Mid-term outcomes of laparoscopic vaginal stump­round (Kakinuma method) and stump­uterosacral (Shull method) ligament fixation for pelvic organ prolapse: A retrospective comparative study

BACKGROUND: Laparoscopic sacrocolpopexy (LSC) and robot-assisted sacrocolpopexy (RSC) using mesh are popular approaches for treating pelvic organ prolapse (POP). However, it is not uncommon that native tissue repair (NTR) should be presented as an option to patients who are expected to have extensive intraperitoneal adhesion or patients for whom LSC or RSC is difficult owing to various risk factors. Laparoscopic vaginal stump-uterosacral ligament fixation (Shull method) has been introduced as a method for NTR in case of POP. However, effective repair using this surgical procedure may not be possible in severe POPs. To solve the problems of the Shull method, we devised the laparoscopic vaginal stump-round ligament fixation (Kakinuma method) in which the vaginal stump is fixed to the uterine round ligament, a histologically strong tissue positioned anatomically higher than the uterosacral ligament. This study aimed to retrospectively and clinically compare the two methods. METHODS: Of the 78 patients who underwent surgery for POP between January 2017 and June 2022 and postoperative follow-up for at least a year, 40 patients who underwent the Shull method (Shull group) and 38 who underwent the Kakinuma method (Kakinuma group) were retrospectively analyzed. RESULTS: No significant differences were observed between the two groups in patient background variables such as mean age, parity, body mass index, and POP-Q stage. The mean operative duration and mean blood loss in the Shull group were 140.5 ± 31.7 min and 91.3 ± 96.3 ml, respectively, whereas the respective values in the Kakinuma group were 112.2 ± 25.3 min and 31.4 ± 47.7 ml, respectively. Thus, compared with the Shull group, the operative duration was significantly shorter (P < 0.001) and blood loss was significantly less (P = 0.003) in the Kakinuma group. Recurrence was observed in six patients (15.0%) in the Shull group and two patients (5.3%) in the Kakinuma group. Hence, compared with the Shull group, recurrence was significantly less in the Kakinuma group (P = 0.015). No patients experienced perioperative complications in either group. CONCLUSIONS: The results suggest that the Kakinuma method can serve as a novel and viable NTR procedure for POP.

Efficacy and safety of standard of care with/without bevacizumab for platinum-resistant ovarian/fallopian tube/peritoneal cancer previously treated with bevacizumab: The Japanese Gynecologic Oncology Group study JGOG3023.

We investigated the efficacy and safety of further bevacizumab therapy in patients with platinum-resistant ovarian cancer whose disease had progressed after bevacizumab plus chemotherapy. In this multicenter, open-label, phase II trial (JGOG3023), patients were randomized 1:1 to a single-agent chemotherapy alone (either pegylated liposomal doxorubicin [40 or 50 mg/m2 administered intravenously], topotecan [1.25 mg/m2 intravenously], paclitaxel [80 mg/m2 intravenously], or gemcitabine [1000 mg/m2 intravenously]) or single-agent chemotherapy + bevacizumab (15 mg/m2 intravenously). The primary endpoint was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary endpoints were overall survival (OS), objective response rate (ORR), and response rate according to Gynecological Cancer Intergroup cancer antigen 125 criteria. In total, 103 patients were allocated to chemotherapy (n = 51) or chemotherapy + bevacizumab (n = 52). Median investigator-assessed PFS was 3.1 and 4.0 mo in each group, respectively (hazard ratio [HR] = 0.54, 95% confidence interval [CI]: 0.32-0.90, P = .0082). Median OS was 11.3 and 15.3 mo in each group, respectively (HR = 0.67, 95% CI: 0.38-1.17, P = .1556). Respective ORRs were 13.7% and 25.0% (P = .0599) and response rates were 16.7% and 21.4% (P = .8273). The incidence of grade ≥3 treatment-related AEs was 42.0% in the chemotherapy group and 54.9% in the chemotherapy + bevacizumab group; AEs were well tolerated, with only 2 and 12 events leading to discontinuation of therapy, respectively. Bevacizumab was effective beyond progressive disease and AEs were manageable. The observed improvement in PFS requires further verification.

