Genetic and epigenetic alterations in precursor lesions of endometrial endometrioid carcinoma.

The hyperplasia-carcinoma sequence is a stepwise tumourigenic programme towards endometrial cancer in which normal endometrial epithelium becomes neoplastic through non-atypical endometrial hyperplasia (NAEH) and atypical endometrial hyperplasia (AEH), under the influence of unopposed oestrogen. NAEH and AEH are known to exhibit polyclonal and monoclonal cell growth, respectively; yet, aside from focal PTEN protein loss, the genetic and epigenetic alterations that occur during the cellular transition remain largely unknown. We sought to explore the potential molecular mechanisms that promote the NAEH-AEH transition and identify molecular markers that could help to differentiate between these two states. We conducted target-panel sequencing on the coding exons of 596 genes, including 96 endometrial cancer driver genes, and DNA methylome microarrays for 48 NAEH and 44 AEH lesions that were separately collected via macro- or micro-dissection from the endometrial tissues of 30 cases. Sequencing analyses revealed acquisition of the PTEN mutation and the clonal expansion of tumour cells in AEH samples. Further, across the transition, alterations to the DNA methylome were characterised by hypermethylation of promoter/enhancer regions and CpG islands, as well as hypo- and hyper-methylation of DNA-binding regions for transcription factors relevant to endometrial cell differentiation and/or tumourigenesis, including FOXA2, SOX17, and HAND2. The identified DNA methylation signature distinguishing NAEH and AEH lesions was reproducible in a validation cohort with modest discriminative capability. These findings not only support the concept that the transition from NAEH to AEH is an essential step within neoplastic cell transformation of endometrial epithelium but also provide deep insight into the molecular mechanism of the tumourigenic programme. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Risk-reducing decisions regarding germline BRCA pathogenic variant: focusing on the timing of genetic testing and RRSO.

BACKGROUND: In Japan, the public insurance policy was revised in 2020 to cover hereditary breast and ovarian cancer (HBOC), including genetic testing and surveillance, for patients with breast cancer (BC). Consequently, the demand for risk-reducing salpingo-oophorectomy (RRSO) has increased. This study aimed to clarify the changes in the demand and timing of genetic testing and RRSO associated with public insurance coverage for HBOC in Japan. METHODS: This retrospective analysis included 350 women with germline BRCA (gBRCA) pathogenic variants (PVs) who had visited gynaecologists; they received gBRCA genetic testing at 45.1±10.6 (20-74) years. The use of medical testing and preventive treatment was compared between the preinsurance and postinsurance groups using Mann-Whitney U and Fisher's exact tests. RESULTS: The findings indicate that RRSO rates doubled from 31.4% to 62.6% among patients with gBRCA-PV. The implementation rate was 32.4% among unaffected carriers and 70.3% among BC-affected patients. Younger patients received genetic testing with significantly shorter intervals between BC diagnosis and genetic testing and between genetic testing and RRSO. CONCLUSION: Overall, the insurance coverage for HBOC patients with BC has increased the frequency of RRSO in Japan. However, a comparison between the number of probands and family members indicated that the diagnosis among family members is inadequate. The inequality in the use of genetic services by socioeconomic groups is an issue of further concern.

Ovarian surveillance including endometrial cytology for patients with hereditary breast and ovarian cancer before risk-reducing salpingo-oophorectomy: A retrospective analysis.

AIM: Ovarian surveillance in women with hereditary breast and ovarian cancer who do not undergo risk-reducing salpingo-oophorectomy has been controversial. Therefore, this study aimed to demonstrate the clinical features of ovarian surveillance at our institution using a technique that combines serum cancer antigen 125 measurements, transvaginal ultrasonography, and uterine endometrial cytology. METHODS: We retrospectively examined 65 women, who had not undergone risk-reducing salpingo-oophorectomy diagnosed with hereditary breast and ovarian cancer between 2000 and 2021 at our hospital. Clinical information was obtained and analyzed through a chart review. The details of the treatment course were reviewed for patients who had developed ovarian cancer. RESULTS: Overall, 5 of the 65 women were diagnosed with ovarian cancer based on abnormal findings during periodic surveillance. All patients who developed ovarian cancer were asymptomatic, even if the cancer was at an advanced stage. Two of the 65 patients had endometrial cytology abnormalities, both of whom had ovarian cancer. All patients who developed ovarian cancer underwent primary debulking surgery, and complete gross resection was achieved. None of the patients experienced ovarian cancer recurrence. CONCLUSIONS: The ovarian surveillance strategy at our institution for women with hereditary breast and ovarian cancer who do not undergo risk-reducing salpingo-oophorectomy can identify asymptomatic ovarian cancer and contribute to achieving complete gross resection during primary surgery. Ovarian surveillance may contribute to a reduction in ovarian cancer mortality.

