Segmental bowel resection for rectal endometriosis using the da Vinci SP.

OBJECTIVE: The da Vinci SP Surgical System (SP) received regulatory approval for use in gynecological surgeries in Japan in 2023. Given the advantages of the precision of a robot, less pain, and the cosmesis of single-port surgery, the da Vinci SP is expected to be further used for minimally invasive surgeries. To the best of our knowledge, this is the first report of the use of SP for the treatment of rectal endometriosis with segmental bowel resection. SETTING: An urban general hospital. Stepwise demonstration of the technique with narrated video footage. PARTICIPANTS: The patient was a 46-year-old woman presented with chronic pelvic pain, pain on defecation and constipation. Magnetic resonance imaging showed uterine large fibroid, left ovarian endometrioma, and 38mm of rectal endometriosis, with complete cul-de-sac obliteration. INTERVENTIONS: We made a 30-mm vertical incision at the umbilicus, then placed the access port, and inserted three articulating instruments and a camera. An assistant port was placed in the right lower quadrant for using the linear stapler. The surgical steps were completely identical to conventional multiport laparoscopic robotic surgery. This suggests that conventional laparoscopic or robotic skills are highly transferrable to SP. SP offer several advantages, including high-resolution three-dimensional visualization, articulating instruments, and improved dexterity and range of motion. In addition, the umbilical access port was particularly useful for proximal bowel resection, specimen retrieval, and anvil positioning during bowel resection. The total operative time was 216 minutes. The estimated blood loss was 100 ml without any complications. The uterine weight was 800 g. The postoperative course was uneventful, with no perioperative complications, including no postoperative bladder dysfunction or low anterior resection syndrome [1, 2]. CONCLUSION: The use of SP with the access port for segmental bowel resection for rectal endometriosis is technically safe and feasible, with good cosmesis and less pain.

Robot-Assisted Hysterectomy Using the Double-Bipolar Method.

OBJECTIVE: To demonstrate the efficacy of the double-bipolar method in a benign hysterectomy. DESIGN: Stepwise demonstration of the technique with a narrative video. SETTING: The double-bipolar method was first reported in 2011 [1] and is gaining popularity in Japan; however, its usefulness in robot-assisted hysterectomy is under-reported. When unexpected bleeding occurs during robot-assisted hysterectomy using a monopolar technique, corrective measures may be prolonged and often require changing forceps. The Maryland forceps have 4 functions, including incision, dissection, grasping, and coagulation, which enable rapid responses to bleeding and reduce forceps changes and cost. Previously, we reported the usefulness of the double-bipolar technique in other surgical procedures [2,3]. Herein, we present a case of robot-assisted hysterectomy using this technique at an urban general hospital, including detailed insights into its execution. INTERVENTIONS: A 45-year-old female patient presented to our hospital with painful menstrual bleeding. Magnetic resonance imaging revealed an 8-cm myoma in the posterior wall of the uterine cervix. Consequently, a robot-assisted hysterectomy was performed using right-handed Maryland forceps (Intuitive, Sunnyvale, CA) and the ForceTriadTM Energy Platform (Medtronic, Minneapolis, MN) in the macro mode, with an output of 60 W. This configuration ensured a consistent electronic output, regardless of the electrical resistivity of the target tissues, facilitating precise incisions using a momentary high voltage [4]. The surgical duration was 60 minutes, and the estimated blood loss was 5 mL. CONCLUSION: The highly versatile double-bipolar method uses one forceps for incision, dissection, coagulation, and grasping and is useful in gynecological surgery. VIDEO ABSTRACT.

Comparison of surgical outcomes between robot-assisted and conventional laparoscopic nerve-sparing modified radical hysterectomy for deep endometriosis.