Paclitaxel-carboplatin and bevacizumab combination with maintenance bevacizumab therapy for metastatic, recurrent, and persistent uterine cervical cancer: An open-label multicenter phase II trial (JGOG1079).

OBJECTIVE: This multicenter, open-label, phase II study aimed to evaluate the efficacy and safety of paclitaxel-carboplatin, bevacizumab, and bevacizumab-based maintenance therapy for metastatic, recurrent, and persistent uterine cervical cancer. METHODS: Patients with measurable diseases that were not adapted to regional therapies, such as surgery or radiotherapy, and were systematic chemotherapy-naïve were eligible. The participants received paclitaxel (175 mg/m2), carboplatin (AUC 5), and bevacizumab (15 mg/m2) every three weeks until disease progression or unacceptable adverse events occurred. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall response rate (ORR), overall survival (OS), safety, and time to treatment failure. RESULTS: Sixty-nine patients were analyzed using our protocol. The median paclitaxel- carboplatin therapy duration was six cycles; 40% of patients received bevacizumab maintenance therapy. The median PFS was 11.3 months. The median OS was not reached; the median time to treatment failure was 5.9 months. The ORR was 79.7% [95% confidence interval (CI) 63.8-88.4]; 16 patients (23.2%) showed complete response (CR) and 39 patients (56.5%) showed partial response (PR). The median PFS was 14.3 months (95% CI 7.3-17 months) for the 25 patients who received maintenance therapy and 7.4 months (95% CI 6.1-11 months) for nonrecipients (p = 0.0449). Gastrointestinal perforation/fistulas occurred in four patients (5.6%), all of whom had a history of radiation therapy. CONCLUSIONS: Paclitaxel-carboplatin and bevacizumab therapy is an acceptable and tolerable treatment for advanced or recurrent cervical cancer.

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.

Association of gBRCA1/2 mutation locations with ovarian cancer risk in Japanese patients from the CHARLOTTE study.

Whether germline (g) breast cancer susceptibility gene (BRCA) mutations are located within or outside the ovarian cancer cluster region (OCCR) (1380-4062 bp for gBRCA1, and between 3249-5681 bp and 6645-7471 bp for gBRCA2) may influence risk variations for ovarian cancers. This ad hoc analysis of the CHARLOTTE epidemiological study in Japan assessed the distribution of gBRCA1/2 mutations in patients with newly diagnosed ovarian cancer, and investigated an association between gBRCA1/2 mutation locations and ovarian cancer risk. Differences in patient background and clinical characteristics in subgroups stratified by gBRCA1/2 mutation locations were also evaluated. We analyzed the data of 93 patients (14.7%) from the CHARLOTTE study who were positive for gBRCA1/2 mutations. After excluding 16 cases with L63X founder mutation, 28 (65.1%) of gBRCA1 mutations were within the OCCR. Of 30 gBRCA2 mutations, 15 (50.0%) were within the OCCR. Of 27 patients (one patient excluded for unknown family history) with gBRCA1 mutations located in the OCCR, 11 (40.7%) had a family history of ovarian cancer; the proportion of patients with a family history of ovarian cancer and gBRCA1 mutations outside the OCCR was lower (13.3%). Sixty percent of patients with gBRCA1 mutations outside the OCCR had a family history of breast cancer; the proportion of patients with a family history of breast cancer and gBRCA1 mutations within the OCCR was relatively lower (33.3%). Understanding the mutation locations may contribute to more accurate risk assessments of susceptible individuals and early detection of ovarian cancer among gBRCA mutation carriers.

Pembrolizumab monotherapy in Japanese patients with advanced ovarian cancer: Subgroup analysis from the KEYNOTE-100.

