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.

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.

Cerebral infarction caused by Trousseau syndrome associated with cervical cancer.

OBJECTIVE: The combination of cancer and hypercoagulable states is often called Trousseau syndrome. In particular, cerebral infarction caused by Trousseau syndrome is reported to have a poor prognosis. In gynecology, there are many reports of ovarian cancer and a few of uterine cancer. Since there has been no comprehensive report of Trousseau syndrome in cervical cancer, we aimed to summarize Trousseau syndrome in cervical cancer. METHODS: Cerebral infarction caused by cancer-related arterial thrombosis was defined as Trousseau syndrome. Patients with cervical cancer diagnosed at our hospital between January 2014 and December 2021 were retrospectively reviewed using the hospital's medical records. RESULTS: A total of 1,432 patients were included in the study. Trousseau syndrome occurred in 6 patients (0.4%). The mean age of patients with Trousseau syndrome was 63 years (range: 53-78 years). Of the 6 patients who developed Trousseau's syndrome, 4 patients had it before or during initial treatment, and 2 during recurrent/relapsed disease treatment. The 4 patients who developed the syndrome before or during initial treatment had advanced disease: 1 in stage IIIC and 3 in stage IVB. In all cases, the disease was associated with progressive distant metastasis. The median survival time from the onset of Trousseau syndrome was 1 month (range: 0-6 months). CONCLUSION: Cervical cancer causes Trousseau syndrome in cases of advanced disease with a short time between the onset of the syndrome and mortality.

Clinical implications of the superficial uterine vein pattern for the dissection of the anterior layer of the vesicouterine ligament in radical hysterectomy.

OBJECTIVE: To describe anatomic patterns of the superficial uterine vein (sUV) and assess their association with aspects of the dissection procedure of the anterior layer of the vesicouterine ligament (aVUL) by retrospectively reviewing surgical videos. METHODS: We analyzed patients who underwent laparoscopic radical hysterectomy for early-stage cervical cancer from 2014 to 2019. The primary endpoint was the time required for aVUL dissection. Multiple linear regression analyses were performed to identify factors influencing the time required for aVUL dissection. RESULTS: Fifty-three Japanese patients were included. Two sUV configurations were observed: type 1 (the vein ran ventral to the ureter along the uterine artery) and type 2 (the vein did not run along the usual ventral course; it ran dorsal to the ureter or was absent). Approximately 30% of the sUVs were type 2. The total time for dissection of both sides of the aVUL was significantly shorter for type 2 sUVs than for type 1 sUVs. The number of hemostatic interventions during dissection of each side of the aVUL was significantly lower for type 2 sUVs than for type 1 sUVs. In the multivariate analysis, the sUV configuration was the factor significantly influencing the duration of aVUL dissection on each side (right side: ß=-143.4; left side, ß=-160.4). CONCLUSION: We demonstrated that the sUV had 2 types of courses, ventral and others, and its course affected the time required for dissection and the number of hemostatic interventions. Our results provide information supportive of improved radical hysterectomy outcomes.

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.

Local Treatment Efficacy for Single-Area Squamous Cell Carcinoma of the Unknown Primary Site.

The prognosis for cancer of unknown primary site (CUP) is poor, and squamous cell carcinoma of the unknown primary site (SCCUP) is a rare histological type. CUP is often treated with aggressive multimodal treatments, while the treatment of single-area localized CUP remains controversial. We retrospectively reviewed the medical records of patients with CUP. SCCUP in women was classified according to several definitions. Based on the histologic type and site, they were classified into favorable and unfavorable subsets. We further divided SCCUP into two types (single and multiple areas) and reviewed treatment and efficacy. Among the 227 female CUP patients, 36 (15%) had SCCUP. The median age was 59.9 years (range, 31-90 years). Most patients (61.1%) had a good performance status. Of the SCCUP patients, 22 had cancer in a single area, and 14 in multiple areas. Single-area SCCUP was further divided into favorable (16 cases) and unfavorable subsets (6 cases). In the favorable subset, local treatment was predominant, and almost all cases had a good prognosis. Even in the unfavorable subset, local therapy was combined with systemic chemotherapy in only two cases, and four cases showed no recurrences. Local treatment may be effective for single-area SCCUP, even in the unfavorable subset.

Osteomyelitis pubis caused by Pseudomonas aeruginosa secondary to surgical site infections subsequent to vulvar cancer surgeries: A case report.

