Oral ulceration in HIV infection: Investigation and pathogenesis

Oral ulcerations associated with HIV infection include recurrent aphthous ulcers (RAU). Whereas RAU prevalence is not increased, lesion severity is: among a group of HIV⁺ patients, 66% had the more severe herpetiform or major RAU. This increased severity suggests that HIV disease-related changes in the immune system may exacerbate RAU. In the peripheral blood of healthy subjects with RAU, CD4:CD8 cell ratios may be reversed and the proportion of T cell receptor-γδ⁺ cells increased. HIV disease-related immune system changes are characterized by reversed CD4:CD8, lowered CD4 cell counts and an inverse correlation between CD4 cell counts and per cent activated γδ lymphocytes. Adhesion molecules and cytokines involved in lymphocyte homing may be important in RAU pathogenesis: ICAM-I and ELAM are strongly expressed, and TNFα production is increased in peripheral blood lymphocytes of healthy patients with RAU. In patients with active HIV disease/AIDS, serum TNFα levels are increased. Thalidomide, which inhibits TNFα production, is effective treatment for RAU. Some RAU patients have vitamin B12 or folate deficiencies, levels of which are commonly low in HIV⁺/AIDS patients. However, in a case control study of HIV⁺ patients, vitamin B12- or folate-deficiencies were not found to be significant risk factors for RAU.     

Extracellular matrix molecules in chronic obstructive sialadenitis: an immunocytochemical and Western blot investigation

The exact pathomechanism of inflammation progress and fibrosis in chronic sialadenitis is unknown. Connective tissue growth factor (CTGF), matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been implicated in the pathogenesis of various fibrotic conditions. These factors are thought to be essential in the regulation of extracellular matrix turnover and the development of tissue fibrosis. In the present study, the expression of CTGF, MMP-2, -3, -9, -13 and TIMP-3 was examined in chronic obstructive sialadenitis. Tissue samples of 13 patients with chronic sialadenitis of the submandibular gland associated with sialolithiasis and 4 normal tissue samples of the submandibular gland were analyzed immunohistochemically and by Western blot analysis. An intense CTGF immunoreactivity was observed in the ductal system of inflamed salivary glands, whereas in normal glands no reactivity or a very low CTGF immunoreactivity was present. Immunohistochemical studies revealed a low to strong reactivity of MMP-2, -3, -9, -13, and TIMP-3 in the ductal system, in acinar cells and in lymphomonocytic infiltrates in normal and inflamed tissues. The expression of MMP-2, -3, -9, -13, and TIMP-3 was confirmed by Western blotting in all cases. Over-expression of CTGF in chronic obstructive sialadenitis suggests that this factor may play a role in glandular fibrosis. However, the physiological role of MMP-2, -3, -9, -13, and TIMP-3 in normal glands, as well as their possible role in inflammation progress and fibrosis in chronic obstructive sialadenitis, remains to be elucidated.     

Epstein-Barr virus BMRF-2 and BDLF-3 expression in hairy leukoplakia

Hairy leukoplakia (HL) is a lesion found on the side of the tongue of immunocompromised individuals, including those with human immunodeficiency virus (HIV) infection. The lesion has unique histopathologic features and is characterised by high-level Epstein-Barr virus (EBV) replication, multiple EBV strains, and extensive inter-and intra-strain recombination. Expression of EBV genes spanning the entire viral life cycle from latency-associated genes to late, replicative genes has been detected in the lesion. HL thus provides a unique opportunity to study EBV expression in oral epithelium, and to study expression of novel EBV genes. We therefore constructed a cDNA library from an HL biopsy and detected expression of two genes not previously described in vivo: BMRF-2 and BDLF-3. Sequence analysis of the cDNAs revealed few amino acid changes from the B95-8 sequence. Expression of both genes was localized to the lower prickle cell layer of the tongue epithelium. BMRF-2 protein expression was primarily detected in the cell nuclei of the upper prickle cell layer. BDLF-3 protein expression was observed in the perinuclear space and Golgi compartment. The function of these proteins is currently under investigation.     

Blickdiagnose bei der transurethralen Resektion von Harnblasentumoren

Introduction

The gold standard for diagnosis and immediate therapy of bladder cancer is a transurethral resection (TURB) followed by histopathologic evaluation. The aim of this study was to assess the reliability of visual diagnosis by the operating urologist concerning dignity (malignant/benign) and staging compared to histopathologic evaluation. This is especially crucial since early mitomycin C instillation is based on the urologist’s first impression.