PURPOSE: Drug resistance and severe pelvic pain often warrant surgical intervention for treating deep endometriosis (DE); however, damage to the autonomic nervous system can occur because of anatomical considerations. We aimed to investigate the advantages of robotic technology in enabling precise dissection, even in DE. METHODS: We retrospectively compared the surgical outcomes of robot-assisted (RA) and conventional laparoscopic (CL) nerve-sparing modified radical hysterectomies (NSmRHs) for DE. RESULTS: Between the two groups (RA-NSmRH group, n = 50; CL-NSmRH group, n = 18), no differences were identified based on patient demographics, such as age, body mass index, previous surgery, revised American Society of Reproductive Medicine classification, Enzian classification, uterine weight, number of removed DE lesions, and concomitant procedures. All patients in both groups achieved complete removal of the DE lesions with complete bilateral pelvic autonomic nerve preservation. The mean operative time (OT) was significantly longer (130 ± 46 vs. 98 ± 22 min, p < 0.01), and estimated blood loss (EBL) was lower (35 ± 44 vs. 131 ± 49 ml, p < 0.01) in the RA-NSmRH group than in the CL-NSmRH group. The hospitalization days (4.3 ± 1.3 vs. 4.1 ± 0.2 days, p = 0.45) and perioperative complications with Clavien-Dindo classification ≥ grade III (0% vs. 0%) were not significant in both the groups. None of the patients required self-catheterization after surgery. CONCLUSION: Compared with CL-NSmRH, RA-NSmRH was associated with longer OT and lower EBL, whereas the number of hospitalization days and complications were similar in both groups. Our results imply that nerve-sparing surgery can be safely and reproducibly performed using conventional or robotic laparoscopic modalities to treat DE.

Extraovarian Dysgerminoma Involving the Uterine Cervix: A Rare Case Report With Literature Review.

Primary extraovarian dysgerminoma (EOD) is a very rare disease. There is no literature about primary EOD involving the uterine cervix. We herein present details of a unique case of primary EOD involving the uterine cervix. A 46-year-old woman with uterine cervical tumor was referred to our institution with atypical genital bleeding. A polypoid tumor localized to the uterine cervix was found. Cervical biopsy detected malignant components of likely nonepithelial cell origin. Preoperative imaging examinations showed a uterine cervical tumor measuring ~5 cm, suggestive of malignancy without distant or lymph node metastases. The patient underwent abdominal radical hysterectomy with pelvic lymph node dissection according to the standard treatment for stage IB3 cervical cancers. The pathological diagnosis was dysgerminoma involving the uterine cervix and the right fallopian tube. Immunohistochemical results were as follows: SALL4 (+), octamer-binding transcription factor 4 (+), D2-40 (+), and c-Kit (+). She received 3 cycles of adjuvant chemotherapy with bleomycin, etoposide, and cisplatin. The disease did not recur up to 14 months after surgery. This is the first-ever published case of primary EOD involving the uterine cervix among previously reported EOD cases. Reported cases of EOD in female genital tract are also reviewed. Our case provides more extensive insights for pathologists to consider the differential diagnosis of cervical lesions. In our case, combination therapy involving a surgical approach-according to cervical cancers and adjuvant chemotherapy as used for ovarian dysgerminomas-was effective. Future verification is needed regarding the best approach for treating uterine cervical dysgerminomas.

Robot-assisted Exploration of Somatic Nerves in the Pelvis and Transection of the Sacrospinous Ligament for Alcock Canal Syndrome.

STUDY OBJECTIVE: Some articles have reported the surgical management of Alcock canal syndrome (ACS) using the transperineal [1], transgluteal [2], or conventional laparoscopic approach [3,4]. In 2015, Rey and Oderda [5] reported the first robotic neurolysis of the pudendum, providing the advantages of robot-assisted surgery: magnified and 3-dimensional vision and greater precision of movements. However, to our knowledge, there have been no reports on the use of a robotic platform for the treatment of ACS in the field of gynecology. Therefore, the objective of this video is to describe the anatomic and technical highlights of robotic exploration of the somatic nerves in the pelvis and transection of the sacrospinous ligament (nerve decompression) for ACS. DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: An urban general hospital. A 48-year-old woman who had no previous surgical history was referred for severe pain when sitting, cyclic pelvic pain, and gluteal and perineal pain, all of which were resistant to medication therapy. Her pain radiated to the posterior aspect of the thigh. Before coming to our hospital, she visited an orthopedic surgeon a few years earlier and was diagnosed with sciatic neuralgia. Magnetic resonance imaging revealed adenomyosis with neither deep endometriosis nor vascular entrapment. On the basis of neuropelveologic evaluation, the patient was suspected to be suffering from ACS owing to compression of the pudendal nerve and the posterior cutaneous nerve of the thigh by the sacrospinous ligament. INTERVENTIONS: The procedure was performed using the following 9 steps while referencing the laparoscopic neuronavigation technique [6]: step 1, opening the peritoneum along the external iliac artery; step 2, exposure of the external iliac artery; step 3, development of the lumbosacral space; step 4, identification of the lumbosacral trunk; step 5, identification of the superior gluteal nerve; step 6, identification of the sciatic nerve; step 7, identification of the inferior gluteal nerve; step 8, identification of the pudendal nerve; and step 9, transection of the sacrospinous ligament. The surgery was completed successfully without any complications, and the postoperative course was uneventful. We considered that there was no relationship between the ACS and endometriosis. The patient reported that her pain decreased gradually at postoperative month 1 and month 3, and finally the neuralgia was completely resolved at month 6. Neuropelveologic evaluation still continues every 6 months. CONCLUSION: Robot-assisted transection of the sacrospinous ligament is a feasible, safe technique for selected patients with ACS. Exploration of the pelvic nerves should be performed for further diagnosis and therapy before prematurely labeling the patient as refractory to the treatment [7].

