Late Effects Following Treatment of Hodgkin Lymphoma During Childhood and Adolescence. Results of the Hodgkin Lymphoma Late Effects Research Project.

Survival rates have been excellent in patients treated for Hodgkin lymphoma (HL) during childhood and adolescence. Unfortunately, severe treatment related late effects have been observed. It was therefore an important aim of the cooperative pediatric HL therapy studies in Germany to reduce the number of late effects without jeopardizing the excellent treatment results. Progress and relapses of HL were analyzed to obtain important information for the future salvage therapy. All late effects were documented and their etiologies analyzed. Information obtained from bacterial infections and late deaths following splenectomy were used to inform patients at risk and their local physicians about necessary preventive measurements. Procarbazine was recognized as major gonadotoxic agent in boys and eliminated successively from the treatment regimens. Parenthood was normal in female patients when compared to the German female population documenting normal ovarian function except in patients with pelvic radiation. Radiation was the most important risk factor for thyroid diseases, cardiac late effects and subsequent malignant neoplasms, especially thyroid and breast cancer. A special screening program was initiated for women with chest radiotherapy, since they had a high risk of breast cancer already at a young age. The results of the HL Late Effects Research Project are important for the aftercare of patients and for the design of future HL treatment regimens.

Pediatric Nodular Lymphocyte-predominant Hodgkin Lymphoma: Treatment Recommendations of the GPOH-HD Study Group.

Nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) is a very rare disease in childhood and adolescence. In Germany, about 15 newly diagnosed patients present with this disease annually; this number comprises less than 10% of all pediatric Hodgkin lymphoma cases. Since the EuroNet-PHL-LP1 trial for early stage nLPHL patients stopped recruiting in Germany in October 2014, the GPOH-HD writing committee reviewed the literature and decided to deliver treatment recommendations for childhood and adolescent nLPHL patients. These guidelines shall be applicable to young nLPHL patients in European countries that will no longer be able to participate in nLPHL trials for young patients. Therefore, the EuroNet-PHL-nLPHL-registry will be installed to provide quality assured central review of staging and response assessment for registered patients by the Central Review Board of EuroNet-PHL in Halle/Leipzig, Germany.

Relapse of TEL-AML1--positive acute lymphoblastic leukemia in childhood: a matched-pair analysis.

PURPOSE: The aim of this study was to investigate whether, in relapsed childhood acute lymphoblastic leukemia (ALL), the frequent genetic feature of TEL-AML1 fusion resulting from the cryptic chromosomal translocation t(12;21)(p13;q22) is an independent risk factor. PATIENTS AND METHODS: A matched-pair analysis was performed within a homogeneous group of children with first relapse of BCR-ABL-negative B-cell precursor (BPC) ALL treated according to relapse trials ALL-Rezidiv (REZ) of the Berlin-Frankfurt-Münster Study Group. A total of 249 patients were eligible for this study: 53 (21%) were positive for TEL-AML1, and 196 (79%) were negative. Positive patients were matched for established most-significant prognostic determinants at relapse, time point, and site of relapse, as well as age and peripheral blast cell count at relapse. RESULTS: Fifty pairs matching the aforementioned criteria could be determined. The probabilities with SE of event-free survival and survival at 5 years for matched TEL-AML1 positives and negatives are 0.63 +/- 0.10 versus 0.38 +/- 0.10 (P =.09) and 0.82 +/- 0.09 versus 0.42 +/- 0.19 (P =.10), respectively. These results were confirmed by multivariate analysis, revealing an independent prognostic significance of time point and site of relapse (both P <.001) but not of TEL-AML1 expression (P =.09). CONCLUSION: TEL-AML1 expression does not constitute an independent risk factor in relapsed childhood BCP-ALL after matching for relevant prognostic parameters. It undoubtedly characterizes genetically an ALL entity associated with established favorable prognostic parameters. High-risk therapeutic procedures such as allogeneic SCT should be considered restrictively.

High cure rates and reduced long-term toxicity in pediatric Hodgkin's disease: the German-Austrian multicenter trial DAL-HD-90. The German-Austrian Pediatric Hodgkin's Disease Study Group.

