Creation of Tissue-Engineered Urethras for Large Urethral Defect Repair in a Rabbit Experimental Model.

Introduction: Tissue engineering is a potential source of urethral substitutes to treat severe urethral defects. Our aim was to create tissue-engineered urethras by harvesting autologous cells obtained by bladder washes and then using these cells to create a neourethra in a chronic large urethral defect in a rabbit model. Methods: A large urethral defect was first created in male New Zealand rabbits by resecting an elliptic defect (70 mm2) in the ventral penile urethra and then letting it settle down as a chronic defect for 5-6 weeks. Urothelial cells were harvested noninvasively by washing the bladder with saline and isolating urothelial cells. Neourethras were created by seeding urothelial cells on a commercially available decellularized intestinal submucosa matrix (Biodesign® Cook-Biotech®). Twenty-two rabbits were divided into three groups. Group-A (n = 2) is a control group (urethral defect unrepaired). Group-B (n = 10) and group-C (n = 10) underwent on-lay urethroplasty, with unseeded matrix (group-B) and urothelial cell-seeded matrix (group-C). Macroscopic appearance, radiology, and histology were assessed. Results: The chronic large urethral defect model was successfully created. Stratified urothelial cultures attached to the matrix were obtained. All group-A rabbits kept the urethral defect size unchanged (70 ± 2.5 mm2). All group-B rabbits presented urethroplasty dehiscence, with a median defect of 61 mm2 (range 34-70). In group-C, five presented complete correction and five almost total correction with fistula, with a median defect of 0.3 mm2 (range 0-12.5), demonstrating a significant better result (p = 7.85 × 10-5). Urethrography showed more fistulas in group-B (10/10, versus 5/10 in group-C) (p = 0.04). No strictures were found in any of the groups. Group-B histology identified the absence of ventral urethra in unrepaired areas, with squamous cell metaplasia in the edges toward the defect. In group-C repaired areas, ventral multilayer urothelium was identified with cells staining for urothelial cell marker cytokeratin-7. Conclusions: The importance of this study is that we used a chronic large urethral defect animal model and clearly found that cell-seeded transplants were superior to nonseeded. In addition, bladder washing was a feasible method for harvesting viable autologous cells in a noninvasive way. There is a place for considering tissue-engineered transplants in the surgical armamentarium for treating complex urethral defects and hypospadias cases.

Long-term outcomes of adult-size and size-matched kidney transplants in small pediatric recipients.

INTRODUCTION: Adult-size kidneys are usually used for kidney transplantation in small pediatric recipients, but the influence of graft size in transplant outcome remains controversial. Our aim is to compare long-term transplant outcomes of using adult-size and size-matched kidneys in small pediatric recipients. MATERIALS AND METHODS: Since 1999, 61 of 226 kidney transplants were achieved in recipients weighing <20 kg with 5 years of follow-up. Patients were analyzed according to the graft size received: (group-A) adult-size (n = 32), (group-B) size-matched (n = 29). Kidney size (KS), glomerular filtration rate (GFR) proteinuria and rejection were compared between groups at transplant time (T0), at one (T1), two (T2), five years (T5), and at the end of the follow-up (TF) (median follow-up 8.47(0-17) years). Graft and patient survival were determined and compared between groups. RESULTS: Mean KS was significantly different between groups at T0 (A:11.3 ± 1.1 cm, B:8.8 ± 0.9 cm), (pT0<0.01), group-B evidenced graft growth, reaching similar sizes to group-A at T5 (A:11.7±1 cm, B:11.2±1 cm; pT5 = 0.13) and TF (A:12.2 ± 1.1 cm, B:12.4 ± 1.2 cm; pTF = 0.63), and group-A had a slight graft growth at TF (pT0-TF<0.01). Mean Schwartz-GFR at T0 was greater in group-A (138 ± 33 ml/min/1.73 m2) than group-B (109 ± 34 mL/min/1.73 m2) (pT0 = 0.01); during follow-up, it evidenced a reduction in group-A (T5:90 ± 27, TF:71 ± 24 mL/min/1.73 m2; pT0-T5<0.01; pT0-TF<0.01), meanwhile in group-B was stable until T5 (104 ± 33 mL/min/1.73 m2; pT0-T5 = 0.54), declining at TF (76 ± 31 mL/min/1.73 m2; pT0-TF<0.01); with no significant differences at T1, T2, T5, and TF between groups. Similar results were observed in mean Filler-GFR of both groups (Figure). Proteinuria and episodes of rejection were no significantly different between groups during the follow-up (p > 0.01; p = 0.23). Graft and patient survival at 5 and 10 years did not show significant differences (p = 0.45; p = 0.10). DISCUSSION: Despite the initial kidney size difference between groups, we have demonstrated that they tended to the same size during the follow-up. Adult-size kidneys presented a slight size increase in the long-term, suggesting that they have some growth potential in small recipients, in contrast to previous literature. Mean GFR between groups showed no significant differences in the long-term, suggesting that optimal graft perfusion and function can be achieved despite the size of the graft. We have demonstrated that there were no significant differences in long-term graft and patient survival; this results were similar to the most recent literature about this topic and different from the 90-2000s decades literature. CONCLUSIONS: Adult-size kidneys may be transplanted to small recipients (<20 kg) with comparable outcomes to size-matched kidneys, with no significant differences in long-term KS, GFR, proteinuria, rejection, graft or patient survival.

