Ichiro Kohno

Expression of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase in early concepti

Indoleamine 2,3-dioxygenase (IDO)-initiated tryptophan degradation in the placenta has been implicated in the prevention of the allogeneic fetus rejection [Munn, Zhou, Attwood, Bondarev, Conway, Marshall, Brown, and Mellor (1998) Science 281, 1191-1193]. To determine how IDO is associated with the development of the fetus and placenta, the time course of IDO expression (tryptophan-degrading activity, IDO protein and IDO mRNA) in the embryonic and extra-embryonic tissues as well as maternal tissues of mice was examined. A high tryptophan-degrading activity was detected in early concepti on days 6.5 and 7.5, whereas IDO protein and its mRNA were not expressed during early gestation, but appeared 2-3 days later, lasted for about 3 days and declined rapidly thereafter. The expression of IDO basically coincided with the formation of the placenta. On the contrary, the early tryptophan-degrading activity was due to gene expression of tryptophan 2,3-dioxygenase (TDO), as shown by Northern and Western analysis. These findings indicate that IDO is transiently expressed in the placenta but that the expression does not last until birth, and that the IDO expression is preceded by expression of another tryptophan-degrading enzyme, TDO, in the maternal and/or embryonic tissues in early concepti.

First-line intraperitoneal carboplatin-based chemotherapy for 165 patients with epithelial ovarian carcinoma: results of long-term follow-up.

OBJECTIVE Currently, no long-term follow-up data are available on intraperitoneal (IP) carboplatin-based chemotherapy for ovarian carcinoma. In this study we evaluated retrospectively the survival and recurrence of a retrospective cohort of patients with epithelial ovarian cancer treated with first-line IP carboplatin-based therapy. METHODS Records were reviewed of 174 patients with epithelial ovarian cancer who received IP carboplatin-based therapy between 1990 and 2000. All patients underwent surgical staging, and implantable port systems were placed regardless of residual tumor size. The pathological slides were submitted and reviewed, and then nine patients were excluded because of borderline malignancies (n = 8), and wrong histology (n = 1). Therefore, the records of 165 patients were analyzed for survival. Tumor grade was determined by the Universal grading system. Statistical analysis included tests for association between potential prognostic factors, and between prognostic factors and survival. Survival probabilities were estimated by Kaplan-Meier methods, and prognostic factors for survival were evaluated by a Cox regression model. RESULTS The mean age of the patients was 53.7 years (range 21-83). The median follow-up was 41 months. The distribution by stage and histology was as follows: high risk (grade 2/3, clear cell, capsule rupture) stage I, 54; II, 21; III, 72; IV, 18; and serous, 75; clear cell, 30; mucinous, 27; endometrioid, 20; others, 13. The chemotherapy regimen was either carboplatin alone (n = 22) or in combination with cyclophosphamide (n = 116) or paclitaxel (n = 27). Catheter-related complications occurred in 16 (9.7%) cases. The chemotherapeutic response in 54 patients with measurable disease was 66.4%. The 5-year survival was 94.4% for stage I, and 87.9% for stage II. The median survival for optimal and suboptimal stage III/IV patients was 51 months and 34 months, respectively. The median survival of patients with stage III/IV disease was 51 months with carboplatin doses of 400 mg/m(2) or more, but it was only 25 months with carboplatin doses smaller than 400 mg/m(2). Poor prognostic factors, determined by Cox regression multivariate analysis, were clear cell histology (P < 0.001) and a carboplatin dose smaller than 400 mg/m(2) (P = 0.002). CONCLUSIONS Survival of patients who underwent carboplatin-based IP chemotherapy was excellent when the dose of carboplatin was higher than 400 mg/m(2). A prospective evaluation of IP carboplatin therapy with modern combination is warranted.

Platelet-sparing effect of paclitaxel in heavily pretreated ovarian cancer patients.

