Treatment guidelines for persistent cloaca, cloacal exstrophy, and Mayer-Rokitansky-Küster-Häuser syndrome for the appropriate transitional care of patients.

We developed treatment guidelines (TGs) for appropriate transitional care of the genitourinary system in patients with persistent cloaca (PC), cloacal exstrophy (CE), or Mayer-Rokitansky-Küster-Häuser syndrome (MRKH). These TGs are in accordance with the Medical Information Network Distribution Service (Minds), published in 2014 in Japan. Clinical questions (CQs) concerning treatment outcomes of the genitourinary system, pregnancy and delivery, and quality of life in adulthood were prepared as six themes for PC and CE and five themes for MRKH. We were able to publish statements on chronic renal dysfunction, hydrometrocolpos, and pregnancy, based on four CQs about PC, four about CE, and two about MRKH, respectively. However, due to the paucity of proper manuscripts, we were unable to make conclusions about the correct timing and method of vaginoplasty for patients with PC, CE, and MRKH or the usefulness of early bladder closure for patients with CE. These TGs may help clarify the current treatments for PC, CE, and MRKH in childhood, which have been carried out on an institutional basis. To improve clinical outcomes, systematic clinical trials revealing comprehensive clinical data of the urinary and reproductive systems, especially the length of the common channel in PC, are essential.

Acquired isolated hypoganglionosis as a distinct entity: results from a nationwide survey.

PURPOSE: Acquired isolated hypoganglionosis (A-IH) is a late-onset intestinal pseudo-obstruction disorder and shows different pathophysiological findings from congenital isolated hypoganglionosis (C-IH). In this study, we retrospectively examined five cases of A-IH and investigated the features of A-IH. METHODS: Five cases of A-IH were extracted from a nationwide retrospective cohort study in 10 years, from which totally 355 cases of Allied Disorders of Hirschsprung's Disease (ADHD) were collected. RESULTS: Ages of onset were between 13 and 17 years in three cases, and 4 years and 4 months in ones. Initial symptoms were abdominal distension and/or chronic constipation in 4 cases, whereas one exhibited intestinal perforation. Affected lesions varied from case to case, extending various length of intestinal tracts. All cases underwent multiple operations (average: 4.6 times), such as enterostomy, resection of dilated intestines, and/or pull-through. Pathological findings showed the decreased numbers of ganglion cells and degeneration of ganglion cells, whereas the size of the plexus was normal. Currently, all cases were alive and almost all eat regular food without requiring parenteral feeding. CONCLUSION: A-IH is rare, but distinct entity characterized by different clinical courses and pathological findings from those of C-IH. The outcome is considered to be favorable after a resection of affected intestine.

Usefulness of 99mTc-DTPA galactosyl human serum albumin liver scintigraphy for evaluating hepatic functional reserve after Kasai procedure.

BACKGROUND/PURPOSE: We investigated whether 99mTc-DTPA galactosyl human serum albumin (GSA) liver scintigraphy could help evaluate post-Kasai procedure hepatic functional reserve in order to inform therapeutic strategies, including liver transplantation. METHODS: GSA scintigraphy was performed post-Kasai procedure. Patients were classified as having favorable (native liver survival) or poor (liver transplantation or death) prognoses. The clearance index (HH15), receptor index (LHL15), and time at which cumulative liver radioactivity reached 85% of heart plus liver activity (T0.85) were compared to laboratory data and prognosis. RESULTS: GSA scintigraphy was performed 106 times on 35 patients. T0.85 correlated well with laboratory variables associated with liver function (platelet count, international normalized ratio of prothrombin time, serum albumin, total cholesterol, and cholinesterase). HH15 correlated moderately and LHL15, poorly. HH15 and T0.85 values were significantly higher in the poor-prognosis than in the favorable-prognosis group, and LHL15 was significantly lower. The T0.85 cutoff value (6.25min) corresponded with division into prognosis groups, and had high sensitivity (0.78) and specificity (0.83). CONCLUSIONS: Hepatic functional reserve post-Kasai procedure can be evaluated using the GSA scintigraphy T0.85 value. A value consistently >6.25min indicates the need for liver transplantation. TYPE OF STUDY: Diagnostic Test. LEVEL OF EVIDENCE: Level III.

Systemic and Local Cytokine Profile in Biliary Atresia.

Purpose Systemic and local immune environments in human biliary atresia (BA) were analyzed. Methods Plasma concentrations of 19 inflammatory components in 16 preoperative BA patients (median age, 51 days), 13 normal controls (NCs) (44 days), and 15 cholestatic controls (CC) (23 days) were measured using flow cytometry, and compared according to post-Kasai outcomes in BA patients. Hepatic mRNA levels of representative helper T (Th) cell cytokines and forkhead box protein 3 (FoxP3) quantified by real-time reverse transcription polymerase chain reaction were compared between BA and non-BA. Results No significant differences were observed between BA and control in serum Th1, Th2, or macrophage markers, while soluble cellular adhesion molecule (CAM) levels were significantly higher in BA (p < 0.0001 for NC; p = 0.0003 for CC). No statistically significant difference was discovered between BA with favorable and unfavorable prognosis. Hepatic mRNA levels of interferon-gamma or interleukin-4 showed no significant differences between BA and non-BA, while FoxP3 was significantly higher in BA (p = 0.01). Conclusions A skewed bias toward specific Th-oriented immunity was not demonstrated in either the systemic or local environment in the early stage of human BA, with patient prognoses not necessarily revealed by preoperative plasma inflammatory component levels. CAM and regulatory T cell roles and functions warrant further investigation.

