Long-term outcomes of surgery for choledochal cysts: a single-institution study focusing on follow-up and late complications.

PURPOSE: The late postoperative complications of choledochal cyst (CC) surgery are serious and include intrahepatic stones and biliary carcinoma; therefore, long-term follow-up is crucial. METHODS: The subjects of this retrospective study were patients who underwent surgery for CC at Kagoshima University Hospital between April, 1984 and December, 2016. We analyzed the operative results, early and late postoperative complications, and postoperative follow-up rate. RESULTS: The study population comprised 110 CC patients (male/female: 33/77) with a median age at surgery of 4 years, 3 months (range 12 days-17 years). The patients underwent hepaticoduodenostomy (n = 1; 0.9%) or hepaticojejunostomy (n = 109; 99.1%). Late complications included intrahepatic bile duct (IHBD) dilatation (n = 1; 0.9%), IHBD stones (n = 3; 2.7%), and adhesive ileus (n = 4; 3.6%). There was no incidence of biliary carcinoma in this series. The rates of follow-up at our institute within 10 years of surgery and more than 20 years after surgery were 69.2% (18 of 26) and 14.5% (8 of 55), respectively. CONCLUSIONS: The follow-up rate after definitive surgery declined with time. Late complications were observed within 20 years, but biliary carcinoma was not observed. The follow-up rate should be increased to detect late complications. Moreover, patient education on long-term follow up is essential to prevent life-threatening events after definitive surgery for CC.

The novel preventive effect of Daikenchuto (TJ-100), a Japanese herbal drug, against neonatal necrotizing enterocolitis in rats.

PURPOSE: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of premature infants. Daikenchuto, a Japanese herbal drug, has several effects on the digestive system, so we investigated its preventive effects in a rat model of NEC. METHODS: NEC was induced in newborn rats via asphyxia (100% N2 for 90 s; every 4 h) + LPS (4 mg/kg/day [administered orally on days 0 and 1]). The effects of Daikenchuto were evaluated in four groups (control: 0 g/kg/day, I: 0.3 g/kg/day, II: 0.6 g/kg/day, and III: 1.0 g/kg/day). Daikenchuto was administered into the stomach through a microcatheter. The incidence and severity of NEC were pathologically assessed using the NEC grade in accordance with Dovorak's previous report. Cell positivity for inflammatory cytokine (IL-6) was also evaluated. RESULTS: Daikenchuto reduced the incidence of NEC in control, Groups I, II, and III to 68.7, 30.0, 30.7, and 13.3%, respectively. High-dose Daikenchuto significantly improved the incidence of NEC, and the rate of IL-6 positive cells in group III was significantly lower than in the control group (p = 0.04). CONCLUSION: We evaluated the effect of Daikenchuto against NEC and found that it reduced the incidence rate of NEC due to a decrease in the IL-6 production.

The changing profile of safe techniques for the insertion of a central venous catheter in pediatric patients - improvement in the outcome with the experiences of 500 insertions in a single institution.

BACKGROUND: The ability to safely insert a central venous catheter (CVC) is critical to avoid associated complications. The aim of this study was to explore appropriate technique to maintain the safety of pediatric patients during CVC. METHODS: We reviewed the surgical records of CVC insertion techniques and associated complications of 503 tunneled CVC insertions performed from 2000 to 2015. RESULTS: Two hundred thirty CVCs (45.7%) were inserted into the subclavian vein using the landmark technique for 10years (first period). Only two pneumothoraxes (0.9%) were experienced. In 2009, we adopted ultrasound-guided venous catheterization from the internal jugular vein, and 103 CVCs (20.5%) were inserted (second period). This procedure led to penetration into the innominate vein (1.0%) by dilater sheath. Patient underwent repair of the penetrated vessel. After this serious complication, 170 CVCs (33.8%) were inserted using the venous cutdown procedure except two catheters. We had two cases whose accessible veins were occluded because of frequent catheterization using venous cutdown technique. No mechanical complications were experienced. CONCLUSIONS: The venous cutdown method is the safest technique for inserting a tunneled CVC in pediatric patients. However, multiple vein occlusions because of repeated catheterizaion by venous cutdown lead to the exhaustion of accessible vessels. LEVEL OF EVIDENCE: Treatment Study - Level IV.

