Soft tissue sarcomas after radiation treatment for breast cancer. Three case studies and review of literature.

AIMS: By means of 3 cases with infield soft tissue carcinomas after radiotherapy for breast cancer, symptoms and therapy are described. Consequences for treatment planning and patient's information before radiotherapy for breast cancer are discussed. PATIENTS: Three of 1,025 patients with breast cancer irradiated from 1984 to 1997 suffered from infield secondary soft tissue sarcomas. The latency periods were 61, 49 and 59 months. Two patients had been treated with breast-conserving therapy (computerized planning, 50 Gy to reference point, 5 times 2 Gy/week, 5-MV photons), 1 patient received a local boost dose of 15 Gy (10-MeV electrons), patient 3 radiotherapy of the thoracic wall and regional lymph nodes after mastectomy using 12-MeV electrons (thoracic wall) and 5-MV photons (lymph node areas) to 50 Gy, 5 times 2 Gy/week. No adjuvant chemotherapy was given. All sarcomas were very extensive, all patients died from local progression and/or distant failure after 17, 13 and 12 months. RESULTS: The incidence of spontaneous sarcomas of the breast is about 0.06%, after operation and radiotherapy 0.09 to 0.45%. No correlations to radiotherapy technique and no risk factors were found. Radiation dose could play a role, but there are very sparse data about this. CONCLUSIONS: Secondary soft tissue sarcomas are very rare, but familiar complications of radiotherapy. Only early diagnosis leads to a chance for cure. Because of unclear correlations to the treatment parameters and rareness of this event, in our opinion no regular information to the patient receiving radiotherapy for breast cancer is mandatory.

Wilms' tumor in adults. Review of 10 cases.

A nephroblastoma (Wilms' tumor) is very rarely found in adult patients. We report on 10 cases to demonstrate the diagnostic and therapeutic problems. In case of flank pain, large tumor mass, fast tumor growth, and young age, the possibility of a Wilms' tumor should be taken into consideration even in adult patients. The chances for a successful treatment by primary surgery with adjuvant therapy are favorable for the lower stages I and II. All our patients presenting with tumor stages I and II have survived and are free of disease since 68 months at the time of the study. One of 2 patients with a Wilms' tumor stage III died 8 months postoperatively, while the other is free of disease since 120 months. In the advanced stage IV no patient survived. In cases of inoperable large tumors in adults, the possibility of primary chemotherapy should be considered under certain circumstances. Rapid tumor regression may confirm the diagnosis and will enable salvage operation in some cases.

Wilms' tumour in adults. Review of 10 cases.

Nephroblastoma (Wilms' tumour) is very rarely found in adult patients. We report on 10 cases to demonstrate the diagnostic and therapeutic problems. In case of flank pain, large tumour mass, fast tumour growth and young age, the possibility of Wilms' tumour should be taken into consideration even in adult patients. The chances for a successful treatment by primary surgery with adjuvant therapy are favourable for the lower stages I and II. All our patients presenting with tumour stages I and II have survived and have been free of disease for 68 months now. One of the patients with stage III Wilms' tumour died 8 months postoperatively while the other one has been free of disease for 120 months now. In the advanced stage IV no patient survived. In cases of inoperable large tumours in adults, the possibility of primary chemotherapy should be considered under certain circumstances. Rapid tumour regression may confirm the diagnosis and will make feasible a salvage operation in some cases.

[Tumoral calcinosis of the ischium]. / Die tumorförmige Kalzinose des Sitzbeins.

The authors report on a case of tumoral calcinosis of the ischium in a 63 year old female. A general review of the literature on pathogenesis, histological characteristics and the way of treatment is given and the prognosis of tumoral calcinosis pointed out.

Serial Doppler echocardiographic assessment of left and right ventricular filling for non-invasive diagnosis of mild acute cardiac allograft rejection.

Detection of acute cardiac allograft rejection (AR) remains an important clinical challenge. The role of Doppler echocardiography for the non-invasive diagnosis of AR is controversial, in particular with regard to milder forms of rejection. This study was designed to evaluate the potential of Doppler echocardiography for the non-invasive diagnosis of mild AR. Serial measurements of left and right ventricular filling parameters were performed in 31 heart transplant recipients and compared with simultaneously obtained endomyocardial biopsies. To account for biological and technical variability, consecutive rejection-free studies were used to calculate 95% confidence limits for mitral and tricuspid maximum early flow velocity and pressure half time. Measurements obtained during mild AR were then compared to these data. The study demonstrated that all parameters varied considerably between consecutive rejection-free examinations. Changes in left and right ventricular filling parameters during mild AR rarely exceeded the calculated 95% confidence limits. Thus Doppler echocardiography appears of little value for the non-invasive diagnosis of mild acute cardiac rejection.

