A Retrospective Registry Study Evaluating the Long-Term Efficacy and Safety of Superficial Radiation Therapy Following Excision of Keloid Scars

BACKGROUND: Surgical treatment of keloid scars is associated with an approximately 70% recurrence rate at the excision site. OBJECTIVE: We sought to assess keloid recurrence rates when superficial radiation therapy (SRT) was applied following surgical excision. METHODS: Medical records were reviewed of subjects treated for keloid scars followed by SRT (SRT-100™; Sensus Healthcare, Boca Raton, Florida) using a biologically effective dose (BED) of 30Gy and for whom the required retrospective data was available. Eligible subjects (N=61) were treated for 96 keloid scars with SRT. Subjects were male (48%) and female (52%) with a mean age of 38.87 years. Subjects were treated for ≥1 keloid scars following removal by sutured excision (93%) or tangential excision with secondary intention technique (7%). Almost all subjects (98%) received BED 30Gy with irradiation scheme of three 6Gy SRT treatments on Days 1, 2 and 3 following surgery. Mean energy of 100KV (73%) or 70KV (27%) were applied. RESULTS: Ten treated keloidectomy sites (10.4%) had recurrences (i.e., presence of any new tissue growth on the surgical scar) within 12 months increasing to 11 (12.7%) at 18 months. Kaplan-Meier survival probability cure rate was 85.6% from 24 months post-SRT treatment onwards. Transient hyperpigmentation was the most frequent adverse event and there were no malignancies in the treatment area during follow-up evaluations. CONCLUSIONS: SRT with a BED value of 30 Gy delivered to keloidectomy excision sites immediately following excision was well-tolerated and resulted in markedly fewer long-term recurrences than reported following keloidectomy alone. Most keloid scar recurrences occurred within one year. There were no malignancies during follow-up evaluations.     

Is residual renal function and better phosphate control in peritoneal dialysis an answer for the lower prevalence of valve calcification compared to hemodialysis patients?

Introduction

Cardiac valve calcification (CVC) has long been regarded as a consequence of abnormal calcium–phosphate metabolism in uremic patient associated with increased cardiovascular mortality in this population. We evaluated the association between residual renal function (RRF), phosphate level and valve calcification in peritoneal dialysis (PD) and hemodialysis (HD) patients.

Methods

We studied 30 stable PD patients (60 % males; mean age 57 ± 12.36 years) and 34 HD patients (58.8 % males; mean age 50.8 ± 10.4 years) on renal replacement therapy (RRT) from 6 up to 36 months. The presence of CVC was assessed by standard bi-dimensional echocardiography. RRF was calculated by standard technique.

Results

Valve calcification was more frequently found in HD compared to PD patients (70.6 vs 29.4 %, p = 0.007). Significantly lower phosphate [1.38 ± 0.41 versus 1.99 ± 0.35 mmol/L (p < 0.0001)], a higher RRF [4.09 ± 2.09 ml/min vs 0.62 ± 0.89 ml/min (p < 0.0001)], and older age [57 ± 12.36 years vs 50.8 ± 10.4 years (p = 0.033)] were observed in PD as compared to HD patients. The logistic regression analysis for the presence of valve calcification when adjusted for age and diabetes, with type of therapy, serum phosphate, RRF, CRP, and serum albumin as variables in the model, revealed significant association between the presence of valve calcification and age and RRF. The correlation between phosphate levels and RRF was even stronger in PD patients than in HD patients (r = ?0.704; p = 0.0001) vs (r = ?0.502; p = 0.02).

Conclusions

Our study shows that the residual renal function in PD patients contributes significantly to the maintenance of phosphate balance and may explain the lower prevalence of valve calcification in PD patients compared with HD patients in the period up to first 3 years under renal replacement therapy.     

Review of stoma site and midline incisional hernias after stoma reversal

Background

The incidence of incisional hernias after stoma reversal is not well reported. The aim of this study was to systematically review the literature reporting data on incisional hernias after stoma reversal. We evaluated both the incidence of stoma site and midline incisional hernias.

Methods

A systematic review identified studies published between January 1, 1980, and December 31, 2012, reporting the incidence of incisional hernia after stoma reversal at either the stoma site or at the midline incision (in cases requiring laparotomy). Pediatric studies were excluded. Assessment of risk of bias, detection method, and essential study-specific characteristics (follow-up duration, stoma type, age, body mass index, and so forth) was done.

Results

Sixteen studies were included in the analysis; 1613 patients had 1613 stomas formed. Fifteen studies assessed stoma site hernias and five studies assessed midline incisional hernias. The median (range) incidence of stoma site incisional hernias was 8.3% (range 0%–33.9%) and for midline incisional hernias was 44.1% (range 8.7%–58.1%). When evaluating only studies with a low risk of bias, the incidence for stoma site incisional hernias is closer to one in three and for midline incisional hernias is closer to one in two.

Conclusion

Stoma site and midline incisional hernias are significant clinical complications of stoma reversals. The quality of studies available is poor and heterogeneous. Future prospective randomized controlled trials or observational studies with standardized follow-up and outcome definitions/measurements are needed.     

