Surgical management of pediatric Crohn's disease.

Management of pediatric-onset Crohn's disease uniquely necessitates consideration of growth, pubertal development, psychosocial function and an increased risk for multiple future surgical interventions. Both medical and surgical management are rapidly advancing; therefore, it is increasingly important to define the role of surgery and the breadth of surgical options available for this complex patient population. Particularly, the introduction of biologics has altered the disease course; however, the ultimate need for surgical intervention has remained unchanged. This review defines and evaluates the surgical techniques available for management of the most common phenotypes of pediatric-onset Crohn's disease as well as identifies critical perioperative considerations for optimizing post-surgical outcomes.

Evaluation of Post-neonatal Intensive Care Unit Home Irrigations Prior to Pull-through: Implications for Hirschsprung Disease Management.

BACKGROUND: Pull-through procedures for Hirschsprung disease (HD) can be performed during the Neonatal Intensive Care Unit (NICU) stay or delayed until discharge following home irrigations. This study assesses the safety of a delayed pull-through as an alternative to neonatal reconstruction in infants with successful abdomen decompression with home irrigations based on Hirschsprung-associated enterocolitis (HAEC) development. METHODS: A single-institution retrospective review of neonates with HD who underwent delayed or neonatal pull-through from July 2018-July 2022. Endpoints included post-pull-through HAEC incidence, recurrence at an 18-month follow-up, time to the first HAEC episode, NICU length of stay (LOS), and HAEC-related LOS. RESULTS: Twenty-four neonates were included. Eighteen were discharged from the NICU with home irrigations. Of these, 3 (28%) developed enterocolitis preoperatively, 12 (67%) underwent a delayed pull-through. NICU LOS in the delayed cohort was 3 times shorter than in the neonatal (6 vs. 18 days, p < 0.01). The incidence of enterocolitis (82% vs. 80%), time to the first episode (43 vs. 57 days), and HAEC-related LOS (median of 3 days) were similar. CONCLUSIONS: Delayed HD pull-through is a viable neonatal reconstruction alternative that reduces NICU stay without increasing the risk of postoperative HAEC development. TYPE OF STUDY: Original Research Article. LEVEL OF EVIDENCE: III.

State of the Art Bowel Management for Pediatric Colorectal Problems: Spinal Anomalies.

BACKGROUND: Patients with spinal abnormalities often struggle with fecal and/or urinary incontinence (up to 87 and 92%, respectively) and require a collaborative approach to bowel management in conjunction. METHODS: To define existing approaches and propose state-of-the-art bowel management, a literature search was performed using Medline/PubMed, Google Scholar, Cochrane, and EMBASE databases and focusing on the manuscripts published July 2013 and July 2023. RESULTS: Patients with spinal anomalies have impaired innervation of the rectum and anal canal, decreasing the success rate from laxatives and rectal enemas. Thus, transanal irrigations and antegrade flushes are widely utilized in this group of patients. Based on spinal MRI, the potential for bowel control in these children depends on age, type, and lesion level. On referral for bowel management, a contrast study is performed to assess colonic motility and evacuation of stool, followed by a series of abdominal X-rays to define colonic emptying and adjust the regimen. The options for management include laxatives, rectal enemas, transanal irrigations, antegrade flushes, and the creation of a stoma. Approximately 22-71% of patients achieve social continence dependent on the type and level of the lesion. CONCLUSION: Patients with spinal anomalies require a thorough assessment for continence potential and stool burden prior to initiation of bowel management. The optimal treatment option is defined according to the patient's age, anatomy, and mobility. The likelihood of independent bowel regimen administration should be discussed with the patients and their caregivers.

State of the Art Bowel Management for Pediatric Colorectal Problems: Hirschsprung Disease.

