Second malignancies after treatment of childhood non-Hodgkin lymphoma – a report of the Berlin-Frankfurt-Muenster study group

Second malignant neoplasms (SMN) pose a concern for survivors of childhood cancer. We evaluated incidence, type and risk factors for SMN in patients included in Berlin-Frankfurt-Muenster protocols for childhood non-Hodgkin lymphoma.3,590 patients <15 years of age at diagnosis, registered between 01/1981 and 06/2010, were analyzed. SMN were reported by the treating institutions and the German Childhood Cancer Registry. After a median follow-up of 9.4 years (quartile [Q] range, Q1 6.7 and Q3 12.1) 95 SMN were registered (26 carcinomas including nine basal cell carcinomas, 21 acute myeloid leukemias/myelodysplastic syndromes, 20 lymphoid malignancies, 12 central nervous system [CNS]-tumors, and 16 others). Cumulative incidence at 20 years was 5.7±0.7%, standard incidence ratio, excluding basal cell carcinomas, was 19.8 (95% Confidence Interval [CI]: 14.5-26.5). Median time from initial diagnosis to second malignancy was 8.7 years (range, 0.2-30.3 years). Acute-lymphoblasticleukemia- type therapy, cumulative anthracycline dose, and cranial radiotherapy for brain tumor-development were significant risk factors in univariate analysis only. In multivariate analysis including risk factors significant in univariate analysis, female sex (hazard ratio [HR] 1.87, 95% CI: 1.23-2.86, P=0.004), CNS-involvement (HR 2.24, 95% CI: 1.03-4.88, P=0.042), lymphoblastic lymphoma (HR 2.60, 95% CI: 1.69-3.97, P<0.001), and cancer-predisposing condition (HR 11.2, 95% CI: 5.52-22.75, P<0.001) retained an independent risk. Carcinomas were the most frequent SMN after non-Hodgkin lymphoma in childhood followed by acute myeloid leukemia and lymphoid malignancies. Female sex, lymphoblastic lymphoma, CNS-involvement, or/and known cancer-predisposing condition were risk factors for SMN-development. Our findings set the basis for individualized long-term follow-up and risk assessment of new therapies.     

Liver resection for breast cancer metastases

BACKGROUND/AIMS: The prognosis of patients with hepatic metastases (HM) from breast cancer receiving no treatment is extremely poor. Results of systemic and regional chemotherapy as well as other treatment modalities, such as immunotherapy or hormonal therapy, are disappointing in this group of patients, with median survival rates hardly exceeding 1 year. METHODOLOGY: We performed a retrospective analysis of patients undergoing resection of isolated HM from breast cancer to determine the morbidity, mortality and prognosis following this procedure. RESULTS: Fifteen female patients underwent liver resection between September 1985 and April 1997. Two patients had synchronous and 13 patients had metachronous HM. The mean number of HM was 3.3 (1-9) (bilobar in 6 patients) with a mean diameter of 5.3 cm (2-11 cm). The following resections were performed: wedge resection (4), left lateral segmentectomy (2), right hemihepatectomy (3), left hemihepatectomy (1), extended right hemihepatectomy (3) and extended left hemihepatectomy (2). There was no hospital mortality. Morbidity (transient hepatic failure (n=2) and intra-operative hemorrhage necessitating splenectomy (n=1)) occurred in 3 patients. Median follow-up was 12 (1-88) months. Six patients developed recurrent liver disease; 2 relapsed elsewhere. Six of these 8 patients died. Overall median survival following liver resection was 57 months with 1-, 2- and 3-year survival rates of 100%, 71.4% and 53.6% respectively. CONCLUSIONS: Liver resection is a viable treatment option for selected patients with isolated HM from breast cancer that can be performed safely. It should be considered in individual patients if the operative risk is low, if no extrahepatic disease is present and provided a complete resection with clear margins is technically feasible.     

Down-regulation of growth hormone releasing factor receptors following continuous infusion of growth hormone releasing factor in vivo

The in vivo chronic infusion of growth hormone releasing factor (GRF) results in a loss of the pituitary growth hormone (GH) response to GRF as well as in a substantial depletion of pituitary GH content. To evaluate if the loss in response is due to the down-regulation of GRF receptors the specific GRF binding capacity of pituitary homogenates prepared from rats infused with saline or GRF (1 or 15 micrograms/h for 24 h) was determined. The pituitary binding capacity of animals infused with GRF was significantly reduced as compared to animals infused with saline.     

