Early complications after percutaneous radiofrequency ablation for hepatocellular carcinoma: an analysis of 1,843 ablations in 1,211 patients in a single centre: experience over 10 years.

AIM: To evaluate the incidence of adverse events and associated factors after radiofrequency ablation (RFA) in patients with hepatocellular carcinoma within 30 days. MATERIALS AND METHODS: The early complications that occurred within 30 days after RFA at a single institution from January 2000 to July 2010 were reviewed in order to evaluate the morbidity, mortality, and risk factors associated with the complications. In total, 1,211 patients (845 men, 70.5%) with a mean age of 68 years (range, 27-88 years) underwent 1,843 RFA procedures. RESULTS: The overall incidence rate of complications was 6.8% (125 cases). Major complications (n=36, 2%) included liver abscess (n=15, 0.8%), intraperitoneal bleeding (n=8, 0.4%), liver failure (n=5, 0.3%), variceal bleeding (n=3, 0.2%), haemothorax (n=2, 0.1%), cholecystitis (n=2, 0.1%), and bowel perforation (n=1, 0.1%). Among the minor complications (n=89, 4.8%), the most common was the post RFA syndrome accompanied by pain and fever (n=75, 4.1%). Other minor complications included significant pleural effusion (n=7, 0.4%), skin wound infection (n=4, 0.2%), and thermal injuries to the skin (n=3, 0.2%). Procedural infections significantly increased with tumour size (OR=1.379; 95% confidence interval [CI], 1.191-1.579; p<0.001), and multiple overlapping ablations (OR=1.118; 95% CI, 1.019-1.227, p=0.018). Thrombocytopenia (<50,000/µl), prothrombin time, and serum albumin level were significantly associated with post-RFA bleeding episodes (p=0.041, p=0.021, and p=0.003, respectively). The overall mortality rate was 0.3% (three cases of hepatic failure, two case of sepsis, and one case of renal failure). CONCLUSIONS: RFA is a safe and effective local treatment for hepatocellular carcinoma. Careful selection of patients and appropriate RFA planning could decrease procedural mortality and morbidity.

The feasibility of endoscopic submucosal dissection for rectal carcinoid tumors: comparison with endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Rectal carcinoid tumors are often found incidentally during screening colonoscopy and can be resected using various endoscopic techniques. This study aimed to compare the safety and efficacy of endoscopic submucosal dissection (ESD) with endoscopic mucosal resection (EMR) for rectal carcinoid tumors. PATIENTS AND METHODS: Between January 2003 and June 2009, 74 patients (74 lesions) underwent either EMR (n = 28) or ESD (n = 46) for rectal carcinoid tumors. The rate of endoscopic complete resection, pathological complete resection, procedure complications, and tumor recurrence were analyzed retrospectively. RESULTS: The endoscopic complete resection rate was significantly higher in the ESD group (46 lesions, 100 %) compared with the EMR group (25 lesions, 89.3 %) ( P = 0.049). The pathological complete resection rate was higher in the ESD group (38 lesions, 82.6 %) compared with the EMR group (18 lesions, 64.3 %); however, this difference was borderline significant ( P = 0.067). Overall complication rate was not significantly different between the EMR group (3.6 %) and the ESD group (6.3 %). There was one case of remnant lesion in the EMR group, which was managed by ESD, and no recurrence has been detected in either the EMR or ESD groups. CONCLUSION: This study suggests that ESD might be a feasible treatment technique for small rectal carcinoid tumors. It showed superior efficacy and comparable safety to EMR.

Where has the tumor gone? The characteristics of cases of negative pathologic diagnosis after endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Discrepancies can occur between the histopathological findings from forceps biopsy and endoscopic mucosal resection (EMR), and occasionally in embarrassing cases tumorous tissue is not found at EMR. The aim of the present study was to evaluate the clinical, endoscopic, and histological features of gastric tumors in patients with pathololgically negative findings at EMR. PATIENTS AND METHODS: We retrospectively reviewed data from all patients with gastric tumor treated with EMR or endoscopic submucosal dissection (ESD) between August 1999 and April 2007 at our institution, and enrolled into the study patients with no tumor tissue found at mucosal resection. Their biopsy and EMR specimen slides were reviewed by a single pathologist. Patient characteristics, including demographic and clinical features, and the endoscopic appearance of mucosal lesions were evaluated. RESULTS: Out of 633 patients treated with EMR or ESD, 20 patients (3.2 %) were included. The mean +/- SD maximal dimension of the mucosal lesions was 6.40 +/- 2.19 mm (range 3 - 10). Mean number of forceps biopsy fragments was 3.80 +/- 1.96 and mean sampling ratio was 2.08 +/- 1.07 mm/fragment. Before resection, histological findings from forceps biopsy were: 13 low grade dysplasias (65.0 %), 2 high grade dysplasias (10.0 %), and 5 intramucosal carcinomas (25.0 %). CONCLUSIONS: In the case of pathologically negative findings at EMR, tumors might have been small enough to have been removed by the previous forceps biopsy. However, the possibility of sampling error or of a different location should be considered. Furthermore, appropriate communication between endoscopists and pathologists is essential.