Rate of recurrent hydronephrosis after laparoscopic ureteroneocystostomy for ureteral endometriosis.

STUDY OBJECTIVE: To investigate the short-term outcomes of laparoscopic ureteroneocystostomy in patients with ureteral endometriosis (UE). DESIGN: Retrospective cohort study of consecutive patients who underwent surgery for the ureter endometriosis with hydronephrosis. SETTING: A private hospital that provide primary, secondary and tertiary care. PATIENTS: 30 consecutive patients with UE who underwent laparoscopic ureteroneocystostomy at our institution between May 2008 and April 2020. INTERVENTIONS: Laparoscopic ureteroneocystostomy, if necessary, hysterectomy, salpingo-oophorectomy, cystectomy, partial bladder resection, or partial bowel resection were performed. MEASUREMENTS AND MAIN RESULTS: The most common chief complaint was pelvic pain (40%). Endometriosis affected only the left ureter in 56.7% of patients, only the right ureter in 33.3%, and both ureters in 6.7%. Involvement of the ipsilateral ovary was confirmed in 64.3%. The most frequent location of UE was 1-3 cm above the UVJ (46.7%). A psoas hitch was performed in 7 patients (23.3%), and the Boari flap was used in 9 patients (30%). Hysterectomy was performed in 12 patients (40%), and 6 of them had a concomitant bilateral salpingo-oophorectomy (20%). In addition, 3 patients (10%) underwent partial bowel resection, and 2 patients (6.7%) underwent partial bladder resection. After surgery, 24 of 27 patients (80.0%) were free of sever hydronephrosis after surgery. Hydronephrosis recurred in a single patient (3.3%), but the grade of hydronephrosis improved significantly after surgery (P < 0.001). At 6 months of follow up, 4 patients (13.3%) experienced urinary tract infections and 2 patients (6.7%) reported dysuria. Patients reported a regression of dysmenorrhea symptoms (P < 0.001). CONCLUSION: This study shows that ureteroneocystostomy provides good results in terms of relapses and symptom control in patients with ureteral endometriosis.

Robot-assisted Nerve Plane-sparing Eradication of Deep Endometriosis with Double-bipolar Method.

