Esophageal stenosis in epidermolysis bullosum: a challenge for the endoscopist

Background/Purpose

Esophageal stenosis is a severe complication in dystrophic epidermolysis bullosa (EB). Endoscopic dilations may cause mucosal injury with stricture recurrence. Our aim was to describe our referral EB-center experience on safety and long-term efficacy of fluoroscopically guided balloon dilation without endoscopy.

Methods

Over 14 years, 34 patients with EB, previously evaluated with barium esophagogram for dysphagia, underwent balloon esophageal dilation. Under fluoroscopy, a guide wire was introduced via a nostril into the stomach. A 12-mm pneumatic balloon, which passed over the wire, was filled using radio-opaque contrast, dilating the stricture. Orotracheal intubation was avoided. Antibiotics, dexamethasone, and proton-pump inhibitors were administered. Study approval was obtained from our ethical board.

Results

Ninety-three dilations were performed. Seventeen patients had a single stenosis. The mean age of onset was 18 years (range, 3-47 years). Thirteen patients underwent one dilation. In 6 cases, endoscopy was necessary to visualize the esophageal lumen. Complications included cervical esophageal perforation (2) and transitory dysphagia (10). Thirty patients were feeding within 24 hours. During the follow-up, 2 patients required a gastrostomy, and 2 patients underwent fundoplication for gastroesophageal reflux disease.

Conclusions

Fluoroscopically guided balloon dilation in EB is a safe and well-tolerated procedure. An experienced endoscopy team is necessary in certain cases.     

Microsatellite instability and compromised mismatch repair gene expression during in vitro passaging of monoclonal human T lymphocytes

An age-related accumulation of DNA damage caused by increased insult and/or decreased repair, could contribute to impaired cellular function. DNA mismatch repair (MMR), the main postreplicative correction pathway, can be monitored by assessing microsatellite instability and has been reported to decrease with age. Here, we analyzed the involvement of the MMR system in the accumulation of genetic damage in a cultured monoclonal human T lymphocyte model. We correlated microsatellite instability (MSI) and MMR gene expression, and replicative senescence of CD4+ clones derived from young, old and centenarian individuals or from CD34+ precursors. Cells were analyzed for MSI at five loci (CD4, VWA, Fes, D2S123, and BAT26), for the methylation status of MLH1 and MSH2 gene promoters, and for the expression of the MMR genes MSH2, MSH6, MSH3, MLH1, PMS2, and PMS1. MSI increased with increasing culture passages, particularly in the CD34+ progenitor-derived clones, but also in those from adult T cells. MSI and MMR gene expression were found to correlate, mostly due to a reduced expression of the components of MutL heterodimers, pointing to a role of MMR in the acquisition of DNA damage with in vitro aging.     

Rhabdoid carcinoma of the colon: a distinct entity with a very aggressive behavior: a case report associated with a polyposis coli and review of the literature

Rhabdoid colon tumors (RCTs) are rare lesions whose existence as an independent distinct entity remains controversial. To date, 6 RCTs have been reported. This study reports a novel case associated with polyposis coli in a 73-year-old woman. Histologically, the neoplasia was heterogeneous consisting of an adenocarcinoma associated with rhabdoid features. In rhabdoid component, an intense expression of MSH2 was noted but MLH1 was negative. A BRAF V600E mutation and no KRAS mutations were identified. The promoter regions of subset of genes highly specific to characterize the CIMP status (NEUROG1, IGF2, RUNX3, SOCS1, including MLH1) were hypermethylated, suggesting the presence of CIMP+ and MSI high tumor. In conclusion, all RCTs have similar clinical features. The presence of polyposis and adenocarcinoma component as well as the expression of mesenchymal marker suggests a sarcomatous dedifferentiation. It is argued that RCT could be a very aggressive entity of colon, which could benefit from new biological colonic treatments.     

