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To assess high-dose carboplatin chemotherapy with or without paclitaxel with filgrastim mobilized peripheral blood progenitor cell (PBPC) support in a phase I/II study, a total of 21 patients with mostly chemonaive disease received four cycles of high-dose chemotherapy. Cycle 1 (cyclophosphamide, 6 g/m2) was followed by two cycles of carboplatin (1600 mg/m2 or 1800 mg/m2). Cycle 4 consisted of carboplatin (1600 mg/m2), etoposide (1600 mg/m2), and melphalan (140 mg/m2). Further chemotherapy intensification was achieved by adding paclitaxel (175 mg/m2) to all cycles with a fixed carboplatin dose (1600 mg/m2). Ototoxicity was dose-limiting for escalation of sequential cycles of carboplatin. Grade 2 and grade 3 ototoxicity, hearing loss not requiring a hearing aid, or hearing loss correctable with a hearing aid, was observed with carboplatin at 1800 mg/m2. The maximum tolerated dose (MTD) of sequential carboplatin, therefore, was identified in this study as 1600 mg/m2. After cycles 1, 2, 3 and 4 the median duration of leukopenia (

We studied 52 patients with lobular carcinoma in situ (LCIS) of the breast, tissue being available from both breasts in 46 patients. Detailed histological examination of the tissue was combined with specimen radiography. By this technique, six invasive cancers were detected within 2 years of the primary diagnosis. five of these six carcinomas were clinically occult and were not suspected at specimen radiography. Three other invasive cancers were discovered 4 years, 7 years, and 10 years after diagnosing LCIS. The extent of the LCIS in the primary biopsy was the only feature which gave a guide to the possible presence and location of an occult invasive lesion.

The application of high estrogen doses (up to a total of 25 mg of ethinylestradiol over five days) resulted in marked endometrial edema with stromal lacerations and severe hyperemia, together with a retardation of the secretory transformation by 3–4 days. There were disturbances both of glandular mucus production and of reticular fibre structure in the second half of the cycle. The similarity of these findings to the atypical endometria of infertile women and to the endometrial changes seen in rhesus monkeys given postcoital doses of estrogen suggest that the changes constitute the morphological basis for the inhibition of nidation by the „morning-after pill“.

Breast diseases in 792 women were studied by biopsy and histological evaluation. In all subjects glucose tolerance was examined by OGTT (100 g glucose). The diabetes frequency of 22% in 326 women with breast cancer was compared with the frequency in women with fibroadenoma (n = 101), papilloma (n = 80), fibrocystic disease (n = 107), lipoma, granuloma, fibrosis (n = 88), papilloma with proliferation (n = 32), mastopathy with proliferation (n = 33) and carcinoma in situ lobulare (n = 11). The statistical evaluation was done with an electronic data processing system. We used matched pairs according to age, height and weight. Diabetogenic factors like age and overweight were thus allowed for. These comparative statistics showed a frequency of diabetes twice or three times higher in women with breast cancer. This result cannot be regarded as a consequence of age, overweight and menopause. In groups with fibroadenoma, fibrocystic disease and lipoma, we found glucose tolerance in 1-3%, whereas the group with proliferation (including carcinoma in situ) showed an incidence of 7%. The remarkably high incidence rate of 14% in women with papilloma can be explained by the higher age and the more frequent obesity in this collective.

Breast duct obliteration and periductal elastosis were studied in 100 breast carcinomas with a maximum diameter of 20 mm or less. Seventy percent of all tumours and 90% of lobular and tubular carcinomas had obliterated ducts with radial scars at the centre of the lesion. Obesity, parity and diabetes mellitus had no apparent association with duct obliteration and periductal elastosis. The striking two peaks in age distribution suggest the presence of endocrine influences. Duct obliteration with periductal elastosis occurs where the breast shows most changes during development and involution making this the high risk zone for carcinogenesis.