OBJECTIVE: To demonstrate anatomic and technical highlights of a robot-assisted nerve plane-sparing eradication of deep endometriosis (DE). DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: An urban general hospital. INTERVENTIONS: Laparoscopic nerve-sparing techniques as represented by the Negrar method reportedly result in lower rates of postoperative bladder, rectal, and sexual dysfunctions than classical approaches [1]. In addition, robotic surgery has become available, and 2 meta-analyses have confirmed that robotic surgery is safe and feasible for the treatment of endometriosis, especially in advanced cases [2,3]. However, few papers have shown the surgical techniques for a nerve-sparing procedure using a robotic approach. The patient was a 45-year-old woman who presented with severe chronic pelvic pain and dysmenorrhea resistant to medication therapy. She had no nerve-specific complaints such as pain in the pudendal distribution or a voiding dysfunction. Magnetic resonance imaging revealed multiple uterine fibromas and adenomyosis with DE, involving the uterosacral ligament and surface of the rectum, with cul-de-sac obliteration. The parametrium was not involved in the DE. Robot-assisted nerve plane-sparing excision of DE with a double-bipolar method was performed using the following 8 steps: step 1, adhesiolysis and adnexal surgery; step 2, checking the ureteral course; step 3, separation of the nerve plane (step 3.1, dissection of the avascular layer below the hypogastric nerve, between the prehypogastric nerve fascia and presacral fascia; and step 3.2, dissection of the avascular layer above the hypogastric nerve, between the prehypogastric nerve fascia and fascia propria of the rectum) [4,5]; step 4, reopening of the pouch of Douglas; step 5, complete removal of DE lesions while avoiding injury to the nerve plane; step 6, hysterectomy (if the patient desires non-fertility-sparing surgery); step 7, checking for rectal injury using an air leakage test; and step 8, barrier agents for adhesion prevention. With regard to step 3, as a result of sharp dissection between avascular layers both above and below the hypogastric nerve, autonomic nerves in the pelvis were separated like a sheet with the surrounding fascia (the nerve plane). We then performed steps 4 to 6 in a step-by-step manner while avoiding injury to the nerve plane. The urinary catheter was removed within 24 hours after the surgery, and no residual urine was seen. The patient developed no perioperative complications; in particular, no postoperative bladder or rectal dysfunctions. The precise sharp dissection of the right embryo-anatomic planes on the basis of the detailed mesoanatomy seems important for improving functional outcomes in nerve-sparing surgery [5]. CONCLUSION: Robot-assisted nerve plane-sparing eradication of DE is as technically feasible as the conventional laparoscopic approach. The step-by-step technique should help surgeons perform each part of the surgery in a logical sequence, making the procedure easier and safer to complete. However, the latent benefits of robot-assisted nerve-sparing surgery in the treatment of DE remain uncertain.

Fertility- and Nerve-sparing Laparoscopic Eradication of Deep Endometriosis with Total Posterior Compartment Peritonectomy: The Kurashiki Method.

OBJECTIVE: To show technical highlights of a nerve-sparing laparoscopic eradication of deep endometriosis (DE) with posterior compartment peritonectomy. DESIGN: Demonstration of the technique with narrated video footage. SETTING: An urban general hospital. A systematic review and meta-analysis has suggested significant advantages of the nerve-sparing technique when considering the relative risk of persistent urinary retention in the treatment of DE [1]. In addition, a recent article has suggested that complete excision of DE with posterior compartment peritonectomy could be the surgical treatment of choice to decrease postoperative pain, improve fertility rate, and prevent future recurrence [2]. However, in DE, nerve-sparing procedures are even more challenging than oncologic radical procedures because the pathology resembles both ovarian/rectal cancer in terms of visceral involvement and advanced cervical cancer in terms of wide parametrial infiltration through the pelvic wall. INTERVENTIONS: The video highlights the anatomic and technical aspects of a fertility- and nerve-sparing surgery in DE with posterior compartment peritonectomy. After adhesiolysis and ovarian surgery, we developed retroperitoneal space at the level of promontory. The hypogastric nerve consists of the upper edge of the pelvic plexus, therefore the autonomic nerves were separated in a "nerve plane" by sharp interfascial dissection of the loose connective tissue layers both above (between the fascia propria of the rectum and the prehypogastric nerve fascia) and below (between the prehypogastric nerve fascia and the presacral fascia) the hypogastric nerve [3,4]. As a result of these dissections, the autonomic nerves in the pelvis were separated like a sheet with surrounding fascia. We then completely resected all DE lesions including peritoneal endometriosis while avoiding injury to the nerve plane. In a small number of our experiences, none of the patients (n = 51) required clean intermittent self-catheterization after this procedure. CONCLUSION: Fertility- and nerve-sparing laparoscopic eradication of DE with total posterior compartment peritonectomy is a feasible technique and may provide both curability of DE and functional preservation. Our nerve-sparing technique can reproducibly simplify this complex procedure.

Peutz-Jeghers syndrome complicated by gastric-type cervical mucinous carcinoma and primary peritoneal carcinoma.

A 45-year-old multiparous woman with a STK11 mutation and a history of Peutz-Jeghers syndrome underwent radical hysterectomy and bilateral salpingo-oophorectomy for a gastric-type cervical mucinous carcinoma. Four and a half years later, blood tests revealed elevations in CEA and CA125 tumor marker levels, and computed tomography showed multiple calcifications in the peritoneum. Peritoneal dissemination was suspected, and a laparoscopic biopsy was performed. Histopathology showed a high-grade serous carcinoma, and the patient was diagnosed with a metachronous stage IIIC primary peritoneal carcinoma. She had no BRCA1/2 mutation. After chemotherapy with docetaxel, carboplatin, and bevacizumab, she achieved complete remission.

