Evaluating the influence of prostate-specific antigen kinetics on metastasis in men with PSA recurrence after partial gland therapy

Purpose

Although current Delphi Consensus guidelines do not recommend a specific definition of biochemical recurrence after partial gland therapy, these guidelines acknowledge that serial prostate-specific antigen (PSA) tests remain the best marker for monitoring disease after treatment. The purpose of this study was to determine whether PSA velocity at failure per the Phoenix (nadir + 2 ng/mL) definition is associated with metastasis and prostate cancer-specific mortality (PCSM) in a cohort of patients who experienced PSA failure after partial gland therapy.

Impact of Consolidation Cycles Before Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission

Background

The optimal number of high-dose cytarabine (HDAC) consolidation cycles before allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia is not fully standardized.

Using additional pressure control lines when connecting a continuous renal replacement therapy device to an extracorporeal membrane oxygenation circuit

Background

The introduction of a continuous renal replacement therapy (CRRT) device into the extracorporeal membrane oxygenation (ECMO) circuit is widely used. However, excessive pressure transmitted to the CRRT device is a major disadvantage. We investigated the effects of using additional pressure control lines on the pressure and the lifespan of the CRRT circuit connected to the ECMO.

Methods

This is an observational study using prospectively collected data from consecutive patients receiving CRRT connected into the ECMO circuit at a university-affiliated, tertiary hospital from January 2013 to December 2016. The CRRT circuit was connected into the ECMO circuit through the Luer Lock connection without an additional pressure control line in 16 patients (9%, no line group), an additional pressure control line on the inlet line in 36 patients (23%, single line group), and additional pressure control lines on both the inlet and outlet lines in 118 patients (77%, double line group). The outcome measures of interest were compared among the three groups.

Results

The median access pressure was higher in the no line group compared to the groups. However, median filter pressure, effluent pressure, and return pressure were higher in the double line group compared to the other groups. There were no significant differences in platelets, lactate dehydrogenase, and plasma hemoglobin among the 3 groups over the time period studied. Median lifespan of the CRRT circuits in the double line group was 45.0 (29.0–63.7) hours, which was higher compared to 21.8 (11.6–31.8) hours in the no line group and 23.0 (15.0–34.6) hours in the single line group, respectively. In addition, in-hospital mortality was lower in the double line group (48.3%) compared to the no line group (68.8%) and the single line group (75.0%).

Conclusions

Additional tubing can be considered a simple and safe method for pressure control and lengthening circuit survival when connecting the CRRT device to the ECMO circuit.

     

Complete metabolic response (CMR) in positron emission tomography–computed tomography (PET‐CT) scans may have prognostic significance in patients with marginal zone lymphomas (MZL)

Although clinical use of positron emission tomography–computed tomography (PET‐CT) scans is well established in aggressive lymphomas, its prognostic value in marginal zone lymphoma (MZL) remains yet unclear. Hence, we investigated potential role of PET‐CT in predicting MZL patients' outcomes following systemic chemotherapy. A total of 32 patients with MZL who received first‐line chemotherapy were included in the analysis. They all underwent pretreatment, interim, and posttreatment PET‐CT scans. The primary objective was to evaluate the role of complete metabolic response (CMR) in posttreatment PET‐CT scans in predicting progression‐free survival (PFS). Compared with non‐CMR group, 5‐year PFS rate was significantly higher in patients who achieved CMR in posttreatment PET‐CT (54.2% vs 0.0%, P = .003) and also in patients gaining CMR in interim PET‐CT scans (62.5% vs 15.6%, P = .026). Interestingly, early CMR group, who achieved and maintained CMR in both interim and posttreatment PET‐CT scans, showed significantly higher 5‐year PFS than those with delayed or never CMR group (62.5% vs 37.5% vs 0%, P = .008). Therefore, interim and/or posttreatment CMR can be prognostic at least in these subsets of patients with MZL treated with chemotherapy.     

Intravascular papillary endothelial hyperplasia of the neck masquerading as malignancy on fine-needle aspiration cytology

Papillary endothelial hyperplasia (PEH) is an exuberant, usually intravascular endothelial proliferation that, in many respects, mimics angiosarcoma. A case of PEH originally suggestive of embryonal carcinoma by fine-needle aspiration is presented. A 12-year-old boy presented with a palpable mass on the right side of the neck. The mass was subsequently aspirated. Cytopathologic features showed cohesive sheets of polygonal pleomorphic cells with vesicular nuclei and prominent multiple nucleoli in a hemorrhagic background. Cytologic findings were strongly suggestive of metastatic embryonal carcinoma. There was no evidence of a primary lesion. After the mass was surgically excised, the pathologic findings showed PEH. A retrospective immunocytochemical stain for factor VIII-related antigen on a destained ethanol-fixed smear confirmed the endothelial nature of the polygonal cells. A vascular lesion should be considered, especially when atypical polygonal cells in a hemorrhagic background are present, as they were in this case.     

