Overlap of coronary disease and pulmonary arterial hypertension in systemic sclerosis.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a common complication of systemic sclerosis (SSc). Symptoms of coronary artery disease (CAD) and PAH are closely related and cardiac catheterisation is needed to confirm their diagnosis. The aim of the present work was to investigate of the extent of overlap between CAD and PAH in patients with SSc. METHODS: Based on non-invasive investigations, 20 patients out of 120 were suspected to have PAH ("suspected PAH" group). Another 10 patients showed signs of coronary disease ("suspected CAD" Group). In these 30 patients, right heart catheterisation and coronary angiography were performed, and the coronary flow reserve (CFR) was assessed by thermodilution technique. RESULTS: In the "suspected PAH" and the "suspected CAD" groups, PAH was found in 12/20 and 2/10 cases, and coronary artery stenosis in 9/20 and 6/10 cases, respectively. Severely reduced CFR was revealed in 7/20 and 3/10 cases, respectively. CONCLUSIONS: PAH, CAD and reduced CFR all show a considerable overlap in symptomatic patients with SSc. The current non-invasive investigations are neither sensitive nor specific enough to make an appropriate distinction between these different disease manifestations. A more invasive approach, such as coronary angiography at the initial catheterisation, is required to properly characterise and treat the different forms of cardiac involvement in SSc.

Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases.

Efaproxiral (Efaproxyn, RSR13), a synthetic allosteric modifier of haemoglobin (Hb), decreases Hb-oxygen (O(2)) binding affinity and enhances oxygenation of hypoxic tumours during radiation therapy. This analysis evaluated the Phase 3, Radiation Enhancing Allosteric Compound for Hypoxic Brain Metastases; RT-009 (REACH) study efficacy results in relation to efaproxiral exposure (efaproxiral red blood cell concentration (E-RBC) and number of doses). Recursive partitioning analysis Class I or II patients with brain metastases from solid tumours received standard whole-brain radiation therapy (3 Gy/fraction x 10 days), plus supplemental O(2) (4 l/min), either with efaproxiral (75 or 100 mg/kg daily) or without (control). Efaproxiral red blood cell concentrations were linearly extrapolated to all efaproxiral doses received. Three patient populations were analysed: (1) all eligible, (2) non-small-cell lung cancer (NSCLC) as primary cancer, and (3) breast cancer primary. Efficacy endpoints were survival and response rate. Brain metastases patients achieving sufficient E-RBC (> or =483 microg/ml) and receiving at least seven of 10 efaproxiral doses were most likely to experience survival and response benefits. Patients with breast cancer primary tumours generally achieved the target efaproxiral exposure and therefore gained greater benefit from efaproxiral treatment than NSCLC patients. This analysis defined the efaproxiral concentration-dependence in survival and response rate improvement, and provided a clearer understanding of efaproxiral dosing requirements.

Effects of tamoxifen and octreotide LAR on the IGF-system compared with tamoxifen monotherapy.

The insulin-like growth factor (IGF)-system was evaluated in 150 breast cancer patients participating in a randomised phase III trial comparing octreotide pamoate and tamoxifen with tamoxifen+placebo. Alterations in the IGF-system in the two treatment arms and individual changes with respect to outcome were compared. Serum IGF-I and -II, free IGF-I, and insulin-like growth factor binding protein 1-3 (IGFBP1-3) were measured by radioimmmunoassay (RIA)/immunoradiometric assay (IRMA) and IGFBPs by Western ligand blots (WLB) before and during treatment. Combined treatment caused a higher increase in IGFBP-1 and larger suppression of total and free IGF-I, IGF-II, and IGFBP-3 (P<0.01 for all), but less suppression of IGFBP-2 (P<0.05) compared with tamoxifen monotherapy. An increase in IGFBP-2 25% was associated with decreased progression-free survival (PFS) in the total patient population and combined treatment group. Similar response rates and time to progression in the treatment arms suggests moderate suppression of circulating IGF-I has no influence on clinical outcome.

HER-2/neu as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel.

