Expression of transforming growth factor beta-1 in gastric cancer and in the gastric mucosa of first-degree relatives of patients with gastric cancer

Transforming growth factors beta (TGF-β) constitute a family of polypeptide growth factors that control cell growth, cell differentiation and migration, as well as the formation of the extracellular matrix. Recent analyses revealed the overexpression of TGF-β1 in human gastric cancers and demonstrated increased cell proliferation in the stomach of patients with gastric cancer and their first-degree relatives. Using human gastric tissues obtained from patients with gastric cancer (n = 19), biopsies from healthy first-degree relatives of gastric cancer patients (n = 18) and healthy individuals (n = 19), we analysed the expression of TGF-β1 using the reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Fifteen of 19 patients with gastric cancer expressed TGF-β1 in the tumour. In 11 of these 15 cases TGF-β1 mRNA was also detectable in the non-tumourous stomach. Interestingly, all but two individuals with a first-degree relative diagnosed with gastric cancer exhibited TGF-β1 expression in either the antrum or corpus biopsy or both. In contrast, only one of 19 individuals without a family history of gastric cancer expressed TGF-β1 in the stomach (P< 0.0001). TGF-β1 expression is detectable in a large proportion of gastric cancers and in the stomach of healthy first-degree relatives of gastric cancer patients. Since individuals without gastric cancers in their family express TGF-β1 only in one of 19 cases, the induction of TGF-β1 expression in first-degree relatives of patients with gastric cancer points to the presence of specific molecular alterations in a subgroup of individuals with an increased risk of developing gastric cancer that may precede the development of gastric cancers. © 2000 Cancer Research Campaig

Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer deaths despite the fact that detection of this cancer in early stages results in over 90% survival rate. Currently less than 45% of at-risk individuals in the US are screened regularly, exposing a need for better screening tests. We performed two case-control studies to validate a blood-based test that identifies methylated DNA in plasma from all stages of CRC. METHODOLOGY/PRINCIPAL FINDINGS: Using a PCR assay for analysis of Septin 9 (SEPT9) hypermethylation in DNA extracted from plasma, clinical performance was optimized on 354 samples (252 CRC, 102 controls) and validated in a blinded, independent study of 309 samples (126 CRC, 183 controls). 168 polyps and 411 additional disease controls were also evaluated. Based on the training study SEPT9-based classification detected 120/252 CRCs (48%) and 7/102 controls (7%). In the test study 73/126 CRCs (58%) and 18/183 control samples (10%) were positive for SEPT9 validating the training set results. Inclusion of an additional measurement replicate increased the sensitivity of the assay in the testing set to 72% (90/125 CRCs detected) while maintaining 90% specificity (19/183 for controls). Positive rates for plasmas from the other cancers (11/96) and non-cancerous conditions (41/315) were low. The rate of polyp detection (>1 cm) was approximately 20%. CONCLUSIONS/SIGNIFICANCE: Analysis of SEPT9 DNA methylation in plasma represents a straightforward, minimally invasive method to detect all stages of CRC with potential to satisfy unmet needs for increased compliance in the screening population. Further clinical testing is warranted

Jejunal Diverticular Perforation due to Enterolith

Jejunal diverticulosis is a rare entity with variable clinical and anatomical presentations. Although there is no consensus on the management of asymptomatic jejunal diverticular disease, some complications are potentially life-threatening and require early surgical treatment. Small bowel perforation secondary to jejunal diverticulitis by enteroliths is rare. The aim of this study was to report a case of small intestinal perforation caused by a large jejunal enterolith. An 86-year-old woman was admitted with signs of diffuse peritonitis. After initial fluid recovery the patient underwent emergency laparotomy. The surgery showed that she had small bowel diverticular disease, mainly localized in the proximal jejunum. The peritonitis was due to intestinal perforation caused by an enterolith 12 cm in length, localized inside one of these diverticula. The intestinal segment containing the perforated diverticulum with the enterolith was removed and an end-to-end anastomosis was done to reconstruct the intestinal transit. The patient recovered well and was discharged from hospital on the 5th postoperative day. There were no signs of abdominal pain 1 year after the surgical procedure. Although jejunal diverticular disease with its complications, such as formation of enteroliths, is difficult to suspect in patients with peritonitis, it should be considered as a possible source of abdominal infection in the elderly patient when more common diagnoses have been excluded

