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Objective: In Japan, no region has introduced primary HPV testing for cervical cancer screening. We assessed the diagnostic value and possible harm of HPV testing in Japan., Methods: This cross-sectional study with historical controls used cytology-based screening and co-testing data in Japan. As surrogate indicators of possible harm, colposcopy referral rate and cervical intraepithelial neoplasm (CIN) 1 detection rates were calculated. As surrogate indicators with diagnostic values, the detection rates of CIN2 or greater (CIN2+) and CIN3+ were calculated., Results: The data of 297 970 women (182 697 for cytology-based, 115 273 for co-testing) were examined. The detection rates of CIN1, CIN2+, and CIN3+ were significantly higher in the co-testing group than in the cytology-based group (P < 0.001, P < 0.0001, P < 0.01, respectively). Between ages 25-49, CIN2+ detection rates were significantly higher in the co-testing group than in the cytology-based group (P < 0.05 for each 5-year age group). Between ages 30-49, CIN3+ detection rates were significantly higher in the co-testing group than in the cytology-based group (P < 0.05 for each 5-year age group)., Conclusion: Limiting the target age group may minimize the possible harm of screening. Cytology/HPV co-testing may be useful in Japanese populations if balance is maintained between benefit and harm., (© 2021 International Federation of Gynecology and Obstetrics.)

In Japan, government support for human papillomavirus (HPV) vaccination began in November 2010. However, the mass media repeatedly reported on severe adverse events. The Japanese Ministry of Health, Labor and Welfare suspended proactive recommendations for HPV vaccines in June 2013. Japan's HPV vaccination rate dropped from 70% to less than 1% in 2017.We examined cervical cancer screening results in terms of abnormal cytology, histology, and HPV vaccination status among 11,903 women aged 20 to 25 y in the fiscal year 2015. The overall rate of HPV vaccination was 26.1% (3,112/11,903). Regarding cytology, the rate of atypical squamous cells of undetermined significance (ASC-US) or worse was 3.3% (103/3,112) in women who received HPV vaccination (vaccine (+) women) and 5.6% (496/8,791) in women who did not (vaccine (-) women). The rate of high-grade squamous intraepithelial lesion (HSIL) or worse was 0.26% (8/3,112) in vaccine (+) women and 0.81% (72/8,791) in vaccine (-) women. Regarding histology, the rate of cervical intraepithelial neoplasia 1 or worse (CIN1+) was 1.4% (42/3,112) in vaccine (+) women and 2.1% (178/8,791) in vaccine (-) women. The rates of CIN2+ and CIN3+ were similar regardless of vaccination. We found a significantly lower incidence of CIN in vaccine (+) women. These results suggest that the resumption of recommending HPV vaccination as primary prevention for cervical cancer is needed in Japan.

Cervical cancer screening has been shifting from primary cytology to primary HPV testing worldwide as primary HPV testing is more sensitive than primary cytology. To the best of our knowledge, the current study is the first in Japan to examine the feasibility of primary HPV testing. One of the disadvantages of this shift is that hrHPV-/≥LSIL/CIN2+ (high-risk HPV negative cancers or pre-cancerous lesions with abnormal cytology results) can be missed. The objectives of the present study are to clarify in detail CIN2+ missed by this shift and to evaluate the feasibility of primary HPV testing in Japan. Data from 115,273 women who underwent co-testing with cytology and HPV testing in cancer screening were used in the current study. The cases with hrHPV-/≥LSIL ('hrHPV-/≥L-SIL' include CIN2-, in contrast, 'hrHPV-/≥L-SIL/CIN2+' doesn't include CIN2-) were analysed in detail. Women with hrHPV-/≥LSIL comprised 0.3% of the total. The prevalence of CIN2, CIN3, SCC or cervical adenocarcinomas in the lesions with HPV-/≥LSIL was 0.03% in the cancer screening group. Only one case of 14 cervical adenocarcinomas in ≥LSIL was hrHPV-. The prevalence of cancer missed by the shift in patients >50 years of age was significantly higher compared with patients younger than 49 years. In conclusion, the prevalence of CIN2+, which might be missed by the shift from primary cytology to primary HPV testing, was remarkably low in this Japanese cancer screening. The data indicated that primary HPV testing, which was more sensitive for CIN2+ than primary cytology, was a feasible method that can be used in Japan. In particular, primary HPV testing should be introduced for women <50 years old., (Copyright: © Kurokawa et al.)

