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Groin lymph node detection and sentinel lymph node biopsy in vulvar cancer
Chieko Sakae,Ken Yamaguchi,Noriomi Matsumura,Hidekatsu Nakai,Yumiko Yoshioka,Eiji Kondoh,Junzo Hamanishi,Kaoru Abiko,Masafumi Koshiyama,Tsukasa Baba,Aki Kido,Masaki Mandai,Ikuo Konishi 대한부인종양학회 2016 Journal of Gynecologic Oncology Vol.27 No.6
Objective: To identify suitable diagnostic tools and evaluate the efficacy of sentinel lymphnode (SLN) biopsy for inguinal lymph node metastasis in vulvar cancer. Methods: Data from 41 patients with vulvar cancer were evaluated retrospectively, includingmagnetic resonance imaging (MRI) measurements, SLN biopsy status, groin lymph nodemetastasis, and prognosis. Results: SLN biopsy was conducted in 12 patients who had stage I to III disease. Groinlymphadenectomy was omitted in five of the nine patients with negative SLNs. All SLNnegativepatients who did not undergo groin lymphadenectomy showed no evidence ofdisease after treatment. On MRI, the long and short diameters of the inguinal node weresignificantly longer in metastasis-positive cases, compared with negative cases, in 25 patientswhose nodes were evaluated pathologically (long diameter, 12.8 mm vs. 8.8 mm, p=0.025;short diameter, 9.2 mm vs. 6.7 mm, p=0.041). The threshold of >10.0 mm for the longaxis gave a sensitivity, specificity, positive predictive value, and negative predictive value of87.5%, 70.6%, 58.3%, and 92.3%, respectively, using a binary classification test. Decisiontree analysis revealed a sensitivity, specificity, and accuracy of 87.5%, 70.6%, and 76.0%,respectively, with the threshold of >10.0 mm for the long axis on MRI. The criteria of >10.0mm for the long axis on MRI predicted an advanced stage and poorer prognosis using avalidation set of 15 cases (p=0.028). Conclusion: Minimally invasive surgery after preoperative evaluation on MRI and SLN biopsyis a feasible strategy for patients with vulvar cancer.
Sachiko Kitamura,Kaoru Abiko,Noriomi Matsumura,Hidekatsu Nakai,Yumiko Akimoto,Hirotoshi Tanimoto,Ikuo Konishi 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.4
Objective: Some, but not all, granulosa cell tumors are characterized by estrogen production. This study was designed to determine whether there are clinical or pathological variations ingranulosa cell tumors in relation to the expression of sex steroid synthesis enzymes. Methods: Clinical symptoms, serum hormonal values, and histology of 30 granulosacell tumor patients who underwent surgery between 2002 and 2014 were retrospectivelyreviewed. Results: Most patients presented with abnormal genital bleeding including abnormalmenstrual cycles. Eight of 16 patients older than 50 years had endometrial hyperplasia andone had endometrial cancer. Serum 17β-estradiol (E2) levels tended to be higher in patientsover 50 years of age (p=0.081). Serum follicle-stimulating hormone (FSH) levels were low inall patients irrespective of serum E2 levels. Magnetic resonance imaging revealed a thickerendometrium in older as compared to younger patients (p<0.05). Tumor cells in the majorityof cases were positive for inhibin α and P450 aromatase, irrespective of age and serum E2levels. P450 17α-hydroxylase (P450c17) expression varied among cases. P450c17 was stronglypositive in luteinized tumor cells and weakly positive in theca cells and fibroblasts. High E2levels were associated with P450c17-positive cells in the tumor (p<0.05). Conclusion: The expression of hormone-synthesizing enzymes divides granulosa celltumors into 2 distinct types; tumors with P450c17-positive cells show elevated serum E2 andrelated clinical symptoms, while tumors without these cells show symptoms related to FSHsuppression by inhibin.
EFFECTS OF RIVER DISCHARGE ON GROWTH OF PERIPHYTON IN SAND RIVER
Toda Yuji,Tsujimoto Tetsuro,Fujimori Noriomi Korea Water Resources Association 2005 Water engineering research Vol.6 No.3
Periphyton is known to be one of major primary producers for river ecosystem. While the growth of periphyton usually observed on the stone surface in gravel river, the large growth of periphyton is sometimes seen even in sand river with relatively small river discharge. In the present study, field observations and numerical simulations were performed to investigate the growth of periphyton in sand river. In the field observation, the growth of periphyton on fixed sand bed was measured weekly. The results of the field observations show that the large growth of periphyton occurs in sand river until the bed material sands have not moved. An integrated numerical simulation model is presented to describe the growth of periphyton at observed river reach, and a series of numerical simulations were performed to study the effect of river discharge on growth of periphyton in the sand river. The results of the numerical simulations show that the net primary production of periphyton decreases with the river discharge. These results suggest that the reduction of river discharge at ordinary water stage strongly affects the primary productivity of periphyton even in sand river.
