Unraveling the efficacy network: A network meta-analysis of adjuvant external beam radiation therapy methods after hepatectomy.

BACKGROUND: Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis. Postoperative adjuvant external radiation therapy (RT) has been shown to effectively prevent recurrence after liver cancer resection. However, there are multiple RT techniques available, and the differential effects of these techniques in preventing postoperative liver cancer recurrence require further investigation. AIM: To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival (OS) and disease-free survival (DFS) and to determine the optimal strategy. METHODS: This study involved network meta-analyses and followed the PRISMA guidelines. The data of qualified studies published before July 10, 2023, were collected from PubMed, Embase, the Web of Science, and the Cochrane Library. We included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary endpoints. The magnitudes of the effects were determined using risk ratios with 95% confidential intervals. The results were analyzed using R software and STATA software. RESULTS: A total of 12 studies, including 1265 patients with hepatocellular carcinoma (HCC) after liver resection, were included in this study. There was no significant heterogeneity in the direct paired comparisons, and there were no significant differences in the inclusion or exclusion criteria, intervention measures, or outcome indicators, meeting the assumptions of heterogeneity and transitivity. OS analysis revealed that patients who underwent stereotactic body radiotherapy (SBRT) after resection had longer OS than those who underwent intensity modulated radiotherapy (IMRT) or 3-dimensional conformal RT (3D-CRT). DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest DFS. Patients who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent SBRT. CONCLUSION: HCC patients who undergo liver cancer resection must consider distinct advantages and disadvantages when choosing between SBRT and 3D-CRT. IMRT, a RT technique that is associated with longer OS than 3D-CRT and longer DFS than SBRT, may be a preferred option.

Decreased expression of ApoF associates with poor prognosis in human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is frequently associated with metabolism dysfunction. Increasing evidence has demonstrated the crucial role of lipid metabolism in HCC progression. The function of apolipoprotein F (ApoF), a lipid transfer inhibitor protein, in HCC is incompletely understood. We aimed to evaluate the functional role of ApoF in HCC in this study. METHODS: We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to detect ApoF mRNA expression in HCC tissues and hepatoma cell lines (SMMC-7721, HepG2, and Huh7). Immunohistochemistry was performed to detect the expression of ApoF in HCC tissues. The associations between ApoF expression and clinicopathological features as well as HCC prognosis were analyzed. The effect of ApoF on cellular proliferation and growth of SMMC-7721 and Huh7 cells was examined in vitro and in vivo. RESULTS: ApoF expression was significantly down-regulated at both mRNA and protein levels in HCC tissues as compared with adjacent tissues. In SMMC-7721 and Huh7 HCC cells, ApoF overexpression inhibited cell proliferation and migration. In a xenograft nude mouse model, ApoF overexpression effectively controlled HCC growth. Kaplan-Meier analysis results showed that the recurrence-free survival rate of HCC patients with low ApoF expression was significantly lower than that of other HCC patients. Low ApoF expression was associated with several clinicopathological features such as liver cirrhosis, Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage. CONCLUSIONS: ApoF expression was down-regulated in HCC, which was associated with low recurrence-free survival rate. ApoF may serve as a tumor suppressor in HCC and be a potential application for the treatment of this disease.

Anillin is required for tumor growth and regulated by miR-15a/miR-16-1 in HBV-related hepatocellular carcinoma.

Anillin (ANLN) is an actin-binding protein essential for assembly of cleavage furrow during cytokinesis. Although reportedly overexpressed in various human cancers, its role in hepatocellular carcinoma (HCC) is unclear. To address this issue, we confirmed that in 436 liver samples obtained from surgically removed HCC tissues, higher ANLN expression was detected in tumor tissues than in adjacent non-tumor tissues of HCC as measured by immunohistochemistry, quantitative real-time PCR and western blotting. Correlation and Kaplan-Meier analysis revealed that patients with higher ANLN expression were associated with worse clinical outcomes and a shorter survival time, respectively. Moreover, ANLN inhibition resulted in growth restraint, reduced colony formation, and a lower sphere number in suspension culture. Mechanistically, ANLN deficiency induced an increasing number of multinucleated cells along with the activation of apoptosis signaling and DNA damage checkpoints. Furthermore, HBV infection increased ANLN expression by inhibiting the expression of microRNA (miR)-15a and miR-16-1, both of which were identified as ANLN upstream repressors by targeting its 3' untranslated region. Thus, we conclude that ANLN promotes tumor growth by ways of decreased apoptosis and DNA damage. Expression level of ANLN significantly influences the survival probability of HCC patients and may represent a promising prognostic biomarker.