Gender-specific molecular heterosis of dopamine D2 receptor gene (DRD2) for smoking in schizophrenia

We examined the genetic effect of DRD2 A1 allele in 167 Korean schizophrenics in relation to their smoking habit. Although there was no apparent difference in the genotype distributions of DRD2 gene among the female schizophrenics (n = 66), the male counterpart (n = 101) showed significant differences in their genotype distributions. The comparison between male smoking and non-smoking patients showed the difference in genotype distribution (P = 0.010) with a higher prevalence of A1 allele (P = 0.020) and frequency of heterozygotes (P = 0.005), but not frequency of the A1 allele. The A1A2 heterozygotes male showed significantly higher smoking rate compared to the A1A1 or A2A2 homozygotes male, and non-smokers were deficient in heterozygotes. By contrast, among female schizophrenics, the heterozygotes showed a lower smoking rate than homozygotes and there were more heterozygotes in non-smokers. The deviation from Hardy-Weinberg expectations was observed in male and female non-smokers showing quite opposite profiles. Highly significant differences were seen between male and female non-smokers in A1 prevalence (P = 0.001), genotype distribution (P = 0.00011), and frequency of heterozygotes (P = 0.00003), but not in A1 frequency. The analyses from both male and female as one group showing no significant difference in the genotype distributions between smokers and non-smokers could be explained by the gender difference in the genetic effect of DRD2 A1 allele. Our findings present the gender-specific molecular heterosis of DRD2 gene in relation specifically to the smoking status of schizophrenic patients. They indicate the importance of heterosis and gender effects that should be taken into consideration for the association studies.     

Comparison of polymerase chain reaction with histopathologic features for diagnosis of tuberculosis in formalin-fixed,paraffin-embedded histologic specimens

Objective.-To investigate the relationship between various histopathologic features and the results of the tuberculosis (TB)-polymerase chain reaction (PCR) method in routinely submitted histologic specimens for the histopathologic diagnosis of TB. Design.-We used 95 formalin-fixed, paraffin-embedded tissue blocks from 81 patients who were clinically suspected of having TB. We assessed the presence of histopathologic features including well-formed granuloma, poorly formed granuloma, caseous necrosis, and Langhans-type giant cells. We performed nested PCR for IS6110 and Ziehl-Neelsen staining for acid-fast bacilli (AFB). Results.-Of the 81 patients studied, 53 patients had chronic granulomatous inflammation, whereas 28 patients had only chronic inflammation without definite granulomatous inflammation. Of the 53 cases with chronic granulomatous inflammation, 17 (32%) were AFB positive and 36 (68%) were TB-PCR positive. Among cases with chronic granulomatous inflammation, the percentage that were positive and negative by TB-PCR differed significantly with the presence of various histopathologic features. All of the 13 cases with well-formed granuloma, caseous necrosis, and Langhans-type giant cells were TB-PCR positive; however, 10 (36%) of the 28 cases with chronic inflammation without granulomatous lesions were also TB-PCR positive. Conclusions.-TB-PCR is a rapid, sensitive method for the diagnosis of TB in routinely processed formalin-fixed, paraffin-embedded histologic specimens and is readily available in histopathology laboratories. We recommend use of TB-PCR when TB is suspected clinically, especially in cases of chronic inflammation without definite evidence of granulomatous inflammation.     

Expression and localization of the transforming growth factor-beta type I receptor and Smads in preneoplastic lesions during chemical hepatocarcinogenesis in rats

Little is known about the involvement of Smad-related molecules in the regulation of the Transforming Growth Factor (TGF)-beta signaling pathway during hepatocarcinogenesis, particularly with respect to preneoplastic lesions of a rat liver. The aims of this study were to investigate the localizations and temporal expressions of TGF-beta Receptor Type 1 (TGR1) and Smads during the promotion stage of chemical hepatocarcinogenesis in rats. We investigated expressions and localizations of TGR1, Smad2, Smad4, and Smad7 by using semi-quantitative RT-PCR and immunohistochemistry in preneoplastic lesions during rat chemical hepatocarcinogenesis induced by Solt and Farber's method. The down-regulation of TGR1, Smad2, and Smad4 was evident during the later steps of the promotion stage of chemical hepatocarcinogenesis. In contrast with other Smads, increased Smad7 expression was evident during the later steps of the promotion stage. Also immunohistochemistry revealed that the main site of TGR1, Smad2, Smad4, and Smad7 expression was mainly in hepatocytes of the preneoplastic lesions of a rat liver. Dysregulation of the downstream effectors of TGF-beta such as TGR1, Smad2, Smad4 and, Smad7 might contribute to the progression of preneoplastic lesions during chemical hepatocarcinogenesis in a rat.     

Studies on the mechanisms of active ion fluxes across alveolar epithelial cell monolayers

Summary To investigate the cell physiologic and biological properties of the alveolar epithelium, we studied rat alveolar epithelial cell monolayers grown on permeable supports in primary culture. Type II alveolar epithelial cells were disaggregated using elastase, and partially purified on a discontinuous metrizamide gradient. These isolated cells were plated onto tissue culture-treated Nuclepore membrane filters at 1.5×10⁶ cells/cm² and maintained in a humidified incubator (5% CO₂ in air, 37° C). After 2 days in culture, the bathing media on both sides of the cell monolayers were changed to fresh culture medium, thus removing nonadherent cells (mostly leukocytes). These monolayers exhibit a high transmonolayer resistance (>2000 -cm²) and actively transport ions. Radionuclide flux studies indicate that Na⁺ is the predominant ionic species absorbed actively under baseline conditions, accounting for about 80% of the total active ion transport. Cl^– seems to be passively transported across the epithelium. However, when the epithelium is exposed to a beta-agonist (terbutaline), active absorption of Na⁺ is increased and active absorption of Cl^– occurs. Although it is clear that both active Na⁺ and Cl^– transport are dependent on Na⁺/K⁺-ATPase activity, and that Na⁺ enters cells predominantly through channels, the specific mechanisms by which Cl^– enters and exits the alveolar epithelial cells remain unclear. The stimulated reabsorption of Na⁺ and Cl^– may be important in helping to remove excess fluid from alveolar air spaces in the lung.