Hiroshi Asano,Katsutoshi Oda,Kosuke Yoshihara,Yoichi M Ito,Noriomi Matsumura,Muneaki Shimada,Hidemichi Watari,Takayuki Enomoto 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.4
Background: Poly (adenosine diphosphate)-ribose polymerase (PARP) inhibitors for tumors with homologous recombination deficiency (HRD), including pathogenic mutationsin , have been developed. Genomic analysis revealed that about 20% of uterine leiomyosarcoma (uLMS) have HRD, including 7.5%–10% of alterations and 4%–6% of carcinomas of the uterine corpus, and 2.5%–4% of the uterine cervix have alterations of. Preclinical and clinical case reports suggest that PARP inhibitors may be effective against those targets. The Japanese Gynecologic Oncology Group (JGOG) is now planning to conduct a new investigator-initiated clinical trial, JGOG2052. Methods: JGOG2052 is a single-arm, open-label, multi-center, phase 2 clinical trial to evaluate the efficacy and safety of niraparib monotherapy for a recurrent or persistent rare fraction of gynecologic malignancies with mutations except for ovarian cancers. We will independently consider the effect of niraparib for uLMS or other gynecologic malignancies with mutations (cohort A, C) and HRD positive uLMS without mutations (cohort B). Participants must have 1–3 lines of previous chemotherapy and at least one measurable lesion according to RECIST (v.1.1). Niraparib will be orally administered once a day until lesion exacerbation or unacceptable adverse events occur. Efficacy will be evaluated by imaging through an additional computed tomography scan every 8 weeks. Safety will be measured weekly in cycle 1 and every 4 weeks after cycle 2 by blood tests and physical examinations. The sample size is 16–20 in each of cohort A and B, and 31 in cohort C. Primary endpoint is the objective response rate.
Ikuo Konishi,Kaoru Abiko,Takuma Hayashi,Koji Yamanoi,Ryusuke Murakami,Ken Yamaguchi,Junzo Hamanishi,Tsukasa Baba,Noriomi Matsumura,Masaki Mandai,Kyoto Study Group for Ovarian Cancer Research 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.5
Epithelial ovarian cancer remains the lethal gynecological malignancy in women. The representative histotype is high-grade serous carcinoma (HGSC), and most patients with HGSC present at advanced stages with peritoneal dissemination. Since the peritoneal dissemination is the most important factor for poor prognosis of the patients, complete exploration for its molecular mechanisms is mandatory. In this narrative review, being based on the clinical, pathologic, and genomic findings of HGSC, chromosomal instability and epigenetic dynamics have been discussed as the potential drivers for cancer development in the fallopian tube, acquisition of cancer stem cell (CSC)-like properties, and peritoneal metastasis of HGSC. The natural history of carcinogenesis with clonal evolution, and adaptation to microenvironment of peritoneal dissemination of HGSC should be targeted in the novel development of strategies for prevention, early detection, and precision treatment for patients with HGSC.
Histopathological subtyping of high- grade serous ovarian cancer using whole slide imaging
Chiho Miyagawa,Hidekatsu Nakai,Tomoyuki Otani,Ryusuke Murakami,Shiki Takamura,Hisamitsu Takaya,Kosuke Murakami,Masaki Mandai,Noriomi Matsumura 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.4
Objective: We have established 4 histopathologic subtyping of high-grade serous ovarian cancer (HGSOC) and reported that the mesenchymal transition (MT) type has a worse prognosis than the other subtypes. In this study, we modified the histopathologic subtyping algorithm to achieve high interobserver agreement in whole slide imaging (WSI) and to characterize the tumor biology of MT type for treatment individualization. Methods: Four observers performed histopathological subtyping using WSI of HGSOC in The Cancer Genome Atlas data. As a validation set, cases from Kindai and Kyoto Universities were independently evaluated by the 4 observers to determine concordance rates. In addition, genes highly expressed in MT type were examined by gene ontology term analysis. Immunohistochemistry was also performed to validate the pathway analysis. Results: After algorithm modification, the kappa coefficient, which indicates interobserver agreement, was greater than 0.5 (moderate agreement) for the 4 classifications and greater than 0.7 (substantial agreement) for the 2 classifications (MT vs. non-MT). Gene expression analysis showed that gene ontology terms related to angiogenesis and immune response were enriched in the genes highly expressed in the MT type. CD31 positive microvessel density was higher in the MT type compared to the non-MT type, and tumor groups with high infiltration of CD8/CD103 positive immune cells were observed in the MT type. Conclusion: We developed an algorithm for reproducible histopathologic subtyping classification of HGSOC using WSI. The results of this study may be useful for treatment individualization of HGSOC, including angiogenesis inhibitors and immunotherapy.