Pediatric Laparoscopic Common Bile Duct Exploration: An Opportunity to Decrease ERCP Complications.

BACKGROUND: Laparoscopic intraoperative cholangiogram (IOC) with common bile duct exploration (CBDE) and endoscopic retrograde cholangiopancreatography (ERCP) are two therapeutic techniques for choledocholithiasis. The preferred technique is unclear. MATERIALS AND METHODS: We identified subjects who underwent laparoscopic cholecystectomy (LC) and IOC/CBDE or ERCP from July 1, 2006, to December 31, 2016. We retrospectively reviewed 81 patients (≤ 18 y) who received these interventions for suspected choledocholithiasis. Main outcomes analyzed were success of intervention and complications. RESULTS: Of the 81 patients, 21 ERCPs and three endoscopic ultrasounds (EUSs) were performed before LC. Eighteen of 21 (85.7%) patients had stones or sludge cleared by ERCP, whereas 3 (14.3%) had normal common bile ducts without evidence of stones. Five of 24 (20.8%) had significant post-ERCP complications. Seven of 24 (29.2%) had more than one admission. Sixty of 81 patients underwent LC with IOC ± CBDE. Twenty one of 60 (36.2%) were found to have abnormal IOC. Eight of 15 (53.3%) attempted laparoscopic CBDE were successful. Eleven of 21 (52.4%) patients with abnormal IOC had post-LC ERCP (10) and EUS (1). Patients admitted to the Pediatric Surgery service were more likely to undergo LC first than ERCP/EUS (OR 3.46, 95% CI 1.26 to 9.45, P = 0.016). Patients undergoing LC first had a shorter length of stay (mean LOS 5.13 d versus 4.07, median 5.0 versus 3.0 d, P-value < 0.05). CONCLUSIONS: Successful and safe laparoscopic treatment of choledocholithiasis is possible in the pediatric patient. A laparoscopic-first approach to suspected choledocholithiasis may reduce the number of procedures needed in this patient population.

Utilization of Ultrasound Guided Tissue-directed Cellular Implantation for the Establishment of Biologically Relevant Metastatic Tumor Xenografts.

Preclinical testing of anticancer therapies relies on relevant xenograft models that mimic the innate tendencies of cancer. Advantages of standard subcutaneous flank models include procedural ease and the ability to monitor tumor progression and response without invasive imaging. Such models are often inconsistent in translational clinical trials and have limited biologically relevant characteristics with low proclivity to produce metastasis, as there is a lack of a native microenvironment. In comparison, orthotopic xenograft models at native tumor sites have been shown to mimic the tumor microenvironment and replicate important disease characteristics such as distant metastatic spread. These models often require tedious surgical procedures with prolonged anesthetic time and recovery periods. To address this, cancer researchers have recently utilized ultrasound-guided injection techniques to establish cancer xenograft models for preclinical experiments, which allows for rapid and reliable establishment of tissue-directed murine models. Ultrasound visualization also provides a noninvasive method for longitudinal assessment of tumor engraftment and growth. Here, we describe the method for ultrasound-guided injection of cancer cells, utilizing the adrenal gland for NB and renal sub capsule for ES. This minimally invasive approach overcomes tedious open surgery implantation of cancer cells in tissue-specific locations for growth and metastasis, and abates morbid recovery periods. We describe the utilization of both established cell lines and patient derived cell lines for orthotopic injection. Pre-made commercial kits are available for tumor dissociation and luciferase tagging of cells. Injection of cell suspension using image-guidance provides a minimally invasive and reproducible platform for the creation of preclinical models. This method is utilized to create reliable preclinical models for other cancers such as bladder, liver and pancreas exemplifying its untapped potential for numerous cancer models.

Alternative NHEJ pathway proteins as components of MYCN oncogenic activity in human neural crest stem cell differentiation: implications for neuroblastoma initiation.