Objective: We conducted a prospective, multicentre study to compare the clinical performance of liquid-based endometrial cytology (LBEC) using SurePath™ with that of suction endometrial tissue biopsy (SETB). This study is officially advocated and reported by the Japan Association of Obstetricians and Gynecologists. By publishing our midterm data, we intend to disseminate the benefits of LBEC system, using the descriptive reporting format and algorithmic interpretational approach., Methods: From April 2014 to December 2015, we consecutively assessed 1116 LBEC specimens and 1044 SETB specimens in our five outpatient clinics., Results: The sensitivity of suction tissue biopsies was 85.2%, whereas the sensitivity of LBEC was 92.2%. The specificity of suction tissue biopsies was 98.9% and that of LBEC was 98.5%. The negative predictive value of LBEC (99.1%) was higher than that of SETB (98.1%), although the difference between these values was not significant., Conclusions: The clinical performance of LBEC for detecting endometrial malignancies was almost identical to the performance of SETB. This indicates that LBEC was not inferior to SETB for the detection of endometrial cancer. The LBEC is appropriate for various clinical situations as the first-step detecting tool. In addition, it could be used for cancer surveillance for women with signs highly suggestive of endometrial malignancies and in Lynch syndrome patients, on a larger scale., (© 2018 John Wiley & Sons Ltd.)

Objective: The aim of this study was to determine the value of human papillomavirus (HPV) testing for primary cervical cancer screening in Japan., Methods: In total, 5065 women who underwent primary screening with cytology and HPV between January 2005 and December 2006 were enrolled. In the baseline phase, these women were stratified by age, and the rates of HPV-positive and abnormal cytology were compared between women younger than and older than 30 years. In the follow-up phase, women aged 20 to 69 years and cytology negative for intraepithelial lesions or malignancy at baseline were followed up until December 2011 (n = 2383). Progression to grade 2/3 cervical intraepithelial neoplasia or worse (CIN2+/CIN3+) was compared between the HPV-positive and HPV-negative groups., Results: In the baseline phase, HPV-positive rates were significantly higher in women younger than 30 years at 20.7% (95% confidence interval [CI], 18.4-22.9; 255/1234) compared with women 30 years or older at 7.2% (95% CI, 6.4%-8.0%; 275/3831; P < 0.001). However, there was no statistical difference for high-grade squamous intraepithelial lesion or worse rates between them, at 2.7% (95% CI, 1.8%-3.6%; 33/1234) and 2.4% (95% CI, 1.9%-2.9%; 91/3831), respectively, P = 0.55. In the follow-up phase, the rate of progression to CIN2+/CIN3+ was significantly higher in the HPV-positive group than in the HPV-negative group (P < 0.001). Moreover, relative risk of progression to CIN2+ was 15.9 times higher in the HPV-positive group, and that of progression to CIN3+ was 16.1 times higher in the HPV-positive group., Conclusions: Human papillomavirus testing is a useful test for predicting progression to CIN and is recommended as a primary screening tool. However, screening with cytology alone is still appropriate for younger women, younger than 30 years, because HPV testing yields more false-positive results in younger women.

