Pretreatment systemic inflammatory markers predict survival in endometrial cancer: A Japanese Gynecologic Oncology Group 2043 exploratory data analysis.

OBJECTIVE: We investigated whether pretreatment systemic inflammatory markers are associated with survival outcomes in patients with endometrial cancer (EC). METHODS: Data from the Japanese Gynecologic Oncology Group 2043 were analyzed. Patients who did not receive chemotherapy or were lost to follow-up were excluded. Associations of pretreatment systemic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin, albumin, lymphocyte, and platelet (HALP) score, with progression-free survival (PFS) and overall survival (OS) were analyzed. The optimal NLR, PLR, and HALP score cutoff values for PFS and OS were determined. Survival estimates were calculated and compared using the Kaplan-Meier method and log-rank test. RESULTS: We included 712 patients (median age: 55 [range, 28-74] years; body mass index [BMI]: 21.1 [15.2-38.6] kg/m2). For PFS, optimal NLR, PLR, and HALP score cutoff values were 1.48, 0.017, and 35.52, respectively, and for OS, the values were 1.88, 0.026, and 19.87, respectively. At optimal PFS-related cutoff values, NLR was associated with BMI; PLR with age, BMI, and clinical stage; and HALP score with BMI, clinical stage, and lymph node metastasis. At optimal OS-related cutoff values, NLR was associated with BMI, PLR, and BMI; the HALP score was associated with age and BMI. The HALP score was a prognostic factor for PFS (p = 0.025), while PLR and HALP scores were prognostic factors for OS (both p = 0.028). CONCLUSIONS: Pretreatment systemic inflammatory markers are associated with survival outcomes in patients with EC, with the HALP score being a prognostic factor for PFS and OS.

Clinical characteristics and prognostic factors of endometrial stromal sarcoma and undifferentiated uterine sarcoma confirmed by central pathologic review: A multi-institutional retrospective study from the Japanese Clinical Oncology Group.

OBJECTIVES: Low-grade and high-grade endometrial stromal sarcomas (LGESS and HGESS) and undifferentiated uterine sarcomas (UUS) are rare tumors whose pathological classification and staging system have changed recently. These tumors are reported to contain fusion genes. We aimed to clarify the genetic background, clinical features, prognostic factors, and optimal therapy of these tumors using a new classification and staging system. METHODS: We analyzed the clinical features and prognostic information of 72 patients with LGESS, 25 with HGESS, and 16 with UUS using central pathological review. Estrogen and progesterone receptors (PgRs) were examined by immunohistochemistry. JAZF1-SUZ12 and YWHAE-NUTM2A/B gene fusions were tested using real-time polymerase chain reaction. RESULTS: The 5-year overall survival (OS) rates of LGESS, HGESS, and UUS were 94%, 53%, and 25%, respectively. In LGESS, stage IV, incomplete surgery, and absence of PgR were associated with poor OS. The presence of JAZF1-SUZ12 fusion gene was not associated with OS. In HGESS, the relationship between stage and prognosis was unclear. None of the 3 patients with YWHAE-NUTM2A/B fusion gene died during follow-up. Adjuvant chemotherapy was associated with a favorable OS. Incomplete resection of UUS was associated with poor OS; however, residual tumors frequently occurred. Although most patients underwent adjuvant chemotherapy, their prognosis was extremely poor even in stage I disease. CONCLUSIONS: Prognosis of LGESS is generally good; however, stage IV, incomplete surgery, and PgR-negative tumors are associated with poor prognosis. Adjuvant chemotherapy may be useful for HGESS. Prognosis of UUS is extremely poor, even with adjuvant chemotherapy.

The sarcopenia index measured using the lumbar paraspinal muscle is associated with prognosis in endometrial cancer.