PURPOSE: To further reduce therapy-related late effects in patients with pediatric Hodgkin's disease (HD) while maintaining the high cure rates achieved with vincristine, prednisone, procarbazine, and doxorubicin (OPPA) or OPPA/cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) chemotherapy and involved-field radiotherapy. The risk of testicular dysfunction was addressed by substituting etoposide for procarbazine (OEPA) in the induction therapy for boys. Radiation doses and fields were further reduced. PATIENTS AND METHODS: Three hundred nineteen boys and 259 girls younger than 18 years with previously untreated HD, enrolled onto the study between 1990 and 1995, were allocated to treatment group (TG)1 (early stages), TG2 (intermediate stages), or TG3 (advanced stages). All groups underwent two cycles of OEPA (boys) or OPPA (girls) for induction chemotherapy. TG2 and TG3 continued on additional two or four cycles, respectively, of COPP. Low-dose radiotherapy was given to the initially involved sites, ie, reduced involved fields. RESULTS: Initial response to OPPA or OEPA induction was virtually identical. Eight of 578 patients experienced early progression of HD. Thirty-seven relapses, three secondary tumors, and no secondary leukemias have been recorded, with a median follow-up duration of 5.1 years (maximum, 8.1 years). Thirteen of 578 patients died. The probability of 5-year event-free survival/overall survival is 91%/98% in the total group, 94%/97% with OPPA, and 89%/98% with OEPA induction therapy. Risk factor analysis showed two significant prognostic factors: histologic subtype NS2 and "B" symptoms. OEPA induction therapy, large mediastinal tumor, and age were not significant. Preliminary studies of testicular function indicate a lower risk of germ cell damage than previously documented with OPPA. CONCLUSION: OEPA is a satisfactory alternative to OPPA. Radiotherapy can be confined to involved sites when combined with appropriate chemotherapy. The DAL-HD-90 regimen represents a comprehensive treatment program for all stages of pediatric HD and offers a favorable benefit/risk ratio, combining excellent disease control, moderate acute toxicity, and reduced long-term toxicity.

Hemodynamic effects of immunoadsorption and subsequent immunoglobulin substitution in dilated cardiomyopathy: three-month results from a randomized study.

OBJECTIVES: The objective of our study was to assess the hemodynamic effects of immunoadsorption (IA) and subsequent immunoglobulin G (IgG) substitution in comparison with the effects of conventional medical treatment in patients with dilated cardiomyopathy (DCM). BACKGROUND: Various circulating cardiac autoantibodies have been detected among patients suffering from DCM. These antibodies are extractable by IA. METHODS: Patients with DCM (n = 18, New York Heart Association III-IV, left ventricular ejection fraction <30%) and who were on stable medication participated in the study. Hemodynamic measurements were performed using a Swan-Ganz thermodilution catheter. The patients were randomly assigned either to the treatment group with IA and subsequent IgG substitution (IA/IgG group, n = 9) or to the control group without IA/IgG (n = 9). In the IA/IgG group, the patients were initially treated in one IA session daily on three consecutive days. After the final IA session, 0.5 g/kg of polyclonal IgG was substituted. At one-month intervals, IA was then repeated for three further courses with one IA session daily on two consecutive days, until the third month. RESULTS: After the first IA course and IgG substitution, cardiac index (CI) increased from 2.1 (+/-0.1) to 2.8 (+/-0.1) L/min/m2 (p < 0.01) and stroke volume index (SVI) increased from 27.8 (+/-2.3) to 36.2 (+/-2.5) ml/m2 (p < 0.01). Systemic vascular resistance (SVR) decreased from 1,428 (+/-74) to 997 (+/-55) dyne x s x cm(-5) (p < 0.01). The improvement in CI, SVI and SVR persisted after three months. In contrast, hemodynamics did not change throughout the three months in the control group. CONCLUSIONS: Immunoadsorption and subsequent IgG substitution improves cardiovascular function in DCM.

Down's syndrome in childhood acute lymphoblastic leukemia: clinical characteristics and treatment outcome in four consecutive BFM trials. Berlin-Frankfurt-Münster Group.

