Hiroyuki Kanao

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.

Step-by-step demonstration of “sciatic-nerve-preserved beyond-LEER” in a Thiel-embalmed cadaver: a novel salvage surgery for recurrent gynecologic malignancies

Laparoscopic resection surgery for malignant transformation of extragonadal endometriosis by the “pincer” approach

Up to 1% of women with endometriosis develop endometriosis-associated neoplasms [1]. Most endometriosis-associated malignant tumors develop from the ovarian endometriomas, whereas those developing from extragonadal lesions are extremely rare, estimated at 0.2% [2]. Because they are uncommon, a treatment protocol for the malignant transformation of extragonadal endometriosis lesions has not been clearly defined. When the lesion is confined to the site of origin and R0 resection is achieved, the 5-year survival rate is between 82% and 100%; therefore, complete resection should be performed [3]. The patient in this video had previously undergone hysterectomy, bilateral salpingo-oophorectomy, left nephrectomy, and low-anterior resection of the rectum due to severe endometriosis. Ten years after the surgery, the patient had a 6 cm endometrioid adenocarcinoma developing from the residual endometriosis lesion at the left uterosacral ligament that involved the bladder, left ureter, and rectum. In this case, the tumor was attached to the pelvis due to infiltration of the left sacrospinous ligament. To completely remove the tumor, we used laterally extended endopelvic resection with abdominoperineal resection of the rectum. We used the laparoscopic-perineal-laparoscopic approach (pincer approach) because improved visualization of the left sacrospinous ligament increases the probability of achieving complete resection [4]. Pathological R0 resection was achieved without intraoperative or postoperative complications. Thus, for tumors that are firmly attached to the pelvic floor, the pincer approach can be useful for achieving R0 resection. The informed consent for use of this video was taken from the patient.

Comparison of survival between primary debulking surgery and neoadjuvant chemotherapy for stage III/IV ovarian, tubal and peritoneal cancers in phase III randomised trial

Regarding the comparison between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) for stage III/IV ovarian, tubal and peritoneal cancers, EORTC55971 and CHORUS studies demonstrated noninferiority of NACT. Previously, we reported reduced invasiveness of NACT in JCOG0602. This is a final analysis including the primary endpoint of overall survival (OS). Patients were randomised to PDS (PDS followed by 8x paclitaxel and carboplatin, i.e. TC regimen) or NACT (4x TC, interval debulking surgery [IDS], 4x TC). The primary endpoint was OS. The noninferiority hazard ratio (HR) margin for NACT compared with PDS was 1·161. The planned sample size was 300. Between 2006 and 2011, 301 patients were randomised, 149 to PDS and 152 to NACT. The median OS was 49·0 and 44·3 months in the PDS and NACT. HR for NACT was 1·052 [90·8% confidence interval (CI) 0·835-1·326], and one-sided noninferiority p-value was 0·24. Median progression-free survival was 15·1 and 16·4 months in the PDS and NACT (HR: 0·96 [95%CI 0·75-1·23]). In the PDS arm, 147/149 underwent PDS and 49/147 underwent IDS. In the NACT arm 130/152 underwent IDS. Complete resection was achieved in 12% (17/147) of PDS and 31% (45/147) of PDS ± IDS in the PDS arm and in 64% (83/130) of IDS in the NACT arm. Optimal surgery (residual tumour  2000 an institution with low study activity was advantageous, whereas clear/mucinous histology was disadvantageous for OS. The noninferiority of NACT was not confirmed. NACT may not always be a substitute for PDS. However, as our study had smaller numbers, the noninferiority of the previous studies cannot be denied. Ministry of Health, Labour and Welfare, Japan and the National Cancer Center, Japan. UMIN000000523.

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.

Relationship between the lateral dissection lines of various radical hysterectomies and anatomical structures in the female pelvis: an educational video from the Sapporo Cadaver Surgical Workshop

Radical hysterectomy with pelvic lymph node dissection is the treatment of choice for cervical cancer. All gynecologic oncologists should master this technique. The surgical procedure requires a wide dissection of the female pelvis. Performing radical hysterectomy without a thorough knowledge of the anatomy of the female pelvis can lead to serious complications. For novice surgeons to safely perform radical hysterectomy, mastering the 3-dimensional anatomy of the pelvis and aligning the dissection lines of radical hysterectomy to the female pelvic anatomy is crucial. Educational materials that demonstrate the anatomical relationship between dissection lines in radical hysterectomy and the surrounding pelvic structures are lacking. We aimed to create educational material to overcome these problems. Laparoscopic nerve sparing, non-nerve sparing, and super-radical hysterectomies, exposing pivotal pelvic anatomical structures, were performed on a Thiel-embalmed cadaver. Nerve sparing, non-nerve sparing, and super-radical hysterectomies were laparoscopically performed in the right hemi-pelvis of the cadaver. We exposed the external and internal iliac vessels; obturator, sciatic, femoral, hypogastric, and pelvic splanchnic nerves and the pelvic nerve plexus; internal obturator, piriform, and coccygeal muscles; sacrospinous ligament; and ischial spine. Thus, we demonstrated where the dissection lines of the various radical hysterectomies are in a female pelvis. Using a Thiel-embalmed cadaver, we demonstrated the relationship between the dissection lines of various radical hysterectomies and pivotal sidewall anatomical structures in a female pelvis. The anatomical detail shown in the video captured during this procedure may assist surgeons to safely perform various radical hysterectomies.

