Akiko Shinagawa

Comparison of 18F-FDG PET and MRI in Assessment of Uterine Smooth Muscle Tumors

The purpose of this study was to prospectively determine whether combined MRI and 18F-FDG PET is more accurate than MRI in assessing nonbenign uterine smooth muscle tumors (USMTs). Methods: Seventy patients (mean age, 49 ± 10 y; range, 28–77 y) suspected of having nonbenign USMTs underwent both MRI and 18F-FDG PET before surgery. Results were evaluated using receiver-operating-characteristic (ROC) analyses and the Cochran Q test. Results: The area under the ROC curve for MRI with 18F-FDG PET was significantly higher than that for MRI (0.97 vs. 0.89, P < 0.05). Although multiple comparisons using the Cochran Q test were not significant, the sensitivity, specificity, and accuracy for MRI with 18F-FDG PET with probable nonbenign USMT cases considered to be positive were higher than those for MRI (93.3% vs. 73.3%; 92.7% vs. 85.5%; and 92.9% vs. 82.9%, respectively). Conclusion: MRI with 18F-FDG PET is useful in assessing nonbenign USMTs, as compared with MRI.

Localisation of phosphorylated mTOR expression is critical to tumour progression and outcomes in patients with endometrial cancer

Correlations between mammalian target of rapamycin (mTOR) expression, and clinicopathological features, outcome and Akt expression in endometrial endometrioid adenocarcinoma (EEC) were investigated. Tumour samples were obtained from 82 patients with EEC who had undergone hysterectomy, and phosphorylated mTOR (p-mTOR) and Akt (p-Akt) expression in the cytoplasm and nucleus was analysed by immunohistochemical staining. Nuclear p-mTOR was significantly elevated in poorly differentiated tumours and positively correlated with lymph node involvement (P = 0.05). Nuclear p-mTOR expression was associated with significantly shorter relapse-free survival (RFS) (P<0.01) and slightly shorter overall survival (OS) (P = 0.08). Cytoplasmic expression of p-mTOR was not correlated with any clinicopathological factors. Although not significant, cytoplasmic p-mTOR expression was associated with shorter PFS and OS (P = 0.09, P = 0.283, respectively). Neither cytoplasmic nor nuclear p-Akt expression was associated with clinicopathological factors or with survival. Localisation of p-mTOR may be critical for tumour progression and outcomes in patients with EEC.

Transient elevation of international normalized ratio during cisplatin-based chemotherapy in patients who are taking warfarin.

Objective: To report 2 cases of a probable interaction between cisplatin and warfarin. Case Summary: Two cases of transient elevation of international normalized ratio (INR) during Irinotecan (60 mg/m2 on days 1, 8, and 15) plus cisplatin (60 mg/m2 on day 1) chemotherapy with concomitant warfarin are presented. In both cases, warfarin dosages were stable at the therapeutic target range prior to initiation of chemotherapy. Granisetron hydrochloride (3 mg on days 1, 6, and 15) and dexamethasone (13.2 mg on day 1 and 6.6 mg on days 2, 3, 8, and 15) were used prior to irinotecan administration in both patients. In addition, aprepitant was administered to both patients for 3–5 days with cisplatin. One of these patients also received aprepitant with irinotecan on days 8 and 15. During chemotherapy, INR was transiently elevated almost 1.5-fold over baseline level on day 3. This variation did not occur in subsequent irinotecan cycles on days 8 and 15. The timing of these increases was similar in each of the cycles. Discussion: Cisplatin was the common drug in the cases presented and therefore could be related to the INR elevations. To our knowledge, these are the first reports of an Interaction between warfarin and irinotecan-cisplatin chemotherapy, but reports of a similar interaction with chemotherapy including platinum derivatives exist. Use of the Horn Drug Interaction Probability Scale indicated a probable interaction between warfarin and cisplatin. Conclusions: Cisplatin might affect the anticoagulation function of warfarin. Careful INR monitoring is necessary during antineoplastic chemotherapy with cisplatin in patients taking warfarin.

Different Prognostic Implications of 18F-FDG PET Between Histological Subtypes in Patients With Cervical Cancer.

AbstractThis study aimed to investigate whether the predictive values of intensity- and volume-based PET parameters are different between histological subtypes in patients with cervical cancer.Ninety patients, 65 with squamous cell carcinoma (SCC) and 25 with non-SCC (NSCC), who underwent pretreatment 18F-FDG PET/CT and pelvic MRI, were studied retrospectively. In addition to SUVmax and SUVmean, metabolic-tumor-volume (MTV) was determined by thresholding of 40% SUVmax and total-lesion-glycolysis (TLG) was calculated. Clinical factors and PET metabolic indices were compared between SCC and NSCC. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method with cut-offs determined by ROC analyses to stratify SCC and NSCC patients separately. Factors associated with survival were assessed with univariate and multivariate analyses using the Cox regression model.No significant differences were observed in clinical factors other than tumor size or 18F-FDG PET metabolic indices between SCC and NSCC. The Kaplan–Meier estimates of 2-year PFS and OS rates were 60% and 70% for SCC and 40% and 76% for NSCC, respectively. Multivariate analyses showed that MTV and TLG were the independent prognostic factors for PFS and OS in SCC; in contrast, SUVmax was the independent prognostic factor for PFS and OS in NSCC.Metabolic burden (MTV and TLG) could be beneficial for the prognostic prediction of cervical SCC patients; in contrast, metabolic intensity (SUVmax) could be beneficial for the prognostic prediction of NSCC patients. The different prognostic implications might be based on the differences of tissue integrity and histological heterogeneity between SCC and NSCC.