Isolated talonavicular arthrodesis in patients with rheumatoid arthritis of the foot and tibialis posterior tendon dysfunction

<p>Abstract</p> <p>Background</p> <p>The foot is often affected in patients with rheumatoid arthritis. Subtalar joints are involved more frequently than ankle joints. Deformities of subtalar joints often lead to painful flatfoot and valgus deformity of the heel. Major contributors to the early development of foot deformities include talonavicular joint destruction and tibialis posterior tendon dysfunction, mainly due to its rupture.</p> <p>Methods</p> <p>Between 2002 and 2005 we performed isolated talonavicular arthrodesis in 26 patients; twenty women and six men. Tibialis posterior tendon dysfunction was diagnosed preoperatively by physical examination and by MRI. Talonavicular fusion was achieved via screws in eight patients, memory staples in twelve patients and a combination of screws and memory staples in six cases. The average duration of immobilization after the surgery was four weeks, followed by rehabilitation. Full weight bearing was allowed two to three months after surgery.</p> <p>Results</p> <p>The mean age of the group at the time of the surgery was 43.6 years. MRI examination revealed a torn tendon in nine cases with no significant destruction of the talonavicular joint seen on X-rays. Mean of postoperative followup was 4.5 years (3 to 7 years). The mean of AOFAS Hindfoot score improved from 48.2 preoperatively to 88.6 points at the last postoperative followup. Eighteen patients had excellent results (none, mild occasional pain), six patients had moderate pain of the foot and two patients had severe pain in evaluation with the score. Complications included superficial wound infections in two patients and a nonunion developed in one case.</p> <p>Conclusions</p> <p>Early isolated talonavicular arthrodesis provides excellent pain relief and prevents further progression of the foot deformities in patients with rheumatoid arthritis and tibialis posterior tendon dysfunction.</p

Helicobacter pylori cag-Pathogenicity Island-Dependent Early Immunological Response Triggers Later Precancerous Gastric Changes in Mongolian Gerbils

Infection with Helicobacter pylori, carrying a functional cag type IV secretion system (cag-T4SS) to inject the Cytotoxin associated antigen (CagA) into gastric cells, is associated with an increased risk for severe gastric diseases in humans. Here we studied the pathomechanism of H. pylori and the role of the cag-pathogenicity island (cag-PAI) for the induction of gastric ulcer and precancerous conditions over time (2–64 weeks) using the Mongolian gerbil model. Animals were challenged with H. pylori B128 (WT), or an isogenic B128ΔcagY mutant-strain that produces CagA, but is unable to translocate it into gastric cells. H. pylori colonization density was quantified in antrum and corpus mucosa separately. Paraffin sections were graded for inflammation and histological changes verified by immunohistochemistry. Physiological and inflammatory markers were quantitated by RIA and RT-PCR, respectively. An early cag-T4SS-dependent inflammation of the corpus mucosa (4–8 weeks) occurred only in WT-infected animals, resulting in a severe active and chronic gastritis with a significant increase of proinflammatory cytokines, mucous gland metaplasia, and atrophy of the parietal cells. At late time points only WT-infected animals developed hypochlorhydria and hypergastrinemia in parallel to gastric ulcers, gastritis cystica profunda, and focal dysplasia. The early cag-PAI-dependent immunological response triggers later physiological and histopathological alterations towards gastric malignancies

Application of magnifying narrow-band imaging endoscopy for diagnosis of early gastric cancer and precancerous lesion