Assessment of postoperative therapy de-escalation for early-stage, intermediate-risk cervical cancer

The objective of this study was to assess the oncologic outcome of surgically-treated patients with early-stage, intermediate-risk cervical cancer according to postoperative therapy modality. This retrospective cohort study queried the Japanese Gynecologic Oncology Group's nationwide surgical data platform. The study population was 1084 patients with stage IB cervical cancer who underwent primary radical hysterectomy and lymphadenectomy from 2004 to 2008. Histology type-incorporated intermediate-risk factor patterns were clustered into three groups based on recurrence risk. Oncologic outcomes were assessed per postoperative therapy: external beam radiotherapy alone, concurrent chemo-radiotherapy, chemotherapy alone, and no treatment. Histology-incorporated intermediate-risk groups included: no lympho-vascular space invasion in any histology, or squamous cell carcinoma with lympho-vascular space invasion but no deep stromal invasion (n=559, 51.6%, group 1); squamous cell carcinoma with both lympho-vascular space invasion and deep cervical stromal invasion (n=281, 25.9%; group 2); and non-squamous histology with lympho-vascular space invasion (n=244, 22.5%; group 3). The 5-year disease-free survival rates were 93.3%, 89.3%, and 82.5% for group 1,-2, and -3, respectively (p0.05). In this retrospective investigation in Japan, active surveillance without postoperative therapy following radical hysterectomy and lymphadenectomy was not associated with oncologic outcome in early-stage, intermediate-risk cervical cancer.

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.

Should indications for laterally extended endopelvic resection (LEER) exclude patients with sciatica?

Previously, indications for laterally extended endopelvic resection (LEER) have excluded patients with sciatica because R0 resection has not been deemed possible [1]. Because laparoscopy optimizes visualization and thus provides for meticulous dissection, we hypothesized that R0 resection can be achieved by means of laparoscopic LEER in patients with sciatica. This video article aimed to clarify the technical feasibility of laparoscopic LEER performed for laterally recurrent previously irradiated cervical cancer with concomitant sciatica. We investigated technical feasibility of laparoscopic LEER performed as a salvage therapy following abdominal radical hysterectomy and concurrent chemoradiotherapy in a patient suffering laterally recurrent cervical carcinoma with concomitant sciatica. The recurrent tumor involved the right external and internal iliac artery and vein, ileocecum, rectosigmoid colon, right ureter, right obturator nerve, and right sciatic nerve, with a resulting fistula between the tumor and the rectosigmoid colon, and severe sciatica. Resection of all these structures was essential for achievement of R0 status, and such resection means concomitant femoral bypass with prosthetic graft interposition and gastrointestinal/urinary tract resection. Laparoscopic LEER with femoral-femoral artery bypass could be conducted without any postoperative complications. Pathological R0 resection could be achieved, and local recurrence could have been controlled. However, the patient died from liver and lung metastasis at 1 year after this resection surgery. Laparoscopic LEER for a laterally recurrent previously irradiated cervical cancer with concomitant sciatica was technically feasible, however, further study involving a greater number of patients and longer follow-up period is warranted to determine the stringent indications.

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.

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.

The impact of cytoreductive surgery on outcomes in high tumor burden ovarian cancer after induction of PARP inhibitors

In advanced ovarian cancer, achieving R0 resection is a critical strategy for improving prognosis. However, even with R0 resection, the prognosis of patients with a high tumor burden remains poor. This study aimed to assess whether the introduction of poly(ADP-ribose) polymerase inhibitors (PARPi) has enhanced outcomes in such cases. We retrospectively analyzed patients with International Federation of Gynecology and Obstetrics (FIGO) stage III-IV ovarian cancer treated between January 2015 and December 2021. Patients were classified into Group A (pre-PARPi introduction) and Group B (post-PARPi introduction). Complete macroscopic resection was defined as R0. Progression-free survival (PFS), stratified by the Aletti Surgical Complexity Score (Aletti_SCS), was the primary endpoint and was evaluated using Cox regression models. A total of 434 patients were included. In Group A, among those who achieved R0, the median PFS was 23.5 months for patients with high Aletti_SCS (95% confidence interval [CI]=14-30) and not reached for those with low Aletti_SCS (95% CI=30-not reached; adjusted hazard ratio [HR]=0.36, 95% CI=0.20-0.62). In Group B, the median PFS was not reached in both patients with high Aletti_SCS (95% CI=not reached-not reached) and low Aletti_SCS (95% CI=22-not reached; adjusted HR=4.98, 95% CI=1.14-21.78). Following the introduction of PARPi, there was a trend toward improved PFS in patients with a higher Aletti_SCS who underwent R0 resection. These findings suggest that R0 resection may improve prognosis even in cases with a high tumor burden in the PARPi era.

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.