Kinetics and dynamics of acute rejection after heterotopic heart transplantation.

Right cervical, heterotopic heart transplantation was performed in 18 mongrel dogs. Study design was based on three different groups (n = 3 x 6). Standard immunosuppression consisted of triple drug therapy in all dogs. Groups II and III received high dose steroids during acute rejection. In group III the native hearts of previous recipients (groups I and II) were used as donors for heterotopic transplantation ("domino" principle). The hearts were examined by daily transmural biventricular biopsies and graded according to Billingham classification. Cytoimmunologic monitoring (n = 345; activation index from peripheral and coronary sinus blood) and fast Fourier transformation ECG (n = 80; area under the curve; surface recordings) served as daily noninvasive methods. Optionally antimyosin scintigraphy (n = 25; single photon emission computed tomography; heart-to-lung ratio) was performed and immunohistologically confirmed by peroxidase staining of the antibody (n = 61). Kinetics of rejection was not uniform in group I (onset after 5.7 days) and biphasic in group II (clear rejection-free interval: 6.8 days). Group III developed a continuously persisting rejection, despite repeated high-dose steroids, with an early onset (3.2 days). The invasive data, consisting of 587 punch biopsies, showed no significant difference between right and left ventricular rejection. Clearly focal rejection appeared in 51.5% of the cases, with subendocardial involvement in 54%. Cytoimmunologic monitoring significantly (p less than 0.001) correlated with daily biopsies in groups I and II. The activation index from coronary sinus blood was two times higher than in peripheral blood. Fast Fourier transform ECG identified the onset of rejection with great accuracy (p less than 0.01). The heart-to-lung ratio of antimyosin scintigraphy corresponded exactly to the various stages of rejection (p less than 0.001). High-dose steroids led to a clear reduction of the ratio in 26% cases. Peroxidase staining showed typical locations of the antibody, depending on the grade of rejection (p less than 0.001). Considering the results of pathology in this transplantation model, relying on endomyocardial biopsy alone in a clinical setting may not seem advisable. Although the results of this study must be confirmed clinically, the simultaneous use of cytoimmunologic monitoring and fast Fourier transformation ECG may prove to be valuable to day-to-day monitoring for acute rejection in the early postoperative course. If both methods indicate the onset of an acute rejection, antimyosin scintigraphy and endomyocardial biopsy, respectively, should be performed to confirm and grade the suspected diagnosis.

[Lennert's lymphoma and glomerulonephritis]. / Lennert-Lymphom und Glomerulonephritis.

A 49-year-old man noticed a swelling below the left ear. The histological diagnosis was chronic lymphadenitis with a small cell epithelioid cell reaction. A short time later he developed oedema of the legs, proteinuria and elevated serum creatinine levels (1.89 mg/dl). Renal biopsy showed mesangioproliferative glomerulonephritis. Over the next two years the tumour in the left side of the neck gradually increased in size. Computed tomography showed a space-occupying lesion 5 x 7 cm in the vicinity of the left parotid gland, with evidence of infiltrative growth. Histological examination of the tumour after removal revealed epithelioid cell tissue with numerous lymphocytes, and led to the diagnosis of a lymphoepithelial lymphoma (Lennert's lymphoma), a T-cell lymphoma of low malignancy. Complete remission was achieved after four chemotherapy cycles (COPP schedule) in reduced doses (creatinine concentration 2.09 mg/dl, creatinine clearance 36 ml/min); creatinine clearance subsequently improved to 63 ml/min. Later, however, the tumour recurred and the patient went into terminal renal failure, dying four years after the lymphoma first appeared. The glomerulonephritis may conceivably have been a paraneoplastic phenomenon.

Contractility of the transplanted, denervated human heart.

