Franz Quehenberger

The association between the diameter of a patent foramen ovale and the risk of embolic cerebrovascular events

PURPOSE We sought to determine whether the size of a patent foramen ovale affected the risk of embolic cerebrovascular events of unknown origin. PATIENTS AND METHODS We ascertained the presence and measured the size of patent foramen ovale using multiplane transesophageal echocardiography in 121 consecutive patients younger than 60 years who had transient ischemic attacks or ischemic strokes and in 123 control subjects. None of the patients had left heart, aortic, or carotid sources of embolism, or echocardiographic signs of elevated left or right atrial pressure. We used multivariate logistic regression to determine whether the size of the patent foramen ovale was an independent risk factor for cerebrovascular events. RESULTS The mean (+/- SD) diameter of a patent foramen ovale was significantly larger in patients (4 +/- 2 mm) than in control subjects (2 +/- 1 mm, P <0.0001). A patent foramen ovale greater than 4 mm was associated with an increased risk of transient ischemic attacks [odds ratio (OR) = 3.4; 95% confidence interval (CI), 1.0 to 11, P = 0.04], ischemic strokes (OR = 12; 95% CI, 3.3 to 44, P = 0.0001), and, especially, having evidence of two or more strokes (OR = 27; 95% CI, 4.7 to 160, P = 0.0002). CONCLUSION The diameter of a patent foramen ovale is an independent risk factor for ischemic events, especially recurrent strokes.

Treatment of Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue Type With Cladribine: A Phase II Study

PURPOSE As chemotherapy has not been extensively studied in patients with lymphoma of the mucosa-associated lymphoid tissue (MALT), we initiated a prospective study to evaluate the activity of the nucleoside analog cladribine (2-chlorodeoxyadenosine [2-CdA]) in this disease. PATIENTS AND METHODS Patients with histologically verified MALT-type lymphoma were enrolled. 2-CdA was administered at a dose of 0.12 mg/kg body weight on 5 consecutive days, as a 2-hour infusion. Cycles were repeated every 4 weeks for a maximum of six cycles. RESULTS Nineteen patients with gastric and seven patients with extragastric MALT lymphoma were enrolled. All patients were chemotherapy-naive, and two had been locally irradiated before systemic relapse of the lymphoma. A total of 102 cycles was administered to our patients (median number of cycles per patient, four). All 25 assessable patients responded to treatment: 21 patients (84%) achieved complete remission (CR) and four patients achieved partial remission. All patients (100%) with gastric presentation, but only three patients (43%) with extragastric presentation, achieved CR. Toxicities were moderate and mainly hematologic and required dose reduction and/or premature discontinuation of therapy in only three cases. Two patients died from vascular events, one shortly after the first cycle because of myocardial infarction and the other from stroke 3 months after the second course. Three patients relapsed after 13, 18, and 22 months and one patient showed progressive disease after 15 months. At present, 24 patients are alive at a median follow-up time of 32 months. CONCLUSION Our data demonstrate that 2-CdA is highly effective in inducing CR in 84% of patients with MALT-type lymphoma.

Multiphasic multidetector-row CT (MDCT) in detection and staging of transitional cell carcinomas of the upper urinary tract

The aim of this study was to evaluate the potential of multiphasic multidetector-row CT (MDCT) in the detection and staging of transitional cell carcinomas (TCC) of the upper urinary tract. We performed a retrospective chart review of 39 consecutive patients with 41 histologically verified TCC of the renal pelvis and/or the ureter. The urinary tract was examined using MDCT performing unenhanced and contrast-enhanced scans during the corticomedullary (CMP), nephrographic (NP) and pyelographic phase (PP). Tumors were staged according to the TNM classification. MDCT and histopathological findings were correlated. The attenuation of the lesions was documented in Hounsfield units (HU). In MDCT, all 41 TCC—including two multicentric TCC—were detected. TCC confined to the organ (stage 0a-II) was correctly staged in 28/29 tumors (96.6%). Stage III-IV tumors were correctly staged in 8/12 patients (66.6%). Overall, MDCT was accurate in predicting pathologic TNM stage in 36/41 upper urinary tract TCC (87.8%). There was no significant difference of mean attenuation of TCC between CMP, NP and PP (P>0.05). MDCT with its high spatial and temporal resolution is an accurate tool for detection TCC of the upper urinary tract, with 87.8% accuracy in predicting its stage.