Secondary osteomyelitis pubis is rare, particularly when it arises due to genitourinary postoperative infections, such as those occurring after vulvar cancer surgeries. Diagnosis and treatment of secondary osteomyelitis pubis are challenging. Here, we report on two cases of osteomyelitis pubis caused by Pseudomonas aeruginosa secondary to surgical site infections after of vulvar cancer surgeries. Both patients were in their 80 s and underwent vulvectomy and vulvar reconstructive surgery using skin flaps. The patients were discharged from the hospital after postoperative antimicrobial treatment for surgical site infections and continued self-cleaning of the wound dehiscence. Both patients presented, respectively, with gait disturbance due to pain in the pubic bone postoperatively at 24 and 7 weeks. Computed tomography (CT) and magnetic resonance imaging (MRI) were performed to confirm the diagnosis of osteomyelitis pubis. The patients underwent pubic bone debridement, and tissue culture revealed the presence of Pseudomonas aeruginosa that required several months of antimicrobial therapy. Pubic pain and gait disturbance improved with treatment, and no osteomyelitis pubis relapse has been observed in both cases 12 and 9 months since treatment initiation. CT and MRI were useful in diagnosing osteomyelitis pubis. Early debridement helped identify the causative organism and appropriate antibiotics selection.

Transperineal endoscopic approach with GelPOINT V-path in laparoscopic pelvic exenteration for postirradiated recurrent cervical cancer.

Pelvic exenteration (PE) is a highly invasive procedure associated with high morbidity and mortality rates. Laparoscopy is a promising option to reduce this invasiveness, and laparoscopic PE significantly reduces blood loss and shortens hospital stays. In the case of a large tumor with invasion to the surrounding organs, laparoscopic dissection around the pelvic floor is sometimes problematic owing to restrictions on handling instruments. To overcome these limitations, we performed a transperineal endoscopic approach using the GelPOINT V-path in addition to laparoscopic PE. This approach enabled dissection around the pelvic floor without the abovementioned obstacles under magnified visualization. As a result, we could dissect the pelvic floor precisely with a reduction of the dead pelvic space, which might contribute to reduced rates of postoperative complications while ensuring oncologic outcomes.

Serum Creatinine Elevation as a Risk Factor for Niraparib-induced Hematologic Toxicity.

BACKGROUND/AIM: Niraparib dosages can be individualized to reduce the starting dose based on body weight and baseline platelet count. However, even with individualized dosing, scattered cases of ≥Grade 3 hematologic toxicity occur. This study explored markers predictive of serious hematologic toxicity in niraparib therapy. PATIENTS AND METHODS: This retrospective observational study investigated patients who started niraparib therapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research between December 2020 and March 2022. Associations between hematologic toxicities and serum creatinine ratio (percentage increase in serum creatinine between baseline and after niraparib initiation) were investigated. RESULTS: Out of 50 ovarian cancer patients who initiated niraparib, 45 patients were included in the final analysis. Twenty-three patients (51.1%) developed ≥Grade 3 hematologic toxicity, with neutropenia in 17 (37.8%), anemia in 9 (20.0%), and thrombocytopenia in 4 (8.9%). Patients with Grade 4 hematologic toxicity showed higher serum creatinine ratios than those with ≤Grade 2. Thrombocytopenia ≥Grade 3 occurred only within 2 months of niraparib initiation and was preceded by an increase in serum creatinine in all affected patients. CONCLUSION: Serum creatinine ratio offers a potential marker for predicting severe hematologic toxicity following niraparib therapy.

Primary ovarian insufficiency associated with lenvatinib therapy in a patient with hepatocellular carcinoma: A case report.

The therapeutic effects of molecular targeted drugs are, in some cases, more pronounced than those of conventional chemotherapy, and their introduction as a standard treatment is increasing. The present report describes a case of ovarian insufficiency in a young woman caused by tyrosine kinase inhibitor lenvatinib. The 25-year-old woman received lenvatinib (8 mg/day) for 98 days as preoperative chemotherapy for hepatocellular carcinoma. Blood testing the day before starting lenvatinib administration indicated 4.40 mIU/ml luteinizing hormone (LH), 5.2 mIU/ml follicle-stimulating hormone (FSH) and age-equivalent hormone values. Amenorrhea occurred after the start of administration, and 48 days later, the LH level was 41.8 mIU/ml and the FSH level was 44 mIU/ml, indicating a decrease in ovarian function. The patient underwent hepatectomy, and 49 days after the end of lenvatinib administration, the LH level had improved to 4.5 mIU/ml and the FSH level had improved to 2.5 mIU/ml. After the hepatectomy, the patient began to have regular menstrual cycles once again. Ovarian toxicity has not been recognized as a side effect of lenvatinib. However, the present report describes primary ovarian insufficiency considered to be caused by this drug. Potential damage to ovarian function may need to be considered when molecular targeted drugs with the same mechanism of action as lenvatinib are used in young women.

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.

Efficacy of intra-abdominal cytoreductive surgery in advanced endometrial cancer with distant metastasis.