OBJECTIVE: The number of type-II endometrial cancer patients has been increasing and the prognosis is not favorable. We aim to investigate whether sarcopenia index in any of several different muscles could serve as a novel biomarker of prognosis in patients with type-II endometrial cancer. METHODS: We retrospectively investigated a total of 194 patients at four hospitals. Ninety patients were treated as derivation set and the other 104 patients as validation set. Using preoperative computed tomography images, we measured the horizontal cross-sectional area at the third lumbar spine level: the (i) psoas major, (ii) iliac and (iii) paraspinal muscle. The clinical information including recurrence-free survival and overall survival were retrospectively collected. These results were validated with external data sets of three hospitals. RESULTS: The median values of the sarcopenia index (cm2/m2) ± standard deviation with the first data of 90 patients using the psoas, iliac and paraspinal muscle were 3.4 ± 1.0, 1.7 ± 0.6 and 12.6 ± 3.2, respectively. In univariate analyses, the sarcopenia indexes measured using the psoas or paraspinal muscle were associated with recurrence-free survival and overall survival. On the other hand, in multivariate analyses, only the sarcopenia index using paraspinal muscle was significantly related to recurrence-free survival (hazard ratio = 3.78, 95% confidence intervals = 1.29-5.97, P = 0.009) and overall survival (hazard ratio = 3.13, 95% confidence interval = 1.18-8.26, P = 0.022). Paraspinal sarcopenia index was also related to overall survival (hazard ratio = 3.74, 95% confidence interval = 1.31-10.72, P = 0.014) even in patients with advanced stage. Serum albumin was significantly correlated with the sarcopenia index (P = 0.012). Within the analysis of the validation set, sarcopenia index using paraspinal muscle was related to recurrence-free survival (hazard ratio = 2.06, P = 0.045) in multivariate analysis and recurrence-free survival (P = 0.009) in patients with advanced stage. CONCLUSIONS: The sarcopenia index using the paraspinal muscle, not psoas, could be a suitable index to predict recurrence-free survival and overall survival in patients with type-II endometrial cancer even in advanced stage.

Immunogenomic landscape of gynecologic carcinosarcoma.

OBJECTIVE: Carcinosarcoma (CS) of the uterus or ovary is a rare, biphasic tumor comprising epithelial and mesenchymal elements, and exhibits more aggressive clinical features than its carcinoma counterpart. Four molecular subtypes of CS were recently established based on genomic aberration profiles (POLE, MSI, CNH, and CNL) and shown to be associated with multiple clinicopathological parameters, including patient outcomes. However, the role of the immune microenvironment in CS remains unclear. Here, we investigated the influence of the immune cells that infiltrate CS to better understand the immunological status of gynecological CS. METHODS: Tumor immune microenvironmental analyses on CS samples were performed using immune cell profiling with RNA-seq, transcriptomic subtyping with microenvironmental genes, and T-cell receptor repertoire assay. Carcinoma and sarcoma elements from CS samples were also assessed separately. RESULTS: Relying on estimations of tumor-infiltrating cell types from RNA-seq data, POLE and MSI (hypermutator) tumors showed an enrichment of M1 macrophages, plasma cells and CD8+ T cells, whereas CNH and CNL (non-hypermutator) tumors had high levels of M2 macrophages. Further subclassification by immune-related, non-cancer genes identified a fraction of tumors with distinct patient outcomes, particularly those with the CNH genomic aberration subtype. T-cell heterogeneity was independently correlated with prolonged progression-free survival. Differential analysis of carcinoma and sarcoma elements identified many shared mutations but there was little overlap in the T-cell receptor repertoire between the two elements. CONCLUSIONS: Tumor immune microenvironmental analyses could offer potential clinical utility in the stratification of gynecological CS above classification by genomic aberration subtype alone.

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

BACKGROUND: The aim of this study was to investigate the safety and clinical usefulness of early oral feeding (EOF) after rectosigmoid resection with anastomosis for the treatment of primary ovarian cancer. METHODS: We performed a retrospective review of all consecutive patients who had undergone rectosigmoid resection with anastomosis for primary ovarian, tubal, or peritoneal cancer between April 2012 and March 2019 in a single institution. Patient-related, disease-related, and surgery-related data including the incidence of anastomotic leakage and postoperative hospital stay were collected. EOF was introduced as a postoperative oral feeding protocol in September 2016. Before the introduction of EOF, conventional oral feeding (COF) had been used. RESULTS: Two hundred and one patients who underwent rectosigmoid resection with anastomosis, comprised of 95 patients in the COF group and 106 patients in the EOF group, were included in this study. The median number of postoperative days until the start of diet intake was 5 (range 2-8) in the COF group and 2 (range 2-8) in the EOF group (P < 0.001). Postoperative morbidity was equivalent between the groups. The incidence of anastomotic leakage was similar (1%) in both groups. The median length of the postoperative hospital stay was reduced by 6 days for the EOF group: 17 (range 9-67) days for the COF group versus 11 (8-49) days for the EOF group (P < 0.001). CONCLUSION: EOF provides a significant reduction in the length of the postoperative hospital stay without an increased complication risk after rectosigmoid resection with anastomosis as a part of cytoreductive surgery for primary ovarian cancer.