Interim results from the two-cohort, phase 2 KEYNOTE-100 study (NCT02674061) of 376 patients with previously treated advanced recurrent ovarian cancer (ROC) showed that pembrolizumab monotherapy was associated with an objective response rate (ORR) of 8.0% (95% CI, 5.4-11.2). We present outcomes for the Japanese patients (n = 21) enrolled in KEYNOTE-100. Patients with epithelial ROC had received either 1-3 prior chemotherapy lines and had platinum-free interval or treatment-free interval (PFI; TFI) of 3-12 months (cohort A) or 4-6 prior chemotherapy lines and had PFI/TFI of ≥3 months (cohort B). All patients received pembrolizumab 200 mg every 3 weeks as monotherapy for 2 years or until progression, death, unacceptable toxicity or consent withdrawal. Primary objectives were ORR per RECIST v1.1 for each cohort and higher programmed death ligand-1 (PD-L1) tumor expression. The relationship between PD-L1 expression (measured as combined positive score [CPS]) and ORR was assessed. Twenty-one Japanese patients (cohort A, n = 19; cohort B, n = 2) were treated. The median (range) age was 57 (37-78) years; 19 (90.5%) patients had ECOG status of 0 and 16 (76.2%) patients had stage III-IV disease. ORR was 19.0% (95% CI, 5.4-41.9) and seemed to increase with increasing PD-L1 expression. A total of 13 (61.9%) patients had treatment-related adverse events (TRAE), and 5 (23.8%) had grade 3-4 TRAE. There were no treatment-related deaths in this subpopulation. Pembrolizumab monotherapy was associated with antitumor activity in Japanese patients with ROC, with no new safety signals identified in this subpopulation. The data suggested a trend toward higher PD-L1 expression among some patients with higher ORR.

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.

Adjuvant treatment of endometrial cancer today.

Endometrial cancer frequently occurs in post-menopausal women, and the endometrium is a well-known site of cancer affecting women. Endometrial cancer is found with genital bleeding and often at an early stage. However, there are some risks of recurrence after hysterectomy. As a medical treatment after the diagnosis of endometrial cancer, appropriate adjuvant therapy is considered to lead to a decrease in the rate of recurrence and improvement of prognosis according to the determination of the cancer stage from the surgical and histopathological results. In this review, we describe post-operative adjuvant therapy administered for endometrial cancer and advanced disease, focusing on chemotherapy, radiation therapy and the combination of both. These treatments are divided according to the risk of recurrence as based primarily on the reported evidence.

Surgical outcomes of early-stage primary vaginal nonsquamous cell carcinoma.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Laparoscopic Ureteral Reimplantation for the Management of Long-segment Ureteral Defect in Gynecologic Surgeries.

OBJECTIVE: To demonstrate techniques of laparoscopic ureteral reconstruction for long-segment ureteral defects in gynecologic surgeries. DESIGN: Step-by-step demonstration of a laparoscopic ureteral reimplantation using the Boari flap and ileal interposition. SETTING: Gynecologic diseases often involve the ureter; hence, knowledge of ureteral reconstruction techniques is imperative in gynecologic surgeries. The important aspect of ureteral reconstruction is to ensure tension-free anastomosis; therefore, various methods are required depending on the length of the ureteral defect [1]. The Boari flap and ileal interposition are preferred for repairing 8-cm to 12-cm and >12-cm ureteral defects, respectively. These methods have traditionally required large incisions [2,3]. Laparoscopic ureteral reimplantation using the Boari flap and ileal interposition has been reported to be as safe as the open technique and superior in terms of postoperative recovery in urologic surgeries [3,4]; however, to the best of our knowledge, it has not been reported in the field of gynecology. To our knowledge, this is the first report to demonstrate the techniques of laparoscopic Boari flap and ileal ureter replacement in gynecologic surgeries. The technique was approved by our institutional review board. INTERVENTIONS: The first case involved an intra-abdominal desmoid tumor, whereas the second case involved recurrent endometrial cancer. In both cases, long-segment ureteral resection was required to achieve complete tumor clearance. Laparoscopic ureteral reimplantation was performed successfully, without any complications, using the Boari flap in the first case and ileal interposition in the second. CONCLUSION: Laparoscopic ureteral reimplantation is technically feasible for the management of long-segment ureteral defects.