Short-term outcomes of robot-assisted versus conventional laparoscopic surgery for early-stage endometrial cancer: A retrospective, single-center study.

AIM: We compared the short-term outcomes between conventional laparoscopic surgery (CLS) and robot-assisted surgery (RAS) to assess the technical feasibility of the latter for early-stage endometrial cancer. METHODS: We retrospectively compared the perioperative outcomes between two groups of 223 patients (CLS group, n = 102; RAS group, n = 121) with early-stage endometrial cancer. Surgical procedures included hysterectomy, bilateral salpingo-oophorectomy and retroperitoneal lymphadenectomy. We analyzed the data from intrapelvic surgery alone because para-aortic lymphadenectomy was performed via conventional endoscopic extraperitoneal approach without robot for both groups. RESULTS: No differences were identified in patients' age and body mass index. The mean operative time was 133 ± 28 versus 178 ± 41 min (P < 0.01), mean blood loss was 196 ± 153 versus 237 ± 146 mL (P = 0.047), mean length of postoperative hospital stay was 9 ± 4 versus 8 ± 3 days (P = 0.01) and mean rate of perioperative complications of Clavien-Dindo grade III or higher was 2.0 versus 3.4% (P = 0.53) for the CLS versus RAS groups, respectively. There was no significant difference in the number of resected lymph nodes. CONCLUSION: The operative time was significantly longer and blood loss was significantly greater in the RAS group than in the CLS group, without a significant difference in the number of resected lymph nodes. These differences are within an acceptable clinical range, showing that RAS is feasible and safe for early-stage endometrial cancer, providing short-term outcomes comparable to those of conventional surgery. Future studies are warranted to compare the long-term oncological outcomes by extending the observation period and including para-aortic lymphadenectomy data.

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

Short-term outcomes of robotic-assisted versus conventional laparoscopic radical hysterectomy for early-stage cervical cancer: A single-center study.

AIM: Our hospital adopted laparoscopic surgery for early-stage cervical cancer in August 1998, with robot-assisted surgery implemented in October 2013. This study aimed to compare short-term outcomes for conventional laparoscopic radical hysterectomy (LRH) and robot-assisted radical hysterectomy (RARH) and assess the technical feasibility of RARH for early-stage cervical cancer. METHODS: We retrospectively compared operative time, blood loss, number of resected lymph nodes, length of postoperative hospital stay, rate of positive vaginal margin and perioperative complications between two groups of 121 patients (LRH group, n = 57; RARH group, n = 64) with stage IA2 to IIB, among 164 patients who underwent endoscopic radical hysterectomy for early-stage cervical cancer performed between January 2010 and December 2017 by an expert surgeon, excluding cases of para-aortic lymphadenectomy. RESULTS: No differences in patient background, in terms of age and body mass index, were identified. For the LRH/RARH groups (mean ± standard deviation), results obtained were as follows: operative time, 211 ± 38/280 ± 59 min (P < 0.01); blood loss, 219 ± 114/370 ± 231 mL (P < 0.01); number of resected lymph nodes, 38.5 ± 15.9/50.2 ± 18.2 (P < 0.01); length of postoperative hospital stay, 11.6 ± 3.3/11.3 ± 4.8 days (P = 0.67); and perioperative complications with Clavien-Dindo classification of grade III or higher, 1.8/7.8% (P = 0.13). CONCLUSION: The operative time was significantly longer and blood loss greater in the RARH than LRH group. A greater number of lymph nodes were removed in the RARH group. However, these differences seem to be within a clinically acceptable range, showing that RARH is as feasible and safe as LRH in terms of short-term outcomes.

Long-term oncological outcomes of minimally invasive radical hysterectomy for early-stage cervical cancer: A retrospective, single-institutional study in the wake of the LACC trial.