PURPOSE: To evaluate the predictive value of HER-2 in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin (A) or with single-agent docetaxel (T). EXPERIMENTAL DESIGN: Patients from this study participated in a phase III clinical trial in which doxorubicin or docetaxel was administered for advanced disease. HER-2 was evaluated by IHC. In all positive cases, FISH was used to confirm the HER-2 positive status. The different cohorts of patients identified by HER-2 were examined to assess a possible relationship between HER-2 status and treatment effect. RESULTS: Tumor samples were available for 176 of the 326 patients entered in the clinical trial (54%). HER-2 positivity was observed in 20% of the study population. A statistically significant interaction was found between response rates to the study drugs and HER-2 status, with HER-2 positive patients deriving the highest benefit from the use of T (odds ratio for HER-2 positive patients treated with T = 3.12 (95% CI 1.11-8.80), p = 0.03). The interaction between HER-2 and response rates to A and T was also confirmed by a multivariate analysis. No statistically significant interaction was found between HER-2 and drugs efficacy evaluated in terms of time to progression and overall survival, although in the HER-2 negative cohort A was at least as effective as T in term of overall survival. CONCLUSIONS: These results suggest that in HER-2 positive breast cancer patients docetaxel might be more active than doxorubicin, while in HER-2 negative patients doxorubicin might be at least as effective as docetaxel. Although the present results cannot have an impact on current practice, they allow us to formulate the hypothesis that HER-2 positive breast cancer is a heterogeneous disease with regard to sensitivity to anthracyclines and taxanes, and that this might be dependent upon other molecular markers including the p-53 and topoisomerase II alpha genes. This hypothesis is currently being tested prospectively in two different 'bench to bed-side' clinical trials.

[Effectiveness of doxorubicin-docetaxel or doxorubicin-cyclophosphamide combination in advanced breast cancer with distant metastasis]. / Doxorubicin + docetaxel-, illetóleg doxorubicin + cyclophosphamid-kezeléssel elérhetó eredmények távoli áttétet adó emlórákban.

Between June 1996 and March 1998 a multinational multicentric phase III randomised comparative study was made for comparing 1. the effectiveness, 2. the adverse events and 3. the quality of life of two combinations i.e. DD versus DC. 18 patients were treated with DD and 15 patients with DC. Age, tumour stage, visceral involvement, receptor status were well matched in the two groups. Good partial remission was obtained in 10 patients treated with DD whereas only seven remissions were seen in the DC arm. Response duration was similar in the 2 arms. No difference in adverse events was observed.

[Irinotecan--experience with second-line treatment in advanced colorectal cancer] . / Irinotecan--második vonalbeli kezeléssel szerzett tapasztalatok elórehaladott colorectalis daganatokban.

The prognosis for patients with advanced colorectal cancer who fail to respond to a 5-FU based therapy is poor. About 7% response rate can be achieved with second line therapeutic regiments, the overall survival is about 6-7 months. The aim of authors was to assess the efficacy and toxicity profile of irinotecan (CAMPTO) in patients with advanced colorectal cancer, resistant to 5-FU based chemotherapy. From October 1996 to November 1998 19 previously treated metastatic colorectal cancer patients with documented progression were recruited. Irinotecan was given at a dose of 350 mg/m2 i.v. over 90 min. every 3 week. Tumor response and toxicity were assessed using WHO criteria. Median age: 59.7 years (42-72). Tumor sites: 12/19 colon, 7/19 rectum. 11/19 patients had 1 metastatic site, 8/19 had 2 or more metastatic sites. CR: 0/19, PR: 3/19, MR: 2/19, SD: 10/19, PD: 4/19. Median time to progression was 9.1 months (range 1.5-22). The overall median survival was 15.5 months (range 2.5-37). Grade 3-4 delayed diarrhoea occurred in 26.3% of patients. Grade 3 neutropenia occurred in 15.7% of patients. Preliminary results confirm the clinical value of irinotecan in 5-FU resistant metastatic colorectal cancer with tolerable toxicity profile. Irinotecan should be considered as the basic chemotherapeutic agent for second line treatment of metastatic colorectal cancer.

[Malignant eccrine poroma presenting as a breast tumor]. / Emlótumor képében megjelenó malignus eccrin poroma.

Malignant eccrine poroma is a rare malignoma of the skin. Number of the publicated cases less than a hundred. Authors detected a case of rapid progression malignant eccrine poroma on a young female following a short onset of symptoms. According to the case survey of literature is reported.

Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer.

