Hidetaka Nomura

Laparoscopy-assisted laterally extended endopelvic resection and sacrectomy (beyond laterally extended endopelvic resection) for platinum-sensitive recurrent ovarian cancer

Laterally extended endopelvic resection (LEER) is a surgical option for patients with laterally recurrent gynecological malignancies to preserve sciatic nerve function [1]. However, when a laterally recurrent tumor involves the sacrum, debulking surgery is generally abandoned because the surgical excision line is outside the standard LEER. Since its technical feasibility and oncological safety have been demonstrated, sacrectomy for recurrent rectal cancer is now considered the treatment of choice [2]. Theoretically, if complete resection is deemed possible, LEER and sacrectomy (beyond-LEER) may be the treatments of choice for recurrent gynecological malignancies. However, the technical feasibility of beyond-LEER has not been reported. In this video, we demonstrate the step-by-step procedure of laparoscopy-assisted beyond-LEER in a patient with platinum-sensitive recurrent ovarian cancer. The patient, with stage IVA ovarian cancer, was in complete remission after debulking surgery and chemotherapy. At the 13-month-platinum-free interval, a solitary recurrent tumor, involving the right internal iliac vessels and infiltrating the right sacral foramen (S3), was detected. Thus, second-line chemotherapy was initially introduced. During 6 months of chemotherapy, the tumor size remained unchanged and no other metastatic lesions were detected. Therefore, surgical resection was planned. Laparoscopy-assisted beyond-LEER was performed, and complete resection without tumor exposure was accomplished. No sign of recurrence 9 months post debulking surgery has been noted. This is the first report to demonstrate the technical feasibility of laparoscopy-assisted beyond-LEER. Table 1 presents a comparison with cases wherein open total pelvic exenteration with low-sacrectomy (TPES) was performed for recurrent rectal cancer. Forty-nine cases of open TPES demonstrated operation time, 11.5 hours; blood loss volume, 2,630 mL; and length of stay, 24.5 days [3]. These results are similar to the findings in our case: operation time, 11 hours; blood loss volume, 1,700 mL; and length of stay, 35 days. We suggest that the benefit of laparoscopy cannot be demonstrated because TPES is a different procedure compared with the beyond LEER. Kimura et al. [4] demonstrated that laparoscopic TPES for recurrent rectal cancer might have a benefit of reduced blood loss. The advantages of laparoscopy during our multidirectional procedure include not only the possibility of reducing blood loss but also the quick closure of abdominal wound and ease of keeping wound clean while changing patient's position during sacrectomy. However, due to the limited case and follow up periods, further studies are required to determine the efficacy of this novel surgery and real advantage of laparoscopy. The informed consent for use of this video was taken from the patient.

Clinical Management of Atypical Endometrial Cells of Undetermined Significance Followed by Negative Cytology

<b><i>Introduction:</i></b> In Japan, endometrial cytology is widely performed to evaluate the status of the endometrium in women with suspected endometrial cancer. A new classification system for endometrial cytology has recently been used: the Yokohama system, based on a descriptive reporting format. This study aimed to clarify the triage for patients with atypical endometrial cells of undetermined significance (ATEC-US) when followed by negative endometrial cytology. <b><i>Methods:</i></b> We enrolled patients diagnosed with ATEC-US at the Cancer Institute Hospital between January 2016 and December 2017, based on the following inclusion criteria: (1) ATEC-US diagnosed by office endometrial cytology, with or without office endometrial biopsy; (2) follow-up endometrial cytology was performed 3–6 months after initial sampling, with a negative result for malignancy; and (3) no prior history of conservative treatment with progestin for endometrial cancer or atypical endometrial hyperplasia (ATEC-A). Among eligible patients, we analyzed those later diagnosed by endometrial biopsy with ATEC-A or carcinoma. <b><i>Results:</i></b> Among 187 patients, 65 met the inclusion criteria. Forty-two patients (64.6%) were observed for more than 24 months. Two patients (3.1%) developed ATEC-A during a median observation time of 26.5 months; the times to diagnosis were 32 months and 22 months. <b><i>Discussion/Conclusion:</i></b> No patient developed ATEC-A or worse within 1 year. For patients with ATEC-US, if negative cytology is obtained at the next examination, a close follow-up is not necessary.

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

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). 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. 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. 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.

Effects of tumor spillage prevention in laparoscopic radical hysterectomy for early-stage cervical cancer: a propensity score-matched analysis

Minimally invasive radical hysterectomy has a worse prognosis than open surgery, but the reasons for the poor prognosis remain unclear. Tumor spillage occurs when the tumor is exposed to the surgical field and has been suggested to be related to a poor prognosis. This study aimed to compare the prognostic value of tumor spillage in laparoscopic radical hysterectomy and evaluate whether tumor spillage prevention improves oncological safety. We compared the prognosis of patients who underwent laparoscopic radical hysterectomy between December 2014 and November 2021 with or without tumor spillage prevention, including surgeries without prevention and those with failed prevention. Prevention consisted of vaginal cuff formation or closure of the vaginal canal with clips to prevent tumor exposure at the time of colpotomy. The primary endpoint was disease-free survival, which was adjusted using propensity scores to compare patients. In total, 165 patients received tumor spillage prevention, and 61 did not or failed to receive such prevention. The median follow-up was 4.4 years. Patients who did not undergo prevention or failed prevention had significantly shorter disease-free survival than those who did (hazard ratio [HR]=3.54; 95% confidence interval [CI]=1.23-10.23). The same trend was observed after adjusting for propensity score matching. Patients who did not or failed to receive prevention were more likely to experience local recurrence (HR=4.01; 95% CI=1.13-14.24). Tumor spillage prevention was associated with longer disease-free survival in laparoscopic radical hysterectomy.