<p>Abstract</p> <p>Background</p> <p>Gastric carcinoma is the second commonest cause of cancer deaths worldwide. Early detection and diagnosis of gastric cancer in the stomach is important for improving the prognosis of gastric cancer. This retrospective study was designed to investigate the value of magnifying narrow-band imaging (NBI) in the diagnosis of precancerous lesions and early gastric cancer.</p> <p>Methods</p> <p>This study included 122 patients who were diagnosed with early gastric cancer or precancerous gastric lesions by endoscopy. The patients underwent an examination with conventional endoscopy, magnifying NBI, and magnifying chromoendoscopy. Images resolution was evaluated, and the morphology, pit patterns and blood capillary forms of lesions were analyzed. The presence of gastric carcinoma and high grade intraepithelial neoplasia in the biopsy samples was considered as a positive pathological result, which is used to assess accuracy of endoscopic diagnosis.</p> <p>Results</p> <p>For image resolution, magnifying NBI and magnifying chromoendoscopy were significantly superior to magnifying conventional endoscopy in morphology, pit pattern and blood capillary form (P < 0.01), and magnifying NBI was significantly superior to magnifying chromoendoscopy in blood capillary form (P < 0.01). IV, V₁, and VI type of gastric pit pattern were detected in 14 cases, 43 cases, and 17 cases in patients with high grade intraepithelial neoplasia, respectively. V₁and VI type of gastric pit pattern were detected in 9 cases and 39 cases in patients with early gastric cancer, respectively. The presence of irregular minute vessels and variation in the caliber of vessels was found in 109 cases. The accuracy, sensitivity, specificity, false positive rate and false negative rate for diagnosis of early gastric cancer and precancerous gastric lesions were 68.9%, 95.1%, 63.1%, 24.5%, and 32.4% for conventional endoscopy, 93.6%, 92.7%, 94.5%, 5.7%, and 6.9% for magnifying NBI, and 91.3%, 88.6%, 93.2%, 13.2%, and 21.48% for magnifying chromoendoscopy, respectively.</p> <p>Conclusions</p> <p>This study demonstrates that magnifying NBI is superior to conventional endoscopy in the diagnosis of early gastric cancer and precancerous gastric lesions, and can be used for screening early malignancies of the stomach.</p

Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder. Swallowed topical-acting corticosteroids are effective in bringing active EoE into remission. However, it is not clear whether these drugs are effective for long-term maintenance of remission. METHODS: We performed a double-blind trial to compare the efficacy and safety of 2 dosages of a budesonide orodispersible tablet (BOT) vs placebo in maintaining remission of EoE. Maintenance of remission was defined as absence of clinical and histologic relapse and no premature withdrawal for any reason. Two hundred and four adults with EoE in clinical and histologic remission, from 29 European study sites, were randomly assigned to groups given BOT 0.5 mg twice daily (n = 68), BOT 1.0 mg twice daily (n = 68), or placebo twice daily (n = 68) for up to 48 weeks. RESULTS: At end of treatment, 73.5% of patients receiving BOT 0.5 mg twice daily and 75% receiving BOT 1.0 mg twice daily were in persistent remission compared with 4.4% of patients in the placebo group (P < .001 for both comparisons of BOT with placebo). Median time to relapse in the placebo group was 87 days. The frequency of adverse events was similar in the BOT and placebo groups. Morning serum levels of cortisol were in the normal range at baseline and did not significantly change during treatment. Four patients receiving BOT developed asymptomatic, low serum levels of cortisol. Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5 mg group and in 11.8% of patients in the BOT 1.0 mg group; all infections resolved with treatment. CONCLUSIONS: In a phase 3 trial, up to 48 weeks of treatment with BOT (0.5 mg or 1.0 mg twice daily) was superior to placebo in maintaining remission of EoE. Both dosages were equally effective and well tolerated. EudraCT number; 2014-001485-99; ClinicalTrials.gov number, NCT02434029