Human papillomavirus vaccine impact on invasive cervical cancer in Japan: Preliminary results from cancer statistics and the MINT study.

The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high-grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis. We also analyzed time trends in HPV16/18 prevalence among 1414 Japanese women aged <40 years newly diagnosed with ICC in the past decade. Based on the population-based cancer registry, the incidence of ICC among young women aged 20-29 years showed a significant decline from 3.6 to 2.8 per 100 000 women-years during 2016-2019, but no similar decline was observed for older age groups (p < 0.01). Similarly, using data from the gynecological cancer registry of the Japan Society of Obstetrics and Gynecology, the annual number of ICCs among women aged 20-29 years also decreased from 256 cases to 135 cases during 2011-2020 (p < 0.0001). Furthermore, a declining trend in HPV16/18 prevalence in ICC was observed only among women aged 20-29 years during 2017-2022 (90.5%-64.7%, p = 0.05; Cochran-Armitage trend test). This is the first report to suggest population-level effects of HPV vaccination on ICC in Japan. Although the declining trend in HPV16/18 prevalence among young women with ICC supports a causal linkage between vaccination and results from cancer registries, further studies are warranted to confirm that our findings are attributable to vaccination.

Retrospective study of the efficacy and safety of docetaxel/carboplatin combination therapy as postoperative adjuvant chemotherapy for nonsquamous cell carcinoma of the cervix.

OBJECTIVE: Optimal adjuvant chemotherapy for nonsquamous cervical carcinoma has not yet been established. This study investigated the efficacy and safety of docetaxel/carboplatin (DC) for early-stage nonsquamous cell cervical carcinoma after radical hysterectomy (RH). METHODS: We evaluated 157 patients with stage IB-IIB nonsquamous cervical carcinoma with intermediate risk and high risk treated at our institution with DC after type II or III RH from 2007 to 2021. Patients received docetaxel (60-70 mg/m2) and carboplatin (area under the curve 5-6) every 3 weeks for six cycles. The primary endpoint was 2 year recurrence-free survival (RFS) and the secondary endpoint was adverse events (AEs). RESULTS: There were 106 intermediate-risk and 51 high-risk patients. The high-risk patients included 11 with positive parametrial involvement, 20 with pelvic lymph node metastases, and 20 with both parametrial involvement and pelvic lymph node metastases. The 2 year RFS rates for intermediate-risk, high-risk, and positive pelvic lymph nodes were 94.8% (95% confidence interval [CI], 87.9-97.8), 80.1% (95% CI, 64.1-89.5), and 74.5% (95% CI, 55.4-86.4), respectively. Sixteen patients had recurrence, including local recurrence (n = 6), distant metastasis (n = 9), and local and distant metastasis (n = 1). Hematologic toxicity was the most frequent AE, especially leukopenia and neutropenia. Nausea and constipation were the most frequent nonhematologic toxicities. CONCLUSION: DC therapy at our institution showed good 2 year RFS, and postoperative adjuvant therapy with DC therapy is suggested as a useful strategy for patients with nonsquamous cervical carcinoma.

Human papillomavirus vaccine effectiveness by age at first vaccination among Japanese women.