Clinical characteristics, treatment response and outcome were evaluated in children with Down's syndrome (DS) and acute lymphoblastic leukemia (ALL) as compared to other children with ALL (NDS). Sixty-one DS and 4049 NDS patients, receiving intensive antileukemic treatment during four consecutive trials (ALL-BFM 81, 83, 86 and 90) of the Berlin-Frankfurt-Münster Group (BFM), were retrospectively analyzed. DS and NDS children did not differ with respect to sex, leukocyte count, CNS leukemia and cytogenetic translocations. The DS cohort was slightly older (P=0.04), presented predominantly with the common while lacking the T immunophenotype (P=0.005), had a lower frequency of hyperdiploidy (P=0.004) and tended to have a better initial steroid response (P=0.057). Therapy-associated morbidity especially during high-dose methotrexate and a subsequent need for treatment modification occurred in 43% of all DS patients. Event-free survival (EFS) was slightly worse in children with DS (58+/-8% vs 70+/-1%, P=0.14), mainly due to rather late bone marrow recurrences. However, EFS in DS patients was comparable to the NDS group once they either received treatment with no major modifications (65+9% vs 70+/-1%, P=0.66) or were <6 years of age, irrespectively of therapy modifications (73+/-9% vs 74+/-1%, P=0.7). Cox regression analysis revealed that DS was an adverse prognostic factor for patients having completed therapy (P=0.0107), but was not prognostic at diagnosis (P=0.103). Age > or = 6 years, suboptimal treatment and infectious problems contributed to the slight inferior EFS in children with ALL and Down's syndrome. Therefore, most of these patients can be successfully treated if receiving intensive antileukemic treatment with no major modifications, but they require more sophisticated management of toxicity.

Response-adapted radiotherapy in the treatment of pediatric Hodgkin's disease: an interim report at 5 years of the German GPOH-HD 95 trial.

PURPOSE: A multinational trial on pediatric Hodgkin's disease (HD) with the aim to reduce the risk of long-term toxicity of combined modality treatment by restricting dose and volume of radiation therapy (RT) while maintaining the excellent treatment results of previous German multicenter trials (DAL-HD82-90). METHODS AND MATERIALS: Patients were treated according to stage of disease (CS) and defined risk factors in three treatment groups (TG) with 2, 4, or 6 cycles of combination chemotherapy. When a complete remission (CR) had been achieved, treatment was terminated without RT independent of initial stage or tumor bulk. Patients with a partial remission (PR) of >75% tumor regression were irradiated with 20 Gy using modified involved fields; in the case of PR <75% RT dose was 30 Gy, residual masses >50 mL received 35 Gy. RESULTS: From August 1995 to July 2000 a total of 956 patients have been registered, 830 as trial patients, 39% in TG1, 27% in TG2, 34% in TG3. 827 patients were evaluable by June 2001 with a median follow-up of 38 months. Chemotherapy (CTx) resulted in CR in 22%, PR >75% in 62%, PR <75% in 12%. Event-free survival (EFS) for the entire group is 90% (SD 0.01), for TG1 94%, TG2 91%, and TG3 84%; the overall survival is 97% in Kaplan-Meier-analysis. Relapse-free survival (RFS) is superior for patients with RT after PR (93%) than for those without RT after CR (89%); the difference is significant (p = 0.01) for advanced stages, however not in TG1. Seventy-two events were observed by June 2001: 28 progressions during the initial therapy or within the first 3 months, 38 relapses, 3 second malignancies, three fatal accidents or infections; 18 patients have died. CONCLUSION: Treatment results of the GPOH-HD 95 trial are excellent thus far. The reduction of RT dose and volume in PR has not caused a significant impairment of overall and event-free survival in comparison to the previous German trials; however, failure rates are higher in advanced stages when RT is omitted after achieving a CR. It is too early to tell whether the HD 95 protocol will be successful in reducing late toxicity.

Computed tomography-guided transtracheal needle aspiration of paratracheal lymphadenopathy in endoscopically normal patients.

RATIONALE AND OBJECTIVES: The authors investigated the diagnostic value of computed tomography-guided bronchoscopic transtracheal needle biopsy of paratracheal lymphadenopathy without any endoscopical signs of stenosis or protrusion. METHODS: Twenty consecutive patients with an age of 22 to 76 years underwent fiberoptic bronchoscopy with transtracheal needle biopsy under computed tomography guidance of paratracheal lymphadenopathies (diameter between 10 to 19 mm). Computed tomography fluoroscopy as a special low-dose computed tomography technique was used in the region of interest. The results of needle aspirates (cytologic examination) were verified by surgical interventions (n = 4), mediastinoscopy (n = 9), percutaneous needle biopsy (n = 1), or clinical/radiologic follow-up (n = 10). RESULTS: All patients were without endoscopic signs of lymphadenopathy or tumor. Sufficient material of lymphatic tissue for cytologic assessment was obtained in 23 out of 24 patients (96%). In 5 of 10 patients with malignant diseases and 13 of 14 patients with benign enlarged lymph nodes, the lymph nodes were demonstrated exactly by transtracheal needle biopsy. There were no bleeding complications. CONCLUSIONS: Computed tomography-guided bronchoscopic needle biopsy of paratracheal lymphadenopathy is a low-risk procedure. If malignant cells can be demonstrated with these technique, other more invasive procedures (surgery, mediastinoscopy) can be avoided. The numerous false-negative results (5 of 10) suggest, that the cytologic evidence of benign cells is without any diagnostic value in cases of paratracheal lymphadenopathy.