After an initial pull-though, patients with Hirschsprung disease (HD) can present with obstructive symptoms, Hirschsprung-associated enterocolitis (HAEC), failure to thrive, or fecal soiling. This current review focuses on algorithms for evaluation and treatment in children with HD as a part of a manuscript series on updates in bowel management. In constipated patients, anatomic causes of obstruction should be excluded. Once anatomy is confirmed to be normal, laxatives, fiber, osmotic laxatives, or mechanical management can be utilized. Botulinum toxin injections are performed in all patients with HD before age five because of the nonrelaxing sphincters that they learn to overcome with increased age. Children with a patulous anus due to iatrogenic damage of the anal sphincters are offered sphincter reconstruction. Hypermotility is managed with antidiarrheals and small-volume enemas. Family education is crucial for the early detection of HAEC and for performing at-home rectal irrigations.

Hirschsprung-Associated Enterocolitis at a Referral Institution: A Retrospective Review.

BACKGROUND: Hirschsprung-associated enterocolitis (HAEC) is the most common cause of morbidity and mortality amongst patients with Hirschsprung disease (HD); rectal Botulinum toxin (Botox) has been reported a possible prevention strategy. We aimed to evaluate our institution's historic cohort of HD patients, first to determine our incidence of HAEC and second to begin assessing the effect of Botox on HAEC incidence. METHODS: Patients with HD seen at our institution between 2005 and 2019 were reviewed. Incidence of HD and frequencies of HAEC and Botox injections were tallied. Associations between initial Botox treatment or transition zone and HAEC incidence were evaluated. RESULTS: We reviewed 221 patients; 200 were included for analysis. One hundred thirteen (56.5%) patients underwent primary pull-through at a median age of 24 days (IQR 91). Eighty-seven (43.5%) patients with initial ostomy had their intestinal continuity reestablished at a median of 318 days (IQR 595). Ninety-four (49.5%) experienced at least one episode of HAEC and 62 (66%) experienced multiple episodes of HAEC. Nineteen (9.6%) patients had total colonic HD and had an increased total incidence of HAEC compared to patients without total colonic HD (89% vs 44%, p < 0.001). Six (2.9%) patients received Botox injections at the time of pull-through or ostomy takedown; one experienced an episode of HAEC (versus 50.7% of the patients who were confirmed to have not received Botox injections at their surgery, p = 0.102). CONCLUSION: Further prospective study on Botox's effect on Hirschsprung-associated enterocolitis is required and is the next step in our investigation. LEVEL OF EVIDENCE: Level III.

Contrast Challenge Algorithms for Adhesive Small Bowel Obstructions Are Safe in Children: A Multi-Institutional Study.

OBJECTIVE: The purpose of this study was to evaluate the safety of a water-soluble contrast challenge as part of a nonoperative management algorithm in children with an adhesive small bowel obstruction (ASBO). BACKGROUND: Predicting which children will successfully resolve their ASBO with non-operative management at the time of admission remains difficult. Additionally, the safety of a water-soluble contrast challenge for children with ASBO has not been established in the literature. METHODS: A retrospective review was performed of patients who underwent non-operative management for an ASBO and received a contrast challenge across 5 children's hospitals between 2012 and 2020. Safety was assessed by comparing the complication rate associated with a contrast challenge against a pre-specified maximum acceptable level of 5%. Sensitivity, specificity, negative (NPV) and positive (PPV) predictive values of a contrast challenge to identify successful nonoperative management were calculated. RESULTS: Of 82 children who received a contrast challenge, 65% were successfully managed nonoperatively. The most common surgical indications were failure of the contrast challenge or failure to progress after initially passing the contrast challenge. There were no complications related to contrast administration (0%; 95% confidence interval: 0-3.6%, P = 0.03). The contrast challenge was highly reliable in determining which patients would require surgery and which could be successfully managed non-operatively (sensitivity 100%, specificity 86%, NPV 100%, PPV 93%). CONCLUSION: A contrast challenge is safe in children with ASBO and has a high predictive value to assist in clinical decision-making.

Prospective quality of life outcomes in pediatric fecal incontinence following bowel management.

