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We present here seven cases of idiopathic multicentric Castleman’s disease (MCD) showing effusion at the initial clinical presentation. This series includes a high proportion of middle-aged and elderly females (5/7). Various autoantibodies were detected in six cases. Anemia (Hb 10 × 109/l) in three and thrombycytopenia (9/l) in five. Positivity for C-reactive protein or elevated erythrocyte sedimentation rate was recorded in all seven cases. Elevated serum IgG level (>2000 mg/dl) was recorded in only three cases. Elevated serum interleukin-6 level was recorded in all four cases examined. At the onset of disease, four cases were associated with idiopathic thrombocytic purpura. During the course of disease, one case each was diagnosed as systemic sclerosis + Sjögren’s syndrome (SJS) and SJS. Histologically, five lesions exhibited a mixed type of Castleman’s disease, and one case each exhibited a hyaline-vascular type and plasma cell type. The non-neoplastic nature of the B-lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. There were no human herpes type-8 virus-positive cells in any of the seven lesions. Good responsiveness to glucocorticoid therapy has been seen in all six cases treated. From a therapeutic perspective, it is important to discriminate this subtype of MCD.

This study was undertaken to establish reliable factors in order to identify chlamydial cervicitis among suspicious patients. Between January and December 2007, 406 patients who were suspected to have cervicitis due to clinical symptoms, were tested with polymerase chain reaction (PCR) for Chlamydia trachomatis (CT), vaginal pH and Nugent score (NS) in our University hospital and related clinics. During the same period, 67 patients who were diagnosed as having other sexually transmitted diseases ( Neisseria gonorrhoeae (NG), Trichomonas vaginalis, Condyloma acuminatum and genital herpes) were also made to participate in this study. Eighty-nine women (22%) were positive for CT PCR. Bacterial vaginosis (BV)-positive women were tested positive for CT PCR (75/288), significantly higher than those without BV (6/66, P = 0.01). In addition, under 20-years old women were positive for CT PCR (24/57), significantly higher than those who were over 30 years old (16/113, P = 0.001). The proportion of patients with high NS (>7) in CT, NG and T. vaginalis cases were 75/89 (84.3%), 22/27 (81.5%) and 11/14 (78.6%), respectively. Whereas the high NS of the C. acuminatum and genital herpes groups were recorded at 7/14 (50%) and 4/12 (33.3%), respectively. Younger women with BV could be at a higher risk for STDs, especially for CT cervicitis.

The object of this study was to determine the efficacy and safety of glycosylated recombinant human granulocyte colony-stimulating factor (rHuG-CSF; lenograstim) after combination chemotherapy consisting of ranimustine, vindesine, melphalan and prednisolone (MCNU-VMP). One hundred thirty-nine consecutive patients with newly diagnosed multiple myeloma (MM) were allocated at random to a lenograstim group (n = 70) or a placebo group (n = 69). Patients were treated with two cycles of MCNU-VMP, and either lenograstim (2 microg/kg daily, s.c.) or placebo was administered from the day neutrophils decreased to less than 1.000/microl and was discontinued when neutrophils exceeded 5,000/microl. The median duration of neutropenia (neutrophils under 1,000/microl) was significantly shorter for the lenograstim group than the placebo group (2 days vs 9 days in the first cycle; 1 day vs 13 days in the second cycle). The incidence of febrile neutropenia in the first cycle was significantly lower in the lenograstim group than in the placebo group (9.2% vs 30.4%). No life-threatening infections were observed in either group. The two cycles of MCNU-VMP therapy were completed in 90.8% of the patients, and a higher average relative dose intensity (ARDI; 0.94) was achieved in the lenograstim group. The tumor response rate of the lenograstim group (57.8%) was higher than that of the placebo group (43.1%), but the difference was not statistically significant (chi2 = 2.634, df = 1, P = 0.105). Lenograstim was well tolerated, and no unexpected adverse events occurred. Lenograstim proved effective in controlling chemotherapy-induced neutropenia in MM patients under MCNU-VMP therapy.