The aim of this study was to evaluate the efficacy of endometrial cytology using the Uterobrush in the collection of samples for the diagnosis of endometrial lesions. The preparation technique for endometrial brushing specimens was also demonstrated. In their earlier study, the authors described the cyto-architectural criteria that appear to be more useful for the cytological assessment of endometrial lesions. Therefore, for the application of the diagnostic criteria, endometrial cytological sampling will become more important. With regard to the cell sample collection, the authors used the Uterobrush because the insertion into the uterine cavity is easy and painless. The authors compared the Uterobrush with the Endocyte, since they thought that cell clumps using the former device tended to be smaller. The purpose of the current study was to improve and evaluate cell preparation methods using the Uterobrush. The authors investigated three methods [i.e., conventional and improved techniques ("flicked" method) with the Uterobrush and the Endocyte] of endometrial cell collection and preparation. Using conventional methods, a brush was rolled along a glass slide and the collected material spread and smeared. However, using the "flicked" method, a brush is strongly flicked with forceps, so that the cells are transferred to the slide and its position is moved along the slide little by little and smeared. The frequency by size of cell clumps with tube or sheet-shaped pattern was examined in the preparations. Cell block specimens with the Uterobrush were also investigated. Endometrial cytology from a total of 90 women was evaluated. Most were outpatients and all were older than 20 yr (ranging from 20 to 54, average 42.7 yr). Of these, 30 cases from each group were examined by three methods. Uterobrush samples prepared by the "flicked" method have a greater quantity of cell clumps than those using the Endocyte sampler, while the frequency-by-size of cell clumps was by degree the same as the Endocyte. The cell clumps obtained in the Uterobrush "flicked" method preparation was considered equivalent or superior as an aid to making a diagnosis of endometrial lesions and it became obvious that the same criteria were applicable to both of instruments. Our cytological examination may be a potent aid to making a diagnosis of endometrial lesions and these findings will be helpful in the standardization of criteria in direct intrauterine cell samples., (Copyright 2006 Wiley-Liss, Inc.)

TK is a pyrimidine metabolic pathway enzyme involved in salvage DNA synthesis. What roles TK may play in epithelial ovarian cancer and the relationships between TK and the other pyrimidine pathway enzymes remain unclear. We examined TK1 gene expression by RT-PCR and related it to gene expression of TS, TP and DPD in 69 samples from epithelial ovarian cancer, 8 low-malignant-potential tumors, 16 benign ovarian tumors and 34 normal ovaries. Additionally, cytosolic and serum TK activities were determined by radioenzymatic assay. TK1 gene expression, the ratio of TK1 to TS gene expression, that of TK1 to TP and that of TK1 to DPD were significantly higher in epithelial ovarian cancer than in normal ovaries. In epithelial ovarian cancer, TK1 gene expression correlated with cytosolic and serum TK activities, TS and TP gene expression and the ratio of TP to DPD gene expression. Patients with high-TK1 gene expression had a significantly poorer survival than those with low TK1 gene expression. Combined analysis demonstrated that the relative risk of cancer death for tumors with high TK1, high TS and high TP gene expression was greater than that for tumors with high TK1 gene expression alone. TK1 gene expression together with TS, TP and DPD gene expression may play important roles in influencing the malignant behavior of epithelial ovarian cancer. Combination therapy including TK inhibitor is a possible therapeutic intervention in patients with epithelial ovarian cancer., (Copyright 2002 Wiley-Liss, Inc.)

Objective: Our purpose was to determine the clinical value of thymidine kinase (TK), which is an important pyrimidine pathway enzyme involved in salvage DNA synthesis, in patients with cervical carcinoma., Methods: We examined TK mRNA expression by reverse transcription polymerase chain reaction in 19 tissue specimens of invasive cervical carcinoma and 9 normal cervices and related it to thymidylate synthase (TS) and thymidine phosphorylase (TP) mRNA expressions. Serum TK level was determined by radioenzymatic assay in 79 patients with invasive cervical carcinoma, 7 patients with microinvasive carcinoma, 21 patients with carcinoma in situ and 32 normal women., Results: TK mRNA expression was upregulated in invasive cervical carcinoma compared with the normal cervix (p < 0.05) and significantly correlated with TS mRNA expression (p < 0.0001) but not with TP mRNA expression. The serum TK level was significantly higher in patients with invasive carcinoma than in normal women and patients with carcinoma in situ (p < 0.01 and p < 0.05). In patients with invasive cervical carcinoma, the serum TK level significantly correlated with TK mRNA expression (p < 0.05), but not with any conventional clinicopathologic factors. High serum TK levels significantly correlated with a poorer survival (p < 0.05), and multivariate analysis showed serum TK level to be an independent prognostic factor (p < 0.05)., Conclusion: TK may play an important role in influencing the malignant behavior of cervical carcinoma, and measurement of the serum TK level may be useful in predicting survival in patients with cervical carcinoma., (Copyright 2001 S. Karger AG, Basel)

