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Complications after Hypospadias Correction: Prognostic Factors and Impact on Final Clinical Outcome

PURPOSE: The purpose of this study was to analyze the influence of patient and treatment characteristics on the occurrence of complications after hypospadias correction and the impact of complications on final clinical outcome. MATERIALS AND METHODS: The study cohort consisted of 205 hypospadias patients who had surgery in the Medical Centre Leeuwarden (1996-2011). Patient and treatment characteristics were hypospadias severity (preoperative meatal location and chordee), number of planned surgeries, reconstruction technique, operation year, and patient's age at the time of surgery. The final clinical outcome was measured with the Hypospadias Objective Scoring Evaluation (HOSE) (maximum score = 16) and compared between patients with and without complications. RESULTS: Sixty-four patients (31%) had complications, most of which were fistulas (n = 40). An increased complication risk was seen in patients with severe hypospadias (preoperative proximal meatus or chordee), multistage reconstruction, reconstruction techniques other than Mathieu, and surgeries performed before 2005. Uncomplicated treatment resulted only in a marginally higher HOSE (15.7) compared with complicated treatment (15.4). Fistulas and multiple complications reduced clinical outcome more (15.3 and 14.9, respectively), while urinary tract infections, wound dehiscence, or prepuce related complications did not (16.0, 16.0, and 15.8, respectively). CONCLUSION: The complication risk after hypospadias correction is influenced by hypospadias severity and type and year of reconstruction. Certain, but not all complications diminish final clinical outcome

Patient Satisfaction with Surgical Outcome after Hypospadias Correction

Item does not contain fulltextBackground: Hypospadias is a congenital malformation in which surgical correction is indicated in most cases. Postoperative patient satisfaction is important because of its influence on the child's psychological development. Objective: To evaluate patient satisfaction with surgical outcome after hypospadias correction, comparison with physician satisfaction, and the influence of patient and treatment characteristics on satisfaction. Design, setting, and participants: Seventy-four patients who had hypospadias surgery between 1996 and 2010 in Medical Centre Leeuwarden participated in the study. Measurements: Patient/parent and physician satisfaction scores were measured using a standardised hypospadias satisfaction questionnaire (maximum score 32), and clinical outcome using the Hypospadias Objective Scoring Evaluation (HOSE; maximum score 16). Patient and treatment characteristics recorded were: preoperative meatal location, preoperative chordee, number of planned surgeries, reconstructive type and timing, patient age during the study, complications, and repeat operations. Results and limitations: Patients (mean age 10.5 yr) had a lower overall satisfaction score (27.1) than the physicians (30.6). Patients were least satisfied with overall genital appearance (3.1), penile length (3.3), and scars (3.3), whereas physician satisfaction was lowest for scars (3.5). The mean HOSE was 15.4 (standard deviation 0.9). Patients with acceptable HOSE (85%) had higher patient and physician satisfaction compared to patients with unacceptable HOSE. Patient satisfaction was lower among patients with a preoperative proximal meatal location or chordee, and with correction techniques other than the Mathieu approach. Physician satisfaction decreased with increasing patient age and was lower for patients with preoperative chordee, postoperative complications, or repeat operations. Conclusions: Overall patient and physician satisfaction and clinical outcome scores were relatively high. Patient satisfaction was lower and based on different factors compared to physician satisfaction. Patient satisfaction seems more influenced by aesthetic appearance, but both patients and physicians appear to incorporate clinical characteristics and outcome in their opinion on satisfaction. Patient summary: Different factors seem to influence patient and physician satisfaction with hypospadias correction, and there is only low correlation between the two. Therefore, patient satisfaction should be evaluated properly instead of making assumptions based on physician satisfaction or clinical outcome only. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved

Partial amino acid sequence of a hemocyanin subunit from Palinurus vulgaris

1. Hemocyanin from the spiny lobster Palinurus vulgaris was separated into two fractions, which were designated as subunits a and b. 2. 55% of the amino acid sequence of subunit b has been determined. A comparison with Panulirus interruptus hemocyanins shows 78% sequence identity with subunit a and 56% with subunit c. It has carbohydrate attached to domain. Two half-cystines have been substituted, indicating that it probably possesses only one disulfide bridge. Heterogeneity has been observed in seven out of 380 positions determined so far 3. Subunit a is almost identical with subunit b. In contrast to Panulirus interruptus and Panulirus japonicus, Palinurus vulgaris hemocyanin contains no c-type subunit 4. A position in the tentative evolutionary tree of arthropod hemocyanins based on sequence differences has been assigned to Palinurus vulgaris subunit

Interaction between MTHFR 677C>T and periconceptional folic acid supplementation in the risk of Hypospadias

BACKGROUND: Hypospadias is a congenital malformation with both environmental factors and genetic predisposition involved in the pathogenesis. The role of maternal periconceptional folic acid supplement use in the development of hypospadias is unclear. As folate levels may also be influenced by the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, we hypothesize that a gene-environment interaction between this polymorphism and folic acid use is involved in the etiology of hypospadias. METHODS: We conducted a case-control study among 855 hypospadias cases and 713 population-based controls from the AGORA data- and biobank. Folic acid supplement use was derived from maternal questionnaires and infant and maternal DNA was used to determine the MTHFR C677T polymorphism using Taqman assays. We performed separate analyses for different hypospadias phenotypes (anterior/middle/posterior). RESULTS: Hypospadias was neither associated with folic acid use or the MTHFR C677T polymorphism, nor with their interaction. However, we did find an association with middle hypospadias when no supplements were used (odds ratio = 1.6; 95% confidence interval, 1.1-2.4), especially in infants carrying the CT/TT genotype (odds ratio = 2.5; 95% confidence interval, 1.4-4.7). In addition, more infants with these genotypes seemed to have posterior hypospadias, regardless of folic acid use. CONCLUSION: Our study does not suggest a major role for folic acid supplements or the MTHFR C677T polymorphism in the etiology of hypospadias in general, but not using folic acid and/or carrying the MTHFR C677T polymorphism may be associated with middle and posterior hypospadias. Therefore, we stress the importance of studying gene-environment interactions preferably in stratified analyses for different hypospadias phenotypes. Birth Defects Research (Part A) 106:275-284, 2016. (c) 2016 Wiley Periodicals, Inc

Neoadjuvant nivolumab and relatlimab in locally advanced MMR-deficient colon cancer: a phase 2 trial.

Mismatch repair deficiency (dMMR) is found in approximately 15% of non-metastatic colon cancers (CCs) and is characterized by a defective DNA mismatch repair system, resulting in hypermutated and highly immunogenic tumors. Although patients with dMMR CC have limited benefit from chemotherapy, these tumors have been shown to respond exceptionally well to neoadjuvant anti-PD-1 plus anti-CTLA-4, with high rates of pathologic responses. Here, based on data from melanoma studies, we postulated a high efficacy and favorable toxicity profile of anti-PD-1 plus anti-LAG-3. In the NICHE-3 study, a total of 59 patients with locally advanced dMMR CC were treated with two 4-weekly cycles of nivolumab (480 mg) plus relatlimab (480 mg) before surgery. Pathologic response was observed in 57 of 59 (97%; 95% confidence interval (CI): 88-100%) patients, meeting the primary endpoint. Responses included 54 (92%; 95% CI: 81-97%) major pathologic responses (≤10% residual viable tumor) and 40 (68%; 95% CI: 54-79%) pathologic complete responses. With a median follow-up of 8 months (range, 2-19), one patient had recurrence of disease. The treatment displayed an acceptable safety profile, with all-grade and grade 3-4 immune-related adverse events (irAEs) occurring in 80% and 10% of patients, respectively. The most common irAEs were infusion-related reactions (29%), thyroid dysfunction (22%) and fatigue (20%). In conclusion, our results show that neoadjuvant nivolumab/relatlimab induces high rates of pathologic responses and that further investigation of this treatment in larger studies is warranted. These data add to the body of evidence in support of neoadjuvant immunotherapy regimens in dMMR CC. ClinicalTrials.gov identifier: NCT03026140