Predicting Full Enteral Feeding in the Postoperative Period in Infants with Congenital Diaphragmatic Hernia.

Introduction The objective of the study is to examine the factors associated with time to achieve full enteral feeding after repair of congenital diaphragmatic hernia. Materials and Methods Demographic, clinical, and therapeutic data were retrospectively assessed, and uni- and multivariate Cox regression were performed to examine factors predictive of achieving full enteral feeding that was defined as time to achieve120 mL/kg/d after surgical repair. Results Of 78 infants, 66 underwent intervention before hospital discharge. All infants who survived had reached full enteral feeding at the time of hospital discharge by a median of 22 days (range: 2-119 days) after surgery and 10 days (range: 1-91) after initiation of postoperative enteral feedings. Independent risk factors associated with a longer time to reach full enteral feeding achievement included gastroesophageal reflux and days of antibiotics in the postoperative period. Daily stool passage preoperatively predicted earlier enteral tolerance. Conclusion Infants who survive congenital diaphragmatic hernia generally are able to achieve full enteral feedings after surgical repair. A longer time to full feeding is needed in the most severe cases, but some specific characteristics can be used to help identify patients at higher risk. Although some of these characteristics are unavoidable, others including rational antibiotic usage and active gastroesophageal reflux prevention and treatment are feasible and may improve enteral tolerance.

Portal Cavernoma in the Era of Mesoportal Shunt (Rex) and Liver Transplant in Children.

OBJECTIVE: The mesoportal shunt (MPS) and liver transplantation (LT) have changed the scenario of extrahepatic portal vein obstruction (EHPVO) since the MPS, the only "curative" technique, can now be offered in asymptomatic patients and also thrombotic complications of LT have increased the incidence of EHPVO. MATERIAL AND METHODS: A retrospective study of patients undergoing surgery for EHPVO was conducted between 1990 and 2015. An analysis was done for the shunt permeability and clinical evolution over time. RESULTS: Of the 73 children with EHPVO, 39 were operated (12 posttransplant and 27 idiopathic). The median age at surgery was 9.36 years (range, 1.60-17.42 years). The MPS was the technique of choice; it was offered in 21 patients but eventually could be performed in only 18 (9 posttransplant and 9 idiopathic). The results of MPS were better in idiopathic (just one thrombosis successfully converted into mesocaval bypass). In the MPS after LT (n = 9), six shunts are permeable, two became thrombotic (one patient requiring retransplantation), and one late thrombosis occurred and the patient died eventually because of gastrointestinal bleeding. In the remaining patients (21 out of the 39), MPS was not performed because of intrahepatic cavernoma, portal vein hypoplasia, or insufficient length of vascular graft (especially in left lateral segment graft LT, since the portal vein is usually located in the right upper quadrant). They underwent 10 distal splenorenal shunts (DSRS) (1 posttransplant and 9 idiopathic), 5 proximal splenorenal shunts (PSRS) (1/4), 6 mesocaval shunts (1/5), and 1 modified Sugiura procedure. The results with DSRS have been favorable (one thrombosis, converted into mesocaval bypass). In the PSRS no thrombosis was identified and in the mesocaval shunt one early thrombosis occurred. Posttransplantation group had higher risk of shunt thrombosis, regardless of the surgical technique (chi-square, 0.021). The total increase of platelets after 6 months was not different in MPS as compared with other surgical techniques (analysis of variance, 0.110). CONCLUSIONS: The MPS is the technique of choice in EHPVO for idiopathic thrombosis as well as secondary to LT. Not all cases are favorable for MPS, so the surgeon must consider the possibility of alternative techniques for EHPVO. The results in terms of shunt patency are much better in idiopathic cavernoma that posttransplant patients.