PURPOSE: This phase III study compared docetaxel and doxorubicin in patients with metastatic breast cancer who had received previous alkylating agent-containing chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive an intravenous infusion of docetaxel 100 mg/m(2) or doxorubicin 75 mg/m(2) every 3 weeks for a maximum of seven treatment cycles. RESULTS: A total of 326 patients were randomized, 165 to receive doxorubicin and 161 to receive docetaxel. Overall, docetaxel produced a significantly higher rate of objective response than did doxorubicin (47.8% v 33.3%; P =.008). Docetaxel was also significantly more active than doxorubicin in patients with negative prognostic factors, such as visceral metastases (objective response, 46% v 29%) and resistance to prior chemotherapy (47% v 25%). Median time to progression was longer in the docetaxel group (26 weeks v 21 weeks; difference not significant). Median overall survival was similar in the two groups (docetaxel, 15 months; doxorubicin, 14 months). There was one death due to infection in each group, and an additional four deaths due to cardiotoxicity in the doxorubicin group. Although neutropenia was similar in both groups, febrile neutropenia and severe infection occurred more frequently in the doxorubicin group. For severe nonhematologic toxicity, the incidences of cardiac toxicity, nausea, vomiting, and stomatitis were higher among patients receiving doxorubicin, whereas diarrhea, neuropathy, fluid retention, and skin and nail changes were higher among patients receiving docetaxel. CONCLUSION: The observed differences in activity and toxicity profiles provide a basis for therapy choice and confirms the rationale for combination studies in early breast cancer.

A randomised, double-blind, parallel-group study to compare the efficacy and safety of ondansetron (GR38032F) plus dexamethasone with metoclopramide plus dexamethasone in the prophylaxis of nausea and emesis induced by carboplatin chemotherapy.

A double-blind, parallel-group study in 189 ovarian cancer patients compared the efficacy of ondansetron 8 mg i.v. (OND) and metoclopramide 60 mg i.v. (MET) both in combination with dexamethasone 20 mg i.v. in the prevention of carboplatin-induced emesis. On day 1, complete or major control of emesis (0-2 emetic episodes) was observed in 97% patients from the OND group compared with 74% patients from the MET group (p < 0.001). Similarly, a worst-day analysis over days 1-3 showed complete or major control of emesis in 87% patients (OND) compared wth 66% patients (MET) (p < 0.001). Similar findings in favour of the OND group were observed for nausea grade on day 1 and the worst-day grade during days 1-3. OND was better tolerated than MET. Fewer patients from the OND group (13%) reported adverse events compared with the MET group (21%). Extrapyramidal type symptoms were observed in 6 (6%) patients from the MET group (paraesthesia, involuntary movement of the jaw and tongue, and restlessness), compared with none from the OND group. Ondansetron plus dexamethasone is a highly effective and well-tolerated treatment and is significantly superior to metoclopramide plus dexamethasone in the prevention of carboplatin-induced emesis.

[Quality assurance, audit and quality control of radiotherapy at radiology departments in Hungary]. / A magyarországi sugárterápiás osztályok minöségbiztosítási, számvetési és minöségellenörzési rendszere.

The first quality assurance, audit and control system in the Hungarian "'health" care industry" is described for the medical specialty of radiotherapy. The prerequisites of the elaboration of the programme were an exact knowledge of the current Hungarian infrastructural and staffing conditions, and the radiotherapeutic activities. The recommendations cover the 5 medical universities including the national institute (the Debrecen, Pécs, Semmelweis, Szent-Györgyk Albert Medical Universities, and Haynal Imre University of Health Sciences) and the 5 regional oncological centres in hospitals (Jósa András, Markusovszky, Petz Aladár, Szentpéteri kapu and Uzsoki Hospitals). The departmental functions (patient care, teaching-education, research work and scientific organizing activity) and the structure (organization, infrastructure, staffing conditions, etc.) are described first, followed by the therapeutic principles and clinical process (patient referral and selection, decision-making, priorities in therapy initiation, treatment preparation and execution, etc.). The informal daily/weekly quality assurance programme long applied in the routine patient care has been formalized and supplemented with a weekly audit conference. In the course of the medical audit, all relevant clinical data are reviewed and scored by an internal or an external expert (not participating directly in the treatment process), e.g. for the adequacy of the medical decision preparative process, conformation to the institutional treatment protocol, equipment selection, treatment planning, simulation and portal film, etc. If a major deviation is detected, an immediate correction is initiated; minor deviations need analysis and then preventive and correcting action. As concern the audit of the other activities of the departments, the important indicators and their minimally desirable level are defined. The final goal of the implementation of this programme is high-precision radiotherapy with the best achievable treatment result.

Generalized secondary amyloidosis in rheumatoid arthritis.

