Comparison of clinicopathological traits and prognostic factors of hepatocellular carcinoma with and without cirrhotic background.

The difference of the patients bearing hepatocellular carcinoma (HCC) with and without cirrhosis at clinical level has not been completely determined. This study compared their differences in clinicopathological traits and prognostic factors for relapse-free survival (RFS) and overall survival (OS). Animal model was established to validate the result of clinical observation. As a result, 82 patients bearing HCC with no cirrhosis (HCC-NC) and 146 patients bearing HCC with cirrhosis (HCC-C) were included. HCC-NC exhibited shorter prothrombin time and higher plasma albumin than HCC-C. In HCC-NC, satellite nodule was an independent risk factor for OS, and high γ-glutamyl transpeptidase was an independent risk factor for RFS. In HCC-C, female sex was an independent risk factor for OS. Stratified analysis showed the OS and RFS of HCC-NC were better than HCC-C in conditions like without cancer embolus (in the portal vein or bile duct), without lymphadenopathy in hepatic portal, without satellite nodule and with small or high-differentiated tumor. Animal model analysis showed HCC-NC had a higher liver/body weight ratio, less tumor count and smaller max tumor volume than HCC-C. In conclusion, clinicopathological traits and risk factors influencing postoperative OS and RFS differed between patients with HCC-C and HCC-NC.

Meta-analysis of randomized clinical trials of adjuvant chemotherapy for resected biliary tract cancers.

BACKGROUND: This meta-analysis was performed by analyzing randomized controlled trials (RCTs) to assess the potential prognostic value of adjuvant chemotherapy (ACT) for patients with resected biliary tract cancers (BTCs). METHODS: PubMed, EMBASE, and the Cochrane Library were searched for relevant articles published. Only RCTs affected by tumors of gallbladder, intrahepatic, perihilar, and distal bile ducts were considered. Data were pooled using a random-effects model. The primary endpoint of the study was overall survival (OS). RESULTS: The study identified 1192 patients who met the inclusion and exclusion criteria. ACT had nearly reached a significant better OS (HR, 0.88; 95% CI, 0.77-1.01; P = 0.07) and achieved a significant better RFS (HR, 0.83; 95% CI, 0.69-0.99; P = 0.04). The effectiveness of ACT for OS was significantly modified by fluorouracil-based ACT (HR, 0.83; 95% CI, 0.70-0.99; P = 0.04), but not by gemcitabine-based ACT (HR, 0.91; 95% CI, 0.74-1.12; P = 0.36). The survival benefit was also not modified by primary disease site, resection margin status, and lymph node status. CONCLUSIONS: ACT is correlated with favorable relapse-free survival compared with non-ACT for resected BTCs patients. Fluorouracil-based ACT could be viewed as a standard practice for resected BTCs patients regardless of the primary cancer site, lymph node or margin status.

Decreased expression of HDAC8 indicates poor prognosis in patients with intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant primary tumor in the liver, and the rates of incidence and mortality are rapidly increasing globally. Histone deacetylase 8 (HDAC8) is a transcriptional regulator and is associated with tumorigenesis of several tumor types. This study aimed to evaluate the correlation between HDAC8 expression and clinicopathological parameters in ICC patients. METHODS: ICC tissues and corresponding nonmalignant bile duct tissues were obtained from 60 patients. HDAC8 and Ki-67 expression were evaluated by immunohistochemistry staining. HDAC8 expression and the clinicopathological features and prognosis of the patients were analyzed. The mRNA level of HDAC8 in ICC was further analyzed using data from The Cancer Genome Atlas (TCGA). RESULTS: The expression of HDAC8 were lower in ICC tissues (39/60, 65%) than in the corresponding nonmalignant bile duct tissues (54/60, 90%) (P = 0.001). Low HDAC8 expression in ICC was significantly associated with lymph node metastases (47.6% vs. 17.9%, P = 0.015). In addition, the positive cells rate of HDAC8 was statistically and negatively correlated with the Ki-67 index in ICC lesions (r = -0.7660, P < 0.001). Importantly, the overall survival rate and recurrence-free survival rate in ICC patients with low HDAC8 expression were lower than those with high HDAC8 expression (P = 0.008 and P = 0.011, respectively). CONCLUSIONS: Decreased HDAC8 expression in ICC is related to poor prognosis, and HDAC8 may be an independent prognostic indicator of ICC patients after curative resection.

Elevated expression of Gsα in intrahepatic cholangiocarcinoma associates with poor prognosis.

