Trends in management of ureteral urothelial carcinoma and effects on survival: a hospital-based registry study

BackgroundHigh-risk ureteral tumors represent an understudied subset of upper tract urothelial carcinoma, whose surgical management can range from a radical nephroureterectomy (NU) to segmental ureterectomy (SU).ObjectivesTo evaluate contemporary trends in the management of high-risk ureteral tumors, the utilization of lymphadenectomy and peri-operative chemotherapy, and their impact on overall survival (OS).Design, setting, and participantsWe performed a retrospective cohort study of patients in the National Cancer Database from years 2006 to 2013 with clinically localized high-risk ureteral tumors treated with NU or SU.Outcome measurements and statistical analysisChi-squared tests were utilized to assess differences in clinicodemographic features and peri-operative treatment delivery between SU and NU cohorts. Cochran-Armitage tests and linear regressions were performed to evaluate temporal trends in treatment utilization. Multivariable logistic regression models were employed to assess predictors of treatment delivery. Multivariable Cox proportional hazards models evaluated associations with OS.ResultsOf the 1,962 patients included, NU was more commonly performed than SU (72.4%, 1,421/1,962 vs. 27.6%, 541/1,962). Only 22.7% (446/1,962) of the population underwent lymphadenectomy, and 24.8% (271/1,092) of those with advanced pathology (≥pT2 or pN+) received adjuvant chemotherapy. Lymphadenectomy was associated with improved OS in NU patients when more than 3 nodes were removed (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.39–0.89). Receipt of adjuvant chemotherapy for advanced pathology had no impact OS in both the NU (HR 1.10, 95% CI 0.84–1.44) and SU (HR 0.94, 95% CI 0.61–1.46) cohorts. Performance of SU was not associated with poorer OS on multivariable analysis (HR 1.02, 95% CI 0.89–1.21, P = 0.83).ConclusionOur study suggests that SU may be an appropriate alternative to NU for the management of high-risk ureteral tumors. Further, lymphadenectomy may play an important role at the time of NU, and adjuvant chemotherapy is infrequently utilized in patients with advanced pathology.     

Law-like relationship between height and weight of school children

Ehrenberg’s Law-like relationship between height and weight [log was applied to a group of public school and Govt. school children in New Delhi. It was found that the model log was comparatively a good fit for public school children and the model log for Govt. school children. On fitting the model to the sample data it was found that the value of ‘a’ was 0.8, with some minor variation in the second decimal point and the value of ‘b’ was 0.39 & 0.36 respectively for public school boys and girls and 0.32 & 0.29 respectively for Govt. school boys & girls. These results corroborates with the findings of the earlier studies that the intercept constant ‘b’ in the Law-like relationship equation is influenced by the nutrition of children. This model is recommended because of its simplicity and practical usefulness using only already available information.     

Is the prevalence of HIV-associated nephropathy decreasing?

Initial reports have suggested that approximately 10% of patients with HIV-infection develop HIV-associated nephropathy (HIVAN). It has also been predicted that by the end of the decade, HIVAN is likely to become a third leading cause of end-stage renal disease (ESRD) in African-Americans between the ages of 20-64 years. As the morbidity and mortality from HIV-infection has decreased in the last few years, it is possible that prevalence of HIVAN is also changing. We therefore screened HIV-1-infected patients followed in our hospital for HIVAN. A screening urinalysis was performed in 557 HIV-1-infected adult patients between March and May 1998. Of these, 252 were outpatients and 305 were Texas Department of Criminal Justice inmates (TDCJI). Demographic and laboratory data of these patients was obtained from the HIV patients' database. Fifty percent of the patients were African-American, 36.6% were Caucasian and 12. 7% were Hispanic. The mean age of patients was 37 +/- 8 years. Seventy-nine percent of the patients were males and a history of intravenous drug abuse (IVDA) was present in 28%. Twenty-three percent of the patients were concomitantly infected with hepatitis C virus, 4.1% were positive for hepatitis B surface antigen, and rapid plasma reagin test for syphilis was positive in 9.1%. In 38 patients who had more than 100 mg/dl (2+) proteins on screening urinalysis, total urinary proteins were quantitated by collecting 24 h urine specimens. Fifteen of these patients had urinary proteins more than 1.5 g/day (12 patients >3.5 g/24 h and 3 patients >1.5 g/24 h). A renal biopsy was done in 14 of these patients and clinical diagnosis of HIVAN was made in one patient who refused biopsy. Renal biopsies revealed HIVAN [9], diabetic nephropathy [2], membranoproliferative glomerulonephritis [2], Fibrillary glomerulonephritis [1]. All 10 patients (5 TDCJI and 5 outpatients) with HIVAN were African-American. Two of these 10 patients had a history of IVDA and another two were concomitantly infected with hepatitis C virus. The plasma viral load (Pvl) and total CD4 count was not different in patients with or without HIVAN [(Pvl log 10.05 +/- 1.39 vs. 9.9 +/- 2.18 copies/ml, p = 0.78) (CD4: 187 +/- 192 vs. 288 +/- 249 cells/microl, p = 1.17) mean +/- SD]. We conclude that in our HIV-infected population HIVAN exclusively affected African-Americans and the prevalence in them was 3.5%. Copyright Copyright 1999 S. Karger AG, Basel     