The clinical courses including thyroid conditions of three infants born to a mother with primary hypothyroidism due to Hashimoto's thyroiditis were studied. The mother was positive for both TSH-binding inhibitor immunoglobulins (TBII) and thyroid stimulating-blocking antibodies (TSBAb) in her serum. The first infant died because of septic shock due to fistula formation between the large intestine and the bladder. Serum thyroid hormone levels during the first pregnancy were extremely low because of incomplete replacement therapy with levothyroxine. The second infant had almost normal thyroid function, so that the replacement therapy was not necessary. The third infant had transient and overt primary hypothyroidism. The replacement therapy was carried out for six months after birth. TSBAb activities in this mother were high in the third pregnancy. In general, these activities gradually increases with the clinical course in TSBAb-positive Hashimoto's patients. From these findings, it was suspected that the thyroid conditions in the second and the third infants reflected the natural course of TSBAb activities in this mother.

Intraperitoneal scintigraphy with Tc-99m MAA was performed in nine patients with carcinomatous peritonitis secondary to ovarian or tubal carcinoma. Tc-99m MAA (370 MBq) and NaCl was delivered through an implantable injection port. For patients with good diffusion on intraperitoneal scintigraphy, intraperitoneal chemotherapy was effective. However, for patients with only local diffusion, intraperitoneal chemotherapy was not effective. Intraperitoneal scintigraphy can predict the effectiveness Intraperitoneal scintigraphy can predict the effectiveness of chemotherapy through the implantable injection port.

The first reported case of cerebellar metastasis from primary clear cell adenocarcinoma of the fallopian tube is presented. Initially diagnosed as stage Ia, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy, followed by cisplatin-based chemotherapy and whole pelvic irradiation. Thirty six months later multiple pulmonary metastases were detected that did not respond to chemotherapy. Later the patient presented with cerebellar metastasis. She received whole brain radiotherapy and steroids. The brain lesion partially responded and the patient's neurologic symptoms improved. Throughout there was no evidence of local recurrence. This case suggests that with the prolonged survival achieved by aggressive treatment occult brain metastases might become apparent.

Sialosyl-Tn (S-Tn) antigen, a cancer-related antigen, was expressed in 56.3% (36 of 64 cases) of the common epithelial carcinoma tissues. This antigen was moderately to strongly expressed in 83.3% (15 of 18 cases) of the mucinous adenocarcinomas. In contrast, it was weakly expressed in 31.3% (5 of 16 cases) of the serous adenocarcinomas. Expression of this antigen in ovarian mucinous tumors of borderline malignancy was 80% (4 of 5 cases), and the staining was moderately intense. S-Tn reactivity was found in 11.5% (3 of 26 cases) of benign ovarian neoplasms. The S-Tn antigen was not found in either normal ovarian tissues or the normal vaginal squamous epithelia. We conclude that the S-Tn antigen may be useful in the histological classification of ovarian carcinomas and in the determination of the malignant potential of such lesions. Moreover, because increases in serum S-Tn antigen were often accompanied by its positive expression in tumor tissues, the S-Tn antigen appears to be a tumor marker in sera with a high specificity for ovarian carcinoma, particularly mucinous adenocarcinoma.

A 40-year-old woman underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymphadenectomy, and omentectomy for Stage IA ovarian surface papillary tumor of borderline malignancy. Microscopic examination revealed endosalpingiosis of ovaries, the peritoneum of uterus, pelvic lymph nodes, and omentum. There was no evidence of disseminated peritoneal malignancy. The several proposed theories of the pathogenesis of endosalpingiosis are reviewed, but that involving metaplasia of the multipotential peritoneal cells is presented as the most acceptable.

A total of 38 cycles of intraperitoneal chemotherapy through implantable injection port were carried out in 9 patients with advanced or recurrent ovarian (tubal) carcinoma. The combination chemotherapy consisted of cisplatin 100 mg or carboplatin 450 mg, 5-FU 500 mg and OK-432 10 KE was administered every four weeks for a total of six cycles. Clinical response was evaluated after chemotherapy. Of the eight evaluated patients (in one patient chemotherapy is not completed yet), 1 had complete response, 3 partial response, 2 stable disease and 2 progressive disease. Therapy-related toxic effects were moderate, consisting chiefly of myelosuppression that seemed dose limiting.