BACKGROUND: Severe fecal incontinence (FI) is common in patients both with and without anorectal malformations. Whether a formal bowel management program (BMP) has significant effects on FI, psychosocial development of the child, and caregiver stress is poorly understood. We hypothesize that BMP participation results in long-term clinical and quality of life (QOL) improvements for patients and caregivers. METHODS: Using a prospective cohort study over three years, 342 children (age 3-12 years) and caregivers were followed for one year after attending a week-long BMP, during which a regimen was tailored to promote daily stool evacuation.FI QOL was measured with the validated Cincinnati Fecal Incontinence Scale (CINCY-FIS), evaluating multiple subscales, including parental stress. Scores were obtained at multiple timepoints following BMP (baseline, 2 weeks, 3 months, 1 year). RESULTS: Within 2 weeks, BMP participation significantly improved FI with increased frequency of daily daytime voluntary bowel movements (20%-70%, p < 0.001) and decreased daily daytime and nighttimeinvoluntary bowel movements (60%-20%, p < 0.001; 30%-10%, p < 0.05). Marked improvements in CINCY-FIS were observed across multiple QOL subscales, with the greatest in parental stress, and sustained through one year. CONCLUSIONS: BMP results in significant and sustained improvement in FI and QOL for patients and caregivers.

A child presents with perianal symptoms - how often is this Crohn's disease?

BACKGROUND: The cumulative incidence and predictors of future diagnosis of Crohn's disease (CD) following presentation with perianal symptoms, such as anorectal abscess, fistula or fissure, is unknown. METHODS: A 5-year retrospective review of children presenting with perianal symptoms without prior CD diagnosis was performed. Institutional cumulative incidence of CD was calculated to determine the risk of CD presenting with perianal symptoms. RESULTS: 1140 children presented for evaluation of an anorectal abscess (n = 232), fistula (n = 49), or fissure (n = 859). Thirty-five were later diagnosed with CD, resulting in an incidence of 3%. Prognostic indicators of future CD diagnosis included increased age per every additional year (RR 1.19, 95% CI: 1.14-1.25, p < 0.001), male sex (RR 2.12, 95% CI 1.07-4.22, p = 0.024), or perianal fistula (RR 4.67, 95% CI 2.26-9.67, p = 0.022). Among those diagnosed with CD, 57% experienced and had a documented history of a CD-associated symptom prior to perianal symptom onset. Absence of symptoms resulted in delayed diagnosis (43 vs 3 days, p < 0.02). CONCLUSION: Of children presenting with a perianal symptom, three percent will eventually be diagnosed with CD. At highest risk (35%) were males aged 10 years or older with a perianal fistula; which should prompt expeditious workup.

Hepatoblastoma-The Evolution of Biology, Surgery, and Transplantation.

The most common primary malignant liver tumor of childhood, hepatoblastoma has increased in incidence over the last 30 years, but little is still known about its pathogenesis. Discoveries in molecular biology provide clues but have yet to define targeted therapies. Disease-free survival varies according to stage, but is greater than 90% in favorable risk populations, in part due to improvements in chemotherapeutic regimens, surgical resection, and earlier referral to liver transplant centers. This article aims to highlight the principles of disease that guide current treatment algorithms. Surgical treatment, especially orthotopic liver transplantation, will also be emphasized in the context of the current Children's Oncology Group international study of pediatric liver cancer (AHEP-1531).

Prognostic factors and survival in non-central nervous system rhabdoid tumors.

INTRODUCTION: Non-central nervous system (non-CNS) rhabdoid tumors tend to present at a young age and have an extremely aggressive course, with dismal overall survival rates. Inactivation of the tumor suppressor gene SMARCB1 has been shown in rhabdoid tumors regardless of anatomic location, suggesting a common genetic basis. We retrospectively analyzed our institutional experience with non-CNS rhabdoid tumors to determine overall survival and prognostic variables. METHODS: We reviewed records of pediatric patients (age<22y) with non-CNS rhabdoid tumor at our institution between 1980 and 2014. Variables evaluated for correlation with survival included: age > or <1.5years (median) at diagnosis, M1 status, and radiation therapy. The log-rank test was used to compare Kaplan-Meier probability distributions with P values adjusted for multiple testing using the false discovery rate approach. RESULTS: Nineteen consecutive patients (10 female) with histologically verified rhabdoid tumor were identified. Mean age at diagnosis was 3.2years (median 1.5y, range 1.3mo-21.8y). Primary tumors were located in the kidney (n=10), head and neck (n=5), and in the liver, thigh, mediastinum and retroperitoneum (n=1 each). SMARCB1 expression was absent in all 10 patients tested. Eight patients had distant metastases at diagnosis. Median overall survival was 1.2years. Age greater than the median and radiation therapy were associated with better outcome, with a median overall survival of 2.7years (P=0.049 and P=0.003, respectively). CONCLUSION: Survival rates for rhabdoid tumor remain poor, but prognosis is better in older children, regardless of primary tumor location. Because of its rarity, clinical trials with present agents are difficult to conduct. Further progress will require a focus on therapies targeted at tumor biology rather than anatomic location for non-CNS rhabdoid tumors.

