Publications by authors named "Brent R Weil"

73 Publications

Belzutifan, a Potent HIF2α Inhibitor, in the Pacak-Zhuang Syndrome.

N Engl J Med 2021 11;385(22):2059-2065

From the Departments of Pediatric Oncology (J.K., K.V.H., J.A.P., C.M.C., A.I., C.B.W., K.A.J., S.G.D.) and Medical Oncology (W.G.K.), Dana-Farber Cancer Institute, Harvard Medical School, the Divisions of Hematology and Oncology (J.K., J.A.P., M.M.H., K.A.J., S.G.D.) and Endocrinology (A.J.W.) and the Departments of Surgery (B.R.W.), Pathology (S.O.V.), and Radiology (S.D.V.), Boston Children's Hospital, Harvard Medical School, and the Manton Center for Orphan Disease Research and the Division of Genetics and Genomics, Boston Children's Hospital (J.A.M., J.L.) - all in Boston; Howard Hughes Medical Institute, Chevy Chase, MD (W.G.K.); and Merck, Kenilworth, NJ (R.F.P., N.J.Z.).

The integration of genomic testing into clinical care enables the use of individualized approaches to the management of rare diseases. We describe the use of belzutifan, a potent and selective small-molecule inhibitor of the protein hypoxia-inducible factor 2α (HIF2α), in a patient with polycythemia and multiple paragangliomas (the Pacak-Zhuang syndrome). The syndrome was caused in this patient by somatic mosaicism for an activating mutation in . Treatment with belzutifan led to a rapid and sustained tumor response along with resolution of hypertension, headaches, and long-standing polycythemia. This case shows the application of a targeted therapy for the treatment of a patient with a rare tumor-predisposition syndrome. (Funded by the Morin Family Fund for Pediatric Cancer and Alex's Lemonade Stand Foundation.).
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http://dx.doi.org/10.1056/NEJMoa2110051DOI Listing
November 2021

Interdisciplinary Management of Malignant Ovarian Tumors in the Pediatric and Adolescent Age Group.

J Pediatr Adolesc Gynecol 2021 Oct 27. Epub 2021 Oct 27.

Attending, Division of Gynecology, Department of Surgery, Boston Children's Hospital; Clinical Instructor, Harvard Medical School.

Malignant ovarian neoplasms are uncommon in the pediatric and adolescent population. Imaging and tumor markers help to guide the preoperative risk/benefit analysis for planned surgical management, which is the mainstay of therapy. An interdisciplinary approach should be taken in the management of this vulnerable population from diagnosis through post-treatment surveillance. In this review, the initial evaluation, risk stratification, and management of various types of malignant ovarian masses will be addressed with a special focus on how to optimize an interdisciplinary approach to ovarian masses.
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http://dx.doi.org/10.1016/j.jpag.2021.10.006DOI Listing
October 2021

Late-onset kidney failure in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

Eur J Cancer 2021 09 11;155:216-226. Epub 2021 Aug 11.

Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.

Background: The incidence of and risk factors for late-onset kidney failure among survivors over the very long term remains understudied.

Materials And Methods: A total of 25,530 childhood cancer survivors (median follow-up 22.3 years, interquartile range 17.4-28.8) diagnosed between 1970 and 1999, and 5045 siblings from the Childhood Cancer Survivor Study were assessed for self-reported late-onset kidney failure, defined as dialysis, renal transplantation, or death attributable to kidney disease. Piecewise exponential models evaluated associations between risk factors and the rate of late-onset kidney failure.

Results: A total of 206 survivors and 10 siblings developed late-onset kidney failure, a 35-year cumulative incidence of 1.7% (95% confidence interval [CI] = 1.4-1.9) and 0.2% (95% confidence interval [CI] = 0.1-0.4), respectively, corresponding to an adjusted rate ratio (RR) of 4.9 (95% CI = 2.6-9.2). High kidney dose from radiotherapy (≥15Gy; RR = 4.0, 95% CI = 2.1-7.4), exposure to high-dose anthracycline (≥250 mg/m; RR = 1.6, 95% CI = 1.0-2.6) or any ifosfamide chemotherapy (RR = 2.6, 95% CI = 1.2-5.7), and nephrectomy (RR = 1.9, 95% CI = 1.0-3.4) were independently associated with elevated risk for late-onset kidney failure among survivors. Survivors who developed hypertension, particularly in the context of prior nephrectomy (RR = 14.4, 95% CI = 7.1-29.4 hypertension with prior nephrectomy; RR = 5.9, 95% CI = 3.3-10.5 hypertension without prior nephrectomy), or diabetes (RR = 2.2, 95%CI = 1.2-4.2) were also at elevated risk for late-onset kidney failure.

Conclusions: Survivors of childhood cancer are at increased risk for late-onset kidney failure. Kidney dose from radiotherapy ≥15 Gy, high-dose anthracycline, any ifosfamide, and nephrectomy were associated with increased risk of late-onset kidney failure among survivors. Successful diagnosis and management of modifiable risk factors such as diabetes and hypertension may mitigate the risk for late-onset kidney failure. The association of late-onset kidney failure with anthracycline chemotherapy represents a novel finding that warrants further study.
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http://dx.doi.org/10.1016/j.ejca.2021.06.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429192PMC
September 2021

Safety of Surgical Fertility Preservation Procedures in Children Prior to Hematopoietic Stem Cell Transplant.

Transplant Cell Ther 2021 08 14;27(8):696.e1-696.e4. Epub 2021 Apr 14.

Division of Pediatric Oncology, Dana Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts; Department of Pediatrics, Harvard University Medical School, Boston, Massachusetts.