Intraoperative and postoperative complications related to CO2 laser conization and cold knife conization were compared. From 1980 to 1984, 66 patients were hospitalized for cold knife conization. The mean operative time was 28.1 minutes, all patients had epidural anesthesia, and the mean time of admission was 6.8 days. Three percent of cases had infections, the mean intraoperative hemorrhage was 66 ml, and the rate of remaining foci of neoplasia was 18.2%. There were 116 patients hospitalized for CO2 laser conization from 1985 to 1987. The mean operative time was 15.6 minutes, 15.5% of patients had local anesthesia, and the mean time of admission was 0.6 days. No patients had infection or postoperative stenosis, the mean intraoperative hemorrhage was 75 ml, and 29.5% of patients had remaining foci of neoplasia. There was no significant difference in hemorrhage amounts at hysterectomy after conization using either method. In the 2 pregnant patients, CO2 laser conization could be performed safely and did not affect pregnancy or delivery. Thus in our experience, CO2 laser conization is more effective for clinical diagnosis and treating of cervical intraepithelial neoplasia.

We report a long-term survival case of metastatic endometrial stromal sarcoma. A 45-year-old woman with acute abdomen was operated at another hospital. Her uterine histology was endometrial stromal sarcoma. She came to our hospital to treat a metastatic endometrial stromal sarcoma. Endometrial stromal sarcomas were found in liver, spleen and lung. Intra-arterial hypertension chemotherapy was repeatedly performed. After this therapy, metastatic legion in the liver and the spleen disappeared on image studies and metastatic lesions in the lung grew smaller.

The present study evaluated the degree of renal impairment caused by intra-arterial hypertensive chemotherapy (CDDP, PEP). In 11 cases of advanced cancer of the uterine cervix, serum and urinary levels of alpha 1-microglobulin (alpha 1-m) and beta 2-microglobulin (beta 2-m), and urinary albumin (Alb) and lysozyme (LZM) were determined before the chemotherapy and 1,2 and 3 weeks after the therapy. Results are summarized as follows: 1. After intra-arterial chemotherapy, the histological classification was Grade I in 1 case (9.1%), Grade IIa in 2 cases (18.2%), and Grade IIb in 8 cases (72.7%). 2. Serum alpha 1-m and beta 2-m levels remained within the normal range after chemotherapy. 3. Urinary alpha 1-m, beta 2-m and LZM levels exceeded the normal limit between 1 and 2 weeks after the therapy, but thereafter they returned to normal. 4. Urinary Alb was significantly increased (p less than 0.05) between 1 and 2 weeks after therapy, but thereafter it returned to normal. These results suggested that intra-arterial chemotherapy (CDDP 100mg and PEP 40 mg in a dose) was effective for advanced cancer of the cervix and that renal disorders including tubular and glomerular impairment, which are the adverse effects of the therapy, were mild and reversible.

Sialyl SSEA-1 antigen (SLX) is a highly specific tumor marker composed of sugar chain antigens that have Lewis X at their terminals and bind to sialic acid. This antigen is rarely detected in normal tissues, and is present in adenocarcinoma and fetal tissues. We studied the clinical usefulness of SLX in gynecological patients and obtained the following results. (1) The antigen was frequently positive in patients with ovarian cancer with a mean of 89.5 +/- 48.3 U/ml (72.8%, 8/11) and in those with endometriosis with a mean of 39.8 +/- 10.3 U/ml (75.0%, 6/8). (2) Among the gynecological malignancies, the percent positivity was low in those with cervical cancer (20.0%, 5/25), endometrial cancer (33.3%, 1/3), and cancer of the fallopian tube (33.3%, 1/3). (3) The antigen was negative in 20 with myoma uteri, 20 normal pregnant women, and 9 nonpregnant healthy women during the follicular, luteal, or menstrual phase. It was negative in 8 of 9 patients with benign ovarian cyst. False negative results were rare. (4) The SLX level was higher in the ascites than in the serum in patients with ovarian cancer and in those with benign ovarian tumors. (5) The serum SLX in patients with ovarian cancer, which was positive before tumor resection, became negative 2 weeks postoperatively. These results suggest that SLX is a tumor marker with a high specificity to adenocarcinoma of the reproductive organs.