Complete hydatidiform mole and coexistent fetus (CMCF) is a rare occurrence and is associated with an increased risk of persistent gestational trophoblastic diseases. The aim of this study was to reveal a potential risk factor and to determine optimum management of CMCF cases. Molar tissues are cytogenetically divided into two types, homozygous and heterozygous. The molar tissue of our case showed a 46, XY heterozygous complete mole. Genomic DNA was analyzed by the polymerase chain reaction using sets of unlabelled forward and Cy-5-labelled reverse primers for DNA marker loci. The patient developed persistent trophoblastic disease (PTD) with lung metastasis. Since 1980 there have been 13 reports (including our case) that cytogenetically revealed CMCF and clarified the clinical outcome. Nine of the 16 CMCF cases before 21 weeks of gestation and seven of the 12 CMCF cases after 22 weeks of gestation developed PTD. The incidence of PTD from CMCF was not related to the gestational age at termination or delivery. There were 10 case reports that analyzed the zygosity of a mole, heterozygous or homozygous. Two of six homozygous and three of four heterozygous moles in CMCF cases developed PTD. A heterozygous mole is thought to be a high risk factor for the incidence of PTD. Cytogenetic study is clinically useful for the optimum management of CMCF cases.

The objectives of the present study were to evaluate whether a schedule-dependent pharmacokinetic and/or pharmacodynamic interaction exists between two sequences of docetaxel and doxorubicin administration and to determine the maximal tolerated dose (MTD) of this combination. Patients with chemotherapy-naïve metastatic or recurrent advanced breast cancer were enrolled. In the crossover design, tandem dose escalation of docetaxel and doxorubicin was performed. Docetaxel, in doses ranging from 50-70 mg/m2, was administered for 1 h by drip infusion either just before or after a 5-min bolus i.v. injection of doxorubicin at dosages from 40-50 mg/ m2. The sequence of drug administration was switched after the first course in each patient, and the sequence of drug administration thereafter depended on the patient's choice. Twenty-five patients were initially assessable for toxicity. The MTD in the sequence of doxorubicin after docetaxel was 40 and 50 mg/m2, respectively, with the dose-limiting toxicity of neutropenia. On the other hand, the MTD of the sequence of docetaxel after doxorubicin was 70 and 50 mg/m2, respectively. The dose-limiting toxicities in this sequence were neutropenia and diarrhea. Duration of grade 4 neutropenia in the sequence of docetaxel followed by doxorubicin was significantly longer than that in the alternate sequence (P = 0.0062). However, there was no difference in pharmacokinetic parameters of docetaxel, doxorubicin, and doxorubicinol between the two sequences. The sequence of 50 mg/m2 doxorubicin followed by 60 mg/m2 docetaxel is recommended for subsequent clinical trials for practical reasons.

Myxoid leiomyosarcoma is a rare variant of uterine sarcoma, exhibiting malignant biologic behavior despite the absence of cytologic atypia and of significant mitotic activity.A 20-year-old female was referred with a cystic pelvic mass. At laparotomy, the tumor, weighed 2,200 g and originating in the left lateral uterine wall, was removed. Microscopic examination revealed well-differentiated smooth muscle cells without atypia and with a few mitotic figures in the copious myxoid matrix, suggesting myxoid leiomyosarcoma. Three years following laparotomy, an irregular mass around the uterus was noted on sonographic examination, suggesting local recurrence. Two years and six months later, the second operation was performed, and a locally recurrent, multicystic tumor weighing 3,500 g was excised. The histopathology was similar to that of the primary tumor. Cytologic findings on imprint material from the tumor revealed a few isolated or sheet like small cells consisting of spindle and polygonal cells with round and oval nuclei. Cytologic atypia was also minimal.Myxoid leiomyosarcoma should be included in the differential diagnosis of smooth muscle neoplasia.

To explore the pathogenesis in placental dysfunction and abruptio placentae, we analyzed the occurrence of placental cell apoptosis and the role of Fas and Fas ligand (L) in that process in an inflammatory placental dysfunction model of pregnant mice, using lipopolysaccharides (LPS). In the present study, Day 13 pregnant mice were injected i.p. with LPS (50 microg/kg) or saline as a control, and the placentas were isolated at various time points after the injection. Analysis of the isolated DNA in agarose-gel electrophoresis revealed a typical ladder pattern of bands consisting of 180-200 base pairs (bp), which is regarded as a hallmark of apoptosis. The intensity of the bands increased time-dependently, reaching a maximum level at 12 h after LPS injection. In accord with the biochemical data, histochemical analysis using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) revealed that nuclei positive for double-stranded DNA breaks were found in decidua, diploid trophoblasts in the basal zone, and spongiotrophoblasts. The number of positive nuclei was maximized at 12 h after LPS injection. As a next step, we investigated the possible involvement of Fas and Fas L in the induction of apoptosis of the placental cells after LPS injection. Western blot analysis indicated that LPS increased the expression of Fas and Fas L in the placenta by about 4-fold at 12 h and 18 h, respectively, after injection. The cells expressing Fas and Fas L were identified, using immunohistochemistry and nonradioactive in situ hybridization, as decidua, diploid trophoblasts in the basal zone, and spongiotrophoblasts. Furthermore, when the expression of 4-hydroxy-2-nonenal (HNE)-modified proteins was assessed to evaluate the relation of oxidative stress elicited by LPS to the induction of apoptosis, once again decidua, diploid trophoblasts in the basal zone, and spongiotrophoblasts were positive. Therefore, the placental dysfunction by LPS may be brought about by the Fas-mediated apoptosis of various placental cells in a paracrine/autocrine fashion, possibly under the influence of oxidative stress.