Study design and methods

This prospective study included 311 cases of TURB from five German institutions. Surgeons were asked to estimate dignity of the neoplasm, tumor stage, and grade according to a standardized questionnaire.

Results

The subjective estimation/visual diagnosis of the operating urologist achieved a sensitivity with respect to identifying malignant tumors as such of 97%, while specificity was only 41%. Accordingly, the positive (PPV) and negative predictive values (NPV) were 76% and 88%, respectively. In general, muscle invasive cancer was predicted more often than confirmed by pathology (PPV 52%). However, whenever muscle invasive cancer was excluded by the urologist, this was confirmed by the pathologist in most the cases (NPV 95%). The educational degree did not influence the reliability and predictive value of visual diagnosis.

Conclusion

This study shows that urologists cannot reliably distinguish benign from malignant lesions of bladder mucosa—regardless of their educational degree. A reliable diagnosis of a pathologist is definitely needed to plan final therapeutic steps.     

Einfluss der Ureterschienung vor ureterorenoskopischer Behandlung von Harnleitersteinen

Background

Due to a worldwide rise of incidence, urolithiasis presents an increasing strain on the health system. Ureterorenoscopy (URS) is a standard treatment to extract stones in case of ureteral calculi. To increase the success rate of URS and to minimize complications, preoperative ureteral stenting (prestenting) has previously been described as suitable. However, published data are still conflicting. This article describes our single-center experience on the influence of prestenting on the outcome of ureterorenoscopic stone therapy.

Methods

A total of 442 patients who had undergone ureterorenoscopic stone extraction at the Wolfsburg Clinic between 2010 and 2011 were retrospectively evaluated regarding peri- and postoperative results. The Fisher’s exact, the χ², and the Mann–Whitney U test were used to compare the group of patients with and without prestenting.

Results

Even though patients with prestenting suffered from stones with larger diameter that were more frequently located in the proximal ureter, the rates for postoperative stenting, perioperative complications, and retreatment were much lower then in the group of patients without prestenting (p<0.001). Furthermore, patients who had received prestenting had a significantly shorter hospital stay (median, 3 vs. 2 days, p<0.001) and higher rates of stone clearance (83.0 vs. 69.7%, p=0.001).

Conclusion

According to our retrospective monocentric analysis, prestenting may significantly reduce the risk of complications as well as intra-/post-URS restenting and can increase the rate of complete stone clearance.     

Temsirolimus in Daily Use: Results of a Prospective Multicentre Noninterventional Study of Patients with Metastatic Kidney Cancer

Background

Temsirolimus (TEMSR) was approved for treating advanced renal cell carcinoma (RCC) in 2007. Based on the data from a single phase 3 trial, it is recommended explicitly as first-line therapy for patients with a poor clinical prognosis.

Objective

The aim of this prospective multicentre trial (STARTOR) was to examine the effectiveness of TEMSR in daily clinical practice with a broader indication in the treatment of metastatic RCC.

Design, setting, and participants

Metastatic RCC patients treated with 25 mg of TEMSR weekly were submitted to a prospective systematic evaluation and follow-up in 87 German centres between January 2008 and October 2011 using standardised procedures.

Outcome measurements and statistical analysis

All data were centrally analysed by an independent clinical research organisation.

Results and limitations

This interim analysis of the STARTOR study included 386 patients. The observed toxicity was tolerable, the median dose intensity was 91% (interquartile range: 79–100%), and the median treatment duration was 20.1 wk (95% confidence interval [CI], 17.0–23.3 wk). Clinical benefit was seen in 157 patients (40.7%); the median progression-free and overall survival were 4.9 mo (95% CI, 4.2–5.6) and 11.6 mo (95% CI, 9.3–13.9), respectively. The effectiveness of TEMSR did not differ significantly in relation to the patient's age, histologic RCC subtype, or line of treatment. The major limitations were the noninterventional study design, limited information about Memorial Sloan-Kettering Cancer Center risk factors and detailed toxicity, and the lack of central radiologic review.

Conclusions

TEMSR is an effective and largely well-tolerated treatment alternative for metastatic RCC patients in daily clinical practice, irrespective of the patient's age, histologic RCC subtype, or line of treatment.