We used a combination assay of serum sialyl SSEA-1 antigen (SLX) and CA125 levels, and evaluated the clinical usefulness of this technique for a differential diagnosis of ovarian cancer, benign ovarian tumor and endometriosis. In 82 patients with ovarian tumors, the sera of 20 (64.5%) of 31 with ovarian cancer and 15 (48.4%) of the 31 with endometriosis (endometrial cyst) were positive for both SLX and CA125, but serum SLX level was 5 U/ml or less in these 14 SLX- and CA125-positive patients with endometriosis. The sera of 16 (80.0%) patients with benign ovarian tumor were negative for both tumor markers. The sera of 3 (9.7%) of 31 with ovarian cancer and the sera of 2 (6.5%) of 31 with endometriosis were negative for both markers. The diagnostic accuracy (true positive rate X true negative rate) of the combination assay for ovarian cancer was 49.0% when the cutoff value of the serum SLX was 38 U/ml but improved to 78.5% when the value was set at 50 U/ml. When the cutoff value of serum SLX was set at 50 U/ml and that of serum CA125 at 35 U/ml, 27 of 37 patients who were positive only for CA125 had endometriosis. From the above observations, a combination assay of serum SLX and CA125 is a promising method for the differential diagnosis of malignant and benign ovarian tumors. Our results also suggest that to improve the diagnostic accuracy, the cutoff value of the serum SLX level should be 50 U/ml for ovarian tumors alone.

In mass screening tests for uterine cancer carried out Shimane Prefecture, we used three different scraping methods. This summary is a report of a comparison of the findings with each method. Results are as follows: From 1973-1982, 214, 798 Japanese women were examined in mass screening tests. Among the 42, 443 examined using a cotton tipped applicator, there were 15 (0.035%) with mild dysplasia, 8 (0.019%) with severe dysplasia, 6 (0.014%) with carcinoma in situ and 8 (0.019%) with invasive carcinoma. In 38,106 women examined using the spatula, 25 (0.066%) had a mild dysplasia, 10 (0.026%) a severe dysplasia, 18 (0.047%) a carcinoma in situ and 26 (0.068%) an invasive carcinoma. In 134,249 examined using a cotton tipped applicator plus colposcopy, 283 (0.211%) had a mild dysplasia 108 (0.080%) a severe dysplasia, 57 (0.042%) a carcinoma in situ and 78 (0.058%) an invasive carcinoma. Thus, the use of a cotton tipped applicator plus colposcopy leads to higher rates of detection of mild and severe dysplasia. In the group with a negative Papanicolaou smear and for whom the cotton tipped applicator plus colposcopy was used, there were 214 with a mild dysplasia, 65 with a severe dysplasia, 11 with a carcinoma in situ and 7 with an invasive carcinoma. The combination of cotton tipped applicator and colposcopy proved to be the most effective for mass screenings for uterine cancer, as the detection rates for severe dysplasia and carcinoma in situ were higher and there were fewer incidences of false negative results.

Unlabelled: We have been treating advanced cancer of the uterine cervix with intra-arterial cisplatin (CDDP) and pepleomycin (PEP) (injected into the bilateral internal iliac artery), combined with radiotherapy and hysterectomy. Concomitant angiotensin II (AT II) administered by intravenous drip infusion was double the tumoral blood flow and thereby enhanced the efficiency of the intra-arterial chemotherapeutic regimen. But CDDP runs the risk of renal and myelotoxicity, so we studied renal dysfunction after treatment by examining serum and urinary beta 2-microglobulin (beta 2-m), and RBC, Hb, WBC, lymphocyte, and PLT., Results: At 1 week after the treatment, evaluation of the histological effects showed, Grade IIb: 72.7% (8/11 cases). Serum beta 2-m was within normal limit and not changed. Urinary beta 2-m levels increased to abnormal levels at 1 and 2 weeks after treatment, and fell to normal levels at 3 weeks after treatment. RBC, Hb, WBC, lymphocyte, and PLT fell most at 3 weeks after treatment and then increased slowly. This suggests that hypertensive intra-arterial chemotherapy (CDDP) impaired kidney and bone marrow, mildly and reversibly, and its appropriate interval is about 4 weeks.

