Masao Shimaoka

Feasibility of concurrent cisplatin use during primary and adjuvant chemoradiation therapy: a phase I study in Japanese patients with cancer of the uterine cervix

BackgroundAlthough the prognostic advantages of concurrent cisplatin (CDDP) chemoradiation therapy (CCRT), for uterine cervical cancer (UCC) has been demonstrated, the feasibility of concurrent CDDP administration has not yet been evaluated. We determined the optimal CDDP dose for both weekly and monthly schedules during primary and adjuvant CCRT in patients with UCC.MethodsThe study was conducted as a phase I, dose-escalation trial. Concurrent CDDP was started at the dose of 30 mg/m2 for the weekly schedule and at 50 mg/m2 for the monthly schedule, and the doses were steadily escalated to the maximum tolerated dose (MTD).ResultsA total of 45 patients with UCC (25 receiving primary CCRT and 20 receiving adjuvant CCRT) were entered in the study. In both the primary and adjuvant CCRT patients, the MTD was observed to be 40 mg/m2 for the weekly schedule and 80 mg/m2 for the monthly schedule. Dose-limiting toxicity was observed in 10 patients (granulocytopenia in 9 patients and diarrhea in 1 patient). Disease recurrence was confirmed in 6 patients in the primary CCRT group during a mean follow-up period of 22.4 ± 13.2 months, and in patients 3 in the adjuvant CCRT group during a mean follow-up period of 17.7 ± 6.8 months.ConclusionFor Japanese patients with UCC receiving primary or adjuvant CCRT therapy, the recommended CDDP dose was determined to be 30 mg/m2 for the weekly schedule and 75 mg/m2 for the monthly schedule.

Total abdominal hysterectomy versus laparoscopically-assisted vaginal hysterectomy versus total vaginal hysterectomy

Introduction: While total abdominal hysterectomy (TAH) and total vaginal hysterectomy (TVH) are conventional procedures, we have actively introduced laparoscopically‐assisted vaginal hysterectomy (LAVH) since its advent. This study was the first attempt to retrospectively compare the surgical results, including invasiveness, among the three methods of performing a hysterectomy.

Reproductive Outcome of Infertile Patients with Fibroids Based on the Patient and Fibroid Characteristics; Optimal and Personalized Management.

Aims: To analyze the detailed clinical course of infertile patients with uterine fibroids and to identify optimal and personalized treatment based on the patient or fibroid characteristics. Methods: Retrospective analysis of a case series was performed on 176 infertile patients with fibroids. The patients were classified into different groups according to different treatments (conservative infertility treatment, myomectomy and non-myomectomy surgery). Patient or fibroid characteristics for different groups were analyzed for a possible correlation with the reproductive outcome. Results: The cumulative pregnancy rates by conservative treatment plateaued in 1 year. Myomectomy improved the reproductive outcome in patients who did not conceive with conservative infertility treatments. The most important determinant of the reproductive outcome in patients by conservative treatment prior to surgery was a past patient history of pregnancy. The most important determinant of the reproductive outcome after myomectomy was patient age. Conclusion: Myomectomy should be considered when infertile patients with fibroids do not conceive within 1 year of conservative infertility treatments. The most important determinant of reproductive outcome after myomectomy is patient age. Therefore, for patients younger than 40, the treatment schedule should be carefully considered so that the patients can sufficiently benefit from myomectomy and assisted reproductive technology.

Exposure to ethinyl estradiol prenatally and/or after sexual maturity induces endometriotic and precancerous lesions in uteri and ovaries of mice

Unrecognizable exposure to estrogenic substance may cause estrogen‐dependent diseases, endometriosis and cancer. Pregnant mice (ICR/Jcl, CLEA) were exposed to 0.01 mg ethinyl estradiol (EE2)/kg per day or vehicle (olive oil) through oral intubation from day 11 to 17 of gestation. They delivered their offspring and raised them. When the experimental female F1 mice were at 8 weeks of age, they were not exposed to EE2 or to the same dose of EE2 or to vehicle twice a week until 20 weeks of age. The control female F1 mice were exposed to the same dose of EE2 or vehicle alone, similarly. All mice were killed at 28 weeks of age. The resected uteri and ovaries were processed for microscopic examinations and for determination of the aromatase mRNA levels and aromatase protein through quantitative RT‐PCR and Western blotting, respectively. Adenomyosis and adenocarcinomatous changes were significantly discernible in the EE2‐exposed uteri, and incidence of ectopic glands and serous cysts were significantly increased in the prenatally EE2‐exposed ovaries as compared with respective controls. Significant upregulation of the aromatase mRNA was seen in the prenatally EE2‐exposed uteri and in the EE2‐exposed ovaries. The aromatase protein was identified in all ovaries examined, and in EE2‐exposed uteri but not in controls and confirmed its localization in eutopic and ectopic glands, abnormally proliferated lesions and the lining of the cysts. Taken together, continuous EE2 exposure may cause endometriotic and precancerous lesions due to excessive estrogen synthesis in both target organs.