In three girls, aged 14, 15 and 16 years, the chromosome analysis revealed a morphologically abnormal, enlarged X-chromosome resembling in size and centromere position the chromosome no. 2. The translocation points were different in all three cases. The Barr-bodies were enlarged. In two girls a 45,X mosaicism (25% and 10%) was found in lymphocyte cultures.The length at birth was 43, 47 and 48 cm, and none of the girls was born before term. The main clinical abnormalities in all three cases were a marked growth retardation, slight morphological dysplasias, lack of sexual development and social immaturity. GH and Cortisol secretion during an insulin tolerance test were normal. LH and FSH were elevated and showed an exaggerated reaction on LH-RH. Oestrogens were low normal and androgens within the normal range. At laparatomy the gonads were found to be streak gonads. For two girls cell cultures of gonadal tissue were set up? the chromosome findings of which corresponded to those of the lymphocyte cultures.The abnormality of the gonosomes reported here seems to represent a special form of gonadal dysgenesis. Although the translocation points were different in the three patients and one had no mosaic, while the other two showed 45,X/46,XX mosaicism, the clinical and hormonal findings were nearly the same for all three girls.

Model biopsy specimens from 100 surgically removed ovaries were studied. They were matched in respect of size, dimensions and examination technique to 110 ovarian biopsy specimens obtained during laparoscopy from 60 amenorrhoeic patients. It was found that ovarian biopsy specimens with an all-round edge length of 4 to 5 mm permit usable conclusions in respect of the structure and hence also of the function of normal ovaries.

The Silverman needle biopsy for the diagnosis of suspicious palpatory findings in the pelvis in cancer patients is recommended. Occasional trauma cannot be avoided but is of secondary importance in the light of the diagnostic value of the procedure. The risk of treatment of a recurrence is much higher. Only 1 trauma necessitated long term antibiotic treatment because of a parametritis. Perforation or biopsy of the bladder or the rectum usually remained asymptomatic. The needle biopsy confirmed the diagnosis of recurrent tumor in 47 out of 74 patients with the first try. In 6 out of 10 patients the tumor diagnosis was confirmed by a second needle biopsy 2 to 3 months later. Two patients had a third negative biopsy. A total of 11 patients were saved from the fate of treatment of a clinically suspected cancer recurrence as confirmed by the subsequent clinical course over the next 1 to 6 years.

Among 412 female patients with fibroadenoma 30 (7.1%) were shown to have considerable epithelial proliferations, 7 (1.7%) carcinoma in situ (n = 4) or carcinoma (n = 3). All patients with carcinoma or carcinoma in situ in the fibroadenoma were older than 40 years of age. Differentiation of coarse or fine granulation of microcalcifications did not improve the accuracy of mammography. In 32% of fibroadenomas with epithelial proliferations similar changes were also found in the adjacent area of the breast whereas only in 8.8% of fibroadenomas without proliferative changes could epithelial proliferation be observed in adjoining areas. With increasing age the risk of carcinomatous degeneration in fibroadenomas rises to 17%. In multiple fibroadenomas only one of them may show carcinomatous changes whereas the others may appear unremarkable. This necessitates excision of all such tumours. In the same way as carcinomas fibroadenomas are most frequently found in the upper outer quadrant of the breast. Total resection including a surrounding layer of healthy tissue remains the treatment of choice.

42 of 86 patients with suppurated ovaries had primary isolated ovarian abscesses (PIOA), 44 secondary tubo-ovarian abscesses (STOA). Parts of ectopic endometrium in the abscess wall could be identified by serial sections in 23 PIOA. With Berlin-blue-staining was a special phenomenon in 28 of 42 PIOA demonstrated: a basal layer of hemosiderophages underlying the abscess membrane. Thus in 36 of 42 PIOA the histogenesis out of cystic ovarian endometriosis or other pathologic ovarian hematomas is assured. The PIOA is a typical major complication of ovarian hematomas, especially in cases of ovarian endometriosis caused by vaginal aplasia (gynatresia). Concomitant salpingitis in PIOA is therefore often better explained as secondary descending infection from pelveoperitonitis. Before laparotomy it is extremely difficult to diagnose PIOA on a clinical basis only. More than laboratory data helps this special consideration if an inflammatory adnexal mass could be or not the result of an ascending infection and if an ovarian endometriosis could exist. Besides the abscesses out of cystic ovarian endometriosis PIOA were observed after hysterectomies and complicated appendectomies possible due to the infection of traumatic ovarian hematomas. The only curative therapy for PIOA is surgery--as soon as possible. Antibiotics are poorly helpful. However the inefficacy of antibiotics usually gives the final indication for laparotomy. Knowing the usual etiology of PIOA out of pathologic (endometriotic) ovarian hematomas we have new guidelines in other clinical problems also: Thus every ovarian endometriosis has to be cured--hormonally or surgically; evacuation of endometriotic cysts during pelvic endoscopy is not a sufficient therapy, for the endometrium would be left in the ovary. During operations provocation of traumatic hematomas of the adnexa should be avoided.