AIM: The objective of this study was to investigate the long-term oncological outcomes of minimally invasive radical hysterectomy (MIRH) for the treatment of early-stage cervical cancer retrospectively in the wake of the laparoscopic approach to cervical cancer (LACC) trial. METHODS: A total of 109 patients with stage IA1 with lymphovascular space involvement, IA2, and IB1 cervical cancers were included in this study. The surgical and oncological outcomes were retrospectively evaluated. All patients underwent type C MIRH with a no-touch isolation technique for cervical tumor. RESULTS: The median number of resected pelvic lymph nodes was 36 (range, 14-94), and 10 patients (9.2%) had positive nodes. One patient (0.9%) had positive surgical margins. Forty-six patients (42%) underwent adjuvant therapy. The median follow-up time was 73 months (range, 30-146 months). Five patients (4.6%) developed recurrent disease, and 3 patients (2.8%) died of cervical cancer. The 5-year disease-free survival and overall survival rates were 96.3% and 97.2%, respectively. A comparison between patients with tumor diameter ≤ 2 cm (n = 59) and those with tumor diameter > 2 cm (n = 50) did not identify any significant differences, with 5-year disease-free survival 96.6% versus 94.0% and 5-year overall survival 98.3% versus 96.0%, respectively. CONCLUSION: In this retrospective study, MIRH with a no-touch isolation technique for stage IA to IB1 cervical cancer was a safe approach in terms of oncological outcomes. However, every surgeon who treats early-stage cervical cancer should inform each patient of the results of the LACC trial because it has an exceedingly high impact.

Proposal for a Risk-Based Categorization of Uterine Carcinosarcoma.

PURPOSE: To propose a categorization model of uterine carcinosarcoma (UCS) based on tumor cell types (carcinoma and sarcoma) and sarcoma dominance. METHODS: This secondary analysis of a prior multicenter retrospective study examined 889 cases of UCS with available histologic evaluation. Based on survival outcome, cases were clustered into three groups: low-grade carcinoma with nondominant homologous sarcoma [type A, n = 96 (10.8%)], (1) low-grade carcinoma with heterologous sarcoma or any sarcoma dominance and (2) high-grade carcinoma with nondominant homologous sarcoma [type B, n = 412 (46.3%)], and high-grade carcinoma with heterologous sarcoma or any sarcoma dominance [type C, n = 381 (42.9%)]. Tumor characteristics and outcome were examined based on the categorization. RESULTS: Women in type C category were more likely to be older, obese, and Caucasian, whereas those in type A category were younger, less obese, Asian, and nulligravid (all P < 0.01). Type C tumors were more likely to have metastatic implants, large tumor size, lymphovascular space invasion with sarcoma cells, and higher lymph node ratio, whereas type A tumors were more likely to be early-stage disease and small (all P < 0.05). On multivariate analysis, tumor categorization was independently associated with progression-free survival (5-year rates: 70.1% for type A, 48.3% for type B, and 35.9% for type C, adjusted P < 0.01) and cause-specific survival (5-year rates: 82.8% for type A, 63.0% for type B, and 47.1% for type C, adjusted P < 0.01). CONCLUSION: Characteristic differences in clinicopathological factors and outcomes in UCS imply that different underlying etiologies and biological behaviors may be present, supporting a new classification system.

Significance of Lymphovascular Space Invasion by the Sarcomatous Component in Uterine Carcinosarcoma.

OBJECTIVE: The aim of this study was to examine the significance of lymphovascular space invasion (LVSI) with a sarcomatous component on the tumor characteristics and clinical outcomes of women with uterine carcinosarcoma (UCS). METHODS: This was a secondary analysis of a prior multicenter retrospective study that examined women with stage I-IV UCS who underwent primary hysterectomy. Archived histopathology slides were reviewed and LVSI was scored as follows: LVSI with a carcinomatous component alone (LVSI-carcinoma; n = 375, 76.8%) or LVSI containing a sarcomatous component with or without a carcinomatous component (LVSI-sarcoma; n = 113, 23.2%). Qualitative metrics of LVSI were correlated to clinicopathological factors and survival outcome. RESULTS: Tumors in the LVSI-sarcoma group were more likely to have sarcoma dominance (82.1 vs. 26.4%) heterologous sarcomatous component (51.3 vs. 37.9%), low-grade carcinoma (42.5 vs. 22.4%), and large tumor size (81.0 vs. 70.2%) in the primary tumor site compared with tumors in the LVSI-carcinoma group (all p < 0.05). On multivariate analysis, LVSI-sarcoma was independently associated with decreased progression-free survival (5-year rates: 34.9 vs. 40.8%, adjusted hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.36-2.50, p < 0.001), and cause-specific survival (5-year rates: 41.8 vs. 55.9%, adjusted HR 1.95, 95% CI 1.39-2.75, p < 0.001) compared with LVSI-carcinoma. Postoperative radiotherapy for women with LVSI-sarcoma had a higher reduction rate of recurrence/progression of disease (54% reduction, p = 0.04) compared with postoperative radiotherapy for women with LVSI-carcinoma (26% reduction, p = 0.08). CONCLUSION: In UCS, the presence of a sarcomatous component in LVSI is particularly prevalent when a tumor has sarcoma dominance. Our study suggests that LVSI containing a sarcomatous component may be a predictor of decreased survival for women with UCS.

