Clinical value of thymidine kinase in patients with cervical carcinoma.

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.

Three-dimensional ultrasonographic visualization of multiple pregnancy.

Our purpose was to describe interrelationships and contacts between twins in utero by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. Thirteen twin pregnancies (3 monochorionic and 10 dichorionic pairs) and one triplet pregnancy (trichorionic triplet) from 9 to 36 weeks of gestation were studied with a specially developed abdominal three-dimensional transducer (3.5 MHz). This imaging system can provide conventional two-dimensional ultrasonography images and can also generate within seconds high-quality three-dimensional images in the surface and transparent mode with no need for an external workstation. Interrelationships and contacts between twins or triplets are described. Various types of contacts (head/body/arm/leg) and interrelationships were clearly visualized. Crowding of in utero twin fetuses increased with advancing gestation. Sometimes two placentas and dividing membrane were beautifully depicted. In one triplet pregnancy, the interrelationships among 3 fetuses and dividing membranes were easily recognized. Three-dimensional ultrasonography provides a novel means of visualizing multiple pregnancies in utero. These results suggest that three-dimensional ultrasonography has the potential to be a supplement to two-dimensional ultrasonography and would be useful in evaluating the interhuman contacts and crowdings of twin and triplet fetuses in utero.

Clinical courses and thyroid conditions in three infants born to a mother with thyroid stimulating-blocking antibodies.

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.

Prediction of effectiveness of intraperitoneal chemotherapy by intraperitoneal scintigraphy in patients with advanced ovarian carcinoma.

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.

Primary clear cell adenocarcinoma of the fallopian tube with brain metastasis: a case report.

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.

Ovarian cystic teratomas: value of chemical fat saturation magnetic resonance imaging.

Chemical fat saturation (FS) magnetic resonance imaging (MRI) for the characterization of ovarian cystic teratoma was evaluated in 19 patients with 22 lesions. The tumour was evaluated for signal intensity, location and size; the presence of chemical shift artefact, debris and fat-fluid level. Ovarian cystic teratoma was diagnosed prospectively if the mass contained fat and/or more than one type of internal pattern on (1) SE T1-, T2-, (2) SE T1-, T2-, FS T1-weighted images. A correct diagnosis was reached in 17 of 22 tumours on conventional T1- and T2-weighted images, and in 21 of 22 tumours when fat-saturation images were added. When fat-saturation images were added, four of five tumours misdiagnosed on conventional images were then correctly diagnosed. These tumours contained only small amounts of fat. Fat-saturation images could detect smaller amounts of fat than conventional images. However, one tumour did not show decreased intensity on fat saturation images, and was not diagnosed even when fat-saturation images were added. Fat saturation images have been shown to be of value in diagnosing cystic teratomas.

Prognostic importance of histologic vascular density in cervical cancer treated with hypertensive intraarterial chemotherapy.

BACKGROUND: Over the past 20 years, various methods have been suggested to determine the histopathologic stage and grade of cervical cancer for predicting biologic behavior during chemotherapy. However, none of these complicated techniques have proved consistently accurate enough to predict chemotherapeutic effects on locally advanced cervical cancer. METHODS: Primary treatment with hypertensive intraarterial chemotherapy and, 4 weeks later, with radical hysterectomy were performed on 20 patients with locally advanced cancer of the uterine cervix (International Federation of Gynecology and Obstetrics [FIGO] Stages IIa-IVa). The vascular densities of biopsy specimens from pretreatment cancers stained by the Elastica-Goldner technique were measured semiquantitatively. Cytologic and histologic changes in the early stages after the intraarterial chemotherapy were simultaneously recorded. Patients were divided into two groups after analysis of the final histologic effects on operation materials in accordance with the criteria of the Japan Society for Cancer Therapy: (1) an effective group (> or = Grade 2; n = 7) or (2) a noneffective group (< Grade 2; n = 13). RESULTS: The vascular densities of the effective and noneffective groups were 6.91 plus or minus 4.51/mm2 and 1.94 plus or minus 1.21/mm2, respectively. The vascular densities of biopsy specimens were significantly higher in the effective group (P < 0.05). The early cytologic and histologic changes 1 week after chemotherapy were significantly greater in the effective group (P < 0.05). CONCLUSIONS: These results indicate that the efficacy of intraarterial chemotherapy for cervical cancers depends on their individual vascular densities, which can be detected beforehand through the study of biopsy specimens. Furthermore, cytologic and histologic changes in the early stages would seem to reflect the overall histologic effect of the treatment as a whole.

Immunohistochemical studies of the uterine cervix after CO2 laser conization.

OBJECTIVE: To investigate the process of the maturation of cervical epithelium after CO2 laser conization. METHOD: Specimens from the uterine cervix (248) resected from 31 premenopausal females who had hysterectomy after CO2 laser conization were studied with 2 kinds of anti-keratin monoclonal antibodies (PKK-1, KL-1). RESULT: (i) The epithelium covered stroma after 4-6 weeks. (ii) In the normal S-C junction, KL-1 was localized to the middle and upper layers, and PKK-1 to the basal layer. (iii) The staining patterns of KL-1 and PKK-1 in the S-C junctions after conization could be classified into 4 groups according to localization and staining intensity. (iv) The S-C junction appeared normal in all specimens 7 weeks after conization. CONCLUSION: The regenerating epithelium covered the stroma within 4-6 weeks, but resolution of squamous epithelial metaplasia only occurred 7 weeks after conization.

Immunohistochemical evaluation of sialosyl-Tn antigens in various ovarian carcinomas.

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.

Morular metaplasia of the endometrium in a patient with polycystic ovary syndrome.