The case histories of 263 patients with histologically proven endometriotic cysts of the ovaries (1962-1979) were studied. The diagnosis frequency increased continuously during the observation period. Most patients were aged 35-39 years. The admission diagnosis was rarely endometriosis. The clinical picture and the extent of the disease rarely showed correlation. At laparotomy 12% of the chocolate cysts had ruptured spontaneously (31 of 263) and half of the cysts ruptured during surgery without adverse effects on the postoperative course. The recurrence rate in patients treated by conservative surgery was 7%. The most frequent accompanying diseases were uterine fibroids (42%) and adenomyosis (42%). One third of the patients presented with bilateral endometriotic cysts. Further foci of endometriosis tissue were frequently found in the affected ovary (55%) and in the other pelvic organs (43%). Only 4% of the ipsilateral oviducts were closed at their fimbrial end, and only 10% showed signs of endosalpingitis. The incidence of infection in endometriotic cysts--formation of an isolated ovarian abscess--was between 8% and 18%, while the risk of carcinoma was less than 1%.

A total of 326 squamous cervical cancer patients treated by radical hysterectomy and lymphadenectomy in the Women's Hospital of Erlangen University were analysed according to their survival rates and to the histological examination results of their surgical specimens. A good relationship was found to exist between the pathological anatomical stage of the cancer, tumour volume, incidence of lymph node involvement, and survival rate. The result showed that good results from surgical treatment can be achieved even for very large cancers (Stage IIb) with a high frequency of lymph node involvement.

Twenty-eight small breast cancers and 17 other breast cancer specimens from which appropriate semi-thin sections had been prepared were examined by electron microscopy and special staining techniques for alterations in the basement membranes and the basal lamina. In each case disruptions of the basement membranes were invariably observed at the point of initial invasion. Two types of invasion were noted: (1) bud-like protrusions of intraduct cancer with disruption of the basement membranes at the point of invasion; (2) extensive basement membrane defects with single cancer cell invasion. Our study confirms that invasive breast cancer originates in intraductal or lobular carcinoma in situ.

Receptor assay results were compared with the ultrastructure of 127 breast cancers (112 primary tumors, six recurrent lesions, nine metastases). Tumors were considered to be receptor positive if the receptor levels were greater than or equal to 15 fmol/mg of soluble tissue protein. Most breast cancer had heterogenous cells with different grades of ultrastructural differentiation. a prevalence of well-differentiated cancer cells and an abundance of intracytoplasmic vacuoles had a significant correlation with a positive estrogen receptor status. The correlation was better than between malignancy grades and receptor content. The type of breast cancer and the menopausal status bore no relation to receptor content. Progesterone receptors were found in well-differentiated tumors of low malignancy.

Under the clinical preoperative diagnosis of mobile ovarian tumor, a laparotomy was done on a 24 month old female. The pyelogram had shown lateral displacement of the right ureter. The colon X-ray showed displacement of the cecum towards the liver. The ultrasound scan showed a unilocular cyst of 23 cm. diameter. At laparotomy a cystic duplication of the intestine in the iliocecal region of 23 cm. diameter was found and resected. The microscopic examination showed extensive benign metaplasia of the epithelium in association with a normal intestinal wall in all layers.