Significance of venous thromboembolism in women with uterine carcinosarcoma.

OBJECTIVE: To identify risk factors for venous thromboembolism (VTE) and to examine the association of VTE and survival in women with uterine carcinosarcoma. METHODS: This multicenter retrospective study examined 906 women who underwent primary surgical treatment for stage I-IV uterine carcinosarcoma. Time-dependent analyses were performed for cumulative incidence of VTE after surgery on multivariate models. RESULTS: There were 72 (7.9%) women who developed VTE after surgery with 1-, 2-, and 5-year cumulative incidences being 5.1%, 7.3%, and 10.2%, respectively. On multivariate analysis, older age (hazard ratio [HR] per year 1.03, P=0.012), non-Asian race (HR 6.28, P<0.001), large body habitus (HR per kg/m2 1.04, P=0.014), residual disease at surgery (HR 3.04, P=0.003), tumor size ≥5cm (HR 2.73, P=0.003), and stage IV disease (HR 2.12, P=0.025) were independently associated with increased risk of developing VTE. A risk pattern analysis identified that obese Non-Asian women with large tumors (13.7% of population) had the highest incidence of VTE (2-year cumulative rate, 26.1%) whereas Asian women with no residual disease (47.1% of population) had the lowest (2-year cumulative rate, 1.6%) (P<0.001). Presence of carcinoma/sarcoma in metastatic sites was significantly associated with increased risk of VTE compared to carcinoma alone (2-year rates, 31.2% versus 8.4%, P=0.049). VTE was independently associated with decreased progression-free survival on multivariate models (5-year rates, 24.9% versus 47.2%, HR 1.46, 95%CI 1.05-2.04, P=0.026). CONCLUSION: Our study suggests that VTE represents a surrogate marker of aggressive tumor behavior and diminished patient condition in uterine carcinosarcoma; obese Non-Asian women with large tumors carry a disproportionally high risk of VTE, suggesting that long-term prophylaxis may benefit this population.

Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery.

BACKGROUND AND OBJECTIVES: To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. METHODS: This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. RESULTS: The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. CONCLUSION: Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery.

Tumor characteristics and survival outcomes of women with tamoxifen-related uterine carcinosarcoma.

OBJECTIVE: To examine tumor characteristics and survival outcome of women with uterine carcinosarcoma who had a history of tamoxifen use. METHODS: This is a multicenter retrospective study examining stage I-IV uterine carcinosarcoma cases based on history of tamoxifen use. Patient demographics, tumor characteristics, treatment pattern, and survival outcomes were compared between tamoxifen users and non-users. RESULTS: Sixty-six cases of tamoxifen-related uterine carcinosarcoma were compared to 1009 cases with no history of tamoxifen use. Tamoxifen users were more likely to be older (mean age, 69 versus 64, P<0.001) and had a past history of malignancy (100% versus 12.7%, P<0.001). Tamoxifen-related uterine carcinosarcoma was significantly associated with a higher proportion of stage IA disease (48.4% versus 29.9%) and a lower risk of stage IVB disease (7.8% versus 16.0%) compared to tamoxifen-unrelated carcinosarcoma (P=0.034). Deep myometrial tumor invasion was less common in uterine carcinosarcoma related to tamoxifen use (28.3% versus 48.8%, P=0.002). On univariate analysis, tamoxifen use was not associated with progression-free survival (5-year rates 44.5% versus 46.8%, P=0.48) and disease-specific survival (64.0% versus 59.1%, P=0.39). After adjusting for age, past history of malignancy, stage, residual disease status at surgery, and postoperative treatment patterns, tamoxifen use was not associated with progression-free survival (adjusted-hazard ratio 0.86, 95% confidence interval 0.50 to 1.50, P=0.60) and disease-specific survival (adjusted-hazard ratio 0.68, 95% confidence interval 0.36 to 1.29, P=0.24). CONCLUSION: Our study suggests that tamoxifen-related uterine carcinosarcoma may have favorable tumor characteristics but have comparable stage-specific survival outcomes compared to tamoxifen-unrelated uterine carcinosarcoma.