Metabolic syndrome and all-cause mortality in older men and women

Eur J Clin Invest 2012; 42 (9): 1000-1009 ABSTRACT: Background Prevalence of metabolic syndrome (MetS) increases with age, but its association with all-cause mortality in older persons remains uncertain. This study investigated the association of all-cause mortality with MetS and its individual components in older men and women. Methods A total of 917 men and 1043 women aged 65?years and older from two Italian population-based cohorts were included in the study. MetS was defined according to four different definitions: National Cholesterol Education Program (NCEP), NCEP revised according to the American Heart Association and National Heart Lung Blood Institute (NCEP-R), International Diabetes Organization (IDF) and Joint Interim Statement (JIS). All of these definitions include abdominal obesity, hyperglycaemia, hypertriglyceridaemia, low high-density lipoprotein cholesterol and hypertension. Hazard Ratios (HR) and their corresponding 95% confidence interval (95%CI) estimated from multivariable-adjusted Cox regression models were used to investigate the associations of all-cause mortality with baseline MetS status and individual MetS components. Results After 6·5?±?1·8?years of follow-up, there were 179 deaths among women and 193 among men. Mortality risk was increased in women with MetS by any definition, regardless of individual components, but limited to age 70-79?years (NCEP, HR?=?2·02, 95%CI, 1·16-3·53; NCEP-R, HR?=?2·51, 95%CI, 1·45-4·34; IDF, HR?=?2·16, 95%CI, 1·26-3·72; JIS, HR?=?2·16, 95%CI, 1·26-3·72). Mortality risk of men was associated with hypertriglyceridaemia below age 70?years (HR?=?2·50, 95%CI, 1·19-5·25), but unrelated to MetS status. Conclusions Metabolic Syndrome is associated with all-cause mortality in older women but not in men. The association, however, is limited to a narrow age range.     

Classical lobular breast carcinoma consistently lacks topoisomerase-IIα gene amplification: implications for the tailored use of anthracycline-based chemotherapies

Brunello E, Brunelli M, Manfrin E, Nottegar A, Bersani S, Vergine M, Molino A, Fiorio E, Chilosi M, Gobbo S, Martignoni G & Bonetti F
(2012) Histopathology  60, 482–488
Classical lobular breast carcinoma consistently lacks topoisomerase‐IIα gene amplification: implications for the tailored use of anthracycline‐based chemotherapies
[Correction added after online publication, 17 January 2012: Title amended to match main article title.] Aims: There is consistent lack of data focusing the topoisomerase‐IIα gene status in lobular breast carcinoma, a subtype that usually shows poor responsiveness to chemotherapies including those using anthracycline drugs. Methods and results: Forty‐six infiltrative lobular carcinomas, 13 with matched metastases, were used. Topoisomerase‐IIα gene amplification was evaluated by chromogenic in situ hybridization (CISH) and fluorescence in situ hybridization (FISH). We also assessed Her2/neu status by CISH, FISH and silver in situ hybridization (SISH). HER2 immunoexpression was assessed by the HercepTest. Forty‐four of 46 (95%) cases revealed no topoisomerase‐IIα amplification, whereas two of 46 (5%) cases were amplified by all three techniques. Eleven of the 13 metastatic sites showed no amplification either in the primary or in the metastases (85%); the remaining two were amplified (15%). Her2/neu was not amplified in 44 of 46 (95%) cases nor was it amplified in 11 of 13 (95%) metastatic tissues. The two cases showing Her2/neu and topoisomerase‐IIα amplification scored 3+; the remaining non‐amplified cases scored 0 or 1+ in 40 and 2+ in four cases. Conclusions: In the era of personalized and tailored therapies, we suggest that patients affected by the classical lobular subtype of breast carcinoma constantly lack the ad hoc predictive rationale for receiving common chemotherapy that includes anthracyclines.     

Comparison of coronary risk factors and quality of life in coronary artery disease patients with versus without diabetes mellitus

It is unclear whether patients with coronary artery disease (CAD) and diabetes mellitus (DM) can make comprehensive lifestyle changes that produce similar changes in coronary risk factors and quality of life compared with patients with CAD and without DM. We examined medical characteristics, lifestyle, and quality of life by diabetic status and gender in the Multicenter Lifestyle Demonstration Project (MLDP), a study of 440 nonsmoking patients with CAD (347 men, 55 with DM; 15.9%; 93 women, 36 with DM; 38.7%). Patients met in groups to improve lifestyle (plant-based, low-fat diet; exercise; stress management) for 1 year. Follow-ups were conducted at 3 and 12 months. At baseline, body mass and systolic blood pressure were significantly higher among patients with DM. Men with DM had a worse medical history (e.g., hypertension, hyperlipidemia, and family history of CAD) than did those without DM. Patients with DM, especially women, reported poorer quality of life than did patients without DM. The 2 groups of patients were able to adhere to the recommended lifestyle, as demonstrated by significant improvements in weight (mean -5 kg), body fat, low-density lipoprotein cholesterol, exercise capacity, and quality of life. No significant changes in triglycerides and high-density lipoprotein cholesterol were noted. By the end of 12 months, improvements in glucose-lowering medications (i.e., discontinuation or a change from insulin to oral hypoglycemic agents) were noted for 19.8% (n = 18) of patients with DM. In conclusion, patients with CAD and DM are able to follow a comprehensive lifestyle change program and show similar improvements in coronary risk factors and quality of life as those without DM.