In Japan, the National Immunization Program against human papillomavirus (HPV) targets girls aged 12-16 years, and catch-up vaccination is recommended for young women up to age 26 years. Because HPV infection rates increase soon after sexual debut, we evaluated HPV vaccine effectiveness by age at first vaccination. Along with vaccination history, HPV genotyping results from 5795 women younger than 40 years diagnosed with cervical intraepithelial neoplasia grade 2-3 (CIN2-3), adenocarcinoma in situ (AIS), or invasive cervical cancer were analyzed. The attribution of vaccine-targeted types HPV16 or HPV18 to CIN2-3/AIS was 47.0% for unvaccinated women (n = 4297), but 0.0%, 13.0%, 35.7%, and 39.6% for women vaccinated at ages 12-15 years (n = 36), 16-18 years (n = 23), 19-22 years (n = 14), and older than 22 years (n = 91), respectively, indicating the greater effectiveness of HPV vaccination among those initiating vaccination at age 18 years or younger (P < .001). This finding was supported by age at first sexual intercourse; among women with CIN2-3/AIS, only 9.2% were sexually active by age 14 years, but the percentage quickly increased to 47.2% by age 16 and 77.1% by age 18. Additionally, the HPV16/18 prevalence in CIN2-3/AIS was 0.0%, 12.5%, and 40.0% for women vaccinated before (n = 16), within 3 years (n = 8), and more than 3 years after (n = 15) first intercourse, respectively (P = .004). In conclusion, our data appear to support routine HPV vaccination for girls aged 12-14 years and catch-up vaccination for adolescents aged 18 years and younger in Japan.

Surgical skill and oncological outcome of laparoscopic radical hysterectomy: JGOG1081s-A1, an ancillary analysis of the Japanese Gynecologic Oncology Group Study JGOG1081.

OBJECTIVES: We investigated whether surgical skill and procedure were related to oncological outcomes in cervical cancer patients who underwent Laparoscopic Radical Hysterectomy (LRH). METHODS: We previously assessed data of LRH from 251 patients with FIGO stage (2009) IA2, IB1and IIA1 cervical cancer collected for JGOG 1081s study. 1) The JGOG 1081s cohort study was re-examined to refine the surgical details and extend the follow-up period as chart review. 2) Unedited videos for recurrent cases and matched non-recurrent control cases were newly compared by experts for various surgical skills and surgical procedures using the modified Objective Structured Assessment of Technical Skills (OSATS) tool, without awareness of the recurrence status as video review. RESULTS: After a median follow-up of 46 months, tumors had recurred in 31 of the 251 patients. The five-year Recurrence-Free Survival rate was 86.9% (81.8-90.6) and five-year Overall Survival rate was 93.7% (87.5-96.8). Multivariate analysis from chart reviews found that an experience with LRH of less than 20 cases per institution was an independent prognostic factor for recurrence (Hazard Ratio (HR) 2.49, 95%CI 1.12-5.53, p = 0.025). For the surgical video review, we compared 23 videos of recurrent cases with 23 background-matched non-recurrent controls. Lower modified OSATS scores from the video review were consistently trended to have a higher risk of recurrence. CONCLUSIONS: Our new study has found that LRH surgical experience and skill trended to have better oncological outcomes.

Current treatment status of older patients with gynecological cancers.

The percentage of older patients with gynecological malignancies has recently been on the rise. Although prospective studies focusing on the treatment of older patients have been conducted for ovarian cancer, mainly in Europe, there have been scarce literature on cervical and endometrial cancers, and information on their treatment is currently lacking. One of the characteristics of older patients is that not only their performance status but also other factors, such as physical, mental and social factors, cause a large variability, and individual differences in their response to treatments. One of the major issues in the treatment of older patients is how to objectively measure these individual differences and link them to the appropriate treatment selection. In this review, clinical evidence for the guided treatment of older patients with gynecological cancer will be reviewed.

Prognostic factors of 2018 FIGO stage IB-IIA cervical cancer with absence of high/ intermediate surgical-pathological risk factors.

