[Early diagnosis of endometrial cancer]. / Früherkennung des Korpuskarzinoms.

The increasing morbidity rate of endometrial carcinoma has prompted the development of methods of examination suitable for the detection of asymptomatic carcinoma of the endometrium. Commercially available instruments for collection of specimens from the uterine cavity employ washing, aspiration or curettage techniques. Under clinical testing conditions, these instruments have been shown to have a high cytomorphological accuracy, namely 80%. It has not yet been possible to reproduce this high level of accuracy under outpatient conditions. Hence, utilization of these techniques as screening methods in a cancer prevention programme for the early detection of endometrial cancer cannot be realized at the present time. Prerequisites for their use would be further technical improvements in instrumentation and a sufficient level of expertise in the assessment of endometrial smears by differential cytological techniques.

Follicle growth in the ovary of the rabbit after ovulation-inducing application of human chorionic gonadotropin.

The growth of tertiary follicles, i.e., the proliferation of cells in the stratum granulosum and in the capillary network of the theca interna, after injection of ovulation-inducing human chorionic gonadotropin (HCG), was investigated in the rabbit by means of autoradiographic and morphometric methods. Based on the frequency distribution of follicles with different sizes and on the labeling index (LI) of granulosa cells as a function of follicle size and of time prior to and after HCG stimulation, two groups of tertiary follicles can be distinguished: growing (250-900 micron in diameter) and mature (greater than 900 micron in diameter) elements. The growth of both groups is influenced by the release of gonadotropins. After HCG stimulation, follicles belonging to the first group grow rapidly. During, and a short time after ovulation, almost all non-ruptured follicles larger than 600 micron in diameter become atretic. Within 35-50 h the ruptured and atretic mature follicles (greater than 900 micron in diameter) are replaced by follicles out of the group of growing follicles. From these results the following concept for regulation of follicle growth is derived: In principle, all growing follicles possess the potential to develop into mature follicles. When a sufficient number of mature follicles is generated, these mature follicles determine the number of succeeding growing follicles. Follicles that are not required for providing mature follicles become atretic as soon as they reach a diameter of 700 micron. When the majority of mature follicles is lost during ovulation (by rupture or atresia), this inhibition regulated by mature follicles is abolished, and all of the growing follicles again are capable to develop into mature follicles. The relative amount of capillaries in the theca interna of growing and mature follicles remains constant with increasing follicle size. This means that the capillary network grows parallel to the increasing size of follicles. No differences are found between intact and atretic follicles; advanced atretic follicles were excluded from this study. The labeling index (LI) of granulosa cells in the stratum granulosum and of endothelial cells in the theca interna, as a function of follicle size and of time after HCG stimulation, are closely correlated. A change in the LI of granulosa cells is usually followed with a certain delay by a similar alteration of the LI of endothelial cells in the theca interna. This suggests that granulosa cells have a certain regulatory function on capillary growth.

Diagnostic problems in differentiation of uterine sarcoma.

A 35 year old patient underwent radical abdominal hysterectomy for uterine malignancy, which was confined on curettage material. Histological examination revealed a wide range of atypical mesenchymal components. For further specification ultrastructural examination was performed. Intracytoplasmic microfilaments, sometimes arranged in bundles, were a feature common to all tumor cells despite their shape and arrangement. The tumor thus was classified as a polymorphcellular fibrosarcoma. The patient is now free from recurrences after a period of two years.

[Invasive squamous cell carcinoma of the uterine cervix three years after cryosurgical treatment of a benign ectopy (author's transl)]. / Kollumkarzinom 3 Jahre nach kryochirurgischer Behandlung der Portio vaginalis uteri.

Report on a 33 years old para 4, who developed invasive squamous cell carcinoma of the cervix three years after cryosurgery for a large ectopy of the ectocervix. The carcinoma developed under an intact layer of normal superficial epithelium. The pap smears were negative at yearly intervals until a positive smear was obtained from a small iodinenegative area. Cases following cryosurgery appear to require careful follow-ups.