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.

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.

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 .

An open-label, randomized, phase II trial evaluating the efficacy and safety of standard of care with or without bevacizumab in platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer patients previously treated with bevacizumab for front-line or platinum-sensitive ovarian cancer: rationale, design, and methods of the Japanese Gynecologic Oncology Group study JGOG3023.

BACKGROUND: We present the study rationale and design of the JGOG3023 study, an open-label, parallel-arm, randomized, phase II trial that aimed to assess the efficacy and safety of chemotherapy with or without bevacizumab in patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who were previously treated with bevacizumab for front-line or platinum-sensitive ovarian cancer. We hypothesize that patients treated with a combination of single-agent chemotherapy and bevacizumab will show improved progression-free survival (PFS) compared with those treated with single-agent chemotherapy alone, in the setting beyond disease progression following prior bevacizumab treatment. METHODS/DESIGN: A total of 106 patients who have recurrence or progression of ovarian cancer, while receiving chemotherapy or within 6 months after the final dose of platinum, after completing at least three cycles of bevacizumab plus platinum chemotherapy will be randomized in a 1:1 ratio to treatment with single-agent chemotherapy or single-agent chemotherapy combined with bevacizumab. For chemotherapy, one of the following four drugs will be chosen by an investigator: pegylated liposomal doxorubicin, topotecan, paclitaxel, or gemcitabine. The primary endpoint is investigator-assessed PFS. The secondary endpoints are overall survival, objective response rate, number of paracentesis, and response rate by CA125. Safety will be evaluated by the incidence of adverse events. DISCUSSION: This study will assess the efficacy and safety of bevacizumab in combination with single-agent chemotherapy, which could be used continuously after disease progression following standard platinum-based chemotherapy with bevacizumab. TRIAL REGISTRATION: UMIN000017247 (registered April 22, 2015).

Maintenance hormonal therapy after treatment with medroxyprogesterone acetate for patients with atypical polypoid adenomyoma.

BACKGROUND: As atypical polypoid adenomyoma (APA) has been reported to be a hormone-related tumor, we aimed to analyze the efficacy and safety of maintenance hormonal therapy after fertility-preserving treatment of these patients with medroxyprogesterone acetate (MPA). METHODS: Data were retrospectively analyzed from patients with APA who were treated with a fertility-preserving regimen including MPA between October 2001 and December 2011. Eighteen patients were treated with MPA and 14 (77.8%) achieved either a complete or a partial response after the planned treatment. Five patients took progestin for maintenance therapy. RESULTS: Eighteen patients were treated for a mean observation period of 96.7 months. While taking the maintenance therapy, no patient had APA relapse. One patient developed well-differentiated endometrioid adenocarcinoma 18 months after she stopped taking maintenance progestin. Eleven patients without maintenance therapy underwent hysterectomy, andnine of them developed well-differentiated endometrial cancer. Through univariate analysis, there was a significant difference in time to hysterectomy between patients with and without maintenance therapy (P = 0.015). Through multivariate analysis, body mass index (BMI), menstrual status before protocol therapy, maintenance treatment, and pregnancy were found to be significantly associated with a lower risk of hysterectomy. No patient had a recurrence of APA after hysterectomy during the observation period (median, 54 months; range, 2-148 months). CONCLUSION: No patient showed progression while receiving hormonal therapy, including initial protocol therapy. Maintenance hormonal therapy after treatment with MPA was highly effective and safe, particularly in patients with BMI ≧24 kg/m2 and irregular menstruation cycle.