Cytologic findings of sarcoma botryoides were still equivocal because sarcoma botryoides of the uterine cervix is an extremely rare neoplasm, and few cases have been reported to date.A 17-year-old female was diagnosed with sarcoma botryoides of the uterine cervix. The entire vaginal canal was occupied with polypoid masses, which arose from the anterior lip of the uterine cervix, and the tumor was classified as group I (Intergroup Rhabdomyosarcoma Study). After wedge resection and six courses of combination chemotherapy, the tumor recurred in the same location of the cervix as the primary lesion. Touch smear of the polypoid mass formed loose clusters and also showed short spindle cells in a necrotic background. The nucleus of the tumor cells had a thin nuclear membrane, fine chromatin pattern and partly clear nucleolus, showing mild nuclear atypia. Immunohistochemically, some of the tumor cells showed positive staining for myoglobin and desmin.The cytologic findings of sarcoma botryoides of the female genital tract are typical features of nonepithelial malignant tumor. Immunohistochemical study is useful for the diagnosis of rhabdomyosarcoma.

To investigate the correlation between the development of low grade cervical intraepithelial neoplasia (LCIN) and human papillomavirus (HPV) infection in cases with long-term follow-up.Forty-three cases of LCIN were followed for more than five years with cytology, colposcopy and Vira Pap. Coexistence of HPV infection was sought using a simplified HPV detection kit, the Vira Pap method (Dot Blot hybridization).Regressive disease was noted in 21 cases, and persistent and progressive disease was noted in 22 cases. HPV DNA was negative in 81% (17 of 21) of regressive disease and positive in 55% (12 of 22) persistent and progressive disease. LCIN had disappeared in 17 (63%) of 27 cases negative for HPV DNA and was persistent or progressive in 12 (75%) of 16 cases positive for HPV DNA.The clinical course of LCIN correlates well with HPV infection.

Few investigations have been made concerning hormonal changes and dyspareunia in fertile aged women with alcoholics experiencing sexual dysfunction. Twenty-seven Japanese woman with alcoholics under 40 years of age excluded with liver cirrhosis were studied to describe alcohol drinking related to sexual dysfunction. Among 21 sexually active women, 20(95.2%) had both symptoms of dyspareunia and vaginal dryness, and only one had neither symptom. Most of patients have lower estradiol levels and 92.0% of patients have the moderately elevated prolactin levels. Eleven of them were having the second grade amenorrhea associated with hyperprolactinemia and hypergonadotropic hypogonadism and 14 were having the first grade amenorrhea. In this study alcoholic abuse women may have deeply related to the hyperprolactinemia, dyspareunia, amenorrhoea, vaginal dryness, ovarian dysfunction and fetal alcohol syndrome.

Ten young adults (15-22 years of age) with acute lymphoblastic leukemia were treated with the protocol of internal medicine and pediatrics co-operative study group since 1989. All patients had complete remission within 5 weeks. Four of 6 patients of low risk group (less than 30,000/microliter of WBC count at diagnosis) and 1 of 4 patients of high risk group have continued the complete remission. Three patients relapsed in bone marrow (BM), and 2 patients in both BM and central nervous system (CNS). All patients could be treated without serious complications except for infection. We obtained the good results of treatment for the low risk group, but did not for the high risk group in this study. Little is known about acute lymphoblastic leukemia in young adults because these individuals are at the borderline age between internal medicine and pediatrics. Taken together with the psychologically distinct age of these patients, it is necessary to establish a closer relationship between internal medicine and pediatrics.

