Multifocal Insulinoma as the Unique Presenting Feature of MEN1 in an Adolescent.

Introduction Multiple Endocrine Neoplasia Type 1 (MEN1) is an autosomal dominant inherited disorder defined by the presence of two of the following endocrinopathies: primary hyperparathyroidism, anterior pituitary tumors, and duodenopancreatic neuroendocrine tumors (NETs). NETs, which can secrete hormones including insulin, gastrin, and glucagon, among others, are common in patients with MEN1 and are a major cause of morbidity and premature death. NETs are more common later in life, with very few cases described in children. Here, we describe a unique case of an adolescent with multifocal pancreatic NETs as the single presenting feature of MEN1. Case Presentation A 13-year-old healthy male presented with severe weakness, altered mental status, and syncope in the setting of a venous blood glucose (BG) of 36 mg/dL. Workup showed an elevated insulin level (14 mcIU/mL) when BG was 39 mg/dL with positive response to glucagon, concerning for hyperinsulinism. Diazoxide and chlorothiazide were started but not well tolerated secondary to emesis. Three suspected NETs were identified by MRI and 68-Ga DOTATATE PET-CT imaging, including the largest, a 2.1 cm mass in the pancreatic head. A fourth mass in the pancreatic tail was identified via intraoperative ultrasound. All lesions were successfully enucleated and excised, and glucose levels normalized off diazoxide by post-op day 2. While the primary lesion stained for insulin and somatostatin by immunofluorescence (IF), consistent with his clinical presentation, the additional tumors expressed glucagon, somatostatin, pancreatic polypeptide, and chromogranin A but were negative for insulin. Genetic testing confirmed a pathogenic heterozygous mutation in MEN1 (c.969C>A, p.Tyr323). He had no other signs of MEN-associated comorbidities on screening. Discussion/Conclusion This case demonstrates that young patients with MEN1 can present with multifocal NETs. These NETs may have polyhormonal expression patterns despite a clinical presentation consistent with one primary hormone. Our patient had clinical symptoms and laboratory evaluation consistent with an insulinoma but was found to have four NETs, each with different IF staining patterns. Advanced pre-operative and intraoperative imaging is important to identify and treat all present NETs. Moreover, serum hormone levels pre- and post-treatment could help evaluate whether NETs are actively secreting hormones into the bloodstream or simply expressing them within the pancreas. Finally, this case highlights the importance of genetic testing for MEN1 in all young patients with insulinomas.

Interventional endoscopy for abdominal transplant patients.

Interventional endoscopy can play a significant role in the care and management of children pre-and post- abdominal solid organ transplantation. Such procedures primarily include endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS), and balloon-assisted enteroscopy (BAE), though additional interventions are available using standard endoscopes (gastroscopes, colonoscopes) for therapeutics purposes such as endoscopic hemostasis. The availability of pediatric practitioners with the advanced training to effectively and safely perform these procedures are most often limited to large tertiary care pediatric centers. These centers possess the necessary resources and ancillary staff to provide the comprehensive multi-disciplinary care needed for these complex patients. In this review, we discuss the importance of interventional endoscopy in caring for transplant patients, during their clinical course preceding the potential need for solid organ transplantation and inclusion of a discussion related to endoscopic post-surgical complication management. Given the highly important role of interventional endoscopy in patients with recurrent and chronic pancreatitis, we also include a discussion related to this complex disease process leading up to those patients that may need pancreas surgery including total pancreatectomy with islet autotransplantation (TPIAT).

Pneumatosis intestinalis after hematopoietic stem cell transplantation: When not doing anything is good enough.

BACKGROUND/PURPOSE: Pneumatosis intestinalis (PI) has been reported in hematopoietic stem cell transplant recipients (HSCT) since 1980s and at present there is no uniform consensus of the significance and management of this condition. METHODS: We retrospectively reviewed medical records of 990 consecutive pediatric HSCT recipients and examined data for clinical PI presentation, management and outcomes RESULTS: PI was identified in 53 patients (5.4%), mainly allogeneic HSCT recipients receiving systemic steroids. Abdominal X-ray was the main diagnostic modality. Forty-seven patients (89%) were evaluated because of clinical concerns and others were identified as incidental findings. Pneumoperitoneum was reported in 15 patients (28%). None of these patients had signs of acute abdomen. The majority of patients (43/53, 81%) had no targeted clinical intervention for PI and resolved PI in a median of 15 days (IQR 3-61). Surgery consult was only requested for 7/53 (13%) patients, three of whom had evidence of pneumoperitoneum. None of these patients required any surgical interventions. CONCLUSIONS: Pneumatosis intestinalis commonly occurs in HSCT recipient receiving steroids, but unlike with NEC, PI rarely poses clinical risk after transplant. The majority of HSCT recipients with PI require only close monitoring without interventions. Surgical evaluation should be based on clinical symptoms and not PI presence alone.

