Kenitiro Kaneko

Pancreaticobiliary maljunction without choledochal cysts in infants and children: Clinical features and surgical therapy

Pancreaticobiliary maljunction (PBM) usually is associated with choledochal cyst. PBM without dilatation of the common bile duct is rare in infants and children. This rare type of the anomaly may lead to the development of malignancy of the bile duct in later life. The authors report the clinical presentation and surgical treatment of seven pediatric patients with PBM. Symptoms and signs included repeated episodes of abdominal pain (7 of 7), nausea and vomiting (6 of 7), intermittent jaundice (3 of 7), and acholic stools (2 of 7). Some patients presented with high levels of serum and urinary amylase. These symptoms and signs might have been related to the temporary obstruction of bile flow in the common channel, where endoscopic retrograde cholangiopancreaticography (ERCP) disclosed a protein plug in four of the patients. The common bile duct proximal to the junction of the main pancreatic duct was excised, and a Roux-en-Y hepaticojejunostomy reconstruction was performed. To prevent iatrogenic injury of the main pancreatic duct, repeat cholangiography was performed with the aid of radiopaque silver clips placed on the line of dissection to evaluate the distance between the site of dissection and the main pancreatic duct. All patients have been free of symptoms since the surgery. PBM without dilatation of the common bile duct can be detected more frequently if ERCP is performed on every patient who has repeated episodes of abdominal pain refractory to conventional therapy. Complete excision of the common bile duct and gallbladder followed by hepaticojejunostomy is recommended for PBM, while the goals of decreasing the high risk of carcinoma of the bile duct and preventing recurrent symptoms.

Treatment of hepatoblastoma : Less extensive hepatectomy after effective preoperative chemotherapy with cisplatin and Adriamycin

BACKGROUND Although the prognosis of hepatoblastoma was improved by the introduction of cisplatin and doxorubicin (Adriamycin) for adjuvant chemotherapy, extensive hepatectomy continues to be the usual practice. We retrospectively reviewed our recent experience with hepatoblastoma to determine whether the new modality of intensive chemotherapy could change the resectability, extent of hepatectomy, operative complications, and prognosis. METHODS The clinical features of 15 children with hepatoblastoma treated between 1985 and 1995 were reviewed. Intensive chemotherapy was added before surgical resection not only when a tumor was unresectable but also when it was large enough to increase the risk of operative morbidity. RESULTS There was 100% resectability, and the overall mortality rate was only 6.7%. Fourteen patients have been free of disease for 2 to 12 years. Preoperative chemotherapy enabled resection of six previously unresectable hepatoblastomas. Moreover, hepatic resection tended to be less invasive in several patients whose tumors had been much reduced after preoperative chemotherapy. Intraoperative and postoperative complications were minimal, with a short operative time and small amount of blood loss, especially in the group with delayed primary operation. CONCLUSIONS The preoperative administration of cisplatin and Adriamycin reduced the tumor size so that a safe hepatectomy could be performed with less blood loss and minimal technical complications. Unnecessary sacrifice of the normal hepatic tissue was avoided by performing the less extensive hepatectomy.

Operative treatment of congenital stenoses of the intrahepatic bile ducts in patients with choledochal cysts

BACKGROUND Postoperative complications including intrahepatic calculi may develop after the complete excision of a choledochal cyst. Since congenital stenoses of the intrahepatic bile ducts are more likely the cause of intrahepatic calculi, operative procedures for intrahepatic stenoses are reported. METHODS There were 16 patients with choledochal cysts who underwent surgery for stenoses of intrahepatic bile ducts. The stenoses were excised at the opening of the common hepatic duct. RESULTS In the 16 patients, 25 of the 26 stenoses that involved an intraluminal membrane or septum could be excised from the divided end of the common hepatic duct at the hepatic hilum. In 1 patient, the stenosis could not be accessed from the hepatic hilum, and a left hepatic lobectomy was required. In postoperative follow-up, all 16 patients were in good health. CONCLUSIONS Stenoses of the intrahepatic bile ducts should be treated from the divided end of the common hepatic duct at the initial operation for choledochal cysts. The need for a second operation or hepatic lobectomy may thus be avoided.