Laparoscopic Mesh Repair for Perineal Hernia after En Bloc Resection of an Aggressive Angiomyxoma Using a Modified Sacral Colpopexy Technique.

STUDY OBJECTIVE: To demonstrate laparoscopic mesh repair of perineal hernia (PH) by a modified sacral colpopexy technique. DESIGN: Step-by-step demonstration of the technique used for the surgical repair of PH after gynecologic surgery. SETTING: PH is defined as a pelvic floor defect through which the intra-abdominal viscera may protrude [1]. The reported incidence of PH ranges from 0.6% to 3%, and it generally occurs after rectal or prostate surgery [2]. Owing to its low incidence, there is no standard procedure to treat PH [3]. Herein, we demonstrate a successful case of PH treatment with a composite mesh (Dual Mesh; W. L. Gore & Associates, Newark, DE) after gynecologic surgery by a modified laparoscopic sacral colpopexy technique, which was approved by our institutional review board. INTERVENTIONS: The patient had undergone extralevator abdominoperineal excision for an aggressive angiomyxoma and developed a sigmoid colon-protrudent PH after the surgery [4]. The patient suffered from defecatory dysfunction and dysmenorrhea. A total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and mesh repair of the PH were performed at 2 years after the primary surgery, and they were successful without any intra- or postoperative complications. Because the pelvic floor defect was too large to secure the mesh by a simple placement, we applied the modified sacral colpopexy technique using 2-0 proline (ETHICON, Tokyo, Japan) to cover and support this defect. At 12 months after the second surgery, there was no sign of recurrence of PH and aggressive angiomyxoma, and the preoperative symptoms had diminished. CONCLUSION: Laparoscopic mesh repair by the modified sacral colpopexy technique is safe and effective to manage PH.

Modified posterior pelvic exenteration with pelvic side-wall resection requiring both intestinal and urinary reconstruction during surgery for ovarian cancer.

OBJECTIVE: Because of the anatomic proximity of the rectosigmoid to the female pelvic organs and its frequent involvement in ovarian cancer, an en bloc resection of ovarian tumors together with the uterus and rectosigmoid, also known as a modified posterior pelvic exenteration (MPPE), is frequently performed to achieve optimal cytoreduction [1]. Additionally, if the tumor has infiltrated the pelvic side-wall, a MPPE combined with pelvic side-wall resection can be selected [2]. We report the details of a technique for this surgery requiring intestinal and urinary reconstruction. METHODS: A 55-year-old woman underwent an up-front cytoreductive surgery for FIGO stage IIIC (pT3c N1 M0) ovarian cancer. Preoperatively, a tumor infiltrating the left pelvic side-wall was suspected; however, hydronephrosis of the left kidney was not observed on an enhanced computed tomography examination. During a laparotomy, tumor involvement of the left ureter and internal iliac vessels was observed; a MPPE with pelvic side-wall resection including a partial ureterectomy was thus performed. After the resection of the pelvic and omental tumors, colorectal and vesicoureteral anastomoses were performed. RESULTS: Histopathologically, a high-grade serous adenocarcinoma spreading into the muscular layer of the rectum, located close to the ureter and artery, and within 5 mm of the left pelvic side-wall was identified. Diet intake was started on postoperative day (POD) 3. The indwelling bladder catheter was removed on POD 10. Spontaneous voiding after surgery was sufficient and the volume of postvoid residual urine was noted to be <50 mL. The postoperative hospital stay was 12 days. No surgery-related complications occurred. Chemotherapy was initiated 3 weeks after the surgery. The ureteral stent was placed until 3 months after surgery. DISCUSSION: A MPPE requiring intestinal and urinary reconstruction is both feasible and safe and can be considered for patients with ovarian cancer involving the pelvic side-wall. Postoperative bladder function was preserved in this patient. However, difficulty in spontaneous voiding after surgery occurs and self-intermittent catheterization is necessary in some patients undergoing a MPPE combined with pelvic side-wall resection. In the previous study, we evaluated the impact of MPPE with or without nerve preservation on bladder function of the patients with ovarian and endometrial cancer [2]. All patients with bilateral nerve-sparing surgery had sufficient micturition from the early postoperative period. Though 40% of the patients with unilateral nerve-sparing surgery had difficulty in spontaneous voiding and needed intermittent catheterization, voiding ability of them improved and no self-catheterization was required 3 months after surgery. The assessment of patient questionnaires suggested that bladder function was acceptable in both groups at 6 months. Patients with bilateral nerve-sacrificing surgery complained of neurogenic bladder requiring self-catheterization even 6 months after surgery. Careful follow-up is required to assess bladder function after MPPE to the extent of pelvic autonomic nerve preservation.