Impact of adjuvant therapy on recurrence patterns in stage I uterine carcinosarcoma.

BACKGROUND: To examine recurrence patterns in women with stage I uterine carcinosarcoma (UCS) stratified by adjuvant therapy pattern. METHODS: We examined 443 cases of stage I UCS derived from a retrospective cohort of 1192 UCS cases from 26 institutions. Adjuvant therapy patterns after primary hysterectomy-based surgery were correlated to recurrence patterns. RESULTS: The most common adjuvant therapy was chemotherapy alone (41.5%) followed by chemotherapy/radiotherapy (15.8%) and radiotherapy alone (8.4%). Distant-recurrence was the most common recurrence pattern (5-year cumulative rate, 28.1%) followed by local-recurrence (13.3%). On multivariate analysis, chemotherapy but not radiotherapy remained an independent prognostic factor for decreased risk of local-recurrence (5-year cumulative rates 8.7% versus 19.8%, adjusted-hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25-0.83, P=0.01) and distant-recurrence (21.2% versus 38.0%, adjusted-HR 0.41, 95%CI 0.27-0.62, P<0.001). The chemotherapy/radiotherapy group had a lower 5-year cumulative local-recurrence rate compared to the chemotherapy alone group but it did not reach statistical significance (5.1% versus 10.1%, adjusted-HR 0.46, 95%CI 0.13-1.58, P=0.22). Radiotherapy significantly decreased local-recurrence when tumors had high-grade carcinoma, sarcoma component dominance, and deep myometrial tumor invasion (all, P<0.05); and combining radiotherapy with chemotherapy was significantly associated with decreased local-recurrence compared to chemotherapy alone in the presence of multiple risk factors (5-year cumulative rates, 2.5% versus 21.8%, HR 0.12, 95%CI 0.02-0.90; P=0.013) but not in none/single factor (P=0.36). CONCLUSION: Adjuvant chemotherapy appears to be effective to control both local- and distant-recurrences in stage I UCS; adding radiotherapy to chemotherapy may be effective to control local-recurrence when the tumor exhibits multiple risk factors.

Salvage chemotherapy with taxane and platinum for women with recurrent uterine carcinosarcoma.

OBJECTIVE: To examine survival after recurrence (SAR) among women with recurrent uterine carcinosarcoma who received a taxane/platinum doublet as the first-line salvage chemotherapy. METHODS: We retrospectively examined 148 women with recurrent uterine carcinosarcoma who received salvage chemotherapy within a cohort of 906 uterine carcinosarcomas. An independent association of salvage chemotherapy type and SAR was examined with multivariate analysis. RESULTS: There were 71 (48.0%) women who received a taxane/platinum regimen. On univariate analysis, women who received a taxane/platinum doublet had a higher 2-year SAR rate compared to women who received non-taxane/platinum regimens (55.5% versus 34.8%, P<0.001). On multivariate analysis, use of taxane/platinum regimen was independently associated with improved SAR compared to the non-taxane/platinum regimens (adjusted-hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.35 to 0.91, P=0.02). When stratified by disease-free interval, women with a disease-free interval ≥6months who received a taxane/platinum doublet had a higher 2-year SAR rate compared to those who received non-taxane/platinum regimens (61.9% versus 40.0%, HR 0.46, 95% CI 0.28 to 0.75, P=0.002); conversely, in women with a disease-free interval <6months, 2-year SAR rates were similar between the two groups (20.5% versus 18.4%, HR 0.80, 95% CI 0.33 to 1.90, P=0.61). Among women who received a taxane/platinum doublet as adjuvant chemotherapy, re-treatment with taxane/platinum doublet as salvage chemotherapy remained beneficial (2-year SAR rate, 62.1% versus 39.7%, HR 0.40, 95% CI 0.18 to 0.86, P=0.019). CONCLUSION: Our study suggests that taxane/platinum doublet may be a more effective chemotherapy regimen compared to other regimens among women with recurrent uterine carcinosarcoma, especially for those who had a disease-free interval of ≥6months.