Kazuyoshi Kato

Modified posterior pelvic exenteration combined with ileocecal resection for locally advanced endometrial cancer

There are several retrospective studies which have suggested that optimal cytoreductive surgery for stage IV endometrial cancer improves survival [1-3]. In addition, some investigators have reported that achieving maximal cytoreduction to a visibly disease-free outcome in the abdominal cavity for endometrial cancer with distant metastases can extend patients' survival [4]. Due to the anatomic proximity of the rectosigmoid colon to the female pelvic organs and its involvement in locally advanced endometrial cancer, an en bloc resection of the uterus, adnexa, and rectosigmoid, also known as a modified posterior pelvic exenteration (MPPE), is performed to achieve optimal cytoreduction [5,6]. Additionally, if the tumor has infiltrated the ileal end and/or cecum, ileocecal resection can be added. I report the details of the technique for this surgery requiring intestinal reconstruction. We routinely placed a transanal drainage tube after a MPPE to decrease the rate of anastomotic leakage and the need for a diverting stoma [7]. No visible tumors were observed after surgery. No intraoperative or early postoperative complications occurred. The patient did not have an impediment in her postoperative bladder and bowel function. Concerning the extent of hysterectomy during surgery, the procedure was performed as described in that of a class II hysterectomy [8]. This might partly explain the preservation of these function. Subsequently, she was treated with 6 cycles of doxorubicin and cisplatin chemotherapy. Two years after surgery, she is alive with no evidence of recurrence. The patient provided informed consent for use of this video.

Real-world safety and efficacy of immune checkpoint inhibitors in Japanese patients with persistent, recurrent, or metastatic cervical cancer: a multicenter prospective and retrospective study

To evaluate the real-world safety and efficacy of immune checkpoint inhibitors (ICIs) in Japanese patients with persistent, recurrent, or metastatic cervical cancer. In this multicenter observational study at four Japanese institutions, 100 patients with recurrent, persistent, or advanced cervical cancer received pembrolizumab or cemiplimab. Primary endpoints were objective response rate (ORR) and the incidence of immune-mediated adverse events (imAEs) and grade 3-5 AEs. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Logistic and Cox regression were used to explore prognostic factors. Eighteen patients (18%) achieved complete response and 44 (44%) partial response, yielding an ORR of 62.0% and a disease control rate of 77.0%. Median PFS and OS were 10.4 and 22.0 months, respectively. ORR was 74.0% in the first-line setting and 29.6% in the second-line setting. Among patients who met KEYNOTE-826 eligibility criteria, ORR was 82.9% and median PFS 16.1 months. Cemiplimab, which was mainly used as off-label retreatment in frail or previously ICI-exposed patients, showed limited activity (ORR 5.6%). ImAEs occurred in 45.0% of patients, with grade 3-5 events in 19.0% and six treatment-related deaths. Poor performance status and recurrent disease were associated with lower response and shorter PFS, whereas PD-L1 tumor proportion score ≥ 50% and grade 3-5 imAEs were associated with longer PFS. In this real-world cohort, ICIs, particularly pembrolizumab, demonstrated substantial antitumor activity with acceptable toxicity in Japanese patients with advanced cervical cancer, especially when used as first-line therapy and in patients fulfilling KEYNOTE-826 eligibility criteria.

Tegafur-uracil maintenance chemotherapy post-chemoradiotherapy for cervical cancer: Randomized trial

Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC), but recurrence rates remain high. This multicenter phase-3 randomized trial (GOTIC-002) evaluated the efficacy of low-dose oral tegafur-uracil (UFT) as maintenance chemotherapy following curative CCRT for LACC. Between 2010 and 2018, 351 patients with stage Ib2-IVa cervical cancer were enrolled. After achieving complete or partial remission post-CCRT, patients were randomized 1:1 into observation (arm O) or UFT maintenance therapy (arm UFT). UFT doses were 300-400 mg/day based on body surface area for 2 years, disease progression or adverse effects occurred. The primary endpoint was progression-free survival (PFS), with overall survival (OS) and safety as secondary endpoints. Patient characteristics were similar between the groups (n = 178 in arm O, n = 173 in arm UFT). During a median follow-up of 3 years, median PFS was not reached in either group. 5-year PFS rates were similar between them (arm O: 61.3 %, arm UFT: 62.0 %, hazard ratio: 0.92, P = .634). 5-year OS rates were also comparable (77.6 % vs 76.1 %, hazard ratio: 1.04, P = .869). Compliance with UFT ranged from 87.8 % to 98.8 %. Although adverse events were more frequent in arm UFT (93.5 % vs 73.9 %, odds ratio: 5.05), most were mild or moderate. Despite its tolerability, UFT did not improve PFS or OS. These findings suggest the need to reconsider maintenance therapy strategies after CCRT for potentially shifting away from cytotoxic chemotherapy towards alternative methods to enhance survival outcomes in patients with LACC.