Efficacy of Transanal Drainage Tube Placement After Modified Posterior Pelvic Exenteration for Primary Ovarian Cancer.

OBJECTIVE: The aim of this study was to investigate the clinical usefulness of the placement of a transanal drainage tube (TDT) to prevent anastomotic leakage after a modified posterior pelvic exenteration (MPPE) for the treatment of primary ovarian cancer. METHODS: We performed a retrospective review of all the consecutive patients who had undergone an MPPE for primary ovarian, tubal, or peritoneal cancer between October 2012 and November 2016 at our institution. Patient-related, disease-related, and surgery-related data were collected. RESULTS: One hundred five patients who underwent an MPPE were included in this study. A TDT was placed in all the patients. A diverting ileostomy was created during cytoreductive surgery in 7 patients (7%). Those who underwent a diverting ileostomy tended to have a greater degree of surgical invasiveness, as was reflected by a longer operative time, a serious loss of blood, and a large quantity of intraoperative blood transfusion. Anastomotic leakage occurred in 1 patient (1%), and a diverting ileostomy was created for this patient. CONCLUSIONS: Transanal drainage tube placement seems to be an effective and safe procedure that can decrease the rate of anastomotic leakage and the need for a diverting stoma after MPPE for ovarian cancer. However, some patients inevitably require a diverting stoma despite the TDT placement.

Survival and safety associated with aggressive surgery for stage III/IV epithelial ovarian cancer: A single institution observation study.

OBJECTIVE: We evaluated the efficacy and safety of aggressive surgery for advanced ovarian cancer at a non-high-volume center. MATERIALS AND METHODS: We evaluated consecutive patients with stage III/IV ovarian, fallopian, and peritoneal cancer undergoing elective aggressive surgery from January 2008 to December 2012, which encompassed the first 5years after implementing an aggressive surgery protocol. After receiving appropriate training for 9months, a gynecological surgical team began performing multi-visceral resections. Primary debulking surgery was chosen when the team considered that optimal surgery was achievable on the initial laparotomy, otherwise interval debulking surgery was chosen (the protocol treatments). Analysis was performed on an intention-to-treat basis (full-set analysis), and outcomes were compared to those of patients who underwent standard surgery between 2000 and 2007. RESULTS: Of 106 consecutive patients studied, 87 (82%) underwent aggressive surgery per protocol and 19 were excluded. Serous carcinoma was the most common disease (78%), followed by clear cell carcinoma (7%), and 32% of the patients had stage IV disease. The respective median progression-free and overall survival rates increased from 14.6 and 38.1months before implementation, respectively, to 25.0 and 68.5months after implementation, respectively. Complete resection was achieved in 83 of the 106 patients (78%), and the surgical complexity score was high (>8) in 61 patients (58%); although there was no mortality within 12weeks of surgery, major complications occurred in 8 patients. CONCLUSIONS: We confirmed that outcomes improved after implementing aggressive surgery for advanced ovarian cancer, without causing a significant increase in mortality. Factors enhancing survival outcomes are discussed.

Clinicopathological Features of Early and Late Recurrence of Endometrial Carcinoma After Surgical Resection.

OBJECTIVES: The incidence of endometrial carcinoma has been increasing annually in developed nations; it is currently the second most common gynecological malignancy. Although the majority of patients are diagnosed at an early stage, 15% to 20% reportedly recur; consequently, patients are usually followed clinically for 3 years after the initial curative surgery. We therefore aimed to determine the incidence and clinicopathological features of early and late recurrences of endometrial carcinoma after surgical resection. MATERIALS AND METHODS: This retrospective study was performed using the clinical records of 2233 patients who underwent surgical resection for endometrial carcinoma between January 1970 and December 2009 at a single cancer center. Tumor recurrences were classified as early (<5 years) and late (>5 years) after initial surgery. Clinicopathological variables and tumor recurrence patterns were compared between the early and late recurrence groups. Survival analysis was performed using the Kaplan-Meier method. RESULTS: Among 2233 study patients, 255 (11.4%) experienced endometrial carcinoma recurrence; of these, early and late recurrences occurred in 232 (91.0%) and 23 (9.0%) patients, respectively. Late recurrence was associated with invasion of less than half of the myometrium at diagnosis and the presence of histopathological features of endometrioid adenocarcinoma with low- or intermediate-grade histological subtype and absence of lymphovascular invasion. After recurrence, there was no significant difference in overall survival between the early and late recurrence groups (P = 0.437). Furthermore, surgical treatment was associated with a significantly improved prognosis in the late recurrence group (P = 0.044). CONCLUSIONS: The findings of this study indicated that patients who initially underwent successful treatment for low-grade and early-stage endometrial carcinoma should be followed clinically for more than 5 years. In cases of late recurrence, surgical management may improve prognosis.

