Joshua Z. Press

Vaginal vault dehiscence after robotic hysterectomy for gynecologic cancers: search for risk factors and literature review.

Introduction Vaginal vault dehiscence following robotic-assisted hysterectomy for gynecologic cancer may be attributed to surgical techniques and postoperative therapeutic interventions. We searched for risk factors in patients with gynecologic cancers and complemented this with a literature review. Methods Evaluation of prospectively gathered information on all consecutive robotic surgeries for gynecologic cancers was performed in a tertiary academic cancer center between December 2007 and March 2012. The literature was reviewed for articles relevant to “gynecologic oncology” and “robotics” with “vaginal cuff dehiscence” in the English and French languages. Respective authors were contacted to complete relevant information. Results Seven dehiscences were identified of 441 cases with established gynecologic cancers. The closures in these 7 were performed using interrupted 1-Vicryl (Ethicon Inc) (3/167; 1.8%), combination of interrupted 1-Vicryl and 1-Biosyn (Covidien Inc) (3/156, 1.9%), and V-Loc (Covidien Inc) (1/118, 0.8%) sutures. Associated risk factors included adjuvant chemotherapy and/or brachytherapy, early resumption of sexual activity, and low body mass index (mean, 23 ± 3.23 kg/m2). Dehiscences occurred regardless of suturing by staff or trainees. Review of operative videos did not reveal a detectable etiologic factor, such as excessive cautery damage to the vaginal cuff or shallow tissue sutured. All 7 colporrhexis repairs were performed through a vaginal approach without the need of laparoscopy or laparotomy. Conclusions Postoperative chemotherapy, brachytherapy, and early resumption of sexual activities are risk factors for vaginal vault dehiscence. Surgical technique, particularly the use of delayed absorbable sutures, deserves further evaluation

Familial small cell carcinoma of the ovary.

Ovarian tumors have a low incidence in childhood, accounting for 1% of malignancies within the ages of 0–17 years. Small cell carcinoma of the ovary is a rare histology and historically has a poor prognosis. We report a case of an 11‐year‐old female diagnosed with small cell carcinoma of the ovary and hypercalcemia (SCCOHT). There was a strong family history of the disease, a reduction in the age of onset in the proband, and the absence of BRCA mutations. This case suggests the phenomenon of genetic anticipation in an ovarian cancer. Pediatr Blood Cancer 2009; 53:1334–1336.

Microparticles from ovarian carcinomas are shed into ascites and promote cell migration

Objective Microparticles are cellular-derived vesicles (0.5–1.0 &mgr;m) composed of cell membrane components, which are actively shed from the surface of various cells, including epithelial cells. We compared microparticles in ascites between women with ovarian carcinoma and women with benign ovarian pathology, and isolated tumor-derived (epithelial cell adhesion molecule [EpCAM]-positive) microparticles for functional analysis and proteomics. Materials and Methods Cases included 8 patients with benign ovarian neoplasms and 41 with ovarian carcinoma. Ascites from a high-grade stage III serous carcinoma was used for functional and proteomic analysis. Cancer cells were isolated using EpCAM-coated beads, microparticles were isolated by ultracentrifugation/flow cytometry, and sorting was achieved using markers (eg, EpCAM). Binding and migrations assays were performed with 3 ovarian cancer cell lines. Proteomic analysis of EpCAM-positive microparticles and ascites cancer cells was performed by mass spectrometry. Results Microparticles in benign pelvic fluid were similar to early and advanced-stage ascites (2.4 vs 2.8 vs 2.0 × 106 microparticles/mL). Advanced stage had a greater proportion of EpCAM-positive microparticles than early or benign disease (13.3% vs 2.5% vs 2.1%; P = 0.001), and serous histology had more than endometrioid (13.2% vs 1.8%; P = 0.01). Microparticles bound to the surface of 3 cultured cell lines, and were internalized into the EpCAM-positive microparticles, resulting in more cell migration than buffer alone or EpCAM-negative microparticles (P = 0.007). A dose-dependent increase was seen with increasing numbers of EpCAM-positive microparticles. Proteomics revealed that most proteins in EPCAM-positive microparticles were shared with cancer cells, and many are associated with cell motility and invasion, such as fibronectin, filamin A, vimentin, myosin-9, and fibrinogen. Conclusions Ascites from advanced-stage and serous ovarian carcinomas contain large numbers of tumor-derived microparticles. In vitro, these microparticles bind to cancer cells and stimulate migration. Tumor-derived microparticles in ascites could mediate the predilection for peritoneal spread in serous ovarian carcinomas.