Congenital Portosystemic Shunts: Clinic Heterogeneity Requires an Individual Management of the Patient.

INTRODUCTION: Congenital portosystemic shunt (CPSS) is a rare entity without insufficiency in treatment issues. The aim of this article is to show our experience in the heterogeneity of this condition. MATERIAL AND METHODS: A retrospective study of 25 CPSS in the period 1995 to 2014 was conducted. Description of the morphology, clinical impact, and treatment is given. RESULTS: According to the imaging techniques (IT), the shunt was apparently intrahepatic in 14 patients, extrahepatic in 10 patients, and mixed in 1 patient. In 14 children, IT showed hepatic portal circulation. In total shunts in which radiological examination was performed, invasive radiological techniques were able to demonstrate intrahepatic portal vein. In other patients, it was not investigated as they are asymptomatic. A child presented multiorgan failure with fulminant hepatic failure at birth. The shunt was radiologically closed and clinical impairment reversed rapidly. He is now asymptomatic with no longer images of CPSS in ultrasound scan controls. Also, seven children are asymptomatic at this time and are monitored periodically. Seven children had prenatal diagnosis, in five the shunt closed spontaneously. Nine children were symptomatic in their evolution (hyperammonemia, regenerative nodules, cholestasis, gastrointestinal bleeding). Of these, in five we performed balloon test occlusion, tolerated in all patients, followed by radiological closure. In our experience, the advancement of interventional radiology techniques avoided surgery to close the shunt. CONCLUSIONS: Morphologically, the CPSS is extremely heterogeneous, with multiple possible connections established. CPSS has multiple clinical presentations, from asymptomatic patients to acute liver failure. The therapeutic approach should be individualized and therefore held in overspecialized centers.

Mesohepatectomy for Centrally Located Tumors in Children.

INTRODUCTION: Central hepatectomy or mesohepatectomy (MH) is a complex surgical technique rarely used in children. It is indicated in central tumors to preserve functioning liver mass avoiding an extended right hepatectomy. The purpose of this article is to analyze our experience with this technique. METHODS: We reviewed five patients who underwent MH in the period from 2008 to 2014. Diagnoses were hepatoblastoma PRETEXT III (two cases), hepatic embryonal sarcoma (one case), focal nodular hyperplasia (one case), and vascular tumor with rapid growth in a newborn causing an acute liver failure, compartment syndrome, and multiple organ failure (one case). In all cases, the tumor was centrally located, including the segment IVb, with large displacement of the hepatic pedicle in two cases. RESULTS: MH was standard in three cases and under total vascular exclusion in two cases. All children are alive with a mean follow-up of 38 (6-70) months. None of the children required reoperation because of bleeding. One child developed a biliary fistula in the cutting area that closed spontaneously. The newborn with the vascular tumor required the placement of a Gore-Tex patch (W. L. Gore & Associates, Inc, Flagstaff, Arizona, United States) to relieve the compartment syndrome. He subsequently underwent partial embolization of the tumor and MH under vascular exclusion. CONCLUSIONS: In selected patients, MH is an alternative to trisegmentectomy and should be available in advanced pediatric hepatobiliary units.