OBJECTIVE: This retrospective analysis of a real-world database of open radical hysterectomy in Japan aimed to reveal the clinicopathological findings and clinical outcomes of low-risk patients with stage IB-IIA cervical cancer. METHODS: A total of 1143 stage IB1, IB2 and IIA1 (reclassified by FIGO 2018 staging system) patients with cervical cancer who underwent radical hysterectomy between January 2004 and December 2008 from the Japanese Gynecologic Oncology Group database were analyzed. Low-risk patients were defined as those without a tumor size exceeding 4 cm, parametrial tumor involvement, deep (outer half) stromal invasion, lymphovascular space invasion or lymph nodal metastasis. RESULTS: 61.2% (772/1262) patients with stage IB1, 32.1% (229/932) with stage IB2 and 16.9% (72/294) of stage IIA1 were classified into the low-risk group. The 5-year overall survival and disease-free survival rates were 98.4 and 93.7%, respectively. Histological classification did not affect the survival rates, but stage IIA cases had significantly lower overall survival and disease-free survival (83.5 and 93.8%, respectively) than stage IB cases. The independent prognostic factors for disease-free survival were older age (≧50), histology, clinical stage and clinical stage as independent prognostic factors for overall survival. Regarding recurrence, older age, non-SCC and stage IIA1 were independent risk factors for local recurrence, but stage IIA1 was the only independent risk factor for distant metastasis. CONCLUSION: We found that stage IIA1 was the strongest risk factor for survival and recurrence of low-risk uterine cervical cancer (FIGO, 2018). In low-risk cases, stage IIA1 should be considered separately from stage IB.

Indocyanine green-guided sentinel lymph node mapping during laparoscopic surgery with vaginal cuff closure but no uterine manipulator for cervical cancer.

BACKGROUND: Lymph node metastasis is a critical prognostic factor in cervical cancer. Considering the potential complications of lymphadenectomy and desirability of avoiding systemic lymphadenectomy, accurate intraoperative prediction of the existence of lymph node metastasis is important in patients undergoing surgery for cervical cancer. We evaluated the feasibility and value of indocyanine green (ICG) use for sentinel lymph node (SLN) mapping during laparoscopic surgery performed for cervical cancer. METHODS: This single-center cohort study included 77 patients undergoing a new laparoscopic radical surgery method with pelvic lymphadenectomy for early-stage cervical cancer. The surgery, performed without using a uterine manipulator, included creation of a vaginal cuff. Bilateral ICG-guided SLN mapping and rapid histopathological examination were performed, and results were analyzed in relation to final histopathologic diagnoses. RESULTS: The SLN pelvic side-specific detection rate was 93.5%, sensitivity (SLN-positive cases/SLN-detected pelvic lymph node-positive cases) was 100%, intraoperative negative predictive value (NPV) was 97.8%, and final pathological NPV was 100%. The detection rate was significantly lower for tumors ≥ 2 cm in diameter than for tumors < 2 cm in diameter. Micrometastases were missed by intraoperative examination in 3 cases. CONCLUSION: The high NPV suggests the feasibility and usefulness of ICG-based SLN mapping plus rapid intraoperative examination for identification of metastatic SLNs. Use of ICG-based mapping for intraoperative identification of SLNs in patients undergoing this new laparoscopic surgery method for early-stage cervical cancer was particularly effective for tumors < 2 cm in diameter. However, incorporating a search for micrometastases into rapid intraoperative histopathologic examination may be necessary.

A mixed-method evaluation of cadaver surgery training for gynecologic oncology.

AIM: Traditional surgical training techniques with using patients, and new advances with live animals, artificial models, and simulation methods have several shortcomings. There are a few reports on the usefulness of cadaver surgery training (CST) in gynecology. Herein, we used a mixed-method evaluation to qualitatively and quantitatively explore the educational efficacy of CST by conducting CST programs at the Sapporo Medical University, Japan. METHODS: In 2020, we conducted two CST programs with 45 participants-13 residents, 8 specialists recognized by Japan Society of Obstetrics and Gynecology, 23 certified endoscopists recognized by Japan Society of Gynecology and Obstetrics Endoscopy and Minimally Invasive Therapy, 15 specialists recognized by Japan Society of Gynecologic Oncology, and 14 certified endoscopists cum oncology. Three participants observed the procedure virtually and 42 were physically present. Laparoscopic radical hysterectomy and pelvic exenteration were performed on five Thiel-embalmed cadavers. Participants were asked to complete pre- and post-training surveys that included qualitative questions, concerning the purpose and cost of CST, and quantitative questions, testing anatomical knowledge. RESULTS: We observed that the rate of score improvement to the quantitative questions increased from 58.6% pre-CST to 75.6% post-CST. Furthermore, oncology specialists and those who performed more surgeries and faced more complications during surgeries recorded high percentage of correct answers. Multiple regression analysis statistically confirmed these results. CONCLUSIONS: This study confirmed the educational efficacy of CST.