During laparoscopy we performed 132 ovarian punch biopsies in seventy one amenorrhoeic patients. With increasing experience, laparoscopic ovarian biopsy is a valuable element in the examination of amenorrhoeic patients. Biopsy specimens with an edge length of 4-5 mm for surface and depth can be obtained during laparoscopy under general anaesthesia without any great risk or difficulty. When performed bilaterally, it provides a representative picture of the cellular structure and function of the ovaries and thus makes a contribution to the prognosis of a disturbance in the endocrine regulating-circuit of ovarian function. In addition, the ovarian biopsy provides information about the basic gonadotrophic situation of the patient as a longitudinal section. It should be included in the synopsis of all endocrine and genetic parameters of a patient, particularly in clinic in which the morphological substrate of disturbed functions and apparent diseases is still examined.

421 patients with positive cytological cervical smears had fractioned surface scraping and curettage of the cervix. The clinical results equaled those of cone biopsy series: in 68,6% the histological diagnosis was exactly the same before and after treatment; in 17,5% there were minimal but clinically unimportant changes in histological assessment; in 10,6% the lesion had been completely removed by scraping and curettage. Thus 407 patients (96,7%) were treated in the same way as if the definitive histological diagnosis would have been known in advance. Only in 5 patients (1,25%) the first step was inadequate retrospectively and further treatment was necessary. Regarding the comparable clinical results the essentially poorer risks and costs favour the surface scraping and endocervical curettage against cone biopsy.

Tissue from contralateral breast was taken from 505 patients with invasive breast cancer. Every 5th patient had simultaneous carcinoma in the opposite breast, 7.7% (39/505) had invasive cancer, and 13.1% (66/505) had carcinoma in situ. Invasive cancers in the opposite breast were diagnosed at an earlier stage as compared with the neoplasm of the primary breast. However, 26% of the patients already had positive axillary nodes. The following risk indicators of the bilateral disease were found: age at time of diagnosis, histologic type of tumours, familial breast cancer, suspicious mammography, P2/DY-breast parenchymal pattern (Wolfe) and multicentric cancer of primary breast. Our findings support the proposal to consider bilaterality of breast cancer as a sign of systemic disease of the breasts, involving the ductal and lobular system within eight quadrants of a paired organ (Ober).

67 breast cancers with a maximum diameter of up to 10 mm on the histological section were retrospectively analysed according to the primary situation for medical consultation and the way to cancer diagnosis. 46 women presented themselves with clinical signs. 19 women had an anamnestical risk, whereas only two women were without any risks or symptoms. 34 tumourspecific clinical signs are followed by 25 tumourspecific mammograms. Eight small invasive carcinomas were detected only under the microscope, two of them in mastectomy specimens. Even small cancers, therefore, are mostly diagnosed from the patients themselves. The contribution of mammography is tremendous. Intensified systematic histological examination of biopsies and mastectomy specimens is mandatory especially in high risk patients.

484 women were operated between July 1, 1975 and December 31, 1978 for carcinoma of the breast. At least 18 months of follow-up was available until July 1, 1980. 273 patients were observed. 151 women had ancillary chemotherapy with cyclophosphamide, methotrexate, vinblastinsulphate and fluoro-uracil for six cycles. In an additional 60 patients chemotherapy was interrupted for post-operative radiotherapy after three cycles. The premenopausal patients were most helped by ancillary chemotherapy. This was not explained by more frequent mistakes in the treatment of post-menopausal patients. The post-operative radiotherapy did not bring a discernible additional advantage to ancillary chemotherapy. The best results were obtained in women who had no regional metastases in the lymph nodes independent on the size of the primary tumour.