We used a combination assay of serum sialyl SSEA-1 antigen (SLX) and CA125 levels, and evaluated the clinical usefulness of this technique for a diagnosis of ovarian cancer and follow-up of the patient with ovarian cancer. In 28 patients with ovarian tumors, the sera of 8 (66.7%) of 12 with ovarian cancer and 5 (71.4%) of the 7 with endometriosis (endometrial cyst) were positive for both SLX and CA125, but serum SLX level was 50 U/ml or less in all these 5 SLX-and-CA125 positive patients with endometriosis. The sera of all 9 patients with benign ovarian tumor were negative for both tumor markers. No patient with endometriosis was negative for both markers. The diagnostic accuracy (true positive rate X true negative rate) of the combination assay for ovarian cancer was 50.3% when the cut-off value of the serum SLX was 38 U/ml but improved to 81.8% when the value was set at 50 U/ml. From the above observations, a combination assay of serum SLX and CA125 is promising method for the differential diagnosis of malignant and benign ovarian tumors. Our results also suggest that to improve the diagnostic accuracy, the cut-off value of the serum SLX level should be 50 U/ml for ovarian tumors alone. We found following-up two cases of ovarian cancer that the serum SLX level is not affected by the ascites and inflammation. We expect that this combination assay of serum SLX and serum CA125 will be beneficial for diagnosis and follow-up of ovarian cancer.

Mass screenings for uterine cancer have been done on 200,000 women in Shimane Prefecture, Japan, from 1972-1981. Up to 1978, a cotton-tipped applicator was used for sample procurement and since that time a wooden spatula type instrument has been used. A central, cytological diagnostic system has been used since 1979. The cytology activity index (CAI) was about 90 each year. The rate of second examination performed is about 60% for women requiring an accurate examination. Cancer detection rates increased from 0.05% to 0.12%, the false negative rate decreased, cytological and histological findings were in close parallel and the mortality rates have decreased. These positive results are attributed to the use of the wooden spatula and central diagnostic systems. By the mass screening for uterine cancer during these 10 years, 81 women were detected as having carcinoma in situ and 107 women as having invasive carcinoma in the histological findings. The number of first screenings has decreased gradually, but the number examined 6 times or more has increased. These results include that same women have tended to undergo the mass screening examination. In women over 50 y.o., particularly those 60 or over, the number screened was low, yet the incidence of invasive cancer exceeded that in other groups.

To assess the value of mass-screening for uterine cervical cancer, we compared data obtained from a "model area" with findings obtained from the whole of Shimane Prefecture. The factors given attention were: Screening ratio, detection ratio and mortality directly related to cancer of the uterine cervix. These data were obtained from 1976-1980. The results are as follows: Screening ratio and mortality rates were 35.7% and 7.8% respectively, in the model area and 8.4% and 11.5% respectively, in Shimane Prefecture. Four years after setting up the "model area", the mortality rate for uterine cervical cancer reached zero. The ratio of cancer detection in the "model area" was 0.204%, that is about twice that in Shimane Prefecture. The ratios of detection of severe dysplasia, carcinoma in situ and infiltrative carcinoma were higher in the "model area" than in Shimane Prefecture. Detection of severe dysplasia and carcinoma in situ was significantly high in the "model area". Therefore, to reduce the mortality rate for cervical cancer, the CAI should be over 350.

The immunological effect has been studied of the non-specific immunopotentiator sizofiran (SPG) on patients with advanced uterine cervical cancer treated with radiation. Ten cases (study group: SPG group) were administered weekly 40 mg of SPG throughout the course of radiation and two weekly 40 mg during 12 months after radiotherapy. Nineteen cases (control group) were treated with irradiation alone. The lymphocyte count, the PHA index and the ratio of CD4 cells/CD8 cells were significantly reduced by radiotherapy, being observed the most remarkable decrease at post-radiotherapy. But in SPG group, these decreasing values were significantly smaller than in control group and the values showed a more progressive rise during the 12 month respectively. There was no significant difference in peripheral T lymphocyte; CD3, CD4, CD8. The NK cytotoxic activity showed a progressive rise during the 12 month period following a minimal change after radiotherapy. These results suggest that the SPG have some enhancing effect on the function of the lymphocytes.