Heparin-binding epidermal growth factor-like growth factor and hepatocyte growth factor inhibit cholestatic liver injury in mice through different mechanisms.

In contrast to hepatocyte growth factor (HGF), the therapeutic potential and pathophysiologic roles of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in liver diseases remain relatively unknown. To address the lack of effective pharmacologic treatments for cholestatic liver injuries, as well as to clarify the biologic features of these growth factors, we explored the effects of HB-EGF and HGF in mice with cholestatic liver injury induced by bile duct ligation (BDL). The mice were assessed 3, 5 and/or 14 days after BDL (acute, subacute and/or chronic phases, respectively) and intravenous injection of adenoviral vector expressing LacZ (control), HB-EGF, HGF, or HB-EGF and HGF. HB-EGF, HGF, or a combination of the growth factors exerted potent antioncotic (antinecrotic), antiapoptotic, anticholestatic, and regenerative effects on hepatocytes in vivo, whereas no robust antiapoptotic or regenerative effects were detected in interlobular bile ducts. Based on serum transaminase levels, the acute protective effects of HB-EGF on hepatocytes were greater than those of HGF. On the other hand, liver fibrosis and cholestasis during the chronic phase were more potently inhibited by HGF compared with HB-EGF. Compared with either growth factor alone, combining HB-EGF and HGF produced greater anticholestatic and regenerative effects during the chronic phase. Taken together, these findings suggest that HB-EGF and HGF inhibited BDL-induced cholestatic liver injury, predominantly by exerting acute cytoprotective and chronic antifibrotic effects, respectively; combining the growth factors enhanced the anticholestatic effects and liver regeneration during the chronic phase. Our results contribute to a better understanding of the pathophysiologic roles of HB-EGF and HGF, as well as to the development of novel effective therapies for cholestatic liver injuries.

Abdominal wall regenerative medicine for a large defect using tissue engineering: an experimental study.

PURPOSE: Treatment for a large abdominal wall defect remains challenging. The aim of this study was to optimize tissue engineering therapy of muscle constructs using a rat model. METHODS: Experimental abdominal wall defects were created in Wister rats. The animal model was divided into three groups: collagen sponge (CS), hybrid scaffold (HS) and hybrid scaffold containing bone marrow liquid (HSBM). Hybrid scaffolds comprised collagen sponge and poly L-lactide (PLLA) sheets. Abdominal wall defects were covered by three kinds of sheets. Thereafter, the bone marrow liquid was spread onto the sheets. Rats were killed at 4, 8, and 16 weeks. Pathological examinations were performed using hematoxylin-eosin and desmin antibody staining. RESULTS: The CS group showed abdominal hernia, whereas the HS and HSBM groups did not. Vascular formation was confirmed in all groups. Muscle tissue was recognized at the marginal area of the sheet only in the HSBM group. CONCLUSION: The HS and HSBM groups show a greater intensity than the CS group. Muscle tissue regeneration is solely recognized in the HSBM group. Our experimental data suggest that the triad of scaffold, cell, and growth factor is fundamental for ideal biomaterials. The HSBM may be useful for reconstruction of abdominal wall defects.

Clinical features of pancreaticobiliary maljunction: update analysis of 2nd Japan-nationwide survey.

