Masahiro Kagabu

Clinical and prognostic insights into Trousseau’s syndrome in gynecologic malignancies: a multicenter study

Cytokine dynamics and quality of life: unraveling the impact of cell-free and concentrated ascites reinfusion therapy in ovarian cancer patients

Abstract Background The quality of life (QOL) of ovarian cancer patients is often impaired by refractory ascites. Cell-free and concentrated ascites reinfusion therapy (CART) is a palliative treatment for refractory ascites, but adverse events, such as fever, are problematic. Several cytokines have been suggested to be responsible for the adverse events, but they have not been investigated in detail. Thus, we comprehensively analyzed cytokines in ascites fluid (AF) and serum before and after CART to determine the influence of cytokines on the safety and efficacy of CART. Methods Thirteen ovarian cancer patients with refractory malignant ascites who underwent CART were enrolled. We comprehensively analyzed 27 cytokines in AF and serum before and after CART. Simultaneously, vital measurements, blood tests, adverse event recordings, and QOL assessments were performed to examine the relationships between the cytokines in AF and serum. Results Interleukin (IL)-5, IL-6, IL-10, and monocyte chemoattractant protein-1 levels were increased in the concentrated AF and in the serum immediately after reinfusion, but they decreased after 24 h. Body temperature also increased immediately after reinfusion, and decreased after 24 h. The CRP level at 24 h after reinfusion was increased, and was positively correlated with the IL-6 level. A QOL assessment using the Cancer Fatigue Scale revealed significantly lower scores after CART. Conclusions The results indicate that the cytokine-induced fever and increased inflammatory response after CART were temporary, and that CART is safe. Additionally, QOL improved after CART. Thus, CART appears safe and effective for treating patients with refractory cancerous ascites.

Safe Trocar Placement by Transvaginal Endoscopic Insertion in Robot‐Assisted Surgery for Endometrial Cancer With Umbilical Incisional Hernia and Prior Mesh Repair: Two Case Reports

ABSTRACT We report two cases of endometrial cancer with umbilical incisional hernia or prior mesh repair, in which robot‐assisted surgery was safely performed using transvaginal laparoscope insertion. Both patients had prior abdominal surgeries, and preoperative imaging raised concerns about adhesions or mesh near the umbilicus, making conventional trocar insertion risky. A laparoscope was inserted via the posterior vaginal fornix, allowing real‐time intra‐abdominal visualization and safe port placement under direct vision. In one case, mesh and adhesions were confirmed at the umbilicus. In the other, no adhesions were found within the hernia sac despite being suspected preoperatively, whereas dense adhesions were identified at Palmer's point, which could not be fully characterized by imaging alone. These cases highlight the limitations of relying solely on imaging and underscore the utility of intraoperative visual assessment. Transvaginal scope insertion offers a simple, reproducible method to enhance trocar safety. To our knowledge, no previous reports have described this technique used solely for observation in robot‐assisted surgery for endometrial cancer.

Safety and oncologic outcomes of total laparoscopic versus abdominal hysterectomy following diagnostic conization for adenocarcinoma in situ and stage IA1 cervical cancer: a multicenter retrospective study

Abstract Background While simple hysterectomy is the standard treatment for adenocarcinoma in situ (AIS) and stage IA1 cervical cancer, minimally invasive surgery has been increasingly adopted. However, evidence on the safety and efficacy of total laparoscopic hysterectomy (TLH) for these conditions remains limited. We compared the safety and efficacy of TLH and total abdominal hysterectomy (TAH) in patients undergoing simple hysterectomy following diagnostic conization. Methods We conducted a multicenter retrospective study of 196 patients with cervical intraepithelial neoplasia grade 3 (CIN3), AIS, or stage IA1 cervical cancer who underwent simple hysterectomy following diagnostic conization. Patients were divided into TLH and TAH groups, and intraoperative and postoperative complications and oncologic outcomes were compared. Results Operative time was significantly longer in the TLH group, whereas intraoperative blood loss was lower and postoperative hospital stay shorter. No significant difference was noted in severe complication rates, although their patterns varied between groups. Recurrence occurred in one patient (0.5%), a case of CIN3 at the vaginal cuff in the stage IA1 TAH group. No recurrences were observed in patients with AIS or stage IA1 disease in the TLH group. Conclusions TLH following diagnostic conization for AIS or stage IA1 cervical cancer demonstrated oncologic efficacy comparable to TAH, with a favorable safety profile. TLH may be a reasonable treatment option for carefully selected patients.

