Morihiko Inamine

Histological and immunohistochemical observations of mucin-depleted foci (MDF) stained with Alcian blue, in rat colon carcinogenesis induced with 1,2-dimethylhydrazine dihydrochloride

The usefulness of mucin‐depleted foci (MDF), which have recently been proposed as a new preneoplastic biomarker in rat colon carcinogenesis, was histologically investigated in rat colonic tissues treated with 1,2‐dimethylhydrazine dihydrochloride (DMH). The relationship among aberrant crypt foci (ACF), MDF and β‐catenin accumulated crypts (BCAC) was examined by comparing the corresponding computer‐captured images. Twelve male F344 rats were given DMH s.c. at a dose of 40 mg/kg body weight, once a week for 2 weeks, and randomly divided into two groups. Rats in group 1 were given normal drinking water, while those in group 2 were given drinking water containing indomethacin (IND) at 16 ppm for 6 weeks. All animals were sacrificed 8 weeks after the first DMH treatment. The resected colons were fixed in 10% formalin, and stained with Alcian blue for observation of ACF and MDF. Histological and immunohistochemical analysis revealed that the numbers of ACF, MDF and overlapping lesions in group 2 (treated with IND) were significantly decreased, compared with those in group 1. The number of BCAC in group 2 was also significantly lower than that in group 1. The reduction (61.5%) of MDF by IND was much greater than that (29.3%) of ACF. Analyses of the computer‐captured images indicated that MDF had more frequent dysplastic changes and overexpression of β‐catenin than did ACF. MDF having over 4 crypts or MDF with the appearance of ACF corresponded well to BCAC. These results suggest that MDF may be useful as an early biomarker in colon carcinogenesis.

Inhibitory effect of dietary monoglucosylceramide 1-O-β-glucosyl-N-2''' '-hydroxyarachidoyl-4,8- sphingadienine on two different categories of colon preneoplastic lesions induced by 1,2- dimethylhydrazine in F344 rats

Sphingolipids display a wide spectrum of biological activities, including cell growth, differentiation and apoptosis. However, precise mechanisms by which these compounds exert anticancer or cancer‐preventive effects are not known. In the present study, we evaluated the preventive efficacy of enriched dietary monoglucosylceramide 1‐O‐β‐glucosyl‐N‐2′‐hydroxyarachidoyl‐4,8‐sphingadienine (G1CM) on 1,2‐dimethylhydrazine (DMH)‐induced aberrant crypt foci (ACF) and β‐catenin‐accumulated crypt (BCAC) formation in F344 rats during initiation stage. We also examined whether G1CM affects cell proliferation and apoptosis in these lesions. Pure G1CM was isolated from rice bran. Forty‐two rats were divided randomly into five experimental groups. Rats in groups 1–3 were given subcutaneous injections of DMH (40 mg/kg body weight) once a week for 2 weeks. One week before the first injection of DMH, rats in groups 2 and 3 were fed a diet containing 200 and 1000 p.p.m. G1CM, respectively, for 5 weeks. Rats in group 4 were fed a diet containing 1000 p.p.m. G1CM. Rats in group 5 were given the basal diet alone and served as untreated controls. The experiment was terminated 5 weeks after the start. Dietary G1CM at both doses (groups 2 and 3) significantly inhibited the induction of ACF and BCAC (P < 0.001) when compared to group 1 treated with DMH alone. In groups 2 and 3, the proliferating cell nuclear antigen labeling indices of epithelial cells in ACF and BCAC were also lower than in group 1 (P < 0.0001 for ACF, P < 0.05 for BCAC). These results, that dietary G1CM has possible chemopreventive effects in the present short‐term colon carcinogenesis bioassays, suggest that longer exposure may cause suppression of tumor development. (Cancer Sci 2005; 96: 876–881)

Concurrent chemoradiation for locally advanced squamous cell carcinoma of the vagina: case series and literature review

BackgroundWe reviewed our experience with patients with primary squamous cell carcinoma of the vagina who received concurrent chemoradiation therapy (CCRT).MethodsWe retrospectively analyzed six patients (median age, 60 years) with squamous cell carcinoma of the vagina who underwent CCRT between 2002 and 2005 at the University of the Ryukyus Hospital. Two patients were in International Federation of Obstetricians and Gynecologists (FIGO) stage II, one in stage III, and three in stage IVA. All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Tumor size ranged from 3.2 to 7.7 cm. All patients were treated with true pelvic external-beam radiotherapy (EBRT) at 50 Gy. Then two of the six patients underwent intracavitary vaginal brachy-therapy. The remaining four patients received boost EBRT with shrinking fields. Total radiation dose to the vaginal tumor ranged from 60 to 66 Gy. All patients received two or three concomitant cycles of cisplatin during EBRT.ResultsAll six patients completed their scheduled CCRT, and achieved a clinical complete response. One stage II patient died of disease 24 months after treatment, and the stage III patient had local failure at 12 months. The remaining four patients were free of their disease at 18, 23, 33, and 55 months, respectively. One patient with stage IVA developed a vesicovaginal fistula during CCRT. Nevertheless, CCRT was well tolerated by all six patients, and no grade 3 or 4 late toxicity was observed, as evaluated by the Radiation Therapy Oncology Group (RTOG) scoring system.ConclusionCCRT is effective for primary squamous cell carcinoma of the vagina and should be considered for treatment in patients with high-risk disease having good performance status.