Direct immunostaining of TSH receptor related autoantibodies in Graves' disease

Ten thyroid specimens from patients with Graves' disease were investigated immunohistologically with respect to the localisation of thyrotropin (TSH) receptor related autoantibodies. After conventional preparation of formalin-fixed and paraffin-embedded thyroid slices for immunostaining, 3-5 micron tissue sections were incubated with a porcine thyrotropin receptor containing membrane preparation (pTSH-R). The TSH receptor containing membrane fragments bound to the thyroid tissue were revealed with a slightly modified unlabelled PAP technique according to Sternberger, using an antiserum to pTSH-R obtained from immunized rabbits. This technique resulted in a staining of a considerable portion of plasma cells within the lymphoplasmacellular infiltrates of all the Graves thyroids. No staining occurred if for negative control either pTSH-R or its antiserum from rabbit was omitted. In addition, the staining reaction was markedly reduced by pretreatment of pTSH-R with serum from patients with Graves' disease in order to occupy its binding sites for autoantibodies prior to the staining procedure. It is concluded that the staining of the intrathyroidal plasma cells is due to their synthesis of autoantibodies directed against TSH receptor related structures of thyroid epithelia. The results are in keeping with the concept that the thyroid as the target organ itself is the site of autoantibody synthesis in Graves' disease.     

Prospective study of early rheumatoid arthritis. I. Prognostic value of IgA rheumatoid factor.

Thirty-three patients with early arthritis, 28 of whom developed classical/definite rheumatoid arthritis (RA), were followed up for two to four years. Rheumatoid factor (RF) levels of the IgM, IgA, and IgG isotypes were measured in serum and synovial fluid by an ELISA technique developed in our laboratory. All seven patients who presented with raised IgA RF developed erosions of their hands and wrists. This was significantly different from the remaining 26. By contrast none of the five patients who presented with isolated elevation of IgM RF developed erosive disease. The patients with raised IgA RF needed significantly more treatment with 'specific' drugs than the remaining 26. It is suggested that the detection of IgA RF in early RA indicates poor prognosis, justifying a more aggressive treatment at an early stage.     

Early vascular response to overlapped paclitaxel-eluting stents in swine coronary arteries

BACKGROUND: The early response to the TAXUS Express2 paclitaxel-eluting stent (PES) system was compared to the response to the Express2 bare metal stent (BMS) system in porcine arteries. METHODS: Swine coronary arteries were implanted with overlapping PES or BMS and examined at 1, 2, 4, 10, and 20 days postimplantation using scanning electron microscopy or light microscopy. RESULTS: Vascular healing in terms of strut coverage, reendothelialization, degree of inflammation, and absence of thrombus was equivalent in both groups from 1 to 20 days. Interstrut member spaces were unaffected by stent deployment and remained covered with endothelium from Day 1. In both groups at 2 days, small patches of endothelial cells covered approximately 5-10% of the stent surface. At 4 days, endothelial cell coverage progressed to nearly 50% in both groups. After 10 days, endothelial cell strut coverage was nearly complete (>90%), with regions of incomplete coverage located primarily in strut overlap regions in both groups. BMS exhibited a fibrocellular neointima and no parastrut fibrin, whereas PES exhibited a developing but immature fibrocellular neointima and prominent parastrut fibrin. By Day 20, an endothelialized neointima was present in both groups, with comparable coverage of proximal and distal stented regions. The neointima of PES was more fibrocellular and parastrut fibrin was still comparable to that at 10 days. CONCLUSION: Early vascular response was comparable for both PES and BMS, with similar rates of reendothelialization, limited inflammatory response, and absence of thrombus, but differed parastrut fibrin clearance and neointimal maturation rate.     