Image-defined risk factors for nephrectomy in patients undergoing neuroblastoma resection.

BACKGROUND: Although nephrectomy rates are higher in children with neuroblastoma who have image-defined risk factors and/or high-risk disease who undergo resection prior to chemotherapy, no published data outline the key radiographic and clinical characteristics associated with nephrectomy. METHODS: With IRB approval, imaging studies of children undergoing primary resection of intraabdominal neuroblastoma between 2000 and 2014 were retrospectively reviewed. Fisher's exact and Wilcoxon rank-sum tests were used to compare categorical and continuous variables, respectively, with p-values adjusted for multiple testing using the false discovery rate approach. RESULTS: Twenty-seven of 380 consecutive patients with CT imaging obtained prior to primary neuroblastoma resection underwent partial or total nephrectomy. On preoperative imaging, renal vessel narrowing and encasement and tumor invasion of the renal hilum, pelvis, and/or parenchyma were present significantly more frequently among patients undergoing nephrectomy. Delayed renal excretion of contrast, hydronephrosis, and tumors with MYCN amplification were also more prevalent in the nephrectomy group. CONCLUSION: Encasement and narrowing of renal vessels, delayed excretion, and tumor invasion into the kidney, particularly pelvis and capsule invasion, are significantly associated with partial or total nephrectomy at initial neuroblastoma resection. These observations provide valuable information for surgical planning as well as presurgical discussions with families prior to neuroblastoma resection.

Salvage rates after progression of high-risk neuroblastoma with a soft tissue mass.

PURPOSE: Treatment of progression in high-risk neuroblastoma remains challenging despite improved survival. We retrospectively evaluated outcomes in children with a first progression that included soft-tissue masses. METHODS: We reviewed records of 903 consecutive children with high-risk neuroblastoma diagnosed between 2004 and 2014, and identified 42 whose first progression included soft-tissue masses. Data on demographics, disease characteristics, treatment, and survival were collected. Primary outcome was 5-year overall survival (OS) from time of first progression. Secondary outcomes were local disease-free progression (LDFR) and progression-free survival (PFS) postprogression. We evaluated the prognostic significance of concomitant bone/bone marrow involvement, MYCN status, and multifocality of soft tissue relapse. RESULTS: Median age at diagnosis was 3.0 (range: 1-10.7) years. Median time to first relapse or progression was 1.2 (range: 0.1-4.5) years after complete remission or minimal stable residual disease. Twelve (29%) patients had concomitant bone or marrow involvement at progression/relapse. There were 11 (26%) patients with International Neuroblastoma Staging System stage 3 disease (all with MYCN amplification), and 31 (74%) with stage 4 disease (12 with MYCN amplification). Nine (21%) patients had multifocal soft tissue progression. R1 resection was achieved in 41 children (95%), 38 (95%) of whom also received salvage radiation therapy. Five-year OS postprogression was 35% (95% CI: 19-51%), 5-year LDFS was 52% (95% CI: 32-72%), and 5-year PFS postprogression was 20% (95% CI: 6-34%). CONCLUSION: Among children with high-risk neuroblastoma who underwent aggressive treatment of a first soft-tissue recurrence, 5-year postprogression overall survival was 34%. Multifocality and MYCN amplification were the predominant prognostic correlates for worse survival.

Gastric Volvulus Following Left Pneumonectomy in an Adolescent Patient.

