Masato Kita

Clinical value of FDG-PET in the follow up of post-operative patients with endometrial cancer

Objective: The clinical usefulness of FDG-PET in the follow up of post-operative patients with endometrial cancer was retrospectively evaluated.Methods: Twenty-one post-operative patients with endometrial cancer received 30 FDG-PET examinations to evaluate recurrence or response to treatment. The findings of FDG-PET were compared with their serum levels of tumor markers, CT and/or MRI findings, and the final outcome. Results of FDG-PET were also correlated with the clinical course of each patient.Results: In detecting recurrent lesions and evaluating treatment responses, FDG-PET, with the help in anatomic information by CT/MRI, showed better diagnostic ability (sensitivity 100.0%, specificity 88.2%, accuracy 93.3%) compared with combined conventional imaging (sensitivity 84.6%, specificity 85.7%, accuracy 85.0%) and tumor markers (sensitivity 100.0%, specificity 70.6%, accuracy 83.3%). FDG-PET had no false-negative results, suggesting the possibility of its use as the first-line examination in a patient’s follow-up. FDG-PET could detect unknown lesions in 4 cases, and, as reported for other malignancies, FDG-PET affected the patient management in one-third of the cases. Furthermore, the results of FDG-PET correlated well with the clinical outcome of the patients, with patients with negative PET results tending to show disease-free courses.Conclusions: These results suggest that, despite the limited number of patients studied, FDG-PET was accurate in detecting recurrence and evaluating therapeutic response, and could afford important information in the management of post-operative patients with endometrial cancer. FDG-PET also appeared to have a possibility to predict the outcome of each patient.

FDG-PET/CT for diagnosis of primary ovarian cancer.

Background and aimTo evaluate the diagnostic value of integrated 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) to discriminate malignant from benign ovarian tumors. MethodsOne hundred and eight women suspected of having ovarian cancer underwent preoperative FDG-PET/CT scans. FDG uptake was quantified by calculating the maximum standardized uptake value (SUVmax) of each tumor. The receiver operating characteristic curve was drawn to determine the optimal cut-off values of SUVmax that would best discriminate between benign and malignant tumors. Histopathologic results served as the reference standard. We assessed the association between SUVmax and with International Federation of Gynecology and Obsterics stage in borderline and malignant tumors, using one-factor analysis of variance and an unpaired t test with Bonferoni correction. ResultsThe SUVmax of benign (n=26), borderline (n=12) and malignant (n=73) lesions was 2.00±1.02, 2.72±1.04, and 7.55±4.29, respectively. Although there were significant differences between benign and malignant, and borderline and malignant lesions (P<0.0001), there was no significant difference between benign and borderline lesions. Using an SUVmax cutoff of 2.55, the sensitivity, specificity and accuracy of FDG-PET/CT scanning to detect malignant or borderline tumors were 82.4, 76.9, and 81.1%, respectively. The SUVmax of stage I (n=35), stage II (n=8), stage III (n=34) and stage IV (n=8) was 3.59±2.32, 5.18±1.34, 8.72±2.69, and 15.05±3.77, respectively, and significant differences were observed between SUVmax values and the various International Federation of Gynecology and Obsterics stage (P<0.0001). ConclusionFDG-PET/CT scanning has a high diagnostic value in differentiating between malignant and benign tumors, and a low diagnostic value in differentiating between borderline and benign tumors.

Low-dose non-enhanced CT versus full-dose contrast-enhanced CT in integrated PET/CT scans for diagnosing ovarian cancer recurrence.