Acute respiratory failure associated with intrathoracic masses in neonates

BACKGROUND Intrathoracic masses are uncommon in children. Occasionally, they present with acute respiratory failure in the neonatal period. Although emergency resection usually is the treatment of choice, other modalities are sometimes necessary to stabilize the patient. METHODS Seven neonates with intrathoracic masses were treated. Five had congenital cystic adenomatoid malformations (CCAM), 1 had a mediastinal teratoma, and 1 had a pneumatocele. These cases were reviewed retrospectively. RESULTS Four of the 7 infants had respiratory failure in the neonatal period. A patient with a large mediastinal teratoma and 1 with a CCAM that increased rapidly after presentation underwent emergency operation, relieving respiratory distress. The other 2 large CCAMs presented with severe respiratory distress immediately after birth because of pulmonary hypoplasia. One neonate with a Stocker-I CCAM died after emergency resection. One more recent patient with a Stocker-III CCAM survived after successful treatment with delayed resection, performed 3 days after birth. Nitric oxide (NO), and extracorporeal membrane oxygenation (ECMO) were instituted as supportive care because of profound persistent fetal circulation (PFC). CONCLUSIONS Acute respiratory failure associated with intrathoracic masses in neonates may be managed in 1 of 2 ways. A small mass that increases rapidly should be resected soon after presentation. In neonates with large masses with associated PFC, surgery can be delayed until the patient is stable. ECMO, NO, and high-frequency oscillation (HFO) can be used aggressively for stabilizing such neonates.

Immunologic and Virologic Analyses in Pediatric Liver Transplant Recipients with Chronic High Epstein-Barr Virus Loads

BACKGROUND Long-term Epstein-Barr virus (EBV) monitoring for potentially life-threatening posttransplant lymphoproliferative disorder (PTLD) has identified asymptomatic patients who maintain high EBV loads over long periods. METHODS Thirty-one pediatric liver transplant recipients were designated as 11 chronic high EBV load carriers (EBV DNA level >5000 copies/mL of whole blood for >6 months) and 20 control recipients. Serial quantification of EBV DNA, measurement of interleukin 10 (IL-10) concentrations, EBV-specific tetramer staining, and relative quantification of EBV gene expression in peripheral blood mononuclear cells were performed. RESULTS Most of the chronic high EBV load carriers were seronegative at transplant, the median time to resolution of a chronic high EBV load was 23 months, and no recipient developed late-onset PTLD. EBV DNA was detected predominantly in CD19(+) cells. The plasma concentration of IL-10 and the EBV-specific CD8(+) cell frequency did not differ significantly between the chronic high EBV load carriers and the control recipients. Analysis of gene expression showed that EBV-encoded small RNA 1, BamHI A rightward transcripts, and latent membrane protein 2 were positive in peripheral blood mononuclear cells from chronic high EBV load carriers. CONCLUSIONS EBV-infected cells in the blood of chronic high EBV load carriers expressed a highly restricted set of latency genes, suggesting that the EBV-infected cells escaped from a T cell response.

Activated pancreatic enzyme and pancreatic stone protein (PSP/reg) in bile of patients with pancreaticobiliary maljunction/ choledochal cysts.

Symptoms of pancreaticobiliary maljunction/choledochal cysts are caused by the obstruction of bile and pancreatic ducts due to protein plugs compacted in the common channel. However, the mechanism of protein plug formation remains unknown. Pancreatic stone protein (PSP) is reported to be a key protein to form protein plugs in chronic pancreatitis. Bile from 13 patients with pancreaticobiliary maljunction and bile from two normal controls were analyzed. Activity of pancreatic enzymes and the concentration of PSP were measured. The mean concentrations of PSP were 76.9 ± 30.9 ng/mL in the bile-duct bile, and 76.9 ± 29.8 ng/mL in the gallbladder bile. PSP was not detected in the controls (P&<0.05). In the bile-duct bile of the patients, trypsin(ogen) was detectable in nine patients, of which seven patients had activated trypsin. In the gallbladder bile, trypsin(ogen) was detectable in 12 patients, of which 9 patients had activated trypsin. Neither activated trypsin nor trypsinogen was detected in the controls. Bile in pancreaticobiliary maljunction patients contained both activated trypsin and PSP. Activated trypsin cleaves soluble PSP and creates insoluble PSP. Protein plugs in pancreaticobiliary maljunction may be formed by assembled insoluble PSP.

The MRI findings of the right-sided fetal lung can be used to predict postnatal mortality and the requirement for extracorporeal membrane oxygenation in isolated left-sided congenital diaphragmatic hernia.

