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.     

Duodenal ulcer and working-class mobility in an African population in South Africa

The number of Africans in Johannesburg presenting with duodenal ulcers has steadily increased over the past 50 years. The characteristics of 105 patients with duodenal ulcer who presented a Baragwanath Hospital were compared with those of matched and unmatched samples of patients without gastrointestinal conditions in the same hospital. Men with duodenal ulcers were found to be significantly better educated than their controls, most had been born in the town, and more of them were employed at higher, though not the highest, educational levels. These data were used to test Susser's proposition that duodenal ulcers are associated with "early urbanisation." Johannesburg blacks with duodenal ulcer did seem to fit the pattern, but the relation between stress and duodenal ulcer remains unclear.     

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.     

Auditory brainstem implantation: The first Indian experience

Multichannel auditory brainstem implants (ABI) are currently indicated for patients with neurofibromatosis type II (NF2) involving both vestibulocochlear nerves. The ABI helps bypass the damaged cochlear nerves and restores a level of auditory sensation via the electrical stimulation of the cochlear nucleus. The implant is usually placed in the lateral recess of the fourth ventricle at the time of tumor resection to stimulate the cochlear nucleus. We report a case of ABI done on a 15-year-old girl with bilateral vestibular schwannomas.