Chromogranin A staining as a prognostic variable in newly diagnosed Gleason score 7-10 prostate cancer treated with definitive radiotherapy.

PURPOSE: To demonstrate the association of neuroendocrine differentiation, as identified by chromogranin A (CgA) staining, with clinical outcomes in newly diagnosed prostatic adenocarcinoma treated with definitive radiotherapy (RT). MATERIALS/METHODS: Patients with Gleason score ≥7 adenocarcinoma were identified from our outcomes database. RT consisted of external beam, brachytherapy, or external beam with brachytherapy boost. Biopsy specimens were stained for neuroendocrine differentiation with CgA. Results were interpreted by a single pathologist. CgA staining was quantified as 0%, <1%, 1-10%, or >10% of tumor cells. Clinical outcomes were blinded at the time of pathologic evaluation. RESULTS: CgA staining was performed on 289 patients. 149 patients had Gleason score 7, and 140 were Gleason score 8-10. Median follow-up was 6.5 years. For patients with <1% versus >1% CgA staining, pretreatment characteristics were well-balanced. CgA staining was detected in 90 cases (31%). 58 patients had focal positive (<1%) CgA staining, and 32 cases had >1% of tumor cells CgA positive. Patients with >1% CgA staining had inferior biochemical control, clinical failure, distant metastases (DM), and cause-specific survival (CSS) rates. Ten-year rates of DM were 8% versus 48% for patients with <1% versus >1% CgA positive cells, respectively (P < 0.001). CSS at 10 years was 95% versus 76%, respectively (P < 0.001). Local control was equivalent in the two patient cohorts. Patients with <1% CgA staining had similar outcomes to those patients with 0% staining. CONCLUSIONS: Neuroendocrine differentiation involving >1% of tumor cells on prostate cancer biopsies is a predictor of DM and CSS in patients treated with primary RT.

Primary cilia metaplasia in renal transplant biopsies with acute tubular injury.

Primary cilia are hair-like organelles singly distributed along the apical surface of proximal and distal nephron tubules as mechanosensors. The goal of this study was to use electron microscopy to systemically evaluate cilia changes in acute tubular injury (ATI) from both transplant and native renal biopsies. Three groups of cases were included: control group 1-native biopsies without major changes in renal tubules; study group 2-native biopsies with prominent ATI; and study group 3-renal transplant biopsies with prominent ATI (delayed renal function group). Extensive search for ciliary structures along renal tubules was conducted in each case, focused on proximal tubular areas with injured (diminished) apical microvilli. Singly located cilia were found in 3/19 specimens in control group 1, 4/18 in group 2 (native ATI), and 6/24 in group 3 (transplant ATI). Importantly, there were clusters of cilia in proximal tubules with markedly diminished apical microvilli in 3/24 biopsies from 2 patients in group 3, but none from groups 1 and 2. The clusters of cilia ranged from 6 to 15 individual cilia along the apical surface with diminished apical microvilli. Under high magnifications, the cilia demonstrated 9 pairs of peripheral microtubules without a central pair of microtubules, consistent with primary cilia (9 + 0) rather than motile cilia (9 + 2). In summary, the authors found clusters of cilia in proximal tubules with remarkable apical microvillar injury in 3 renal transplant biopsies with ATI, implying a reactive, or repairing, process following tubular injury, thus they name this finding "cilia metaplasia".

Infectious organisms on Papanicolaou smears should not influence the diagnosis of atypical squamous cells of undetermined significance.

