Evaluation of the role of bile acids and serotonin as markers of pruritus in children with chronic cholestatic liver disease.

BACKGROUND AND STUDY AIMS: Pruritus is an annoying symptom with an unclear pathogenesis accompanied by chronic cholestasis. This cross-sectional study was conducted to define the relationship between serum levels of presumed pruritogens (bile acids (BAs) and serotonin) and severity of pruritus in pediatric patients with chronic cholestatic liver disease. PATIENTS AND METHODS: A total of 28 children suffering from pruritus due to chronic cholestatic liver disease and 29 age- and sex-matched healthy control subjects were examined. Scores obtained used the 5-D itch scale were evaluated among patients. Serum levels of BAs and serotonin were determined using enzymatic assays and high-performance liquid chromatography, respectively. RESULTS: Patients had higher serum BA levels and lower serotonin levels than control subjects. Serum BA levels were significantly elevated in 61% of patients. The 5-D itch scale scores were significantly higher in cholestatic individuals with normal γ-glutamyl transpeptidase levels. Neither BA nor serotonin levels correlated with the severity of the 5-Ditch scale score. CONCLUSION: Neither BA nor serotonin levels correlated with the severity of pruritus, indicating that they may not be good laboratory markers for the intensity of itch in children with cholestasis. Our findings suggest that it is necessary to identify another potential pruritogenic mediator, most probably of a biliary origin.

Adjuvant Sandwich Chemotherapy Plus Radiotherapy vs Adjuvant Chemotherapy Alone for Locally Advanced Bladder Cancer After Radical Cystectomy: A Randomized Phase 2 Trial.

Importance: Locoregional failure for patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity and mortality. Adjuvant radiotherapy (RT) can decrease locoregional failure but has not been studied in the chemotherapy era. Objective: To investigate if adjuvant sequential RT plus chemotherapy can improve locoregional recurrence-free survival (LRFS) compared with adjuvant chemotherapy alone. Design, Setting, and Participants: A randomized phase 3 trial was opened to compare adjuvant RT vs sequential chemotherapy plus RT after RC for LABC, but a third arm was added later as a randomized phase 2 trial to compare chemotherapy plus RT vs adjuvant chemotherapy alone, an emerging standard. The intent-to-treat phase 2 trial reported herein enrolled patients from December 2002 to July 2008. Data were analyzed from August 3, 2015, to January 6, 2016. Routine follow-up and surveillance pelvic computed tomographic (CT) scans every 6 months during the first 2 years were performed. The setting was an academic center. Patients with bladder cancer 70 years or younger having 1 or more risk factors (≥pT3b, grade 3, or positive nodes) with negative margins after radical cystectomy plus pelvic lymph node dissection were eligible. Patients had Eastern Cooperative Oncology Group performance status of 0 to 2, no evidence of distant metastases on CT scan of the abdomen and pelvis or on chest imaging, and adequate renal, hepatic, and hematologic function. Ninety-one percent (109 of 120) had ≥ pT3 disease. Interventions: Chemotherapy plus RT included 2 cycles of gemcitabine (1000 mg/m2 intravenously on days 1, 8, and 15) and cisplatin (70 mg/m2 intravenously on day 2) before and after RT to 4500 cGy in 150 cGy twice-daily fractions over 3 weeks using 3-dimensional conformal techniques. Chemotherapy alone included 4 cycles of gemcitabine and cisplatin. Main Outcome and Measure: Locoregional recurrence-free survival. Results: The chemotherapy plus RT arm accrued 75 patients, and the chemotherapy-alone arm accrued 45 patients, with a weighted randomization to speed accrual. Fifty-three percent (64 of 120) had urothelial carcinoma, and 46.7% (56 of 120) had squamous cell carcinoma or other. The arms were balanced except for age (median, 52 vs 55 years; P = .04) and tumor size (mean, 4.9 vs 5.8 cm; P < .01), both favoring chemotherapy plus RT. Two-year outcomes and overall adjusted hazard ratios (HRs) for chemotherapy plus RT vs chemotherapy alone were 96% vs 69% (HR, 0.08; 95% CI, 0.02-0.39; P < .01) for LRFS, 68% vs 56% (HR, 0.53; 95% CI, 0.27-1.06; P = .07) for disease-free survival, and 71% vs 60% (HR, 0.61; 95% CI, 0.33-1.11; P = .11) for overall survival (OS). Five patients (7%) had RT-associated late grade 3 gastrointestinal tract adverse effects in the chemotherapy plus RT arm. Conclusions and Relevance: Adjuvant chemotherapy plus RT was reasonably well tolerated and was associated with significant improvements in LRFS and marginal improvements in disease-free survival vs chemotherapy alone in LABC. The addition of adjuvant RT should be considered for LABC. This regimen warrants further study in phase 3 trials. Trial Registration: clinicaltrials.gov Identifier: NCT01734798.

Rhabdomyosarcoma in childhood: a retrospective analysis of 190 patients treated at a single institution.

OBJECTIVES: The study goal was to retrospectively review the treatment results of childhood rhabdomyosarcoma and identify prognostic factors that affect treatment outcome. PATIENTS AND METHODS: The records of 190 patients with childhood rhabdomyosarcoma treated between January 1991 and December 1999 were reviewed. The data were analyzed for clinico-epidemiological factors and the impact of potential prognostic factors on failure-free survival. Factors evaluated were age, gender, histology type, primary site, tumor size, Intergroup Rhabdomyosarcoma Study (IRS) group, surgical procedure, and the use of radiation treatment. RESULTS: The 5-year actuarial FFS and OS were 40% and 50%, respectively. The only significant prognostic factors as estimated by univariate analysis were histology type (p=0.01), primary site (p=0.002), tumor size (p=0.049), IRS-group (p=0.003), surgical procedure (p=0.002), and radiation treatment (p=0.001). Multivariate analysis showed that histology type (p=0.02), primary site, and IRS-group (p=0.02) were the only independent prognostic factors. CONCLUSIONS: This analysis demonstrates that failure-free survival for rhabdomyosarcoma is dependent on several factors at the time of initial diagnosis, including histologic subtype, primary site and disease group. Our treatment results were inferior compared to IRS-studies as the patients during this period were treated on individual bases and not standardized protocol.