<Emphasis Type="Italic">PTEN</Emphasis>-mediated AKT activation contributes to the reduced apoptosis among Indian oral squamous cell carcinoma patients

Purpose  

The tumor suppressor gene PTEN negatively regulates Akt, a downstream mediator phosphoinositol 3-kinase. Several studies have reported the role of PTEN gene in Akt downregulation and apoptosis induction in different cancers and cell lines. However, the role of loss of PTEN expression in Akt activation and spontaneous apoptosis in oral squamous cell carcinoma clinical specimens is not well established.     

Value of conventional and tissue Doppler echocardiography in the noninvasive measurement of right atrial pressure

Background: Evaluation of right atrial pressure (RAP) provides useful diagnostic, therapeutic, and prognostic information. Aim: To assess the utility of several conventional and tissue Doppler parameters in the estimation of RAP. Methods: Among 50 consecutive patients (median age: 50 years; all in sinus rhythm), invasively measured RAP was simultaneously correlated with pulsed Doppler of tricuspid inflow (peak E and A velocities, E‐wave deceleration time) and pulsed tissue Doppler of lateral tricuspid annulus (peak E’ and A’ velocities, isovolumic relaxation time [IVRT], acceleration time and rate of E’‐wave, deceleration time and rate of E’‐wave). These ratios were calculated: E/A, E’/A’, E/E’, and E/IVRT. Results: The median RAP was 14 mmHg (range 1–27 mmHg) with 29 patients (58%) having an elevated RAP (>10 mmHg). Among all studied Doppler variables, E/E’ ratio showed the strongest correlation with RAP (r = 0.84, P < 0.001) with the following regression equations: RAP = 1.24 + (1.69 × E/E’). The mean difference between Doppler and invasively measured RAP was 0.21 ± 2.6 mmHg. E/ E’ ratio ≥ 4.5 provides 89% sensitivity and 100% specificity for detection of elevated RAP (receiver operating characteristic area 0.95; P < 0.001). Conclusion: Of all echocardiographic variables investigated, tricuspid annular E/E’ ratio is identified as the best index for noninvasive determination of RAP.     

An exploratory, placebo-controlled, dose–response study of the efficacy and safety of onabotulinumtoxinA in spinal cord injury patients with urinary incontinence due to neurogenic detrusor overactivity

Purpose

To explore the dose response to onabotulinumtoxinA 50, 100, and 200 U in patients with spinal cord injury (SCI) with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO).

Methods

Patients (N = 73) with SCI (level T1 or lower) with NDO and UI (≥14 UI episodes/week) received 30 intradetrusor injections of onabotulinumtoxinA (50 U [n = 19], 100 U [n = 21], or 200 U [n = 17]) or placebo (n = 16) via cystoscopy, avoiding the trigone. Changes from baseline in UI episodes/week, volume voided/micturition, maximum cystometric capacity, and maximum detrusor pressure (MDP) during first involuntary detrusor contraction (IDC) were evaluated. Adverse events (AEs) were assessed.

Results

A significant linear dose response for UI episodes/week was identified at weeks 18, 30, 36, 42, and 54 (P < 0.05) with a similar trend (P = 0.092) at week 6 (primary time point). A significant linear dose response was observed in volume/void at all post-treatment time points up to week 54 (P < 0.05) and in MDP during first IDC at week 6 (P = 0.034). The proportion of patients who achieved continence at week 6 was highest in the 200 U group. Duration of effect was longest with the 200 U dose, compared with other treatment groups. The AEs were comparable across groups; urinary tract infection was the most common AE across all treatment groups.

Conclusions

In this exploratory dose–response study of SCI patients with UI due to NDO, onabotulinumtoxinA 200 U was the most effective dose. The AE profile was comparable across all groups.     

The impact of surveillance and rapid reduction in immunosuppression to control BK virus‐related graft injury in kidney transplantation

We prospectively screened 609 consecutive kidney (538) and kidney‐pancreas (71) transplant recipients for BK viremia over a 4‐year interval using polymerase chain reaction viral load detection and protocol kidney biopsies. We found that BK viremia is common at our center: total cases 26.7%, cases during first year 21.3% (mean 4 months), and recipients with ≥10 000 copies/ml 12.3%. We found few predictive clinical or demographic risk factors for any BK viremia or viral loads ≥10,000 copies/ml, other than prior treatment of biopsy confirmed acute rejection and/or higher immunosuppressive blood levels of tacrolimus (P = 0.001) or mycophenolate mofetil (P = 0.007). Viral loads at diagnosis (<10 000 copies/ml) demonstrated little impact on graft function or survival. However, rising copy numbers demand early reductions in immunosuppressive drug doses of at least 30–50%. Viral loads >185 000 copies/ml at diagnosis were predictive of BK virus‐associated nephropathy (BKVAN; OR: 113.25, 95% CI: 17.22–744.6, P < 0.001). Surveillance for BK viremia and rapid reduction of immunosuppression limited the incidence of BKVAN to 1.3%. The addition of leflunomide or ciprofloxacin to immunosuppressive dose reduction did not result in greater rates of viral clearance. These data support the role of early surveillance for BK viremia to limit the impact on transplant outcome, although the most effective schedule for screening awaits further investigation.     

Renal impairment in children with posterior urethral valves

Background

Posterior urethral valves (PUV) are a common cause of end-stage renal failure in childhood. Our aim was to describe a cohort of patients with PUV and to investigate the predictors of renal impairment.

Methods

We performed a retrospective chart review of children with PUV who were followed at King Abdulaziz University hospital between 2002 and 2011.