BACKGROUND: The stimulatory G protein a subunit (Gsα) plays important roles in diverse cell processes including tumorigenesis. Activating mutations in Gsα gene (GNAS) have been reported to be associated with poor prognosis in various human carcinomas. Furthermore, Gsα signaling is crucial in promoting liver regeneration by interacting with growth factor signaling, indicating that Gsα might play a promoting role in cancer development. However, little is known about the correlation between Gsα levels and clinicopathological parameters in intrahepatic cholangiocarcinoma (ICC). METHODS: We performed immunoblotting to examine the expression levels of Gsα and Ki67 proteins in tumor tissues and the corresponding adjacent tissues. A total of 74 pair of specimens resected from 74 ICC patients were examined. The association between Gsα levels and clinicopathological findings and prognosis of the patients was evaluated. RESULTS: Western blotting demonstrated that the expression of Gsα was significantly higher in ICC tissues compared with that in their corresponding adjacent tissues. Gsα protein was highly expressed in about half of ICC tissues (48.6%, 36/74) while only 28.4% (21/74) of tumor adjacent tissues showed Gsα high expression (P=0.011). High Gsα expression in ICC was significantly associated with the numbers of tumor nodules (P=0.037) and lymph node metastases (P=0.010). Moreover, the level of Gsα was significantly and positively correlated with Ki67 expression (P<0.001). In addition, the recurrence-free survival rate and overall survival rate in the Gsα high group were significantly lower than those in the Gsα low group (P=0.004 and P=0.005, respectively). CONCLUSIONS: High Gsα expression is correlated with poor prognosis in ICC patients. Gsα might serve as a potential prognostic indicator of ICC.

HDAC11 is related to breast cancer prognosis and inhibits invasion and proliferation of breast cancer cells.

OBJECTIVE: Histone deacetylases (HDACs) not only regulate histone acetylation but also participate in many pathophysiologic processes, especially the development of cancer, including breast cancer. However, whether Histone deacetylase 11 can influence breast cancer is still unknown. This study investigated the relationship between HDAC11 expression in breast cancers and clinicopathologic parameters, and used small interference RNA (siRNA) to determine the biological behavioural changes after knockdown of HDAC11. METHODS: Immunohistochemical (IHC) staining was employed to detect the expression of HDAC11 in a tissue microarray (TMA) of 145 patients with invasive ductal breast carcinoma. Transwell and wound healing assays were employed to analyze cell invasion and migration. The proliferation ability of cells was determined by Cell Counting Kit (CCK8). RESULTS: The results show that the expression of HDAC11 was positively correlated with the overall survival (OS) of breast cancer patients. Specific HDAC11 knockdown enhanced MDA-MB-231 cell proliferation, migration, and invasion. CONCLUSION: In conclusion, this study found that HDAC11 expression is positively correlated with the overall survival rate of patients. HDAC11 can inhibit the invasion and proliferation of breast cancer cells to a certain extent and can be used as a good prognosis marker.

PI3K-CCL2-CCR2-MDSCs axis: A potential pathway for tumor Clostridia-promoted CD 8+ T lymphocyte infiltration in bile tract cancers.

BACKGROUND: Most patients with resected bile tract cancers (BTCs) survive for less than 5 years; however, some achieve better prognosis. The tumor microbiome can improve survival by regulating the tumor immune microenvironment. However, whether the tumor microbiome promotes immune cell infiltration in BTCs is unknown. This study aimed to determine the association between CD8+ T lymphocyte infiltration and the tumor microbiome in patients with resected BTCs. METHODS: Archived formalin-fixed paraffin-embedded tumor specimens were collected from patients with resected BTCs and analyzed using 16S rRNA gene sequencing to identify that prognosis-related and significantly differentially enriched taxa. Gene ontology (GO) analysis of the differentially enriched taxa was used to assess how CD8+ T lymphocyte infiltration is affected by the tumor microbiome of BTCs. RESULTS: We enrolled 32 patients with resected BTCs. The high CD8+ lymphocyte-infiltration (CD8hi) group had four significantly enriched taxa, and in the low CD8+ lymphocyte-infiltration (CD8low) group comprised one significantly enriched taxon. Patients with higher Clostridia abundance (enriched in the CD8hi group) experienced longer overall survival than those with lower abundance. The enrichment of Clostridia in the CD8hi group corresponded with lower CCL2 expression and downregulation of phosphatidylinositol 3-kinase activity, which might decrease myeloid-derived suppressor cell recruitment to the tumor milieu, thus increasing CD8+ lymphocyte infiltration in BTCs. CONCLUSIONS: The tumor microbiome is related to CD8+ T lymphocyte infiltration in patients with resected BTCs. The relationship between tumor Clostridia and high infiltration of CD8+ T lymphocytes might reflect decreased recruitment of myeloid-derived suppressor cells via the PI3K-CCL2-CCR2 axis.