Moderate-Risk Genes for Hereditary Ovarian Cancers Involved in the Homologous Recombination Repair Pathway.

Approximately 20% of cases of epithelial ovarian cancer (EOC) are hereditary, sharing many causative genes with breast cancer. The lower frequency of EOC compared to breast cancer makes it challenging to estimate absolute or relative risk and verify the efficacy of risk-reducing surgery in individuals harboring germline pathogenic variants (GPV) in EOC predisposition genes, particularly those with relatively low penetrance. Here, we review the molecular features and hereditary tumor risk associated with several moderate-penetrance genes in EOC that are involved in the homologous recombination repair pathway, i.e., ATM, BRIP1, NBN, PALB2, and RAD51C/D. Understanding the molecular mechanisms underlying the expression and function of these genes may elucidate trends in the development and progression of hereditary tumors, including EOC. A fundamental understanding of the genes driving EOC can help us accurately estimate the genetic risk of developing EOC and select appropriate prevention and treatment strategies for hereditary EOC. Therefore, we summarize the functions of the candidate predisposition genes for EOC and discuss the clinical management of individuals carrying GPV in these genes.

Utilization and perioperative outcome of minimally invasive pelvic exenteration in gynecologic malignancies: A national study in the United States.

OBJECTIVE: To examine characteristics and short-term perioperative outcomes related to minimally invasive pelvic exenteration for gynecologic malignancy. METHODS: This comparative effectiveness study is a retrospective population-based analysis of the National Inpatient Sample from 10/2008-9/2015. Women with cervical, uterine, vaginal, and vulvar malignancies who underwent pelvic exenteration were evaluated based on the use of laparoscopic or robotic-assisted surgery. Patient demographics and intraoperative/postoperative complications related to a minimally invasive surgical approach were assessed. RESULTS: Among 1376 women who underwent pelvic exenteration, 49 (3.6%) had the procedure performed via a minimally invasive approach. The majority of minimally invasive cases were robotic-assisted (51.0%). Women in the minimally invasive group were more likely to be old, white, have cervical/uterine cancers, and receive urinary diversion, but less frequently received vaginal reconstruction or colostomy when compared to those in the open surgery group (P < 0.05). Overall perioperative complication rates were similar between the minimally invasive and open surgery groups (79.6% versus 77.7%, P = 0.862), but the minimally invasive group had a decreased risk of high-risk complications compared to the open surgery group (adjusted-odds ratio 0.19, 95% confidence interval 0.07-0.51). Specifically, a minimally invasive approach was associated with decreased incidence of sepsis and thromboembolism compared to an open approach (P < 0.05). The minimally invasive group had a shorter length of stay (median, 9 versus 14 days) and lower total charge (median, $127,875 versus $208,591) compared to the open surgery group (P < 0.05). CONCLUSION: Laparotomy remains the main surgical approach for pelvic exenteration for gynecologic malignancy and minimally invasive surgery was infrequently utilized during the study period in the United States. Before widely adopting this surgical approach, the utility and role of minimally invasive pelvic exenteration requires further investigation.

Laparoscopic pelvic exenteration and laterally extended endopelvic resection for postradiation recurrent cervical carcinoma: Technical feasibility and short-term oncologic outcome.