Factors related to lymph node metastasis and the feasibility of endoscopic mucosal resection for treating poorly differentiated adenocarcinoma of the stomach.

BACKGROUND AND AIM: Endoscopic mucosal resection (EMR) is currently not accepted as an alternative treatment to surgery in early gastric cancer (EGC) of the undifferentiated histologic type. The present retrospective analysis examined the correlation of various histologic factors with the presence of lymph node metastasis (LNM). PATIENTS AND METHODS: A retrospective analysis on 234 patients with poorly differentiated EGC who underwent radical gastrectomy with D2 lymph node dissection was undertaken. Several clinicopathologic factors were investigated to identify predictive factors for LNM: age, sex, type of operation, tumor location, tumor size, gross type, ulceration, lymphatic invasion, and depth of invasion. RESULTS: Of the 234 lesions with poorly differentiated EGC, half (n = 116) already showed submucosal invasion in the resection specimen; 25.9 % of those (30/116) were limited to the upper third (SM1). Of the lesions confined to the mucosa, LNM was found in 3.4 % (4/118). With minor submucosal infiltration (SM1), the LNM rate was lower (0/30) in our patient population. Only with SM2/3 infiltration did the LNM rate sharply rise to around 30 %. The cut-off for submucosal infiltration depth was 500 microm (0/32 LNM), above which LNM rates were substantial (31.2 %; 24/77). There was limited correlation between the SM1-3 classification and actual measurement of submucosal infiltration depth. In a multivariate analysis, tumor size ( P = 0.033), depth of invasion ( P = 0.004), and lymphatic invasion ( P < 0.001) were associated with LNM. CONCLUSION: Poorly differentiated EGC confined to the mucosa or with minimal submucosal infiltration (

Hyperglycaemia, hypercholesterolaemia and the risk for developing gastric dysplasia.

BACKGROUND/GOALS: Gastric dysplasia is believed to be the penultimate stage of gastric carcinogenesis. Few studies have evaluated whether there is a relationship between such risk factors and gastric dysplasia. This case-control study was conducted to investigate the associations between obesity, serum glucose, lipids and gastric dysplasia. STUDY: Endoscopic findings and pathology specimens were reviewed from 1 July 1997 to 31 December 2006 in the Health Promotion Center. One hundred thirty patients have the dysplasia in the stomach during screening endoscopy. The same number of controls was evaluated and matched to the gastric dysplasia group for age and gender. RESULT: The univariate analysis showed that the dysplasia risk was slightly increased among persons with a higher low-density lipoprotein, lower high-density lipoprotein, impaired fasting glucose and higher total cholesterol. However, a higher body mass index and higher triglyceride level were not associated with the diagnosis of gastric dysplasia. In the multivariate-adjusted model, a higher low-density lipoprotein cholesterol and glucose were strongly associated with an increased risk of dysplasia compared to the controls. However, the body mass index, triglyceride and total cholesterol were not associated with the risk for dysplasia. CONCLUSION: Hyperglycaemia and low-density lipoprotein cholesterol appear to be associated with the risk for gastric dysplasia. Further epidemiologic studies including a large cohort of patients with gastric dysplasia and adenocarcinoma are needed to clarify the association of low-density lipoprotein cholesterol, serum glucose and gastric carcinogenesis.

CD40 activates NF-kappa B and c-Jun N-terminal kinase and enhances chemokine secretion on activated human hepatic stellate cells.

Activated hepatic stellate cells (HSCs) are the main producers of extracellular matrix in the fibrotic liver and contribute to hepatic inflammation through the secretion of chemokines and the recruitment of leukocytes. This study assesses the function of CD40 on human HSCS: Activated human HSCs express CD40 in culture and in fibrotic liver, as determined by flow cytometry, RT-PCR, and immunohistochemistry. CD40 expression is strongly enhanced by IFN-gamma. Stimulation of CD40 with CD40 ligand (CD40L)-transfected baby hamster kidney cells induces NF-kappaB, as demonstrated by the activation of I-kappaB kinase (IKK), increased NF-kappaB DNA binding, and p65 nuclear translocation. CD40-activated IKK also phosphorylates a GST-p65 substrate at serine 536 in the transactivation domain 1. Concomitant with the activation of IKK, CD40L-transfected baby hamster kidney cell treatment strongly activates c-Jun N-terminal kinase. CD40 activation increases the secretion of IL-8 and monocyte chemoattractant protein-1 by HSCs 10- and 2-fold, respectively. Adenovirally delivered dominant negative (dn) IKK2 and TNFR-associated factor 2dn inhibit IKK-mediated GST-I-kappaB and GST-p65 phosphorylation, NF-kappaB binding, and IL-8 secretion, whereas IKK1dn and NF-kappaB-inducing kinase dominant negative do not have inhibitory effects. We conclude that the CD40-CD40L receptor-ligand pair is involved in a cross-talk between HSCs and immune effector cells that contributes to the perpetuation of HSC activation in liver fibrosis through TNFR-associated factor 2- and IKK2-dependent pathways.