S14G-humanin confers cardioprotective effects against chronic adrenergic and pressure overload-induced heart failure in mice.

S14G-humanin (HNG), an analog of the mitochondria-derived peptide humanin, has demonstrated protective effects against various cardiovascular diseases. However, the specific pharmacological effects of HNG in heart failure (HF) have not been previously reported. Therefore, in this study, we aimed to investigate the potential protective effect of HNG in HF using a mouse model. HF was induced in mice through intraperitoneal injection of isoproterenol or transverse aortic constriction, followed by separate administration of HNG to assess its therapeutic impact. Our results revealed that HNG treatment significantly delayed the onset of cardiac dysfunction and structural remodeling in the HF mouse model. Furthermore, HNG administration was associated with reduced infiltration of inflammatory cells, improved myocardial fibrosis, and attenuation of cardiomyocyte apoptosis in the treated cardiac tissues. Additionally, we identified the involvement of the transforming growth factor-beta signaling pathway in the beneficial effects of HNG in isoproterenol-induced HF mice. Collectively, these findings underscore the therapeutic potential of HNG in preventing the progression of HF, as demonstrated in two distinct HF mouse models.

Prognostic and diagnostic value of SOX9 in cirrhotic and noncirrhotic hepatocellular carcinoma.

BACKGROUND: This study was designed to explore the prognostic and diagnostic value of Sex-Determining Region Y-Box 9 (SOX9) in cirrhotic hepatocellular carcinoma HCC (CHCC) and noncirrhotic hepatocellular carcinoma (NCHCC). METHODS: SOX9 tissue expression was detected using data from The Cancer Genome Atlas (TCGA) database and our cohort. The Kaplan-Meier method was used to analyze differences in survival between high/low SOX9 expression groups. Univariate analysis and multivariate analysis were used to identify independent risk factors associated with overall survival (OS). Receiver operating characteristic (ROC) curve and area under the curve (AUC) were utilized for evaluation of the diagnostic efficacy of SOX9. RESULTS: SOX9 was found to exhibit differential expression between HCC and adjacent normal tissues but not between CHCC and NCHCC, which was confirmed by RNA sequencing, quantitative real-time polymerase chain reaction and immunohistochemical staining. Kaplan-Meier survival analysis and multivariate analysis revealed that high SOX9 expression was closely related to the OS in NCHCC but not that in CHCC. In CHCC and NCHCC, SOX9 expression was positively associated with serum α-fetoprotein levels. The AUC of SOX9 in differentiating HCC and adjacent normal tissues in CHCC and NCHCC was 0.77 and 0.78, respectively, and no significant difference was found between them. CONCLUSIONS: High SOX9 expression may aid prognostic evaluation in NCHCC but not in CHCC. SOX9 expression was not different between CHCC and NCHCC, but it has reliable and comparable diagnostic value in both CHCC and NCHCC.

Current status and future perspectives of minimally invasive surgery in gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma (GBC) is the most common biliary tract malignancy, which is characterized by easy local invasion, lymph nodes metastasis, local vascular invasion. Hence, minimally invasive surgery (MIS) can be performed in a limited number of patients. In our study, we reviewed the current studies on laparoscopic surgery (LS) and robotic surgery (RS) for GBC and analysed the limitations and difficulties of MIS for GBC. METHODS: Multiple electronic databases were used for a systematic literature retrieval. All studies involving MIS of GBC were included (up to August 2019). RESULTS: A total of 24 studies were included, of which 18 studies involved LS for GBC and six studies concerned RS of GBC. For LS, 16 studies contained relevant information of T stage, and 323 patients (98.8%) had T3 or lower stage; the average rate of R0 resection, conversion, postoperative complications and mortality was 95.3% (range 80.5-100%), 1.9% (range 0-16.7%), 13.4% (range 0-33.3%) and 1.0% (range 0-10%), respectively. For RS, four studies contained relevant information of T stage, and all patients were T3 or lower stage; the average rate of R0 resection, conversion and postoperative complications was 96.8% (range 81.8-100%), 5.5% (range 0-14.8%) and11.9% (range 0-36.4%), respectively. In addition, no patient had perioperative mortality. CONCLUSIONS: MIS for GBC is limited to highly selected patients and is considered to be technically feasible in experienced surgeons. However, improvements in technical and instrumental are needed to reduce the associated postoperative complications and implantation metastasis, and to promote MIS in the treatment of GBC.