INTRODUCTION: Pancreaticobiliary maljunction (PBM) is a congenital anomaly, which can be defined as a union of the pancreatic and biliary ducts located outside off the duodenal wall. We herein investigate clinical features of PBM including as the 2nd report of a Japanese nationwide survey. PATIENTS AND METHODS: During a period of 18 years (from 1990 to 2007), 2,561 patients with PBM were registered at 141 medical institutions in Japan. Among them, eligible patients (n = 2,529) were divided into two groups: adult (n = 1,511) and pediatric patients (n = 1,018). Comparisons of clinical features including associated biliary cancers were performed according to the biliary dilatation (BD), age factor, and time era. RESULTS: Only one case in pediatric patients with BD combined with a bile duct cancer (0.1 %). In adult patients, the bile duct cancer and the gallbladder cancer was seen in 6.9 and 13.4 % patients with BD and in 3.1 and 37.4 % patients without BD, respectively. In adult patients with BD, the occurrence rates of biliary cancers were increased in latter period (00'-07') compared with former period (90'-99'). The ratio of biliary cancer localization was changed between former and latter period, and the bile duct cancer was increased in latter period (from 5.5 to 9.3 %). CONCLUSIONS: The largest series of PBM were evaluated to clarify the clinical features including the associated biliary cancer in this Japan-nationwide survey. This report could be widely used in the future as a reference data for diagnosis and treatment of PBM.

Therapeutic effects of vitamin A on experimental cholestatic rats with hepatic fibrosis.

PURPOSE: The aim of this study is to investigate the role of hepatic stellate cells (HSCs) and the effect of vitamin A administration on liver damage induced by bile duct ligation (BDL) and administration of CCl(4). METHODS: Two types of animal model were used; one was BDL as a model of biliary atresia, the other was CCl(4)-induced hepatic fibrosis. Pathological changes of the liver with or without administration of vitamin A were compared by light and electron microscopy with focusing on HSCs in each experimental group. Immunohistochemical examination was performed with anti-keratinocyte growth factor (KGF), anti-alpha-smooth muscle actin (α-SMA), and anti-glial fibrillary acidic protein (GFAP) antibodies, as markers of fibrosis. RESULTS: On light microscopic findings, periportal inflammation with bile ductular proliferation was obvious in BDL group and pericentral necrosis with fatty degeneration was observed in CCl(4) group, both of which were ameliorated by subcutaneous injection of vitamin A. Electron microscopy showed lipid droplets were almost depleted in the HSCs treated with BDL or CCl(4), which improved with vitamin A administration. Immunohistochemistry demonstrated that enhanced expression of all three fibrotic markers in the BDL group was diminished by vitamin A administration. CONCLUSIONS: Although most of our data are qualitative observation, vitamin A may ameliorate hepatic fibrosis in the BDL model by restoring vitamin A in the HSCs.

A review of 331 rhabdomyosarcoma cases in patients treated between 1991 and 2002 in Japan.

BACKGROUND: To prepare for a Japanese nationwide group study of patients with rhabdomyosarcoma (RMS), we examined the characteristics and outcomes of RMS patients treated recently in Japan. METHODS: We classified 331 RMS patients treated between 1991 and 2002 at 63 institutions according to the Intergroup Rhabdomyosarcoma Study V (IRS-V) risk-group classification. RESULTS: Ten-year survival rates were 86.3% for patients in low-risk subgroup A, 80.7% for low-risk subgroup B, 62.7% for intermediate-risk subgroup A, 61.7% for intermediate-risk subgroup B, and 38.1% for the high-risk group. The outcomes of the patients in the former three groups were 8%, 12%, and 21% worse than the outcomes of the respective patients in the IRS-III and early IRS-IV data. The frequency of the alveolar histological subtype was 21.8%. Chimera genes, which are useful markers for the alveolar subtype, had been examined in only 10% of the patients treated in the period of this investigation. The survival rates of our patients with embryonal and alveolar histological subtypes (65.9% and 63.4%, respectively) were not significantly different. Among the patients in the high-risk group, the 5-year survival of patients who received high-dose chemotherapy (HDC; 58.2%) was significantly better than that of patients who did not receive HDC (18.4%). CONCLUSION: Patients in the lower-risk groups with embryonal-type tumors had poorer outcomes in this retrospective study. The better outcome of patients in the high-risk group is apparently due to the outstanding results obtained with an HDC regimen in a single institution. These results suggest that there is a need for: (1) a standard therapy, (2) a rapid central pathology review including a chimera gene analysis for the lower-risk group, and (3) evaluation of the efficacy of the high-dose regimen for the high-risk group in Japan.

