[Rational radiologic diagnosis of breast carcinoma]. / Rationelle radiologische Diagnostik des Mammakarzinoms.

For a favourable prognosis breast cancer must be diagnosed as early as possible. Among available imaging modalities (mammography, sonography, DAS, thermography, CT, MR) only mammography has been shown to produce a significant reduction in mortality, but unfortunately only for women above 50 years of age. The technical requirements, and the standard techniques and the appearance of benign and malignant breast tissues are described. The routine use of ultrasound in the evaluation of palpable masses remains controversial. Ultrasound technology is incapable of detecting early-stage cancers reliably. By "using dynamic MRM", i.e., repetitive imaging of the same slice before and at short time intervals after the injection of a contrast medium, high sensitivity and specificity is achieved in detecting breast cancer of different histologies. MR-mammography should be used in all cases where there is a discrepancy among radiographic, sonographic or clinical findings.

[Surgical therapy strategies in carcinoma in situ of the breast]. / Operative Therapiestrategien beim Ca in situ der Mamma.

The surgical treatment of carcinoma in situ of the breast depends on the histological type. After detecting a lobular carcinoma in situ (CLIS) either an intensive (aftercare) follow-up is recommended or a bilateral mastectomy. The choice for one of these two very different forms of therapy can be done only after intensive psychological dialog with patient. The reason for the different forms of further treatment is the multicentric and often bilateral occurrence of CLIS and the potential risk of developing an invasive cancer. The therapy of the ductal carcinoma in situ (DCIS), which often spread out in a segment of one breast, is the total excision of the lesion with clear margins. The Van Nuys Prognostic Index depending on the histological results (tumor-diameter, thickness of clear margins, pathocytologic classification) indicates further treatment such as radiotherapy or mastectomy to lower the chance of local recurrence.

Early cancer detection programmes for women at high risk for breast and ovarian cancer: a proposal of practical guidelines.

Women from families with multiple breast and/or ovarian cancers may be at increased risk to develop breast/ovarian cancer themselves. Due to personal experience with family members having these diseases they are anxious and ask for specific prophylactic measurements or treatment. The detection of two susceptibility genes, BRCA1 and BRCA2, has given insight into the genetic background of part of the familial breast/ovarian cancer syndromes. This has led to an increased demand in genetic counselling, testing, and early cancer detection programmes. Prospective data from early cancer detection programmes in this high risk population are yet not available. Based on data from epidemiological risk studies, breast and ovarian screening programmes and follow up data from breast cancer trials recommendations for an early cancer detection programme have been summarized. At the present these recommendations are tested in a prospective trial.

Clinical impact of detection of loss of heterozygosity of BRCA1 and BRCA2 markers in sporadic breast cancer.

The development of familial and sporadic breast cancer is based on genetic alterations of tumour-suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation. To investigate LOH of BRCA1 (17q21) and BRCA2 (13-q12-13) in sporadic breast cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for detection of microsatellite polymorphisms was applied. A total of 137 breast cancer and 15 benign breast specimens with matched normal tissue were examined. Fluorescent-labelled PCR products were analysed in an automated DNA sequencer (ALFTM Pharmacia). Losses at both loci were correlated with different histological types, age, tumour size, lymph node status, grading and steroid hormone receptor expression, [SHR: oestrogen receptor (ER), progesterone receptor (PgR)]. For BRCA1 (D17S855, THRA1, D17S579) losses could be detected in invasive ductal carcinoma (IDC; n = 108) in 32-38%, invasive lobular carcinoma (ILC; n = 19) in 21-42% depending on the marker applied, but not in benign breast tumours (n = 15). Losses of BRCA1 markers correlated with larger tumour size, higher grade, and PgR expression. For BRCA2 (D13S260, D13S267, D13S171) losses could be detected in 108 IDCs in 30-38%, in 19 ILCs in 17-39% depending on the marker applied, but not in benign breast tumours. Losses of BRCA2 markers correlated only with higher grade. Microsatellite analyses combined with detection of fluorescent-labelled PCR products by an automated laser DNA sequencer can be used for routine determination of LOH. In sporadic breast cancer, LOH of BRCA1 of BRCA2 does not add decisive prognostic value as stated for familial breast cancer.

