Infiltrative lamina propria invasion pattern as an independent predictor for cancer‐specific and overall survival of instillation treatment‐naïve stage T1 high‐grade urothelial bladder cancer

Objectives

To investigate established prognostic factors and relatively new histopathological tumor characteristics including metric substage and lamina propria invasion patterns in a large series of T1 high‐grade non‐muscle‐invasive bladder cancer.

Methods

Between 1989 and 2012, 322 patients with initial stage T1 high‐grade bladder cancer underwent transurethral resection, followed by re‐transurethral resection and a conservative approach with follow‐up regime alone or instillation treatment. Transurethral resection specimens were reassessed by two experienced urological pathologists for tumor grade according to the World Health Organization 1973 classification, metric T1 substage, lamina propria invasion pattern and associated carcinoma in situ. The median follow‐up period was 42 months (interquartile range 25–72 months). In addition to Kaplan–Meier analyses, uni‐ and multivariable Cox regression analyses were used to compare progression‐free survival, cancer‐specific survival and overall survival for the studied parameters comparing two subcohorts.

Results

While in patients after instillation treatment no examined feature was shown as an independent predictor for prognosis, there were predictive histopathological features in multivariable Cox regression analyses in instillation treatment‐naïve patients: associated carcinoma in situ (hazard ratio 2.278, 95% confidence interval 1.119–4.634, P = 0.023) and World Health Organization 1973 grade 3 (hazard ratio 2.950, 95% confidence interval 1.021–8.536, P = 0.046) for worse progression‐free survival, infiltrative lamina propria tumor pattern for worse cancer‐specific survival (hazard ratio 2.369, 95% confidence interval 1.034–5.429, P = 0.042) and overall survival (hazard ratio 1.049, 95% confidence interval 1.024–1.075, P = 0.001).

Conclusions

The results of the present T1 high‐grade bladder cancer series suggest that lamina propria invasion pattern is a promising parameter to predict the prognosis of T1 high‐grade bladder cancer in an instillation treatment‐naïve subcohort. Prospective multicenter evaluations are warranted. The need for instillation treatment in T1 high‐grade bladder cancer is clearly demanded.     

Induction of proliferation of B prolymphocytic leukemia cells by phorbol ester and native or recombinant interferon-gamma

Phorbol ester phorbol myristate acetate (PMA) induces proliferation in nonmalignant human B cells and B cells from a patient with B prolymphocytic leukemia (B-PLL). Mitogen-free T cell-derived conditioned medium acts synergistically with PMA in inducing proliferation of B-PLL cells but does not enhance the PMA-stimulated outgrowth of nonmalignant B cells. Interleukin 2 (IL-2) has no effect on the outgrowth of B-PLL cells, and monoclonal antibodies against the IL-2 receptor do not influence the response to PMA and conditioned medium. Recombinant interferon-gamma (IFN-gamma), in contrast, is a potent enhancer of PMA-induced proliferation of B-PLL cells. With gel filtration techniques and with the use of anti-IFN-gamma antibodies, it is shown that IFN-gamma in the conditioned medium is responsible for the observed increase in B-PLL cell proliferation. Preincubation of B- PLL cells with IFN-gamma induces responsiveness to PMA, whereas IFN- gamma alone had no effect on these cells when pretreated with PMA. The combined data show that, in the presence of PMA, native and recombinant IFN-gamma are growth factors for B cells from a B-PLL patient and that IL-2 is not involved in this process.     

A web-based simulation of a longitudinal clinic used in a 4-week ambulatory rotation: a cohort study

Background  

Residency training takes place primarily on inpatient wards. In the absence of a resident continuity clinic, internal medicine residents rely on block rotations to learn about continuity of care. Alternate methods to introduce continuity of care are needed.     

An assessment of polymorphonuclear leukocyte rigidity in HIV-infected individuals after immune recovery

PURPOSE: To determine whether polymorphonuclear leukocytes (PMNs) remain rigid after immune reconstitution in human immunodeficiency virus (HIV)-infected individuals with a history of severe immunosuppression. METHODS: PMN rigidity was measured in vitro in three groups: (1) HIV-infected individuals with a history of CD4+ T-lymphocyte counts of less than 50/microL, but with current counts of more than 200/microL attributable to potent antiretroviral therapy (group 1); (2) HIV-infected individuals whose CD4+ T-lymphocyte counts had always been more than 200/microL (group 2); and (3) HIV-negative control subjects. Rigidity was determined with a cell transit analyzer (containing a micropore filter with 30 identical, 8-microm diameter pores), representing a simple in vitro model of a capillary bed. A longer PMN pore transit time reflects increased PMN rigidity. RESULTS: PMN transit time (median) in group 1 (n = 11) was 3.34 ms, in group 2 (n = 9) was 3.19 ms, and in control subjects (n = 15) was 2.66 ms. PMN rigidity was significantly greater in groups 1 (P = 0.014) and 2 (P = 0.046) than in control subjects (Wilcoxon rank-sum test). A significant difference was not identified between groups 1 and 2 (P = 0.518). CONCLUSIONS: The increased PMN rigidity known to occur in severely immunosuppressed HIV-infected individuals persists after immune reconstitution. Furthermore, PMN rigidity is increased in those HIV-infected individuals who do not have a history of severe immunosuppression. Because PMN rigidity can alter microvascular blood flow, HIV-infected individuals may remain at risk for retinal vascular damage in the era of potent antiretroviral therapy.     

