Hereditary multiple exostoses and juvenile colon carcinoma: A case with a common genetic background?

A case of obstructing colon cancer is described in a 31‐year‐old patient affected by hereditary multiple exostoses. The association of these two rare conditions, which has never been described previously, and their early onset prompt us to discuss the clinical and genetic elements of a potential common pathogenic scenario. J. Surg. Oncol. 2009;100:520–522. © 2009 Wiley‐Liss, Inc.     

Respiratory symptoms and pulmonary functional changes in patients with irritable bowel syndrome

OBJECTIVE: Scientific evidence of functional interface between the immune and sensory motor systems of the gut and respiratory systems has been reported. In recent studies excess prevalence of bronchial hyper-responsiveness has been shown among patients with irritable bowel syndrome (IBS). The purpose of our study was to investigate the possible relationship between IBS and asthma. METHODS: One hundred thirty-three patients with IBS (108 women, 25 men) and 137 control subjects (105 women, 32 men) were included in this study. Both for IBS and the control group, the mean ages were 41.64+/-9.45 yr and 39.94+/-10.62 yr, respectively. Patients more than 50 yr old, with any organic GI disease, acute respiratory system infection, current or ex-smokers, and patients using drugs affecting smooth muscle and autonomic nervous system were not included in the study. Respiratory symptoms were questioned and pulmonary function tests were performed for every subject. RESULTS: There were 45 (33.8%) and eight (5.8%) subjects with respiratory symptoms in IBS and control groups, respectively (p < 0.0001). Twenty-one (15.8%) patients from the IBS group and two (1.45%) patients from the control group had the diagnosis of asthma according to history, clinical, and PFT findings. There was no statistical difference between two groups with respect to percentage of forced vital capacity and forced expiratory volume in 1 s-to-forced vital capacity. The difference between the two groups in forced expiratory volume in 1 s, flow after 50% of the vital capacity has been exhaled, peak expiratory flow rate, and maximal mid-expiratory flow rate was statistically significant (p < 0.01). CONCLUSION: We found that the prevalence of asthma was more common in the IBS group than in controls. Our finding supports the speculation that asthma and IBS may share common pathophysiological processes.     

Predictive factors for postoperative severe hypocalcaemia after parathyroidectomy for primary hyperparathyroidism

Hypocalcaemia is a complication of parathyroidectomy. We retrospectively analyzed data on patients who underwent parathyroidectomy for primary hyperparathyroidism (pHPT) to identify predictive factors for severe postoperative hypocalcaemia. Since 2004 we performed 87 parathyroidectomies for pHPT. We divided the patients into two groups: subjects who presented with postoperative hypocalcaemia (group B) or otherwise (group A). We looked for a correlation between several variables and the incidence of postoperative hypocalcaemia. The median calcemia in group B (19 patients) was 6.9 mg/dL on the first postoperative day and 7.6 mg/dL on the third day. We observed hypocalcemia related clinical symptoms in every patient. In all 19 cases the reduction of intraoperative parathyroid hormone above 85 per cent after parathyroidectomy was related to the development of severe postoperative hypocalcaemia (P = 0.042). We found that the reduction of intraoperative parathyroid hormone over 85 per cent after parathyroidectomy can be considered a reliable predictive factor of postoperative hypocalcaemia after parathyroidectomy for primary hyperparathyroidism.     

The effect of recombinant hepatitis B vaccine therapy in chronic hepatitis B infection.