[Techniques of breast-conserving therapy in breast carcinoma]. / Techniken der brusterhaltenden Therapie beim Mammakarzinom.

Partial mastectomy usually has been subcategorized into lumpectomy, wide excision, or segmental mastectomy. This operation is generally used in tumors less than 4 cm in diameter. Local recurrences usually occur near the previous excision site and are reduced, if the initial resection margins are free of tumor. Partial mastectomy has obvious psychologic advantages for the patient but must be performed correctly to avoid unacceptable distortion of the breast. The axillary dissection should be done through a separate incision. The steps of the surgical procedure are described in detail.

[Locoregional intra-arterial chemotherapy of primary incurable local recurrence of breast cancer]. / Die lokoregionäre intraarterielle Chemotherapie bei primär inkurablen Lokalrezidiven eines Mammakarzinoms.

Approximately one third of all local recurrences of breast cancer are incurable at the time of diagnosis. Locoregional intraarterial chemotherapy is one of the new therapy modalities besides laser therapy and combined radiotherapy/hyperthermia. The results of a phase I-II study, in which 15 patients with advanced, partly pretreated local recurrences as well as 2 patients with T4N2/N3 tumours were included, are reported as follows. All in all, 39 superselective intraarterial chemotherapy courses were carried out. Mitomycin (10 mg) and Mitoxantrone (25 mg) were infused over 90 min. The side effects due to the catheter system were two haematomas and one thrombosis attributed to an insufficient heparin dose. Locally, the chemotherapy was well tolerated. One severe systemic side effect, a leucopenia WHO 4 degrees was observed. Nausea, thrombocytopenia and alopecia rates were low (7 x nausea 1 degree, 5 x thrombocytopenia 1 degree, 2 x thrombocytopenia 2 degrees, 2 x alopecia 1 degree). 6 Complete remissions (3 x pCR, 3 x cCR) as well as 6 partial remissions and 5 no changes were found. We believe that this method, because of the low side-effect profile and the temporary good results, represents a good alternative in otherwise incurable locoregional recurrence of breast carcinoma and in specified cases of locally advanced disease. 1 degree and 2 x thrombocytopenia 2 degrees, 2 x alopecia 1 degree). Altogether, 6 complete remissions were found (3 x cCR, 3 x pCR), 6 partial remissions with 4 x no change occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunohistochemical investigations of estrogen receptors in normal and neoplastic squamous epithelium of the vulva.

Atrophic disease of the vulvar epithelium can be treated with steroids, but carcinoma of the vulva cannot be influenced with any hormone therapy. Seventy-one vulvar specimens were tested for estrogen receptor (ER) content by means of immunohistochemistry. Slight ER staining was found in nonkeratinizing squamous epithelium in 17 of 22 cases. A weak ER reaction in the basal and parabasal layers was found in only 2 of 17 specimens of keratinizing squamous epithelium. However, no ER was found in any neoplastic tissue of the vulva or the adjacent stroma. The loss of ER in neoplastic cells could explain the clinical experience that antihormonal treatment of vulvar carcinomas produces no appreciable improvement.

Immunohistochemical investigations of steroid receptors in normal and neoplastic squamous epithelium of the uterine cervix.

The proliferation of squamous cells of the vagina and cervix uteri is induced by steroid hormones during the menstrual cycle. However, carcinoma of the cervix cannot be influenced by any hormone therapy. Forty-four different cervical specimens (different days in the menstrual cycle of healthy women and those with dysplastic lesions and carcinomas of the cervix) have been tested for estrogen (ER) and progesterone (PR) receptor protein content by means of immunohistochemistry. The ER content of the squamous epithelium depends upon the menstrual cycle: in the early proliferative phase cells of all layers are negative. In the midphase of proliferation the basal and parabasal layers become positive, and in the secretory phase positive cell nuclei can be found up to the superficial layers. A weak reaction to ER staining is found only in mild dysplastic lesions of the uterine cervix; severe dysplastic forms and invasive carcinomas were all negative. No positive PR was found in any squamous cell tissue. Stroma cells of the uterine cervix showed different straining intensity for ER and PR, regardless of the menstrual cycle. The loss of ER in the neoplastic cell could be an explanation for three clinical experiences: premenopausal patients have no tumor progression of the cervix uteri despite normal ovarian function; the duration of survival shows no relation to the receptor status of cervical carcinomas; and antihormonal treatment of cervical carcinomas produces no appreciable therapeutic success.