OBJECTIVE To evaluate low-dose non-enhanced CT (ldCT) and full-dose contrast-enhanced CT (ceCT) in integrated 18F-fluorodeoxyglucose (FDG)-PET/CT studies for restaging of ovarian cancer. MATERIALS AND METHODS One hundred and twenty women who had undergone treatment for ovarian cancer underwent a conventional PET/CT scans with ldCT, and then ceCT. Two observers interpreted and decided in consensus on the PET/ldCT and PET/ceCT images by a 3-point scale (N: negative, E: equivocal, P: positive) per patient and lesion site. Final diagnoses were obtained by histopathological examinations, or clinical follow-up for at least 6 months. RESULTS Patient-based analysis showed that the sensitivity, specificity, and accuracy of PET/ceCT was 86.9% (40/46), 95.9% (71/74), and 92.5% (111/120), respectively, whereas those of PET/ldCT were 78.3% (36/46), 95.0% (70/74), and 88.3% (106/120), respectively. All sensitivity, specificity, and accuracy significantly differed between two methods (McNemar test, p<0.0005, p=0.023, and p<0.0001, respectively). The scales of detecting 104 recurrent lesion sites were N:14, E:6, P:84 for PET/ceCT, and N:15, E:17, P:72 for PET/ldCT, respectively. Eleven equivocal and one negative regions by PET/ldCT were correctly interpreted as positive by PET/ceCT. CONCLUSION PET/ceCT is a more accurate imaging modality with higher confidence for assessing ovarian cancer recurrence than PET/ldCT.

Cyclical change of hMSH2 protein expression in normal endometrium during the menstrual cycle and its overexpression in endometrial hyperplasia and sporadic endometrial carcinoma

The role of hMSH2 protein, one of the major DNA repair proteins, until now, had not been elucidated in terms of normal endometrial function during the menstrual cycle. The current study was designed to address this issue and to determine whether the expression of hMSH2 is altered in the course of endometrial carcinogenesis.

Plasma dehydroepiandrosterone-to-cortisol ratios as an indicator of stress in gynecologic patients

To evaluate the usefulness of the plasma dehydroepiandrosterone (DHEA)-to-cortisol ratio (D/C) and the plasma aldosterone-to-plasma renin activity ratio (ALDO/PRA) as indicators of stress, we first monitored changes in these ratios associated with surgery in 13 patients who were healthy except for their localized gynecologic diseases. D/C and ALDO/PRA ratios were reduced by 37 and 42%, respectively, 4-5 days postsurgery compared to those 3-4 days before surgery (P less than 0.05 and P less than 0.01, respectively) and returned to preoperative levels 11-13 days after surgery. In contrast, individual hormone levels showed no significant changes associated with surgery. Having documented that these ratios may serve as indicators of stress, we then sequentially measured D/C ratios in patients with gynecologic malignancy subjected to cytotoxic chemotherapy or radiation therapy and in patients in the terminal stage. Although such therapies did not affect D/C ratios to a measurable extent, patients in the terminal stage gave consistently low D/C ratios in spite of normal vital signs (a D/C ratio below 6 was deemed low). Such low ratios occurred only sporadically in other patients and, again, individual values for DHEA and cortisol showed no consistent pattern. We believe that use of D/C ratios as an indicator of stress warrants further investigation.