Long-term survival following hematopoietic stem cell transplant (HSCT) in childhood continues to improve, and patients are thus increasingly faced with the late effects of treatment. Infertility is very common for both males and females following HSCT and is one of the most distressing sequelae. Adoption and surrogate egg or sperm donation are possibilities for some patients, but post-HSCT reversal of gonadal failure is not possible. We have recently initiated an oncofertility program with a dedicated practitioner with specific expertise in this area. Our practice is for her to meet with all families and age-appropriate patients during the pre-HSCT evaluation period. This allows patients and families to be accurately informed about the expected treatment-related infertility risk and the available options for fertility preservation. Sperm banking and egg or embryo cryopreservation are established approaches but are not achievable for many children and adolescents. Recently, the harvesting and cryopreservation of ovarian and testicular tissue represents a novel surgical option that allows for the possibility of fertility preservation to be extended to children of all ages. The purpose of this investigation is to evaluate the safety of these procedures proximal to conditioning therapy and HSCT. This is a retrospective report on a consecutive cohort of all patients aged 0 to 25 years who, after discussion with our oncofertility specialist, chose to undergo surgical fertility preservation (laparoscopic unilateral oophorectomy or testicular biopsy) at our institution between March 2018 and April 2020. These procedures occurred under general anesthesia at the time of central line placement prior to the initiation of HSCT conditioning. We assess the safety of the procedures in terms of postoperative complications and impact on HSCT course. Twenty-two patients underwent fertility preservation surgical procedures. Thirteen patients (59%) were female, median age 13 years (1 to 22 years), and 9 (41%) were male, median age 8 years (5 to 12 years). Fourteen (63%) were prepubertal and 8 (36%) pubertal. HSCT indications were hematologic malignancies/solid tumor (40%) and nonmalignant diseases (60%). Most received an allogenic graft (68%) and 81% had myeloablative conditioning. All patients became neutropenic at a median of 10 days (0 to 51 days) from the surgical procedure; 1 was neutropenic at the time of testicular tissue cryopreservation (TTC). The mean duration for the procedures performed, including ovarian tissue cryopreservation (OTC) or TTC, was 98 minutes (49 to 260 minutes) and 97 minutes (56 to 178 minutes), respectively. Estimated blood loss was minimal and no postoperative site infections occurred. One postprocedure, blood culture-negative fever was reported without an identifiable source; the patient completed 48 hours of antibiotics with resolution of fever. Sixty-two percent of females and 56% of males started conditioning within 24 hours of OTC/TTC (15 hours to 113 days; median, 1 day). The median time to engraftment was 22 days (9 to 33 days) in females and 17 days (11 to 67 days) in males, consistent with our institutional benchmarks. One patient with aplastic anemia had primary graft failure, attributed to low cell dose. This patient engrafted after a second transplant from an alternative donor but ultimately died of multiorgan failure. He was neutropenic for over 60 days and never experienced surgical site infection. There were no procedure-related delays to start of conditioning or to discharge. Children of all ages can now be offered the possibility of fertility preservation following HSCT for benign and malignant conditions. Our review suggests that these procedure for both females and males can be performed close to the start of conditioning, which allows for coupling with central access placement. These procedures appear to be safe and do not add to transplant-related morbidity.
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http://dx.doi.org/10.1016/j.jtct.2021.04.001DOI Listing
August 2021

Management of Germ Cell Tumors in Pediatric Patients.

Surg Oncol Clin N Am 2021 04 3;30(2):325-338. Epub 2021 Feb 3.

Department of Pediatric Surgery, Riley Hospital for Children at Indiana University Health, 705 Riley Hospital Drive, Indianapolis, IN 46202, USA.

Germ cell tumors arise from primordial germ cells. Most develop in the gonads or along midline structures of the body. Genetic aberrations leading to disruption in the molecular signaling responsible for primordial germ cell migration early in development may provide rationale for why germ cell tumors originate in extragonadal locations. Establishing best practices for treating pediatric germ cell tumors remains an area of active investigation. Recent advances focused on limiting toxicities of therapy, identifying new therapies for relapsed and refractory tumors, defining best practices for surgical staging and resection, and developing novel methods to monitor for disease relapse.
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http://dx.doi.org/10.1016/j.soc.2020.11.011DOI Listing
April 2021

Neonatal Malignant Disorders: Germ Cell Tumors.

Clin Perinatol 2021 03;48(1):147-165

Department of Pediatric Oncology, Children's Cancer and Blood Disorders Center, Children's Hospital Dana-Farber Cancer Center, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA.

Germ cell tumors (GCTs) comprise a wide spectrum of benign and malignant tumors. Neonatal GCTs are predominantly teratomas (mature or immature), which are typically cured with surgery alone. Relapses are infrequent even in the setting of microscopic residual disease; therefore, negative surgical margins at the cost of significant morbidity are not recommended. In neonates with metastatic malignant disease or malignant disease for which upfront surgical resection is not feasible without significant morbidity, an initial biopsy followed by neoadjuvant chemotherapy and delayed surgical resection is recommended. Carboplatin-based regimens should be considered when chemotherapy is indicated.
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http://dx.doi.org/10.1016/j.clp.2020.11.010DOI Listing
March 2021

Epidemiology of abdominal wall and groin hernia repairs in children.

Pediatr Surg Int 2021 May 1;37(5):587-595. Epub 2021 Jan 1.

Department of Surgery, Boston Children's Hospital, Boston, MA, USA.

Purpose: We sought to estimate the prevalence, incidence, and timing of surgery for elective and non-elective hernia repairs.

Methods: We performed a retrospective cohort study, abstracting data on children < 18 years from the 2005-2014 DoD Military Health System Data Repository, which includes > 3 million dependents of U.S. Armed Services members. Our primary outcome was initial hernia repair (inguinal, umbilical, ventral, or femoral), stratified by elective versus non-elective repair and by age. We calculated prevalence, incidence rate, and time from diagnosis to repair.

Results: 19,398 children underwent hernia repair (12,220 inguinal, 5761 umbilical, 1373 ventral, 44 femoral). Prevalence of non-elective repairs ranged from 6% (umbilical) to 22% (ventral). Incidence rates of elective repairs ranged from 0.03 [95% CI: 0.02-0.04] (femoral) to 8.92 [95% CI: 8.76-9.09] (inguinal) per 10,000 person-years, while incidence rates of non-elective repairs ranged from 0.005 [95% CI: 0.002-0.01] (femoral) to 0.68 [95% CI: 0.64-0.73] (inguinal) per 10,000 person-years. Inguinal (median = 20, interquartile range [IQR] = 0-46 days), ventral (median = 23, IQR = 5-62 days), and femoral hernias (median = 0, IQR = 0-12 days) were repaired more promptly and with less variation than umbilical hernias (median = 66, IQR = 23-422 days).

Conclusions: These data describe the burden of hernia repair in the U.S. The large variation in time between diagnosis and repair by hernia type identifies an important area of research to understand mechanisms underlying such heterogeneity and determine the ideal timing for repair.

Level Of Evidence: Prognosis study II.
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http://dx.doi.org/10.1007/s00383-020-04808-8DOI Listing
May 2021

Sex-Specific Associations Between Chemotherapy, Chronic Conditions, and Neurocognitive Impairment in Acute Lymphoblastic Leukemia Survivors: A Report From the Childhood Cancer Survivor Study.

J Natl Cancer Inst 2021 May;113(5):588-596

St Jude Children's Research Hospital, Psychology Department, Memphis, TN, USA.

Background: The purpose was to examine associations between treatment and chronic health conditions with neurocognitive impairment survivors of acute lymphoblastic leukemia (ALL) treated with chemotherapy only.

Methods: This cross-sectional study included 1207 ALL survivors (54.0% female; mean age 30.6 years) and 2273 siblings (56.9% female; mean age 47.6 years), who completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire. Multivariable logistic regression compared prevalence of neurocognitive impairment between survivors and siblings by sex. Associations between neurocognitive impairment with treatment exposures and chronic conditions (graded according to Common Terminology Criteria for Adverse Events) were also examined. Statistical tests were 2-sided.

