Robert A. Cusick

Pediatric Inguinal Hernias, Hydroceles, and Undescended Testicles

Pediatric inguinal hernias are extremely common, and can usually be diagnosed by simple history taking and physical examination. Repair is elective, unless there is incarceration or strangulation. Hydroceles are also quite common, and in infancy many will resolve without operative intervention. Undescended testicles harbor an increased risk of infertility and malignancy, and require orchiopexy in early childhood.

Pathologic changes in biliary dyskinesia

PURPOSE For children with upper abdominal pain and evaluation for acalculous biliary disease, laparoscopic cholecystectomy is an accepted treatment with inconsistent outcomes. The purpose of this study was to identify predictors of outcomes. METHODS One hundred sixty-seven children underwent laparoscopic cholecystectomy at a single childrens hospital. Radiographic findings, histopathology, family history, and demographics (sex, age, height, weight, body mass index-for-age percentile) were evaluated as predictors of postoperative symptomatic resolution using a binomial probability model. The data for radiologic studies and pathologic specimens were obtained via re-review in a blinded fashion. RESULTS Of 167 children, 43 (25.7%) had a preoperative diagnosis of biliary dyskinesia and 41 (95.3%) had documented follow-up. Mean follow-up was 8.4 months. Twenty-eight patients (68.3%) had symptom resolution. Ejection fraction less than or equal to 15%, pain upon cholecystokinin injection, and a family history of biliary disease were not predictors of symptomatic resolution. Nonoverweight patients (body mass index-for-age <85th percentile) were more likely to have symptom resolution than their overweight counterparts (odds ratio, 2.13). Most patients (68.3%) had a pathologic gallbladder on blinded review. However, this did not correlate with outcome. CONCLUSIONS Most gallbladders removed for biliary dyskinesia are pathologic. Being overweight can be considered a relative contraindication to cholecystectomy for biliary dyskinesia.

Undescended testes: Does age at orchiopexy affect survival of the testis?

PURPOSE The optimal age at which to perform orchiopexy for cryptorchidism has long been debated. The aim of this study was to determine if age at orchiopexy affected testicular atrophy. METHODS A retrospective review of patients undergoing orchiopexy from 2000 to 2010 was conducted. An individual testis, rather than patient, was used as the dependent variable. A total of 349 testicles from 1126 charts (ICD-9=752.51) were identified. Primary study outcome was testicular survival without atrophy. RESULTS Mean follow up for the study was 25 months. There was postoperative atrophy in 27 testes (7.7%). Intraabdominal testicle was independently associated with increased postsurgical atrophy (p<0.0001). The odds of postsurgical atrophy were 15.66 times higher for an abdominal vs. inguinal location (95% CI: 5.5-44.6). Testicular atrophy was highest for orchiopexy at ages 13-24 months (n=16 of 133, 12%) vs. those less than 13 months (n=3 of 64, 5%), and those greater than 24 months (n=8 of 152, 5%) (p=0.0024). After adjusting for location, age was not statistically significant with postsurgical atrophy (p=0.055). CONCLUSIONS From this study we conclude that there is no increase in testicular atrophy in patients less than 13 months.

Identifying strategies to decrease infectious complications of gastroschisis repair

PURPOSE We describe the infectious complications of gastroschisis in order to identify modifiable factors to decrease these complications. METHODS Data from 155 gastroschisis patients (2001-2013) were reviewed. Complicated gastroschisis (intestinal atresia, necrotic bowel, or perforation) were excluded, leaving 129 patients for review. Patient demographics, surgical details, postoperative infections and complications, and length of stay were reviewed. We used CDC definitions of infectious complications. RESULTS The average gestational age of patients was 35.97weeks. Silos were used in 46% of patients (n=59) for an average of 7.4days. Thirty-one patients (24%) acquired an infection within the first 60days of life. Patients who developed an infection were born earlier in gestation (P=0.02), weighed less (P=0.01), required silos more often (P=0.01), and received a sutured repair (P=0.04). Length of stay of patients with an infection was longer than in patients without infection (P=0.01). CONCLUSIONS Infectious complications following gastroschisis repair are common. Subsets of gastroschisis patients at increased risk of infection include patients with silos, preterm delivery, low birth weight, and sutured repair. Based on our findings, our recommendation would be to carry gastroschisis patients to term and advocate against the routine use of silos, reserving their use for those cases when primary closure is not possible.