The purpose of the study was to characterize the contractility of the transplanted human heart and to evaluate possible adverse effects of denervation or structural changes of the myocardium or coronary vessels. As an index of contractility, the linear slope k of the end-systolic pressure/dimension relationship during afterload increase with angiotensin II was determined by M-mode echocardiography in 34 heart transplant recipients and 20 healthy control subjects. Baseline findings for end-systolic diameter and systolic blood pressure were normal and similar in both groups, but the transplanted hearts performed at a significantly lower end-systolic wall stress (40.4 +/- 12 gm/cm2 vs 49.9 +/- 11 gm/cm2, p less than 0.001). Comparable increase of afterload was achieved in heart transplant recipients with significantly (p less than 0.001) less angiotensin II, which indicates increased vasoconstrictor sensitivity. Contractility index k did not differ between heart transplant recipients (12.95 +/- 4.9 mm/100 mm Hg) and control subjects (12.78 +/- 2.8 mm/100 mm Hg). This finding is consistent with a normal contractility of the transplanted, denervated human heart. Normal baseline contractility therefore is an intrinsic property of the intact heart, which is independent of autonomic neural control. Contractility was not compromised by increasing interval from transplantation or the presence of mild acute rejection or mild interstitial fibrosis. Mildly impaired contractility (k greater than 2 SD of k in control subjects) in four heart transplant recipients (12%) was neither associated with structural myocardial or coronary changes nor with rejection episodes or graft ischemic time. One may speculate that impaired contractility, which is present in a minority of heart transplant recipients, results from pretransplantation damage.

[Detection of acute graft rejection with Fourier transformation of the surface ECG in long-term follow-up of heart transplantation]. / Erkennung akuter Abstossungsreaktionen mit Fourier-Transformation des Oberflächen-EKG im Langzeitverlauf nach Herztransplantation.

Up to now, diagnosis of acute rejection after heart transplantation (HTx) has been based on endomyocardial biopsy (EMB), but there is the need for reliable noninvasive parameters. Spectral analysis of the surface ECG with fast Fourier transformation (FFT) has been shown to be useful for rejection monitoring in the immediate postoperative phase. We tested the method in the chronic phase after HTx: the QRS complex (2 bipolar leads, position tattooed with Indian ink) was repeatedly analyzed with FFT (segment size 120 ms, 512 points. Blackman-Harris window) in 38 patients for 4-36 months after HTx. In mean intervals of 3 months, 254 checkups with FFT and EMB were performed on the same day. EMB revealed 28 acute rejection episodes in 21 patients, and ongoing rejection was diagnosed in 17 EMB. During rejection the frequency content of the QRS complex between 70 and 110 Hz increased in 25/28 rejection episodes (89%) and in 15/17 ongoing rejection cases, whereas in the time domain no specific changes could be seen. The QRS-amplitudes did not reliably indicate rejection, but decreased slowly during follow-up. After therapy the spectral changes disappeared within weeks. No signs of acute rejection were evident in 209 EMB: in 156/209 frequency analyses (77%) the spectra were constant, in 45/209 cases the frequency content increased, and eight analyses could not be evaluated. As the number of rejection crises decreased in the first postoperative months, there was an increasing number of false positive FFT analyses (positive predictive value 35%). Thus, a change of frequency content requires control by biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of HLA-D subloci DR and DQ by breast carcinomas is correlated with distinct parameters of favourable prognois.

The expression of HLA-D region products HLA-DR, DQ and DP by primary breast carcinomas was examined for its relationship to standard prognostic parameters. A positive correlation was found between the expression of HLA-DR and the differentiation state of the tumour (P = 0.02) and the expression of progesterone receptors (P = 0.002), two parameters which are associated with good prognosis and with each other. No correlation was seen between these parameters and the expression of HLA-DQ or HLA-DP. In contrast, tumour diameter was inversely correlated with the expression of HLA-DQ (P = 0.0004) although no association was observed between this parameter and HLA-DR expression. Essentially all HLA-DQ positive tumours had a diameter of less than 2 cm although these represented only 50% of the tumours of this size examimed. These data show that in breast carcinomas HLA class II expression is correlated with several distinct parameters of good prognosis and suggest that HLA-DQ expression may define a subtype of T1 tumours.

Fatal infantile mitochondrial cardiomyopathy and myopathy with heterogeneous tissue expression of combined respiratory chain deficiencies.

