Effect of bevacizumab and everolimus combination treatment on peritoneal sclerosis in an experimental rat model.

The aim of this study was to investigate whether bevacizumab and everolimus combination therapy is superior to bevacizumab treatment alone as a treatment for peritoneal sclerosis. Forty Wistar albino rats were divided into five equal groups. The control group received isotonic saline solution (2 mL/day) intraperitoneal (IP) daily for 3 weeks. The CG group received 2 mL 0.1% chlorhexidine gluconate (CG) and 15% ethanol dissolved in saline IP daily for 3 weeks. Peritoneal tissue samples were taken at the end of 3 weeks. The resting group received CG (weeks 0-3), plus isotonic saline solution (2 mL/day) IP daily and tap water (2 mL/day) via a feeding tube daily (weeks 3-6).The bevacizumab group received CG (weeks 1-3) plus bevacizumab at 2.5 mg/kg/day (2 mL) IP daily and tap water (2 mL/day) via a feeding tube daily (weeks 3-6). The bevacizumab+everolimus group received CG (weeks 1-3) plus bevacizumab at 2.5 mg/kg/day (2 mL) IP daily and everolimus at 0.3 mg/kg/day (2 mL) via a feeding tube daily (weeks 3-6). Peritoneal tissue samples were taken from these three groups at the end of 6 weeks and were examined after staining with hematoxylin-eosin and Masson's trichrome. Inflammation, vasculopathy, fibrosis, and peritoneal thickness were evaluated under light microscopy. The samples were also stained with anti-TGF-ß and anti-MMP-2. Inflammation and vasculopathy scores were significantly decreased in the VEGF-i group compared to the CG group. The addition of everolimus to VEGF-i showed significantly lower inflammation, vasculopathy, fibrosis scores, and an evident decrease in peritoneal thickening (respectively, 2.29 ± 0.76 vs 0.57 ± 0.53, P = .003; 2.71 ± 0.76 vs 1.43 ± 0.53, P = .008; 2.57 ± 0.79 vs 1.57 ± 0.79, P = .04; 247.5 ± 136.1 vs 84.5 ± 48.6, P = .048). MMP-2 levels were lower in the combination group compared to the resting group (2.63 ± 0.74 vs 1.86 ± 0.38, P = .019). The study results demonstrated that bevacizumab and everolimus combination therapy was more effective than bevacizumab therapy alone.

Primary mesenchymal tumors of the colon: a report of three cases.

Primary mesenchymal tumors of the colon are extremely rare tumors among soft tissue sarcomas. These tumors are more aggressive and have poorer prognosis than adenocarcinoma of the colon. Here, we presented 3 cases of primary mesenchymal tumors of the colon. Their histopathological diagnoses are leiomyosarcoma, pleomorphic liposarcoma, and desmoplastic small round cell tumor, respectively. The rarity of primary mesenchymal tumors of the colon makes it difficult to approach the treatment and predict the prognosis of these rare tumors.

Gastric histopathological findings and ghrelin expression in morbid obesity.

OBJECTIVE: The role of Ghrelin, also known as the appetite hormone, is not fully explained in the development of morbid obesity. Plasma Ghrelin level is low in obese and high in slim subjects. Ghrelin-expressing cells were investigated histopathologically in the stomach of morbid obese patients in this study. Tissue Ghrelin expression was also compared with various parameters such as the distribution of endocrine cells, age, gender, body mass index, preoperative plasma Ghrelin level and presence of accompanying diseases. MATERIAL AND METHOD: The study included 33 morbidly obese patients, and 8 non-obese control patients. Plasma Ghrelin levels were measured preoperatively. Sleeve gastrectomy resection materials of 33 cases were evaluated with histopathological and immunohistochemical (Ghrelin and Chromogranin-A) techniques. The results were statistically evaluated by nonparametric tests. RESULTS: Histopathological findings observed in sleeve gastrectomy resection materials were interstitial lymphocytic infiltration (63.6%), hyperplasia of lymphoid follicles in the lamina propria (60.7%) and microvesiculation / dilatation of parietal cells (57.6%). The number of Ghrelin immunopositive cells in the gastric mucosa in females was significantly higher compared to males (p=0,007). Additionally, the number of Ghrelin immunopositive cells was significantly higher at the fundus-proximal corpus compared to the distal corpus of the stomach (p=0.0001). No significant correlation was found between Ghrelin-chromogranin immunopositive endocrine cell distribution and preoperative plasma Ghrelin levels and endocrine cell hyperplasia. CONCLUSION: Our study confirms that Ghrelin producing cells are most dense in the proximal stomach. Increased number of Ghrelin expressing cells in the gastric mucosa in females compared to males suggests that gender may also be a factor in determining the method for treatment of morbid obesity.

Effects of retinoic acid and zinc on the treatment of caustic esophageal burns.

PURPOSE: An experimental study was carried out to investigate the efficacy of an anti-inflammatory and antiproliferative agent all-trans retinoic acid (ATRA) and an antioxidant agent zinc sulphate (ZnSO(4)) in the prevention of stricture after caustic esophageal burn in rats. METHODS: Esophageal burn was induced using 50% NaOH. Rats were divided into four groups as follows: group A (sham; n = 8), group B (control; n = 8), group C (treated with ATRA; n = 8) and group D (treated with ZnSO(4); n = 8). All rats were killed on the 28th day and esophageal tissues were evaluated for histopathologic damage score, hydroxyproline (HP) content and TGF-beta1 expression. RESULTS: Significant difference was detected in terms of histopathologic damage score between groups B and C (p = 0.002). Although mean HP levels of groups C and D were lower than group B, statistical comparison was not significant. TGF-beta1 expression in group C was significantly lower than group B. CONCLUSION: Zinc has not been found effective in the prevention of stricture formation. The results indicate that ATRA has a preventive effect in the development of fibrosis in an experimental model of caustic esophageal burns in rats.