Results: Relative to same-sex siblings, male and female ALL survivors reported increased prevalence of impaired task efficiency (males: 11.7% vs 16.9%; adjusted odds ratio [OR] = 1.89, 95% confidence interval [CI] = 1.31 to 2.74; females: 12.5% vs 17.6%; OR = 1.50, 95% CI = 1.07 to 2.14), as well as impaired memory (males: 11.6% vs 19.9%, OR = 1.89, CI = 1.31 to 2.74; females: 14.78% vs 25.4%, OR = 1.96, 95% CI = 1.43 to 2.70, respectively). Among male survivors, impaired task efficiency was associated with 2-4 neurologic conditions (OR = 4.33, 95% CI = 1.76 to 10.68) and with pulmonary conditions (OR = 4.99, 95% CI = 1.51 to 16.50), and impaired memory was associated with increased cumulative dose of intrathecal methotrexate (OR = 1.68, 95% CI = 1.16 to 2.46) and with exposure to dexamethasone (OR = 2.44, 95% CI = 1.19 to 5.01). In female survivors, grade 2-4 endocrine conditions were associated with higher risk of impaired task efficiency (OR = 2.19, 95% CI = 1.20 to 3.97) and memory (OR = 2.26, 95% CI = 1.31 to 3.92).

Conclusion: Neurocognitive impairment is associated with methotrexate, dexamethasone, and chronic health conditions in a sex-specific manner, highlighting the need to investigate physiological mechanisms and monitor impact through survivorship.
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http://dx.doi.org/10.1093/jnci/djaa136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096369PMC
May 2021

The use of interval-compressed chemotherapy with the addition of vincristine, irinotecan, and temozolomide for pediatric patients with newly diagnosed desmoplastic small round cell tumor.

Pediatr Blood Cancer 2020 10 19;67(10):e28559. Epub 2020 Jul 19.

Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts.

Background: Desmoplastic small round cell tumor (DSRCT) is a rare aggressive sarcoma that affects children and young adults, and portends poor outcomes despite intensive multimodal treatment approaches. We report toxicity, response, and outcomes of patients with DSRCT treated with the addition of vincristine, irinotecan, and temozolomide (VIT) to interval-compressed chemotherapy as per Children's Oncology Group ARST08P1.

Methods: All newly diagnosed pediatric patients with DSRCT treated at Dana-Farber Cancer Institute and Boston Children's Hospital between 2014 and 2019 as per ARST08P1, Arm P2 with replacement of VAC cycles with VIT, were identified. Medical records were reviewed for clinical and disease characteristics, and treatment response and outcomes.

Results: Six patients were treated as per the above regimen. Median age at diagnosis was 15.1 years (range 3.2-16.4) and five patients were male. Five patients had abdominal primary tumors, of which one had exclusively intraabdominal and four had extraabdominal metastases. Two initial cycles of VIT were well tolerated with nausea, vomiting, diarrhea, and constipation as the most common adverse events. Overall response rate defined as partial or complete response after two initial cycles of VIT was 50%. For local control, all patients had surgical resection followed by radiotherapy, and two patients received hyperthermic intraperitoneal chemotherapy at the time of surgery. Of the four patients who have completed therapy to date, three remain disease-free with median follow-up time of 46.7 months.

Conclusions: The addition of VIT to interval-compressed chemotherapy is tolerable and active in DSRCT, with activity warranting additional investigation.
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http://dx.doi.org/10.1002/pbc.28559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721987PMC
October 2020

Incidence of and risk factors for late cholecystectomy in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

Eur J Cancer 2020 07 15;133:4-13. Epub 2020 May 15.

Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Department of Paediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.

Background: Gallbladder disease and need for cholecystectomy are common and significant contributors to patient morbidity and healthcare costs. Childhood cancer survivors are at elevated risk for developing cholelithiasis. However, their incidence of and risk factors for late (>5 years from diagnosis) cholecystectomy have not been studied.

Methods: A total of 25,549 survivors (median age at diagnosis 6.9 years, range 0-21.0; current age 30.7 years, range 5.6-65.9) diagnosed between 1970 and 1999 and 5037 siblings were queried for self-reported cholecystectomy occurring five or more years from primary cancer diagnosis. Piecewise exponential models evaluated associations between cancer treatment exposures and late cholecystectomy.

Results: Over a median follow-up period of 21.9 and 26.0 years, respectively, 789 survivors and 168 siblings underwent late cholecystectomy (cumulative incidence 7.2%, 95% confidence interval [CI] = 6.5-7.8% and 6.6%, 95% CI = 5.4-7.6%, respectively; rate ratio [RR] = 1.3, 95% CI = 1.1-1.5). Compared with siblings, survivors of acute lymphoblastic leukaemia (RR = 1.4, 95% CI = 1.2-1.8), soft tissue sarcoma (RR = 1.4, 95% CI = 1.0-1.8) and bone cancer (RR = 1.3, 95% CI = 1.0-1.8) were at the greatest risk. In addition to attained age, female sex and increasing body mass index, exposure to high-dose (≥750 mg/m) platinum chemotherapy (RR = 2.6, 95% CI = 1.5-4.5), vinca alkaloid chemotherapy (RR = 1.4, 95% CI = 1.1-1.8) or total body irradiation (TBI; RR = 2.2, 95% CI = 1.2-4.2) were each associated with late cholecystectomy.

Conclusions: Independent of traditional risk factors for gallbladder disease, exposure to high-dose platinum chemotherapy, vinca alkaloid chemotherapy or TBI increased risk for late cholecystectomy. These findings should inform current long-term follow-up guidelines and education regarding risk for late cholecystectomy.
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http://dx.doi.org/10.1016/j.ejca.2020.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365349PMC
July 2020

Comparison of Military Health System Data Repository and American College of Surgeons National Surgical Quality Improvement Program-Pediatric.

BMC Pediatr 2019 11 8;19(1):419. Epub 2019 Nov 8.

Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Background: Given the rarity of pediatric surgical disease, it is important to consider available large-scale data resources as a means to better study and understand relevant disease-processes and their treatments. The Military Health System Data Repository (MDR) includes claims-based information for > 3 million pediatric patients who are dependents of members and retirees of the United States Armed Services, but has not been externally validated. We hypothesized that demographics and selected outcome metrics would be similar between MDR and the previously validated American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P) for several common pediatric surgical operations.

Methods: We selected five commonly performed pediatric surgical operations: appendectomy, pyeloplasty, pyloromyotomy, spinal arthrodesis for scoliosis, and facial reconstruction for cleft palate. Among children who underwent these operations, we compared demographics (age, sex, and race) and clinical outcomes (length of hospital stay [LOS] and mortality) in the MDR and NSQIP-P, including all available overlapping years (2012-2014).

Results: Age, sex, and race were generally similar between the NSQIP-P and MDR. Specifically, these demographics were generally similar between the resources for appendectomy (NSQIP-P, n = 20,602 vs. MDR, n = 4363; median age 11 vs. 12 years; female 40% vs. 41%; white 75% vs. 84%), pyeloplasty (NSQIP-P, n = 786 vs. MDR, n = 112; median age 0.9 vs. 2 years; female 28% vs. 28%; white 71% vs. 80%), pyloromyotomy, (NSQIP-P, n = 3827 vs. MDR, n = 227; median age 34 vs. < 1 year, female 17% vs. 16%; white 76% vs. 89%), scoliosis surgery (NSQIP-P, n = 5743 vs. MDR, n = 95; median age 14.2 vs. 14 years; female 75% vs. 67%; white 72% vs. 75%), and cleft lip/palate repair (NSQIP-P, n = 6202 vs. MDR, n = 749; median age, 1 vs. 1 year; female 42% vs. 45%; white 69% vs. 84%). Length of stay and 30-day mortality were similar between resources. LOS and 30-day mortality were also similar between datasets.