Erythropoietin is involved in hemoprotein syntheses in developing human decidua.

Before establishment of feto‐placental circulation, decidua can synthesize hemoproteins to maintain oxygen homeostasis in situ. Using the human decidua of induced abortions ranging from 5 to 8 weeks of gestation, we determined the expression levels of erythropoietin, erythropoietin receptor, cytoglobin, myoglobin, embryonic‐, fetal‐ and adult hemoglobin mRNA by quantitative RT‐PCR analysis and identified their proteins by Western blot and immunohistochemical analyses. Erythropoietin signaling was demonstrated in phosphatidylinositol‐3‐kinase/protein kinase B pathway by Western blot, and the transcriptional factors for erythroid and non‐erythroid heme synthesis were examined by RT‐PCR analysis. In decidua, erythropoietin and its receptor mRNAs, erythropoietin receptor protein and phosphatidylinositol‐3‐kinase, were expressed with a peak at 6 weeks of gestation. Moreover, the decidua during 5 to 8 weeks of gestation expressed embryonic, fetal and adult hemoglobins additionally cytoglobin and myoglobin at transcriptional and protein levels. The heme portion of these hemoproteins is considered to be synthesized by non‐erythroid δ‐aminolevulinate synthase. These hemoproteins were discernible especially in decidual cells concomitant with cytotrophoblast cells and macrophage in these developing decidua. Considering the different capacity for oxygen binding and dissociation among hemoglobins with the oxygen storage capacity for cytoglobin and myoglobin, these hemoproteins appear to play a role in oxygen demand in decidua in situ before development of feto‐placental circulation under the control of erythropoietin signaling.

Efficacy of preoperative gonadotropin‐releasing hormone agonist therapy for laparoscopic myomectomy

Objective: In this article, we evaluate efficacy of preoperative gonadotropin‐releasing hormone agonist (GnRHa) therapy prior to laparoscopic myomectomy (LM).

Definitive diagnosis of primary adenocarcinoma of the appendix by laparoscopic appendectomy

We report a 62‐year‐old woman with a primary adenocarcinoma of the appendix mimicking ovarian tumor. We had diagnosed it definitively by laparoscopic appendectomy, and additional surgery was required in this case. However, the present case suggests that, in some cases, if cancer of the appendix can be diagnosed early, laparotomy can be avoided and the cancer treated with minimally invasive laparoscopic surgery alone.

Nontuberculous Mycobacterial Infection in the Uterine Cervix Mimics Invasive Cervical Cancer in Immunocompetent Woman.

Nontuberculous mycobacterial (NTM) infection is increasing across the world. Although the most common clinical manifestation of NTM disease is lung disease, a rare form of disseminated NTM disease has also been documented. Disseminated NTM usually develops in severely immunocompromised individuals, especially those with advanced AIDS. This manifestation is rare in non-HIV-infected hosts and is associated with immunosuppressed conditions. However, recent reports have suggested that disseminated NTM disease in immunocompetent patients without HIV infection has been increasing. Dissemination may involve any organ system, but a case in the female genital tract has never been reported. We report a case in a 67-yr-old previously healthy woman who presented with a disseminated NTM infection in the uterine cervix. The primary presentation was general fatigue and body weight loss. The patient also presented with a mass formation that mimicked cervical cancer on magnetic resonance imaging. In addition to the cervical mass, the patient presented with a mass formation in the omentum; wall thickening of the vagina, bladder, and ureter; and retention of pleural/peritoneal fluid. Vaginal cytology was negative. A diagnosis was made only after detecting acid-fast bacilli in a biopsy specimen of cervical mass, which was conducted under suspicion of cervical malignancy. Then, Mycobacterium avium was confirmed in a polymerase chain reaction test of cervical tissue. After administration of antimycobacterial therapy, the mass and other findings on magnetic resonance imaging disappeared. Infection in multiple organs leads to the diagnosis of disseminated NTM. This case indicates that, for prompt and accurate diagnosis, efforts to detect specific lesions by an imaging study and to confirm diagnosis pathologically are equally important, especially when local cytology is not convincing. The clinical course of this case may serve as a useful reference in the diagnosis and treatment of NTM.