The successful management of a Bronchoesophageal fistula after lung transplantation: a case report

We describe an unprecedented, disastrous complication after bilateral lung transplantation (BLT), a bilateral bronchial dehiscence with a right bronchoesophageal fistula leading to life‐threatening septic shock. We also report the successful endoscopic management of this complication by double stenting and stress the efficacy of the multidisciplinary approach to this critical case.     

Locally-advanced prostate cancer in the elderly: should we revisit our treatment paradigms?

Prostate cancer (PCa) represents the most common malignancy in adult males with an estimated number of 280 000 newly diagnosed cases only in the United States in 2015.1 Due to the introduction of PSA in clinical practice, the majority of the patients are currently diagnosed with organ-confined and sometimes indolent disease. However, a nonnegligible proportion of individuals are still diagnosed with locally-advanced tumors. In their recently published article, Bekelman et al.2 focused on elderly patients with locally-advanced PCa in the attempt to determine the best treatment approach in this patient category, and concluded that, even in these individuals, androgen deprivation therapy (ADT) plus radiotherapy (RT) may confer a survival benefit relative to ADT alone. The importance of the current article resides in the fact that it focuses on a patient population that has not been, or has been only scarcely, included in previous studies on the same topic.The survival benefit of RT plus ADT versus ADT alone in patients with locally-advanced PCa has been recently demonstrated by two randomized controlled trials (RCTs).3,4 Specifically, Widmark et al. recruited 875 patients from 47 Scandinavian centers who were randomized to receive either ADT or ADT plus RT.3 Inclusion criteria for this study were age ≤75 and a life expectancy ≥10 years. According to this trial, the 10-year cancer-specific mortality rate was 23.9% in the ADT group relative to 11.9% in the ADT plus RT group. The same study demonstrated a slightly higher, but still acceptable, proportion of urinary, rectal and sexual problems in the latter group of patients. Similarly, Warde et al.4 evaluated the outcomes of 1205 individuals randomly assigned to be treated either with ADT or with ADT plus RT. Patients aged ≤80 years and with an Eastern Cooperative Oncology Group performance status between 0 and 2 were included. At 7 years, an 8% overall survival benefit was observed in the ADT plus RT group relative to patients receiving ADT alone. As in the previous study, gastrointestinal toxicities were most frequent in the ADT plus RT group.While both of these RCTs represent well-designed and well-conducted studies supporting the effectiveness of ADT plus RT in locally-advanced PCa, their strict inclusion criteria may limit the applicability of their findings to the general population. To overcome this issue and provide further evidences supporting the role of ADT plus RT in patients with high-risk PCa, Bekelman et al.2 used a population-based (SEER-Medicare) dataset to extrapolate three different groups of patients with locally-advanced PCa diagnosed between 1995 and 2007: (1) the RCT cohort (n = 12.924), consisting of patients selected according to the same inclusion criteria defined by the two previously cited studies; (2) the elderly cohort (n = 14.340), consisting of men aged between 76 and 85 years with locally-advanced PCa; (3) the screen-detected cohort (n = 4277), consisting of patients aged between 65 and 85 years with high-risk clinically undetectable disease. Besides standard survival analysis, the authors also adopted two statistical methodologies, namely the propensity score approach and instrumental variable analysis in order to adjust for possible confounders. In all of the three scenarios (unadjusted, propensity-score and instrumental variable adjusted), ADT plus RT resulted in a significant increase both in cancer-specific and overall mortality rates as compared to ADT alone. Interestingly, the survival benefit was observed not only in the RCT cohort, but also in the elderly and in the screen-detected ones. In consequence, this study provides evidences to expand the indications for ADT plus RT also to these patients. This is even more important when considering that, despite the potential survival benefits, older patients with locally-advanced PCa are less likely to receive local therapies relative to their younger counterparts.5However, while the population-based nature of this study may support the generalizability of its findings, it also represents a potential limitation that should be taken into account when interpreting the results. As correctly stated by the authors, several important data, such as total PSA and radiation dose/field, were missing. The retrospective nature of the dataset along with the risk of a misclassification bias also represents a limitation. In addition, no information was provided regarding the toxicities of ADT plus RT versus ADT alone and whether differences in the rate of side effects existed between the three groups. Finally, the oncological outcomes and morbidities of ADT plus RT in locally-advanced PCa should also be compared to those of radical prostatectomy with or without adjuvant RT, especially in carefully selected patients with a life expectancy ≥10 years.In conclusion, the study by Bekelman et al.2 adds important evidences regarding the oncological effectiveness of ADT plus RT relative to ADT alone in locally-advanced PCa even in older individuals. However, the clinical applicability of their findings should be further corroborated by prospective randomized trials focusing on this patient category.     

Laparoscopic Radiofrequency Thermal Ablation for Uterine Adenomyosis

Background and Objectives:

Symptomatic uterine adenomyosis, unresponsive to medical therapy, is a challenging condition for patients who desire to preserve their uterus. This study was an evaluation of the feasibility and efficacy of laparoscopic radiofrequency thermal ablation of symptomatic nodular uterine adenomyosis.

Methods:

Fifteen women with symptomatic nodular adenomyosis, who had no plans for pregnancy but declined hysterectomy, underwent radiofrequency thermal ablation. Ultrasonography was performed at baseline and at postoperative follow-ups at 3, 6, 9, and 12 months. The impact of uterine adenomyosis–related symptoms was assessed according to the visual analog scale.