OBJECTIVE: The efficacy of intra-abdominal cytoreductive surgery in patients with endometrial cancer and distant metastasis is equivocal. We investigated the effectiveness of such surgical treatment and whether it should be performed before or after chemotherapy (CT). METHODS: This study included patients with an International Federation of Gynecology and Obstetrics stage IVB endometrial cancer who received initial treatment at our hospital between January 2006 and December 2017. RESULTS: We retrospectively reviewed 67 patients with stage IVB endometrial cancer with distant metastases and classified them into preceding surgery (PS, n=23), chemotherapy followed by a surgery (CS, n=27), and CT (n=17) groups. We examined the achievement of resection with [R (1)] or without [R (0)] intra-abdominal macroscopic residue and survival. The median survival time for R (0) was 44 (95% confidence interval [CI]=9-not available [NA]) months in the PS group and 27 (95% CI=11-NA) months in the CS group. The median survival time for R (1) was 9 (95% CI=0-24) months in the PS group and 12 (95% CI=7-19) months in the CS group. The similar prognosis in both groups was worse with R (1) than with R (0). The survival curve for R (1) in the resection groups was similar to that of the CT group. CONCLUSION: Achieving resection without intra-abdominal macroscopic residue for endometrial cancer with distant metastases, whether before or after CT, could extend patients' survival.

Mucinous tumors arising from ovarian teratomas as another source of pseudomyxoma peritoneii: MR findings comparison with ovarian metastases from appendiceal mucinous tumors.

Objective: The origin of pseudomyxoma peritoneii (PMP) has been established as low-grade appendiceal mucinous tumors (AMT). However, intestinal-type ovarian mucinous tumors are known as another source of PMP. Recently, it is advocated that ovarian mucinous tumors causing PMP originates from teratomas. However, AMTs are often too small to detect on imaging; then, differentiating metastatic ovarian tumors of AMT from ovarian teratoma-associated mucinous tumors (OTAMT) is important. Therefore, this study investigates the MR characteristics of OTAMT compared to the ovarian metastasis of AMT. Methods: MR findings of six pathologically confirmed OTAMT were retrospectively analyzed compared to ovarian metastases of low-grade appendiceal mucinous neoplasms (LAMN). We studied the existence of PMP, uni- or bilateral disease, the maximum diameter of ovarian masses, the number of loculi, a variety of sizes and signal intensity of each content, the existence of the solid part, fat, calcification within the mass, and appendiceal diameters. All the findings were statistically analyzed using the Mann-Whitney test. Results: Four of the six OTAMT showed PMP. OTAMT showed unilateral disease, had a larger diameter, more frequent intratumoral fat, smaller appendiceal diameter than those in AMT, and they were statistically significant (p < .05). On the other hand, the number, variety of size, signal intensity of loculi, and the solid part, calcification within the mass did not differ from each other. Conclusion: Both OTAMT and ovarian metastasis of AMT appeared as multilocular cystic masses with relatively uniform signal and size of loculi. However, a larger unilateral disease with intratumoral fat and smaller size of the appendix may suggest OTAMT. Advances in knowledge: OTAMT can be another source of PMP, as AMT. MR characteristics of OTAMT were very similar to ovarian metastases of AMT; however, in cases with PMP combined with fat-containing multilocular cystic ovarian mass, we can diagnose them as OTAMT, not PMP caused by AMT.

Reconstruction of the diaphragm with autologous fascia lata during cytoreduction in patients with advanced ovarian cancer.

Cytoreductive surgery for patients with advanced ovarian cancer often requires full-thickness resection of the diaphragm [1]. In most cases, the diaphragm can be closed directly; however, when the defect is wide and simple closure is difficult, reconstruction using a synthetic mesh is usually performed [2]. However, the use of this type of mesh is contraindicated in the presence of concomitant intestinal resections because of the risk of bacterial contamination [3]. Autologous tissue shows a higher resistance to infection than artificial materials [4]; thus, we introduce diaphragm reconstruction using autologous fascia lata during cytoreduction for advanced ovarian cancer. A patient with advanced ovarian cancer underwent right diaphragmatic full-thickness resection with concomitant resection of the rectosigmoid colon, and complete resection was achieved. The defect of the right diaphragm measured 12×8 cm, and direct closure was impossible. A section of the right fascia lata measuring 10×5 cm was harvested and sutured to the diaphragmatic defect with a 2-0 proline continuous suture. The harvesting of the fascia lata required only 20 minutes, with little blood loss. No intraoperative or postoperative complications were experienced, and adjuvant chemotherapy was initiated without any delay. Diaphragm reconstruction with the fascia lata is a safe and simple method, and we propose this reconstruction technique especially for patients with advanced ovarian cancer who undergo concomitant intestinal resections. The informed consent for use of this video was taken from the patient.

Impact of the coverage of risk-reducing salpingo-oophorectomy by the national insurance system for women with BRCA pathogenic variants in Japan.