Conclusion: For the selected common pediatric surgical operations, patients included in the MDR were comparable to those included in the validated NSQIP-P. The MDR may comprise a valuable clinical outcomes research resource, especially for studying infrequent diseases with follow-up beyond the 30-day peri-operative period.
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http://dx.doi.org/10.1186/s12887-019-1795-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839070PMC
November 2019

Late-onset anorectal disease and psychosocial impact in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

Cancer 2019 11 19;125(21):3873-3881. Epub 2019 Jul 19.

Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.

Background: The prevalence and associated psychosocial morbidity of late-onset anorectal disease after surgery and radiotherapy for the treatment of childhood cancer are not known.

Methods: A total of 25,530 survivors diagnosed between 1970 and 1999 (median age at cancer diagnosis, 6.1 years; age at survey, 30.2 years) and 5036 siblings were evaluated for late-onset anorectal disease, which was defined as a self-reported fistula-in-ano, self-reported anorectal stricture, or pathology- or medical record-confirmed anorectal subsequent malignant neoplasm (SMN) 5 or more years after the primary cancer diagnosis. Piecewise exponential models compared the survivors and siblings and examined associations between cancer treatments and late-onset anorectal disease. Multiple logistic regression with generalized estimating equations was used to evaluate associations between late-onset anorectal disease and emotional distress, as defined by the Brief Symptom Inventory 18 (BSI-18), and health-related quality of life, as defined by the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36).

Results: By 45 years after the diagnosis, 394 survivors (fistula, n = 291; stricture, n = 116; anorectal SMN, n = 26) and 84 siblings (fistula, n = 73; stricture, n = 23; anorectal neoplasm, n = 1) had developed late-onset anorectal disease (adjusted rate ratio [RR] for survivors vs siblings, 1.2; 95% confidence interval [CI], 1.0-1.5). Among survivors, pelvic radiotherapy with ≥30 Gy within 5 years of the cancer diagnosis was associated with late-onset anorectal disease (adjusted RR for 30-49.9 Gy vs none, 1.6; 95% CI, 1.1-2.3; adjusted RR for ≥50 Gy vs none, 5.4; 95% CI, 3.1-9.2). Late-onset anorectal disease was associated with psychosocial impairment in all BSI-18 and SF-36 domains.

Conclusions: Late-onset anorectal disease was more common among childhood cancer survivors who received higher doses of pelvic radiotherapy and was associated with substantial psychosocial morbidity.
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http://dx.doi.org/10.1002/cncr.32395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788933PMC
November 2019

Therapeutic Impact and Complications Associated with Surgical Lung Biopsy after Allogeneic Hematopoietic Stem Cell Transplantation in Children.

Biol Blood Marrow Transplant 2019 11 28;25(11):2181-2185. Epub 2019 Jun 28.

Boston Children's Hospital, Boston, Massachusetts; Dana-Farber and Boston Children's Hospital Cancer and Blood Disorders Center, Boston, Massachusetts.

Hematopoietic stem cell transplantation (HSCT) in the pediatric population is associated with pulmonary complications in 25% of recipients. The role of surgical lung biopsy (SLB) remains unclear because of concerns about both the therapeutic impact and morbidity associated with the procedure. A retrospective review of consecutive allogeneic HSCT recipients at Dana-Farber and Boston Children's Hospital Cancer and Blood Disorders Center between 2006 and 2016 was performed. All recipients who underwent SLB during the study period were identified and charts reviewed for perioperative complications, histopathologic findings, and changes in therapy delivered. Pearson's chi-square test and Student's t-test (or appropriate nonparametric test) were used to evaluate the associations between perioperative complication and categorical and continuous variables, respectively. Five hundred fifty-five HSCTs were included, among which 48 SLBs (8.6%) were identified. Median follow-up time was 24 months (range, 0 to 139). Thirty-day postoperative morbidity was 16.7% and 30-day postoperative mortality 10.4% (n = 5). The overall 30-day postoperative complication rate (including mortality) was 20.8% (n = 10). No mortalities were directly attributable to SLB. Definitive diagnoses were identified in 70.8% of SLBs (n = 34), and therapeutic changes occurred in 79.2% (n = 38). Overall, 83.3% of SLBs (n = 40) either provided a diagnosis or led to a change in therapy. SLB has an acceptable risk of perioperative complications in this medically complicated and often severely ill population. In most HSCT patients, SLB aids in defining the etiology of pulmonary infiltrates and can inform therapeutic decisions in patients where noninvasive diagnostic modalities have failed to provide a definitive diagnosis.
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http://dx.doi.org/10.1016/j.bbmt.2019.06.026DOI Listing
November 2019

Multicenter pre-operative assessment of pediatric ovarian malignancy.

J Pediatr Surg 2019 Sep 25;54(9):1921-1925. Epub 2019 Feb 25.

Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA; Department of Pediatric Oncology, Dana-Farber/Boston Children's Cancer Center and Harvard Medical School, Boston, MA.

Purpose: The purpose of this study was to develop a pre-operative risk assessment tool for childhood and adolescent ovarian malignancy, in order to guide operative management of pediatric ovarian masses.

Methods: We conducted a retrospective analysis of patients <18 years old who underwent ovarian surgery at two quaternary care pediatric centers over 4 years (1/1/13-12/31/16). Probability of malignancy was estimated based on imaging characteristics (simple cyst, heterogeneous, or solid), maximal diameter, and tumor markers (α-fetoprotein, β-human chorionic gonadotropin).

Results: Among 188 children with ovarian masses, 11% had malignancies. For simple cysts, there were no malignancies (0/24, 95% CI = 0-17%). Among solid lesions, 44% (15/34, 95% CI = 28-62%) were malignant. Among marker-elevated heterogeneous masses, 40% (2/5, 95% CI = 12-77%) were malignant. Conversely, small (≤10 cm) and large (>10 cm) marker-negative heterogeneous lesions had malignancy proportions of 0% (0/39, 95% CI = 0-11%) and 5% (2/40, 95% CI = 1-18%), respectively.

Conclusions: Given the malignancy estimates identified from these multi-institutional data, we recommend an attempt at ovarian-sparing resection for simple cysts or tumor marker-negative heterogeneous lesions ≤10 cm. Oophorectomy is recommended for solid masses or heterogeneous lesions with elevated markers. Finally, large (>10 cm) heterogeneous masses with non-elevated markers warrant a careful discussion of ovarian-sparing techniques. Complete surgical staging is mandatory regardless of operative procedure.

Type Of Study: Study of Diagnostic Test.

Level Of Evidence: Level I.
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http://dx.doi.org/10.1016/j.jpedsurg.2019.02.019DOI Listing
September 2019

Fertility and hormone preservation and restoration for female children and adolescents receiving gonadotoxic cancer treatments: A systematic review.

J Pediatr Surg 2019 Nov 22;54(11):2200-2209. Epub 2019 Jan 22.

Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Division of Pediatric Surgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. Electronic address:

Background/purpose: The purpose of this systematic review by the American Pediatric Surgical Cancer Committee was to summarize evidence from the current medical literature regarding fertility restoration and hormone replacement for female children and adolescents treated with gonadotoxic treatments.