OBJECTIVE: Surgery is the only treatment for cervical cancer recurrence in a previously irradiated field. Pelvic exenteration (PE) and laterally extended endopelvic resection (LEER) are indicated for select patients; however, morbidity and mortality rates remain high, and new treatment modalities are required. Laparoscopy optimizes visualization and allows meticulous dissection while also reducing intraoperative blood loss and postoperative complications without worsening the outcomes. We aimed to clarify the feasibility and outcomes of laparoscopic PE and LEER for previously irradiated recurrent cervical cancer. METHODS: We prospectively investigated the outcomes of laparoscopic PE and LEER in 28 patients with recurrent cervical carcinoma after radiotherapy. RESULTS: Seventeen laparoscopic PEs for central recurrences and 11 laparoscopic LEERs for lateral recurrences were performed. The median operation time and blood loss were 454mins and 285 mL in the PE group, and 562mins and 325 mL in the LEER group, respectively, with no conversions to laparotomy. R0 resection was achieved in all patients in the PE group and 73% in the LEER group. The morbidity and mortality rates were 41% and 0% in PE group, and 55% and 0% in LEER group, respectively. The 2-year disease-free survival and overall survival were 68.9% and 76% in the PE group, and 27.3% and 29.6% in the LEER group, respectively. CONCLUSION: Laparoscopic PE is feasible for previously irradiated central recurrent cervical cancer and has acceptable outcomes. Laparoscopic LEER is also feasible for lateral recurrence, but oncologic outcome may be modest in this limited preliminary study. Further studies using a larger sample size with a longer follow-up period is warranted to determine the indications for laparoscopic LEER.

A retrospective assessment of the safety and efficacy of laparoscopic radical hysterectomy in Japan during the early years following its introduction: a Japanese Gynecologic Oncology Group study (JGOG1081S).

OBJECTIVE: To evaluate the safety and efficacy of laparoscopic radical hysterectomy (LRH) for cervical cancer, in terms of morbidity and short-term oncologic outcome following LRH's introduction into Japan. METHODS: We conducted a retrospective analysis of patients with early-stage cervical cancer (FIGO staging IA2, IB1, and IIA1) who underwent LRH from Dec 2014 to Dec 2016. We assessed the morbidity, overall survival (OS) and recurrence-free survival (RFS), and prognostic factors for RFS. RESULTS: A total of 251 patients were included from 22 facilities across Japan. There were 8 cases of stage IA2 cervical cancer, 226 of IB1, and 17 of IIA1. The median operating time was 343 min and the median blood loss was 190 ml. Two patients (0.8%) had a postoperative complication with a Clavien-Dindo classification of grade 3 or higher. After a median follow-up time of 15.6 months, the 2-year RFS was 87.4%, and the 2-year OS was 97.8%. When the 2-year RFS rate was compared with whether the patient pathologically had tumors of less than 2 cm, versus 2 cm or more, the RFS was 95.8% and 80.4%, respectively. Multivariate analysis found that tumor size and the route of lymph node removal were independent prognostic factors for recurrence. CONCLUSION: When LRH was first introduced into Japan, we found that the route of lymph node removal was an independent prognostic factor for recurrence in addition to large tumors (≥ 2 cm). Our results suggest that prognosis may be secured by paying attention to the lymph node removal route.

Clinical and pathological outcomes of risk-reducing salpingo-oophorectomy for Japanese women with hereditary breast and ovarian cancer.

BACKGROUND: To clarify the clinical as well as pathological outcomes in Japanese women with germline pathogenic BRCA1/2 variants who underwent risk-reducing salpingo-oophorectomy (RRSO). METHODS: This prospective study examined the rate of occult cancer and primary peritoneal cancer after RRSO at our institution in the period from 2011 to 2020. Clinical records of genetically confirmed patients with germline pathogenic BRCA1/2 variants who desired to undergo RRSO were reviewed. Specimens obtained during RRSO were pathologically diagnosed as per SEE-FIM protocol. All the participants underwent magnetic resonance imaging (MRI) about 1 month preoperatively. RESULTS: One hundred and seventeen women underwent RRSO during this period. Of these, the numbers of women with germline pathogenic BRCA1 and BRCA2 variants were 72 and 45, respectively. The mean observational time after RRSO was 35.8 months. Despite negative preoperative screening results, three (2.6%) serous tubal intraepithelial carcinoma and three (2.6%) invasive carcinomas were identified. Of the three invasive carcinomas cases, two were International Federation of Gynecology and Obstetrics (FIGO) stage I primary fallopian tube cancer, and the third case was double cancer (ovarian cancer and fallopian tube cancer) with FIGO stage IC3. CONCLUSIONS: The rate of occult neoplasms was similar to those reported by studies performed in other countries. Although women with occult cancer were diagnosed with FIGO stage I, the MRI performed 1 month preoperatively did not show any such malignant findings. Thus, RRSO is the only promising method that can improve the prognosis in women with germline pathogenic BRCA1/2 variants.