The role of Smad3 in mediating mouse hepatic stellate cell activation.

Transforming growth factor beta (TGF-beta) is the most potent profibrogenic mediator in liver fibrosis. Although Smad proteins have been identified as intracellular mediators in the TGF-beta signaling pathway, the function of individual Smad proteins remains poorly understood. The aim of this study was to explore the contribution of Smad3 in mediating TGF-beta responses in a model of acute liver injury in vivo and in culture-activated hepatic stellate cells (HSCs). Wild-type, Smad3 heterozygous or Smad3 homozygous knockout mice were treated with a single intragastric administration of CCl(4). After 72 hours, the induction of hepatic collagen alpha1(I) and alpha2(I) messenger RNA (mRNA) levels in Smad3 knockout mice was only 42% and 64%, respectively, of the levels induced in wild-type mice. However, smooth muscle alpha-actin (alpha-SMA) was expressed at a slightly higher level in livers from knockout mice compared with wild-type mice. In culture-activated HSCs from Smad3 knockout mice, collagen alpha1(I) mRNA was 73% of wild-type HSCs, but alpha-SMA expression was the same. HSCs from knockout mice showed a higher proliferation rate than wild-type HSCs. Smad3-deficient HSCs did not form TGF-beta1-induced Smad-containing DNA-binding complexes. In conclusion, (1) maximal expression of collagen type I in activated HSCs requires Smad3 in vivo and in culture; (2) Smad3 is not necessary for HSC activation as assessed by alpha-SMA expression; (3) Smad3 is necessary for inhibition of proliferation of HSCs, which might be TGF-beta-dependent; and (4) Smad3 is required for TGF-beta1-mediated Smad-containing DNA-binding complex formation in cultured HSCs.

Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B.

BACKGROUND: Activation of hepatic stellate cells is the earliest step in fibrogenesis. Alpha-smooth muscle actin (alpha-SMA), expressed by activated hepatic stellate cells, and C-terminal procollagen alpha1(III) propeptide (PIIICP) are early markers of fibrogenesis and should precede fibrosis. AIM: Determine if suppression of hepatitis B virus replication with lamivudine would decrease fibrogenesis as measured by immunohistochemical markers. METHODS: Paired liver biopsies from patients with hepatitis B before and after therapy with lamivudine (n=47) or placebo (n=33) were studied. alpha-SMA and PIIICP were detected in paraffin-embedded tissue by immunohistochemistry and quantified in a blinded manner by video imaging analysis. RESULTS: Liver biopsies from patients treated with lamivudine showed a significant decrease in alpha-SMA expression (1.06+/-0.23 vs. 0.58+/-0.11, pre vs. post, P<0.05). Placebo recipients had increased levels of alpha-SMA (0.82+/-0.14 vs. 1.32+/-0.21, P<0.05). PIIICP was similarly decreased after lamivudine. Among subjects whose Histologic Activity Index fibrosis score was unchanged or worsened, the mean change in alpha-SMA expression was significantly decreased in the lamivudine group compared with placebo. CONCLUSIONS: Lamivudine decreased markers of hepatic stellate cell activation and collagen synthesis. Immunohistochemical techniques are sensitive for assessing fibrogenesis and will be useful in trials of antiviral and antifibrotic agents.

Gastric lymphangioma.

Gastric lymphangioma is a rare benign gastric tumor composed of unilocular or multilocular lymphatic spaces. On gastrofiberscopy a submucosal tumor covered with smooth transparent normal mucosa is revealed in the stomach with or without a stalk. Endoscopic ultrasonography has become an indispensable tool for differentiating these gastric tumors. Treatment of lymphangioma depends on its size, location, and presence of complications. Endoscopic resection is safe and easy and plays an important role in confirming the diagnosis and treatment of the tumors especially of small-sized ones. We report a case of gastric lymphangioma in a 68-yr-old woman who presented with nausea and vague epigastric discomfort for two months. She was diagnosed by gastrofiberscopy with endoscopic ultrasonography and treated successfully with endoscopic resection by strip biopsy method.