Clinical characteristics and outcome of Wilms tumors with a favorable histology in Japan: a report from the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan.

BACKGROUND/PURPOSE: Since 1996, the standard treatment of Wilms tumors in Japan has been based on the regimen of the Japanese Wilms Tumor Study. However, in Japan, there have been no reports about Wilms tumors that analyzed the clinical features and patient outcome in a large series until now. This study aims to assess the clinical characteristics of patients with Wilms tumor with a favorable histology from a retrospective standpoint in the Kyushu area in Japan and, furthermore, to analyze the historical changes of clinical features and outcome from the 1980s to the 1990s. METHODS: Between 1982 and 1996, 90 cases of Wilms tumors with a favorable histology were registered in the Kyushu area. Regarding the clinical feature and outcome, they were divided into 2 groups (group A, 1982-1989, n = 50; group B, 1990-1996, n = 40). The outcome was analyzed based on the 5-year overall survival rate. RESULTS: The clinical features (age, sex, initial symptom, location, stage) demonstrated no definite differences between group A and group B. Regarding the operation, the rate of an initial complete resection in the early stages was significantly higher in group B than in group A. All stage V cases in group B undewent a bilateral tumor biopsy instead of a radical nephrectomy as the initial operation. The 5-year overall survival rate throughout the whole period was 87.8%, whereas the rates were 84.0% for group A and 90.0% for group B (P = NS), respectively. Of particular note, the outcome of patients with stage I and stage V in group B substantially improved in comparison to that in group A. However, in advanced cases, no significant improvement in the outcome was noted. CONCLUSIONS: This is the first report about the clinical features and outcome for Wilms tumors with a favorable histology in Japan from the 1980s to the 1990s. The present study suggested that in the early-stage cases, an initially complete resection followed by standard postoperative chemotherapy substantially improved the outcome of the patients in group B. In the stage V cases, the performance of renal salvage surgery may have positively contributed to the improvement in the outcome in group B. However, in the advanced stage cases, no definite improvement was noted. In the future, an improved efficacy of the treatments for Wilms tumors based on the standard protocol established by the Japanese Wilms Tumor Study in 1996 is expected in Japan.

Successful treatment of an endodermal sinus tumor of the vagina by chemotherapy alone: a rare case of an infant diagnosed by pathological examination of discharged tumor fragment.

A 7-month-old infant was noted to have vaginal bleeding that was accompanied by a discharged tumor fragment. The histological diagnosis was endodermal sinus tumor. Her serum alpha-fetoprotein (AFP) was increased to 358.7 ng/mL, and magnetic resonance imaging showed a 1.8 x 1.0 cm tumor in the vagina. She received combination chemotherapy with cyclophosphamide, pirarubicin, carboplatin, and etoposide. The tumor in the images disappeared and the serum level of AFP returned to the normal range after 2 cycles. Treatment was complete without surgical or radiological therapy. More than 45 months after the completion of chemotherapy, she is alive without signs of recurrence.

Response of heavily treated and relapsed hepatoblastoma in the transplanted liver to single-agent therapy with irinotecan.

We describe here a patient with relapsed hepatoblastoma after LDLT who developed heart failure, which was treated with irinotecan hydrochloride (CPT-11). His native liver was replaced by a liver graft from his mother at 26 months from the onset. However, LDLT failed to induce complete remission and he was diagnosed as relapsed hepatoblastoma six months after LDLT. We again administered cisplatin and doxorubicin. After six courses of chemotherapy, he developed congestive heart failure because of anthracycline toxicity. The chemotherapy regimen was therefore switched to irinotecan at 35 mg/m2 daily for three days/wk for two consecutive weeks, and repeated every 28 days. After four courses of irinotecan, metastatic lesions were remarkably reduced in size, and the serum level of AFP decreased from 0.7 million to 927 ng/mL. No severe side effects were documented and congestive heart failure improved. These results suggest that irinotecan may be safely given to a patient with relapsed hepatoblastoma after LDLT without serious side effects and may contribute to prolonging the survival.