The autopsy material of 215 RA patients was studied to determine 1) the frequency of generalized secondary amyloidosis (GSA), 2) the frequency and extent of amyloid deposits in various organs, 3) the chronological succession of amyloid deposition in various organs. The tissue specimens were fixed in 8% formaldehyde solution and embedded in paraffin. Serial sections were cut and stained with HE and Congo-red according to Romhányi, without alcoholic differentiation. The average amount of amyloid deposition in various organs was determined on a 0 to 4 plus scale. Thirty-seven cases were found to contain stainable amyloid (17.2%). The frequency and degree of amyloid deposition in different organs of RA cases with GSA are summarized in the following table. [table: see text] The frequency and extent of amyloid deposits in various organs may be linked to the ratio of cardiac output distributed over a different tissue mass. In conclusion, the tissues and organs often showing high quantities of amyloid are the sites where the deposits begin. Where deposits are infrequent or of low quantity deposits develop later. Amyloid deposits early in the wall of blood vessels, first of all within the GI tract, heart, kidneys, thyroid gland, spleen and the adrenal glands.

[Pancreatitis in rheumatoid arthritis found in autopsy material]. / Hasnyálmirigy gyulladás rheumatoid arthritisben, autopsziás anyagon.

Authors have studied in autopsy samples of 80 patients having suffered from rheumatoid arthritis the incidence and types of pancreatitis. There were 6 acute, 4 chronic-recurrent and 11 chronic severe or moderately severe pancreatitis observed. In the ethiology of pancreatites the ductal origin, cholelithiasis and uraemia were not found to be of exclusively significance. In 3 cases a pancreatitis was found accompanied by vasculitis and a typical histological pattern characterized by the vasculitis-thrombovasculitis of arterioles and small arteries with simultaneously occurring necrotic foci. In one case a pancreatitis due to severe amyloidosis could be verified. Authors draw attention to the frequent occurrence of pancreatitis in patients suffering from rheumatoid arthritis and the difficulties of a clinical diagnosis.

[Immunohistochemical and immunologic changes in aponeurosis in Dupuytren's disease]. / Immunhisztokémiai és immunológiai változások Dupuytren-kóros aponeurosisban.

Authors examined the aponeurosis of 23 patients with Dupuytren's contracture and of 5, formerly healthy persons, who died in consequence of accidents. It was found that the IgA and IgM content of the palmar aponeurosis is significantly elevated in Dupuytren's disease. The distribution of the immunglobulin containing cells and the fibronection localisation of the aponeurosis was also examined. On the basis of their examinations they think that the autoimmun mechanism may have a role in the development of Dupuytren's disease.

Fine structural alterations of the palmar aponeurosis in Dupuytren's contracture. A combined scanning and transmission electronmicroscopic examination.

The authors examined the fine structural alterations of palmar aponeurosis in Dupuytren's contracture. Two types of the fibroblasts can be identified: classic fibroblasts and myofibroblasts. In the Dupuytren's tissue one fourth of all non-inflammatory cells were regarded as myofibroblasts. In the Dupuytren's aponeurosis the orientation of the thin and thick collagen fibers varied. The Paccini corpuscles were hypertrophised and around them compact collagen tissue was increased.

Immunopathological study on palmar aponeurosis in Dupuytren's disease.

The authors examined the immunological and immunohistochemical alterations of palmar aponeurosis in Dupuytren's contracture. In the IgG-content no difference were found between the intact and diseased aponeurosis. The mean of IgA content was 2 fold, the IgM content 3 fold higher in Dupuytren's aponeurosis than in normal ones. The immunoglobulin containing cells localised around the Dupuytren's nodules and in fibrotic, but not nodular parts of aponeurosis. Extracellular immunoglobulin deposits were not found.

[Effect of lumbar peridural analgesia on the evolution of the number of delivery-associated operations]. / Der Einfluss der lumbalen periduralen Analgesie auf die Entwicklung der Zahl geburtsbeendender Operationen.

The authors analyse the obstetric material of ten years of their institute in terms of the rate of delivery-completing operations. Lumbar peridural analgesia was introduced in the fourth year of the period under scrutiny. In the course of ten years we delivered 16,582 patients. 2,797 parturients of them were given peridural analgesia. In spite of the widespread use of this method of pain control during labor, the rate of vaginal operative deliveries in percentage terms did not change. The result corroborates the authors' assumption that an increase in the number of obstetric vaginal operations is not a necessary concomitant of lumbar peridural analgesia.