BACKGROUND/AIMS: Immune-modulator and antiviral treatments for carriers of hepatitis B virus are known to have poor efficacy with a high cost and frequent side effects, which has led to investigation of new treatment modalities. The aim of this study was to determine the efficacy of recombinant hepatitis B vaccine in the treatment of patients with chronic hepatitis B (HBV DNA >5 pg/ml, ALT>60) infection diagnosed histopathologically and asymptomatic carriers (HBV DNA<5 pg/ml, ALT <40, Anti Hbe positive) of the virus. METHODS: The vaccine (Gen Hevac B Pasteur) was administered at baseline and at months one and six to patients with chronic hepatitis and asymptomatic carriers. Ten cases with chronic hepatitis B infection were assigned to a control group to whom no treatment was given. Biochemical and microbiological investigations were performed at baseline and at months three, six and twelve in all cases. Seroconversion of Hbe Ag, loss of HBV DNA and normalization of ALT were considered as a positive response. RESULTS: Patients with chronic hepatitis B who were given the vaccine were found to have significantly low levels of HBV DNA at 12 months (63.2+/-20pg/ml) compared to baseline values (174.4+/-36.9pg/ml), while controls were found to have high levels of HBV DNA at 12 months (223.1+/-33pg/ml) compared to baseline values (165.2+/-33.2pg/ml) (p<0.05). At 12 months, HBV DNA had become negative in seven of 19 patients given the vaccine (36.8%) Four patients with chronic hepatitis (36.35%) were observed to have HBeAg seroconversion and one patient (5.2%) HBsAg seroconversion at the end of 12 months and there were four (21.05%) patients who responded positively to vaccine therapy in this group. Asymptomatic carriers and controls did not have seroconversion of HBs Ag. Also, HBV DNA did not become negative in controls. CONCLUSION: It may be concluded that recombinant hepatitis B vaccine is effective in the treatment of chronic hepatitis B.     

Correlation between clinical phenotype and electromyographic parameters in amyotrophic lateral sclerosis

Introduction

Even if electromyography (EMG) is routinely used to confirm the diagnosis of amyotrophic lateral sclerosis (ALS), few studies have analysed the correlation between electrophysiological parameters and clinical characteristics of ALS. We assessed if the quantification of active denervation (AD) and chronic denervation (CD) provides clinicians with information about phenotype, disease progression and survival in ALS patients.

Methods

We studied a cohort of 689 ALS patients recording the following parameters: age and site of onset, survival, MRC scale for muscle strength evaluation, burden of upper and lower motor signs as measured with specific scales (PUMNS and LMNS, respectively), ALSFRS-R, progression rate (ΔFS), MITOS and King’s Staging systems (KSS). We performed EMG on 11 muscles, and calculated semiquantitative AD and CD scores for each limb, as well as for the bulbar and spinal regions.

Results

We found a positive correlation between AD and CD scores with LMNS (respectively p = 4.4 × 10^–37 and p = 2.8 × 10^–45) and a negative correlation with MRC (respectively p = 4.5 × 10^–35 and p = 3.0 × 10^–35). Furthermore, patients with higher spinal AD and CD scores had significantly lower ALSFRS-R scores, and higher KSS and MITOS stages. Conversely, only AD was associated to higher ΔFS (p = 1.0 × 10^–6) and shorter survival (p = 1.1 × 10^–5).

Conclusion

Our results confirmed that EMG examination represents not only a diagnostic instrument, but also a prognostic tool. In this context, AD seems to be a reliable predictor of disease’s progression and survival while CD better describes functional disability.

     

Human centenarian–associated SIRT6 mutants modulate hepatocyte metabolism and collagen deposition in multilineage hepatic 3D spheroids

Non-alcoholic fatty liver disease (NAFLD), encompassing fatty liver and its progression into nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), is one of the rapidly rising health concerns worldwide. SIRT6 is an essential nuclear sirtuin that regulates numerous pathological processes including insulin resistance and inflammation, and recently it has been implicated in the amelioration of NAFLD progression. SIRT6 overexpression protects from formation of fibrotic lesions. However, the underlying molecular mechanisms are not fully delineated. Moreover, new allelic variants of SIRT6 (N308K/A313S) were recently associated with the longevity in Ashkenazi Jews by improving genome maintenance and DNA repair, suppressing transposons and killing cancer cells. Whether these new SIRT6 variants play different or enhanced roles in liver diseases is currently unknown. In this study, we aimed to clarify how these new centenarian-associated SIRT6 genetic variants affect liver metabolism and associated diseases. We present evidence that overexpression of centenarian-associated SIRT6 variants dramatically altered the metabolomic and secretomic profiles of unchallenged immortalized human hepatocytes (IHH). Most amino acids were increased in the SIRT6 N308K/A313S overexpressing IHH when compared to IHH transfected with the SIRT6 wild-type sequence. Several unsaturated fatty acids and glycerophospholipids were increased, and ceramide tended to be decreased upon SIRT6 N308K/A313S overexpression. Furthermore, we found that overexpression of SIRT6 N308K/A313S in a 3D hepatic spheroid model formed by the co-culture of human immortalized hepatocytes (IHH) and hepatic stellate cells (LX2) inhibited collagen deposition and fibrotic gene expression in absence of metabolic or dietary challenges. Hence, our findings suggest that novel longevity associated SIRT6 N308K/A313S variants could favor the prevention of NASH by altering hepatocyte proteome and lipidome.