The first Japanese nationwide multicenter study of BRCA mutation testing in ovarian cancer: CHARacterizing the cross-sectionaL approach to Ovarian cancer geneTic TEsting of BRCA (CHARLOTTE).

INTRODUCTION: BRCA gene mutations are associated with hereditary ovarian cancer. BRCA plays a key role in genome integrity, and mutations result in an increased risk for ovarian cancer. Although various guidelines recommend BRCA testing in patients with ovarian cancer, data on germline BRCA (gBRCA) mutation frequency in ovarian cancer in Japan are scarce. OBJECTIVE: This study aimed to determine gBRCA1/2 mutations in Japanese patients with ovarian cancer, stratified by clinicopathological characteristics, and to assess patients' satisfaction with pre-test genetic counseling. METHODS: The CHARLOTTE study (CHARacterizing the cross-sectionaL approach to Ovarian cancer: geneTic TEsting of BRCA; UMIN000025597) is the first large multicenter epidemiological survey of Japanese women, aged ≥20, with newly diagnosed ovarian cancer (epithelial, primary peritoneal, or fallopian tube cancer), with histologically confirmed specimens. Patients were enrolled sequentially and underwent pre-test genetic counseling for BRCA testing. Blood samples were centrally tested for the presence or absence of known gBRCA mutations. A questionnaire was used to assess patient satisfaction with pre-test genetic counseling. RESULTS: A total of 634 patients with a mean age of 56.9 years were included. Most patients (84.2%) had epithelial ovarian cancer, and 51.1% had FIGO stage III-IV cancer. Nearly all patients (99.5%) received genetic counseling before the BRCA testing, either by an obstetrician-gynecologist (42.0%) or a clinical geneticist (42.0%). The overall prevalence of gBRCA1/2 mutations was 14.7% (93/634), with gBRCA1 mutations (9.9%) more common than gBRCA2 mutations (4.7%). High-grade serous carcinoma showed a prevalence of gBRCA mutations of 28.5%. Most patients were satisfied with pre-test counseling, irrespective of the service provider's professional position. DISCUSSION: Patients with high-grade serous carcinoma and family history of ovarian cancer had a slightly higher prevalence of gBRCA mutations, but none of the subgroups had considerably high gBRCA mutation prevalence. These data suggest that gBRCA testing should be carried out in all patients with ovarian cancer.

Clinical background and outcomes of risk-reducing salpingo-oophorectomy for hereditary breast and ovarian cancers in Japan.

BACKGROUND: This study aimed to identify the clinical background and treatment outcomes of risk-reducing salpingo-oophorectomy (RRSO) in Japan for women with hereditary breast and ovarian cancer (HBOC). METHODS: In the present retrospective observational study, we examined the Japanese HBOC Consortium's (JHC) database. This database contains 11,711 probands who received BRCA genetic testing, or their relatives, with any cancer in 2433 pedigrees. This study was supported by the registration committee of the JHC. RESULTS: We analyzed 488 individuals diagnosed with HBOC, of which 153 (31.4%) underwent RRSO. Of the latter patients, 88 carried BRCA1 mutation (B1); 62 carried BRCA2 mutation (B2); and 3 carried both mutations. During a mean follow-up period of 2.6 years (range 0-12.6), one patient developed a primary peritoneal cancer (PPC). Clinical background comparison for individuals who underwent RRSO vs. those > 45 years of age who did not undergo RRSO revealed that significant factors were represented by B1 (p < 0.0001); child bearing (p < 0.00001); and breast cancer history (p < 0.01). However, family history of ovarian cancer and menopause status were not significantly different. CONCLUSION: Over 30% HBOC's in Japan underwent RRSO. In Japan, individuals with breast cancer history and B1 generally underwent RRSO, whereas those who did not bear a child mostly avoided RRSO.