Bilateral asynchronous adrenocortical adenoma in a girl with beckwith-wiedemann syndrome.

We report a case of asynchronous occurrence of bilateral adrenocortical adenoma in a 13-yr-old girl with Beckwith-Wiedemann syndrome. A right virilizing adrenal adenoma was surgically removed at age 6, following clinical manifestation of virilization such as acne, voice change, clitoris hypertrophy and overgrowth. Histopathological examination of the resected specimen revealed an adrenocortical adenoma predominantly composed of eosinophilic tumor cells expressing all the steroidogenic enzymes. High serum levels of DHEA-S (6,380 ng/ml) and testosterone (547 ng/dl) were noted prior to the operation. Postoperative course was unremarkable. Menstruation started at age 11, with a regular interval. At the age of 13 yr old, a high serum level of DHEA-S (8,250 ng/ml) was detected. In contrast to the episode of virilization at age 6, however, the serum testosterone level was not so high (122 ng/dl), and no clinical symptoms of virilization were apparent. Abdominal ultrasonography demonstrated the presence of a left adrenocortical adenoma. Pathological examination of the resected specimen revealed a circumscribed and well encapsulated tumor with essentially the same histological features as the tumor previously removed, except that the tumor cells showed a more prominent morphological similarity to the fetal adrenal cortex and did not express 3ß HSD. The absence of virilization at the second episode was due to the relatively low serum level of testosterone compared with that of DHEA-S.

Postoperative corticosteroid therapy for bile drainage in biliary atresia--a nationwide survey.

PURPOSE: Members of the Japanese Biliary Atresia Society were surveyed to determine their current practice regarding early use of corticosteroids after Kasai's operation. METHODS: Questions included the patient's background data, dosage, timing, complications, and outcome. Anicteric survival with the native liver was statistically compared between groups categorized by steroid dosage using Kaplan-Meier analysis. RESULTS: Among 54 institutions surveyed, a total of 222 patients with uncorrectable BA were collected from 34 responders, including 208 patients who received steroid therapy and 14 without it. Prednisolone was started during the first postoperative week in 31% and during the second week in 64%. Perforation and peritonitis occurred in 1 patient given 3 mg/kg/d of prednisolone on postoperative day 1. The survival rates of the steroid and nonsteroid groups were 58.0% and 35.7%, respectively (P = .052). The initial dose of prednisolone was or=4.0 mg/kg/d in 108 patients. The survival rates of the group receiving >or=4.0 mg/kg/d and the nonsteroid group were 58.9% and 35.7%, respectively (P = .0494). CONCLUSIONS: (1) Most surgeons use steroids. (2) Although the anicteric survival rate was higher in the steroid group, the number of patients in the nonsteroid group was too small to draw conclusions. (3) The recommended initial steroid dose is >or=4.0 mg/kg/d. (4) Complications are uncommon if administration is not started too early.

Iliopsoas abscess in the neonate.

Iliopsoas abscess (IPA) is rare, especially in the neonatal period. The major presenting symptoms of IPA are leg or groin swelling, limitation of leg motion, and pain. The etiologies of IPA in many cases remain unknown, and the etiologic agent in many cases is Staphylococcus aureus. Ultrasonography and computed tomography are useful in diagnosing this disease. Antibiotics therapy and appropriate drainage are effective, and the prognosis is good. The authors present a neonatal case of IPA and discuss clinical symptoms, etiologic agents, methods of diagnosis and therapy, and prognosis.

Fetal ultrasonography to prevent irreversible neurological sequelae of neonatal neuroblastoma.

An intra-abdominal mass was observed by fetal ultrasonography at 32 weeks of gestation. The baby was diagnosed as having neuroblastoma at the time of delivery at 39 weeks and its lower extremities were completely paralyzed. The chemotherapy after birth was quite effective to reduce the mass volume but neurological sequelae failed to improve. By carefully monitoring the movement of extremities, it may have been possible to prevent irreversible by inducing delivery before that state was reached.