Kaoru Sakumoto

Combination external beam radiotherapy and high-dose-rate intracavitary brachytherapy for uterine cervical cancer: Analysis of dose and fractionation schedule

PURPOSE To determine an appropriate dose and fractionation schedule for a combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) for uterine cervical cancer. METHODS Eighty-eight patients with uterine cervical squamous cell carcinoma treated with EBRT and HDR-ICBT were analyzed. Twenty-five patients were classified as early disease (nonbulky Stage I/II, less than 4-cm diameter) and 63 patients as advanced disease (greater than 4 cm diameter or Stage IIIB) according to the American Brachytherapy Society definition. Tumor diameter was measured by MRI. Pelvic EBRT was delivered before applications of ICBT. HDR-ICBT was performed once a week, with a fraction point A dose of 6 Gy. Source loadings corresponded to the Manchester System for uterine cervical cancer. No planned optimization was done. A Henschke-type applicator was mostly used (86%). Median cumulative biologic effective dose (BED) at point A (EBRT + ICBT) was 64.8 Gy(10) (range: 48-76.8 Gy(10)) for early disease, and 76.8 Gy(10) (range: 38.4-86.4 Gy(10)) for advanced disease. Median cumulative BED at ICRU 38 reference points (EBRT + ICBT) was 97.7 Gy(3) (range: 59.1-134.4 Gy(3)) at the rectum, 97.8 Gy(3) (range: 54.6-130.4 Gy(3)) at the bladder, and 324 Gy(3) (range: 185.5-618 Gy(3)) at the vagina. Actuarial pelvic control rate and late complication rate were analyzed according to cumulative dose and calculated BED. RESULTS The 3-year actuarial pelvic control rate was 82% for all 88 patients: 96% for those with early disease, and 76% for advanced disease. For pelvic control, no significant dose-response relationship was observed by treatment schedules and cumulative BED at point A for both early and advanced disease. The 3-year actuarial late complication rates (Grade > or =1) were 12% for proctitis, 11% for cystitis, and 14% for enterocolitis. There were significant differences on the incidence of proctitis (p < 0.0001) and enterocolitis (p < 0.0001), but not for cystitis by the treatment schedules and cumulative point A BED. All 4 patients treated with 86.4 Gy(10) at point A suffered both proctitis and enterocolitis. Patients with cumulative BED at rectal point of > or =100 Gy(3) had significantly higher incidence of proctitis (31% vs. 4%, p = 0.013). CONCLUSIONS In view of the therapeutic ratio, cumulative BED 70-80 Gy(10) at point A is appropriate for uterine cervical cancer patients treated with a combination of EBRT and HDR-ICBT. Present results and data from other literatures suggested that cumulative BED at the rectal point should be kept below 100-120 Gy(3) to prevent late rectal complication.

Tumor diameter/volume and pelvic node status assessed by magnetic resonance imaging (MRI) for uterine cervical cancer treated with irradiation

PURPOSE To evaluate the prognostic value of tumor diameter/volume and pelvic node status assessed by magnetic resonance imaging (MRI) in patients with uterine cervical cancer treated with radiation therapy. METHODS AND MATERIALS Forty-four patients with intact uterine cervical squamous carcinoma treated with a combination of external irradiation and high-dose-rate intracavitary therapy were analyzed. Actuarial disease-free survival (DFS), pelvic control rate (PC), and distant metastasis-free rate (DMF) were analyzed by tumor diameter, volume, and pelvic node status assessed by pretreatment MRI. RESULTS Anteroposterior (AP) and lateral (RL) tumor diameter significantly affected DFS. The 2-year DFS was 74% for patients with < 40 mm in AP diameter tumor, and 24% for > or = 40 mm tumor (p = 0.02). Whereas PC was not influenced, DMF was significantly affected by AP tumor diameter. Tumor volume did not significantly affect any endpoints. Patients with enlarged pelvic nodes had significantly poorer outcome compared to those with none on PC, DMF, and DFS. The 2-year DFS was 78% for node-negative, and 10% for node-positive patients (p = 0.0001). CONCLUSION AP tumor diameter and pelvic lymph node status assessed by MRI were the significant prognostic factors in uterine cervical cancer treated with irradiation. Prognostic value of tumor volume should be reassessed prospectively with an appropriate imaging technique. AP tumor diameter predominantly affected the incidence of distant metastasis, and lymph node status affected both pelvic control and distant metastasis.