Ultrasound-guided percutaneous microwave coagulation therapy with a "cooled-tip needle" for the treatment of hepatocellular carcinoma adjacent to the gallbladder.

BACKGROUND: Curative percutaneous microwave coagulation therapy is difficult or contraindicated in patients with tumors adjacent to the gallbladder because of the associated risk of injury. To date, no clinical data have been published regarding the effects and safety of percutaneous microwave coagulation therapy on tumors that are adjacent to the gallbladder. AIMS: We investigated the efficacy and safety of a combined treatment involving laparoscopic cholecystectomy and subsequent percutaneous microwave coagulation therapy in patients with hepatocellular carcinoma adjacent to the gallbladder. METHODS: Twenty-three patients with hepatocellular carcinoma nodules (of less than 5 cm diameter) and adjacent to the gallbladder were treated by percutaneous microwave coagulation therapy with a "cooled-tip needle" after laparoscopic cholecystectomy. The therapeutic efficacy was evaluated with enhanced helical computed tomography and sonography, and the rates of complete necrosis as well as postoperative complications were also analyzed. RESULTS: All of the patients exhibited complete necrosis of their tumor lesions after treatment with percutaneous microwave coagulation therapy. During the follow-up period (which lasted more than 21 months), 22 of 23 patients were alive. Recurrent nodules appeared in other subsegments, but not at the original site treated with percutaneous microwave coagulation therapy. Of note, no fatal complications were observed in any of the patients treated with percutaneous microwave coagulation therapy. CONCLUSION: Our results suggest that combined treatment comprising both laparoscopic cholecystectomy and subsequent percutaneous microwave coagulation therapy is an effective and safe approach for patients with small (<5 cm) hepatocellular carcinomas that are adjacent to the gallbladder.

Deficient proliferation of bone marrow-derived mesenchymal stem cells in patients with chronic hepatitis B viral infections and cirrhosis of the liver.

In this study, we determined whether the proliferation of bone marrow-derived mesenchymal stem cells (MSCs) is impaired in patients with chronic hepatitis B viral infection and cirrhosis of the liver. MSCs from 15 patients with chronic hepatitis B and cirrhosis of the liver (CIR-MSCs) and 11 normal donors (ND-MSCs) were collected and characterized in vitro. CIR-MSCs displayed an intact immunophenotype. The percentage of S-phase nuclei in CIR-MSCs (4.34%), however, was significantly lower than that in ND-MSCs (P < 0.001), indicating impaired proliferation of CIR-MSCs. Growth factor receptor expression (e.g., IGF1, PDGFalpha, and PDGFbeta) on the surface of CIR-MSCs decreased compared to that on ND-MSCs (P < 0.03). We found no evidence that CIR-MSCs were infected with the hepatitis B virus (HBV). Deficient proliferation of CIR-MSCs may result from the decreased expression of growth factor receptors and unbalanced production of cytokines in patients with HBV infection. Our results indicate that autologous MSCs of patients with chronic hepatitis B and cirrhosis of the liver may not be suitable for therapeutic purposes.

A novel canine model of esophageal varices with a balloon dilatation constrictor.