Optimum viscosity of barium suspension for use in the double contrast barium meal

The effect of viscosity of barium sulphate suspensions on coating was assessed by glass slides as in vitro, and the rat as in vivo models. It was found that below a certain viscosity (as measured by a cup viscometer) coating was impaired. As increasing viscosity is associated with increasing bubble retention and, eventually, when very high viscosities are reached, poor surface flow of suspension, it is recommended that the viscosity of the medium employed should be kept within a narrow range, approximately equal to 70% w/v Baritop, 80% Micropaque, 115% E--Z-paque, 150% Barosperse, or 200% HD 200.     

The infectious intestinal disease study of England: a prospective evaluation of symptoms and health care use after an acute episode

The sequelae of Infectious Intestinal Disease (IID) in a population-based sample of cases and matched controls were investigated for a period of 3 months following the initial infection. Incident cases of IID presenting to GPs or occurring in the community and controls were studied at 3 weeks and over a 3-month follow-up period. Cases were six times more likely than controls to have gastrointestinal symptoms, particularly diarrhoea, at 3 weeks. Ten per cent of cases consulted their GP in the 3 months after episode and 2.3% were referred to hospital. GP presentation rates were twice as high in cases. Gastrointestinal symptoms persist after IID, leading to an increased likelihood of GP consultation and hospital referral. Diagnosis of irritable bowel syndrome may be more likely following IID. The burden of IID is likely to be considerable given its high incidence and the frequency of such sequelae.     

Decreased macular leukocyte velocity in human immunodeficiency virus-infected individuals

PURPOSE: To determine whether human immunodeficiency virus (HIV)-infected individuals have decreased macular capillary blood flow in vivo. DESIGN: Case control study. METHODS: Macular leukocyte velocity and perceived leukocyte density were determined in 41 HIV-infected individuals without cytomegalovirus retinitis and 31 HIV-negative control subjects using the blue field simulation technique (BFS-2000, Oculix, Inc., Jenkintown, PA). Velocity and density measurements for HIV-infected individuals were compared to current and lowest previous CD4+ T-lymphocyte counts, HIV RNA blood levels, and blood leukocyte counts. RESULTS: Mean macular leukocyte velocity was lower in HIV-infected individuals than in controls (P = 0.0006). No correlations were identified between velocity measurements and the following factors in HIV-infected individuals: current or lowest previous CD4+ T-lymphocyte count; or HIV RNA blood level. Mean perceived leukocyte density in HIV-infected individuals was lower than in controls (P = 0.003), but was not correlated with blood leukocyte count in HIV-infected individuals. No relationships were identified between macular leukocyte velocity and duration of medication use or duration of elevated CD4+ T-lymphocyte count in patients receiving potent antiretroviral therapy. CONCLUSIONS: Reduced macular leukocyte velocity may have important implications for understanding the retinal microvasculopathy of HIV disease, the pathogenesis of opportunistic retinal infections, and visual dysfunction in HIV-infected individuals who do not have opportunistic retinal infections. We found no evidence that macular leukocyte velocity increased with immune reconstitution.     

Assessment of the efficacy of an IgM-elisa and microscopic agglutination test (MAT) in the diagnosis of acute leptospirosis

In a prospective study in Barbados between 1979 and 1989, 321 cases were diagnosed in 638 patients presenting at a hospital with symptoms of leptospirosis. Initial diagnosis was based on patient history and characteristic signs and symptoms. In 92 cases (29%), diagnosis was confirmed by isolation of organisms from the blood, urine, or dialysate fluid; in the remaining 229 cases (71%) diagnosis was confirmed by serology alone. Results of an IgM-ELISA and microscopic agglutination test (MAT) in cases with isolates and in non-leptospirosis cases were used to assess the sensitivity and specificity of the tests. The sensitivity of IgM detection by ELISA was 52% in the first acute-phase specimen, increasing to 89% and 93% in the second acute-phase and convalescent specimens, respectively. The specificity of the IgM-ELISA was high (> or = 94%) in all specimens. The sensitivity of the MAT was low (30%) in the first acute-phase specimen, increasing to 63% in the second acute-phase specimen and 76% in the convalescent specimen. The specificity of the MAT was > or = 97% in all specimens.