Endometrial cytology in nine cases of ectopic pregnancy was examined in order to elucidate the cellular characteristics of the Arias-Stella reaction and decidual change.The cellular findings of epithelial and stromal cells were compared with histologic findings in each case. Furthermore, the immunocytochemical reactivity of each type of cell cluster-epithelial cells without atypia, epithelial cells with atypia, deep stromal cells and sheetlike stromal cells-to epithelial membrane antigen (EMA) or vimentin was investigated and compared with cytologic findings in smears stained with Papanicolaou stain.The distribution of each type of cell cluster correlated fairly well with the histologic findings on the endometrium. Immunocytochemical examination revealed that EMA expression coincided with cell origin identified by Papanicolaou stain. Epithelial cells with atypia, probably corresponding to the Arias-Stella reaction, frequently showed positive reactivity to antivimentin antibody as well as anti-EMA antibody. Endometrial stromal cells usually indicated negative reactivity to anti-EMA antibody. Deep stromal cells expressed vimentin, but sheetlike stromal cells, thought to be decidual cells, infrequently expressed vimentin.The Arias-Stella reaction may be the result of the regenerating and proliferating activity of endometrial glands. It is still controversial whether sheet-like stromal cells are identical to decidual cells.

To investigate the accuracy rates of cytology, colposcopy and punch biopsy in early cervical neoplasia confirmed by conization.During the 10 years from 1984 to 1993, cold knife conization was performed on 151 patients with early cervical neoplasia proven by punch biopsy at our department. The accuracy rates of cytology, colposcopy and punch biopsy were investigated.The accuracy rates of cytology, colposcopy and punch biopsy were 52% (78 of 151), 66% (100 of 151) and 66% (100 of 151), respectively.These results suggest that a composite diagnosis with cytology, colposcopy and punch biopsy is necessary for a correct evaluation. Early cervical neoplasms are frequently seen in young women, and conservative procedures, such as conization, cryosurgery and laser vaporization, are the treatments of choice in order to preserve reproductive function. We recommend conization as the best conservative procedure, with preservation of reproductive function.

The remarkable contraction of small arteries occurred in the perimetrium of the uteri with leiomyomas by a presurgical medication P6th the luteinizing hormone-releasing hormone (LHRH) agonist (buserelin). The contracted vessels showed a significant increase in number of the Weibel-Palade (WP) bodies which occasionally underwent the degranulation and the discharge in a manner of exocytosis. By immunoelectron microscopy, localizations of endothelin (ET)-1 immunoreactive gold particles on the WP bodies as well as on cisterns of the rough endoplasmic reticulum (rER) and Golgi apparatus were pronounced in the buserelin-medicated group when compared to the non-medicated one. These findings indicate that the increase of the WP bodies storing ET-1, of which synthesis in the rER-Golgi system enhances, predominantly occurred in the small arteries in the perimetrium by the buserelin-medication prior to the hysterectomy. ET-1, released into the subendothelial layer, seems to play an important role in the contraction of the vascular media in a manner of paracrine.

A 56-year-old woman was admitted with pyrexia, cough, and dyspnea on August 21, 1991. Physical examination revealed anemia in the palpebral conjunctivas and moist rales at the right lower lung field. Neither the Liver nor spleen was enlarged. Examination of the peripheral blood showed a hemoglobin level of 8.1 g/dl, a platelet count of 14.8 x 10(4)/microliters, and a white blood cell count of 2,800/microliters, with 7% blasts and 8% megakaryocytes. Tear drop-like erythrocytes, agranular neutrophils, and erythroblasts were also seen in the peripheral blood. Examination of the bone marrow showed 15% peroxidase positive blasts, and many micromegakaryocytes. Cytogenetic studies for bone marrow cells revealed the existence of the Philadelphia (Ph1) chromosome. Bone marrow biopsy showed normal cellularity with increase of megakaryocytes and advanced myelofibrosis. Breakpoint cluster region (bcr) rearrangement analysis using the peripheral blood mononuclear cells revealed M-bcr rearrangement. According to the Hannover classification for myeloproliferative disease, she was diagnosed as having CML with advanced myelofibrosis followed by CML with megakaryocytic increase. Since she had neutrocytopenia and severe infectious disease, she received a subcutaneous injection of 125 micrograms of G-CSF. Not only increase of the white blood cell count, but also disappearance of blasts, improvement of anemia, increase of the platelet count, and improvement of myelofibrosis were observed.

Cytologic findings on various vulvar squamous lesions are described in order to elucidate the usefulness of vulvar cytology. Lichen sclerosus, hyperplastic dystrophy and dysplasia with a few exfoliated anucleate squamous cells could not be differentiated cytologically. Numerous parakeratotic cells and dyskaryotic cells were identified in squamous cell carcinoma in situ. Three cytologic patterns were presented in cases of frankly invasive squamous cell carcinoma: negative cytology with parakeratotic cells, suspicious cytology with dyskaryotic cells and positive cytology with malignant cells. Verrucous carcinoma yielded only anucleate squamous cells. Parakeratotic cells without nuclear atypia seemed to be neoplastic cells on vulvar cytology.