Histological features of primary tumors after induction or high-dose chemotherapy in high-risk neuroblastoma.

PURPOSE: In the recent years in Japan, an increasing number of patients with neuroblastoma (NB) are being treated by the "delayed local treatment (DL)" policy, undergoing surgery after the completion of high-dose chemotherapy with hematopoietic stem cell rescue (HDC). We reviewed the histopathological findings of second-look operations, including those of patients treated with DL. PATIENTS: From 1998 to 2013, 26 patients with high-risk NB underwent radical operation following chemotherapy. Surgery was performed after induction chemotherapy in 17 cases (standard; STD), whereas 9 cases completed induction chemotherapy and HDC before undergoing tumor resection (DL). The amount of necrosis and the degree of differentiation within the post-treatment tumor were assessed. RESULTS: Eighty-eight percent of the tumors showed necrosis in more than 1/3 of the specimen. Two DL cases showed complete disappearance of viable tumor cells. Amount of necrosis did not affect the prognosis of the patient. Tumors with immature, poorly differentiated phenotypes showed an extremely aggressive thereafter. Though not statistically proven, (123)I-MIBG (metaiodobenzylguanidine) uptake may be correlated with the amount of viable cells remaining within the tumor, but not with the degree of differentiation. CONCLUSIONS: Our results support the previous reports advocating that tumors that sustain unfavorable histology after chemotherapy behave aggressively thereafter.

Optimal surgical treatment and urological outcomes in boys with pelvic and urogenital rhabdomyosarcomas and soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas (STS) of pelvic origin in boys often involve the urogenital organs. The optimal extensiveness of radical surgery has long been an issue of discussion, since exenterative surgeries result in severe urogenital adverse effects. We conducted a retrospective review of patients with pelvic STS treated in two regional center hospitals and assessed the radicality of surgery and the functional outcome of the bladder. PATIENTS: Medical records and surgical reports of nine cases (embryonal rhabdomyosarcoma 6, malignant triton tumor 2, suspected rhabdomyosarcoma 1) treated within 1997-2012 were reviewed. Site of origin was prostate in seven, retroperitoneal in two. Average follow-up period was 96 months. TREATMENT AND OUTCOME: All cases were subjected to neoadjuvant chemotherapy. Response was PR in four, SD in two, and PD in two. Radical surgery resulted in gross total resection in eight, and partial resection in one. Three underwent cystoprostatectomy, two cases underwent prostatectomy, and bladder-preserving tumor resection was carried out in four cases. At the last follow-up, three retained a functional bladder. Two required augmentation cystoplasty with intestinal conduits. CONCLUSIONS: The majority of the on-going clinical trials recommend conservative surgery for bladder/prostate rhabdomyosarcoma, and to preserve the bladder function particularly in chemosensitive tumors. Some other groups, however, advocate the importance of radical surgery to prevent local relapse. These reports include heterogenous group of patients in the cohort, and therefore it is difficult to draw a conclusion of which approach truly contributes to the survival of the patients better. Future studies should evaluate bladder and sexual function objectively to establish reliable evidence regarding the benefit and adverse effects of different surgical approaches. These data would be informative to optimize the treatment balance for children with pelvic rhabdomyosarcomas.

Diagnosis of Biliary Atresia Can not be Excluded by Declining Trend of Serum Direct Bilirubin.

The aim of this paper is to investigate the clinical courses of patients with biliary atresia (BA) during neonatal period. We examined 19 patients with BA, who underwent blood tests including direct bilirubin (D-Bil) within 20 days of age, in 3 tertiary hospitals in Japan. The first blood sample was collected at 8.4±6.5 days of age. The acholic stool was observed within 2 weeks of age in 16 cases (84.2%). Decrease of T-Bil was observed in all the subjects, with a range of reduction of 6.5±3.3 mg/dL, from 10.4±7.5 to 29.8±9.1 days of age. Decrease of D-Bil was also observed in 17 out of 19 cases (89%), with a range of reduction of 1.1±1.0 mg/dL, from 15.5±8.0 to 24.9±9.6 days of age. A significant decrease of D-Bil was observed in 2 cases of biliary atresia splenic malformation syndrome. We therefore conclude that clinicians treating icteric infants should not exclude a diagnosis of BA even if the level of D-Bil has a declining tendency.

Etiology of neonatal gastric perforation: a review of 20 years' experience.

PURPOSE: Gastric perforation (GP) of the newborn is a rare, serious, and life-threatening problem, and its etiology remains unclear. Although historically GP has often been described as "spontaneous'', some cases are non-spontaneous. The aim of the present study was to review cases of GP and to discuss its etiology in a single prefecture in Japan over a period of 20 years. METHODS: Eleven cases with GP that underwent surgery in 4 institutions in the Chiba Prefecture from 1991 to 2010 were reviewed and divided into 2 groups: the early (1991-2000, n = 7) and late (2001-2010, n = 4) groups. RESULTS: No factors were observed that could have caused GP other than malformations associated with distal obstruction (3 midgut volvulus, 1 jejunal stenosis, 1 diaphragm eventration). Distal obstruction was present in 1 case in the early group and all 4 cases in the late group (p = 0.015). While the incidence of GP did not change over the 20-year period reviewed, the incidence of GP without distal obstruction significantly decreased in the late group. CONCLUSION: The proportion of patients with GP and distal obstruction increased and true "spontaneous" cases of GP decreased over time. The possible presence of distal obstruction should be evaluated during surgery for GP.