Modifying effects of Terminalia catappa on azoxymethane- induced colon carcinogenesis in male F344 rats

The modifying effects of dietary administration of an herb, Terminalia catappa (TC), were investigated on rat colon carcinogenesis induced by a carcinogen azoxymethane (AOM). The number of aberrant crypt foci (ACF) and &bgr;-catenin accumulated crypts (BCACs) in the colon, and proliferating cell nuclear antigen (PCNA) labelling index in the colonic epithelium were examined in a total of 36 male F344 rats. All animals were randomly divided into five experimental groups (4–10 rats in each group). At 6 weeks of age, rats in groups 1, 2 and 3 were given s.c. injections of AOM once a week for 2 weeks at a concentration of 20 mg/kg body weight. One week before the first injection of AOM, rats in groups 2 and 3 were fed a diet containing 0.02 and 0.1% TC, respectively, throughout the experiment. Rats in group 4 were fed a diet containing 0.1% TC. Rats in group 5 were served as untreated controls. All animals were sacrificed at the experimental week 5 after the start of the experiment. Oral administration of TC at both doses significantly decreased the numbers of both ACF/colon/rat (P<0.05 for 0.02% TC, P<0.005 for 0.1% TC) and BCAC/cm2/rat (P<0.05 for both 0.02 and 0.1% TC), when compared with the control group (group 1). Colonic PCNA labelling index in groups 2 and 3 was also significantly lower than that in group 1 (P<0.001 for 0.02% TC, P<0.005 for 0.1% TC). These results suggest that TC has a potent short-term chemopreventive effect on biomarkers of colon carcinogenesis and this effect may be associated with the inhibition of the development of ACF and BCACs.

External beam boost irradiation for clinically positive pelvic nodes in patients with uterine cervical cancer

The purpose of this study was to retrospectively analyze the treatment results of boost external beam radiotherapy (EBRT) to clinically positive pelvic nodes in patients with uterine cervical cancer. The study population comprised 174 patients with FIGO stages 1B1–4A cervical cancer who were treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT). Patients with positive para-aortic or common iliac nodes (≥10 mm in the shortest diameter, as evaluated by CT/MRI) were ineligible for the study. Fifty-seven patients (33%) had clinically positive pelvic nodes. The median maximum diameter of the nodes was 15 mm (range, 10–60 mm) and the median number of positive lymph nodes was two (range, one to four). Fifty-two of 57 patients (91%) with positive nodes were treated with boost EBRT (6–10 Gy in three to five fractions). The median prescribed dose of EBRT for nodes was 56 Gy. The median follow-up time for all patients was 66 months (range, 3–142 months). The 5-year overall survival rate, disease-free survival rate and pelvic control rate for patients with positive and negative nodes were 73% and 92% (P = 0.001), 58% and 84% (P < 0.001), and 83% and 92% (P = 0.082), respectively. Five of 57 node-positive patients (9%) developed pelvic node recurrences. All five patients with nodal failure had concomitant cervical failure and/or distant metastases. No significant difference was observed with respect to the incidence or severity of late complications by application of boost EBRT. The current retrospective study demonstrated that boost EBRT to positive pelvic nodes achieves favorable nodal control without increasing late complications.

Outcome of pregnancy after laser conization: Implications for infection as a causal link with preterm birth

Objective:  To investigate a causal link between infection and preterm birth in women with a shortened cervix induced by prior laser conization.

Recurrent juvenile granulosa cell tumor of the ovary managed by palliative radiotherapy

Prognosis in the few patients with advanced-stage juvenile granulosa cell tumor (JGCT) of the ovary has traditionally been unfavorable. We report a recurrent JGCT patient managed by palliative radiotherapy. A 37-year-old woman with recurrent JGCT received a combination of paclitaxel–carboplatin chemotherapy and then single-agent docetaxel, but her disease progressed with multiple abdominal masses and ascites. We chose palliative radiation therapy to relieve her complaints. Whole-abdominal external beam radiotherapy with pelvic boost was delivered. She tolerated the treatment well. After the completion of radiotherapy, ultrasonography showed shrinkage of the tumor, and the ascites disappeared. We should consider using radiation therapy in a palliative setting for such patients with recurrent JGCT suffering from abdominal complaints

Radiotherapy- or radical surgery-induced female sexual morbidity in stages IB and II cervical cancer.

Objective The objective of this study was to evaluate the sexual function in cervical cancer survivors after radiotherapy (RT) or radical surgery (RS). Methods This was an observational and cross-sectional study. The Female Sexual Function Index (FSFI) self-reported questionnaires were distributed to 175 patients after RT (RT group) or RS (RS group) and 521 healthy women (control) between 2011 and 2012. Sexual functions were compared among these 3 groups. Results Eligible 92 patients (46 in RT group, 46 in RS group) and 148 control subjects were included for analysis. There was a significant difference in median (range) FSFI total score of 5.5 (3.6–34.7) in the RT group, 18.9 (3.4–31.2) in the RS group, and 22.1 (2–34.2) in the control group (P < 0.001). The median FSFI total score in the RT group was significantly lower than that in the control group (P < 0.001). Six sexual domains (desire, arousal, lubrication, orgasm, satisfaction, pain) were all significantly affected in the RT group, and no significant differences, except pain, were observed in the RS group as compared with the control group. Conclusions Interventions involving counseling and rehabilitation for female sexual function should be provided in cervical cancer survivors, especially after RT.

Massive ovarian edema with torsion: unusual hemorrhage and the recovery of contrast enhancement

We report a case of massive ovarian edema due to left adnexal torsion. On initial magnetic resonance (MR), unusual hemorrhages were demonstrated as several hypointense areas on T2-weighted images. The lack of contrast enhancement was also observed in the left adnexa. Abdominal pain resolved spontaneously, and then follow-up MR demonstrated the recovery of enhancement and hemorrhages as hyperintense signals on T1-weighted images.

Ovarian preservation in young women with endometrial cancer of endometrioid histology.

To clarify the frequency and risk factors of ovarian metastasis in women with endometrial cancer of endometrioid histology.