The immunocytochemical localization of hCG in the syncytiotrophoblast of hydatidiform moles was observed by means of the immunoglobulin gold technique with rabbit anti-human hCG serum. Immunoreactive gold particles of hCG are preferentially localized in the distal portion of the Golgi complexes, Golgi-derived secretory granules 200-300 nm in diameter, and large electron dense bodies 500-1,000 nm in diameter. The secretory granules exist throughout the cytoplasm above the nuclear region and are occasionally released by exocytosis from the syncytiotrophoblast. On the other hand, the large electron dense granules seem to be cytolysosomes in nature and are involved in uptake and storage of hCG.

Magnetic Resonance Imaging (MRI) has been widely used for the diagnosis of gynecologic disease. We studied the clinical usefulness of MRI in 34 patients with endometrial cancer from July, 1988 to August, 1991. Pre-operative pelvic MRI was carried out to evaluate the myometrial invasion in these patients. MRI was accurate in predicting the presence or absence of myometrial invasion in 23 of 34 cases (68%), while echo or CT (computed tomography) was accurate in 26% and 8%. In conclusion, MRI is considered to be the most useful examination for the evaluation of myometrial invasion in endometrial cancer.

The usefulness of MR imaging (MRI) in uterine cervical cancer after radiotherapy was evaluated in 18 patients. MRI was performed before and within one month after radiotherapy. In eight patients the uterus assumed a nearly normal appearance with resolution of the tumor on MRI. In another eight patients the tumors resolved, but an area of high signal intensity remained at the cervix. In these patients the tumors were well controlled at clinical examinations and during the mean follow-up period of 15-18 months. Therefore a persistent area of high signal intensity alone at the cervix on MRI is not itself indicative of residual tumor. An area of high signal intensity and a residual cervical mass persisted in two cases, and they were histologically proven to be due to residual tumor. Both patients died of recurrent disease at seven and 11 months after their radiotherapy. We conclude that MRI is useful for evaluating patients with cervical cancer at the completion of radiotherapy, and that MRI complements conventional clinical examinations.

Combination chemotherapy with Cyclophosphamide, Adriamycin and Cisplatin (CAP) is one of the most effective chemotherapies for ovarian cancer. Severe vomiting induced by this treatment may cause a disorder of the serum electrolytes. Severe hyponatremia was observed in one patient who complained of convulsions and unconsciousness. Accordingly we studied the disorder of serum electrolytes in 158 courses of CAP treatment (44 patients) during the five years from 1984 to 1988. The serum electrolytes were influenced by the amount of vomiting in this study. Consequently frequent examination of serum electrolytes is necessary during this treatment.

To elucidate the accuracy of cytology in diagnosing cervical intraepithelial neoplasia (CIN) during pregnancy, cytologic screenings for uterine cervical cancer in pregnant women were reviewed for a five-year period. Of the 967 pregnant women screened, abnormal cytologic findings were recorded for 15 (1.6%). Only nine of these were subsequently examined by colposcopy and punch biopsy, which demonstrated CIN in all cases, for an incidence of documented CIN during pregnancy of 0.93%. Including two referral cases also examined by colposcopy and biopsy, cytology and histology agreed on the degree of CIN in four cases and disagreed by one degree in four cases, by two degrees in two cases and by three degrees (mild dysplasia versus carcinoma in situ) in one case. Review of the specimens from these cases did not readily explain the poor concordance between cytology and punch biopsy; some findings suggest that overestimation of the punch biopsy sample may be the explanation.

In the management of a chorionic disease, human chorionic gonadotropin (hCG) is the most reliable tumor marker. However, hCG has a low titer, so that it cannot be strictly distinguished from the human luteinizing hormone (hLH) by the traditional method that uses a hemagglutinin reaction (HAR) or by a radioimmunoassay (RIA). Recently, however, the detection of the beta-COOH-terminal peptide of hCG (hCG-CTP) by an enzyme immunoassay has made it possible to clearly distinguish hCG from hLH, and from April, 1987 to December, 1989, 13 trophoblastic diseases have been managed using this new technique. Results have shown that human chorionic gonadotropin-CTP, when compared to other methods of measurement, is the most sensitive tumor marker and as it is the most accurate, it should be used in careful follow-up observations of a chorionic disease.