Methods: Using PRISMA guidelines, questions were addressed by searching Medline, Cochrane, Embase Central and National clearing house databases using relevant search terms. Eligible studies included those that addressed ovarian tissue cryopreservation (OTC), oocyte harvest, ovarian transposition, and ovarian tissue auto-transplantation for females under the age of 20. Four reviewers independently screened studies for eligibility, extracted data and assessed the risk of bias. Study outcomes were summarized in a narrative synthesis.

Results: Two thousand two hundred seventy-six studies were identified by database search and manual review and 2185 were eliminated based on defined exclusion criteria. Ninety-one studies served as the basis for the systematic review. There were 1019 patients who underwent OTC with ages ranging from 0.4 to 20.4 years old, with 298 under the age of 13. Twenty patients aged 13-20 years old underwent successful oocyte harvest. Thirty-seven children underwent ovarian transposition as a means of fertility preservation. Eighteen patients underwent auto-transplantation of thawed ovarian cortical tissue that was harvested before the age of 21 years resulting in 10 live births.

Conclusions: Clinically accepted and experimental fertility preservation options such as OTC, oocyte cryopreservation, and ovarian transposition are available to females aged 20 years and younger who are at risk for premature ovarian insufficiency and infertility due to gonadotoxic treatments. There is a large cohort of pediatric-aged patients, with a wide variety of diagnoses and treatments, who have undergone fertility preservation. Currently, fertility and hormone restoration experience for patients who were 20- years of age or younger at the time of fertility preservation remains limited.

Level Of Evidence: IV.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.12.021DOI Listing
November 2019

Opioid Prescription Patterns for Children Following Laparoscopic Appendectomy.

Ann Surg 2020 12;272(6):1149-1157

Department of Surgery, Boston Children's Hospital, Boston, MA.

Objective: To describe variability in and consequences of opioid prescriptions following pediatric laparoscopic appendectomy.

Summary Background Data: Postoperative opioid prescribing patterns may contribute to persistent opioid use in both adults and children.

Methods: We included children <18 years enrolled as dependents in the Military Health System Data Repository who underwent uncomplicated laparoscopic appendectomy (2006-2014). For the primary outcome of days of opioids prescribed, we evaluated associations with discharging service, standardized to the distribution of baseline covariates. Secondary outcomes included refill, Emergency Department (ED) visit for constipation, and ED visit for pain.

Results: Among 6732 children, 68% were prescribed opioids (range = 1-65 d, median = 4 d, IQR = 3-5 d). Patients discharged by general surgery services were prescribed 1.23 (95% CI = 1.06-1.42) excess days of opioids, compared with those discharged by pediatric surgery services. Risk of ED visit for constipation (n = 61, 1%) was increased with opioid prescription [1-3 d, risk ratio (RR) = 2.46, 95% CI = 1.31-5.78; 4-6 d, RR = 1.89, 95% CI = 0.83-4.67; 7-14 d, RR = 3.75, 95% CI = 1.38-9.44; >14 d, RR = 6.27, 95% CI = 1.23-19.68], compared with no opioid prescription. There was similar or increased risk of ED visit for pain (n = 319, 5%) with opioid prescription [1-3 d, RR = 1.00, 95% confidence interval (CI) = 0.74-1.32; 4-6 d, RR = 1.31, 95% CI = 0.99-1.73; 7-14 d, RR = 1.52, 95% CI = 1.00-2.18], compared with no opioid prescription. Likewise, need for refill (n = 157, 3%) was not associated with initial days of opioid prescribed (reference 1-3 d; 4-6 d, RR = 0.96, 95% CI = 0.68-1.35; 7-14 d, RR = 0.91, 95% CI = 0.49-1.46; and >14 d, RR = 1.22, 95% CI = 0.59-2.07).

Conclusions: There was substantial variation in opioid prescribing patterns. Opioid prescription duration increased risk of ED visits for constipation, but not for pain or refill.
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http://dx.doi.org/10.1097/SLA.0000000000003171DOI Listing
December 2020

Update on neuroblastoma.

J Pediatr Surg 2019 Mar 19;54(3):383-389. Epub 2018 Sep 19.

Ann & Robert H Lurie Children's Hospital of Chicago, Northwestern University, Chicago, IL.

Neuroblastoma is an embryonic cancer arising from neural crest stem cells. This cancer is the most common malignancy in infants and the most common extracranial solid tumor in children. The clinical course may be highly variable with the possibility of spontaneous regression in the youngest patients and increased risk of aggressive disease in older children. Clinical heterogeneity is a consequence of the diverse biologic characteristics that determine patient risk and survival. This review will focus on current progress in neuroblastoma staging, risk stratification, and treatment strategies based on advancing knowledge in tumor biology and genetic characterization. TYPE OF STUDY: Review article. LEVEL OF EVIDENCE: Level II.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.09.004DOI Listing
March 2019

Update on Wilms tumor.

J Pediatr Surg 2019 Mar 19;54(3):390-397. Epub 2018 Sep 19.

Department of Surgery, Division of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI.

This article reviews of the current evidence-based treatment standards for children with Wilms tumor. In this article, a summary of recently completed clinical trials by the Children's Oncology Group is provided, the current diagnostic evaluation and surgical standards are discussed, and the surgical impact on current risk stratification for patients with Wilms tumor is highlighted. LEVEL OF EVIDENCE: This is a review article of previously published and referenced LEVEL 1 studies, but also includes expert opinion LEVEL V, represented by the American Pediatric Surgical Association Cancer Committee.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542630PMC
March 2019

Long-Term Risk of Venous Thromboembolism in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.

J Clin Oncol 2018 Sep 14:JCO2018784595. Epub 2018 Sep 14.

Arin L. Madenci, Brent R. Weil, and Christopher B. Weldon, Boston Children's Hospital; Arin L. Madenci and Larissa Nekhlyudov, Brigham and Women's Hospital; Brent R. Weil, Larissa Nekhlyudov, Lisa R. Diller, and Christopher B. Weldon, Dana-Farber Cancer Institute; Arin L. Madenci, Brent R. Weil, Larissa Nekhlyudov, Lisa R. Diller and Christopher B. Weldon, Harvard Medical School, Boston, MA; Qi Liu, University of Alberta, Edmonton, Alberta, Canada; Andrew J. Murphy, Todd M. Gibson, Yutaka Yasui, Christopher L. Tinkle, and Gregory T. Armstrong, St Jude Children's Research Hospital, Memphis, TN; Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Rebecca M. Howell, The University of Texas MD Anderson Cancer Center, Houston, TX; and Kevin C. Oeffinger, Duke University School of Medicine, Durham, NC.