Surveillance of radical hysterectomy for early-stage cervical cancer in the early experienced period of minimally invasive surgery in Japan.

OBJECTIVE: The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy. METHODS: In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients' characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival. RESULTS: The median patient age was 44 (20-80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49-51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS. CONCLUSION: The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.

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

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.

Positive surgical margin is an independent predictor of overall survival of patients with vulvar squamous cell carcinoma.

AIM: It is uncertain whether curative surgical treatment or a less radical surgery with adjuvant treatment should be provided to preserve function in patients with vulvar squamous cell carcinoma (SCC) that is adjacent to the urethra, anus, and vagina. The aim of this study was to investigate the surgical margin in patients with vulvar SCC with regard to local recurrence and overall survival. METHODS: Thirty-four patients were identified as having a diagnosis of vulvar SCC without distant metastasis. They had been treated surgically with curative intent at the Cancer Institute Hospital. Clinical data were analyzed retrospectively. RESULTS: Rates of 5-year local recurrence-free survival among patients with positive, <3-mm, <5-mm, <8-mm, and ≥8-mm surgical margins were 32%, 30.3%, 42.5%, 55.5%, and 73%, respectively. Rates of 5-year overall survival of patients with positive, <3-mm, <5-mm, <8-mm, and ≥8-mm surgical margins were 15.5%, 53.8%, 58.8%, 67.6%, and 83.3%, respectively. In the multivariable analysis, a tumor size of more than 2-cm (hazard ratio [HR] = 17.7, 95% confidence interval [CI] = 1.39-226) and a positive surgical margin (HR = 0.0092, 95% CI = 0.011-0.53) were risk factors for local recurrence, and a lymph node involvement (HR = 1.41, 95% CI = 0.31-6.43) and a positive surgical margin (HR = 0.0046, 95% CI = 0.011-0.53) were significant risk factors for overall mortality. CONCLUSIONS: To improve the prognosis, thorough resection with an adequate surgical margin is needed. But narrow surgical margin may be acceptable, particularly to preserve the function of adjacent organs.

Step-by-step demonstration of laparoscopic laterally extended endopelvic resection for a recurrent endometrial cancerous tumor at a sciatic foramen, with a detailed explanation of the pelvic sidewall anatomy.

OBJECTIVE: Laterally extended endopelvic resection (LEER) is regarded as a surgical salvage therapy for patients with laterally recurrent gynecologic carcinomas [1]. A prerequisite for R0 resection using this excision technique is carcinoma location remote from the sciatic foramen [1,2]. However, considering the advantages provided by laparoscopy in terms of visualization and dissection, laparoscopic LEER can potentially be used to achieve R0 resection of a laterally recurrent carcinoma at the sciatic foramen [3]. METHODS: The patient underwent an abdominal radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection due to stage II endometrial carcinoma. Almost 30 years later, a recurrent endometrial carcinoma, diagnosed by needle biopsy, was detected at the pelvic sidewall. Abdominal CT scan revealed that the recurrent tumor involved the bladder, right ureter, and rectum, and was located at the right sciatic foramen. Due to a long recurrence-free interval, resection surgery was chosen as the treatment. RESULTS: Tumor resection (LEER) and reconstructive surgery were performed laparoscopically. The operation time was 540 minutes, and blood loss volume was 350 ml, with no blood transfusion. R0 resection was achieved without any intraoperative and postoperative complications. There has been no sign of recurrence during the 6 months that have passed since this surgery. CONCLUSIONS: Total laparoscopic LEER and reconstructive surgery for a recurrent endometrial carcinoma located at the right sciatic foramen is technically feasible in experienced hands.