Trends in surgical management of urachal anomalies

PURPOSE We have noted an increasing frequency of diagnosed urachal anomalies. The purpose of this study is to evaluate this increase, as well as the outcomes of management at our institution over 10 years. METHODS A retrospective analysis of urachal anomalies at our institution was performed. Inclusion criteria were Anomalies of Urachus (ICD 753.7) or Urinary Anomaly NOS (ICD 753.9) between January 2000 and December 2010. Exclusion criteria were having an asymptomatic urachal remnant incidentally excised. RESULTS Eighty-five patients (49 male, 36 female) presented between 0 and 17 years of age (mean 1.5 years). Diagnoses increased from 0 in 2000 to 21 in 2010. Zero was surgically managed in 2000 while 21 were managed in 2010 (p=0.0145). Fifteen patients (17.6%) were observed with 13 (13/15, or 15.3%) resolving without complication while 2 were operated on. Average time to resolution (clinical or radiologic) was 4.9 months (Range: 0.4-12.6). A total of seventy-two patients (84.7%) underwent excision. Thirty-nine (54%) surgical cases were outpatient while 33 (46%) were admitted. Thirteen (18%) had post-operative complications. Ten (77%) of the complications were wound infections. Patients under 6 months of age accounted for 60% (6 of 10) of all wound infections and 52% (17 of 33) of hospitalizations. CONCLUSIONS Our experience and review of the literature suggest a high complication rate with surgical management in young patients, mostly from infections and support non-operative management of all non-infected urachal remnants in children.

Genetic analysis of de novo variants reveals sex differences in complex and isolated congenital diaphragmatic hernia and indicates MYRF as a candidate gene

Congenital diaphragmatic hernia (CDH) is one of the most common and lethal birth defects. Previous studies using exome sequencing support a significant contribution of coding de novo variants in complex CDH cases with additional anomalies and likely gene-disrupting (LGD) variants in isolated CDH cases. To further investigate the genetic architecture of CDH, we performed exome or genome sequencing in 283 proband-parent trios. Combined with data from previous studies, we analyzed a total of 357 trios, including 148 complex and 209 isolated cases. Complex and isolated cases both have a significant burden of deleterious de novo coding variants (1.7~fold, p= 1.2×10−5 for complex, 1.5~fold, p= 9.0×10−5 for isolated). Strikingly, in isolated CDH, almost all of the burden is carried by female cases (2.1~fold, p=0.004 for likely gene disrupting and 1.8~fold, p= 0.0008 for damaging missense variants); whereas in complex CDH, the burden is similar in females and males. Additionally, de novo LGD variants in complex cases are mostly enriched in genes highly expressed in developing diaphragm, but distributed in genes with a broad range of expression levels in isolated cases. Finally, we identified a new candidate risk gene MYRF (4 de novo variants, p-value=2×10−10), a transcription factor intolerant of mutations. Patients with MYRF mutations have additional anomalies including congenital heart disease and genitourinary defects, likely representing a novel syndrome.

Global Outreach Using a Systematic, Competency-Based Training Paradigm for Inguinal Hernioplasty

Importance Sustainable, capacity-building educational collaborations are essential to address the global burden of surgical disease. Objective To assess an international, competency-based training paradigm for hernia surgery in underserved countries. Design, Setting, and Participants In this prospective, observational study performed from November 1, 2013, through October 31, 2015, at 16 hospitals in Brazil, Ecuador, Haiti, Paraguay, and the Dominican Republic, surgeons completed initial training programs in hernia repair, underwent interval proficiency assessments, and were appointed regional trainers. Competency-based evaluations of technical proficiency were performed using the Operative Performance Rating Scale (OPRS). Maintenance of proficiency was evaluated by video assessments 6 months after training. Certified trainees received incentives to document independent surgical outcomes after training. Main Outcomes and Measures An OPRS score of 3.0 (scale of 1 [poor] to 5 [excellent]) indicated proficiency. Secondary outcomes included initial vs final scores by country, scores among surgeons trained by the regional trainers (second-order trainees), interval scores 6 months after training, and postoperative complications. Results A total of 20 surgeon trainers, 81 local surgeons, and 364 patients (343 adult, 21 pediatric) participated in the study (mean [SD] age, 47.5 [16.3] years; age range, 16-83 years). All 81 surgeons successfully completed the program, and all 364 patients received successful operations. Mean (SD) OPRS scores improved from 4.06 (0.87) before the initial training program to 4.52 (0.57) after training (P < .001). No significant variation was found by country in final scores. On trainee certification, 20 became regional trainers. The mean (SD) OPRS score among 53 second-order trainees was 4.34 (0.68). After 6-month intervals, the mean (SD) OPRS score among participating surgeons was 4.34 (0.55). The overall operative complication rate during training series was 1.1%. Conclusions and Relevance Competency-based training helps address the global burden of surgical disease. The OPRS establishes an international standard of technical assessment. Additional studies of long-term surgeon trainer proficiency, community-specific quality initiatives, and expansion to other operations are warranted.