Synchronous endocrine tumors of small intestine: report of a case.

As with most endocrine tumors, the malignant potential depends on evidence of local or distant invasion (metastasis), so it is important to differentiate synchronous/metachronous endocrine tumors from their metastases. A 90-year-old man was operated due to tumor of the ampulla of Vater. As the surgical specimen was examined macroscopically, a second tumor focus, measuring 1 cm in diameter, was detected at the duodenum. There were no clinical syndromes due to hormone hypersecretion. Microscopically, the ampullary tumor had trabecular and rosette-like patterns, with many necrotic areas. It had invaded the muscularis mucosa at the duodenal wall. The latter duodenal tumor was located in the submucosa and had distinct borders. This tumor consisted of trabecular structures with stroma rich in lymphoid aggregates. Immunohistochemistry revealed positivity for synaptophysin and gastrin and negativity for somatostatin. In addition, the whole antral portion of the Whipple resection material showed diffuse parietal cell hyperplasia. The tumors were diagnosed as well-differentiated endocrine carcinoma in the ampulla of Vater according to the WHO classification 2000, a gastrin-producing well-differentiated endocrine tumor in the first portion of the duodenum without regional lymph node metastases, and a diffuse parietal cell hyperplasia at the antral portion of the stomach. In conclusion, clinical findings and the postoperative diagnosis suggest that this patient had primary synchronous neuroendocrine tumors of the small intestine.

Apoptotic cell death and its relationship to gastric carcinogenesis.

AIM: To investigate the apoptotic process of cells within the intestinal metaplasia areas co-localizing with chronic gastritis and gastric carcinomas and to analyze the involvement of proteins regulating apoptosis in the process of intestinal metaplasia related gastric carcinogenesis. METHODS: Forty-two gastric carcinoma and seventeen chronic gastritis cases were included in this study. All cases were examined for the existence of intestinal metaplasia. Ten cases randomly selected from each group were processed for TUNEL assay. TUNEL positive cells within the intestinal metaplasia areas, co-localizing either to gastric carcinoma or chronic gastritis, were counted and converted to apoptotic indices. In addition, p53, bcl-2 and bax expression patterns within these tissues were analyzed on the basis of immunohistochemistry. RESULTS: Twenty-eight of the cases were intestinal and 14 of the cases were diffuse type adenocarcinomas. 64% (27/42) of the gastric carcinoma cases had intestinal metaplasia. Intestinal metaplasia co-localized more with intestinal type carcinomas compared with diffuse type carcinomas [75% (21/28) vs 42% (6/14), respectively; P

Investigation of HER-2 codon 655 single nucleotide polymorphism frequency and c-ErbB-2 protein expression alterations in gastric cancer patients.

AIM: To investigate both whether the risk of gastric cancer is associated with the Ile/Val single nucleotide polymorphism (SNP) of human epidermal growth factor receptor-2 (HER-2) transmembrane domain-coding region at codon 655 and the suggested existence of HER-2 expression in gastric cancer cases in a Turkish patient group. METHODS: Polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) strategy was used to analyze the presence of HER-2 SNP at codon 655. c-erbB-2 expression pattern was analyzed by immunohistochemistry. The results were compared between gastric carcinoma group and chronic gastritis group, as well as between clinicopathological parameters and carcinoma. RESULTS: Results showed that Ile/Val genotype accounted for 20% within the Turkish gastric carcinoma group, and none in chronic gastritis group, and this genotyping was associated with stage IV gastric cancers (P=0.04). Positive membranous HER-2 immunoreactivity, on the other hand, accounted for 24% within the Turkish gastric carcinoma group and none from chronic gastritis cases; further, it was correlated with intestinal type carcinomas (P=0.007), and stage III-IV carcinomas (P=0.004). CONCLUSION: These observations imply that the tested HER-2 SNP may participate in the development and progression of gastric cancer. Thus, after confirming these results with large sample groups, HER-2 codon 655 SNP and/or c-erbB-2 overexpression may also be used as a poor prognostic indicator for gastric carcinomas.

[Correlation of histological classifications of gastric carcinomas with location and prognosis]. / Comparaison histopronostique des classifications des carcinomes gastriques en fonction de leur localisation.

AIM: To evaluate the prognostic impact of different histological classifications of gastric adenocarcinoma. METHODS: Between 1993-2000, 94 patients with gastric adenocarcinoma were studied. Tumors were classified according to TNM staging, WHO, Lauren and Goseki classifications. Twenty five patients (27%) had a proximal tumor and 69 (73%) a distal tumor. Intestinal type according to Lauren were more often observed among the proximal carcinomas (19/25) than in distal ones (32/69) (P=0.01). According to Goseki, lymph node metastasis were less frequently found in group III (5/13) than in other groups (64/81) (P=0.033). The mean follow-up was 23 months. Survical was not influenced by WHO, Lauren, and Goseki classifications. Survival significantly varied according to the different groups of the TNM classification. The proximal location of the tumor was associated with poorer prognosis than distal location (P=0.0373). Number of metastatic lymph nodes, invasion of perineurium, and vascular invasion had significant prognostic value in proximal carcinomas. CONCLUSION: The results of this study suggest that gastric carcinomas should be divided into proximal and distal tumors using the Goseki classification in addition to the Lauren classification because the Goseki classification recognizes tumor groups with different dissemination routes.