Bilateral basal ganglia lucencies following acute febrile illness

Bilateral striatal necrosis in children without damage elsewhere in the brain can present as an acute neurological disorder or as a progressive disorder. Three children of 6, 7 and 12 years age developed dystonic posture of limbs without any cranial nerve involvement or alteration of sensorium soon after recovery from acute high grade febrile illness of 3–4 days duration. Computerized tomographic scan of head showed bilateral necrosis of basal ganglia. We think that these patients probably constitute a clinically and radiologically distinct subgroup of disorder that prouce bilateral striatal necrosis in children. The cause of the syndrome is unknown.     

Staging papillary carcinoma of the thyroid: magnetic resonance imaging vs ultrasound of the neck

AIM: To evaluate the role of magnetic resonance imaging (MRI) for staging local disease and lymph node metastases in papillary carcinoma of the thyroid by comparing MRI with ultrasound (US) of the neck. MATERIALS AND METHODS: Fourteen patients with papillary carcinoma underwent MRI and US. The images were prospectively reviewed for (1) identification of the primary lesion; (2) presence of multifocal thyroid disease; (3) extracapsular extension; (4) invasion into the trachea, oesophagus and major vessels; and (5) presence of lymph node metastases. Correlation was made with the surgical findings. RESULTS: The site of the primary lesion was correctly identified by US in 14 of 14 (100%) and by MRI in 13 of 14 (93%) of patients. Multifocal thyroid tumour was correctly identified by US in two of two patients (100%) and by MRI in zero of two (0%). Extracapsular extension (n = 9), oesophageal invasion (n = 1) and tracheal invasion (n = 2) were identified by MRI in seven, zero, and one, and by US in six, zero and zero patients, respectively. Invasion of the major vessels was not seen. Metastatic cervical nodes were present in 19 nodal groups in 10 patients involving the internal jugular chain (n = 10), posterior triangle (n = 4) supraclavicular fossa (n = 1) and central group (n = 4). Both MRI and US failed to identify metastatic nodes in the central group but correctly identified 14 of the 15 nodal groups outside the central group. CONCLUSION: Ultrasound should be used as the first line of investigation for detecting the primary lesion, multifocal disease and cervical lymphadenopathy. In cases where the primary tumour is not surrounded by normal thyroid tissue MR imaging should be added to assess extracapsular spread, especially into the trachea.     

Unusual presentation of a giant glomus tumor

Giant glomus tumors pose a challenge to the Otologist by virtue of their location and vascularity. A vast majority of them present with tinnitus, conductive hearing loss and cranial nerve palsies. We report the case of a 16-year-old male patient who presented with sudden right-sided sensorineural hearing loss. This is an unusual presentation of a giant glomus tumor. We present the clinical features and management of this unusual case.     

In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5.

Midazolam, triazolam (TRZ), testosterone, and nifedipine have all been widely used as probes for in vitro metabolism of CYP3A. We used these four substrates to assess the contributions of CYP3A4 and CYP3A5 to in vitro biotransformation in human liver microsomes (HLMs) and in recombinant enzymes. Recombinant CYP3A4 and CYP3A5 (rCYP3A4 and rCYP3A5) both produced 1-OH and 4-OH metabolites from midazolam and triazolam, 6 beta-hydroxytestosterone from testosterone, and oxidized nifedipine from nifedipine. Overall, the metabolic activity of CYP3A5 was less than that of CYP3A4. Ketoconazole potently inhibited midazolam, triazolam, testosterone, and nifedipine metabolite formation in HLMs and in rCYP3A4. The inhibitory potency of ketoconazole in rCYP3A5 was about 5- to 19-fold less than rCYP3A4 for all four substrates. In testosterone interaction studies, testosterone inhibited 1-OH-TRZ formation, but significantly activated 4-OH-TRZ formation in HLMs and rCYP3A4 but not in rCYP3A5. Oxidized nifedipine formation was inhibited by testosterone in rCYP3A4. However, in rCYP3A5, testosterone slightly activated oxidized nifedipine formation at lower concentrations, followed by inhibition. Thus, CYP3A4 and CYP3A5 both contribute to midazolam, triazolam, testosterone, and nifedipine biotransformation in HLMs, with CYP3A5 being metabolically less active than CYP3A4 in general. Because the inhibitory potency of ketoconazole in rCYP3A5 is substantially less than in rCYP3A4 and HLMs, CYP3A5 is probably less important than CYP3A4 in drug-drug interactions involving ketoconazole and CYP3A substrates.