BACKGROUND AND OBJECTIVE: The canine model of esophageal varices with an agar constrictor has been used for studies of the endoscopic treatment of esophageal variceal bleeding, but it has limitations in both stability and successful rate. This study was designed to enhance the model's efficiency and success rate by using a novel approach with a balloon dilatation constrictor. METHODS: We used 22 adult mongrel dogs to establish the model by progressively compressing and constricting the portal vein through a rechargeable balloon dilatation constrictor in combination with side-to-side portocaval shunt and inferior vena cava (IVC) ligation to increase portal vein pressure (PVP). The rechargeable balloon dilatation constrictor was composed of a hyaline polypropylene (PP) ring, a silica gel tube with a balloon, and an injection pedestal (silica gel) in an implantable vascular access port. The effects were evaluated with pre- and post-shunt PVP measurement, weekly gastroscopy, and portocaval venography. RESULTS: The mean PVP increased significantly from a preoperative (before side-to-side portocaval shunt and IVC ligation) 12.86 +/- 0.18 cmH(2)O to 26.75 +/- 0.39 cmH(2)O after the model had been established (P < 0.05). After the model was established, gastroscopy performed to assess esophageal varix size demonstrated four varicose veins of grade I, six of grade II, eight of grade III and four of grade IV. The portocaval angiography showed that the IVC and portal vein were completely blocked, that the anastomosis stoma was unobstructed and that the blood flow through esophageal varices via splenetic and gastric veins was blocked. CONCLUSION: The novel canine model developed with a rechargeable balloon dilatation constrictor is feasible and reliable for modeling esophageal varices.

[A survey of bile duct injuries sustained during laparoscopic cholecystectomy].

OBJECTIVE: To summarize the reasons for bile duct injury (BDI) after laparoscopic cholecystectomy (LC), and to determine the effect of multiple treatment after BDI. METHODS: A retrospective cohort study was performed. The medical records of 110 patients diagnosed with BDI after LC from October 1993 to November 2007, in ten large hospitals in Guangdong of China, were reviewed. RESULTS: Among 110 patients with BDI, 58 cases (52.7%) were local patients, whereas 52 cases (47.3%) were transferred from outside hospitals. Reasons for BDI following LC were: (1) Lack of experience of the LC operator (48.2%); (2) LC performed during acute cholecystitis (20.0%); (3) The structure of Calot triangle was unclear (15.5%); (4) Variable anatomical position (11.8%); (5) Intra-operation bleeding (4.5%). The commonest sites of injury were the choledochus and common hepatic duct (76.4%). Following BDI, endoscopic stenting or operative repair was performed in 106 patients. The overall success rate was 95.3% (101/106), with a mortality rate was 0.9% (1/106). Cholangitis occurred in 3.8% (4/106) cases. Choledocho-enterostomy operation was performed in almost 60.0% (63/106) cases, and the success rate was 93.7% (59/63). Endoscopic stenting or operative repair was performed immediately following BDI in 23.6% (25/106) patients, the success rate was 100%; and within 30 days in 63.2% (67/106) patients. Eighty-eight out of 106 patients who underwent repair were successful following the first operative procedure. CONCLUSIONS: Factors such as an un-experienced operator and unclear anatomical position were causes of BDI following LC. Early operative repair should be regarded as the treatment of choice, in patients diagnosed with BDI. Early refer to an experienced hepatobiliary operator ensures a high success rate.

Predictive value of D-dimer for portal vein thrombosis after portal hypertension surgery in hepatitis B virus-related cirrhosis.

AIM: To evaluate the predictive value of D-dimer as a predictive indicator of portal vein thrombosis (PVT) after portal hypertension surgery in hepatitis B virus-related cirrhosis. METHODS: A prospective study was carried out in 52 patients who had undergone surgery for portal hypertension in hepatitis B virus-related cirrhosis. Changes in perioperative dynamic D-dimer were observed. The sensitivity, specificity, positive predictive values and negative predictive values of D-dimer were calculated, and ROC curves were analyzed. RESULTS: The D-dimer levels in the group developing postoperative PVT was significantly higher than those in the group not developing PVT (P = 0.001), and the ROC semiquantitative and qualitative analysis of D-dimer showed a moderate predictive value in PVT (semi-quantitative value Az = 0.794, P = 0.000; qualitative analysis: Az = 0.739, P = 0.001). CONCLUSION: Dynamic monitoring of D-dimer levels in patients with portal hypertension after surgery can help early diagnosis of PVT, as in cases where the D-dimer levels steadily increase and exceed 16 microg/mL, the possibility of PVT is very high.

Association of serum vascular endothelial growth factor-C and lymphatic vessel density with lymph node metastasis and prognosis of patients with gastric cancer.