Results

The cohort comprised 68 boys. There was a significant difference in the duration of follow-up (p?=?0.024), nadir serum creatinine (p?<?0.001), and last known serum creatinine level (p?=?0.001) between the patients with and without renal impairment. The duration of follow-up appeared to be a significant predictor for serum creatinine doubling (p?=?0.003; odds ratio, 1.8). There was no difference in the age of presentation, age at the time of the study, and first or last serum creatinine between children who initially had vesicostomy and children who had ablation.

Conclusions

Ablation of PUV or vesicostomy did not influence kidney function in our study cohort. Children with a normal nadir serum creatinine who presented early had a better outcome.     

Changes in weight and co-morbidities among adolescents undergoing bariatric surgery: 1-year results from the Bariatric Outcomes Longitudinal Database

BackgroundBariatric surgery is 1 of the few effective treatments of morbid obesity. However, the weight loss and other health-related outcomes for this procedure in large, diverse adolescent patient populations have not been well characterized. Our objective was to analyze the prospective Bariatric Outcomes Longitudinal Database (BOLD) to determine the weight loss and health related outcomes in adolescents. The BOLD data are collected from 423 surgeons at 360 facilities in the United States.MethodsThe main outcome measures included the anthropometric and co-morbidity status at baseline (n = 890) and at 3 (n = 786), 6 (n = 541), and 12 (n = 259) months after surgery. Adolescents (75% female; 68% non-Hispanic white, 14% Hispanic, 11% non-Hispanic black, and 6% other) aged 11 to 19 years were included in the present analyses.ResultsThe overall 1-year mean weight loss for those who underwent gastric bypass surgery was more than twice that of those who underwent adjustable gastric band surgery (48.6 versus 20 kg, P < .001). Similar results were found for all other anthropometric changes and comparisons within 1 year between surgery types (P < .001). In general, the gastric bypass patients reported more improvement than the adjustable gastric band patients in co-morbidities at 1 year after surgery. A total of 45 readmissions occurred among gastric bypass patients and 10 among adjustable gastric band patients, with 29 and 8 reoperations required, respectively.ConclusionsThe weight loss at 3, 6, and 12 months after surgery is approximately double in adolescent males and females who underwent gastric bypass surgery versus those who underwent adjustable gastric band surgery. Bariatric surgery can safely and substantially reduce weight and related co-morbidities in morbidly obese adolescents for ≥1 year.     

Laparoscopic Roux en-Y Gastric Bypass Using a Modified Retrocolic–Supracolic Approach: Outcomes from 300 Patients

Background

Laparoscopic Roux en-Y gastric bypass (LRYGB) achieves sustained long-term weight loss and reduced mortality in morbidly obese patients. It is routinely performed using an ante- or retrocolic approach with the jejuno-jejunostomy constructed in the infracolic compartment. We have modified the standard technique of performing LRYGB by constructing both anastomoses in the supracolic compartment. This study describes the outcomes of consecutive primary LRYGB performed using this novel retrocolic–supracolic approach.

Methods

Data were prospectively collected on consecutive primary LRYGB performed in a tertiary-referral Bariatric Centre in the United Kingdom from September 2009 to March 2013. Data included demographics, operative outcomes (duration of surgery, postoperative anastomotic leak/bleeding/reoperations), development of strictures, length of stay, excess weight loss (EWL) and resolution of diabetes mellitus.

Results

Hand-sewn LRYGB was successfully performed using the retrocolic–supracolic approach in 300 of 307 (98 %) consecutive patients (72 % female). Median (IQR) age, weight and baseline body mass index were 49 (41–56) years, 146 (134–163) kg and 52.9 (48.8–57.2) kg/m², respectively. There were 4 (1.3 %) anastomotic leaks and 8 (2.6 %) postoperative bleeds. The 30-day reoperation rate was 1.6 %. Median (IQR) hospital stay was 2 (2–2) days. Postoperative dysphagia requiring endoscopic balloon dilatation occurred in 19 (6.3 %) patients. Mean ± SD 12-month EWL was 69.9 ± 19.0 %. Within the follow-up period, 81 % of patients with type II diabetes mellitus achieved remission and 19 % reduced dosage of diabetes medication.

Conclusions

LRYGB performed using the retrocolic–supracolic approach was safe, feasible, technically advantageous and resulted in clinical outcomes akin to the standard infracolic approach.

     

Transanal Minimally Invasive Surgery for Rectal Lesions

Methods:From November 2011 through May 2016, 31 patients (21 females, 68%), with a median age of 65 years who underwent single-port TAMIS were prospectively enrolled. Mean distance from the anal verge of the rectal tumors was 9.5 cm. Seventeen patients presented with T1 cancer, 10 with large adenoma, 2 with gastrointestinal stromal tumor (GIST) and 2 with carcinoid tumor. Data concerning demographics, operative procedure and pathologic results were analyzed.Results:TAMIS was successfully completed in all cases. In 4 (13%) TAMIS was converted to standard Park''s transanal technique. Median postoperative stay was 3 days. The overall complication rate was 9.6%, including 1 urinary tract infection, 1 subcutaneous emphysema, and 1 hemorrhoidal thrombosis. TAMIS allowed an R0 resection in 96.8% of cases (30/31 cases) and a single case of local recurrence after a large adenoma resection was encountered.Conclusion:TAMIS is a safe technique, with a short learning curve for laparoscopic surgeons already proficient in single-port procedures, and provides effective oncological outcomes compared to other techniques.