Up until 31 December 1975, 1646 galactograms were made in 1150 female patients. The intentional segment resection and then the histologic preparation via complicated technique adapted to the excision was conducted 371 times. - In 99 out of 100 cases, an anatomic substrate could be found for the discharge. We were unable to discover any pathological finding to explain the discharge in only 3 cases (0.8%). Included in the benign processes were 170 cases of duct papillomas (45.8%). In these cases segment resection is also adequate therapy. - Approximately 8% of the excisions revealed cancer. In additional 12%, serious proliferative processes in the breast were found which should, at least, be kept under careful clinical supervision. - Galactography used in combination with an adapted surgical and histologic technique to diagnose not only a carcinoma which has evaded other methods of detection but also possible preliminary stages is a valuable procedure.

Of 75 scalene node biopsies 18 (24%) were positive. In 56 metastasizing carcinomas of the cervix 11 (20%) scalene node biopsies were positive. In primary inoperable cases (57%) or in recurrent spreading cases (54%) of carcinoma of the cervix the scalene node biopsy is valuable for the treatment plan. Irrespective of treatment the patients with metastases to the scalene node survived a mean of 10--11 months. The scalene node biopsy has few complications (6.7%). In the less than 3% carcinomas of the cervix confined to metastases in the lesser pelvis, the scalene node biopsy is not necessary. 2/3 of the prescalene lymph node metastases can be palpated by an experienced examinar.

Among 50 little starlike shadows in about 13,500 mammograms during the years 1973-1975 there were seven pictures proved histologically not to be cancers but "radial scars". We found no X-ray features to differentiate between scars and cancers. The uniform histologic picture of a centrally placed elastotic periductal scar with radial processes allowed however the exact differentiation. Especially significant for these radial scars is the storage of elastotic amorphous material around obliterated central ducts. Cystic atrophy or highgrade papillary epithelial proliferation in the surroundings may be combined with the central scar. Cancerous growth in this area is diagnosed without difficulty by the infiltration beyond the border of the star area.

Microcalcifications on the mammogram could be an important indication for an occult carcinoma. Up until 31 December 1976, we intentionally removed such grouped microcalcifications 218 times in a group of 17,523 examined females (32,245 mammographs). The selection was confirmed radiologically. The acquired material was then examined histologically via an complicated technique. We found 35 carcinomas and 89 proliferating mastopathies of which 34 required at least strict supervision and sometimes additional treatment. - With strict indications, one-third of the previously clarified cases revealed disorders requiring treatment. In over one-half of the cases, the films indicated nothing of a serious nature. It must, however, be noted that an existing cancer is not always discovered in spite of the intentional excision of microcalcifications. This only serves as an indirect indication.

Pirprofen was well absorbed by man, rhesus monkey, rat, and mouse after oral administration of a solution of 14C-labeled compound. The major route of elimination of radioactivity in all four species was renal, mostly in the form of metabolites. Twelve metabolites of pirprofen, accounting for 80% or more of the urinary radioactivity, were identified in the urine of the four species. The metabolic pathways of pirprofen involved oxidation to the pyrrole analogue, and oxidation of the pyrroline double bond to an epoxide, followed by opening of the oxirane ring to a trans-diol derivative. Scission of the pyrroline or pyrrole ring was also observed, leading to the corresponding aniline-type metabolite, part of which underwent subsequent acetylation. Conjugation of the propionic acid functionality with glucuronic acid was found to be extensive in the mouse, rhesus monkey, and man, but not in the rat. Conjugation with taurine was also observed in the rat and mouse.

Sonography can yield indirect visualization only of microcalcifications in the female breast. In order to obtain an image of the echo pattern of the grouped microcalcifications, it is essential that the device employed possesses suitable dynamic characteristics, and it is also necessary to employ the technique of additive tomography. The investigator must familiarize himself with the proper interpretation of reflex patterns. Microcalcifications cannot be detected via sonography with the same degree of accuracy as with the help of mammography. However, sonographic detection is easier if the microcalcifications are more closely grouped. Nevertheless, the authors were able to show in a small comparative series that grouped calcifications can be detected even without previous information of their presence.

Case report on a 80 year old patient with recurrent bleeding from a papillary adenofibroma of the uterus. The clinical and morphological findings of this case were compared with previous cases. A polypoid papillary adenofibroma of the endometrium is a benign mixed muellerian tumour.