?2, 7%), ovarian cancer (n?=?1, 3%) and neuroendocrine tumor of small intestine (n?=?1, 3%). Two (7%) patients died perioperatively. Median follow-up was 76.4 (range 21-132) months. 5-year and overall survival rates were 82% (mRCC 89% vs. non-mRCC 67%) and 70% (mRCC 78% vs. non-mRCC 57%), respectively. Patients with mRCC had shorter disease-free survival (14 vs. 22 months) than patients with other primary tumor entities. CONCLUSION:Despite malignant disease, overall survival of patients after metastasectomy for pancreatic metastasis is acceptable. Better survival appears to be associated with the primary tumor entity. Further research should focus on molecular markers to elucidate the mechanisms of pancreatic metastasis to choose the suitable therapeutic approach for the individual patient.

| S-EPMC7138763 | biostudies-literature

Peritumoral EpCAM Is an Independent Prognostic Marker after Curative Resection of HBV-Related Hepatocellular Carcinoma.

Project description:Accumulating evidence suggests that the tumor microenvironment has a profound influence on tumor initiation and progression, opening a new avenue for studying tumor biology. Nonetheless, the prognostic values of the peritumoral expression of EpCAM and CD13 remain to be elucidated in hepatocellular carcinoma (HCC) patients. In this study, the expression of EpCAM and CD13 was assessed by immunohistochemistry in peritumoral liver hepatocytes from 106 hepatitis B virus- (HBV-) related HCC patients who had undergone curative hepatectomy. The peritumoral EpCAM-positive group had a significantly worse overall survival (OS) (p = 0.003) and recurrence-free survival (RFS) (p = 0.022) compared to the negative group. Peritumoral CD13-positive patients were also associated with poor OS (p = 0.038), while not significantly associated with RFS. The adjusted multivariate COX proportional hazard regression analysis suggested that only the positive expression of peritumoral EpCAM precisely predicted poor OS. Being peritumoral EpCAM positive was also significantly associated with a larger tumor size, liver cirrhosis, and more frequent vascular invasion; however, no statistically significant association was observed between CD13 and any clinicopathological features. Taken together, peritumoral EpCAM and CD13 expression was associated with a poor prognosis, but EpCAM may be a better prognostic marker than CD13 in HBV-related HCC patients. In the future, peritumoral EpCAM could be a good target for adjuvant therapy after curative hepatectomy.

| S-EPMC5442434 | biostudies-literature

Towards HBV curative therapies.

Project description:Tremendous progress has been made over the last 2 decades to discover and develop approaches to control hepatitis B virus (HBV) infections and to prevent the development of hepatocellular carcinoma using various interferons and small molecules as antiviral agents. However, none of these agents have significant impact on eliminating HBV from infected cells. Currently the emphasis is on silencing or eliminating cccDNA, which could lead to a cure for HBV. Various approaches are being developed including the development of capsid effectors, CRISPR/Cas9, TALENS, siRNA, entry and secretion inhibitors, as well as immunological approaches. It is very likely that a combination of these modalities will need to be employed to successfully eliminate HBV or prevent virus rebound on discontinuation of therapy. In the next 5 years clinical data will emerge which will provide insight on the safety and feasibility of these approaches and if they can be applied to eradicate HBV infections globally. In this review, we summarize current treatments and we highlight and examine recent therapeutic strategies that are currently being evaluated at the preclinical and clinical stage.

| S-EPMC6481632 | biostudies-literature

Overexpression of interleukin-35 in intrahepatic cholangiocarcinoma is a prognostic indicator after curative resection.

Project description:Interleukin-35 (IL-35) is implicated in tumorigenesis, but its exact impact on intrahepatic cholangiocarcinoma (ICC) is not clear. The aim of the present study was to explore the specific effect of IL-35 on patient prognosis. Additionally, we formulated an effective prognostic nomogram for ICC patients after curative resection. Immunohistochemistry was applied to explore IL-35 expression as well as IL-35 receptor (IL-35R) in 102 ICC patients. Results showed that IL-35 was highly expressed in ICC tumor tissues and was positively associated with lymph node metastasis (LNM), TNM stage and vascular invasion and was an independent prognostic factor for patients' overall survival (OS) and recurrence-free survival (RFS). High expression of IL-35R (gp130 and IL-12Rβ2) was also observed in ICC cancer tissues, but only gp130 was an independent prognostic factor for OS and RFS and was indispensable in IL-35-mediated ICC clinical prognosis. The nomogram comprising carcinoembryonic antigen, LNM, IL-35 and gp130 expression achieved better predictive accuracy compared with TNM stage for OS. Our data support that high IL-35 expression correlates with ICC aggressiveness and emerges as a valuable biomarker for evaluating ICC progression and prognosis in clinical work.

| S-EPMC5891208 | biostudies-literature

Lactate dehydrogenase is a prognostic indicator in patients with hepatocellular carcinoma treated by sorafenib: results from the real life practice in HBV endemic area.