Removal of autoantibodies in dilated cardiomyopathy by immunoadsorption.

Immunoadsorption with Ig-Therasorb leads to a marked decrease in serum levels of immunoglobulins including of the agonist-like anti-beta 1-adrenoceptor autoantibody found in the serum of patients with idiopathic dilated cardiomyopathy. The reduction in autoantibody levels was accompanied by an improvement of heart function and a shift to a lower NYHA state. In this disease, as in a variety of other autoimmune disorders, apheresis with Ig-Therasorb led to a rapid improvement of the clinical status and could be used in end-stage dilated cardiomyopathy (with autoantibodies) as a bridge for transplantation.

[C-reactive protein, Il-6 and procalcitonin as infection parameters in children with oncologic diseases]. / CRP, IL-6 und PCT als Infektionsparameter bei onkologisch kranken Kindern.

BACKGROUND: Due to anti-neoplastic therapy, there is a high incidence of infections and fever in pediatric patients with malignant disease. We have searched for parameters that may be of value in the early diagnosis of infection, in discriminating between bacterial and non-bacterial causes and for monitoring the response to antimicrobiotic therapy. PATIENTS: 46 febrile episodes in 33 children with malignant diseases under anti-neoplastic therapy, aged 0.5 to 17 years, were included. Each patient was supplied with a central venous catheter (Hickman catheter). METHODS: Blood was taken for the evaluation of C-reactive-protein (CRP), Interleukin-6 (IL-6) and Procalcitonin (PCT). Laboratory data included WBC, blood cultures, as well as microbiologic and serologic tests for important infectious agents. Patients were grouped as follows: 1. Patients with febrile diseases and positive blood cultures, 2. Patients with localized bacterial or mycotic infections and negative blood cultures, 3. Patients with fever of unknown origin, 4. Patients with viral infections, 5. Control group. RESULTS: CRP and IL-6 were more sensitive than PCT in detecting bacterial and mycotic diseases in leukopenic children, because of low PCT-levels in patients with localized infections. IL-6 values were high shortly after onset of fever and decreased under sufficient antimicrobiotic therapy until day three. CONCLUSIONS: Because of the quick response, IL-6 may be helpful in monitoring antimicrobiotic therapy. Using Procalcitonin-levels, we were not able to distinguish between localized bacterial and viral infection in leukocytopenic patients.

[Pulmonary blastoma in childhood--a case report and review of the literature]. / Das pulmonale Blastom im Kindesalter--Eine Kasuistik und eine Ubersicht über die Literatur.

The paper deals with a pulmonary blastoma with CNS involvement in a young child 2 years after resection of congenital cysts from the other lung. Further 25 pulmonary blastomas in infants are compiled from the literature serving as the basis for a discussion of epidemiology, pathogenesis, classification, definition and prognosis as well as diagnostic and therapeutic problems involved in these rare malignant lung tumours.

[18-FDG-PET-findings in children and adolescents with Hodgkin's disease: retrospective evaluation of the correlation to other imaging procedures in initial staging and to the predictive value of follow up examinations]. / 18-FDG-PET-Befunde bei Kindern und Jugendlichen mit Morbus Hodgkin: Retrospektive Auswertung zur Korrelation mit anderen bildgebenden Verfahren bei der initialen Stagingdiagnostik und zum prädiktiven Wert bei Verlaufsuntersuchungen.

