Seiji Mabuchi

Trends in incidence and hormonal management of endometrial cancer during potentially reproductive age in Japan: a population-based study

We aimed to investigate the trends in the incidence and treatment of endometrial cancer (EC) during potentially reproductive age in Japan, with a special focus on the relative oncologic safety of hormonal therapy (HT) over surgery. This population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry from 2004 to 2018. Women with EC were first identified and then distributions of age, stage, histology, and initial treatment were examined. Then, the relative oncologic safety of HT over surgery in patients under the age of 50 years was evaluated. Among the 9417 patients with EC, 1937 were diagnosed during their potentially reproductive age (< 50 years). The incidence of EC during potentially reproductive age has increased from 18.5% in 2004-2011 to 21.9% in 2012-2018. ECs during potentially reproductive age more frequently displayed favorable characteristics, such as endometrioid histology, and lower histological grade than those in non-potentially reproductive age. Among the 1223 patients diagnosed with localized endometrioid EC, 74 cases (6.0%) received HT as an initial treatment, while 1100 cases (90.0%) underwent surgery as their initial treatment. When the two treatment groups were compared, there was no significant difference in overall survival (p = 0.3713). The estimated 5-year survival rates were 100 and 98.8% in the HT and surgery groups, respectively. EC is increasingly diagnosed during potentially reproductive age in Japan. The use of HT as an initial treatment is increasing, and achieved comparable survival outcomes to urgery against localized endometrioid EC during the potentially reproductive age.

Evaluation of survival outcomes between minimally invasive and open surgery in the treatment of early-stage endometrial cancer: a population-based study in Osaka Japan

Abstract Objective To compare the oncological outcomes between Japanese women who underwent minimally invasive surgery and those who underwent open surgery for early-stage endometrial cancer. Methods This population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry from 2011 to 2018. Surgically treated patients for localized (uterine-confined) endometrial cancer were identified. Patients were classified into two groups according to the type of surgery (minimally invasive surgery group and open-surgery group), pathological risk factors (low-risk and high-risk), and year of diagnosis (Group 1, 2011–14; Group 2, 2015–18). Overall survival was compared between the minimally invasive surgery and open-surgery groups. Results In the analyses including all patients, there was no difference in overall survival between the minimally invasive surgery and open-surgery groups (P = 0.0797). The 4-year overall survival rate was 97.1 and 95.7% in the minimally invasive surgery and open-surgery groups, respectively. When investigated according to pathological risks, there were no differences in overall survival between the minimally invasive surgery and open-surgery groups in both the low- and high-risk groups. In the low-risk group, the 4-year overall survival rates in the minimally invasive surgery and open-surgery groups were 97.7 and 96.5%, respectively. In the high-risk group, the 4-year overall survival rates in the minimally invasive surgery and open-surgery groups were 91.2 and 93.2%, respectively. Similarly, there were no differences in overall survival between the minimally invasive surgery and open-surgery groups in both Group 1 (P = 0.4479 in low-risk and P = 0.1826 in high-risk groups) and Group 2 (P = 0.1750 in low-risk and P = 0.0799 in high-risk groups). Conclusion Our study provides epidemiological evidence that minimally invasive surgery is an effective alternative to open surgery in Japanese patients with early-stage endometrial cancer.

Robotic salvage radical hysterectomy for locally recurrent cervical cancer: A comparison with open surgery in a single‐surgeon series

AbstractAimTo compare the surgical and oncologic outcomes between patients with locally recurrent cervical cancer undergoing robotic‐assisted salvage radical hysterectomy (RH) and those undergoing conventional open salvage RH, performed by a single surgeon.MethodsThis retrospective comparative observational study utilized data obtained from consecutive patients with locally recurrent cervical cancer, developed after definitive radiotherapy. These patients either underwent robot‐assisted RH (robotic group) or conventional open RH (open group). Clinicopathological characteristics, surgical outcomes, and oncological outcomes were compared between the two groups.ResultsThe operative time was slightly longer in the robotic group; however, this difference was not statistically significant. Estimated blood loss was significantly lower in the robotic group (median; 0 mL [robotic group] vs. 700 mL [open group]: p &lt; 0.01). The incidence of intraoperative and early and late complications did not statistically differ between the two groups. The mean follow‐up was 29.0 and 17.1 months in the open and robotic groups, respectively. Disease recurrence rates were similar between the two groups (40% [robotic group] vs. 44.4% [open group]). Kaplan–Meier survival analysis for progression‐free survival and overall survival did not show statistically significant differences between the two groups.ConclusionRobot‐assisted salvage RH in women with locally recurrent cervical cancer showed perioperative and oncological outcomes comparable to those of the open procedure. Although our results suggest that the robot‐assisted approach is as good as or better than the open approach, further investigation is required to establish a more robust conclusion.

