Loss of beta-catenin expression in metastatic gastric cancer.

PURPOSE: Beta-catenin (beta-catenin) participates in intercellular adhesion and is an integral part of the Wnt signaling pathway. The role of beta-catenin in the pathogenesis of gastric cancer and its metastasis is largely unknown. PATIENTS AND METHODS: Immunohistochemistry and Western blot analysis were used to analyze the expression of beta-catenin in 87 human gastric cancers, in metastasis and cancer cell lines. The beta-catenin and the adenomatous polyposis coli (APC) genes were analyzed for gene mutations. Furthermore, methylation of the beta-catenin promoter in cell lines was assessed by treatment with 5'-azadeoxycytidine and sodium bisulfite genomic sequencing. RESULTS: beta-Catenin expression was present at either the cell membrane or the cytoplasm in 34 of 75 primary gastric cancers. Expression of beta-catenin was significantly more frequent in intestinal-type (P =.0049) and well-differentiated gastric cancers (P <.001). There were no quantitative differences between gastric cancers and the nonmalignant gastric tissues, as determined by Western blot analysis. One of 18 metastatic cancer lesions and four of five gastric cancer cell lines expressed beta-catenin protein. N87 cells, derived from the liver metastasis of a gastric cancer, did not express beta-catenin. Treatment with 5'-azadeoxycytidine restored beta-catenin protein levels in this cell line, which exhibited significantly more 5-methylcytosines in the beta-catenin promoter compared with the other cell lines. CONCLUSION: beta-Catenin expression is lost in a subgroup of primary gastric cancers, is frequently absent in metastases, and exhibits nuclear localization in cancers with either beta-catenin or APC gene mutations. Interestingly, the loss of beta-catenin expression in metastatic gastric cancers may result from hypermethylation of the beta-catenin promoter.     

Thermally stable mesoporous tetragonal zirconia through surfactant-controlled synthesis and Si-stabilization

Thermally stable, highly mesoporous Si-stabilized ZrO₂ was prepared by sol–gel-synthesis. By utilizing the surfactant dodecylamine (DDA), large mesopores with a pore width of ∼9.4 nm are formed. Combined with an NH₃-treatment on the hydrogel, a high specific surface area of up to 225 m² g⁻¹ and pore volume up to 0.46 cm³ g⁻¹ are obtained after calcination at 973 K. The individual contributions of Si-addition, DDA surfactant and the NH₃-treatment on the resulting pore system were studied by inductively coupled plasma with optical emission spectrometry (ICP-OES), X-ray diffraction (XRD), N₂ sorption, and transmission electron microscopy (TEM). Electron tomography was applied to visualize and investigate the mesopore network in 3D space. While Si prevents the growth of ZrO₂ crystallites and stabilizes the t-ZrO₂ phase, DDA generates a homogeneous mesopore network within the zirconia. The NH₃-treatment unblocks inaccessible pores, thereby increasing specific surface area and pore volume while retaining the pore width distribution.

Schematic representation of ZrO₂ crystallites; (a) monoclinic ZrO₂, (b) tetragonal ZrO₂ following Si-stabilization, (c) mesoporous t-ZrO₂ following Si-stabilization and use of surfactant dodecylamine.     

Fulminant Adenoviral-Induced Hepatitis in Immunosuppressed Patients

Human adenovirus (HAdV) can often lead to fulminant hepatitis in immunocompromised patients, mostly after reactivation of HAdV. Different risk factors, e.g., transplantation and chemotherapy, increase the risk of developing a HAdV hepatitis. We retrospectively analyzed three patients who showed the characteristics of a HAdV hepatitis observed in disseminated disease. In addition to PCR, diagnosis could be proven by pathology, CT scan, and markedly elevated transaminases. All patients had a hemato-oncologic underlying disease. Two had received a stem-cell transplant, and one was under chemotherapy including rituximab. Despite therapy with cidofovir, all patients died. As the incidence of HAdV hepatitis is low, diagnosis may be easily overlooked. No treatment approaches have yet been established. HAdV hepatitis should be considered as a differential diagnosis, especially when risk factors are present. To avoid dissemination, treatment should be initiated as soon as possible.     

APC promoter methylation and protein expression in hepatocellular carcinoma

Purpose We investigated the impact of promoter methylation on APC protein expression in patients with hepatocellular carcinoma (HCC). Materials and methods 50 patients [HCC (n=19), liver metastasis (n=19), cholangiocellular cancer (n=7), and benign liver tumors (n=5)] were studied for methylation using Methylight analysis. APC mutation was investigated by protein truncation test and direct sequencing of genomic DNA. The protein expression was evaluated by immunohistochemistry and Western blot analysis. Results The APC promoter was hypermethylated in 81.8% of non-cancerous liver tissue samples. All HCC samples and ten patients with liver metastasis (52.6%) exhibited APC promoter methylation. The degree of methylation was significantly higher in samples from HCC compared to the non-cancerous liver tissue samples (63.1% vs. 24.98%; p=0.001). The level of APC protein expression was significantly reduced in HCC samples compared to that of the corresponding non-tumor liver tissue (p<0.05). Conclusions Promoter methylation of the APC gene seems to be of significance in hepatocarcinogenesis and results in reduced protein expression in HCC. Interestingly, APC promoter methylation is also present in the vast majority of non-cancerous liver tissue whose (patho)physiological function remains unresolved.     