[The optimal treatment of carcinoma in situ of the uterine cervix (author's transl)]. / Zur optimalen Therapie des Carcinoma in situ der Portio

The results of treatment of carcinoma in situ of the uterine cervix in 380 patients seen between January 1, 1966 and December 31, 1973 are reported. There were 134 women age 40 or less. There were 246 patients age 40 or older. In 334 patients a total hysterectomy with removal of a vaginal cuff was carried out (87.9%). A large therapeutic cone biopsy was done in 46 patients (12.1%). In the 334 patients treated by hysterectomy, 2 recurrent carcinomas in situ of the vaginal vault were observed (0.6%). In 16 of the cases treated by conization later suspicious colposcopic and/or cytologic findings made hysterectomy necessary. In 5 of these cases a recurrent carcinoma in situ was likely. The postoperative morbidity after total hysterectomy was low. There was no postoperative death. The total vaginal hysterectomy with removal of a vaginal cuff is recommended as treatment for carcinoma in situ of the uterine cervix in order to avoid the diagnostic difficulties in the follow-up after treatment by conization and because of the low recurrence rate after hysterectomy. Conservative treatment should only be employed in patients who desire later child bearing. tthe psychological stresses of the continually required follow-up examinations after conization should not be underestimated.

[Light and electronmicroscopic examinations on granulosa and theca of preovulatory and freshly ruptured follicles of human ovaries (author's transl)]. / Die differenzierte Struktur und Funktion der Granulosa und Theka in verschiedenen Follikelstadien menschlicher Ovarien. 2. Der reifende, reife, sprungreife und frisch geplatzte Follikel

In a first paper, the structural and functional relationship of granulosa and theca of follicles during early development stages was reported. On the special question of whether and from which moment these two tissue formations are involved in the steroidbiosynthesis, our electronmicroscopic examinations have given a further insight to this. Neither the granulosa nor the theca folliculi of primordial, primary and secondary follicles show definite morphologic submicroscopic criteria of the steriodbiosynthesis. In the resting tertiary follicle, the electronmicroscopy defines the theca cells as steroidbiosynthetic active cells, whereas the granulosa cells of this stages of follicle demonstrate the morphologic characteristics of protein-synthetic active cells. Our, under physiological conditions, systematically conducted light and electronmicroscopic studies of preovulatory and freshly ruptured follicles showed remarkable structural changes in the granulosa, as well as in the theca folliculi. For the follicle granulosa cells of the preovulatory follicle, the studies could demonstrate a structural transformation process of proteinsynthetic active to steroidbiosynthetic active cells. This transformation process can be seen in the nucleus. Especially recognizable is the continuous change from rough to smooth endoplasmatic reticulum in the cytoplasm of most of the follicle granulosa cells, which apart from that, often displayed whorle-like formations. Furthermore, we noticed striking changes of the paraplasmatic structures, especially of the fat, present in various stages in the cytoplasm of the follicle granulosa cells. We also noticed large mitochondria, which showed a lot of vesicular cristae. Numerous existing Golgi-fields contained many little homogenous fat-like droplets, which were surrounded by a thin osmiophilic membrane. This recognizable transformation process of the proteinsynthetic active granulosa cells to the steroid cells is quite completed in freshly ruptured follicles, according to our examinations. Although the theca cells have already been defined submicroscopically in the resting tertiary follicle as steroidbiosynthetic active cells, we see in this cellgroup in the preovulatory, as well as in the freshly ruptured follicle a remarkable conspicuous size-increase of the mitochondria. Apart from that, there are wide areas which are solely occupied by smooth endoplasmatic reticulum, whereas other structures, for example fat, are scarely seen. As our examinations have shown, there is a close relationship between the transformation process in the granulosa and the theca of preovulatory follicles and the theca of preovulatory follicles that, the increasing concentration of progesteron in serum, which begins prior to the ovulation can be regarded as a product of the follicle granulosa cells being transformed to steroid cells.