The activity of immune checkpoint inhibitors in patients with recurrent cervical cancer developed in previously irradiated field: clinical and immunohistochemical investigations

We aimed to 1) evaluate the efficacy of immune checkpoint inhibitors (ICIs) in cervical cancer patients according to the site of disease, 2) investigate the mechanism responsible for differential ICIs sensitivities with focuses on CD8⁺ T lymphocytes and programmed death-ligand 1 (PD-L1) expression. We retrospectively reviewed clinical data from patients with recurrent or metastatic cervical cancer treated with pembrolizumab or cemiplimab between January 2019 and January 2024 (clinical cohort). Target diseases were classified according to the site of diseases: within previously irradiated field (in-field diseases), out-of-field diseases, and both. Immunohistochemical investigations were performed using paired tumor samples (i.e. initial cervical tumor and locally-recurrent tumor developed after definitive radiotherapy: Immunohistochemical cohort). Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test. Fifty patients treated with pembrolizumab-containing chemotherapies (n=39) or cemiplimab (n=11) were assessed. Of these, six patients (12.0%) had in-field diseases alone, twenty-eight patients (56.0%) had out-of-field diseases, and the remaining sixteen (32%) patients had both types of diseases. In-field diseases demonstrated a significantly lower response rate compared to out-of-field diseases (36.3% vs. 72.7%, p=0.004). Patients with in-field diseases demonstrated significantly shorter progression-free survival (p=0.003) and overall survival (p=0.003) than those with out-of-field diseases. In-field diseases were associated with decreased tumor-infiltrating CD8⁺ T lymphocytes and PD-L1 expression. In-field cervical cancer recurrence was associated with decreased sensitivity to ICIs-containing chemotherapies when compared to out-of-field diseases. Decreased tumor-infiltrating CD8⁺ T lymphocytes and PD-L1 expression are possible reasons for this differential sensitivity to ICI-containing chemotherapies.

Significance of Pretreatment C-Reactive Protein, Albumin, and C-Reactive Protein to Albumin Ratio in Predicting Poor Prognosis in Epithelial Ovarian Cancer Patients

To investigate the prognostic significance of pretreatment C-reactive protein (CRP), albumin, and the CRP to albumin ratio (CRP/Alb) in epithelial ovarian cancer (EOC) patients. Clinical data from 308 EOC patients between April 2007 and March 2016 were collected and retrospectively reviewed. The cutoff values for CRP, albumin, and CRP/Alb were defined by receiver operating characteristics (ROC) analyses. Univariate or multivariate analysis was conducted to evaluate the prognostic significance of these factors for disease-specific survival. The cutoff values for CRP, albumin, and CRP/Alb were 0.76, 3.8, and 0.048 by ROC analysis, respectively. Cox regression analyses demonstrated that an elevated CRP/Alb is an independent predictor of short disease-specific survival irrespective of clinical stage or optimal surgery rate. When examined according to clinical stage, elevated CRP/Alb was associated with short disease-specific survival in both early-stage and advanced-stage patients. Cox regression analyses demonstrated that an elevated CRP, but not lower albumin, is also an independent predictor of short disease-specific survival. When two prognosticators were compared, CRP/Alb was found to be superior to CRP for predicting disease-specific survival in EOC patients. Pretreatment elevated CRP/Alb is a predictor of shorter survival in EOC patients regardless of clinical stage.

The role of myeloid-derived suppressor cells in increasing cancer stem-like cells and promoting PD-L1 expression in epithelial ovarian cancer

The aim of this study was to investigate the role of myeloid-derived suppressor cells (MDSC) in the induction of cancer stem-like cells (CSC) and programmed death ligand 1 (PD-L1) expression in ovarian cancer. CSC were defined as tumor cells expressing high levels of aldehyde dehydrogenase 1 (ALDH 1). We inoculated G-CSF-expressing or Mock-expressing ovarian cancer cells into mice, and the frequencies of MDSC and CSC in tumors of these models were compared by flow cytometry. To directly demonstrate the role of MDSC in the induction of CSC and the increase in PD-L1 expression, we performed in vitro co-culture. MDSC and CSC (ALDH-high cells) were more frequently observed in G-CSF-expressing cell-derived tumors than in Mock-expressing cell-derived tumors. Co-culture experiments revealed that MDSC increased the number of CSC via the production of PGE2. Moreover, PGE2 produced by MDSC increased tumor PD-L1 expression via the mammalian target of rapamycin (mTOR) pathway in ovarian cancer cells. In an in vitro experiment in which ovarian cancer cells were co-cultured with MDSC, higher expression of PD-L1 was observed in CSC than in non-CSC (ALDH-low cells). Furthermore, by immunofluorescence staining, we found that PD-L1 was co-expressed with ALDH1 in in vivo mouse models. In conclusion, PGE2 produced by MDSC increases the stem cell-like properties and tumor PD-L1 expression in epithelial ovarian cancer. Depleting MDSC may be therapeutically effective against ovarian cancer by reducing the number of CSC and tumor PD-L1 expression.