We evaluated whether a correlation existed between fetal pulmonary magnetic resonance imaging (MRI) findings and postnatal mortality, as well as the requirements for extracorporeal membrane oxygenation (ECMO) in infants with prenatally diagnosed, isolated left-sided congenital diaphragmatic hernia (CDH). Twenty-one pregnant women carrying fetuses with CDH underwent 30 MRI scans, and the right-sided fetal lung volume (FLV) was measured. In the control, a regression analysis was performed to associate FLV with gestational age. This yielded a formula that enabled the calculation of the expected right fetal lung volume (ERFLV). In cases with CDH, the right-sided observed FLV/ERFLV (= %RFLV) was compared with both the postnatal mortality and whether ECMO was required. Additionally, we investigated the relationship between the lung shape on MRI (whether there was a complete pulmonary baseline present) and postnatal mortality. The %RFLV was significantly lower in nonsurvivors compared with survivors. Among survivors, the %RFLV was significantly lower in infants who required ECMO compared with those who did not. The pulmonary baseline was completely present in 3 (38%) and 13 (100%) of the nonsurvivors and survivors, respectively. In isolated left-sided CDH, the %RFLV is a good predictor not only of postnatal mortality but also of the requirement for ECMO.

Surgical removal of Protein plugs complicating choledochal cysts : Primary repair after adequate opening of the pancreatic duct

BACKGROUND/PURPOSE Recently, pancreaticoduodenectomies have been performed for choledochal cysts complicated by protein plugs. The authors describe a new surgical procedure for removal of protein plugs or pancreatic stones that does not involve pancreatectomy. METHODS Protein plugs were detected in 43 (34.1%) of 126 pediatric patients with choledochal cysts. The plugs disappeared spontaneously in 26 patients and were removed using nonsurgical methods in seven. The 10 patients treated surgically are considered here. RESULTS Protein plugs were removed with the residual cyst in one patient. The plugs in the common channel were flushed into the duodenum by irrigation with saline through the narrow segment beneath choledochal cyst in another. The plugs were removed through the narrow segment using a blunt spoon in four. In the other four patients, the plugs that were too large or too hard to be removed through the narrow segment were taken away through an incision in the main pancreatic duct. This was followed by primary closure of the main pancreatic duct using the narrow segment as a flap to prevent stricture formation. All of the patients have done well. CONCLUSIONS Protein plugs complicating choledochal cysts can be removed without pancreatectomy. Particularly, primary repair of the pancreatic duct using a flap made of the narrow segment beneath the choledochal cyst is a safe and feasible method to remove large or hard protein plugs.

Increased cell proliferation and transforming growth factor-α (TGFα) in the gall-bladder epithelium of patients with pancreaticobiliary maljunction

Pancreaticobiliary maljunctlon is associated frequently with gall‐bladder carcinoma. Although increased turnover of the gall‐bladder epithelium in patients with pancreaticobiliary maljunction is thought to predispose to carcinogenesis, there is little data to confirm this hypothesis. In addition, no previously published study has addressed the process underlying cell proliferation. In this study, cell kinetics were first evaluated using two methods, proliferating cell nuclear antigen (PCNA) Immunohistochemical staining and argyrophilic nucleolar organizer region (AgNOR) staining. Second, immu‐nohistochemistry was used to investigate the expression of transforming growth factor‐α (TGFα), a potential regulator of cell proliferation in the gall‐bladder. The gall‐bladders of 11 patients with pancreaticobiliary maljunction were studied, and 11 gall‐bladders removed from patients during other surgery were used as controls. The number of PCNA‐positive cells and the number of AgNOR per nucleus were significantly greater in the gall‐bladders of patients with pancreaticobiliary maljunction than in the control gall‐bladders. The expression of TGFα was also significantly greater in the gallbladders of patients with pancreaticobiliary maljunction than in the control gall‐bladders. In conclusion, these results suggest that the increased TGFα expression induced by pancreaticobiliary maljunction promotes proliferation of the gall‐bladder epithelium, which may lead to carcinogenesis.

Effectiveness and safety of inactivated influenza vaccination in pediatric liver transplant recipients over three influenza seasons

Gotoh K, Ito Y, Suzuki E, Kaneko K, Kiuchi T, Ando H, Kimura H. Effectiveness and safety of inactivated influenza vaccination in pediatric liver transplant recipients over three influenza seasons.
Pediatr Transplantation 2011: 15:112–116.