Standardization of clinical care pathway leads to sustained decreased length of stay following Nuss pectus repair: A multidisciplinary quality improvement initiative.

BACKGROUND AND PURPOSE: Postoperatively, standardized clinical care pathways (SCCPs) help patients reach necessary milestones for discharge. The objective of this study was to achieve 90% compliance with a pectus specific SCCP within 9 months of implementation. We hypothesized that adherence to a pectus SCCP following the Nuss procedure would decrease postsurgical length of stay (LOS). METHODS: A multidisciplinary team implemented the pectus SCCP, including goals for mobility, lung recruitment, pain control, intake, and output. The full protocol included 42 components, tracked using chart reviews and a patient-directed checklist. The primary process measure was compliance with the pectus SCCP. The primary outcome measure was LOS; secondary outcomes were patient charges, patient satisfaction, and hospital readmission. RESULTS: Total study patients were n = 509: 159 patients pre-intervention, 350 patients post-intervention (80 implementation group; 270 sustain group). SCCP compliance data were collected on 164 patients post-intervention - 80 implementation, 84 sustain. LOS, ED visits, and hospital readmissions were recorded for all 509 patients. Mean LOS decreased from 4.5 days to 3.4 days, with >90% adherence to the pectus SCCP postintervention. There were no readmissions owing to pain despite earlier termination of epidural analgesia. Total patient charges decreased by 30% and patient satisfaction was high. CONCLUSION: Using quality improvement methodology with strict adherence to a pectus SCCP, we had significant reduction in LOS and patient charge without compromising effective postoperative pain management or patient satisfaction. TYPE OF STUDY: Clinical research; quality improvement. LEVEL OF EVIDENCE: V.

Minimally invasive surgery for abdominal and thoracic neuroblastic tumors: A systematic review by the APSA Cancer committee.

BACKGROUND: Minimally invasive surgery has broad applicability to pediatric diseases, including pediatric cancer resection. Neuroblastic tumors of childhood are highly variable in presentation, and so careful selection of appropriate candidates for minimally invasive resection is paramount to achieving safe and durable surgical and oncological outcomes. METHODS: The American Pediatric Surgical Association Cancer Committee developed questions seeking to better define the role of minimally invasive surgery for neuroblastic tumors. A search using PubMed, Medline, Embase, Web of Science, ProQuest Dissertations, and Clinical Trials was performed for articles published from 1998 to 2018 in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. RESULTS: The evidence identified is all retrospective in nature. Minimally invasive surgical resection of neuroblastic tumors is safe for carefully selected smaller (4-6 cm) image defined risk factor (IDRF)-negative abdominal tumors when oncologic principles are followed. Size is a less-well defined criterion for thoracic neuroblastic tumors. Open approaches for both abdominal and thoracic tumors may be preferable in the presence of IDRF's. CONCLUSION: Small tumors without IDRF's are reasonable candidates for minimally invasive resection. Surgical oncologic guidelines should be closely followed. The quality of data supporting this systematic review is poor and highlights the need for refinement in the study of such surgical techniques to improve knowledge and outcomes for patients with neuroblastic tumors. TYPE OF STUDY: Systematic Review. LEVEL OF EVIDENCE: Level III and Level IV.

Topical sirolimus for the treatment of cutaneous manifestations of vascular anomalies: A case series.