Standard liver weight model in adult deceased donors with fatty liver: A prospective cohort study.

BACKGROUND: Standard liver weight (SLW) is frequently used in deceased donor liver transplantation to avoid size mismatches with the recipient. However, some deceased donors (DDs) have fatty liver (FL). A few studies have reported that FL could impact liver size. To the best of our knowledge, there are no relevant SLW models for predicting liver size. AIM: To demonstrate the relationship between FL and total liver weight (TLW) in detail and present a related SLW formula. METHODS: We prospectively enrolled 212 adult DDs from West China Hospital of Sichuan University from June 2019 to February 2021, recorded their basic information, such as sex, age, body height (BH) and body weight (BW), and performed abdominal ultrasound (US) and pathological biopsy (PB). The chi-square test and kappa consistency score were used to assess the consistency in terms of FL diagnosed by US relative to PB. Simple linear regression analysis was used to explore the variables related to TLW. Multiple linear regression analysis was used to formulate SLW models, and the root mean standard error and interclass correlation coefficient were used to test the fitting efficiency and accuracy of the model, respectively. Furthermore, the optimal formula was compared with previous formulas. RESULTS: Approximately 28.8% of DDs had FL. US had a high diagnostic ability (sensitivity and specificity were 86.2% and 92.9%, respectively; kappa value was 0.70, P < 0.001) for livers with more than a 5% fatty change. Simple linear regression analysis showed that sex (R2, 0.226; P < 0.001), BH (R2, 0.241; P < 0.001), BW (R2, 0.441; P < 0.001), BMI (R2, 0.224; P < 0.001), BSA (R2, 0.454; P < 0.001) and FL (R2, 0.130; P < 0.001) significantly impacted TLW. In addition, multiple linear regression analysis showed that there was no significant difference in liver weight between the DDs with no steatosis and those with steatosis within 5%. Furthermore, in the context of hepatic steatosis, TLW increased positively (non-linear); compared with the TLW of the non-FL group, the TLW of the groups with hepatic steatosis within 5%, between 5% and 20% and more than 20% increased by 0 g, 90 g, and 340 g, respectively. A novel formula, namely, -348.6 + (110.7 x Sex [0 = Female, 1 = Male]) + 958.0 x BSA + (179.8 x FLUS [0 = No, 1 = Yes]), where FL was diagnosed by US, was more convenient and accurate than any other formula for predicting SLW. CONCLUSION: FL is positively correlated with TLW. The novel formula deduced using sex, BSA and FLUS is the optimal formula for predicting SLW in adult DDs.

Schwannoma in the hepatoduodenal ligament with portal vein invasion: A case report.

RATIONALE: Schwannomas are mesenchymal tumors with low malignant potential that originate from Schwann cells. They can occur in most parts of the body, such as the head, neck, and extremities. Schwannoma in the hepatoduodenal ligament is extremely rare, and only four cases have been reported in the literature. PATIENT CONCERNS: Herein, we describe a 58-year-old female who presented with right epigastric pain for 10 days. Preoperative computed tomographic (CT) revealed a 4.5 cm × 3.8 cm tumor in the hepatic hilar area. DIAGNOSES: Schwannoma in the hepatoduodenal ligament with portal vein invasion. INTERVENTIONS: Intraoperative findings revealed that the tumor was identified in the hepatoduodenal ligament, and the left branch of the portal vein was compressed. Complete tumor resection with reparation of the portal vein was performed for the patient. Postoperative pathological examination confirmed the final diagnosis of benign schwannoma, characterized by abundant spindle-shaped cells and positive reactivity for S-100 protein. OUTCOMES: The patient had a good prognosis and had no recurrence after 37 months of follow-up. LESSONS: Our case of schwannoma in the hepatoduodenal ligament is unique owing to the portal vein invasion, aimed at helping recognize the difficulty of preoperative diagnosis.

Biliary antibiotics irrigation for E. coli-induced chronic proliferative cholangitis and hepatolithiasis: A pathophysiological study in rabbits.