Surgical Rehabilitation Techniques in Children with Poor Prognosis Short Bowel Syndrome.

Intestinal failure (IF) requires a multidisciplinary management based on nutritional support, surgical and medical rehabilitation, and transplantation. The aim of this study is to review our experience with surgical rehabilitation techniques (SRTs: enteroplasty, Bianchi, Serial Transverse Enteroplasty Procedure [STEP]) in patients with short bowel syndrome (SBS) and poor prognosis due to complex abdominal pathology. We performed a single-center retrospective study of patients with IF evaluated for intestinal transplantation in the Intestinal Rehabilitation Unit who underwent an SRT. Nonparametric tests were used for statistical analysis.A total of 205 patients (107 males/98 females) with mean age of 25 ± 7 months were assessed for IF. A total of 433 laparotomies were performed on 130 patients including intestinal resection, enteroplasties, adhesiolysis, and transit reconstruction. SRT were performed in 22 patients: 12 enteroplasties, 8 STEPs, and 4 Bianchi procedures. All patients were parenteral nutrition (PN) dependent with different stages of liver disease: mild (13), moderate (5), and severe (4). The adaptation rate for patients who underwent enteroplasty, STEP, and Bianchi were 70, 63, and 25%, respectively, although the techniques are not comparable. Overall, intestinal adaptation was achieved in nine (41%) patients, and four (18%) patients showed significant reduction of PN needs. One child did not respond to SRT and did not meet transplantation criteria. The remaining eight (36%) patients were included on the waiting list for transplant: four were transplanted, two are still on the waiting list, and two died. Better outcomes were observed in milder cases of liver disease (mild 77%, moderate 40%, severe 25%) (p < 0.05). Conversely, a trend toward a poorer outcome was observed in cases with ultrashort bowel (p > 0.05). One patient required reoperation after a Bianchi procedure due to intestinal ischemia and six needed further re-STEP or adhesiolysis procedure several months later. The median follow-up was 62 (3-135) months. Overall mortality was 19%, and was due to end-stage liver disease and/or central venous catheter-related sepsis. SRT led to intestinal adaptation in a significant number of patients with poor prognosis SBS referred for intestinal transplantation. However, SRT requires a multidisciplinary evaluation and should be attempted only in suitable cases. Careful assessment and optimal surgical timing is crucial to obtain a favorable outcome.

Quality of Life in Female Epispadias.

Introduction and Aim Female epispadias is a rare congenital anomaly associated with significant urinary incontinence. This study aims to evaluate the results of its treatment in terms of continence, sexuality, and impact of incontinence on quality of life. Materials and Methods We retrospectively reviewed nine patients (5-39 years) treated of female epispadias in our hospital during the period 1976-2013. Urinary continence (ICIQ-SF), sexuality, impact of incontinence on quality of life (Potenziani-14-CI-IO-2000-QOL), and overall quality of life (SF-36) were evaluated. Results All nine women were treated by bladder neck reconstruction (Young-Dees-Leadbetter) and genitoplasty; four received 2.5 (R = 1-5) endoscopic bladder neck injections; one required enterocystoplasty, urinary diversion, and bladder neck closure because of persistent incontinence; five performed pelvic floor rehabilitation; and two took anticholinergics. Three achieved continence; five had mild urinary incontinence; and 1 had moderate urinary incontinence and was awaiting an endoscopic injection. Of the seven who were older than 18 years, five answered the questionnaires of quality of life and sexuality. All had a general quality of life (SF-36) that does not differ from the normal population and had a slight impact (7 [0-15] points) of incontinence on quality of life (Potenziani-14-CI-IO-QOL-2000). Four had a normal sex life, and the fifth had lack of self-confidence due to her incontinence. Conclusion Patients with female epispadias have good long-term results regarding quality of life and sexuality, despite having some degree of urinary incontinence.