Neuroblastoma is a cancer of neural crest stem cell (NCSC) lineage. Signaling pathways that regulate NCSC differentiation have been implicated in neuroblastoma tumorigenesis. This is exemplified by MYCN oncogene targets that balance proliferation, differentiation, and cell death similarly in normal NCSC and in high-risk neuroblastoma. Our previous work discovered a survival mechanism by which MYCN-amplified neuroblastoma circumvents cell death by upregulating components of the error-prone non-canonical alternative nonhomologous end-joining (alt-NHEJ) DNA repair pathway. Similar to proliferating stem cells, high-risk neuroblastoma cells have enhanced DNA repair capacity, overcoming DNA damage with higher repair efficiency than somatic cells. Adequate DNA maintenance is required for lineage protection as stem cells proliferate and during tumor progression to overcome oncogene-induced replication stress. On this basis, we hypothesized that alt-NHEJ overexpression in neuroblastoma is a cancer cell survival mechanism that originates from DNA repair systems of NCSC, the presumed progenitor cell of origin. A human NCSC model was generated in which inducible MYCN triggered an immortalized phenotype capable of forming metastatic neuroectodermal tumors in mice, resembling human neuroblastoma. Critical alt-NHEJ components (DNA Ligase III, DNA Ligase I, and Poly [ADP-ribose polymerase 1]) were highly expressed in normal early NCSC, and decreased as cells became terminally differentiated. Constitutive MYCN expression maintained high alt-NHEJ protein expression, preserving the expression pattern of the immature neural phenotype. siRNA knockdown of alt-NHEJ components reversed MYCN effects on NCSC proliferation, invasion, and migration. DNA Ligase III, Ligase I, and PARP1 silencing significantly decreased neuroblastoma markers expression (TH, Phox2b, and TRKB). These results utilized the first human NCSC model of neuroblastoma to uncover an important link between MYCN and alt-NHEJ expression in developmental tumor initiation, setting precedence to investigate alt-NHEJ repair mechanics in neuroblastoma DNA maintenance.

Magnetic resonance imaging (MRI)-assisted laparoscopic anorectoplasty for imperforate anus: a single center experience.

PURPOSE: Surgical procedures for high imperforate anus have ranged from the posterior sagittal anorectoplasty (PSARP) to laparoscopic-assisted anorectoplasty (LAARP). PSARP bisects the sphincter muscle complex, introducing muscle injury and scarring. LAARP uses a straight trocar to traverse an often non-linear sphincter muscle complex. MRI-assisted LAARP (MRI-LAARP) guides the neorectum precisely through the middle of the entire sphincter complex along its trajectory. We present our experience utilizing MRI intraoperatively during LAARP. METHODS/PROCEDURE: Ten children underwent MRI-LAARP procedures. Intraoperative MRI was performed to delineate the sphincter complex, and to guide the advancement of an MRI-compatible needle through the center of the complex from skin to the peritoneal cavity. The remainder of the procedure was completed using the standard LAARP technique. RESULTS: All had successful MRI needle placement through the sphincter complex. Nine patients had successful laparoscopic pull-through procedures; one was converted to open due to severe intraperitoneal adhesions. Postoperative stay averaged 5.4 ± 4.4 days. Out of the ten patients, one child had mild dehiscence of the anal anastomosis requiring revision 11 days postoperatively. CONCLUSION: The theoretical advantage of the MRI-LAARP is placing the neorectum through the entire sphincter complex without transecting the muscle. Follow-up of these patients shows good short-term results; however, long-term follow-up will be needed to best assess sphincter and bowel function.

Ovarian steroid cell tumor, not otherwise specified, associated with congenital adrenal hyperplasia: rare tumors of an endocrine disease.

Ovarian steroid cell tumors, not otherwise specified (OSCTs), are extremely rare and present a diagnostic challenge when evaluating an ovarian mass. We present a case of such a tumor in a patient with known Congenital Adrenal Hyperplasia (CAH), secondary to 21-hydroxylase deficiency, who was noncompliant with her medications. The workup, diagnosis, and treatment of this rare condition are described.