BACKGROUND: The gram-negative bacteria secreted endotoxin, Lipopolysaccharide (LPS), plays important roles in the formation and recurrence of hepatolithiasis and chronic biliary inflammation in patients of Southeast Asia. We aimed to elucidate the anti-inflammatory effect and mechanism of local antibiotics irrigation on chronic proliferative cholangitis (CPC) and hepatolithiasis. METHODS: Escherichia coli was injected into rabbit bile ducts to induce CPC. Rabbits were divided into sham operation (SO), povidone-iodine, Metronidazole plus chlorhexidine, ofloxacin, furacillin, Neosporin® G.U., and CPC groups. Local irrigation was performed for 28 days after CPC was established. Residual E. coli and LPS, and the expression of MCP-1, CD14, COX-2, VEGF, IL-6, NF-κB, TNF-α, Fas, TGF-ß1, α-SMA, Collagen-I, ß-glucuronidase, PKC, C-myc, and Mucin 5AC were assessed in bile duct tissues. RESULTS: The residual E. coli and LPS, and expression of MCP-1, CD14, COX-2, IL-6, NF-κB, TNF-α, Fas, TGF-ß1, α-SMA, ß-glucuronidase, PKC, C-myc, and Mucin 5AC in the SO, povidone-iodine, Metronidazole plus chlorhexidine, ofloxacin, and Neosporin® G.U. groups were significantly lower than those in the furacillin and CPC groups (P<0.05). VEGF and Collagen-I levels in the SO, povidone-iodine, metronidazole plus chlorhexidine, and ofloxacin groups were significantly lower than those in the furacillin, Neosporin® G.U., and CPC groups (P<0.05). CONCLUSIONS: LPS affects the pathophysiology of E. coli caused chronic proliferative cholangitis and hepatolithiasis recurrence. Local antibiotics irrigation could prevent chronic proliferative cholangitis and stones formation by decreasing LPS-induced proinflammatory and profibrotic cytokines release. Povidone iodine, metronidazole plus chlorhexidine, and ofloxacin were more effective than Neosporin® G.U. and furacillin.

Is combined extra-hepatic bile-duct resection justified for advanced gallbladder carcinoma?

BACKGROUND: Whether the extra-hepatic bile duct (EHBD) should be routinely resected for gallbladder carcinoma (GBC) remains controversial. The current study aimed to determine the clinical impact of combined EHBD resection during curative surgery for advanced GBC. METHODS: In total, 213 patients who underwent curative surgery for T2, T3 or T4 GBC were enrolled. The clinicopathological features were compared between the patients treated with EHBD resection and those without EHBD resection. Meanwhile, univariable and multivariable Cox-proportional hazards regression models were used to identify risk factors for overall survival (OS). RESULTS: Among the 213 patients identified, 87 (40.8%) underwent combined EHBD resection. Compared with patients without EHBD resection, patients with EHBD resection suffered more post-operative complications (33.3% vs. 21.4%, P = 0.046). However, the median OS of the EHBD resection group was longer than that of the non-EHBD resection group (25 vs. 11 months, P = 0.008). Subgroup analyses were also performed according to tumor (T) category and lymph-node metastasis. The median OS was significantly longer in the EHBD resection group than in the non-EHBD resection group for patients with T3 lesion (15 vs. 7 months, P = 0.002), T4 lesion (11 vs. 6 months, P = 0.021) or lymph-node metastasis (12 vs. 7 months, P < 0.001). No survival benefit of EHBD resection was observed in GBC patients with T2 lesion or without lymph-node metastasis. T category, lymph-node metastasis, margin status, pre-operative CA19-9 level and EHBD resection were identified as independent prognostic factors for OS of patients with advanced GBC (all P values <0.05). Conclusions EHBD resection can independently affect the OS in advanced GBC. For GBC patients with T3 lesion, T4 lesion and lymph-node metastasis, combined EHBD resection is justified and may improve OS.

Minimally invasive surgery for hilar cholangiocarcinoma: state of art and future perspectives.

BACKGROUND: Hilar cholangiocarcinoma (HCCA) occurs in the core section of the biliary system and has a strong tendency to broadly invade the surrounding vascular system, perineural tissue and major liver parenchyma. Thus, minimally invasive resection can only be achieved in limited cases. This article reviews the current laparoscopic and robotic surgery techniques for HCCA and analyses the difficulties and limitations of the current minimally invasive surgical techniques for HCCA. METHODS: A systematic literature search was conducted using multiple electronic databases. All studies involving minimally invasive resections of HCCA were included (up to November 2017). RESULTS: Twelve studies were included, of which eight concerned laparoscopic surgery of HCCA and four involved robotic surgery for HCCA. For laparoscopic surgery, most of the surgical procedures were limited to partial hepatectomy or even bile duct resection; the post-operative morbidity rate was approximately 38.9% (range 0-100%); those with fewer complications were mostly restricted to Bismuth type I or type II carcinomas. For robotic surgery, only one study concerned caudate lobectomy of HCCA, with a reported median operative time of 703 min and post-operative morbidity of 90%. CONCLUSIONS: Minimally invasive surgery for HCCA is restricted to highly selected cases and is deemed technically achievable in experienced hands. However, technical and instrumental improvement is needed to reduce the relevant morbidity and popularize the use of minimally invasive surgery to treat HCCA.

