Ayako Takenouchi

Endoscopic sphincterotomy is a useful preoperative management for refractory pancreatitis associated with pancreaticobiliary maljunction.

BACKGROUND Pancreatitis associated with pancreaticobiliary maljunction (PBM) is commonly treated nonoperatively before surgery. It is, however, sometimes uncontrollable, and little has been reported about the management. METHODS Focusing on the preoperative management, we reviewed clinical courses of 4 PBM cases (ages 1 to 7 years old). Each had pancreatitis that was totally resistant to medical treatment and was applied endoscopic sphincterotomy (ES). RESULTS The first case underwent percutaneous transhepatic catheter drainage (PTCD) primarily. In spite of daily lavage using the drainage tube for a week, plugs located in the common channel were not removed, and clinical findings were not improved. Therefore, ES followed by removal of protein plugs was performed to improve pancreatitis dramatically. Through this experience, 3 subsequent cases with refractory pancreatitis all underwent successful ES primarily soon after the medical treatments turned out to be ineffective. In all 4 cases, protein plugs were impacted in common channels, and ES could successfully remove the plugs that were impossible to remove by using PTCD. Improved preoperative pancreaticobiliary decompression by ES shortens the duration of recalcitrant acute pancreatitis associated with PBM allowing for a subsequent safe operation. CONCLUSIONS Endoscopic sphincterotomy is one of the useful preoperative managements for refractory pancreatitis associated with PBM.

Use of preoperative, 3-dimensional magnetic resonance cholangiopancreatography in pediatric choledochal cysts

BACKGROUND Standard choledochal cyst (CC) operations involve dilated extrahepatic bile duct excision followed by biloenterostomy. However, biliary variants and associated intrahepatic bile duct (IHBD) stenoses or dilatations triggering postoperative sequelae require additional procedures. The usefulness of preoperative 3-dimensional magnetic resonance cholangiopancreatography (3D MRCP) and virtual cholangioscopy (VES) for observing biliary morphology and pancreaticobiliary maljunction (PBM) was evaluated. METHODS In 16 pediatric CC patients (age range, 4 months to 9 years; median, 3 years), visualization of PBM and aberrant bile duct anatomy and IHBD morphology at the hepatic hilum (HH), umbilical portion (UP), and posterior branch (POST) were compared between 3D-MRCP and intraoperative cholangiography (IOC). VES and intraoperative cholangioscopy (IOS) findings were compared. RESULTS HH, UP, and POST visualization rates were 100%, 94%, and 94%, respectively, by 3D-MRCP, and 100%, 69%, and 69%, respectively, by IOC. IHBD stenosis detection rates at each region were 38%, 13%, and 13%, respectively, by 3D-MRCP, and 25%, 0%, and 9%, respectively, by IOC. IHBD dilatation detection rates at each part were 75%, 47%, and 60%, respectively, by 3D-MRCP, and 88%, 82%, and 91%, respectively, by IOC. PBM was confirmed in 56% and 93% of cases on 3D-MRCP and IOC, respectively. Both 3D-MRCP and IOC showed biliary variants in 5 cases (31%). VES showed membranous strictures at HH, UP, and POST in 6, 2, and 2 cases, respectively, whereas IOS did so at HH in 4 cases and POST in 2. CONCLUSION Preoperative 3D-MRCP and VES accurately depict biliary morphology, allowing concrete operative planning in pediatric CC patients, complementing IOC and IOS.

Kaposiform hemangioendothelioma of the choledochus

Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular neoplasm that mainly occurs during childhood. Although KHE may involve various organs, involvement of the choledochus has not been reported. We report a case of KHE in a 5-month-old male infant. The patient was admitted with icterus and acholic stool. Contrast computed tomography revealed a vascular tumor in the hepatic portal region causing biliary obstruction. Excision of the extrahepatic duct and hepatoportoenterostomy were performed successfully, and he has been well during 3 years of postoperative follow-up.

Reevaluation of trkA expression as a biological marker of neuroblastoma by high-sensitivity expression analysis--a study of 106 primary neuroblastomas treated in a single institute.