Sonography in Crohn disease--the conclusions of an experts' group

Sonography is adding a new dimension to diagnosis of Crohn's disease: the analysis of the transmural and peri-intestinal manifestations of the chronic inflammation. Distortions in the structure of intestinal wall are recognizable, the impact on transport of intestinal content can be judged, penetration of inflammation into the bowel surrounding as fistula, abscess, mesenteriitis und peritonitis is safely seen. Differential diagnosis on a strictly sonographic basis is difficult. The paper represents the results of an expert meeting held at the University of Frankfurt/M.     

Effects of cachaça,a typical Brazilian alcoholic beverage,on submandibular glands of rats: a histomorphometric and biochemical study

Objective

This study aimed to evaluate the effects of chronic consumption of cachaça, a Brazilian beverage containing alcohol, on submandibular glands (SM) of rats by using histomorphometric and biochemical parameters.

Materials and methods

Twenty-four male rats (40 days of age) were assigned into the following four groups (n = 6): two control groups for 75 days (C75) and 105 days (C105), and two experimental groups of cachaça ingestion with ascending concentrations for consecutive 75 days (CA75) and 105 days (CA105). On the right SM glands, the striated, granular and acini ducts were processed for histomorphometric analysis. The left SM glands were weighed and stored at − 80 °C, to evaluate through biochemical tests carried out by spectrophotometric methods, the functional activity of total acid phosphatase (TAP), tartrate-resistant acid phosphatase (TRAP), and alkaline phosphatase (ALP) and to determine the mucin levels.

Results

The absolute and relative weights of the SM glands in both experimental groups were reduced in relation to the controls (p < 0.05). The histomorphometric analysis showed a significant reduction of the acini area (p < 0.05) and non-relevant reduction of striated ducts (p > 0.05). The granular ducts did not show a significant increase of the area (p > 0.05). The TAP and TRAP activities were significantly decreased in the experimental groups (p < 0.05), while the ALP functional activity decreased moderately (p > 0.05). Mucin levels also had a significant reduction when compared with the control groups (p < 0.05).

Conclusions

Chronic consumption of cachaça can cause morphological changes associated with glandular atrophy, loss of biochemical functionality of phosphatases, and the reduction of mucin synthesis.

Clinical relevance

The consumption of cachaça can compromise the functions of the submandibular glands by altering their morphology and enzymatic activity.

     

Single-Port Robotic-Assisted Adrenalectomy: Feasibility,Safety, and Cost-Effectiveness

Methods:We performed a matched-cohort study comparing 16 single-port robotic-assisted adrenalectomies with 16 patients from a pool of 148 laparoscopic adrenalectomies, matched for age, gender, operative side, pathology, and body mass index. All were operated on by 1 surgeon.Results:The pathology included aldosteronoma in 44% of patients, adrenocorticotropic hormone–dependent Cushing syndrome (bilateral adrenalectomy) in 19%, pheochromocytoma in 13%, and other pathology in 24%. The operative time was 183 ± 33 minutes for single-port robotic-assisted adrenalectomy and 173 ± 40 minutes for laparoscopic adrenalectomy (P = .58). The total time in the operating room was 246 ± 33 minutes for single-port robotic-assisted adrenalectomy and 240 ± 39 minutes for laparoscopic adrenalectomy (P = .57). There was 1 conversion to open adrenalectomy (6%) in each group, both because of bleeding on the right side during bilateral adrenalectomy. Two right-sided single-port robotic-assisted adrenalectomy patients required conversion to laparoscopic adrenalectomy, one because of poor visualization. There were no deaths. Complications occurred in 2 patients in each group (intensive care unit admission, prolonged ileus). Both groups had similar pain scores (mean of 3.7 on a scale from 1 to 10) on postoperative day 1, and patients in the single-port robotic-assisted adrenalectomy group used less narcotic pain medication in the first 24 hours after surgery (43 mg vs 84 mg in laparoscopic adrenalectomy group, P < .001). The differences between the single-port robotic-assisted adrenalectomy group and laparoscopic adrenalectomy group in length of stay (2.3 ± 0.5 days vs 3.1 ± 0.9 days, P = .23), percentage of patients discharged on postoperative day 1 (56% vs 31%, P = .10), and hospital cost (16% lower in single-port robotic-assisted adrenalectomy group, P = .17) did not reach statistical significance.Conclusion:Single-port robotic adrenalectomy is feasible; patients require less narcotic pain medication whereas costs appear equivalent compared with laparoscopic adrenalectomy.