Gastric volvulus is a rare post-pneumonectomy complication. Although it has been described previously, published cases are limited to an older patient population. We report the youngest case of postpneumonectomy gastric volvulus to date, occurring in an 18-year-old male with a history of inflammatory myofibroblastic pseudotumor who underwent left intrapericardial pneumonectomy, and presented 13 years later with chronic intermittent mesenteroaxial gastric volvulus. While postpneumonectomy gastric volvulus is a rare occurrence, it should remain in the differential diagnosis in postoperative thoracic surgical patients presenting with chest pain.

Experience with retroperitoneal partial nephrectomy in bilateral Wilms tumor.

INTRODUCTION: Retroperitoneal partial nephrectomy has not been studied as a surgical approach for children with bilateral Wilms tumor. There are advantages to this technique, including isolation of urine leaks to the retroperitoneum, decreased risk of bowel injury, and decreased time to resuming a diet. Presently, all bilateral Wilms tumors are treated with neoadjuvant chemotherapy and attempted nephron-sparing surgery. In this study, we compare the outcomes of the retroperitoneal and transabdominal approaches in doing partial nephrectomy for bilateral Wilms tumor. METHODS: With the institutional review board approval, we reviewed records of 14 pediatric patients with metachronous or synchronous bilateral Wilms tumors who underwent surgery after chemotherapy between 1994 and 2014. Only operative procedures with the intent to cure were included (n=15) and of these, 5 procedures were retroperitoneal and 10 were transabdominal in approach. Individual kidneys operated upon (n=26) were analyzed using the preoperative radius exophytic/endophytic nearness anterior/posterior location nephrometry score to ensure that resected tumors were comparable between the two surgical groups. Charts were retrospectively analyzed for intraoperative parameters and postoperative course. Differences between parameters were evaluated using Mann-Whitney and chi-square tests. RESULTS: Resected tumors in both surgical treatment groups had comparable sizes, nephrometry scores, and rates of anaplasia. Operative time, blood loss, and transfusion requirement were similar between the two groups. The extent of lymph node sampling and rates of R0 resection were equivalent. One adverse intraoperative event, a bowel enterotomy, was seen in the transabdominal group. Patients after retroperitoneal partial nephrectomy required half the time to return to an oral diet as compared with those after a transabdominal surgery, approaching statistical significance (p=0.08). Rates of the postoperative urine leak were similar, though two in the transabdominal group required reoperation for drainage. There were four recurrences, all in the transabdominal group. CONCLUSION: Our experience demonstrates that the retroperitoneal approach is equivalent to the transabdominal technique with regards to intraoperative complications, lymph node dissection, and R0 resection. Advantages include less time to resumption of oral feeding, decreased risk of bowel injury, and isolation of urine leaks to the retroperitoneum. It should be considered a viable surgical option in the treatment of bilateral Wilms tumors.

Advances in fibrolamellar hepatocellular carcinoma: a review.

Fibrolamellar hepatocellular carcinoma is a rare primary liver tumor that often arises in the absence of cirrhosis or viral hepatitis. Compared with hepatocellular carcinoma, patients are typically younger with less comorbidities. Diagnosis is often multimodal and requires a high level of suspicion, as traditional liver pathology markers, such as serum α fetoprotein and transaminases, are often normal. Overall, patients respond well to surgical resection but recurrences are frequent, and alternative therapies, such as chemotherapy and radiation, are not well studied. Currently, there are no established chemotherapy regimens; there are only limited case reports of select agents, such as 5-fluorouracil with interferon-α and gemcitabine with oxaliplatin, used with varying degrees of success. Because little is known about this rare tumor, the development of serum markers and alternative therapies continues to be a challenge. A major advancement in the understanding of this rare disease is the discovery of a functional chimeric transcript incorporating DNAJB1 and PRKACA. This finding may finally provide the basis for specific diagnostic markers and chemotherapies that patients with this disease have long needed. Here, we present advances in the surgical treatment of fibrolamellar hepatocellular carcinoma, as well as recent data on its tumor biology and pathogenesis.

Endogenous antibodies for tumor detection.