One hundred and sixteen patients with cervical intraepithelial neoplasia were treated by CO2 laser excisional conization, from 1985 to 1987. All operations in this series were performed in the outpatient unit. 1) In this series, 83.6% (97 out of 116) were patients with CIN and 44.0% (51 out of 116) were patients under the age 39 who can be pregnant. 2) There was no remaining in the 16 materials out of 44 obtained by hysterectomy due to cervical dysplasia and carcinoma in situ (CIS). 3) In our series, 10.3% (6 out of 58) of the women with dysplasia or CIS (surgical margin negative) required two treatments respectively to eradicate their disease from 9 months to 16 months after laser conization. 4) None of 72 women developed postoperative cervical stenosis and cervical infection. 5) Much of the epithelial cover, although originating from columnar cells, became squamous epithelium by 28 days. 6) There were 5 pregnancies in 72 patients, from 5 months to 13 after laser conization. From our studies, a CO2 laser conization for treating CIN preserved the architecture of the cervix, permitting adequate colposcopic and cytological follow-up, and preserved cervical function, so that fertility is not affected and so that there is no interference with pregnancy.

A total of 290 measurements of the size of the fetal liver in utero were made from 19 through 42 weeks of gestation. The right hepatic lobe circumference and area, considered to be the liver size, increased linearly with the advance of gestation. A statistical analysis of these results showed a highly significant correlation between liver size and gestational age (0.87, 0.77: p less than 0.001). The liver size also closely correlated with such growth parameters as biparietal diameter, femur length, and abdominal circumference (0.86, 0.76; 0.85, 0.76; 0.85, 0.73; p less than 0.001). When the liver size of normally grown fetuses was compared with that of growth-retarded fetuses, the liver of the growth-retarded fetuses was found to be significantly smaller (p less than 0.01). We conclude from this study that the measurement of fetal liver size aids in assessing the intrauterine growth of the fetus.

To study the clinical usefulness and false-positive results of CA 125 as a tumor marker of ovarian cancer, we measured serum CA 125 levels in 197 patients with gynecological diseases, 274 normal, pregnant and postpartum women, 14 patients with abnormal pregnancy, 82 healthy women with a normal ovulatory menstrual cycle and 107 healthy non-pregnant subjects, using RIA kits. A level below 34 U/ml was considered the normal CA 125 range. The positive ratio of serum CA 125 in patients with malignant ovarian tumor was 81.3 per cent, and in those with serous cystadenocarcinoma the rate was 100 per cent. On the other hand, only one patient with benign ovarian tumor had a positive CA 125 value. Therefore, we suggest that CA 125 is useful for differentiation between benign ovarian tumor and ovarian cancer. However, because the positive ratio of CA 125 level is high in patients with recurrences of uterine cervical adenocarcinoma, those with tubal cancer, endometriosis, early pregnancy, abnormal pregnancy plus intrauterine fetal death and menstruating women, such situations must be given due attention when CA 125 is used as a tumor marker of ovarian cancer.

To differentiate pre-operatively between leiomyomata uteri and adenomyosis, we measured serum levels of an antigen (CA 125) common to most nonmucinous epithelial ovarian carcinoma in patients with benign uterine tumor (11 of leiomyomata uteri, 7 of adenomyosis and 1 of adenomyosis with leiomyomata uteri). CA 125 in serum samples pre and postoperatively were measured using an RIA Kit. The normal range of CA 125 levels was below 35U/ml. The mean CA 125 level (+/- S.D.) was 18.3 +/- 6.1U/ml in patients with leiomyomata uteri and 93.3 +/- 49.4U/ml in those with adenomyosis. Student's t-test showed a significant correlation (0.001 less than p less than 0.01). The mean CA 125 level in patients with adenomyosis was statistically higher than that in disease-free women. Among 7 patients with surgically demonstrable adenomyosis, the CA 125 values were over 35U/ml (87.5%). In all 11 patients with surgically demonstrable leiomyomata uteri, the CA 125 level was below 35U/ml. The CA 125 level in patients with adenomyosis gradually decreased postoperatively and in all was below 35U/ml up to one month postoperatively. Using this approach, leiomyomata uteri and adenomyosis can be differentiated, pre-operatively.