Hyperbaric oxygen – an effective tool to treat radiation morbidity in prostate cancer

PURPOSE We report the results of hyperbaric oxygen therapy (HBO) used in the treatment of radiation cystitis and proctitis following irradiation of prostate cancer. MATERIALS AND METHODS Between June 1995 and March 2000, 18 men (median age 71 years) with radiation proctitis (n=7), cystitis (n=8), and combined proctitis/cystitis (n=3) underwent HBO therapy in a multiplace chamber for a median of 26 sessions (range 2-60). The treatment schedule (2.2-2.4 atmospheres absolute, 60 min bottom time, once-a-day, 7 days a week) was set at a lower limit of 20 sessions; the upper limit was left open to symptom-related adjustment. Prior to HBO treatment, RTOG/EORTC late genitourinal (GU) morbidity was Grade 2 (n=3), Grade 3 (n=6) or Grade 4 (n=2); modified RTOG/EORTC late gastrointestinal (GI) morbidity was either Grade 2 (n=4) or Grade 3 (n=6). RESULTS Sixteen patients underwent an adequate number of sessions. RTOG/EORTC late GU as well as modified GI morbidity scores showed a significant improvement after HBO (GI, P=0.004; GU, P=0.004; exact Wilcoxon signed rank test); bleeding ceased in five out of five patients with proctitis and in six out of eight patients with cystitis; one of those two patients, in whom an ineffective treatment outcome was obtained, went on to have a cystectomy. CONCLUSIONS HBO treatment seems to be an effective tool to treat those patients with late GI and GU morbidity when conventional treatment has led to unsatisfactory results. Particularly in patients with radiation cystitis, HBO should not be delayed too long, as in the case of extensive bladder shrinkage improvement is hard to achieve.

Quality assurance for detection of estrogen and progesterone receptors by immunohistochemistry in Austrian pathology laboratories.

Abstract.Steroid hormone receptors are important prognostic and predictive factors in breast carcinomas. Thus their determination is of essential importance. The aims of this study were to assess the quality of the immunohistochemical assays, and to assess the interlaboratory and interobserver variability performed by different laboratories in Austria. Ten unstained slides for interlaboratory variability evaluation and ten immunohistochemically prestained slides for interobserver variability evaluation from breast carcinomas known to show different degrees of steroid hormone receptor expressions were sent to 32 surgical pathology laboratories in Austria (participation rate 97%). The participants were requested to perform their in-house immunohistochemistry (IHC) technique for estrogen receptors (ERs) and progesterone receptors (PRs) on the unstained slides. All slides were evaluated by estimating percentage and intensity of stained nuclei semiquantitatively. From these data the Reiner, Remmele and the Allred scores were calculated. A less than 10% cut-off level was chosen as threshold for positive cases. Regarding the series of prestained slides, both sensitivity and specificity were very high (>96.88%); false-positive and -negative rates were low (<3.31%). Interobserver variability showed moderate multirater kappa values concerning the ER (Reiner score: kappa=0.57) and PR scores (Reiner score: kappa=0.53). The agreement among observers was better for negative cases than positive cases. In-house slides representing interlaboratory variability showed fair to moderate kappa values concerning the ER and PR scores (kappa for ER Reiner score=0.41; PR=0.32). In this slide series, sensitivity and specificity were high (>82.2%) and false-positive or -negative rates were low in ER cases (<3.03) and moderately low in PR cases (17.46%). These results demonstrate that variability is higher when participants use their own staining method. In more detailed analysis, the automated IHC techniques showed an advantage over manual techniques concerning interlaboratory variability. There exists no difference in reproducibility with respect to scoring systems for steroid hormone receptor estimation.

Efficacy of psoralen plus ultraviolet A therapy vs. biologics in moderate to severe chronic plaque psoriasis: retrospective data analysis of a patient registry.

Background  Few studies have directly compared the clinical efficacy of psoralen plus ultraviolet A (PUVA) vs. biologics in the treatment of psoriasis.

Frequency, onset and clinical impact of somatic DNMT3A mutations in therapy-related and secondary acute myeloid leukemia

The recent identification of DNMT3A mutations in de novo acute myeloid leukemia prompted us to determine their frequency, patterns and clinical impact in a cohort of 98 patients with either therapy-related or secondary acute myeloid leukemia developing from an antecedent hematologic disorder. We identified 24 somatic mutations in 23 patients with a significantly higher frequency in secondary acute myeloid leukemia (35.1%) as compared to therapy-related acute myeloid leukemia (16.4%, P=0.0486). DNMT3A mutations were associated with a normal karyotype and IDH1/2 mutations, but did not affect survival. In contrast to de novo acute myeloid leukemia, most mutations did not affect arginine on position 882, but were predominantly found in the methyltransferase domain. All DNMT3A mutations identified in secondary acute myeloid leukemia were already present in the antecedent disorders indicating an early event. Reduction to homozygosity by uniparental disomy was observed in 2 patients with secondary acute myeloid leukemia during disease progression.

Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review.