Purpose To estimate the incidence of late-occurring venous thromboembolism (VTE) among survivors of childhood cancer and to identify risk factors for VTE to facilitate diagnosis and prevention. Methods The Childhood Cancer Survivor Study is a multi-institutional cohort of 24,355 5-year childhood cancer survivors (diagnosed between 1970 and 1999; median age at last follow-up, 28.7 years [range, 5.6 to 58.9 years]; median follow-up since diagnosis, 21.3 years [range, 5.0 to 39.2 years]) and 5,051 sibling participants. The primary end point was self-reported late (≥ 5 years after cancer diagnosis) VTE. Rate ratios (RRs) were estimated with multivariable piecewise exponential models. Results Late VTE incidence among survivors and siblings was 1.1 and 0.5 events per 1,000 person-years, respectively (RR, 2.2; 95% CI, 1.7 to 2.8), with 2.5 excess events per 100 survivors over 35 years. Among survivors, risk factors for VTE were female sex (RR, 1.3; 95% CI, 1.1 to 1.6), cisplatin (reference none; 1 to 199 mg/m: RR, 3.0 [95% CI, 1.4 to 6.5]; 200 to 399 mg/m: RR, 1.9 [95% CI, 1.0 to 3.6]; ≥ 400 mg/m: RR, 2.0 [95% CI, 1.2 to 3.3]), l-asparaginase (RR, 1.3; 95% CI, 1.0 to 1.7), obesity or underweight (reference body mass index [BMI] 18.5 to 24.9 kg/m; BMI ≥ 30.0 kg/m: RR, 1.6 [95% CI, 1.2 to 2.0]; BMI < 18.5 kg/m: RR, 2.4 [95% CI, 1.7 to 3.4]), and late cancer recurrence or subsequent malignant neoplasm (RR, 4.6; 95% CI, 3.6 to 5.8). Among lower-extremity osteosarcoma survivors, limb salvage (reference amputation; RR, 3.1; 95% CI, 1.2 to 7.5) and cisplatin 200 to 399 or ≥ 400 mg/m (reference none; RR, 4.0 [95% CI, 1.1 to 14.6] and 2.9 [95% CI, 1.1 to 8.0], respectively) were independently associated with late VTE. VTE was associated with increased risk for nonexternal cause late mortality (RR, 1.9; 95% CI, 1.6 to 2.3). Conclusion Childhood cancer survivors are at increased risk for VTE across their lifespan and a diagnosis of VTE increases mortality risk. Interventions that target potentially modifiable comorbidities, such as obesity, warrant consideration, with prophylaxis for high-risk survivors, including those treated with cisplatin and limb-sparing approaches.
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http://dx.doi.org/10.1200/JCO.2018.78.4595DOI Listing
September 2018

Incidence and risk factors for sepsis after childhood splenectomy.

J Pediatr Surg 2019 Jul 25;54(7):1445-1448. Epub 2018 Jun 25.

Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States.

Background: Children who have undergone splenectomy may develop impaired immunologic function and heightened risk of overwhelming postsplenectomy infection. We sought to define the long-term rate of and risk factors for postsplenectomy sepsis.

Methods: We leveraged the Military Health System Data Repository, a nationally representative claims database including >3 million children registered as dependents of members of the United States Armed Services (2005-2014). Inclusion criterion was splenectomy at age 18 years or prior. The primary outcome was hospitalization for sepsis.

Results: Among 195 children who underwent splenectomy, 7% (n = 13) were hospitalized with sepsis, with an incidence of 1.8 (95% CI = 1.0-3.1) events per 100 person-years. The median time to sepsis was 224 days (IQR = 109-606) and 38% (5/13) of events occurred within the first postsplenectomy year. The postsplenectomy mortality rate was 1% (n = 3). After adjusting for underlying diagnosis, older age at splenectomy (HR = 0.90 per year, 95% CI = 0.81-0.99) was associated with decreased hazard of sepsis.

Conclusions: In a contemporary national cohort, the prevalence of postsplenectomy sepsis was 7% (1.8 events per 100 person-years). Although most presented during the first year after splenectomy, many (62%) sepsis events occurred later, suggesting that postsplenectomy immunologic dysfunction persists beyond one year. The immunologic consequences of asplenia must continue to be acknowledged, as postsplenectomy sepsis remains a serious concern.

Type Of Study: Prognosis study.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.06.024DOI Listing
July 2019

New Agents, Emerging Late Effects, and the Development of Precision Survivorship.

J Clin Oncol 2018 07 6;36(21):2231-2240. Epub 2018 Jun 6.

Eric J. Chow and Rebecca Gardner, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, and University of Washington, Seattle, WA; Zoltan Antal, Weill Cornell Medical College, New York Presbyterian Hospital, and Memorial Sloan Kettering Cancer Center, New York; Louis S. Constine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY; W. Hamish Wallace, Royal Hospital for Sick Children, University of Edinburgh, Edinburgh, United Kingdom; Brent R. Weil and Jennifer M. Yeh, Boston Children's Hospital, Harvard Medical School, Boston, MA; and Elizabeth Fox, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA.

Incremental improvements in the treatment of children and adolescents with cancer have led to 5-year survival rates reaching nearly 85%. In the past decade, impressive progress has been made in understanding the biology of many pediatric cancers. With that understanding, multiple new agents have become available that offer the promise of more-effective and less-toxic treatment. These include agents that target various cell surface antigens and engage the adaptive immune system, as well as those that interfere with key signaling pathways involved in tumor development and growth. For local control, surgery and radiation techniques also have evolved, becoming less invasive or featuring new techniques and particles that more precisely target the tumor and limit the dose to normal tissue. Nevertheless, targeted agents, like conventional chemotherapy, radiotherapy, and surgery, may have off-target effects and deserve long-term follow-up of their safety and efficacy. These include injury to the endocrine, cardiovascular, and immunologic systems. New radiation and surgical techniques that theoretically reduce morbidity and improve long-term quality of life must also be validated with actual patient outcomes. Finally, with advances in genomics, information on host susceptibility to late effects is beginning to emerge. Such knowledge, coupled with improved metrics that better describe the spectrum of potential late effects across the entire lifespan, can lead to the development of decision models that project the potential long-term health outcomes associated with various treatment and follow-up strategies. These developments will help extend the current focus on precision medicine to precision survivorship, where clinicians, patients, and families will have a better grasp of the potential risks, benefits, and tradeoffs associated with the growing number of cancer treatment options.
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http://dx.doi.org/10.1200/JCO.2017.76.4647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053298PMC
July 2018

Hernia recurrence following inguinal hernia repair in children.

J Pediatr Surg 2018 Nov 24;53(11):2214-2218. Epub 2018 Mar 24.

Department of Surgery, Boston Children's Hospital, Boston, MA.

Purpose: We aimed to describe the incidence, timing, and predictors of recurrence following inguinal hernia repair (IHR) in children.

Methods: We used the TRICARE claims database, a national cohort of >3 million child dependents of members of the U.S. Armed Forces. We abstracted data on children <12y who underwent IHR (2005-2014). Our primary outcome was recurrence (ICD9-CM diagnosis codes). We calculated incidence rates for the population and stratified by age, time from repair to recurrence, and multivariable logistic regression to determine predictors.

Results: Nine thousand nine hundred ninety-three children met inclusion criteria. Age at time of IHR was ≤1y in 37%, 2-3y in 23%, 4-5y in 16%, and 5-12y in 24%. Median follow-up time was 3.5y (IQR:1.6-6.1). 137 patients recurred (1.4%), with an incidence of 3.46 per 1000 person-years. Over half occurred in children 0-1y at repair (60%). The majority occurred within a year following repair (median 209 days [IQR:79-486]). Children 0-1y had 2.53 times greater odds of recurrence (compared to >5y). Children with multiple comorbidities had 5.45 times greater odds compared to those with no comorbidities.