Prognostic value of cervical size and pelvic lymph node status assessed by computed tomography for patients with uterine cervical cancer treated by radical radiation therapy

PURPOSE To determine the prognostic impact of cervical size and pelvic lymph node status assessed by computed tomography (CT) in uterine cervical carcinoma treated with irradiation alone. METHODS AND MATERIALS Seventy patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IIB and IIIB uterine cervical squamous cell carcinoma treated with a combination of external and high dose-rate intracavitary irradiation were entered into analyses. Univariate and multivariate analyses using the Cox regression model were performed to determine statistical significance of some tumor-related factors. RESULTS There were no significant differences in pelvic control rate (PC), distant metastases-free rate (DMF), cause-specific disease-free survival rate (CSDFS) among subgroups with cervix < 60 mm in diameter. However, PC (p = 0.023), DMF (p = 0.000025), and CSDFS (p = 0.0023) were significantly lower for patients with cervix > or = 60 mm than < 60 mm. The 5-year CSDFS was 77.5% for < 60 mm, and 28.6% for > or = 60 mm. Pelvic node status assessed by CT scans had significant prognostic impact on outcome. the 5-year CSDFS rate was 84.9% for patients with no enlarged nodes, and 58.9% for those with enlarged nodes greater than 1 cm in minimum diameter (p = 0.023). Whereas PC was not significantly affected, the DMF was strongly correlated with nodal status (p = 0.00027). Pelvic node status was taken as an independent predictor for DMF (p = 0.019) on multivariate analysis. CONCLUSION Although cervical size assessed by CT had limited prognostic value, pelvic node status assessed by CT is the significant prognostic factor for patients with uterine cervical carcinoma treated with radical irradiation.

Treatment of malignant ovarian germ cell tumors with preservation of fertility: reproductive performance after persistent remission.

To describe our experience with malignant ovarian germ cell tumors with special reference to reproductive performance after remission, medical records of 31 patients were reviewed. The mean age at diagnosis was 18.6 years. Tumor by stage was I in 16 cases, II in 5, III in 5, IV in 3, and recurrence in 2. Histology was dysgerminoma in 7 cases, yolk sac tumor in 10, immature teratoma in 7, choriocarcinoma in 1, and mixed-type tumor in 6. Conservative surgery for fertility preservation was performed in 21 cases. Postoperative chemotherapy was given to all cases except two with stage Ia dysgerminoma. Of 31 cases, 4 including one fertility-preserved case died of disease. The other 27 cases including 20 fertility-preserved cases were successfully treated. Twenty-five cases (92.6%) have been followed longer than 60 months and 13 cases (48.1%) longer than 120 months. By the last follow-up, 8 of the 20 fertility-preserved cases delivered a total of 9 normal babies. Of the remaining 12 nonpregnant cases, 3 married, 9 have had regular menses, and 3 have had menstrual problems. Two of the latter three cases have been in hypergonadotropic anovulatory cycles. One patient has been diagnosed with tubal infertility caused by peritubal adhesion. Thus, management of the disease with fertility preservation is safe and the majority of patients can attain or retain normal ovarian function and reproductive potential.

Elective Use of Aortic Balloon Occlusion in Cesarean Hysterectomy for Placenta Previa Percreta

Background: Only few reports are available on the use of aortic balloon catheter for cesarean hysterectomy in placenta previa percreta. Case: A 32-year-old woman with placenta previa percreta underwent cesarean hysterectomy at 34 weeks of gestation. Before starting the surgery, an aortic occlusion balloon catheter (30 mm balloon, 5 Fr) was inserted. For total hysterectomy, the aortic balloon catheter was inflated and there was a sudden and dramatic reduction in blood loss, and the surgery was completed safely. An aortic occlusion was sustained for 80 min, with blood loss estimated at 3,200 ml. The postoperative course was uneventful. At 3 months after the operation, the mother and baby remained healthy. Conclusion: An aortic balloon is rapidly and easily inserted, and is an option for major hemorrhage in placenta previa percreta.