Today no evidence based medicine analyses exist about the value of positron emission tomography (PET) in children and adolescents with Morbus Hodgkin. The increasing number of registered PET-examinations within the scope of the GPOH-HD 95 trial motivated to analyse the validity of 18-FDG-PET-examination findings in comparison to the conventional diagnostic methods (CT/MRI/ultrasound) and to the patients follow up. 67 PET-primary staging findings and 48 PET-follow up findings of altogether 106 patients from 27 PET-centres were analysed. Concerning the primary staging findings a concordance of 92% of the PET-findings and the findings of the CT/MRI/ultrasound-examinations per localisation was found, but in more than 50% of the patients a discrepancy occurred in at least one of the 9 investigated localisations. The analysis of the PET follow up findings showed a negative predictive value of 94% in regularly examinations (without previous suspicion of relapse), but only a positive predictive value of 25%. In case of relapse suspicion there was a negative predictive value of 83% and a positive predictive value of 76% in PET. A good prognosis is possible to predict from negative PET follow up findings (relapse risk in regularly controls 7%, at relapse suspicion 17%), whereas the probability for a true relapse in positive PET follow up findings is only markedly increased in case of former relapse suspicion (relapse risk in regularly controls 25%, at relapse suspicion 82%). A prospective multicenter PET study should be realized to analyse systematically the value of PET diagnostics in staging and restaging examinations of children and adolescents with Hodgkin's disease, especially to validate the PET diagnostics in exclusion of vital tumor residuals.

[The irradiation sequelae in children with lymphogranulomatosis]. / Bestrahlungsfolgen bei Kindern mit Lymphogranulomatose.

1. 37 children with M. Hodgkin received radiotherapy to the involved cervical lymph nodes at the II. Children's Hospital in Berlin-Buch during 1971-1986. 2. Localised growth disturbances and muscle atrophies were observed as late effects. 12 children had severe sequelae and 19 patients moderate late effects. 3. The effects were stronger the younger the children were at the time of irradiation.

[Endotracheal silicon stents in therapy management of benign tracheal stenoses]. / Endotracheale Silikonstents im Therapiemanagement benigner Trachealstenosen. Ergebnisse nach 5-jähriger Anwendung.

BACKGROUND: Advances in endoscopic technique and the development of new materials have made stenting an interesting alternative to surgical treatment for extended tracheal stenoses. This 5 years' retrospective study describes long term results of silicon stents in patients with benign chronic tracheal stenoses. PATIENTS AND METHODS: 45 adult patients (mean age: 45 years) had endotracheal Dumon (Endoxane) stent placement as surgical therapy was not indicated. Fiberoptic controls were performed every 3-6 months. RESULTS: In 42 patients therapy proved successful with improved ventilation and high level of tolerance. Acut stent-removal was necessary in 2 patients because of edema of the vocal cords, in 1 patient because of stent independent paralysis of both recurrents nerves. Further complications included migration (16.6%), granuloma formation (33.3%) and airway obstruction due to heavy secretion (2.3%). CONCLUSIONS: Long term results have shown that this technique is associated with high efficiency and infrequent complications which are not life-threatening. Advantages consist in a minor-invasive technique with small expenditure of time.

[The endocrinological aspects of the therapy of testicular involvement in children with acute leukemias]. / Endokrinologische Aspekte zur Therapie des Hodenbefalls bei Kindern mit akuten Leukämien.

Orchidectomy or testicular irradiation with 24 to 30 Gy are recommended for testicular involvement in boys with acute lymphoblastic leukemia. But, recommended radiation doses for the only occultly involved other testis differ, i.e. they range from 12 to 24 Gy. Low dose (12 or 15 Gy) "preventive" testicular irradiation was delivered to 5 of 14 patients; only one of these 5 experienced a further testicular relapse. According to our observation, in contrast to higher doses, the dose limitation allows spontaneous pubertal development including normal testosterone production and normal development of the masculine stature.

[Experiences with miconazole in the prevention and therapy of candidiasis]. / Erfahrungen mit Miconazol. in der Prophylaxe und Therapie von Sprosspilzinfektionen.

1. The treatment of 26 children suffering from haemoblastoses and tumors by the antimycotic Miconazol is reported on. 2. The application took place prophylactically as well as therapeutically by an oral or intravenous administration. Mycological examinations (stools, urine, throat swab, blood) have been carried through before, during and after the treatment in weekly intervals. 3. The result of treatment is altogether to be called good, invasive mycoses have been prevented and proved Blastomyces infections successfully treated. 4. Side effects like nausea and vomiting were observed only in one case, damages of the haematopoietic system, the liver and kidneys could not have been demonstrated.

[Effect of various therapeutic protocols on growth and final height of children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma]. / Einfluss verschiedener Therapieprotokolle auf das Wachstum und die Endgrösse von Kindern mit akuter lymphoblastischer Leukämie oder Non-Hodgkin-Lymphom.