Seventeen multiple primary cancers including 16 double cancers and one triple cancer were found in 316 patients with gynecologic malignancies who were treated in our department from 1984 to 1988. All pathologic slides but one were reviewed, and cases with possible metastasis or recurrence were not included in this study. The incidence of multiple primary cancers in gynecologic malignancies was 5.4%. Multiple primary cancers were encountered in 4.4% of 205 cervical cancers (including carcinoma in situ), 15.2% of 33 endometrial cancers, and 8.6% of 58 ovarian cancers (including low potential malignancy), respectively. The most frequent sites of other cancers were seen in the large intestine and rectum (5/17), breast (4/17), and gynecologic organs (3/17). Higher incidences were seen in our study that in those in domestic literature. This is probably because detailed anamnesis and gastrointestinal series were obtained in most gynecologic malignancies (especially in endometrial or ovarian cancer).

Chronic idiopathic intestinal pseudoobstruction (CIIP)の2症例を報告した.症例1は32才女性.過去2度腸閉塞の疑いで開腹を受けるも器質的異常なく,術後多発腸穿孔にて広範腸切除を行った.以後も悪心,嘔吐は変わらず持続.症例2は35才女性.脂肪性下痢,腹部膨満を訴え腸閉塞の疑いで開腹を受けたが器質的異常はなかった.両症例とも腹部X線像では鏡面形成をみた.食道内圧検査では自発性収縮の出現, LESP低値,嚥下時収縮の低下を,さらにレノグラムにおいて腎排泄相の著しい遅延を認めた.なお, total parenteral nutrition (以下TPN)にて両者とも栄養状態は改善した.本邦でのCIIPの報告は11例で内7例が成人発症,腸管の他食道と尿路系に異常を認めたのは自験の2症例のみであった.

The cells in a case of multifocal vulvar Paget's disease were studied by cytology, histology, ploidy analysis and electron microscopy. The Paget cells in smears were seen in an isolated or a sheetlike arrangement. The cells had peripherally located nuclei, prominent nucleoli and unevenly distributed melanin granules of various sizes in their cytoplasms. The histologic sections contained multifocal microscopic lesions that were larger than the macroscopic lesion. Paget cells in the histologic sections demonstrated positive cytoplasmic staining with the periodic acid-Schiff, Alcian blue, mucin, glandular cytokeratin, epithelial membrane antigen and carcinoembryonic antigen reactions. The nuclear DNA histogram of the Paget cells in the cytologic smears showed a polyploid pattern, with a sharp peak at 4c; the cells in sheets had a ploidy level between 2c and 4c while a few of the isolated cells had a ploidy level that extended past 8c. Various nuclear DNA patterns were observed in the histologic samples; a recurrent lesion was later found in an area adjacent to the primary lesions that had higher ploidy levels. Ultrastructurally, the Paget cells contained lysosomes and tiny electron-dense secretory granules in their cytoplasms, suggestive of a glandular cell origin. These findings suggest that Paget cells may be derived from the secretory portion of sweat glands.

The cytomorphologic observations of ascites from three patients with ovarian dysgerminomas are presented. As compared with those in adenocarcinoma, the cytologic findings in this rare malignant ovarian tumor showed more cells lying isolated or in sheetlike arrangements, fewer cells with discrete cytoplasmic vacuoles, less frequent thickening of the nuclear membrane and more frequent multinucleolation.

Estrogen receptor (ER) content in myoma and myometrium was determined by radioreceptor assay (RRA), and ER staining was performed by immunocytochemical staining, i.e., the peroxidase-antiperoxidase (PAP) method, in uterine samples from eight patients with uterine leiomyoma. ER content in myoma tended to be higher than that in myometrium, but the difference was not significant. The distribution pattern of ER staining was thought to be an important criterion. When the data were compared on the basis of the number of cells in the site where the largest number of positive cells aggregated, the number for myoma was significantly higher than that for myometrium (p less than 0.05). These results suggest that myoma contains more ER positive cells and more efficiently absorbs estrogen than myometrium.

Malignant lymphoma is a rare entity in the neoplasms of the female genital tract, and thus a case of malignant lymphoma of the vulva is reported in this paper. On admission, the patient, a 37-year-old, Japanese female, had complained of vulvar swelling and pain that had persisted for one month. Stage IV tumors were noted in the vulva and bladder and a histological diagnosis indicated non-Hodgkin's lymphoma with diffuse, large cell and B cell types, according to the classification of the Lymphoma Study Group. The patient thus was treated with CH* OP therapy, which consisted of Cyclophosphamide, Aclarubicin Vincristine (Oncovin), and Prednine , and given brain irradiation. Unfortunately her condition has rapidly deteriorated during the 5 months since her admission.