     

Mortality risk analysis following routine vs selective defunctioning stoma formation after total mesorectal excision for rectal cancer

Objective  To answer the question whether a defunctioning stoma (DS) should be constructed routinely after total mesorectal excision or whether it could be used selectively to ensure patient safety.
Method  A PubMed search was performed. All randomized trials on the role of a DS were included. Also, observational articles published between January 1997 and August 2007 were reviewed. Sensitivity analysis of the mortality risk was performed.
Results  The clinical anastamotic leak (CAL) rate was 17% in 358 patients from four randomized trials and 9.6% in 4059 patients from 39 observational studies. The CAL rate increased significantly from 9.6% with DS to 24.4% without DS in four randomized trials, and from 7.9% with DS to 13.2% without DS in 17 observational studies. The re-operation rate as a result of anastomotic leakage was lower in patients with DS than in patients without DS in both study types. Leak-related mortality was not significantly different: 7.2% with vs 7.7% without DS in observational studies, and 0% with vs 4.6% without DS in randomized trials. Sensitivity analysis indicated that a selective DS strategy is acceptable if the CAL rate without DS is less than 16.6% with a CAL-related mortality of no more than 4.6%.
Conclusion  The results of this review support the routine construction of a protective stoma. However, selective use of a DS is justified from a patient safety point of view if the CAL-rate and its related mortality are limited. Each unit should audit its performance.     

Improvement of Metabolic Syndrome Following Intragastric Balloon: 1 Year Follow-up Analysis

Objective  This study aimed to assess the impact of intragastric balloon (IGB)-induced body weight loss on metabolic syndrome in obese patients and evaluate what happens during 1-year follow-up. Methods  To this end, data were collected on 143 obese patients (body mass index (BMI) 36.2 ± 5.7 kg/m2) who underwent IGB insertion between January 2000 and December 2005. Outcomes were recorded at BioEnterics Intragastric Balloon removal time (t ₀) and at 6-month (t ₆) and 12-month (t ₁₂) follow-up. Results  Significant BMI, excess body weight loss percentage, and body weight loss percentage (BWL%) were observed at t ₀ (29.6 ± 4.6 kg/m2; 29.3 ± 4.8%; 14.1 ± 5.7%), followed by partial weight regain at t ₁₂ (32.4 ± 4.3 kg/m2; 26.1 ± 4.9%; 11.2 ± 4.6%). Incidence of metabolic syndrome dropped from 34.8% (pre-IGB value) to 14.5% (t ₀) and 11.6% (t ₁₂). Likewise, type 2 diabetes mellitus (DM), hypertriglyceridemia, hypercholesterolemia, and blood hypertension (BH) incidence decreased from 32.6%, 37.7%, 33.4%, and 44.9% (pre-IGB values) to 20.9%, 14.5%, 16.7%, and 30.4% at t ₀ and 21.3%, 17.4%, 18.9%, and 34.8% at t ₁₂. HbA1c blood concentration shifted from an initial value of 7.5 ± 2.1% to 5.7 ± 1.9% (t ₀), 5.6 ± 0.7% (t ₆), and 5.5 ± 0.9% (t ₁₂). Patients suffering from DM or BH stopped or diminished relative drug consumption at t _12. Negligible modifications were reported as regards HDL cholesterol and hyperuricemia. Conclusion  Weight regain is commonly observed during long-term follow-up after IGB removal. Nevertheless, the maintenance of at least 10% of the BWL%, as reported at 1-year follow-up, is associated with an improvement in metabolic syndrome.