Conclusions: The incidence of recurrence following IHR is 3.46 per 1000 person-years. The majority occurred within a year of repair. Children ≤1y and those with multiple comorbidities were at increased risk.

Level Of Evidence: Prognosis Study, Level II.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.03.021DOI Listing
November 2018

Late Infection-Related Mortality in Asplenic Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.

J Clin Oncol 2018 06 17;36(16):1571-1578. Epub 2018 Apr 17.

Brent R. Weil, Arin L. Madenci, and Christopher B. Weldon, Boston Children's Hospital; Brent R. Weil, Arin L. Madenci, Lisa R. Diller, and Christopher B. Weldon, Harvard Medical School; Brent R. Weil, Lisa R. Diller, and Christopher B. Weldon, Dana-Farber Cancer Institute; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Qi Liu, University of Alberta, Edmonton, Alberta, Canada; Rebecca M. Howell and Susan A. Smith, The University of Texas MD Anderson Cancer Center, Houston, TX; Todd M. Gibson, Yutaka Yasui, Christopher L. Tinkle, and Gregory T. Armstrong, St Jude Children's Research Hospital, Memphis, TN; Joseph P. Neglia, University of Minnesota, Minneapolis, MN; Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Emily S. Tonorezos and Danielle N. Friedman, Memorial Sloan Kettering Cancer Center, New York; Louis S. Constine, University of Rochester Medical Center, Rochester, NY; and Kevin C. Oeffinger, Duke University, Durham, NC.

Purpose Infection-related outcomes associated with asplenia or impaired splenic function in survivors of childhood cancer remains understudied. Methods Late infection-related mortality was evaluated in 20,026 5-year survivors of childhood cancer (diagnosed < 21 years of age from 1970 to 1999; median age at diagnosis, 7.0 years [range, 0 to 20 years]; median follow-up, 26 years [range, 5 to 44 years]) using cumulative incidence and piecewise-exponential regression models to estimate adjusted relative rates (RRs). Splenic radiation was approximated using average dose (direct and/or indirect) to the left upper quadrant of the abdomen (hereafter, referred to as splenic radiation). Results Within 5 years of diagnosis, 1,354 survivors (6.8%) had a splenectomy and 9,442 (46%) had splenic radiation without splenectomy. With 62 deaths, the cumulative incidence of infection-related late mortality was 1.5% (95% CI, 0.7% to 2.2%) at 35 years after splenectomy and 0.6% (95% CI, 0.4% to 0.8%) after splenic radiation. Splenectomy (RR, 7.7; 95% CI, 3.1 to 19.1) was independently associated with late infection-related mortality. Splenic radiation was associated with increasing risk for late infection-related mortality in a dose-response relationship (0.1 to 9.9 Gy: RR, 2.0; 95% CI, 0.9 to 4.5; 10 to 19.9 Gy: RR, 5.5; 95% CI, 1.9 to 15.4; ≥ 20 Gy: RR, 6.0; 95% CI, 1.8 to 20.2). High-dose alkylator chemotherapy exposure was also independently associated with an increased risk of infection-related mortality (RR, 1.9; 95% CI, 1.1 to 3.4). Conclusion Splenectomy and splenic radiation significantly increase risk for late infection-related mortality. Even low- to intermediate-dose radiation exposure confers increased risk, suggesting that the spleen is highly radiosensitive. These findings should inform long-term follow-up guidelines for survivors of childhood cancer and should lead clinicians to avoid or reduce radiation exposure involving the spleen whenever possible.
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http://dx.doi.org/10.1200/JCO.2017.76.1643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978467PMC
June 2018

Testicular atrophy following inguinal hernia repair in children.

Pediatr Surg Int 2018 May 28;34(5):553-560. Epub 2018 Mar 28.

Department of Surgery, Boston Children's Hospital, Boston, MA, USA.

Purpose: We sought to determine the incidence and timing of testicular atrophy following inguinal hernia repair in children.

Methods: We used the TRICARE database, which tracks care delivered to active and retired members of the US Armed Forces and their dependents, including > 3 million children. We abstracted data on male children < 12 years who underwent inguinal hernia repair (2005-2014). We excluded patients with history of testicular atrophy, malignancy or prior related operation. Our primary outcome was the incidence of the diagnosis of testicular atrophy. Among children with atrophy, we calculated median time to diagnosis, stratified by age/undescended testis.

Results: 8897 children met inclusion criteria. Median age at hernia repair was 2 years (IQR 1-5). Median follow-up was 3.57 years (IQR 1.69-6.19). Overall incidence of testicular atrophy was 5.1/10,000 person-years, with the highest incidence in those with an undescended testis (13.9/10,000 person-years). All cases occurred in children [Formula: see text] 5 years, with 72% in children < 2 years. Median time to atrophy was 2.4 years (IQR 0.64-3), with 30% occurring within 1 year and 75% within 3 years.

Conclusion: Testicular atrophy is a rare complication following inguinal hernia repair, with children < 2 years and those with an undescended testis at highest risk. While 30% of cases were diagnosed within a year after repair, atrophy may be diagnosed substantially later.

Level Of Evidence: Prognosis Study, Level II.
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http://dx.doi.org/10.1007/s00383-018-4255-zDOI Listing
May 2018

Autoamputation of the Appendix Presenting as a Calcified Abdominal Mass Following Necrotizing Enterocolitis.

Pediatr Dev Pathol 2017 Jul-Aug;20(4):335-339. Epub 2017 Jan 25.

1 Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.

Autoamputation of the appendix has previously been reported in the literature, but it is likely an unusual event. We report a 2-year-old male child who had previously undergone laparotomy and bowel resection for necrotizing enterocolitis. Two years later a calcified intra-abdominal mass was identified on abdominal radiography and ultrasonography. Eventual laparotomy revealed a densely calcified mass within the transverse mesocolon. The mass was uneventfully resected. Pathologic evaluation showed appendiceal tissue, consistent with prior autoamputation of the vermiform appendix. Autoamputation of the appendix has not to our knowledge previously been associated with a calcified mass nor been associated with a history of necrotizing enterocolitis, and these factors distinguish this case as noteworthy.
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http://dx.doi.org/10.1177/1093526616686256DOI Listing
May 2019

Primary laparoscopic gastrojejunostomy tubes as a feeding modality in the pediatric population.

J Pediatr Surg 2017 Sep 20;52(9):1421-1425. Epub 2017 May 20.

Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Purpose: Outcomes associated with primary laparoscopic gastrojejunal (GJ) tube placement in the pediatric population were evaluated.

Methods: A single-institution, retrospective review examined patients undergoing laparoscopic GJ tube placement between June 2011 and December 2014. Outcomes included gastric feeding tolerance, subsequent fundoplication, complications, and mortality.