To establish the differential diagnosis of repair cells from malignant cells, 624 repair cells from 11 cases, 547 cells derived from 8 adenocarcinomas and 593 cells from 8 squamous-cell carcinomas were analyzed, with stress on the morphology of the nucleoli. Such planimetric data as mean cellular areas, mean nuclear areas, mean nucleolar areas, nuclear-cytoplasmic ratios and nucleolar-nuclear ratios were fairly similar among the three cell groups. However, the even distribution of nucleoli in the nuclei, the decrease in C-type nucleoli and nucleoli consistently linked with nucleolus-associated chromatin were noted to be reliable criteria for the diagnosis of repair cells along with such well-known morphologic characteristics as the sheetlike arrangement of repair cells, the lack of isolated forms, the finely granular chromatin pattern and the round, smooth nuclear configuration with a thin nuclear membrane.

Therapeutic efficacy of cervical conization was examined on 93 patients with borderline lesions of the uterine cervix who underwent hysterectomy following conization. No lesions or only minimal residual lesions were found at subsequent hysterectomy when the surgical margins of cone specimens were not involved in the malignant or premalignant lesions. From these results, we concluded that cervical conization could be considered as a therapeutic procedure when the following conditions were fulfilled. Cone specimens are sufficient in size. Both endocervical and exocervical margins are negative. No malignancy is found on endocervical curettage. No abnormal cytologic findings are found after conization. Another follow-up study was performed on 69 patients who received therapeutic conization between 1971 and 1981. Among them one developed stage II cervical cancer two years after the last follow up. Two other patients had recurrent CIN in the cervix and another patient was found to have an endometrial cancer. These patients were successfully treated after early detection of the lesions by the cytological examination. From these facts, cytological examination is recommended in the follow-up after therapeutic conization.

The effectiveness of the prophylactic chemotherapy was evaluated in 420 patients with molar pregnancy. All patients were followed for 5 to 15 years after the evacuation. Twenty-two (7.5%) of 293 patients with prophylactic chemotherapy and 23 (18.1%) of 127 patients without prophylactic chemotherapy (control) developed secondary trophoblastic disease. The prophylactic chemotherapy could reduce the occurrence of secondary trophoblastic disease. In these secondary trophoblastic diseases, 5 (22.7%) of 22 patients in the prophylactic chemotherapy group and 5 (21.7%) of 23 in the control had metastatic trophoblastic disease. Choriocarcinoma after the molar pregnancy developed in two patients (0.7%) of the prophylactic chemotherapy group and two (1.6%) of the control. Prophylactic chemotherapy did not eliminate the occurrence of choriocarcinoma. The complication of the prophylactic chemotherapy was seen in 27.3% of the patients. Neither severe complication nor death were related to the toxicity.

The cytologic findings in 15 endometrial hyperplasias were compared with those of normal endometrium and well-differentiated endometrial adenocarcinoma. Differences in tumor diathesis, hypercellularity, uneven internuclear distance, severe piling up of nuclei, anisokaryosis, nuclear size and macronucleoli were the main cytologic findings that were noted among the three conditions. These features varied in the different types of endometrial hyperplasia. It is not clear that these cytologic findings can be used to cytologically diagnose endometrial hyperplasia because some of the findings involve subjective judgments by different cytologists. Further studies on larger series of cases will be necessary to establish the cytologic criteria for the correct interpretation of endometrial abnormalities.

Four patients with recurrent or advanced endometrial cancer have undergone combination chemotherapy with Cyclophosphamide, Adriamycin and Cisplatin (CAP). All drugs were administered by I.V. on day 1 in the following doses: Cyclophosphamide 500 mg/m2, Adriamycin 50 mg/m2 and Cisplatin 50 mg/m2. The treatment was repeated every 4 weeks and continued as long as there was disease progression. Two complete clinical responses and two partial responses were achieved. Based on these good results, we have initiated post-operative prophylactic chemotherapy using CAP in high risk patients. Adverse effects including myelo-suppression, nausea, and vomiting, and alopecia were seen in almost all patients. In no case, however, did any patient experience life-threatening toxicity. Based on our experience, CAP therapy appears tolerable when used per our schedule.

This paper reviews scanning electron microscope (SEM) observation of the circulatory system of the human spleen, based on our findings on freeze-cracked surfaces and vascular casts of the spleen. Central arteries ran straight in the white pulp without branching out follicular arteries and became penicillar arteries in the red pulp. Some penicillar arteries returned to the marginal zone. Some of their branches ended by opening there, whereas others passed through the marginal zone, entered the white pulp and became follicular arteries. Some of them took the shape of an "arteriolar-capillary bundle". Most of the follicular capillaries ended opening into the marginal zone. The penicillar arteries usually ran straight or gently curved among the sinuses of the red pulp and opened into cordal spaces. Occasional arteries formed a labyrinthine structure of arterial channels which directly connected with thin sinuses. This study reveals that three different modes of arterial terminals are available in the human spleen: arterial openings in the marginal zone which seem significant for presentation of antigens to the white pulp, openings into the cords of Billroth which facilitate culling and pitting of blood cells, and direct connections with sinuses (closed circulation) which account for the physiologically known quick blood flow through the spleen.