The Development of a New Uterine Manipulation Method during Minimally Invasive Radical Hysterectomy

The use of a vaginal uterine manipulator may compromise the oncological outcomes of patients with cervical cancer undergoing minimally invasive radical hysterectomy (MIS-RH). We aimed to describe the safety and efficacy of a novel uterine manipulation device during MIS-RH. Retrospective study. A university hospital and a tertiary care hospital. Patients with early-stage cervical cancer who were treated with MIS-RH. We developed the U-traction, a new device that consists of a 65-mm half-curved cutting needle with a 2.5-mm polyester tape (45-cm long), and investigated its utility to manipulate the uterus during MIS-RH. This study describes the utility and safety of the U-traction for uterine manipulation during laparoscopic or robotic RH in 8 patients with cervical cancer. Uterine manipulation was successfully and safely performed using the U-traction during laparoscopic or robotic RH in patients with cervical cancer without any complications. The application time was less than 5 minutes. In all cases, the use of a vaginal manipulator, an additional incision for an extra port, or the need for assistant surgeons for uterine manipulation was avoided. The novel U-traction device allows for easy and reproducible uterine manipulation during MIS-RH. With this device, the use of a vaginal uterine manipulator can be avoided, and MIS-RH can be safely performed without the need for an assistant surgeon for uterine manipulation.

Skeletal muscle metastasis as a first site of recurrence of cervical cancer

Abstract Rationale: Cervical cancer primarily spreads through direct invasion or via local lymphatics, and hematogenous metastasis is infrequent. Previous reports have shown that lung, liver, and bone are the organs most frequently affected by hematogenous metastasis of cervical cancer, while skeletal muscle is very rarely involved. Patient concerns: A 75-year-old Japanese woman presented with a painful muscular mass in her right lower abdomen. Five years ago, she was treated for her International Federation of Gynecology and Obstetrics stage IB2 cervical adenocarcinoma with radical surgery plus adjuvant chemotherapy. Diagnoses: The patient was diagnosed with isolated oblique muscle metastasis from cervical adenocarcinoma as a first site of recurrence. Interventions: The patient was treated with salvage surgery consisting of partial resection of the oblique muscle and ilium. The tumor was completely excised with an adequate surgical margin by a partial resection of the oblique muscle and ilium Outcomes: The patient is currently free of disease at 10 months after the development of recurrent disease. Lessons: We describe a rare case of isolated oblique muscle metastasis as a first site of recurrence of the International Federation of Gynecology and Obstetrics stage IB2 cervical adenocarcinoma, which was successfully treated with surgery. Although skeletal muscle metastasis is rare, this condition should be considered during the follow-up period, especially when patients complain of muscular pain with insidious progression. The present case and our literature review highlighted the possibility that loco-regional treatment may be curative for selected recurrent cervical cancer developed in skeletal muscles.

Impact of lymphadenectomy in patients with locally recurrent or persistent cervical cancer treated with salvage hysterectomy

AbstractAimTo investigate the role of lymphadenectomy (LND) in locally recurrent or persistent cervical cancer patients treated with salvage hysterectomy.MethodsLocally recurrent or persistent cervical cancer patients treated with salvage hysterectomy, with or without LND, were identified. Patients were divided into two groups according to the status of radiologic evidence of lymph node metastasis, and the impact of LND was investigated by evaluating postoperative survival.ResultsThis study included 72 patients; 48 did not show radiological evidence of lymph node metastasis (Group 1) while 24 did (Group 2). Overall, the addition of LND to salvage hysterectomy resulted in increased postoperative complications. In Group 1, salvage hysterectomy plus LND resulted in the identification of five cases with false‐negative lymph nodes (19.2%), but showed no advantage over salvage hysterectomy alone in terms of postoperative survival. In Group 2, all patients underwent LND, which resulted in the identification of eight cases with false‐positive nodes (33.3%), and reasonably long postoperative survival. The estimated 3‐year postoperative survival rate in this group was 39.7%.ConclusionIncluding LND in salvage hysterectomy allows for precise lymph node staging but increases risk of postoperative complications. However, considering the inability to improve survival, LND should not be performed during salvage hysterectomy in patients without radiological evidence of lymph node metastasis. In patients with radiological evidence of lymph node metastasis, salvage hysterectomy plus LND can only be performed in those who understand the risk of postoperative complications and the limited evidence supporting its survival advantage.