Tumor mutational load predicts time to first treatment in chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis beyond the CLL international prognostic index

Next-generation sequencing identified about 60 genes recurrently mutated in chronic lymphocytic leukemia (CLL). We examined the additive prognostic value of the total number of recurrently mutated CLL genes (i.e., tumor mutational load [TML]) or the individually mutated genes beyond the CLL international prognostic index (CLL-IPI) in newly diagnosed CLL and high-count monoclonal B-cell lymphocytosis (HC MBL). We sequenced 59 genes among 557 individuals (112 HC MBL/445 CLL) in a multi-stage design, to estimate hazard ratios (HR) and 95% confidence intervals (CI) for time-to-first treatment (TTT), adjusted for CLL-IPI and sex. TML was associated with shorter TTT in the discovery and validation cohorts, with a combined estimate of continuous HR = 1.27 (CI:1.17-1.39, P = 2.6 × 10⁻⁸; c-statistic = 0.76). When stratified by CLL-IPI, the association of TML with TTT was stronger and validated within low/intermediate risk (combined HR = 1.54, CI:1.37-1.72, P = 7.0 × 10⁻¹⁴). Overall, 80% of low/intermediate CLL-IPI cases with two or more mutated genes progressed to require therapy within 5 years, compared to 24% among those without mutations. TML was also associated with shorter TTT in the HC MBL cohort (HR = 1.53, CI:1.12-2.07, P = .007; c-statistic = 0.71). TML is a strong prognostic factor for TTT independent of CLL-IPI, especially among low/intermediate CLL-IPI risk, and a better predictor than any single gene. Mutational screening at early stages may improve risk stratification and better predict TTT.     

Giant retroperitoneal leiomyosarcoma. Multiorgan block removal

INTRODUCTION

Retroperitoneal tumors are rare, mostly malignant. Locally aggressive, and more frequent in women in their 5th decade of life. Its symptoms are nonspecific, including abdominal pain and palpable mass. To diagnosis is helpful computed tomography and biopsy. It needs surgery for absolute healing.

PRESENTATION OF CASE

67 years old man was admitted with back pain and fever. Abdominal imaging tests showed a 15 cm abdominal mass without clear organodependencia. Endoscopy with biopsies evidenced mesenchymal neoplasia of undetermined origin. In surgery we confirm its resecability and was necessary multiorgan resection. Pathologic diagnosis: well differentiated retroperitoneal leiomyosarcoma. Started adjuvant radiotherapy. In subsequent tests showed the presence of liver metastases.

DISCUSSION

Retroperitoneal tumors are developed from nerve, vascular, muscular, connective, supportive and fibroareolar tissue from this space. Its size does not modificate survival or resectability. We used TC and biopsy for its diagnose. Adjuvant therapy does not affect survival or quality of life, surgery remains the only curative option. Locoregional recurrence is the most influential figure in the prognosis. A large percentage of patients required a second surgery (between 45 and 82%).

CONCLUSION

The only curative option of retroperitoneal sarcomas is surgery, which usually requires multiple organ resection. Chemotherapy and radiotherapy are mostly a surgical supplement. Chemotherapy has not shown significant increase in survival.     

Subpicomolar diphenyleneiodonium inhibits microglial NADPH oxidase with high specificity and shows great potential as a therapeutic agent for neurodegenerative diseases

Activation of microglial NADPH oxidase (NOX2) plays a critical role in mediating neuroinflammation, which is closely linked with the pathogenesis of a variety of neurodegenerative diseases, including Parkinson's disease (PD). The inhibition of NOX2‐generated superoxide has become an effective strategy for developing disease‐modifying therapies for PD. However, the lack of specific and potent NOX2 inhibitors has hampered the progress of this approach. Diphenyleneiodonium (DPI) is a widely used, long‐acting NOX2 inhibitor. However, due to its non‐specificity for NOX2 and high cytotoxicity at standard doses (µM), DPI has been precluded from human studies. In this study, using ultra‐low doses of DPI, we aimed to: (1) investigate whether these problems could be circumvented and (2) determine whether ultra‐low doses of DPI were able to preserve its utility as a potent NOX2 inhibitor. We found that DPI at subpicomolar concentrations (10^?14 and 10^?13 M) displays no toxicity in primary midbrain neuron‐glia cultures. More importantly, we observed that subpicomolar DPI inhibited phorbol myristate acetate (PMA)‐induced activation of NOX2. The same concentrations of DPI did not inhibit the activities of a series of flavoprotein‐containing enzymes. Furthermore, potent neuroprotective efficacy was demonstrated in a post‐treatment study. When subpicomolar DPI was added to neuron‐glia cultures pretreated with lipopolysaccharide, 1‐methyl‐4‐phenylpyridinium or rotenone, it potently protected the dopaminergic neurons. In summary, DPI's unique combination of high specificity toward NOX2, low cytotoxicity and potent neuroprotective efficacy in post‐treatment regimens suggests that subpicomolar DPI may be an ideal candidate for further animal studies and potential clinical trials. GLIA 2014;62:2034–2043