Total Laparoscopic Resection Surgery for a Cervical Carcinoma that Recurred in the Pelvic Sidewall After Radical Hysterectomy and Adjuvant Concurrent Chemoradiotherapy.

STUDY OBJECTIVE: To show total laparoscopic resection of a cervical carcinoma that recurred at the left pelvic sidewall after radical hysterectomy and concurrent chemoradiotherapy (CCRT). DESIGN: A step-by-step demonstration of the technique in a surgical video, including the strategy for achieving complete surgical resection with negative margins (R0 resection) (Canadian Task Force Classification III). SETTING: For high-risk cervical carcinoma, radical hysterectomy and adjuvant CCRT is the standard treatment, but even this multimodal therapy cannot prevent recurrence. When the recurrent mass is localized in the pelvic cavity, R0 resection offers the most promise; however, for laterally recurring cervical carcinoma, the resectability rate is low, owing mainly to severe adhesion and fibrosis, and thus the morbidity and mortality rates are high. Because laparoscopy optimizes visualization and provides for meticulous dissection, laparoscopic surgery can be advantageous over open surgery for resection of cervical carcinoma recurring at the pelvic sidewall after radical hysterectomy and adjuvant CCRT. INTERVENTIONS: A 48-year-old woman with stage IB2 cervical adenocarcinoma had undergone radical hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and, because lymph node metastasis was found in the removed lymph nodes, adjuvant CCRT. At 6 months after completion of this multimodal therapy, a recurrent mass was detected at the left pelvic sidewall. The mass involved the left ureter, bladder, left internal iliac vessels, and endopelvic fascia, and left renal function was unrecoverable. Tumor excision and left nephroureterectomy were performed laparoscopically. The total operating time was 608 minutes, blood loss volume was 250 mL, and blood transfusion was not required. Complete tumor clearance (R0 resection) was achieved by resection of the left internal iliac vessels, left internal obturator muscle, left pubococcygeal muscle, left ureter, and bladder. There were no postoperative complications. Institutional Review Board approval was obtained through our local Ethics Committee in Cancer Institute hospital. CONCLUSION: Complete laparoscopic resection surgery for recurrent cervical carcinoma at the pelvic sidewall after radical hysterectomy and adjuvant CCRT is technically feasible. The good visualization and meticulous dissection provided during laparoscopic surgery make the approach advantageous for the management of laterally recurrent cervical carcinoma.

Extraction of a specimen through an umbilical zigzag incision during laparoscopic surgery for endometrial cancer.

BACKGROUND: Though laparoscopic surgery has recently been applied in the treatment of early-stage endometrial cancer, the presence of a large uterus is a hindrance to specimen extraction from the abdominal cavity. We describe a laparoscopic surgical technique for endometrial cancer involving the extraction of the resected specimen through an umbilical zigzag incision. CASE PRESENTATION: A 63-year-old woman with endometrial cancer underwent a total hysterectomy and bilateral salpingo-oophorectomy that was performed laparoscopically. The surgical specimen was extracted through an umbilical zigzag incision. This umbilical zigzag incision created a larger fascial and peritoneal opening, facilitating the removal of the specimen. The final histopathologic results revealed stage 1A G1 endometrioid adenocarcinoma and multiple uterine leiomyomas. Three months after surgery, the wound in the umbilical region was inconspicuous, along with the inward movement of the umbilicus. CONCLUSIONS: A laparoscopic surgical technique for endometrial cancer involving the extraction of the specimen through an umbilical zigzag incision seems to reduce the difficulties associated with laparoscopic surgery and maintains cosmesis. Further analyses involving larger numbers of cases and long-term follow-up periods are warranted to evaluate this surgical method.