A total of 74 children suffering from acute lymphoblastic leukaemia (ALL) or non-Hodgkin lymphoma (NHL) were involved in a retrospective analysis of their physical growth during and after the therapy. Out of this total number, 54 children were subjected to radiochemotherapy in compliance with the VII/(81) scheme, and another 20 children in compliance with the LSA2L2 scheme. At the beginning of the therapy the average height-standard deviation score (H-SDS) for both groups of patients corresponded with the population average. The patients subjected to the VII/(81) scheme showed, throughout the observation period of five years from the beginning of the therapy, a height normal for their age group. Contrary to this observation, the patients subjected to the LSA2L2 scheme experienced a significantly different growth in the period under observation and continually lost height in comparison to the normal population. The same results were experienced with a smaller group of patients whose growth was followed up for eight years from the beginning of therapy. 16 patients (VII/81 n = 4/LSA2L2 n = 12) reached their final height. For the patients of the VII/(81) scheme the final height showed an average H-SDS of 0.27 and for the patients of the LSA2L2 scheme of -1.22 (p = 0.068). Considering that the same cranial radiotherapy (max. 18 Gy for both schemes) and a comparable intensive induction therapy were applied, it must be concluded that the intensity and duration of the maintenance treatment are the critical factors initiating a different growth behaviour of the two groups subjected to radiochemotherapeutical schemes.

Antiviral therapy of varicella-zoster virus infection in immunocompromised children--a prospective randomized study of aciclovir versus brivudin.

Both aciclovir and brivudin are effective in the treatment of immunocompromised children with varicella-zoster virus infection. To determine which drug is preferable, a prospective randomized trial aciclovir vs. brivudin was conducted. Forty-three immunocompromised children were randomly assigned to receive aciclovir intravenously at a dose of 1,500 mg/m2/d and brivudin orally at a dose of 15 mg/kg/d, respectively. Twenty-two patients were treated with aciclovir and 21 with brivudin. In all children the general status improved within two days. The eruption of new lesions stopped within one to five days, fever stopped within one to nine days, complete remission occurred within five to six days after introduction of the virustatic therapy. There was no difference in therapeutic efficacy between aciclovir and brivudin. Two children in each group did not respond to the medication. No myelo-, hepato- and nephrotoxic side effects due to aciclovir or brivudin were observed. All obviously immunocompromised children with varicella or zoster may be treated with aciclovir or brivudin.

[Secondary malignant neoplasms in patients with breast cancer]. / Sekundäre maligne Neoplasien bei Patientinnen mit Mammakarzinom.

OBJECTIVE: This report analyzes the occurrence of secondary malignancies among patients with breast cancer. MATERIAL AND METHODS: We evaluated all women diagnosed with breast cancer who were reported to the National Cancer Institute of the former GDR in 1976. There was a follow up of 5,485 patients from 1976 to 1988 (38,231 person-years at risk). Cancer incidence rates of the whole female population specific for age and calendar year were used for calculation of the standardized incidence ratio (SIR). RESULTS: Significantly increased risks were observed for neoplasms of the bilateral breast (SIR 2.44; 95% CI 2.04-2.93), colon (SIR 1.53; 95% CI 1.06-2.12), rectum (SIR 1.65; 95% CI 1.10-2.40), endometrium (SIR 1.55; 95% CI 1.02-2.27), and ovary (SIR 1.71; 95% CI 1.09-2.57). Neoplasms of the lung (SIR 1.65; 95% CI 0.93-2.73), kidney (SIR 1.51; 95% CI 0.69-2.87), bladder (SIR 1.32; 95% CI 0.48-2.87), connective tissue (SIR 3.54; 95% CI 0.73-10.34), and multiple myeloma (SIR 1.98; 95% CI 0.54-5.06) were also increased, not reaching statistical significance. Risk reduction was observed for malignant tumors of the gallbladder (SIR 0.36; 95% CI 0.12-0.83). CONCLUSION: In proposing recommendations for the follow-up and management of women with breast cancer, it is important to recognize their long-term predisposition to an array of secondary cancers.

[Primary amyloidosis AL as a cause of restrictive cardiomyopathy]. / Primäre Amyloidose AL als Ursache der restriktiven Kardiomyopathie.

In a 71-year-old woman with macroglossia and heart failure, a monoclonal protein (kappa-light chains) was found in the serum. Congestive heart failure was diagnosed on the basis of heart catheterization and echocardiography. The tongue biopsy showed numerous amyloid fibrils, and plasmacytosis was present in the bone marrow. All these findings indicated a restrictive cardiomyopathy as part of a primary systemic amyloidosis.