Microscopic diseases remain in initial disseminated sites after neoadjuvant chemotherapy for stage III/IV ovarian, tubal, and primary peritoneal cancer

This study aimed to evaluate the presence of pathological residual tumor (pRT) in each initial disseminated site after neoadjuvant chemotherapy (NACT) to assess the appropriate surgical margins during interval debulking surgery (IDS) for a favorable prognosis. This prospective descriptive study included patients with stage IIIC-IV epithelial ovarian, fallopian tubal, and peritoneal cancer. One hundred eleven patients underwent diagnostic exploratory laparotomy, and their initial intra-abdominal dissemination statuses were recorded. Any tumor >1 cm in diameter found during the exploratory laparotomy was resected during IDS even if it was macroscopically invisible after NACT. The pRT rate after NACT and negative predictive value (NPV; probability that sites with macroscopically invisible tumors have no pRT) during IDS were assessed in each disseminated site. A median of 5 NACT cycles were performed. Sites with a high incidence of pRT and low NPV included the rectosigmoid colon (71.4%, 38.6%), transverse mesentery (70.3%, 50.0%), greater omentum (68.3%, 51.7%), right diaphragm (61.9%, 48.1%), paracolic gutters (61.1%, 50.0%), and vesicouterine pouch (56.6%, 50.0%). Organs/tissues with a high incidence of pRT featured a low NPV. The median progression-free survival and overall survival in this cohort were 27.7 and 71.9 months, respectively. Even if a disseminated site >1 cm in diameter before NACT is invisible during IDS, microscopic disease remains present within it. The appropriate surgical margins for IDS with a favorable prognosis could be secured by resecting a lesion of >1 cm before NACT even if it is invisible during IDS.

Well-trained gynecologic oncologists can perform bowel resection and upper abdominal surgery safely

This study was performed to examine the safety of bowel resection and upper abdominal surgery in patients with advanced ovarian cancer performed by gynecologic oncologists after training in a monodisciplinary surgical team. We implemented a monodisciplinary surgical team consisting of specialized gynecologic oncologist for advanced ovarian cancer. In the initial learning period in 65 patients with International Federation of Gynecology and Obstetrics (FIGO) III/IV, a gynecologic oncologist who had a certification as a general surgeon trained 2 other gynecologic oncologists in bowel resection and upper abdominal surgery for 4 years. After the initial learning period, the trained gynecologic oncologists performed surgeries without the certificated general surgeon in 195 patients with FIGO III/IV. The surgical outcomes and perioperative complications during the 2 periods were evaluated. The rates of achieving no gross disease after cytoreductive surgery were 80.0% in the initial learning period and 83.6% in the post-learning period (p=0.560). The incidence of anastomotic leakage after rectosigmoid resection, symptomatic pleural effusion or pneumothorax after right diaphragm resection, and pancreatic fistula after splenectomy with distal pancreatectomy in the 2 periods were 2 of 34 (6.0%), 1 of 33 (3.0%), and 3 of 15 (20.0%) patients in the initial learning period, and 12 of 147 (8.2%), 1 of 118 (0.8%), and 11 of 84 (13.1%) patients in the post-learning period, respectively. There were no significant differences between the 2 groups (p=0.270, p=0.440, p=0.520, respectively). Bowel resection and upper abdominal surgery can be performed safely by gynecologic oncologists.

Early oral feeding is safe and useful after rectosigmoid resection with anastomosis during cytoreductive surgery for primary ovarian cancer