Twin pregnancy in each half of a uterus didelphys with a delivery interval of 66 days

A 29-year-old woman complained of secondary infertility. Her first pregnancy resulted in a spontaneous miscarriage three years previously. A uterus didelphys was diagnosed by hysterosalpingography (Fig. 1) and laparoscopy. Intravenous pyelography showed that she had no renal or urinary collecting system abnormalities. The longitudinal vaginal septum separating two small cervices was removed surgically. Her present pregnancy developed following induction of ovulation by clomiphene citrate and human menopausal gonadotrophin, combined with transcervical insemination into each uterine cavity. Ultrasound examinations revealed a gestational sac containing an embryo in each uterine cavity at the eighth gestational week. She had preterm rupture of the membranes at the 25th gestational week. Clear amniotic fluid flowed from the left horn of the uterus, with a decreasing amniotic fluid index. Her temperature increased to 38.5jC with elevation of her white blood count and C-reactive protein. Spontaneous regular contractions occurred in the left horn, accompanied by severe variable decelerations of the fetal heart rate. The right horn of the uterus rarely contracted, and the fetus had no abnormal heart rate patterns. An emergency caesarean section was performed under epidural analgesia. Uterus bicornis bicollis was found. The fetus in the left horn was delivered through a transverse incision of the lower uterine segment of the left horn. A little boy weighing 764 g with Apgar scores of 3 and 4 at 1 and 5 minutes, respectively, was resuscitated immediately and transferred to the neonatal intensive care unit. The placenta weighed 180 g with no findings of chorioamnionitis. Prophylactic intravenous ritodrine chloride was given post-operatively for a few days. No significant regular contractions were noted in the right horn during and after surgery. Her post-operative course was uneventful with no signs of infection. Serial obstetric ultrasound examinations indicated no abnormal findings in the fetus in the right horn of the uterus. At the 35th gestational week, 66 days after delivery of the first twin, spontaneous labour started in the right horn, and the second twin was born spontaneously, a little boy weighing 2360 g with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. The placenta weighed 520 g with no abnormal findings. The first and second babies were discharged without complication on the 108th day after birth, weighing 2090 g, and on the 18th day weighing 2456 g, respectively.

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.

Warfarin-associated fetal intracranial hemorrhage in woman with mitral valve replacements: a case report.

Warfarin-associated fetal hemorrhage is a fatal event. We report the case of a 39-year-old woman who had been taking warfarin for 23 years since undergoing mitral valve replacement. Thereafter, when she was found to be pregnant, the medication was switched to heparin from 6 to 21 weeks of gestation. Following this, she was prescribed oral warfarin again (3.5 mg per day), with a strict control of prothrombin time/international normalized ratio (PT/INR). At 23 weeks of gestation, fetal intracranial hemorrhage occurred because of maternal exposure to warfarin. Maternal PT/INR does not correlate well with the activity of warfarin in the fetus and currently, there is no direct way to prevent fetal intracranial hemorrhage. Hence, further research on the optimal coagulation therapy in pregnant women with valve replacement should be encouraged.

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.

Clearance of Antiphospholipid antibodies in pregnancies treated with heparin

Objective To describe the natural history of serum antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) in pregnant women treated with heparin, and to identify a possible association between changes in antibody status and outcomes of subsequent pregnancies. Methods Thirty-six women with antiphospholipid antibodies who had three or more repeated miscarriages were enrolled. Intravenous heparin was used for each of the first pregnancies after referral. Changes in antibody status were investigated with relation to outcomes of the index and subsequent pregnancies. Results Eighteen of 23 pregnancies in 36 antibody-positive women treated with heparin resulted in term or preterm deliveries with live-born infants, and five ended in abortions. Antibodies cleared in ten of 12 term pregnancies, in five of six preterm pregnancies, and in one of five abortions. There was a statistically significant difference between the term pregnancy and abortion groups (P < .05). Eleven second and third pregnancies in nine women in whom antibodies cleared resulted in term or preterm deliveries of live-born infants, without heparin therapy. The second and third pregnancies in one woman whose antibodies persisted ended in miscarriages despite repeated heparin administration. Conclusion Antiphospholipid antibodies cleared spontaneously in some pregnant women treated with heparin. Subsequent pregnancies among women in whom antibodies cleared were managed successfully without medication, whereas pregnancies in women with persistent antibodies required treatment.