BACKGROUND: Vascular anomalies (VA), characterized by the abnormal development or growth of blood and/or lymphatic vessels, encompasses a spectrum of conditions with a range of symptoms and complications. VA are frequently associated with cutaneous complications that can cause significant morbidity. Systemic sirolimus has previously been shown to be effective in the treatment of complicated VA. There are limited studies to date on the use of topical sirolimus for the treatment of cutaneous manifestations of VA. METHODS: Retrospective review of medical records of pediatric patients with VA treated with topical sirolimus at a single quaternary pediatric institution. Response was determined by clinical subjective and objective measures of improvement. RESULTS: Twenty-three patients with cutaneous VA manifestations were treated with topical sirolimus. Median age was 14 (range 4-27 years). The main indication for treatment was complication of lymphatic blebbing (82%, n = 19) including lymphatic fluid leakage, bleeding, pain, pruritus, swelling, or recurrent infection. Treatment course ranged from 109 to 1424 days with median of 622 days. No major side effects were reported. Eighty-six percent of patients (n = 20) had subjective or objective improvement of cutaneous lesions. Lymphatic blebbing complications improved in 90% (n = 17) of individuals. Eighty-two percent (n = 14) of patients not receiving concurrent systemic sirolimus demonstrated improvement with topical therapy. One patient electively stopped treatment due to pruritus and burning sensation. CONCLUSION: Topical sirolimus appears to be a beneficial therapy for lymphatic blebbing associated with lymphatic malformations or mixed malformations with a lymphatic component, although benefit in other VA remains unclear. Topical sirolimus was well-tolerated with minimal side effects.

Thrombopoietin Contributes to Extreme Thrombocytosis After Pediatric Pancreatectomy With Islet Autotransplantation.

OBJECTIVE: This study aims to explore the role of thrombopoietin (TPO) production in extreme thrombocytosis that is often observed after pancreatectomy with islet autotransplantation (IAT) and the effectiveness of hydroxyurea in thrombocytosis management. METHODS: Retrospective chart review was performed for all patients who underwent pancreatectomy with IAT at our institution between April 1, 2015, and December 31, 2016. Data evaluated included demographics, platelet counts, TPO levels, and thrombocytosis management strategies. RESULTS: Twelve total and 1 subtotal pancreatectomy with IAT cases were reviewed. All operations included splenectomy. No major surgical or thrombotic complications occurred. Thrombopoietin levels, normal preoperatively, rose significantly (median, 219 pg/mL) soon after surgery, peaking on median postoperative day 3. Platelet counts, also normal preoperatively, increased within a week of surgery, with 92% over 1000 K/µL (median peak platelet count, 1403 K/µL). Platelet counts and TPO levels dropped after hydroxyurea initiation in most patients. CONCLUSIONS: After pancreatectomy with IAT, patients experienced marked TPO rise and subsequent thrombocytosis, and both decreased significantly after hydroxyurea initiation. These data suggest that TPO elevation and associated increased platelet production may be one driver of early extreme post-total pancreatectomy with islet autotransplantation thrombocytosis, and this process may be modulated by hydroxyurea.

Don't Get Stuck: A Quality Improvement Project to Reduce Perioperative Blood-Borne Pathogen Exposure.

BACKGROUND: Blood-borne pathogen exposure (BBPE) represents a significant safety and resource burden, with more than 380,000 events reported annually across hospitals in the United States. The perioperative environment is a high-risk area for BBPE, and efforts to reduce exposures are not well defined. A multidisciplinary group of nurses, surgical technologists, surgeons, and employee health specialists created a BBPE prevention bundle to reduce Occupational Safety and Health Administration (OSHA) recordable cases. METHODS: Mandatory double gloving, a safety zone, engineered-sharps injury prevention devices, and clear communication when passing sharps were implemented in an evidence-based fashion at one institution. Days between exposures and total number of exposures were monitored. Analysis by specialty, role, location, type of injury, and timing was performed. RESULTS: During fiscal year (FY) 2015, 45 cases were reported. During the first year of implementation, cases decreased to 38 (a 15.6% decrease; p < 0.65). In the postimplementation period (FY 2017), only 21 cases were reported (an additional 44.7% decrease; p < 0.12), for a total decrease of 53.3% (p < 0.01). The mean number of days between injuries significantly increased (2.5 to 16.3) over the study period. For FY 2017, the main cause of BBPE was needlestick while suturing (47.6%); fellows and attendings combined had the most injuries (52.4%); among divisions, pediatric surgery (19.0%), operating room staff (19.0%), and orthopedics (19.0%) had the most events. CONCLUSION: A comprehensive and multidisciplinary approach to employee safety, focused on reduction of BBPE resulted in a significant progressive annual decrease of injuries among perioperative staff.

Rhabdomyosarcoma and Extraosseous Ewing Sarcoma.