Results: Ninety laparoscopic GJ tubes were placed. Median follow-up was 342days (interquartile range [IQR]=141-561days). Median patient age was 5months (IQR=3-11months) and weight was 5.2kg (IQR=4-8.4kg). The most common indications for placement were gastroesophageal reflux (n=85, 94.4%) and/or aspiration (n=40, 44.4%). Most common comorbidities included cardiac (n=34, 37.8%) and respiratory (n=29, 32.2%) diseases. The complication rate was 17.8%, including one case of intestinal perforation. Thirty-four (37.7%) patients transitioned to gastric feeding within 1year; time to conversion was 156days (IQR=117-210days); of those, 18.9% patients transitioned to oral feedings. A fundoplication was later performed in 4 children for persistent reflux. Mortality was 23.3% with no procedural-related deaths.

Conclusion: Primary laparoscopically placed GJ tubes are a reliable means of enteral access for pediatric patients with gastric feeding intolerance. Many of these children are successfully transitioned to gastric and/or oral feedings over time. Further studies are needed to characterize which patients are best served with a GJ tube versus alternatives such as fundoplication.

Level Of Evidence: III (treatment) TYPE OF STUDY: Retrospective.
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http://dx.doi.org/10.1016/j.jpedsurg.2017.05.015DOI Listing
September 2017

The role of thymectomy in the treatment of juvenile myasthenia gravis: a systematic review.

Pediatr Surg Int 2017 Jun 11;33(6):683-694. Epub 2017 Apr 11.

Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.

Background: The role of thymectomy in the treatment of juvenile myasthenia gravis (JMG) is poorly defined. The objective of this systematic review was to evaluate the effect of thymectomy on survival, disease severity, and peri-operative complications for patients with JMG.

Methods: A search of MEDLINE, EMBASE, and the Cochrane Library (1/1/2000-3/1/2016) identified all English language, human studies of thymectomy for JMG. The population was patients with JMG age ≤18 years who underwent thymectomy (comparator group was unexposed to thymectomy). Outcomes included survival, disease severity, and post-operative complications. Data extraction was performed by independent reviewers.

Results: Sixteen retrospective studies included 1131 participants with JMG and 488 (43%) underwent thymectomy. Post-operative improvement in JMG severity occurred for 77% (n = 376/488). Comparisons of thymectomy to non-operative management were mixed. Post-operative complications were poorly recorded. Power to compare surgical approaches was limited. Outcomes specific to antibodies, surgical pathology findings, severity of JMG, and timing of thymectomy were sparse.

Conclusions: Existing data regarding thymectomy for JMG are limited and entirely retrospective. The majority of patients who underwent thymectomy had improvement in disease severity and post-operative complications were rare. Prospective, multicenter study of thymectomy for JMG is warranted.
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http://dx.doi.org/10.1007/s00383-017-4086-3DOI Listing
June 2017

Safety and cost-effectiveness of port removal outside of the operating room among pediatric patients.

J Pediatr Surg 2016 Nov 23;51(11):1891-1895. Epub 2016 Aug 23.

Department of Anesthesiology, Preoperative and Pain Medicine, Boston Children's Hospital, Boston, MA. Electronic address:

Purpose: The current emphasis on fiscally responsible health spending in the era of the Affordable Care Act and other health care reform necessitates cost-conscious delivery of care. "Value" in health care is defined as the quality of care divided by the cost. As such, health systems optimize value by providing the most cost-effective care possible without sacrificing safety or outcomes. Elective, minimal risk surgical procedures in children may be value-enhanced by moving from an operating room (OR) to a more cost-efficient setting. The purpose of this study was to assess the safety and cost of performing the removal of implantable central venous access devices ("ports") in locations other than the main OR.

Methods: We compared port removal at three sites: 1. Main OR, 2. Satellite OR, and 3. Clinic Procedure Room. This was a mixed-methods study including a retrospective review of medical records and prospective observation/interviewing. To calculate cost without the inherent biases of hospital charges, costs, and payments, we utilized the methodology of time-driven activity based costing. Specifically, we recorded time spent by the patient in hospital facilities and with health care personnel. This duration was then weighted with the hourly cost of each health care professional and hospital space. The Mann-Whitney U test compared time and cost across the three sites. Overall cost at each site was divided by overall cost at the referent site (Main OR) to obtain a ratio of cost savings.

Results: A total of 120 patients (40 per site) were included in the analysis. Demographic and clinical factors were not significantly different between sites. No complication occurred with port removal at any site. Time of the entire care episode was significantly decreased in the Clinic (median 161min, 95% confidence interval [CI] 134-188min), compared to the Main OR (median 235min, 95% confidence interval [CI] 209-251min) or Satellite OR (median 228min, 95% confidence interval [CI] 211-245min). Overall cost was decreased by 25% (95% CI: 13-34%) at the Clinic and by 6% (95% CI: -2-11%) at the Satellite OR, compared to the Main OR (referent, P<0.01).

Conclusion: In our study, port removal in the Clinic Procedure Room was not associated with increased risk of negative outcomes. Shifting port removal from the Main OR to the Clinic may result in substantial cost savings.
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http://dx.doi.org/10.1016/j.jpedsurg.2016.07.017DOI Listing
November 2016

Commentary on "Simultaneous Resection of High-risk Liver Tumors and Pulmonary Metastases in Children".

Ann Surg 2015 Jul;262(1):e4

Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA,

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July 2015

Prospective determination of percutaneous endoscopic gastrostomy complication rates in children: still a safe procedure.

Surgery 2012 Oct 31;152(4):714-9; discussion 719-21. Epub 2012 Aug 31.

Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.

Background: Percutaneous endoscopic gastrostomy (PEG) placement in children has come under scrutiny with reports of improved safety profiles using laparoscopic-assisted techniques. However, these reports are generally limited by their retrospective nature and the inclusion of historically determined PEG complication rates in children. Complication rates associated with PEG placement in children have not been prospectively studied, and a true modern understanding of the safety profile of PEG when performed in children is unknown. We prospectively followed children undergoing PEG to establish a clear and current understanding of the complication rates associated with this procedure.

Methods: Consecutive PEG procedures performed between December 2009 and August 2010 at a single, tertiary-care pediatric hospital were enrolled for study. Patients were followed prospectively for 90 days with data regarding complications acquired via standardized interviews at 7, 30, and 90 days postoperatively.

Results: We enrolled 103 patients for study. Median age and weight at time of operation was 8 months (range, 2 weeks-21 years) and 6.9 kg (range, 2-42). Patients underwent primary placement of either a PEG button (n = 70) or PEG tube (n = 33). There were no intraoperative complications, with a 100% procedure completion rate. Six deaths occurred during this follow-up time period (mean of 37 days postoperatively) and were attributed to causes other than PEG placement. Four patients were lost to follow-up. One PEG tube was electively discontinued before the end of the follow-up period without complication. Of the remaining 92 patients with complete data, 13 complications were observed in 10 patients. Total complication rate was 14%.

Conclusion: Rates of PEG complications observed in this prospective study are low and are generally minor. Observed rates of PEG-specific complications are lower than historic reports. The safety profile of PEG when performed in today's pediatric population remains comparable in safety to techniques such as laparoscopic-assisted gastrostomy.
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http://dx.doi.org/10.1016/j.surg.2012.07.018DOI Listing
October 2012
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