Project description:PurposeLactate dehydrogenase (LDH), which was an indirect marker of hypoxia, was a potentially prognostic factor in several malignancies. There is a lack of evidence about the prognostic value of serum LDH level in patients with hepatocellular carcinoma (HCC) receiving sorafenib treatment from hepatitis B virus endemic areas.Materials and methodsA total of 119 HBV-related HCC patients treated by sorafenib from a Chinese center were included into the study. They were categorized into 2 groups according to the cut-off value of pre-treatment LDH, which was determined by the time dependent receiver operating characteristics (ROC) curve for the overall survival. The prognostic value of LDH was evaluated. The relationships between LDH and other clinicopathological factors were also assessed.ResultsThe cut-off value was 221 U/L. With a median follow up of 15 (range, 3-73) months, 91 patients reached the endpoint. Multivariate analysis proved that pre-treatment serum LDH level was an independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). For patients whose pre-treatment LDH ≥ 221 U/L, increased LDH value after 3 months of sorafenib treatment predicted inferior OS and PFS. And patients with elevated pre-treatment LDH level predisposed to be featured with lower serum albumin, presence of macroscopic vascular invasion, advanced Child-Pugh class, advanced T category, higher AFP, and higher serum total bilirubin.ConclusionsSerum LDH level was a potentially prognostic factor in HCC patients treated by sorafenib in HBV endemic area. More relevant studies with reasonable study design are needed to further strengthen its prognostic value.

| S-EPMC5349941 | biostudies-literature

Case Report: Congenital Intracranial Kaposiform Hemangioendothelioma Treated With Surgical Resection.

Project description:BackgroundKaposiform hemangioendothelioma (KHE) is a locally aggressive but non-metastatic vascular neoplasm. Most studies have been restricted to small case series of limited generalizability. Intracranial KHE is extremely rare with only three cases reported in the literature. Here, we report a case of congenital intracranial KHE who underwent surgical resection, and no lesion recurrence was seen during the follow-up period of 13 months.Case descriptionA 2-month-old boy initially presented with a left temporal mass following birth. Antenatal ultrasound at 36 weeks of gestation demonstrated a hyperechoic signal present in the left frontal lobe, with clear borders and irregular morphology. There were neither cutaneous abnormalities nor other neurologic examination abnormalities. No laboratory abnormality was identified. Computed tomography (CT) scans suggested that a massive hematoma was noted under the left frontal skull plate, with a little subdural hemorrhage in the adjacent temporal area. The adjacent meninges enhanced and thickened on contrasted T1 magnetic resonance (MR). After the multidisciplinary diagnostic assessment, the surgery was performed by the left frontotemporal craniotomy approach. The operation was extremely difficult. We completely removed the tumor, and the involved dura and brain tissue were resected with the lesion in a piecemeal fashion. On postoperative-day (POD) 3 and POD 14, the head CT re-examination revealed that cerebral perfusion improved gradually. The MRI of 6- and 12-month after operation showed no local recurrence or metastasis.ConclusionsIntracranial KHE is difficult to diagnose early and the prognosis has been uniformly poor. We supposed that meticulous intraoperative hemostasis is the key for a successful operation, and the radical resection of the tumor and involved structures are essential to reduce recurrence.

| S-EPMC9012330 | biostudies-literature

Overexpression of interleukin-35 associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection.

Project description:Aberrant expression of interleukin-35 (IL-35) has been implicated in dampening antitumour immunity. The aim of this study was to explore the prognostic significance of IL-35 expression in patients with hepatocellular carcinoma (HCC) following curative resection. Furthermore, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy.Immunohistochemistry was applied to explore IL-35 expression as well as CD39(+)Foxp3(+) and Foxp3(+) regulatory T cell (Treg) infiltration in tissue microarrays in primary cohort comprising 210 randomly selected HCC patients who underwent curative resection. The results were further verified in an independent validation cohort of 138 HCC patients.Patients with higher expression of IL-35 are more likely to suffer postoperative recurrence. Interleukin-35 was also identified as an independent prognostic factor for recurrence free survival in multivariate analysis. No correlation was detected between IL-35 expression and Foxp3(+) Treg infiltration, whereas significant positive correlation was found between IL-35 expression and CD39(+)Foxp3(+) Treg infiltration. In addition, CD39(+)Foxp3(+) Treg infiltration was also an independent predictor for postoperative recurrence. The nomogram comprising tumour size, tumour vascular invasion, IL-35 and CD39(+)Foxp3(+) Tregs had better predictive accuracy when compared with BCLC stage for RFS. These results were further validated in the validation cohort.Our data suggest for the first time that IL-35 expression correlates with HCC aggressiveness and emerged as a novel independent prognostic factor for recurrence, thus conferring the rationale to develop a novel therapy of targeting IL-35. Furthermore, IL-35 should be incorporated into nomogram to generate a more accurate predictive model.

| S-EPMC4984866 | biostudies-other

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