Macroscopic appearance of a uterus with a cesarean scar pregnancy

Cesarean scar pregnancy (CSP) is an ectopic pregnancy implanted in a previous cesarean scar. Such implantation occurs in approximately 1 in 2000 pregnancies and accounts for 6% of ectopic pregnancies among women with a prior cesarean delivery in high-income countries [1]. Diagnosis is usually made via vaginal or abdominal ultrasound. Many ultrasonographic and magnetic resonance imaging photographs of CSPs have been published [1–3]; however, there are only a few published images showing themacroscopic appearanceof a uteruswith a CSP [2,3]. In their obstetrics textbook, Cunningham et al. [2] included a color photograph of a hysterectomy specimen with a CSP, which was transversely sectioned at the level of the uterine isthmus and the gestational sac. In a recent case series, Maekawa et al. [3] included a black-and-white photograph of a hysterectomy specimen with a CSP (in which the gestational sac can be observed directly), which was opened in the anterior muscle layer just beneath the endometrium. In 2004, awomanpresented to theKobe CityMedical Center General Hospital, Kobe, Japan,with a CSP. Shehad alreadygivenbirth to3 infants via cesarean delivery and did not desire uterine preservation; she underwent hysterectomy at 7 weeks of pregnancy (Fig. 1). Resection of the uterus was achieved by abdominal hysterectomy via laparotomy. The uterine corpus muscle layer was opened in the posterior wall just beneath the endometrium. The endometrium was opened in the posterior wall. The uterine cavity was observed in the center of the uterus. Thick endometrium was also observed. A gestational sac was observed in the thick endometrium at the depressed part of the lower anterior uterine wall. The endometrium just beyond the gestational sac was opened, and the gestational sac was easily extracted from the depressed part of the previous cesarean scar. The embryo was embedded within the amniotic membrane, which was surrounded by a small amount of chorion. The functional endometrium was flapped over and the uterine muscle layer with thin basic endometrium (endometrium contagiosum) was observed. The previous cesarean scar silk suture was observed in the right side of the depressed part of the cesarean scar. The amniotic membranewas opened and the embryo observed directly. Adhesion among themuscle layer, the endometrium, and the gestational sac was loose. As indicated in the present case, pregnancy contents are loosely adhered to each other, and the gestational sac is comparatively small until 7 weeks of gestation. Extraction of the contents of a CSP can be undertaken safely via a vaginal approach with abdominal ultrasound guidance and ample anesthesia.

Preeclampsia as a Manifestation of New-Onset Systemic Lupus Erythematosus during Pregnancy: A Case-Based Literature Review

Introduction New-onset systemic lupus erythematosus (SLE) during pregnancy is rare and difficult to diagnose, especially in cases that manifest as preeclampsia. We report a patient with new-onset SLE that manifested as preeclampsia during pregnancy and provide a review of the literature to identify factors for a rapid diagnosis. Case A 32-year-old primigravid Japanese woman was diagnosed with severe preeclampsia and underwent emergent cesarean section at 29 weeks of gestation. Her hypertension and renal disorder gradually improved after the operation, but her thrombocytopenia and anemia worsened. SLE was diagnosed on postoperative day 5 by a comprehensive autoimmune workup. She was discharged on postoperative day 34 with remission. Conclusion Our case and previous reports suggest that distinguishing underlying SLE from preeclampsia in the third trimester is particularly difficult. Helpful factors for diagnosis of suspected SLE in these cases were persistence of symptoms and new atypical symptoms for preeclampsia revealed after delivery (e.g., fever, renal disorder, and thrombocytopenia).

Incidence of death from congenital toxoplasmosis in 0–4-year-old children in Japan

Congenital toxoplasmosis is caused by Toxoplasma gondii. The incidence of death due to congenital toxoplasmosis in Japan from 1974 to 2007 was calculated using the autopsy database of the Japanese Society of Pathology and vital statistics from the Ministry of Health, Labour and Welfare. Two neonatal deaths due to congenital toxoplasmosis were reported during that time. As there were 161 195 neonatal deaths during this period and 32 465 autopsies were performed, the yearly neonatal death from congenital toxoplasmosis was calculated as 2 × 161 195/32 465/34 = 0.29 and the autopsy rate as 32 465/161 195 = 0.2014 (20.14%). The calculated number of annual deaths in infants was 0.82 and in children aged 1–4 years it was 2.09; thus, although few, deaths from congenital toxoplasmosis do still occur in neonates, infants, and young children. Therefore, obstetricians and pediatricians should be aware of the potential for congenital toxoplasmosis, and pregnant women should make every effort to avoid T. gondii infection.