18 F-FDG/ 18 F-FES standardized uptake value ratio determined using PET predicts prognosis in uterine sarcoma

We investigated whether 16α-[18F]-fluoro-17β-estradiol (18F-FES) and 18F-fluoro-deoxyglucose (FDG) uptake measured using positron emission tomography (PET) predicted prognosis in 18 patients with different histological subtypes of uterine sarcoma. Standardized uptake values (SUVs) and 18F-FDG/18F-FES SUV ratios were determined, and their correlations with progression-free (PFS) and overall survival (OS) were examined. Ten patients died from local recurrence or metastasis, and one more experienced recurrence, during the at least 36-month follow-up period. Patients with higher 18F-FDG SUVs (> 5.5) had worse OS (p = 0.007) and tended toward worse PFS (p = 0.11), while patients with lower 18F-FES SUVs (≤ 1.5) had worse PFS (p = 0.03) and tended toward worse OS (p = 0.19). Patients with 18F-FDG/18F-FES ratios > 2.6 had worse PFS (p = 0.009) and OS (p = 0.005). The 5-year PFS and OS rates were 75% and 88% for patients with lower ratios, but were only 10% and 20% for those with higher ratios. These results suggest that pretreatment tumor 18F-FDG/18F-FES ratio is useful for predicting the prognosis of uterine sarcoma patients.

Relation between outcomes and expression of estrogen receptor-α phosphorylated at Ser167 in endometrioid endometrial cancer

Both ligand‐dependent and ligand‐independent activation of estrogen receptor (ER)α is modulated by receptor phosphorylation and results in activation of the ERα‐dependent pathways that are involved in endometrioid endometrial cancer (EEC) pathogenesis. It is also known that the mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) and MAPK/p90 ribosomal S6 kinase (RSK) signaling pathways coordinately regulate phosphorylated‐ERα at Ser167 (p‐Ser167‐ERα). However, the expression of p‐Ser167‐ERα in EEC and its prognostic role in ECC is largely unexplored. The purpose of the present study was to investigate the expression of p‐Ser167‐ERα in ECC and its relationship with prognosis. Immunohistochemical staining of primary EEC surgical specimens (n = 103) was carried out using antibodies specific for p‐Ser167‐ERα and for p‐mTOR/p‐S6K1 and p‐MAPK/p‐RSK. The correlation of p‐Ser167‐ERα expression with clinicopathological features and survival of ECC was studied. Patients that were positive for nuclear p‐Ser167‐ERα had significantly shorter relapse‐free survival, and although the result was not significant, levels of nuclear p‐Ser167‐ERα tended to be higher in advanced‐stage ECC patients. Nuclear p‐Ser167‐ERα was significantly positively correlated with p‐MAPK and p‐S6K1, and with significantly shorter relapse‐free survival in EEC.

Locally‑advanced unresected uterine leiomyosarcoma with triple‑modality treatment combining radiotherapy, chemotherapy and hyperthermia: A case report

Advanced uterine leiomyosarcoma (LMS) is a rare and extremely aggressive disease. In patients with advanced and unresected uterine LMS, multidisciplinary therapy is the best treatment option, although no consensus exists on the efficacy of the treatment. The present study describes the case of a 41-year-old female who underwent laparotomy due to a large uterine tumor. Exploratory laparotomy revealed a large tumor that had extended from the pelvic wall to the outside of the pelvis and then invaded the colon. Large residual tumors remained present in the pelvis following suboptimal debulking surgery. Subsequent to surgery, the patient was treated with adjuvant radiotherapy, followed by chemotherapy with regional whole pelvis hyperthermia (HT). Computed tomography revealed stable disease prior and subsequent to combination treatment. While treatment was being administered for third/fourth-degree burns and subcutaneous fatty necrosis, the patient developed multi-organ failure and succumbed. The present case report describes the potential for using a combination of chemotherapy, HT and radiotherapy in patients with LMS. The development of an effective protocol is required for the administration of chemotherapy, HT and radiotherapy in patients with advanced unresected LMS.

Evaluation of the benefit and use of the new terminology in endometrial cytology reporting system

The introduction and establishment of a new classification system for endometrial cytology, the “New Terminology in Endometrial Cytology (NTEMC) system,” which is based on the Bethesda System for uterine cervical cytology, has recently been reported. However, the clinical management for new categories in the NTEMC system, particularly atypical endometrial cells (ATEC), has not been clarified. The objective of the present study is to determine how the ATEC category should be treated and whether the introduction of the system has decreased the number of unnecessary endometrial biopsies.

The ideal strategy for cervical cancer screening in Japan: Result from the Fukui Cervical Cancer Screening Study

The aims of the Fukui Cervical Cancer Screening (FCCS) study are to determine the frequency of women with high‐risk HPV (hrHPV), whether HPV16 or HPV18 (HPV16/18), in the Japanese cancer screening population for the first time and to identify the best strategy for cervical cancer screening in Japan.

Cervical adenocarcinoma associated with persistent human papilloma and human immunodeficiency viral infections

Women infected with the human immunodeficiency virus face a higher risk of developing squamous cell carcinoma of the uterine cervix, but the association with glandular cervical lesions is not well known. A 39-year-old woman infected with human immunodeficiency virus was treated with conization for carcinoma in situ and adenocarcinoma in situ with complete resection. Fourteen years later at the age of 53, the squamous lesions had not progressed, but the glandular lesion developed into cervical adenocarcinoma. Increased risk of squamous cervical lesions in women with human immunodeficiency virus is related to immunosuppression. Local immunosuppression in cervical lesions may interact with persistent human papillomavirus infection. The interplay between human papilloma virus type 18 and local immunosuppression may be associated with development of cervical adenocarcinoma.