Cytoreduction of diaphragmatic metastasis from ovarian cancer with involvement of the liver using a ventral liver mobilization technique.

OBJECTIVE: Upper abdominal spreading of advanced-stage ovarian cancer often involves the diaphragm. In addition, bulky diaphragmatic tumors occasionally infiltrate the liver. Here, we describe our early experiences with a ventral liver mobilization technique to remove diaphragmatic tumors with liver involvement. METHODS: Two patients with primary ovarian cancer and 1 patient with recurrent ovarian cancer underwent en bloc resections of a diaphragmatic tumor together with the full-thickness diaphragm and the liver tissue using a ventral liver mobilization technique. The surgical technique involved a full-thickness division of the diaphragm at the central tendon and a ventral mobilization of the right lobe of the liver, with entry into the pleural cavity. During the parenchymal transection of the liver, the posterior area of the right lobe of the liver was pressed using the surgeon's hand to reduce bleeding from the resection surface. After the completion of the en bloc resection, the diaphragmatic opening was closed using running sutures. RESULTS: All the diaphragmatic tumors were completely removed without severe bleeding in the current series. No intraoperative or postoperative complications occurred. CONCLUSION: Diaphragmatic tumors with involvement of the liver can be safely and effectively removed using a ventral liver mobilization technique. This surgical procedure may be suitable for the management of bulky diaphragmatic tumors in select patients.

Secondary debulking surgery for isolated pelvic nodal recurrence requiring external iliac vein excision and reconstruction in a patient with ovarian cancer.

OBJECTIVE: We report the details of a cytoreduction technique for pelvic lymph node recurrence with involvement of the external iliac vein (EIV) requiring a partial resection and reconstruction of the EIV. METHODS: A 51-year-old woman presented with ovarian cancer and isolated nodal recurrence located on the right side of the pelvis. As the tumor had infiltrated the EIV wall, we performed the EIV excision and reconstruction using an autogenous graft. RESULTS: EIV reconstruction was achieved using a right ovarian vein patch. No intra- or early postoperative complications occurred. A postoperative enhanced magnetic resonance imaging examination confirmed the patency of the EIV. CONCLUSION: An en bloc EIV excision and reconstruction for contiguous tumor involvement seems to be a feasible and safe surgical option.

Timing of Intrauterine Manipulator Insertion During Minimally Invasive Surgical Staging and Results of Pelvic Cytology in Endometrial Cancer.

STUDY OBJECTIVE: Considering the hypothetical concern of retrograde tumor spread to the peritoneal cavity by insertion of an intrauterine manipulator, we examined the correlation between the timing of manipulator insertion and the results of pelvic cytology during total laparoscopic hysterectomy (TLH) in endometrial cancer. DESIGN: Case-control study (Canadian Task Force classification II-2). SETTING: University-based hospitals. PATIENTS: Stage I to IV endometrial cancer patients who underwent TLH in which an intrauterine manipulator was used. Medical records were reviewed for patient demographics, surgical details, and tumor characteristics. INTERVENTIONS: Archived medical record review. MEASUREMENTS AND MAIN RESULTS: A total of 333 patients was identified. Cases were divided into those with intrauterine manipulator insertion after pelvic cytology sampling (Group 1, n = 103) and those with intrauterine manipulator insertion before pelvic cytology sampling (Group 2, n = 230). Types of intrauterine manipulator were similar across the 2 groups (p = .77). There was no statistical difference in the results of pelvic cytology between the 2 groups: Group 1 versus 2, atypical cells 2.9% versus 4.8% and malignant cells 5.8% versus 9.6% (p = .36). Uterine perforation related to intrauterine manipulator insertion was seen in 1.0% and .4% of each group (p = .52). In a multivariate analysis controlling for demographics and tumor characteristics, advanced-stage disease remained an independent risk factor associated with increased risk of atypical and malignant cells (adjusted odds ratio, 10.3; 95% confidence interval, 4.44-23.8; p < .001). CONCLUSION: Our study suggested that the timing of intrauterine manipulator insertion during TLH for endometrial cancer is not associated with the results of pelvic cytology.