Rhabdomyosarcoma (RMS) is a malignant tumor that represents the most common form of pediatric soft tissue sarcoma. It arises from mesenchymal origin and forms part of the group of small round blue cell tumors of childhood. It has a constant annual incidence of 4.5 cases per 1,000,000 children. The known histological diagnosis of the two major subtypes (embryonal and alveolar) has been recently enhanced by tumor biological markers and molecular differentiation diagnostic tools that have improved not only the updated classification based on risk stratification, but also the treatment approach based on the clinical group. Ewing sarcoma (ES) is a round cell tumor, highly malignant and poorly differentiated that is currently the second most common malignant bone tumor in children. In rare instances, it develops from an extraskeletal origin, classified as extraosseous Ewing sarcoma (EES). We provide an updated, evidence-based and comprehensive review of the molecular diagnosis, clinical and diagnostic approach and a multidisciplinary medical and surgical management according to the latest standard of care for the treatment of pediatric RMS and EES.

Pediatric trauma undertriage in Ohio.

BACKGROUND: Appropriate and timely triage is an essential component of a trauma system. In the state of Ohio, there are 6 verified pediatric trauma centers (PTCs) across 8 state regions. The purpose of this study was to better understand the pediatric undertriage rates in the state. METHODS: We used the Ohio Trauma Registry from 2007 to 2012, consisting of 14,045 records of children younger than 16 years admitted to a hospital for more than 48 hours or who sustained a traumatic death. Pediatric undertriage was defined as not being directly transported to a PTC when one was available within 30 minutes or not being transferred to a PTC within 2 hours of injury. RESULTS: The state pediatric undertriage rate was 52%, only decreasing to 35% when up to a 4-hour transfer time was allowed. Across state trauma regions, undertriage rates varied from 94% to 40%. More than 28% of injured children had access to a PTC within 30 minutes of their home. A trauma center (adult or pediatric) was within 30 minutes for 66% of the children, yet 32% of the children went to a nontrauma center first. Overall, 29% of children never made it to a PTC, and 4% of children remained at a nontrauma center, with regional variation from 5% to 0.5%. Statewide mortality was nearly 3%, with regional variations between 5% and 0.4%. Mortality rate within the appropriately triaged group was 5.3%, while mortality rate in the undertriage group was only 0.7%. Overall, 53% of transferred patients had a more than 2-hour transfer time. CONCLUSIONS: Despite the significant number of PTCs in Ohio, there remains a high undertriage rate with significant regional variations and long transfer times. Continued analysis will be useful in furthering trauma system development for the injured child. LEVEL OF EVIDENCE: Therapeutic/care management study, level IV; epidemiological, level IV.

Spindle cell sarcomatoid carcinoma of the trachea: first case report of surgical resection.

BACKGROUND: Primary malignant tracheal tumors are rare, accounting for approximately 0.2 % of respiratory tract tumors yearly, with squamous cell carcinomas and adenoid cystic carcinomas accounting for two-thirds of these cases. Sarcomatoid carcinomas are a group of poorly differentiated non-small cell lung carcinomas containing a component of sarcoma or sarcoma-like (spindle and/or giant cell) differentiation, categorized into five morphologic subgroups. Spindle cell sarcomatoid carcinoma is a rare variant of sarcomatoid carcinomas, consisting of only spindle-shaped tumor cells. Only one other case has been reported as a primary tracheal tumor. CASE PRESENTATION: We present a 75-year-old male, having progressive dyspnea and cough, with a spindle cell sarcomatoid carcinoma tumor visualized on chest computed tomography scan and confirmed with biopsy. CONCLUSIONS: Due to its low incidence, knowledge of treatment methods, prognostic factors, and etiology is limited thus approaches to eradication have widely varied. We are reporting the second published case of spindle cell sarcomatoid carcinoma of the trachea and the first reported successful outcome of definitive treatment with tracheal resection.

Surgical treatment of nonalcoholic fatty liver disease in severely obese patients.

Obesity is a multi-organ system disease with underlying metabolic abnormalities and chronic systemic inflammation. Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of obesity metabolic dysfunction and its associated cardiovascular- and liver-related morbidities and mortality. Our current understanding of NAFLD pathogenesis, disease characteristics, the role of insulin resistance, chronic inflammation, gut-liver and gut-brain crosstalk and the effectiveness of pharmacotherapy is still evolving. Bariatric surgery significantly improves metabolic and NAFLD histology in severely obese patients, although its positive effects on fibrosis are not universal. Bariatric surgery benefits NAFLD through its metabolic effect on insulin resistance, inflammation, and insulinotropic and anorexinogenic gastrointestinal hormones. Further studies are needed to understand the natural course of NAFLD in severely obese patients and the role of weight loss surgery as a primary treatment for NAFLD.