BACKGROUND/PURPOSE It has previously been shown that neuroblastomas with favorable prognosis often express a high level of nerve growth factor receptor trkA. We performed an expression analysis of trkA in 106 NB samples based on the quantitative real-time polymerase chain reaction (PCR) and reevaluated the prognostic power of trkA. MATERIALS AND METHODS A total of 106 primary tumors from NB patients treated from 1988 to 2009 were analyzed. MYCN was amplified in 13 cases. TaqMan probe method was used for quantitative PCR. Primers and probes were designed to detect trkA I and trkA II, but not the oncogenic splice variant trkA III. RESULTS Expression analysis by real-time PCR revealed a wide range of expression levels of trkA within neuroblastoma tissues. Extremely low levels of trkA that were undetectable by semiquantitative PCR were able to be quantified by this method. trkA was predominantly expressed in tumors with favorable outcome. Further analysis of trkA expression was performed in a cohort excluding mass-screened neuroblastomas. Strikingly, multivariate analysis containing age, MYCN status, and trkA expression identified trkA as the only variable that independently predicts the prognosis of the 44 patients who presented clinically. CONCLUSION High-resolution expression analysis targeting trkA and trkA II may add more statistical power on trkA as a biological marker.

Oncolytic viral therapy for neuroblastoma cells with Sindbis virus AR339 strain

PurposeWith current treatment regimens, high-risk neuroblastoma (NB) remains largely incurable. Oncolytic viral therapy uses replication-competent viruses, like Sindbis virus (SINV), to kill cancers. The SINV AR339 strain is blood borne and relatively non-virulent. We evaluated the feasibility of SINV AR339 for treating human NB.MethodsThe cytotoxicity and viral growth of SINV AR339 were evaluated for five human NB cell lines, SK-N-SH, IMR-32, LAN-5, GOTO, and RT-BM-1. SINV-induced apoptosis was confirmed by TUNEL assays and PARP-1 cleavage. In vivo effects of SINV on neuroblastoma cell xenografts in nude mice were assessed by intratumoral or intravenous SINV inoculation.ResultsIn five human NB cell lines, SINV infections induced remarkable cytotoxicity. The mRNA expressions of anti-apoptotic genes, Bcl-2 and Bcl-xL, in LAN-5 and RT-BM-1, which were less sensitive to SINV infection, increased in response to SINV infection, while the other NB cell lines sensitive to SINV infection failed to respond. In nude mice, intratumoral and intravenous SINV inoculations caused significant regression of NB xenograft tumors.ConclusionOur results suggested that SINV AR339 was significantly oncolytic against human NB. Thus, SINV showed promise as a novel therapy for treating NB.

Neonates undergoing gastrointestinal surgery have a higher incidence of non-IgE-mediated gastrointestinal food allergies

PurposeWe aimed at investigating the incidence and risk factors of non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs) in neonates and infants.MethodsA total of 126 infants who underwent neonatal gastrointestinal surgeries were grouped into those with (n = 13) and those without an onset of non-IgE-GI-FAs (n = 113). The characteristics of the two groups (e.g., birth weight, delivery type, small intestinal surgeries, and pre-/postoperative nutrition) were compared. Small intestinal surgeries were classified into those with and those without full-layer invasion of the small intestine. For the statistical analysis, postoperative nutrition was classified into breast milk only, formula milk, and elemental diet only.ResultsExcept for full-layer surgical invasion of the small intestine and the period of parenteral nutrition, no significant differences were found between the two groups. Surgery with full-layer invasion was a risk factor of non-IgE-GI-FAs (odds ratio (OR) 10.70, 95% confidence interval (95% CI) 2.11–54.20; p = 0.004). Formula milk after surgery was a risk factor of non-IgE-GI-FAs when compared to breast milk (OR 5.65, 95% CI 1.33–24.00; p = 0.019).ConclusionNeonates undergoing gastrointestinal surgery have a higher incidence of non-IgE mediated gastrointestinal food allergies. We recommend that formula milk should not be administered to newborns who underwent neonatal gastrointestinal surgeries with full-layer invasion of the small intestine.