Bevacizumab combined with platinum-taxane chemotherapy as first-line treatment for advanced ovarian cancer: a prospective observational study of safety and efficacy in Japanese patients (JGOG3022 trial).

BACKGROUND: This was the first large-scale prospective observational Japanese study evaluating the safety and efficacy of bevacizumab combined with paclitaxel and carboplatin for newly diagnosed advanced ovarian cancer. METHODS: Patients were prospectively enrolled in the primary analysis cohort if they had Stage III or IV epithelial ovarian/fallopian tube/primary peritoneal cancer and were scheduled to receive paclitaxel plus carboplatin every 3 weeks in Cycles 1-6 and bevacizumab every 3 weeks in Cycles 2-22. Primary endpoints were bevacizumab-specific adverse events and adverse events ≥ Grade 3. Secondary endpoints were progression-free survival (PFS) and the response rate. RESULTS: Among 346 patients enrolled, 293 patients formed the primary analysis cohort. Regarding bevacizumab-specific adverse events ≥ grade 3, incidence rates of thromboembolic events (1.4%), gastrointestinal perforation (0.3%), fistula (0.7%), wound dehiscence (0%), and bleeding (0%) were very low. While incidence rates of hypertension (23.2%) and proteinuria (12.6%) were high, all such events were tolerable. No patient with prior bowel resection developed perforation or fistula. Median PFS was 16.3 months (95% CI 14.5-18.9). The response rate was 77.5% (95% CI 67.4-85.7). The response rate was 63.6% in patients with clear cell carcinoma, which tended to be better than previously reported. The median platinum-free interval was 11.5 months, and the platinum-resistant recurrence rate was 24.5%. CONCLUSIONS: Combining bevacizumab with chemotherapy was tolerable and efficacy was acceptable in Japanese patients with advanced epithelial ovarian cancer. Bevacizumab seems to reduce platinum-resistant recurrence and is promising for clear cell carcinoma.

En Bloc Resection of an Aggressive Angiomyxoma by a Novel Combination Laparoscopic and Open Perineal Approach.

STUDY OBJECTIVE: To show a novel combination laparoscopic and open perineal approach to complete resection of aggressive angiomyxoma. DESIGN: Step-by-step video demonstration of the combination approach (Canadian Task Force classification III). SETTING: Combined laparoscopic and open perineal approach was performed in the tertiary center. PATIENT: A 46-year-old woman presented with an 8-cm vulvar mass, diagnosed as an aggressive angiomyxoma. The patient, who strongly desired to preserve her uterus and ovaries, provided informed consent for resection of the tumor by our combination approach, also approved by our Institutional Review Board. INTERVENTION: Combined laparoscopic and open perineal approach. MEASUREMENTS AND MAIN RESULTS: Aggressive angiomyxoma is a rare mesenchymal neoplasm that occurs most often in the female pelviperineal region [1]. Aggressive angiomyxoma is locally infiltrative, and high postoperative local recurrence rates (36%-72%) due to incomplete resection have been reported [2]. Therefore, until recently, wide surgical excision with tumor-free margins have been the most commonly accepted treatment. However, aggressive angiomyxoma is a benign, slow-growing tumor, and because extensive surgical resection, which is associated with high operative morbidity rates, has not been shown to have a significant effect on prognosis, a more conservative procedure may be preferable [3]. The mass was located mainly at the left ischiorectal fossa, but it extended above the pelvic diaphragm and was attached to internal obturator muscle, vagina, bladder, urethra, and rectum. We excised the tumor completely and without complications by a combined laparoscopic and open perineal approach. Twelve months have passed since the surgery, and there has been no adjuvant treatment and no sign of recurrence. CONCLUSION: Our combination approach to aggressive angiomyxoma in the pelviperineal region is technically feasible, and the good visualization and meticulous dissection provided during the laparoscopic portion of the surgery contribute to complete resection.