The nuclear DNA content of trophoblasts was measured in 25 cases of normal pregnancy, 46 cases with hydatidiform mole, ten cases with destructive mole and six cases of chorionepithelioma (choriocarcinoma). In normal pregnancy, DNA distribution in syncytiotrophoblasts and cytotrophoblasts showed a sharp peak at the diploid region, although a few cytotrophoblasts with increased DNA content were observed in the first trimester. In chorionepithelioma the DNA content of the trophoblastic cells showed extremely wide distribution without any special peak. In destructive mole, although a wide distribution was observed, the sharp peak was usually noted at the diploid range. Cases with hydatidiform mole were divided into two categories according to the DNA distribution patterns. Type I showed the patterns similar to the first trimester of normal pregnancy and type II resembled the patterns of destructive mole. In hydatidiform mole of type II, subsequent progress towards destructive mole was frequently encountered.

To elucidate the pathogenesis of leiomyoma, myoma tissues and myoma-derived cultured cells were stained with desmin, vimentin and fibronectin by the enzyme-labelled antibody method. Desmin staining was positive in both the myoma tissues and the cultured cells. Vimentin staining was positive in endothelial cells in the blood vessels of the myoma and in the cultured cells. Fibronectin staining was positive in both the myoma and cultured cells. These findings demonstrate that the leiomyoma was derived from myogenic cells. It was suggested that the myoma-derived cultured cells were myofibroblasts with myoblasts and fibroblasts, and had the ability to differentiate. It appears that the original cells of the myoma differentiate to myofibroblasts, which then differentiate into myoblasts and fibroblasts.

From January, 1973 to December, 1980, 396 cases of cervical cancer were treated with radical hysterectomy under the diagnoses of stage Ib, IIa and IIb. Precise postoperative pathological examinations about the extirpated uterus revealed that 63 of them had only early invasive cancer or less advanced lesions though they had been considered as frank invasive cancer by preoperatively performed biopsies. The major causes of the misinterpretations were, 1) misjudging the glandular involvements as frank invasive lesions, or 2) misjudging the tangentially sectioned lesions of the bulky outgrowth as frank invasions. Furthermore, it is sometimes difficult to identify the invasive lesions in the biopsy specimens whether they are early invasive or frank invasive. Colposcopic and cytological examinations were simultaneously performed to each cases. Either cytology or colposcopy did not suggest frank invasions in 44.2% of cases. Both of them did not suggest frank invasions in 37.2% of cases. At least, cone biopsy should have been performed to identify the degree of invasions of these 37.2% cases. The authors emphasize that the directed biopsies are not always accurate to diagnose the early invasions, and one should use colposcopy, cytology and directed biopsy to make an accurate diagnosis.

The cytologic features of six cases of stomach cancer metastatic to the uterine cervix are presented. Atypical cells were found in cytology samples from four patients. Fewer atypical cells, larger cellular and nuclear areas, more discrete vacuoles, increased frequencies of thickening of the nuclear membrane and more coarsely granular chromatin patterns were the characteristic cytologic findings of metastatic cervical adenocarcinoma as compared with primary endocervical adenocarcinoma.

One hundred and three patients with dysplasia, carcinoma in situ, or microinvasive carcinoma of the uterine cervix were treated with cryosurgery during 8 years from 1972 to 1978. Twenty-nine patients underwent several types of operations during 4-41 days (mean 18 days) after cryosurgery, and 74 patients were followed for 3-78 months (mean 3 years) after treatment. Seventy-six per cent of the patients who underwent an operation had residual lesions in their histologic materials. Seventy per cent of the patients who were followed, on the other hand, showed consecutively negative cytology and pathology after cryosurgery. It is necessary for the more effective management of CIN with cryosurgery to perform endocervical curettage in every case, to select small lesion for treatment, and to use more powerful method of cryocauterization.

Melphalan is widely used in the chemotherapeutic treatment of an ovarian cancer. Bone marrow depression, nail change, hypersensitivity, chronic pulmonary fibrosis, and nausea and vomiting, are the side effects reported as a result of the toxicity of Melphalan. So far as we know, renal toxicity caused by Melphalan has not been reported in the past literature. A case of acute renal failure induced by Melphalan in a patient with 3rd stage ovarian cancer is presented in this paper. This therefore is the first report of renal toxicity caused by Melphalan.