Über das Vorkommen sog. heller Zellen in Speicheldrüsentumoren

Zusammenfassung Zu den hellzelligen Speicheldrüsentumoren gehören monomorphe hellzellige Adenome, hellzellige Carcinome, hellzellige Varianten der Acinus- und Mucoepidermoidtumoren, Talgdrüsentumoren, Speichelgang-Carcinome und pleomorphe Adenome mit hellzelligen Abschnitten. Der lichtmikroskopische, deskriptive Begriff der hellen Zelle umfaßt bei einer weiteren cytochemischen und elektronenmikroskopischen Analyse Zellformen unterschiedlicher Herkunft und funktioneller Bedeutung. Folgende Zelltypen wurden näher analysiert: indifferente Gangzellen (geringe Organellenausbildung, Desmosomen), speichernde Streifenstückzellen (Glykogengranula, zahlreiche Mitochondrien, basales Labyrinth), Myoepithelzellen (Myofilamente, Pinocytose-Vesicel, Lipofuscingranula, Hemidesmosomen), epidermoide Zellen (Tonofilamente, Desmosomen), Becherzellen (Schleimvacuolen, basales endoplasmatisches Reticulum), Talgdrüsenzellen (Lipidtropfen, Mikrovilli, Desmosomen) und helle Acinuszellen (elektronenoptisch helle Sekretgranula, kleine Mitochondrien, kleiner Golgiapparat). In die Differentialdiagnose müssen auch hellzellige Tumorformen der Speicheldrüsenregion einbezogen werden, welche primär nicht vom Speicheldrüsengewebe ausgehen. Hierzu gehören Metastasen hypernephroider Nieren-Carcinome, Paragangliome, Glomustumoren Masson, Granularzelltumoren und alveoläre Weichteilsarkome.Mit Unterstützung der Deutschen Forschungsgemeinschaft und der Aktion Kampf dem Krebs e.V. der Deutschen Krebsgesellschaft     

Management of patients with community-acquired pneumonia in a primary care hospital: a critical evaluation

The aim of the study was to evaluate routine management of patients with community-acquired pneumonia (CAP) with regard to severity patterns, diagnostic approaches and results, as well as initial empiric antimicrobial treatment and its impact on outcome. Two hundred and thirty-two consecutive patients with CAP admitted to a primary care hospital were studied prospectively. Patients were classified according to Fine's severity score. Severe pneumonia was defined as admission at the ICU. Diagnostic approaches and initial antimicrobial treatment were judged according to the guidelines of the European Respiratory Society (ERS). Fifty-five patients (24%) had mild, 156 (67%) moderate, and 21 (9%) severe CAP. At least one microbial examination was performed in 124 patients (54%). There was no association between microbial investigation and severity of CAP. Inadequate initial antimicrobial treatment was significantly more frequent in severe (18/21, 86%), than in mild (5/55, 9%) and moderate CAP (39/156, 25%, P < 0.0001). Conversely, antimicrobial overtreatment occurred significantly more often in mild (30/55, 55%) and moderate (77/156, 49%) than in severe CAP (0/21, 0%, P < 0.0001). Inadequate initial antimicrobial treatment was more frequent in non-responders [18/62 (29%) vs. 31/170, (18%), RR 1.6 95% CI 0.9-2.6, P = 0.07] and was associated with a longer duration of hospitalization (17 +/- 11 vs. 14 +/- 8 days, P = 0.03). Mortality was not affected by inadequate initial antimicrobial treatment [5/62 (8%) vs. 10/170 (6%), RR 1.4 95% CI 0.5-3.9, P=0.55]. Principal conceptual weaknesses which might be subject to intervention were (1) the hospitalization of patients with mild pneumonia at low risk of mortality; (2) the lack of association between microbial investigation and severity of CAP; (3) antimicrobial overtreatment of patients with non-severe CAP; and (4) inadequate antimicrobial treatment with increased number of primary treatment failures and duration of hospitalization.     

Disseminated gonococcal infection in a married couple

Summary The rare occurence of disseminated gonococcal infection in a married couple is reported. These cases support the concept that bacterial rather than host factors are more important in determining the disease manifestations in gonorrhoea.     

Non-compliance in surveillance for patients with previous resection of large (≥1 cm) colorectal adenomas

AIM: To assess the extent and reasons of noncompliance in surveillance for patients undergoing polypectomy of large (≥ 1 cm) colorectal adenomas.METHODS: Between 1995 and 2002, colorectal adenomas ≥ 1 cm were diagnosed in 210 patients and subsequently documented at the Erlangen Registry of Colorectal Polyps. One hundred and fifty-eight patients (75.2%) could be contacted by telephone and agreed to be interviewed. Additionally, records were obtained from the treating physicians.RESULTS: Fifty-four out of 158 patients (34.2%)neglected any surveillance. Reasons for non-compliance included lack of knowledge concerning surveillance intervals (45.8%), no symptoms (29.2%), fear of examination (18.8%) or old age/severe illness (6.3%).In a multivariate analysis, the factors including female gender (P = 0.036) and age ≥ 62 years (P = 0.016)proved to be significantly associated with non-compliance in surveillance.CONCLUSION: Efforts to increase compliance in surveillance are of utmost importance, This applies particularly to women's compliance. Effective strategies for avoiding metachronous colorectal adenoma and cancer should focus on both the improvement in awareness and knowledge of patients and information about physicians for surveillance.