Abstract. Carboplatin has proven to be effective in the treatment of patients with recurrent ovarian cancer who have responded to platinum-based first-line chemotherapy. However, thrombocytopenia is a problem in heavily pretreated patients. Paclitaxel has a so-called platelet-sparing effect, but until now it was unknown whether this effect could be obtained in heavily pretreated patients. We treated four patients with recurrent epithelial ovarian cancers who had previously undergone heavy chemotherapy. Because these patients had responded to platinum-based first-line therapy, single carboplatin administration was employed. Although satisfactory tumor marker responses were obtained, thrombocytopenia occurred. When paclitaxel was administered before the carboplatin infusion in the subsequent treatments, the thrombocytopenia became milder. It was concluded that a platelet-sparing effect was also observed in patients who had undergone heavy prior chemotherapy.

Florid Endocervical Glandular Hyperplasia with Pyloric Gland Metaplasia: A Radiologic Pitfall

A case of florid endocervical glandular hyperplasia with pyloric gland metaplasia is described. MR images showed multiple and conjugated cysts in the uterine cervix, which suggested adenoma malignum. A postoperative examination revealed florid but definitely benign endocervical glandular hyperplasia. Hitherto described radiologic features considered suggestive of adenoma malignum are not necessarily specific and can be a diagnostic pitfall.

Adenoid basal carcinoma of the cervix uteri: A case report

We report a rare case of adenoid basal carcinoma of the uterine cervix, unexpectedly found in a uterus resected for the treatment of cervical Intraepithelial neoplasia (CIN) 3. The patient was a 47‐year‐old Japanese female. She received a total abdominal hysterectomy under a diagnosis of CIN 3 of the cervix. Grossly, there were no significant findings in the surgical specimens. Microscopically, in seven of the 12 blocks of the cervix examined, scattered small nests of uniform small cells, which extended 4 mm below the epithelial surface, with dark nuclei and scant cytoplasm were observed. Peripheral palisading as well as the formation of gland‐like or acinar structures were noted. The latter were positive for mucicarmine. Stromal reaction was not obvious. There were also foci of squamous differentiation in some portions of the small nests. Occasional mitoses as well as large atypical cells were also seen in this area. Immunohistochemically, the foci of squamous differentiation were positive for carcinoembryonic antigen. The epithelial surface In other portions showed CIN 3 with crypt extension. Distinction between adenoid basal carcinoma of the cervix and other diseases, such as adenoid cystic carcinoma and squamous cell carcinoma with basaloid features, is Important for clinical management because the clinical behavior of adenoid basal Carcinoma is less malignant.

Basement membrane material and tigroid background in a fine needle aspirate of clear cell adenocarcinoma of the cervix : A case report

BACKGROUND Although cytologic findings of clear cell adenocarcinoma of the female genital tract have been reported sporadically, the background on the smear has received little attention. CASE A 16-year-old female had a large, necrotic mass in the cervix. As cervical brushing cytology and a punch biopsy of the mass could not make a definitive diagnosis, fine needle aspiration cytology was performed from the mass. The smears revealed loose, three-dimensional clusters and sheet arrangements of atypical cells. Dispersed atypical cells were also seen. The atypical cells were large and had abundant, weakly stained cytoplasm and round or oval nuclei with large nucleoli. There were a few tumor cells with clear cytoplasm and distinct cell borders in Papanicolaou-stained smears. The background in Diff-Quik-stained smears revealed a tigroid background and basement membrane material. CONCLUSION The malignant tumor, revealing both a tigroid background and basement membrane material, seems to have been clear cell adenocarcinoma. Both features are diagnostic clues to clear cell adenocarcinoma in the female genital tract. Our case indicates that aspiration cytology is also an effective method of diagnosing a cervical tumor when the tumor is polypoid and the surface is extensively necrotic.

A feasibility study on biweekly administration of docetaxel for patients with recurrent ovarian cancer