To determine the impact of the coverage of risk-reducing salpingo-oophorectomy (RRSO) and mastectomy (RRM) as well as genetic testing for BRCA pathogenic variants by the national insurance system in Japan. We compared the clinical background of women who underwent RRSO at our institution before and after its coverage by the national insurance system. Those who underwent RRSO between January 2017 and December 2019 and between April 2020 and March 2022 were classified as Period. A and B, respectively. Overall, 134 women underwent RRSO during the study period. In Period A and B, 45 and 89 women underwent RRSO for the study period was 36 and 24 months, respectively. Compared with Period A, the number of women who underwent RRSO per month increased by threefold in Period B (p < 0.01). In addition, the number of women who underwent surgery for breast cancer along with RRSO increased in Period B (p < 0.01). Although the number of women who underwent concurrent RRM with RRSO in Period B increased, the difference was not statistically significant. Compared with Period A, the number of women diagnosed with BRCA pathogenic variant increased by 3.9-fold, and the proportion of women who underwent concurrent hysterectomy at the time of RRSO decreased from 66 to 7.9% in Period B (p < 0.01). Owing to the introduction of the national insurance system, the number of women who underwent RRSO and concurrent surgery for breast cancer at the time of RRSO increased in Japan.

Transvaginal cervical tumor-concealing no-look no-touch technique in minimally invasive radical hysterectomy for early-stage cervical cancer: a novel operation technique.

The Laparoscopic Approach to Cervical Cancer (LACC) trial demonstrated that minimally invasive radical hysterectomy was inferior to the open approach [1]; this unexpected result could be attributed to the spillage of cancer cells [2]. Following the LACC trial, laparoscopic radical hysterectomy without an intrauterine manipulator upon completion of a vaginal cuff closure became the new standard treatment method [3]. However, the lack of intrauterine manipulator results in poor visualization and inadequate paracervical tissue resection. This study describes the no-look no-touch technique to address this difficulty. The core procedures in our no-look, no-touch laparoscopic radical hysterectomy are: (Step 1) Creation and closure of a vaginal cuff; (Step 2) Manipulation of the uterus without an intra-uterine manipulator; and (Step 3) Exposure of the paracervical tissues by the suspension technique. The patient eligibility for our procedure is as follows: 1) previously untreated cervical cancer (those who underwent diagnostic conization could be included); 2) clinical stage IA2, IB1, IB2, and IIA1 based on the 2018 International Federation of Gynecology and Obstetrics staging system; 3) histologically confirmed cervical cancer, including squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma. The important indication for this procedure is in cases where the tumor is less than 4 cm in diameter. We previously reported that our no-look no-touch technique enables smooth performance of laparoscopic radical hysterectomy without worsening oncologic outcomes [4]. According to a recent systematic review and meta-analysis [5], minimally invasive radical hysterectomy with vaginal cuff closure is a safe treatment option; however, it involves a steep learning curve, which has impeded its increased application. This video will hopefully make minimally invasive radical hysterectomy with protective maneuvers against cancer cell spillage more accessible. Based on our experiences, we propose that our transvaginal cervical tumor-concealing no-look no-touch technique will mitigate the risk of surgical spill of tumor cells during minimally invasive radical hysterectomy. The informed consent for use of this video was taken from the patient.

Minimally invasive radical hysterectomy and the importance of avoiding cancer cell spillage for early-stage cervical cancer: a narrative review.

Radical hysterectomy is a standard surgery to treat early-stage uterine cervical cancer. The Laparoscopic Approach to Cervical Cancer (LACC) trial has shown that patients receiving minimally invasive radical hysterectomy have a poorer prognosis than those receiving open radical hysterectomy; however, the reason for this remains unclear. The LACC trial had 2 concerns: the learning curve and the procedural effects. Appropriate management of the learning curve effect, including surgeons' skills, is required to correctly interpret the result of surgical randomized controlled trials. Whether the LACC trial managed the learning curve effect remains controversial, based on the surgeons' inclusion criteria and the distribution of institutions with recurrent cases. An appropriate surgical procedure is also needed, and avoiding intraoperative cancer cell spillage plays an important role during cancer surgery. Cancer cell spillage during minimally invasive surgery to treat cervical cancer is caused by several factors, including 1) exposure of tumor, 2) the use of a uterine manipulator, and 3) direct handling of the uterine cervix. Unfortunately, these issues were not addressed by the LACC trial. We evaluated the results of minimally invasive radical hysterectomy while avoiding cancer cell spillage for early-stage cervical cancer. Our findings show that avoiding cancer cell spillage during minimally invasive radical hysterectomy may ensure an equivalent oncologic outcome, comparable to that of open radical hysterectomy. Therefore, evaluating the importance of avoiding cancer cell spillage during minimally invasive surgery with a better control of the learning curve and procedural effects is needed.

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.