PurposeThis study reports clinicopathological features and outcome of thymic tumors. Twenty-seven patients with invasive thymoma and 6 patients with thymic carcinoma who had received radiotherapy either primary or postoperatively were analyzed retrospectively.Patients and MethodsAll 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) or biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients.ResultsIn patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77.4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p = 0.04). Considering local control, radiation dose was a significant prognostic factor (p = 0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5-year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p = 0.007) and DFS (p = 0.0007).ConclusionPostoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival.ZusammenfassungZielBericht über 27 Patienten mit invasivem Thymom und sechs Patienten mit Thymuskarzinom nach primärer oder postoperativer Strahlentherapie unter besonderer Berücksichtigung der pathohistologischen Befunde und klinischen Ergebnisse.Patienten und MethodenAlle 33 Patienten wurden nach kompletter Resektion (n = 16), Teilresektion (n = 9) oder Biopsie (n = 8) mit einer mittleren Dosis von 50 Gy (30 bis 60 Gy) bestrahlt. Die Stadieneinteilung nach Masaoka (Tabelle 1) ergab jeweils zwolf Patienten in Stadium II und III sowie neun Patienten im Stadium IV (Tabelle 2).ErgebnissePatienten mit einem invasivem Thymom Masaoka-Stadium II bis IV (mediane Nachsorgezeit 54,4 Monate) hatten ein Fünf-Jahres-Gesamüberleben, krankheitsspezifisches und krankheitsfreies Überleben von 63,7% (95%Konfidenzintervall [KI] 42 bis 84%), 88,3% (KI 75 bis 100%) sowie 77,4% (KI 58 bis 95%). Bei den untersuchten prognostischen Faktoren, wie Alter, Myasthenia gravis, chirurgische Radikalität, histologische Subgruppe, Bestrahlungsdosis und Masaoka-Stadium, hatte nur letzteres einen stätistisch signifikanten Einfluß auf das Überleben (p = 0.04). (Tabelle 8). Bei alleiniger Berücksichtigung der lokalen Kontrolle war die Bestrahlungsdosis ein stätistisch signifikanter prognostischer Parameter (p = 0,0006) (Tabelle 7). Patienten mit Thymuskarzinom (mediane Nachsorgezeit 43,3 Monate) hatten ein krankheitsspezifisches und krankheitsfreies Fünf-Jahres-Überleben von 22,2% (KI 0 bis 60%) sowie 16,7% (KI 0 bis 46%). Patienten mit Thymomen hatten im Vergleich zu Patienten mit Thymuskarzinomen sowohl ein statistisch signifikant besseres krankheitsspezifisches (p = 0,007) als auch krankheitsfreies Überleben (p = 0,0007) (Abbildung 1).SchlußfolgerungPostoperative Strahlentherapie mit adäquater Dosis spielt eine wichtige Rolle als adjuvante Therapie bei inkomplett und komplett resezierten invasiven Thymomen Stadium II bis III. Bei primär inoperablen Thymomen und bei Thymuskarzinom sollte ein multimodales Vorgehen in Erwägung gezogen werden, urn die Überlebensraten zu verbessern.

Hyperhomocyst(e)inemia, but not methylenetetrahydrofolate reductase C677T mutation, as a risk factor in branch retinal vein occlusion

OBJECTIVE To determine whether hyperhomocyst(e)inemia and methylenetetrahydrofolate reductase (MTHFR) C677T mutation are associated with branch retinal vein occlusion (BRVO). DESIGN Retrospective, case-control study. PARTICIPANTS The study cohort consisted of 84 consecutive patients with branch retinal vein occlusion and 84 controls, matched for age and gender. MAIN OUTCOME MEASURES Fasting plasma homocyst(e)ine, folate, and vitamin B(12) levels, MTHFR C677T genotypes. RESULTS Mean plasma homocyst(e)ine levels were significantly higher in patients than in controls (11.4 +/- 4.3 micromol/l vs. 9.9 +/- 2.8 micromol/l; P = 0.002). An increase of plasma homocyst(e)ine level by 1 micromol/l was associated with an odds ratio of 1.19 (95% confidence interval 1.06-1.34; P = 0.004). Mean plasma folate levels were significantly lower in patients than in the control group (4.5 +/- 2.1 ng/ml vs. 5.6 +/- 2.1 ng/ml; P = 0.007). The prevalence of the homozygous genotype of the MTHFR C677T mutation did not differ significantly between patients and controls. CONCLUSIONS Our results suggest that hyperhomocyst(e)inemia, but not homozygosity for the MTHFR C677T mutation, is associated with BRVO. Increased plasma homocyst(e)ine levels in our study are not the result of an increased prevalence of the homozygous genotype of MTHFR C677T mutation.

Randomized double-blinded placebo-controlled intra-individual trial on topical treatment with a 1,25-dihydroxyvitamin D3 analogue in polymorphic light eruption

Background  Polymorphic light eruption (PLE) is a very frequent photodermatosis whose pathogenesis may involve resistance to ultraviolet (UV)‐induced immune suppression. Similar to UV radiation, calcitriol (1,25‐dihydroxyvitamin D3) and its analogues such as calcipotriol have been shown to exhibit immunosuppressive properties.