The association between congenital diaphragmatic hernia and undescended testes

BACKGROUND Undescended testes (UDT) is a common abnormality treated by pediatric surgeons. Embryological development of the genitourinary ridge is in close proximity with the pleuroperitoneal fold. The purpose of this paper is to describe the association between congenital diaphragmatic hernia (CDH) and UDT. MATERIALS/METHODS As part of the DHREAMS (Diaphragmatic Hernia Research and Exploration: Advancing Molecular Science) study (www.cdhgenetics.com), all living children had tissue banked and analyzed for common genetic mutations and had a health assessment performed by telephone consultation with the parents at two years of age. The incidence of UDT was then compared to clinical and genetic findings previously identified. RESULTS Sixty-five males had complete information from their 2year health assessment. Of these, twelve (18%) had a UDT repaired by the time of the 2year assessment. Of the twelve who had a repair, no child had a unilateral UDT which was contralateral to the side of the CDH. There were no differences in rate or number of mutations of any of the genes we checked as part of our study. CONCLUSION It appears that a deficiency of diaphragm tissue may affect the first or transabdominal phase of the testicular descent, leading to an increased incidence of UDT.

Mutations in BMPR2 are not present in patients with pulmonary hypertension associated with congenital diaphragmatic hernia

BACKGROUND Congenital diaphragmatic hernia (CDH) is a prevalent major congenital anomaly with significant morbidity and mortality. Thirty to 40% mortality in CDH is largely attributed to pulmonary hypoplasia and pulmonary hypertension (PH). We hypothesized that the underlying genetic risk factors for hereditary PH are shared with CDH associated PH. METHODS Participants were recruited as part of the Diaphragmatic Hernia Research & Exploration; Advancing Molecular Science (DHREAMS) study, a prospective cohort of neonates with a diaphragmatic defect enrolled from 2005 to 2012. PH affected patients with available DNA for sequencing had one of the following: moderate or severe PH on echocardiography at 3months of age; moderate of severe PH at 1month of age with death occurring prior to the 3month echocardiogram; or on PH medications at 1month of age. We sequenced the coding regions of the hereditary PH genes bone morphogenetic protein receptor type II (BMPR2), caveolin 1 (CAV1) and potassium channel subfamily K, member 3 (KCNK3) to screen for mutations. RESULTS There were 29 CDH patients with PH including 16 males and 13 females. Sequencing of BMPR2, CAV1, and KCNK3 coding regions did not identify any pathogenic variants in these genes. TYPE OF STUDY Prognosis study LEVEL OF EVIDENCE: Level IV.

Does Surgical Volume Influence the Need for Second Surgery? A Pilot Study:

Objective To examine outcomes of pediatric thyroidectomy in the context of training background, institution, and experience of the surgeon. Study Design Case series with chart review. Setting A tertiary academic medical center and a pediatric hospital. Subjects and Methods Eighty-one thyroidectomy patients younger than 18 years. Outcomes were major complications (recurrent laryngeal nerve injury, permanent hypocalcemia, and wound infection), length of stay (LOS), and need for repeat surgery. Results Eighty-one patients, 39 from the University of Nebraska Medical Center and 42 from the Children’s Hospital and Medical Center–Omaha, were identified over a 12-year time period. No difference was found in surgeon training (otolaryngology/head and neck surgery vs general/pediatric surgery) for complications (1 vs 1, odds ratio [OR] = 0.76, 95% confidence interval [CI] = [0.05, 13.1]), LOS >1 day (5 vs 13, OR = 0.39, 95% CI = [0.13, 1.24]), or need for second surgery (4 vs 7, OR = 1.47, 95% CI = [0.39, 5.49]). Higher surgeon volume (≥12 surgeries) was found to be significant for decreased need for second surgery (3 vs 8, OR = 6.67, 95% CI = [1.57, 27.17]). Patients of higher-volume surgeons were 4.2 times more likely to stay in the hospital 1 day or less compared with those patients operated on by surgeons with less experience (7 vs 11, 95% CI = [1.59, 15.0]). Conclusions Need for second surgery in pediatric thyroidectomy may be predicted by surgical volume.