A 5-month-old boy died of progressive heart failure that started at the age of 3 months. Autopsy revealed a mitochondrial cardiomyopathy and a mitochondrial myopathy of the limb muscle and diaphragm. Cytochemically random defects of cytochrome c oxidase were visualized by light and electron microscopy in the diaphragm and especially the heart muscle, the limb muscle showing a diffuse attenuation whereas the liver and kidneys reacted normally. The activities of NADH-dehydrogenase (complex I) and cytochrome c oxidase (complex IV) were severely diminished (20% residual activity of controls) in the skeletal and heart muscle. In the heart, succinate cytochrome c reductase (complex II/III) was additionally decreased to the same degree. Loss of cytochrome c oxidase activity was based on a reduction of both mitochondrial and nuclear derived subunits in the heart and diaphragm as revealed by immunohistochemical analysis, whereas the limb muscle showed a normal immunoreactive protein content. The results illustrate heterogeneous tissue expression of respiratory chain enzyme defects and demonstrate that a cardiomyopathy may be the leading presentation of a mitochondrial disorder in early infancy.

Antimyosin monoclonal antibodies for early detection of cardiac allograft rejection.

Sixty-eight indium 111-labeled antimyosin Fab-DTPA imaging studies (0.5 mg intravenously with a radioactivity of 65 to 75 MBq) were executed on 37 of 116 patients undergoing heart transplantation to assess diagnostic accuracy and clinical utility. As controls, 21 patients with cardiomyopathy (n = 8), unstable angina (n = 9), and myocardial infarction (n = 4) were selected. After 48 hours, single photon emission computed tomographic images were evaluated visually, and heart/lung ratios were measured, using the "region of interest" technique. They were compared with echocardiographic and endomyocardial biopsy results. In 40 studies a heart/lung ratio less than or equal to 1.6 corresponded to a negative biopsy result in 98% (40/41). Echocardiography enabled correct identification of 95% of the patients with normal biopsy findings. In 91% (22/24) a positive biopsy finding correlated with a heart/lung ratio greater than 1.6 including 20 mild rejections, but in only 64%, with an increase in wall thickness and/or decrease of fractional diameter shortening seen on echocardiogram. In addition, the various stages of rejection episodes determined the amount of the heart-lung ratio. There was a significant relationship between the histologic findings and the antimyosin uptake. In 13 patients a second investigation was performed after rejection therapy. All patients had a negative biopsy result, and the heart/lung ratio decreased to normal ranges (less than or equal to 1.6). Five antimyosin antibody studies were excluded, as in these cases, negative uptake results were found during rejection therapy with high-dose steroids. The overall sensitivity was calculated at 93% and the specificity at 98%.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of rejection episodes on the development of coronary artery disease after heart transplantation.

Since 1981, 77 of 116 patients undergoing heart transplantation (HTx) have survived from 6 months to 8 years. Graft control involved a total of 871 endomyocardial biopsies (EMB) and 141 angiographies. Sixteen patients developed coronary artery disease (CAD) manifesting itself 7-60 months after HTx (20.7%). These patients (15 male, 1 female) experienced multiple rejection episodes (RE) and more than half suffered from hypercholesterolaemia and hypertension (n = 10). A mean rejection score (Billingham grading) of greater than 1 (mean = 1.6 +/- 1.1) was calculated in all patients with CAD at the time of angiography or autopsy. By contrast, the mean rejection score ranked less than 1 in patients with undetectable or resolved CAD (means = 0.4 +/- 0.38). This rate is not remarkably different from the rejection score in patients (n = 61) without CAD (mean = 0.2 +/- 0.4). The 8 patients alive (56 +/- 18 months) showed a low number of RE/year (mean = 1.1 +/- 0.4) compared with means = 1 +/- 0.9 in patients without CAD. Eight patients expired within a short period (mean = 31 +/- 26.9) and had a significantly higher number of RE/year (mean = 4.3 +/- 2.9; P less than 0.01 vs. no CAD, CAD alive). Autopsy (n = 6) and angiographic studies (n = 46) demonstrated diffuse, concentric, obliterative arterial disease in all vessels (type A) in 6 patients (RE/yr: mean = +/- 5.5 +/- 2.3), single stenoses in major coronary vessels (type B) in 7 patients and ordinary atherosclerosis (3-vessel disease) comparable to ischaemic heart disease (type C) in 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)