Combined metallothioneins and p53 proteins expression as a prognostic marker in patients with Dukes stage B and C colorectal cancer

Our study aimed to evaluate metallothionein and p53 expression in colorectal cancer and to correlate their combined expression with selected clinical and pathologic variables of the disease, to define their prognostic significance. Colorectal cancer specimens from 99 patients were retrospectively analyzed by immunohistochemistry for metallothionein and p53 expression. Survival curves were generated according to the Kaplan-Meier method, and univariate survival distributions were compared with the use of the log-rank test. Multivariate models were computed using Cox proportional hazards regression. This research was approved by the institutional review boards of all centers. Tumors showing concomitant high metallothionein expression and negative p53 (metallothionein(H)/p53(-)) were significantly inversely related to depth of invasion, frequency of nodal metastasis, and Dukes stage (P < .01). In univariate analysis, patients with metallothionein(H)/p53(-) phenotype showed a better overall survival (hazard ratio [HR], 2.83; P < .05) and disease-free survival (HR, 2.03; P < .05). In multivariate analysis, considering staging, metallothionein, and metallothionein + p53 variables, in 83 patients with Dukes stages B and C, metallothionein(H)/p53(-) combination was the sole factor showing an independent prognostic value for overall survival (HR, 3.88; P < .1) and disease-free survival (HR, 2.56; P < .1). In conclusion, the combined analysis of metallothionein and p53 may enhance the prognostic power of each individual marker by predicting the progression of the disease and contributing to a better identification of patients at low risk for mortality, especially for those with Dukes stage B and C colorectal cancer.     

Balint's syndrome and post-acute brain injury rehabilitation: a case report

Background: Balint's syndrome includes the clinical symptom triad of simultagnosia, ocular apraxia and optic ataxia. These symptoms, in combination, are rare and can be quite debilitating as they impact visuospatial skills, visual scanning and attentional mechanisms. Case Study: The literature addressing rehabilitation of individuals with Balint's syndrome is sparse. The current case report describes the outcome of a 58-year old male who presented with Balint's syndrome secondary to severe traumatic brain injury and following completion of a comprehensive post-acute brain injury rehabilitation programme. The patient was 4-months post-injury onset upon admission and received 6 months of rehabilitation services as an inpatient. The patient's comprehensive rehabilitation programme involved a 3-pronged approach including the implementation of (a) compensatory strategies, (b) remediation exercises and (c) transfer of learned skills in multiple environments and situations with implementation of psychoeducation and psychotherapy. Comprehensive neuropsychological and occupational therapy evaluations were performed at admission and at discharge in order to monitor cognitive, affective, neurological and functional change over time. Conclusions: Neuropsychological test improvements were noted on tasks that assess visuospatial functioning, although most gains were noted for functional and physical abilities.     

Hybrid natural orifice transluminal endoscopic cholecystectomy: prospective human series

Background  

Natural orifice transluminal endoscopic surgery (NOTES) makes it possible to perform intraperitoneal surgical procedures with a minimal number of access points in the abdominal wall. Currently, it is not possible to perform these interventions without the help of abdominal wall entryways, so these procedures are hybrids fusing minilaparoscopy and transluminal endoscopic surgery. This report presents a prospective clinical series of 25 patients who underwent transvaginal hybrid cholecystectomy for cholelithiasis.     

Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study)

OBJECTIVE

This study evaluated the effects of testosterone replacement therapy (TRT) on insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS).

RESEARCH DESIGN AND METHODS

The efficacy, safety, and tolerability of a novel transdermal 2% testosterone gel was evaluated over 12 months in 220 hypogonadal men with type 2 diabetes and/or MetS in a multicenter, prospective, randomized, double-blind, placebo-controlled study. The primary outcome was mean change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were measures of body composition, glycemic control, lipids, and sexual function. Efficacy results focused primarily on months 0−6 (phase 1; no changes in medication allowed). Medication changes were allowed in phase 2 (months 6−12).

RESULTS

TRT reduced HOMA-IR in the overall population by 15.2% at 6 months (P = 0.018) and 16.4% at 12 months (P = 0.006). In type 2 diabetic patients, glycemic control was significantly better in the TRT group than the placebo group at month 9 (HbA_1c: treatment difference, −0.446%; P = 0.035). Improvements in total and LDL cholesterol, lipoprotein a (Lpa), body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate.

CONCLUSIONS

Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS.Low serum testosterone is common in men with type 2 diabetes and/or metabolic syndrome (MetS) and numerous studies have reported an association between testosterone deficiency and visceral obesity, insulin resistance (IR) and dyslipidemia (1–4). In men with type 2 diabetes, low testosterone is associated with a high prevalence of symptomatic hypogonadism (3), frequently due to hypogonadotrophic hypogonadism (5).Small studies have demonstrated that testosterone replacement therapy (TRT) in hypogonadal men with and without type 2 diabetes is associated with reductions in IR, waist circumference, cholesterol, glycated hemoglobin (HbA_1c), and fasting plasma glucose (FPG) concentrations (6–9). Conversely, withdrawal of TRT in hypogonadal men leads to decreased insulin sensitivity (10). Furthermore, androgen suppression therapy for prostate cancer can result in alterations of individual cardiovascular risk factors and increases the occurrence of incident diabetes, myocardial infarction and sudden cardiac death (11,12). Epidemiologic studies have reported that low testosterone in men is associated with increased all-cause and cardiovascular mortality (13).The TIMES2 (Testosterone replacement In hypogonadal men with either MEtabolic Syndrome or type 2 diabetes) study investigated the effects of transdermal TRT on IR, selected cardiovascular risk factors, and symptoms in hypogonadal men with MetS and/or type 2 diabetes. The safety and tolerability of a novel, metered-dose, transdermal 2% testosterone gel were also examined.     

Pseudoaneurysm of the superficial palmar arch, following endoscopic carpal tunnel release. A case report

Pseudo-aneurysm of the superficial palmar arch following carpal tunnel release is exceptional and thus poorly reported. We present one observation, recorded on more than 1300 hands treated by endoscopic release using the "Chow" technique by a single surgeon. Ultra-sonography could be used in an attempt to locate the superficial palmar arch and thus prevent vascular damage at surgery.