AIM: To investigate whether serum vascular endothelial growth factor-C (SVEGF-C), VEGF-C, and lymphatic vessel density (LVD) in tumor tissues are related to lymph node metastasis (LNM) and prognosis in gastric cancer. METHODS: SVEGF-C levels of 80 gastric cancer patients and 20 healthy donors were examined using ELISA. VEGF-C expression and LVD were examined using immunohistochemical staining. Kaplan-Meier survival analysis was performed to determine their influence on the prognosis of the patients. RESULTS: The SVEGF-C level in gastric cancer patients (595.9 +/- 201.0 ng/L) was significantly higher (P = 0.000) than controls (360.0 +/- 97.4 ng/L). Both SVEGF-C and LVD were significantly higher in poorly differentiated adenocarcinomas, T3 and T4, LNM, distant metastasis, and pTNM groups III and IV (P = 0.000). The sensitivity and specificity of SVEGF-C for predicting LNM were 82.8% and 81.8%, respectively (cut-off = 542.5 ng/L). The positive expression rate of VEGF-C was significantly higher in cancerous than in normal tissues (65% vs 20%; P = 0.001). VEGF-C expression up-regulation was significantly related to differentiation, depth of invasion, LNM, distant metastasis, and pTNM stage (P = 0.000). LVD was 10.7 +/- 3.1/200 HP in the experimental group vs 4.9 +/- 1.3/200 HP in controls (P = 0.000); LVD in cancerous tissues with and without LNM was 12.0 +/- 2.7/200 HP vs 7.6 +/- 0.5/200 HP, respectively (P = 0.000). SVEGF-C and LVD were significantly higher in VEGF-C positive than in negative patients (P = 0.000); SVEGF-C level was related to LVD (P = 0.000). Kaplan-Meier survival analysis factors predicating poor prognosis were: SVEGF-C level (P = 0.001), VEGF-C expression and LVD (both P = 0.000). CONCLUSION: SVEGF-C level, VEGF-C and LVD are related to LNM and poor prognosis of patients with gastric cancer. SVEGF-C may be a biomarker for LNM in gastric cancer.

Splenectomy with endoscopic variceal ligation is superior to splenectomy with pericardial devascularization in treatment of portal hypertension.

AIM: To investigate the therapeutic efficacy and complications of splenectomy with endoscopic variceal ligation (EVL) and splenectomy with pericardial devascularization (i.e. Hassab's operation) in patients with portal hypertension. METHODS: A total of 103 patients with liver cirrhosis and portal hypertension were randomly selected to receive either splenectomy with EVL (n = 53, group A) or Hassab's operation (n = 50, group B). RESULTS: The portal blood flow volume, the presence of portal vein thrombosis, gastric emptying time and free portal venous pressure (FPP) before and after the operation were determined. Patients were followed up for up to 64 mo with an average of 45 mo, and the Dagradi classification of variceal veins and the grading of portal hypertension gastropathy (PHG) were evaluated. It was found that all esophageal varices were occluded or decreased to grade II or less in both groups. There was little difference in the recurrence rate of esophageal varices (11.9% vs 13.2%) and the re-bleeding rate (7.1% vs 5.3%) between groups A and B. The incidence of complications and the percentage of patients with severe PHG after the operation were significantly higher in group B (60.0% and 52.0%) than in group A (32.1% and 20.8%, P < 0.05). No patients died of operation-related complications. There was no significant difference in gastric emptying time, FPP and portal blood flow volume between the two groups. CONCLUSION: The results suggest that splenectomy with EVL achieves similar therapeutic efficacy to that of Hassab's operation in terms of the recurrence rate of esophageal varices and the re-bleeding rate, but the former results in fewer and milder complications.

Evaluation of the effects of combined endoscopic variceal ligation and splenectomy with pericardial devascularization on esophageal varices.