Peripheral blood lymphocyte and eosinophil dynamics with chemotherapy and pembrolizumab in cervical cancer

Cervical cancer poses a significant global health burden, particularly in its metastatic and recurrent forms, for which treatment options are limited. Although immune checkpoint inhibitors (ICIs) such as pembrolizumab have improved outcomes, predictive markers for efficacy are still undefined. This retrospective study investigated changes in peripheral blood eosinophil and lymphocyte counts as potential prognostic indicators in patients with metastatic or recurrent cervical cancer undergoing pembrolizumab-based therapy. Forty-one patients treated with pembrolizumab plus taxane-platinum chemotherapy (± bevacizumab) were analyzed. Peripheral blood eosinophil and lymphocyte counts were measured before and 3 weeks after treatment initiation. Statistical analyses included Kaplan-Meier curves, Cox regression, and log-rank tests. Immune-related adverse events ≥ grade 2 emerged as a significant independent factor associated with prolonged progression-free survival (PFS) in this cohort (p = 0.014). Patients with decreased eosinophil count ratios post-treatment demonstrated longer PFS, particularly among those with recurrence and those who had received prior radiotherapy (p = 0.0001). Conversely, increased lymphocyte count ratios correlated with improved PFS in patients undergoing primary treatment (p = 0.018). Changes in peripheral eosinophil and lymphocyte counts following pembrolizumab initiation may serve as predictive indicators of treatment efficacy in specific cervical cancer subgroups. Incorporating these hematologic parameters could help optimize patient selection and therapeutic strategies. Further research is needed to clarify their role as predictive markers of pembrolizumab efficacy in cervical cancer.

Enhanced immune checkpoint inhibitor therapy for advanced recurrent cervical cancer: the key to treatment efficacy and maintenance of quality of life

SLFN11 is a BRCA Independent Biomarker for the Response to Platinum-Based Chemotherapy in High-Grade Serous Ovarian Cancer and Clear Cell Ovarian Carcinoma

Abstract BRCA1/2 mutations are robust biomarkers for platinum-based chemotherapy in epithelial ovarian cancers. However, BRCA1/2 mutations in clear cell ovarian carcinoma (CCC) are less frequent compared with high-grade serous ovarian cancer (HGSC). The discovery of biomarkers that can be applied to CCC is an unmet need in chemotherapy. Schlafen 11 (SLFN11) has attracted attention as a novel sensitizer for DNA-damaging agents including platinum. In this study, we investigated the utility of SLFN11 in HGSC and CCC for platinum-based chemotherapy. SLFN11 expression was analyzed retrospectively by IHC across 326 ovarian cancer samples. The clinicopathologic significance of SLFN11 expression was analyzed across 57 advanced HGSC as a discovery set, 96 advanced HGSC as a validation set, and 57 advanced CCC cases, all of whom received platinum-based chemotherapy. BRCA1/2 mutation was analyzed using targeted-gene sequencing. In the HGSC cohort, the SLFN11-positive and BRCA mutation group showed significantly longer whereas the SLFN11-negative and BRCA wild-type group showed significantly shorter progression-free survival and overall survival. Moreover, SLFN11-positive HGSC shrunk significantly better than SLFN11-negative HGSC after neoadjuvant chemotherapy. Comparable results were obtained with CCC but without consideration of BRCA1/2 mutation due to a small population. Multivariate analysis identified SLFN11 as an independent factor for better survival in HGSC and CCC. The SLFN11-dependent sensitivity to platinum and PARP inhibitors were validated with genetically modified non-HGSC ovarian cancer cell lines. Our study reveals that SLFN11 predicts platinum sensitivity in HGSC and CCC independently of BRCA1/2 mutation status, indicating that SLFN11 assessment can guide treatment selection in HGSC and CCC.

Expectations and Challenges of First-Line Maintenance Therapy for Advanced Ovarian Cancer

The incidence of ovarian cancer, which has had a poor prognosis, is increasing annually. Currently, the prognosis is expected to improve with the use of molecular-targeted drugs and immune checkpoint inhibitors as maintenance therapies after the first-line chemotherapy. The GOG218 and ICON7 studies reported the usefulness of bevacizumab and the SOLO-1 and PRIMA (A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy) studies have reported the usefulness of olaparib and niraparib, respectively. The ATHENA study investigating the usefulness of rucaparib is currently ongoing. Although clinical studies of immune checkpoint inhibitors are lagging in the field of gynecology, many clinical studies using programmed death cell-1 (PD-1) and PD-1 ligand 1 (PD-L1) antibodies are currently ongoing. Some biomarkers have been identified for molecular-targeted drugs, but none have been identified for immune checkpoint inhibitors, which is a challenge that should be addressed in the future.

