Mesenchymal Stem Cells and PRP Therapy Favorize Leak Closure After Sleeve Gastrectomy in Zucker Rats.

INTRODUCTION: Sleeve gastrectomy (SG) is the most performed bariatric surgery but gastric leaks following SG occur in up to 2% of cases. Regenerative medicine is emerging as a promising field offering multiple possibilities in wound healing. We studied the efficiency of locally administered mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) on leak closure following SG in rats. METHODS: The amount of PRP and MSCs extracted from one rat was analyzed and a model of gastric leak was developed in 10-week-old male Zucker rats. Twenty-four rats underwent SG fashioned with a leak. After 24 h, a second surgery was performed. The control group was treated by peritoneal lavage and drainage only while the experimental group received an additional treatment of locally administered MSCs and PRP at the leak orifice. Analysis of the leak healing process was done by an anatomopathological examination of the stomach 1, 2, 3, and 4 weeks after SG. RESULTS: The extraction of MSCs and PRP from one rat was necessary for three recipients. Anatomopathological examination suggests that the closure of the leak orifice was faster in the experimental group. Statistical analysis revealed a significantly increased mucosae renewal and fibrosis score at the leak orifice after treatment with MSCs and PRP (p < 0.001). CONCLUSION: These results suggest that PRP and MSCs may accelerate the closure of leaks following SG in rats and may become a new tool in the treatment of human gastric leaks but more research on this topic is needed to confirm these findings.

Feasibility and Efficiency of Sutureless End Enterostomy by Means of a 3D-Printed Device in a Porcine Model.

Objective. The aim of this study is to present a 3-dimensional (3D)-printed device to simply perform abdominal enterostomy and colostomy. Summary Background Data. Enterostomy and colostomy are frequently performed during abdominal surgery. 3D-printed devices may permit the creation of enterostomy easily. Methods. The device was designed by means of a CAD (computer-aided design) software, Rhinoceros 6 by MC Neel, and manufactured using 3D printers, Factory 2.0 by Omni 3D and Raise 3D N2 Dual Plus by Raise 3D. Colostomy was scheduled on a human cadaver and on 6 Pietrain pigs to test the device and the surgical technique. Results. The test on the cadaver showed that the application of the device was easy. Test on porcine models confirmed that the application of the device was also easy on the living model. The average duration of the surgical procedure was 32 minutes (25-40 minutes). For the female pigs, return to full oral diet and recovery of a normal bowel function was observed at postoperative day 2. The device fell by itself on average on the third day. Until day 10, when euthanasia was practiced, the stoma mucosa had a good coloration indicating a perfect viability of tissues. No complications were observed. Conclusions. This is the first study that describes the use of a 3D-printed device in abdominal surgery. End-type colostomy using a 3D-printed device can be safely and easily performed in an experimental porcine model, without postoperative complications. Further studies are needed to evaluate its utility in the clinical setting.

Childhood pulmonary Langerhans cell histiocytosis: a comprehensive clinical-histopathological and BRAFV600E mutation study from the French national cohort.

Childhood pulmonary Langerhans cell histiocytosis (PLCH) is a rare disease. Its pulmonary histopathology, according to comprehensive clinical-radiological findings and BRAFV600E mutation status, has not yet been thoroughly documented. From the 167 childhood PLCH cases entered in the French National Histiocytosis Registry (1983-2016), we retrieved lung biopsies from a consecutive retrospective series of 17 patients, diagnosed when they were 2 weeks to 16 years old (median, 9.4 years), and report the clinical and histopathological findings herein. Histological analyses of biopsies (16 surgical and 1 postmortem) found the following features, alone or associated: Langerhans cell (LC) nodules with cavitation (9/17), cysts (14/17), fibrotic scars (2/17), peribronchiolar topographic distribution of the lesions (10/17), and accessory changes, like stretch emphysema (7/17). Those characteristics closely resemble those describing adult PLCH. However, unusual findings observed were 2 large nodules and a diffuse interstitial LC infiltrate. BRAFV600E mutation was detected in 4 of 12 samples tested, notably in the 3 with unusual features. In conclusion, childhood PLCH mostly shares the common histology features already described in adult PLCH, regardless of age. Because smoking is considered the major trigger in PLCH pathogenesis, the findings based on this series suggest other inducers of bronchiolar LC recruitment, especially in very young patients.

Gains and complex rearrangements of the 12q13-15 chromosomal region in ordinary lipomas: the "missing link" between lipomas and liposarcomas?

Well-differentiated liposarcomas (WDLPS) classically contain high-level amplification of 12q14-15 sequences, including the MDM2 and CDK4 genes, while lipomas are characterized by simple structural chromosome aberrations often involving HMGA2 at 12q15. Previous studies have shown that low-level gain of the 12q14-15 region, such as trisomy 12 and 12q15-24 duplication, might be sufficient for the development of minimal atypia and formation of WDLPS. Moreover, because some features, such as overexpression of HMGA2, are shared by both lipomas and WDLPS, it has been hypothesized that lipomas and WDLPS may form a genetic and morphological continuum. We report here the results of molecular cytogenetic analysis of 8 lipomas that had unusual chromosomal features resulting in gains of 12q14-15. While 3 cases had simple numerical rearrangements (trisomy 12) or structural rearrangements (unbalanced translocations with 12q gains), 5 cases were particularly intriguing because of peculiar features such as giant chromosomes, supernumerary chromosomes or neocentromeres that usually are the hallmark of WDLPS. Gain of 12q14-15 sequences including extra copies of MDM2 and CDK4 were detected by fluorescence in situ hybridization analysis in all analyzed cases but no expression of MDM2 and CDK4 was observed suggesting that these genomic imbalances had no functional consequence. We observed rearrangements of HMGA2 in 5 out 8 cases. Altogether, our results indicate that moderate gains of 12q are not always associated with a malignant phenotype, and that some intermediary forms exist between classical lipomas and classical WDLPS. Some of these intermediary forms may correspond to a genomic premalignant condition while some may have no malignant potential.

Kaposi's sarcoma in transplant and HIV-infected patients: an epidemiologic study in Italy and France.

BACKGROUND: A follow-up study was conducted in Italy and in France to compare the epidemiology of Kaposi's sarcoma (KS) between human immunodeficiency virus (HIV)-infected people and transplant recipients. METHODS: In all, 8,074 HIV-positive individuals (6,072 from France and 2,002 HIV-seroconverters from Italy) and 2,705 Italian transplant recipients (1,844 kidney transplants, 702 heart transplants, and 159 liver transplants) were followed-up between 1970 and 2004. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were computed to estimate the risk of KS, as compared to sex- and age-matched Italian and French populations. Incidence rate ratios (IRRs) were used to identify risk factors for KS. RESULTS: A 451-fold higher SIR for KS was recorded in HIV-infected subjects and a 128-fold higher SIR was seen in transplant recipients. Significantly increased KS risks were observed in HIV-infected homosexual men (IRR=9.7 in France and IRR=6.7 in Italy vs. intravenous drug users), and in transplant recipients born in southern Italy (IRR=5.2 vs. those born in northern Italy). HIV-infected patients with high CD4+ cell counts and those treated with antiretroviral therapies had reduced KS risks. In relation to duration of immunosuppression, KS occurred earlier in transplant patients than in HIV-seroconverters. CONCLUSIONS: This comparison highlighted that the risk of KS was higher among HIV-infected individuals than in transplant recipients, and that different co-factors are likely to influence the risk of KS. Moreover, the early KS occurrence in transplant recipients could be associated with different patterns of progressive impairment of the immune function.