AIM: To detect the hemodynamic alterations in collateral circulation before and after combined endoscopic variceal ligation (EVL) and splenectomy with pericardial devascularization by ultrasonography, and to evaluate their effect using hemodynamic parameters. METHODS: Forty-three patients with esophageal varices received combined EVL and splenectomy with pericardial devascularization for variceal eradication. The esophageal vein structures and azygos blood flow (AZBF) were detected by endoscopic ultrasonography and color Doppler ultrasound. The recurrence and rebleeding of esophageal varices were followed up. RESULTS: Patients with moderate or severe varices in the esophageal wall and those with severe peri-esophageal collateral vein varices had improvements after treatment, while the percentage of patients with severe para-esophageal collateral vein varices decreased from 54.49% to 2.33%, and the percentage of patients with detectable perforating veins decreased from 79.07% to 4.65% (P < 0.01). Color Doppler flowmetry showed a significant decrease both in AZBF (43.00%, P < 0.05) and in diameter of the azygos vein (28.85%, P < 0.05), while the blood flow rate was unchanged. The recurrence rate of esophageal varices was 2.5% (1/40, mild), while no re-bleeding cases were recorded. CONCLUSION: EVL in combination with splenectomy with pericardial devascularization can block the collateral veins both inside and outside of the esophageal wall, and is more advantagious over splenectomy in combination with pericardial devascularization or EVL in preventing recurrence and re-bleeding of varices.

[Effects of different treatment complex on esophageal vascular structures in patients with portal hypertension].

OBJECTIVE: To assess the effects of different treatment complex on esophageal vascular structures in patients with portal hypertension. METHODS: Patients (142 cases) with esophageal varices received either endoscopic variceal ligation (EVL) alone (54 cases), pericardial devascularization procedure (PDP) alone (23 cases), a combination of EVL and partial splenic embolization (PSE) (34 cases), or a combination of EVL and PDP (31 cases) for variceal eradication. Esophageal vascular structures were examined with miniature ultrasonic probe. The recurrence and rebleeding of esophageal varices were investigated. RESULTS: Esophageal submucous varices were obliterated and collateral veins remained unchanged in patients treated by EVL or EVL combined with PSE; esophageal submucous varices were diminished in size and collateral veins were obliterated by PDP, and both esophageal submucous varices and collateral veins were obliterated by the combination of EVL and PDP. CONCLUSIONS: The combination of EVL and Hassab's procedure can effectively shut off the portoazygous shunt, prevent esophageal varices from bleeding and recurrence. It's a simply and less cost procedure.

Expression of growth hormone receptor and its mRNA in hepatic cirrhosis.

AIM: To investigate the expression of growth hormone receptor (GHR) and mRNA of GHR in cirrhotic livers of rats with the intension to find the basis for application of recombinant human growth hormone (rhGH) to patients with liver cirrhosis. METHODS: Hepatic cirrhosis was induced in Sprague-Dawley rats by administration of thioacetamide intraperitoneally for 9-12 weeks. Collagenase IV was perfused in situ for isolation of hepatocytes. The expression of GHR and its mRNA in cirrhotic livers was studied with radio-ligand binding assay, RT-PCR and digital image analysis. RESULTS: One class of specific growth hormone-binding site, GHR, was detected in hepatocytes and hepatic tissue of cirrhotic livers. The binding capacity of GHR (R(T), fmol/mg protein) in rat cirrhotic liver tissue (30.8+/-1.9) was significantly lower than that in normal control (74.9+/-3.9) at the time point of the ninth week after initiation of induction of cirrhosis (n=10, P<0.05), and it decreased gradually along with the accumulation of collagen in the process of formation and development of liver cirrhosis (P<0.05). The number of binding sites (X10(4)/cell) of GHR on rat cirrhotic hepatocytes (0.86+/-0.16) was significantly lower than that (1.28+/-0.24) in control (n=10, P<0.05). The binding affinity of GHR among liver tissue, hepatocytes of various groups had no significant difference (P>0.05). The expression of GHR mRNA (riOD, pixel) in rat cirrhotic hepatic tissues (23.3+/-3.1) was also significantly lower than that (29.3+/-3.4) in normal control (n=10, P<0.05). CONCLUSION: The growth hormone receptor was expressed in a reduced level in liver tissue of cirrhotic rats, and lesser expression of growth hormone receptors was found in a later stage of cirrhosis. The reduced expression of growth hormone receptor was partly due to its decreased expression on cirrhotic hepatocytes and the reduced expression of its mRNA in cirrhotic liver tissue.