Results:

The median number of nodular lesions treated per patient was 1 (range, 1–2). The median baseline volume of the adenomyosis area was 60 cm³ (range, 18–128). The median reduction in volume was 32, 49.4, 59.6, and 65.4% at 3, 6, 9, and 12 months, respectively. A significant progressive improvement in the symptoms score was observed at the 4 follow-ups.

Conclusion:

In this study, laparoscopic radiofrequency thermal ablation reduced uterine adenomyosis–related symptoms and volume, with significant relief of symptoms.     

AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs

Phenotypic changes induced by extracellular vesicles have been implicated in mesenchymal stromal cell–promoted recovery of AKI. MicroRNAs are potential candidates for cell reprogramming toward a proregenerative phenotype. The aim of this study was to evaluate whether microRNA deregulation inhibits the regenerative potential of mesenchymal stromal cells and derived extracellular vesicles in a model of glycerol-induced AKI in severe combined immunodeficient mice. We generated mesenchymal stromal cells depleted of Drosha to alter microRNA expression. Drosha-knockdown cells produced extracellular vesicles that did not differ from those of wild-type cells in quantity, surface molecule expression, and internalization within renal tubular epithelial cells. However, these vesicles showed global downregulation of microRNAs. Whereas wild-type mesenchymal stromal cells and derived vesicles administered intravenously induced morphologic and functional recovery in AKI, the Drosha-knockdown counterparts were ineffective. RNA sequencing analysis showed that kidney genes deregulated after injury were restored by treatment with mesenchymal stromal cells and derived vesicles but not with Drosha-knockdown cells and vesicles. Gene ontology analysis showed in AKI an association of downregulated genes with fatty acid metabolism and upregulated genes with inflammation, matrix-receptor interaction, and cell adhesion molecules. These alterations reverted after treatment with wild-type mesenchymal stromal cells and extracellular vesicles but not after treatment with the Drosha-knockdown counterparts. In conclusion, microRNA depletion in mesenchymal stromal cells and extracellular vesicles significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of microRNAs in recovery after AKI.     

Enzyme replacement therapy in juvenile glycogenosis type II: a longitudinal study

Glycogenosis type II, a genetic muscle-wasting disorder, results in a spectrum of clinical phenotypes. Enzyme replacement therapy is effective in the infantile form of the disease, while little is known about its effectiveness in late-onset disease, especially in juvenile patients. The purpose of this retrospective cohort study was to assess the long-term effects of enzyme replacement therapy (ERT) in juvenile glycogenosis type II (GSDII). Eight Italian juvenile GSDII patients, receiving biweekly infusions of 20 mg/kg recombinant human α-glucosidase for at least 72 months, were enrolled (median age at therapy start was 11.8 years). Six-minute walk test (6MWT) and forced vital capacity (FVC), measured in upright position, were chosen as the principal outcome measures. Global motor disability (modified Walton scale (WS)), muscle enzymes levels [creatine phosphokinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT)] and body mass index (BMI) were also analysed both at baseline (therapy start) and annually afterwards. At baseline, most patients (six out of eight) did not show muscle function impairment (WS?≤?2). The performance at 6MWT showed a slight improvement during follow-up as well as FVC. Muscle enzymes levels showed a clear decrease after the 1st year of treatment while remained stable afterwards. An overall decrease in BMI was also observed during follow-up, although at the individual level, trends were variable. Conclusion: ERT is effective in stabilising both motor and lung functions in juvenile patients with GSDII, possibly slowing down the rate of disease progression. Randomised controlled trials are needed to understand whether early treatment allows juvenile patients to reach adulthood with a more beneficial residual muscular function than untreated patients.     

Ventral stream sensitivity in “healthy” preterm-born adolescents: Psychophysical and neuropsychological evaluation

Background

Deficits of motion processing have been reported in premature and very low birth-weight subjects during infancy, childhood and adolescence. Less is known about ventral stream functioning in preterms.

Aim

The aim of this study is to investigate ventral stream functioning in a sample of “healthy” adolescents born preterm with normal outcome and without brain damage.

Study design

We enrolled thirty preterm-born adolescents (mean age: 14.2 years, mean gestational age 28.9 weeks, mean birth weight 1097 g), and 34 age-matched term-born controls (mean age: 14.5 years). All subjects were administered a psychophysical test known as “Form Coherence Task” and a comprehensive standardized battery of neuropsychological tests suitable for investigating ventral stream functioning including Street Completion Test, Poppelreuter–Ghent Test and the first part of the Visual Object and Space Perception (VOSP) battery. Dorsal stream visual functioning was investigated by the second part of the VOSP.

Results

Preterm (PT) subjects showed the same results in all “ventral” tasks with respect to full-term controls without any correlation to gestational age or birth weight. We found a significant negative correlation between Form Coherence Task and Letters Task (p = .014) and between Form Coherence and Silhouette Tasks (p = .017). No correlation was observed between Form Coherence Task and Street and Ghent Tests. A statistical difference was instead found between PTs and controls in two tasks of the VOSP battery that mostly involve the dorsal stream.

Conclusions

Preterm birth per se (in absence of evident brain lesions) is not sufficient to compromise the development of ventral pathway.