[Follicular granulosa cells in relationship to steroid biosynthesis in the periovulation phase]. / Die Follikel-Granulosazellen in Beziehung zur Steroid-Biosynthese in der Periovulationsphase

PIP: Systematic electron microscopic and enzyme histochemical investigations were carried out to study the steroid biosynthetic function of follicle granulosa cells in human ovaries with 18 regularly menstruating patients as the subjects. The findings strongly suggested transformation of granulosa from protein to steroid-biosynthetically active tissue in human ovaries in the periovulation phase. Submicroscopic observations revealed transformations from rough to smooth endoplasmic reticulum and finely differentiated fat. Increase of enzyme activity in steroid metabolism was obvious in this tissue layer. The transformation process begins before ovulation and, according to the findings of this study, is closely related to the course of gonadotropin concentration. The study also concluded that serum progesterone concentration, which begins before ovulation, is produced during transformation of the follicle granulosa cell into steroid cell.^ieng

[Light- and electronmicroscopic examinations on granulosa and theca of primordial-, primary-, secondary- and resting tertiary follicles of human ovaries (author's transl)]. / Die differenzierte Struktur und Funktion der Granulosa und Theka in verschiedenen Follikelstadien menschlicher Ovarien.

Light- and electromicroscopic examinations were performed on granulosa and theca of primordial-, primary-, secondary- and resting tertiary follicles of human ovaries. These examinations were intended to clarify how far correlation exist between the structural components of the different tissue formations of the follicles and their determined functions. Remarkably many intraplasmatic filaments were found in the cytoplasm of granulosa cells of primordial-, primary- and secondary follicles. In the resting tertiary follicles the electronmicroscopy defines the majority of the follicle granulosa cells as proteinsynthetic active cells with abundant rough endoplasmatic reticulum. Most of the nuclei contain several nucleoli. An interesting finding compared with the granulosa cells of earlier developing stages of the follicle is the presence of single or grouped fat droplets in the cytoplasm, whereas metaplastic structures like filaments and/or microtubules are rare. The theca cells aroung the primordial-, primary- and secondary follicle were characterized by electromicroscopy as typical stroma cells. These cells of the resting tertiary follicles in the theca interna and externa show characteristic submicroscopic criteria of active steroidbiosynthesis. Their cytoplasm is especially rich of smooth endoplasmatic reticulum about from that there are tubular mitochondria and diffus fat droplets. Regarding the functional meaning of the different tissue formation of the follicles the existence of filamentous material in the membrana granulosa of primordial-, primary- and secondary follicles demonstrates an important finding. Apparently the presence of these metaplastic structures in the follicle granulosa cells play a role in the formal development of the zona pellucida and the Call-Exner-bodies. The structural organisation of the granulosa cells of resting tertiary follicles shows a high proteinsynthetic activity which plays a role in the metabolism of oocyte and the follicular fluid production. So far there are no definite submicroscopic criteria for steroidbiosynthesis. The structural differentiation of the normal stroma cells around primordial-, primary- and secondary follicles leads to definite submicroscopic steroidcells in the resting tertiary follicle. According to our results the process of the transformation of follicular granulosa cells in steroidbiosynthetic active cells in the resting tertiary follicle is not complete.

[Therapy of ovarian stage-Ia carcinoma (review of 103 cases)]. / Zur Therapie des Ovarialkarzinoms im Stadium Ia. (Eine Ubersicht über 103 Fälle)

103 cases of carcinoma of the ovary stage IA are presented, which have been operated upon at our clinic from 1944 to 1970. The 5 year cure rate of the 94 cases which had been treated until 1967 was 67%. 10 of the eleven patients who had been operated upon by preserving the opposite ovary -- in 4 cases additional radiotherapy was given -- were free of carcinoma after 5 years. When radical operation was performed (bilateral salpingo-oophorectomy with or without removal of the uterus) the 5 year cure rate was 55%, with additional postoperative radiation 70%. This difference is not statistically significant. -- The therapy of choice of cancer of the ovary stage IA should be bilateral salpingo-oophorectomy and total hysterectomy with additional radiotherapy. -- Instead it may be justified in some cases to preserve the opposite ovary.