[Nonpuerperal mastitis. 3 possible causes including mammography correlates]. / Nonpuerperale Mastitis. Drei mögliche Ursachen einschliesslich mammographischer Korrelate.

We present three cases of non-puerperal mastitis including the corresponding mammographies to illustrate three possible causes: mastitis with abscess, artificial mastitis and breast carcinoma. The clinic picture did not reveal the cause of mastitis. Ultrasonography and mammography should be performed early in the evaluation of non-puerperal mastitis.

[Prenatal diagnosis of disorders of fetal kidney function--a critical analysis of 95 cases]. / Pränatale Diagnose fetaler Nierenfunktionsstörungen--eine kritische Analyse von 95 Fällen.

Ninety-five gravidae were examined at Düsseldorf University Gynecological Clinic for assessment of the fetal renal system. Suspected disorders were ruled out in 33 cases by sonography. Urogenital malformations without major loss of function were diagnosed in 25 fetuses. The prognosis was unfavorable in 15, and 22 fetuses had other disorders. In 5 out of 22 infants on whom autopsy was performed, the kidneys were found to be normally developed, contrary to the sonographic diagnosis. However, all five of these infants had anomalies of the umbilical artery. It is well known that cases of anhydramnios in the first half of pregnancy have a poor prognosis. In order to assess such cases better, the authors consider the following examination procedure appropriate: 1) filling with amniotic fluid; 2) Lasix provocation test; 3) thorough sonographic examination of the fetus; 4) karyotyping; and 5) identification of maternal infections. It is at present impossible to say whether there is a statistical relationship between changes in the umbilical cord and disorders of renal function.

Hypomyelination neuropathy in a female newborn presenting as arthrogryposis multiplex congenita.

A female newborn delivered at 32 weeks of gestation presented with multiple joint contractures consistent with arthrogryposis multiplex congenita (AMC). The girl died after a four days course of severe respiratory distress. Autopsy revealed slightly hypoplastic and immature lungs with acute necrotizing bronchopneumonia, and marked consecutive hypoxic brain lesions with severe periventricular haemorrhages. The peripheral nerves including the cranial and spinal nerve roots showed a hypomyelination radiculoneuropathy with well preserved axons and a normal content of Schwann cells. In the skeletal muscles of the arms and legs some fascicles of the extensors were replaced by lipomatous tissue. Since myelination of the white matter in the central nervous system was adequate to the age, this case represents an exclusive maturation disorder of the peripheral myelin sheaths that may be considered causal for AMC.

Inhibition of peripheral deiodination of 3, 5, 3'-triiodothyronine: an adverse effect of propylthiouracil in the treatment of T3-thyrotoxicosis.

An inhibition of peripheral conversion of T4 to T3 is thought to be of benefit in the treatment of thyrotoxicosis. Therefore, propylthiouracil (PTU) has been considered to be more effective in the therapy of hyperthyroidism than methimazole, since the former has the additional peripheral effect of decreasing the conversion of T4 to T3, From in vitro studies PTU is known, however, to inhibit the deiodination at the 5' as well as at the 5 position of the iodothyronine molecule. To study if PTU blocks degradation in T3 in vivo as well, the effect of PTU on thyroid hormone concentrations in serum and liver tissue during a constant and high administration of T4 or T3 to rats was followed. It was shown that PTU clearly inhibits T4 and reverse T3 degradation. Moreover, simultaneous treatment of the rats with T3 and PTU resulted in a significantly higher increase of T3 concentration in liver tissue (11.5 ng/g liver vs 5.6 ng/g liver) and serum (615 ng/di vs 345 ng/dl) than with T3 alone. This effect may be explained by an inhibition of the T3 degradation by PTU in vivo as well. Provided the results obtained from these animal experiments can be applied to the situation in man, the inhibition of peripheral deiodination could have an adverse effect at least in the treatment of T3-thyrotoxicosis.