OBJECTIVE A recent study demonstrated that docetaxel (DTX) was an effective agent for second line chemotherapy against ovarian cancer. Weekly administration of taxane compounds had been more effective compared with a 3 week interval administration in ovarian cancer. The role of biweekly administration of DTX has been unknown. We conducted a dose determination and feasibility study of biweekly DTX administration in patients with ovarian cancer. METHODS Patients with histologically confirmed epithelial ovarian cancer who received one or more regimens of prior chemotherapy with more than 4 weeks of treatment-free interval were eligible. DTX was administered as 1-h intravenous infusion every two weeks for at least four courses. The starting dose was 40 mg/m(2) (level 1) and the dose was escalated to 50 mg/m(2) (level 2) and 60 mg/m(2) (level 3) in consequent patient cohorts. RESULTS Nine patients were examined in this study. The treatments were completely performed in all cohorts. Mean treatment delay ranged from 0 to 2.0 days. Dose level did not affect treatment delay. At the first dose level, no patients experienced grade 3/4 neutropenia. Two patients in level 2 experienced grade 3/4 neutropenia. In level 3, all patients had grade 4 neutropenia. Nonhematologic toxicities were tolerable. Of eight patients with measurable disease, all patients in level 1 showed progressive disease, and all patients in level 2 were no-change. There were two responders showing complete response and partial response and one case was no-change in level 3. CONCLUSION The present study showed that biweekly administration of 60 mg/m(2) DTX was feasible for recurrent ovarian cancer.

Papillary squamous cell carcinoma of the uterine cervix: diagnostic pitfalls

A case of papillary squamous cell carcinoma (PSCC) of the uterine cervix is reported. The patient was a 73‐year‐old Japanese woman with acute renal failure and bilateral hydronephrosis. A cauliflower‐like mass was found in the uterine cervix. A uterine cervical biopsy specimen revealed PSCC in situ, while clinically it was an invasive carcinoma. Uterine cervical biopsy was performed a second time to confirm its stromal invasion. However, only small fragments were obtained because of heavy bleeding from the tumor and they showed PSCC in situ again. Following this, computed tomography of the pelvis revealed a 5 cm mass in the uterine cervix, invading the vagina and urinary bladder. Though deep‐wedge biopsy, loop electrosurgical excision, or cone biopsy is recommended to evaluate PSCC, it may be impossible to perform any of these procedures because of bleeding such as that seen in our case. In these circumstances, good communication between pathologists and clinicians is important since lack of communication may cause PSCC to be microscopically misinterpreted as in situ carcinoma rather than invasive carcinoma.

Adenocarcinoma in situ of the fallopian tube. A case report.

BACKGROUND So far only a few cases of carcinoma in situ of the fallopian tube have been reported, but its detailed clinical and pathologic findings, including cytology, have not been fully described. CASE A 70-year-old female was admitted to our hospital because of irregular genital bleeding. Endometrial smear revealed a small number of atypical cells with a clear background. Hysterectomy, bilateral salpingo-oophorectomy and omentectomy were performed. Grossly, a grayish white papillary tumor, measuring 1.5 x 1.0 cm, was observed within the lumen of the left fallopian tube. Microscopically, the diagnosis of papillary adenocarcinoma in situ of the left fallopian tube was made according to 1992 International Federation of Gynecologists and Obstetricians fallopian tube staging. CONCLUSION Although endometrial brush cytology is not sensitive enough to detect a primary carcinoma of the fallopian tube, our case indicates that it may contribute useful information on extrauterine diseases and can detect a stage 0 cancer of the fallopian tube. Clinicians, as well as pathologists, should consider the possibility of fallopian tube cancer if cervical or endometrial cytology shows atypical cells with papillary patterns with a clear background but endometrial curettage cannot prove malignancy.

Subcutaneous transposition of the ovary following hysterectomy

Objectives: Preservation of ovarian function at hysterectomy in pre‐menopausal women is desirable. A possibly malignant tumor from retained ovary is a concern. We demonstrate a new technique for exteriorization of the ovaries. Method: In 27 patients, the infundibulopelvic ligament was mobilized. The retroperitoneal space was then widely opened. The ovary was gently pulled through a fascial incision and fixed on the fascia followed by skin closure. Results: Cystic formation was common (66.7%). Four patients had extreme enlargement of the transposed ovary. A needle puncture revealed intra‐ovarian hematomas or fluid retention. One had puncture of the translocated ovary for in vitro fertilization more than two years following transposition. Conclusions: Possible advantages are (1) early detection and diagnosis of ovarian cysts, (2) easy surgical access to remove ovarian cysts, (3) transposition of ovaries outside the radiation field and (4) in vitro fertilization is facilitated. Comparative study for ovarian function is ongoing.