BACKGROUND: Atypical squamous cells of undetermined significance (ASCUS) remain the center of diagnostic controversy and patients' stress despite recent advances in cervical cancer screening and the introduction of human papilloma virus (HPV) testing. The role of infectious agents in the induction of such changes is not well understood. AIM: We aim at reviewing the effect of the different infectious organisms in Papanicolaou (PAP) smears on the ASCUS diagnosis. MATERIAL: 133 ASCUS cases associated with variable infectious organisms (ASCUS-infection group) with secondary HPV testing and appropriate follow-up studies were reviewed. A control group of 310 ASCUS cases without any organisms (ASCUS-only group) was selected for comparison. RESULTS: The ASCUS-infection group had a significantly higher proportion of HPV-positive tests than the ASCUS-only group (p = 0.0027). There was no significant difference on follow-up PAPs and biopsies between the two groups (p = 0.4272). They showed an overall mean of 75% negative, 20% low-grade lesions, and 5% high-grade lesions/carcinoma in situ on follow-up. CONCLUSION: Our study demonstrates no significant effect of infections on the cytological changes diagnostic of ASCUS. The cytologist should make this diagnosis neglecting any background infections even when predominant.

Tele-infrasonic studies of hard-rock mining explosions.

The Lac-du-Bonnet infrasound station, IS-10, and the Minnesota iron mines 390 km to the southeast are ideally located to assess the accuracy of atmospheric profiles needed for infrasound modeling. Infrasonic data from 2003 associated with explosions at the iron mine were analyzed for effects of explosion size and atmospheric conditions on observations with well-constrained ground truth. Noise was the determining factor for observation; high noise conditions sometimes prevented unequivocal identification of infrasound arrivals. Observed arrivals had frequencies of 0.5 to 5 Hz, with a dominant frequency of 2 Hz, and generally had durations on the order of 10 s or less. There was no correlation between explosive amount and observability. Tele-infrasonic propagation distances (greater than 250 km) produce thermospheric ray paths. Modeling is based upon MSIS/HWM (Mass Spectrometer Incoherent Scatter/Horizontal Wind Model) and NRL-G2S (Naval Research Laboratory Ground to Space) datasets. The NRL-G2S dataset provided more accurate travel time predictions that the MSIS/HWM dataset. PE modeling for the NRL-G2S dataset indicates energy loss at higher frequencies (around 4 Hz). Additionally, applying the Sutherland/Bass model through the NRL-G2S realization of the atmosphere in InfraMAP results in predicted amplitudes too small to be observed.

Prognostic significance of neuroendocrine differentiation in patients with Gleason score 8-10 prostate cancer treated with primary radiotherapy.

PURPOSE: To determine the prognostic significance of neuroendocrine differentiation (NED) in Gleason score 8-10 prostate cancer treated with primary radiotherapy (RT). METHODS AND MATERIALS: Chromogranin A (CgA) staining was performed and overseen by a single pathologist on core biopsies from 176 patients from the William Beaumont prostate cancer database. A total of 143 had evaluable biopsy material. Staining was quantified as 0%, <1%, 1-10%, or >10% of tumor cells. Patients received external beam RT alone or together with high-dose-rate brachytherapy. Cox regression and Kaplan-Meier estimates determined if the presence/frequency of neuroendocrine cells correlated with clinical endpoints. RESULTS: Median follow-up was 5.5 years. Forty patients (28%) had at least focal positive CgA staining (<1% n = 21, 1-10% n = 11, >10% n = 8). No significant differences existed between patients with or without staining in terms of age, pretreatment prostate-specific antigen, tumor stage, hormone therapy administration, % biopsy core involvement, mean Gleason score, or RT dose/modality. CgA staining concentration independently predicted for biochemical and clinical failure, distant metastases (DM), and cause-specific survival (CSS). For patients with <1% vs. >1% staining, 10-year DM rates were 13.4% vs. 55.3%, respectively (p = 0.001), and CSS was 91.7% vs. 58.9% (p < 0.001). As a continuous variable, increasing CgA staining concentration predicted for inferior rates of DM, CSS, biochemical control, and any clinical failure. No differences in outcomes were appreciated for patients with 0% vs. <1% NED. CONCLUSIONS: For Gleason score 8-10 prostate cancer, >1% NED is associated with inferior clinical outcomes for patients treated with radiotherapy. This relates most directly to an increase in distant disease failure.