Surgical outcomes of early-stage primary vaginal nonsquamous cell carcinoma

Definitive radiation therapy (RT), using external beam RT and/or brachytherapy, is a standard treatment option for primary vaginal carcinoma. However, this treatment has poor prognosis when applied to vaginal nonsquamous cell carcinoma (non-SCC). We aimed to clarify treatment outcome and surgical safety in early-stage primary vaginal non-SCC. After receiving approval from the institutional review board, we retrospectively reviewed the clinical records and pathological samples of patients treated at our hospital between 1991 and 2018. Among 49 patients with primary vaginal carcinoma, 12 with histologically confirmed early-stage primary vaginal non-SCC were included in this study. In total, 40% of patients with primary vaginal carcinoma treated at our hospital had primary vaginal non-SCC. The average observation time was 34 months (median 53.3 months). Three patients had local recurrence: 2 in pelvic lymph nodes and 1 in the vagina. Furthermore, 2 patients died of their disease. Five-year local control rate of stage I and stage II non-SCC was 75% and 100%, respectively. Disease-specific survival rate of stage I and stage II non-SCC was 81.8% and 100%, respectively. No major morbidity was observed. Three patients required allogeneic blood transfusion, whereas 1 underwent autotransfusion. None of the 12 patients were discharged with self-catheterization. Five-year local control and disease-specific survival rates of patients surgically treated for vaginal non-SCC were favorable. Therefore, surgery could be a safe and reasonable option for early-stage primary vaginal non-SCC.

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.

Influence of COVID‐19 on the clinical characteristics of patients with uterine cervical cancer in Japan: A single‐center retrospective study

AbstractAimThis study investigated the impact of coronavirus disease 2019 (COVID‐19) on the clinical characteristics and interregional movement of patients with uterine cervical cancer.MethodsThis study included 1189 patients who underwent treatment for cervical cancer, including cervical intraepithelial neoplasm and adenocarcinoma in situ, at our hospital in Tokyo, Japan, in 2017–2018 and in 2021, before and after the pandemic, respectively. The patients' clinical information was compared during both periods. The clinical stage was unified using the International Federation of Gynecology and Obstetrics (FIGO) 2008 staging.ResultsThe number of patients treated for cervical cancer was 355, 420, and 414 in 2017, 2018, and 2021, respectively. The percentage of invasive carcinomas significantly increased from 158 (44.5%) and 196 (46.7%) to 219 (52.9%) (p = 0.049). In all periods, no significant differences were observed in median age, histological type, and treatment. The proportions of FIGO Stage IA1 were significantly elevated from 3.9% and 3.8% to 11.4% (p < 0.001). The percentage of patients from prefectures other than Tokyo significantly increased from 34.9% to 40.8% (p = 0.049). Furthermore, the proportion of patients with invasive carcinoma in private clinics increased from 28.0% to 37.9% (p = 0.014).ConclusionsThe number of patients with invasive carcinoma and the percentage of patients with invasive carcinoma referred from private clinics increased, indicating that the COVID‐19 pandemic influenced patients to delay consultations. Furthermore, the surge in patients from other prefectures indicates that medical resources were more limited in rural areas, another impact of COVID‐19.

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

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. 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. 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: β=-143.4; left side, β=-160.4). 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.

Cerebral infarction caused by Trousseau syndrome associated with cervical cancer

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. 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. 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). Cervical cancer causes Trousseau syndrome in cases of advanced disease with a short time between the onset of the syndrome and mortality.

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

AbstractAimOvarian 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.MethodsWe 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.ResultsOverall, 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.ConclusionsThe 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.

The efficacy and safety of lenvatinib plus pembrolizumab in vulnerable patients with metastatic or recurrent endometrial cancer: a single institution experience

Effective management with second-line therapy with the lenvatinib + pembrolizumab regimen for patients with advanced endometrial cancer is necessary. This retrospective study enrolled patients with endometrial cancer treated with the lenvatinib + pembrolizumab regimen. We evaluated progression-free survival (PFS), overall survival (OS), safety for patients non-eligible for the KEYNOTE775 trial, aged ≥65 years, or with ECOG performance status 1-2. Forty-five patients were analyzed: 21 (47%) were aged ˃ 65 years, 16 (36%) had performance status 1-2, and 15 (33%) were non-eligible for KEYNOTE775 trial participation. Overall, the median PFS was 8.5 months (95% confidence interval [CI] 4.6-12.4), and the median OS was 15.6 months (95% CI 9.4-NA). Median PFS was significantly shorter in patients not eligible for KEYNOTE775 participation and with performance status 1-2. The median OS was significantly shorter in patients with performance status 1-2. Grade ˃3 adverse events (AEs) occurred in 78% of patients who received the lenvatinib + pembrolizumab regimen. AEs resulted in lenvatinib dose reductions in 35 patients (78%) and lenvatinib and pembrolizumab discontinuation in 3 (7%) and 5 (11%), respectively. The median time to the first lenvatinib dose reduction was 1.5 (0.92-2.3) months in all patients and was significantly shorter in patients aged >65 years. The current regimen has favorable efficacy and manageable safety with appropriate dose reduction of lenvatinib in the real world. However, the efficacy may be inferior in patients with performance status 1 or 2, heavily treated patients, and those with organ dysfunction. The current treatment status should reflect real-world data relative to the medical environment and management.