Laparoscopic Anterior Pelvic Exenteration with Super Radical Parametrectomy for a Recurrent Low-Grade Endometrial Sarcoma That is Resistant to Hormone Therapy and Chemotherapy.

STUDY OBJECTIVE: To show total laparoscopic complete resection of a recurrent low-grade endometrial sarcoma. DESIGN: Step-by-step demonstration of the technique of laparoscopic anterior pelvic exenteration with super radical parametrectomy, including the explanation of detailed pelvic anatomy (Canadian Task Force classification III). SETTING: Low-grade endometrial stromal sarcoma (LGESS) is a rare malignancy that makes up around 0.2% of all uterine malignancies [1]. Total abdominal hysterectomy and bilateral salpingo-oophorectomy is a standard treatment; however, the recurrence risk is quite high [2]. For a recurrent LGESS that is resistant to hormone therapy and chemotherapy, complete resection with negative surgical margins (R0 resection) can be the most promising method [3]. PATIENT: The patient had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy because of a LGESS. Almost 20 years later, a recurrent LGESS was detected at the vaginal stump, and the patient underwent several rounds of chemotherapy and hormonal therapy. These treatments were inefficacious, and the recurrent tumor progressed. An abdominal computed tomographic scan revealed that the recurrent tumor occupied the vaginal stump, involved the bladder and the left ureter, and extended to the left pelvic sidewall. INTERVENTIONS: Anterior pelvic exenteration with super radical parametrectomy was performed laparoscopically with no blood transfusion. R0 resection could be achieved without any intraoperative and postoperative complications. Without any adjuvant treatment, there has been no sign of recurrence during the 12 months that have passed since the surgery. This video obtained institutional review board approval through our local ethics committee in the Cancer Institutional Hospital (institutional review board number 2016-1007). CONCLUSION: The good visualization and meticulous dissection provided during laparoscopic surgery can make the approach advantageous and may contribute to R0 achievement.

Comparison of the Technical Feasibility and Safety of Three Contained Morcellation Techniques: A Pilot Study in an Animal Model.

STUDY OBJECTIVE: To compare 3 laparoscopic contained morcellation techniques in terms of feasibility and safety. DESIGN: Pilot study in an animal model (Canadian Task Force classification II-1). SETTING: Gynecologic oncology department at a cancer institute in Japan. PATIENTS: Porcine model. INTERVENTIONS: Three contained morcellation techniques were tested, each multiple times in 1 of 3 anesthetized female pigs: manual morcellation (8 times), dual-site power morcellation (8 times), and single-site power morcellation (6 times). All were tested on beef tongue introduced abdominally. MEASUREMENTS AND MAIN RESULTS: The following variables were compared: bag insertion time, morcellation time, bag removal time, total in-bag morcellation time, and the volume of pneumoperitoneum CO2 consumed. Bag rupture was evaluated ex vivo on completion of the procedure. Bag insertion time (in minutes) was significantly greater for dual-site morcellation (10.91 ± 3.38) than for manual (4.58 ± 2.47, p = .003) or single-site power (7.25 ± .77, p = .014) morcellation. Bag removal time (in minutes) was also significantly greater for dual-site morcellation (.85 ± .11 vs .27 ± .14, p<.001, vs .33 ± .59, p = .001). Total in-bag morcellation time, although greatest for manual morcellation at 21.4 ± 10.2 minutes, did not differ significantly between techniques. CO2 consumption was significantly low for manual morcellation. Visual inspection revealed no bag damage when manual morcellation was performed, but bag damage occurred in 3 dual-site cases and in 1 single-site case. CONCLUSION: Considering preventing specimen leakage as the main aim of contained morcellation, the bag used for power morcellation needs improvement. Although manual morcellation requires an umbilical wound of about 25 mm, the absence of bag damage, acceptable total morcellation time, relatively low CO2 consumption, and nonuse of a power device, which translate to an economic benefit, lead us to conclude that manual morcellation will remain advantageous into the future.