A 31-year-old women with polycystic ovary syndrome underwent dilatation and curettage (D&C) as part of her infertility workup. Pathologic examination revealed endometrial morular metaplasia without malignant potential. Follow-up D&C had no evidence of endometrial hyperplasia or carcinoma. The diagnostic difficulties and pathogenesis are discussed.

Studies on repair of the uterine cervix after CO2 laser conization with anti-keratin monoclonal antibodies.

Histological repair of the cervical epithelium after CO2 laser conization was studied using resected uterus specimens. (1) Squamous epithelium (ectocervical side) and reserve cells (endocervical side), were seen immediately after conization; (2) HE staining showed that the S-C junction was formed within 4 weeks. (3) Endocervical epithelial repair of the S-C junction tended to be delayed, and the new S-C junction was deeper in the endocervical canal than before conization; (4) The stroma was repaired within 7 weeks, by prompt collagenization.

Endosalpingiosis in association with ovarian surface papillary tumor of borderline malignancy.

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.

Basic evaluation of an immunoradiometric competitive inhibition assay for sialosyl-Tn antigen in sera in women. Assay conditions and normal values.

The assay conditions needed for an immunoradiometric competitive inhibition assay of sera in healthy women were studied using the monoclonal antibody TKH2, which is known to recognize specifically sialosyl-alpha 2,6-GalNAc alpha 1-0-serine/threonine (S-Tn) antigen, a mucinous cancer-related antigen. Stable results were obtained with an incubation time of 1.5 hours at room temperature. The intra-assay and inter-assay coefficients of variation were 3.27% and 3.07%, respectively. The mean (+/- standard deviation [SD]) levels of serum S-Tn in 602 healthy women was 21.2 U/ml (+/- 8.4 U/ml). Values showed a normal logarithmic distribution. Although slightly higher levels were seen in postmenopausal compared with premenopausal women, the differences were not significant. The cutoff value of 41 U/ml was determined from data obtained in 602 healthy women; higher levels were observed in only 2%. Serum S-Tn levels were not strongly influenced by Lewis or ABO (H) blood type, smoking, pregnancy, parturition, or phase of menstrual cycle. The use of the S-Tn antigen as a tumor marker for various gynecologic cancers requires study.

Clinical evaluation of serum sialosyl-Tn antigen levels in comparison with CA 125 levels in gynecologic cancers.

The serum levels of sialosyl-alpha 2,6GalNAc alpha 1-0-serine/threonine (S-Tn) antigen and CA 125 antigen were measured in 205 patients with gynecologic tumors, including 48 ovarian cancers, 20 endometrial cancers, 29 cervical cancers, 57 benign ovarian tumors, 37 uterine leiomyomas, and 14 adenomyosis. Using a cutoff value of 41 U/ml for S-Tn and 35 U/ml for CA 125, positive findings were obtained in ovarian cancers in 31 of 48 (64.6%) patients with S-Tn antigen, and in 36 of 48 (75%) patients with CA 125. In uterine malignancies, positive findings were obtained in 11 of 49 (22.4%) patients and in 8 of 49 (16.3%) patients with the serum S-Tn and CA 125 antigens, respectively. In ovarian benign tumors, false-positive findings with CA 125 were observed in 16 of 57 (28.1%) patients, but with S-TN antigen in only 3 of 57 (5.3%) patients (P less than 0.01). For the ovarian tumors, excluding patients with recurrent disease, the specificity, positive predictive value, and accuracy of the serum S-Tn antigen level for detecting cancer exceeded that of the serum CA 125. The combined assay of serum S-Tn and CA 125 antigens gave positive results in 38 of 48 (79.2%) patients with ovarian cancers; most of the negative findings were obtained in Stage I disease. A significant decreases in serum S-Tn level was observed after cytoreductive surgery in 14 patients with ovarian cancer (P less than 0.01). Four patients with a subsequent recurrence showed a concomitant rise in serum S-Tn. The cyst fluid and ascitic fluid showed high levels of S-Tn antigen in patients with ovarian cancer, in contrast to findings in patients with benign ovarian tumors. In conclusion, serum S-Tn antigen has limited use in diagnosing early stage ovarian cancer and uterine malignancies, but it can detect with accuracy ovarian cancers when used in a combination assay with CA 125 and can monitor the status of disease after therapy.

[Intraperitoneal chemotherapy through implantable injection port in patients with advanced ovarian (or tubal) carcinoma].

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.

CO 2 laser conization for cervical intraepithelial neoplasia: a comparison with cold knife conization during pregnancy.

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.

[Metastatic endometrial stromal sarcoma successfully treated by intra-arterial hypertension chemotherapy with CDDP and ADM].

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.

[Studies on renal dysfunction after intra-arterial hypertensive chemotherapy (CDDP, PEP) for advanced cancer of the uterine cervix--serum.urinary alpha 1-microglobulin, beta 2-microglobulin and urinary lysozyme, albumin].

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.

Detection of intrauterine growth retardation based on measurements of size of the liver.

A total of 646 ultrasonic measurements of fetal liver size were made from 18 weeks of gestation through to term. After 29 weeks, size of the liver in the growth-retarded fetuses was significantly small as compared to findings in the control fetuses. The sensitivity and specificity for the detection of growth retardation were 0.86 and 0.89 at 33 weeks, 0.89 and 0.94 at 38 weeks and 0.89 at 40 weeks of gestation. Growth rate of the liver in the growth-retarded fetus was diminished as compared with findings in the control fetus. Also, a method of estimating fetal weight by ultrasonic measurement of the fetal liver size is described.

Clinical evaluations of the tumor marker sialyl SSEA-1 antigen for clinical gynecological disease.

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.