The efficacy of a third-generation oncolytic herpes simplex viral therapy for an HPV-related uterine cervical cancer model

Cervical cancer is the fourth most common cancer in women and the seventh most common of all human cancers. Development of new treatments is mandatory to improve the outcome of this disease. Replication-selective oncolytic herpes simplex viruses (HSVs) have emerged as a new platform for cancer therapy. The therapeutic potential of a triple-mutated oncolytic HSV (T-01) for human papillomavirus (HPV)-related cervical cancer was evaluated with immunodeficient and immune-complete models. (1) The in vitro efficacy of T-01 on human cervical cancer cell lines, TC-1, HeLa, CaSki, and SKG IIIa was evaluated. (2) The in vivo efficacy of T-01 was examined in human HeLa xenograft and TC-1 syngeneic models of human cervical cancer. After flank tumors reached 5 mm in diameter, the first intratumoral (i.t.) administration of T-01 was performed. Intratumoral administration of T-01 was performed with a 5 day interval a total of 6 times. In the in vitro study, T-01 was highly cytotoxic for all cell lines (48 h after infection with T-01 at 1 × 10 These results demonstrate that T-01 has cytotoxic efficacy and inhibited against HPV-related cervical cancer cells. These findings indicate that T-01 has therapeutic potential for HPV-related cervical cancer.

Comparison of Postoperative Adjuvant Chemotherapy and Concurrent Chemoradiotherapy for FIGO2018 Stage IIIC1 Cervical Cancer: A Retrospective Study

Background and Objectives: In October 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its classification of advanced stages of cervical cancer. The main points of the classification are as follows: stage IIIC is newly established; pelvic lymph node metastasis is stage IIIC1; and para-aortic lymph node metastasis is stage IIIC2. Currently, in Japan, radical hysterectomy is performed in advanced stages IA2 to IIB of FIGO2014, and concurrent chemoradiotherapy (CCRT) is recommended for patients with positive lymph nodes. However, the efficacy of CCRT is not always satisfactory. The aim of this study was to compare postoperative adjuvant chemotherapy (CT) and postoperative CCRT in stage IIIC1 patients. Materials and Methods: Of the 40 patients who had undergone a radical hysterectomy at Iwate Medical University between January 2011 and December 2016 and were pathologically diagnosed as having positive pelvic lymph nodes, 21 patients in the adjuvant CT group and 19 patients in the postoperative CCRT group were compared. Results: The 5 year survival rates were 77.9% in the CT group and 74.7% in the CCRT group, with no significant difference. There was no significant difference in overall survival or progression-free survival between the two groups. There was no significant difference between CT and CCRT in postoperative adjuvant therapy in the new classification IIIC1 stage. Conclusions: The results of the prospective Japanese Gynecologic Oncology Group (JGOG) 1082 study are pending, but the present results suggest that CT may be a treatment option in rural areas where radiotherapy facilities are limited.

Sentinel node navigation surgery in cervical cancer: a systematic review and metaanalysis

Sentinel node navigation surgery (SNNS) is used in clinical practice for the treatment of cervical cancer. This study aimed to elucidate the appropriate sentinel lymph node (SLN) mapping method and assess the safety and benefits of SNNS. We searched the PubMed, Ichushi, and Cochrane Library databases for randomized controlled trials (RCT) and studies on SLN in cervical cancer from January 2012 to December 2020. Two authors independently assessed study quality and extracted data. We quantitatively analyzed the detection rate, sensitivity/specificity, and complications and reviewed information, including the survival data of SLN biopsy (SLNB) without pelvic lymphadenectomy (PLND). The detection rate of SLN mapping in the unilateral pelvis was median 95.7% and 100% and in the bilateral pelvis was median 80.4% and 90% for technetium-99 m (Tc) with/without blue dye (Tc w/wo BD) and indocyanine green (ICG) alone, respectively. The sensitivity and specificity of each tracer were high; the area under the curve of each tracer was 0.988 (Tc w/wo BD), 0.931 (BD w/wo Tc), 0.966 (ICG), and 0.977 (carbon nanoparticle). Morbidities including lymphedema, neurological symptoms and blood loss were associated with PLND. One RCT and five studies all showed SNNS without systematic PLND does not impair recurrence or survival in early-stage cervical cancer with a tumor size ≤ 2-4 cm. Both Tc w/wo BD and ICG are appropriate SLN tracers. SNNS can reduce the morbidities associated with PLND without affecting disease progression in early-stage cervical cancer.