Abstract Background The aim of this study was to investigate the safety and clinical usefulness of early oral feeding (EOF) after rectosigmoid resection with anastomosis for the treatment of primary ovarian cancer. Methods We performed a retrospective review of all consecutive patients who had undergone rectosigmoid resection with anastomosis for primary ovarian, tubal, or peritoneal cancer between April 2012 and March 2019 in a single institution. Patient-related, disease-related, and surgery-related data including the incidence of anastomotic leakage and postoperative hospital stay were collected. EOF was introduced as a postoperative oral feeding protocol in September 2016. Before the introduction of EOF, conventional oral feeding (COF) had been used. Results Two hundred and one patients who underwent rectosigmoid resection with anastomosis, comprised of 95 patients in the COF group and 106 patients in the EOF group, were included in this study. The median number of postoperative days until the start of diet intake was 5 (range 2–8) in the COF group and 2 (range 2–8) in the EOF group ( P < 0.001). Postoperative morbidity was equivalent between the groups. The incidence of anastomotic leakage was similar (1%) in both groups. The median length of the postoperative hospital stay was reduced by 6 days for the EOF group: 17 (range 9–67) days for the COF group versus 11 (8–49) days for the EOF group ( P < 0.001). Conclusion EOF provides a significant reduction in the length of the postoperative hospital stay without an increased complication risk after rectosigmoid resection with anastomosis as a part of cytoreductive surgery for primary ovarian cancer.

Comparison of ArtiSential and Conventional Laparoscopic Instruments in Hysterectomy for Gynecologic Cancers: A Hybrid Observational Study on Surgical Outcomes, Pain Control, and Oncologic Safety

To evaluate the clinical and oncologic outcomes of gynecologic cancer surgeries performed using multi-joint laparoscopic instruments (ArtiSential) compared to conventional instruments, focusing on hysterectomy. A hybrid observational study combining prospective data for the ArtiSential group (n = 44) and retrospective data for the conventional group (n = 136). International multicenter study conducted in Korea, Taiwan, and Japan. 180 patients who underwent hysterectomy for gynecological cancers. Laparoscopic hysterectomy using either ArtiSential or conventional laparoscopic instruments. No significant differences were observed in operative time (100.1 min vs. 99.7 min, p = .95) or estimated blood loss (111.6 mL vs. 125.0 mL, p = .39) between the ArtiSential and conventional groups. The ArtiSential group showed numerical reduction in moderate-to-severe postoperative pain without statistical significance in total group (6.8% vs. 18.4%, p = .09), but a statistically significant reduction in uterine cancer patients (3.6% vs. 21.4%, p = .04). Complication rates were generally lower in the ArtiSential group across all cancer types, although not statistically significant. In radical hysterectomy, the ArtiSential group demonstrated shorter operative times (109.2 min vs. 135.9 min, p = .14) and reduced estimated blood loss (150.0 mL vs. 162.9 mL, p = .75). Multivariate Cox analysis revealed that FIGO stage, operative time, and estimated blood loss significantly affected progression-free survival in uterine cancer, while ArtiSential use did not (p = .47) CONCLUSIONS: ArtiSential instruments appear to be feasible for gynecological cancer surgeries, offering potential benefits such as reduced postoperative pain and fewer complications but without statistical significance. While these findings highlight the utility of ArtiSential in complex pelvic surgeries, further prospective multicenter studies with larger cohorts and longer follow-up periods are required to confirm oncologic safety and long-term complication.

Validation of the 2023 FIGO staging system and its concordance with the JSGO guidelines in endometrial cancer: A multi‐institutional retrospective study in Japan

Abstract Aim To validate the prognostic accuracy of the 2023 FIGO staging system and assess its alignment with the Japan Society of Gynecologic Oncology (JSGO) guidelines for endometrial cancer treatment. Methods This retrospective cohort study included 1207 patients with endometrial cancer treated at four academic hospitals in Kanagawa, Japan, between 2018 and 2022. Patients were reclassified according to the FIGO 2023 system and the JSGO recurrence risk categories. Primary endpoints included stage migration, recurrence risk (RR), overall survival (OS), and concordance between the two classification systems. Results Under FIGO 2023, the stage distribution was: I, 741 (61.4%); II, 203 (16.8%); III, 149 (12.3%); and IV, 114 (9.4%), with stage migration observed in 36.3% of cases. The FIGO 2023 system provided clearer stratification of 3‐year RR than FIGO 2009, with the RR gap widening from 80.0% to 90.1%. Sixteen patients (3.5%) with stage IA3 were classified as high risk by JSGO criteria, while 14.4% of patients considered high risk by JSGO were downstaged under FIGO 2023. Additionally, 46 patients (19.6%) with FIGO stage IA were reclassified as intermediate risk owing to focal lymphovascular space invasion (LVSI). Substantial LVSI was significantly associated with recurrence and poor prognosis (3‐year OS rates: none 94.3%, focal 89.9%, and substantial 40.7%; p  < 0.05). Molecular testing was limited: p53 in 30.2%, MSI in 5.9%, and POLE was not available. Conclusions FIGO 2023 improves prognostic precision. Incorporating LVSI extent and molecular data may refine JSGO classifications and support more individualized adjuvant therapy strategies.