The study of cancer immunology has provided diagnostic and therapeutic instruments through serum autoantibody biomarkers and exogenous monoclonal antibodies. While some endogenous antibodies are found within or surrounding transformed tissue, the extent to which this exists has not been entirely characterized. We find that in transgenic and xenograft mouse models of cancer, endogenous gamma immunoglobulin (IgG) is present at higher concentration in malignantly transformed organs compared to non-transformed organs in the same mouse or organs of cognate wild-type mice. The enrichment of endogenous antibodies within the malignant tissue provides a potential means of identifying and tracking malignant cells in vivo as they mutate and diversify. Exploiting these antibodies for diagnostic and therapeutic purposes is possible through the use of agents that bind endogenous antibodies.

Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma.

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare liver tumor affecting adolescents and young adults with no history of primary liver disease or cirrhosis. We identified a chimeric transcript that is expressed in FL-HCC but not in adjacent normal liver and that arises as the result of a ~400-kilobase deletion on chromosome 19. The chimeric RNA is predicted to code for a protein containing the amino-terminal domain of DNAJB1, a homolog of the molecular chaperone DNAJ, fused in frame with PRKACA, the catalytic domain of protein kinase A. Immunoprecipitation and Western blot analyses confirmed that the chimeric protein is expressed in tumor tissue, and a cell culture assay indicated that it retains kinase activity. Evidence supporting the presence of the DNAJB1-PRKACA chimeric transcript in 100% of the FL-HCCs examined (15/15) suggests that this genetic alteration contributes to tumor pathogenesis.

Diagnostic accuracy of cardiac computed tomography angiography for myocardial infarction.

AIM: To investigate diagnostic accuracy of high, low and mixed voltage dual energy computed tomography (DECT) for detection of prior myocardial infarction (MI). METHODS: Twenty-four consecutive patients (88% male, mean age 65 ± 11 years old) with clinically documented prior MI (> 6 mo) were prospectively recruited to undergo late phase DECT for characterization of their MI. Computed tomography (CT) examinations were performed using a dual source CT system (64-slice Definition or 128-slice Definition FLASH, Siemens Healthcare) with initial first pass and 10 min late phase image acquisitions. Using the 17-segment model, regional systolic function was analyzed using first pass CT as normal or abnormal (hypokinetic, akinetic, dyskinetic). Regions with abnormal systolic function were identified as infarct segments. Late phase DE scans were reconstructed into: 140 kVp, 100 kVp, mixed (120 kVp) images and iodine-only datasets. Using the same 17-segment model, each dataset was evaluated for possible (grade 2) or definite (grade 3) late phase myocardial enhancement abnormalities. Logistic regression for correlated data was used to compare reconstructions in terms of the accuracy for detecting infarct segments using late myocardial hyperenhancement scores. RESULTS: All patients reported prior history of documented myocardial infarction, with most occurring more than 5 years prior (n = 18; 75% of cohort). Fifty-five of 408 (13%) segments demonstrated abnormal wall motion and were classified as infarct. The remaining 353 segments were classified as non-infarcted segments. A total of 1692 segments were analyzed for late phase enhancement abnormalities, with 91 (5.5%) segments not interpretable due to artifact. Combined grades 2 and 3 compared to grade 3 only enhancement abnormalities demonstrated significantly higher sensitivity and similar specificity for detection of infarct segments for all reconstructions evaluated. Evaluation of different voltage acquisitions demonstrated the highest diagnostic performance for the 100 kVp reconstruction which had higher diagnostic accuracy (87%; 95%CI: 80%-90%), sensitivity (86%-93%; 95%CI: 54%-78%) and specificity (90%; 95%CI: 86%-93%) compared to the other reconstructions. For sensitivity, there were significant differences noted between 100 kVp vs 140 kVp (P < 0.0005), 100 kVp vs mixed (P < 0.0001), and 100 kVp vs iodine only (P < 0.005) using combined grade 2 and grade 3 perfusion abnormalities. For specificity, there were significant differences noted between 100 kVp vs 140 kVp (P < 0.005), and 100 kVp vs mixed (P < 0.01) using combined grades 2 and 3 perfusion abnormalities. CONCLUSION: Low voltage acquisition CT, 100 kVp in this study, demonstrates superior diagnostic performance when compared to higher and mixed voltage acquisitions for detection of prior MI.