Resectable Single Hepatic Epithelioid Hemangioendothelioma in the Left Lobe of the Liver: A Case Report.

Hepatic epithelioid hemangioendothelioma (HEHE) is an extremely rare malignancy of vascular origin. When most patients with HEHE are diagnosed, they have a diffuse nodular phenotype, which is usually unresectable. A single nodular phenotype is found in only a small proportion (13%) of patients, and most are reported to be located in the right lobe of the liver. Although the prognosis of HEHE is considered more favorable than that of other hepatic malignant tumors, the 5-year survival rate is reported to be 64% after treatment. Herein, we present an unusual case of resectable HEHE of a single nodular type in the left lobe of the liver. The patient survived 15 years without recurrence after the multimodal treatment of radical resection and postoperative chemotherapy with thalidomide. The aim of the present study is to emphasize that multimodal treatment of radical resection followed by chemotherapy with thalidomide may achieve a relatively good survival outcome in patients with resectable HEHE of a single nodular type.

Effectiveness of additional resection of the invasive cancer-positive proximal bile duct margin in cases of hilar cholangiocarcinoma.

BACKGROUND: The survival benefits of additional resection of the positive proximal ductal margin (PM) in hilar cholangiocarcinoma (HCCA) remains controversial. This retrospective study investigated the effectiveness of additional resection of the invasive cancer PM under different levels of preoperative carbohydrate antigen 19-9 (CA19-9). METHODS: Patients who underwent hepatectomy for HCCA from 2000 to 2017 were analyzed. Surgical variables, resection margin status, length of the PM (LPM), prognostic factors, and survival were evaluated. RESULTS: A total of 228 patients were enrolled: 175 PM(-) without additional resection patients (group A), 21 PM(-) after additional resection (group B), 16 PM(+) without additional resection (group C), and 16 PM(+) after additional resection (group D). The median survival of group B (20.99 months) was similar to that of group A (23.00 months; P=0.16), and both were significantly better than those of group C (11.60 months) and D (9.50 months), especially when preoperative CA19-9>150 U/mL (P<0.05). The survival of patients with an LPM >10 mm was significantly better compared with those with an LPM ≤10 mm, especially when preoperative CA19-9 was >150 U/mL (P<0.05). Only in the LPM >10 mm group, the survival of group B was comparable with that of group A (P>0.05). CONCLUSIONS: HCCA patients could get a survival benefit from a negative PM resulting from additional resection. Survival could be comparable with that of negative PM without additional resection among HCCA patients. An LPM >10 mm is possibly more associated with better survival compared with whether additional resection of the positive PM is performed under different levels of preoperative CA19-9.

Histone deacetylase 3 promotes liver regeneration and liver cancer cells proliferation through signal transducer and activator of transcription 3 signaling pathway.

Histone deacetylase 3 (HDAC3) plays pivotal roles in cell cycle regulation and is often aberrantly expressed in various cancers including hepatocellular carcinoma (HCC), but little is known about its role in liver regeneration and liver cancer cells proliferation. Using an inducible hepatocyte-selective HDAC3 knockout mouse, we find that lack of HDAC3 dramatically impaired liver regeneration and blocked hepatocyte proliferation in the G1 phase entry. HDAC3 inactivation robustly disrupted the signal transducer and activator of transcription 3 (STAT3) cascade. HDAC3 silencing impaired the ac-STAT3-to-p-STAT3 transition in the cytoplasm, leading to the subsequent breakdown of STAT3 signaling. Furthermore, overexpressed HDAC3 was further associated with increased tumor growth and a poor prognosis in HCC patients. Inhibition of HDAC3 expression reduced liver cancer cells growth and inhibited xenograft tumor growth. Our results suggest that HDAC3 is an important regulator of STAT3-dependent cell proliferation in liver regeneration and cancer. These findings provide novel insights into the HDAC3-STAT3 pathway in liver pathophysiological processes.