Insulin-Producing Mediastinal Teratoma in Early Pregnancy

A 33-year-old woman was referred to our hospital for a growing shadow on her chest radiograph (Figure 1A, B). Chest computed tomography revealed an 8-cm multilocular cyst in the anterior mediastinum (Figure 1C). In addition, she was in the sixth gestational week at the first visit to our department. On admission, hypoglycemia (fasting blood glucose [FBG]: 57 mg/dl [80–110]) and hyperinsulinemia (immunoreactive insulin [IRI]: 16 U/ml [5–10]) were recognized, although there had been no previous episode suggesting hypoglycemia. Radiological findings indicated a benign cystic lesion. To reduce any risks associated with continuing with the pregnancy and to fetal growth, we planned initially to postpone performing a surgical resection. However, the tumor grew to 11 cm in 2 months, and this rapid enlargement increased the risk of rupture. Consequently, a tumorectomy via median sternotomy was performed at 18 weeks of gestation. The tumor was located within the thymus but had not invaded the surrounding structure. The histopathological evaluation indicated a mature teratoma (Figure 1D). In addition, insulin immunoreactivity could be seen in the pancreatic islet cells (Figure 1E). Both the FBG and IRI levels returned to within normal range (80 mg/dl and 7.6 mU/ml, respectively) on the postoperative day 8. Both the mother and baby were discharged in healthy condition on postoperative day 15. At 17 months after surgery, the baby is normally developing. Mature teratomas consist of a variety of triploblastic components.1 In the present case, insulin production by neoplastic pancreatic tissue was suspected because of the presence of insulin-positive cells in the tumor and by the fact that the IRI level promptly returned to within normal range after surgery. There are many reports of teratomas with pancreatic tissue.2 However, we could find only one article reporting hypoglycemia caused by an insulin-producing teratoma.3 Bordi et al.4 showed that pancreatic tissue in mature teratomas was histologically differentiated and that its function was under endocrinological control. In the present case, although insulin secretion was not evaluated by a sugar tolerance test because of the pregnancy, the change in FBG levels implies that the endocrine function of the intratumoral pancreatic islets was not completely under homeostatic control. It is notable that the preoperative biparietal diameter of the fetus was below average but that the size returned to within the normal range after surgery (Figure 2). At 37 weeks of gestation, the baby was born without any complications and weighed 2666 g. This suggests that the maternal hypoglycemia caused by the excessive insulin might have affected intrauterine growth. Waugh et al.5 reported that pregnant females with anorexia nervosa were at a high risk of intrauterine growth restriction (IUGR), which suggests that maternal malnutrition, including hypoglycemia caused by starvation, influences IUGR. Therefore, if the surgery had been delayed even longer, the intratumoral islet cells would have kept on producing high levels of insulin above the physiologically required level, and the resulting maternal hypoglycemia could have caused IUGR and/or led to other unexpected complications.

Plasma dehydroepiandrosterone‐to‐cortisol ratios as an indicator of stress in gynecologic patients

PJasma dehydroepiandraaterone-to-cortisol ratios aa an indicator of stress ia gyoecologic patients Ozasa H; Rita M; lnoue T, Mori T Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoro University, Sakyo-ku. Kyoto 606. JPN GYNECOL ONCOL 1990, 37/2 (178-182) To evaluate the usefulness of the plasma dehydroepiandrosterone (DHEA)-to-cortisol ratio (D/C) and the plasma aldosterone-to-plasma renin activity ratio (ALDOIPRA) as indicators of stress, we first monitored changes in these ratios associated with surgery in 13 patients who were healthy except for their localized gynecologic diseases. D/C and ALDOIPRA ratios were reduced by 37 and 42%, respectively, 4-5 days postsurgery compared to those 3-4 days before surgery (P < 0.05 and P < 0.01, respectively) and returned to preoperative levels 1 l-13 days after surgery. In contrast, individual hormone levels showed no significant changes associated with surgery. Having documented that these ratios may serve as indicators of stress, we then sequentially measured D/C ratios in patients with gynecologic malignancy subjected to cytotoxic chemotherapy or radiation therapy and in patients in the terminal stage. Although such therapies did not affect D/C ratios to a measurable extent, patients in the terminal stage gave consistently low D/C ratios in spite of normal vital signs (a D/C ratio below 6 was deemed low). Such low ratios occurmd only sporadically in other patients and, again, individual values for DHEA and cortisol showed no consistent pattern. We believe that use of D/C ratios as an indicator of stress warrants further investigation.