Clinical management of the status of atypical endometrial cells using the descriptive reporting format for endometrial cytology.

OBJECTIVE: We aimed to develop and reinforce a clinical management regimen for atypical endometrial cell (ATEC) categories within the descriptive reporting format for endometrial cytology. METHODS: Between January 2013 and December 2014, 215 samples, for which histological examination was performed immediately or within 3 months after cytology, were cytologically diagnosed as ATEC. For these samples, the medical records were retrospectively reviewed to identify risk factors for malignancy. RESULTS: Among 152 samples diagnosed as ATEC, of undetermined significance, 19 (12.5%) were malignant. In the younger group (age <55 years), the χ2 values of body mass index (BMI) ≥25 kg/m2 (5.85), gravidity (5.64) and parity (5.15) were relatively high, suggesting that these were risk factors for malignancy. Of the nulligravida patients, those with BMI ≥25 kg/m2 , 28% were diagnosed with malignant disease. In the older group (≥55 years), endometrial thickening (6.84), atypical genital bleeding (6.43) and BMI ≥25 kg/m2 (3.79) were found to be risk factors for malignancy. Of the patients with endometrial thickening and atypical genital bleeding, 67% were diagnosed with malignant disease. Among 63 samples diagnosed as ATEC, cannot exclude atypical endometrial hyperplasia or more, 35 (55.6%) samples were positive for malignancy. CONCLUSIONS: High-risk patients diagnosed with ATEC, of undetermined significance were identified. Endometrial biopsy should be considered for nulligravida patients aged <55 years with a BMI ≥25 kg/m2 .

Laparoscopic laterally extended endopelvic resection (LEER) for cervical carcinoma recurring at the pelvic sidewall after concurrent chemoradiotherapy: Our experience in three cases.

OBJECTIVE: Patients in whom laterally recurrent cervical carcinoma develops in the previously irradiated pelvis are usually abandoned because the resectability rate is low, and the 5-year survival rate is close to zero when complete margin-negative resection is not achieved [1]. Höckel described laterally extended endopelvic resection (LEER) as an approach in which the line of resection extends to the pelvic sidewall [2]. Complete margin-negative resection (R0 resection) was achieved in all 100 patients who underwent LEER for laterally recurrent cervical carcinoma, and 5-year survival was very good at 62%. However, two procedure-related deaths occurred, and morbidity was 70% [3]. When cervical carcinoma recurs in the previously irradiated pelvis, fibrosis and adhesion around the recurrent mass increase morbidity and mortality. Because laparoscopy optimizes visualization and thus provides for meticulous dissection, laparoscopic LEER can be advantageous over open LEER for treatment of such recurrent tumors. METHODS: We performed laparoscopic LEER in three cases of previously irradiated laterally recurrent cervical carcinoma under the following criteria: the recurrent tumor was solitary and without distant metastasis; no equally effective alternative treatment existed, preoperative evaluation of the tumor showed R0 resection to be achievable; and the patient provided informed consent for the procedure. RESULTS: In all three cases, R0 resection was achieved without the need for blood transfusion and without intraoperative or postoperative complications. There was no associated morbidity or mortality. One patient died from recurrent disease 24months after the operation, but neither of the other two patients has suffered recurrence during the respective 3 and 4months that have passed since the surgery. CONCLUSION: Laparoscopic LEER is a very complicated procedure; the surgeon must possess detailed knowledge of the pelvic anatomy and high-level technical skill. Our experience indicates that laparoscopic LEER is feasible for cervical carcinoma that recurs laterally after irradiation and that low morbidity and mortality can be expected. Oncologic outcomes of the procedure will become clear with an accumulation of cases and long-term follow-up data.