A prospective investigation of fluorescence imaging to detect sentinel lymph nodes at robotic-assisted endometrial cancer staging

BACKGROUNDnThe accuracy of sentinel lymph node mapping has been shown in endometrial cancer, but studies to date have primarily focused on cohorts at low risk for nodal involvement. In our practice, we acknowledge the lack of benefit of lymphadenectomy in the low-risk subgroup and omit lymph node removal in these patients. Thus, our aim was to evaluate the feasibility and accuracy of sentinel node mapping in women at sufficient risk for nodal metastasis warranting lymphadenectomy and in whom the potential benefit of avoiding nodal procurement could be realized.nnnOBJECTIVEnTo evaluate the detection rate and accuracy of fluorescence-guided sentinel lymph node mapping in endometrial cancer patients undergoing robotic-assisted staging.nnnSTUDY DESIGNnOne hundred twenty-three endometrial cancer patients undergoing sentinel lymph node sentinel node mapping using indocyanine green were prospectively evaluated. Two mL (1.0 mg/mL) of dye were injected into the cervical stroma divided between the 2-3 and 9-10 oclock positions at the time of uterine manipulator placement. Before hysterectomy, the retroperitoneal spaces were developed and fluorescence imaging was used for sentinel node detection. Identified sentinel nodes were removed and submitted for touch prep intraoperatively, followed by permanent assessment with routine hematoxylin and eosin levels. Patients then underwent hysterectomy, bilateral salpingo-oophorectomy, and completion bilateral pelvic and periaortic lymphadenectomy based on intrauterine risk factors determined intraoperatively (tumor size >2 cm, >50% myometrial invasion, and grade 3 histology).nnnRESULTSnOf 123 patients enrolled, at least 1 sentinel node was detected in 119 (96.7%). Ninety-nine patients (80%) had bilateral pelvic or periaortic sentinel nodes detected. A total of 85 patients met criteria warranting completion lymphadenectomy. In 14 patients (16%) periaortic lymphadenectomy was not feasible, and the mean number of pelvic nodes procured was 13 (6-22). Of the 71 patients undergoing pelvic and periaortic lymphadenectomy, the mean nodal count was 23.2 (8-51). Of patients undergoing lymphadenectomy, 10.6% had lymph node metastasis on final hematoxylin and eosin evaluation. Notably, the sentinel node was the only positive node in 44% of cases. There were no cases in which final pathology of the sentinel node was negative and metastatic disease was detected upon completion lymphadenectomy in the non-sentinel nodes (no false negatives), yielding a sensitivity of 100%. Of the 14 sentinel nodes ultimately found to harbor metastases, 3 were negative on touch prep, yielding a sensitivity of 78.6% for intraoperative detection of sentinel node involvement. In all 3 of the false-negative touch preps, final pathology detected a single micrometastasis (0.24 mm, 1.4 mm, 1.5 mm). As expected, there were no false-positive results, yielding a specificity of 100%. No complications related to sentinel node mapping or allergic reactions to the dye were encountered.nnnCONCLUSIONnIntraoperative sentinel node mapping using fluorescence imaging with indocyanine green in endometrial cancer patients is feasible and yields high detection rates. In our pilot study, sentinel node mapping identified all women with Stage IIIC disease. Low false-negative rates are encouraging, and if confirmed in multi-institutional trials, thisxa0approach would be anticipated to reduce the morbidity, operative times, and costs associated with complete pelvic and periaortic lymphadenectomy.

Virtual reality robotic surgery simulation curriculum to teach robotic suturing: a randomized controlled trial

The objective of this randomized, controlled trial was to assess whether voluntary participation in a proctored, proficiency-based, virtual reality robotic suturing curriculum using the da Vinci® Skills Simulator™ improves robotic suturing performance. Residents and attending surgeons were randomized to participation or non-participation during a 5xa0week training curriculum. Robotic suturing skills were evaluated before and after training using an inanimate vaginal cuff model, which participants sutured for 10xa0min using the da Vinci® Surgical System. Performances were videotaped, anonymized, and subsequently graded independently by three robotic surgeons. 27 participants were randomized. 23 of the 27 completed both the pre- and post-test, 13 in the training group and 10 in the control group. Mean training time in the intervention group was 238xa0±xa0136xa0min (SD) over the 5xa0weeks. The primary outcome (improvement in GOALS+ score) and the secondary outcomes (improvement in GEARS, total knots, satisfactory knots, and the virtual reality suture sponge 1 task) were significantly greater in the training group than the control group in unadjusted analysis. After adjusting for lower baseline scores in the training group, improvement in the suture sponge 1 task remained significantly greater in the training group and a trend was demonstrated to greater improvement in the training group for the GOALS+ score, GEARS score, total knots, and satisfactory knots.

Outcome of robotic surgery for endometrial cancer as a function of patient age.

Objective This study aimed to evaluate and compare robot-assisted surgical staging on clinical outcomes, including quality of life and survival, as a function of patient age. Methods Evaluation and comparison of perioperative morbidity, survival, and postoperative quality of life after prospective accumulation of clinical information including outcome measures for patients with endometrial cancer during the first 5 years of a robotic program, based on the following 3 age categories: women older than 80 years, women between 70 and 80 years, and women younger than 70 years. Results All consecutive patients with endometrial cancer undergoing robotic surgery (n = 303) were included, with 197 women younger than 70 years, 75 women between 70 and 80 years, and 31 women older than 80 years. There were significantly more patients with advanced stage (stage II to IV in 17%, 34%, and 35%, P = 0.02) and grade 3 disease (26%, 43%, and 58%, P = 0.002) with increasing age. The perioperative data showed similar grade I or II complications (Clavien-Dindo classification) between the groups, but significantly more grade III and IV complications for women older than 80 years compared with women 80 years or younger (10% vs 1%, P = 0.004). The time needed to resume chore activities was significantly shorter for patients 70 years or older than patients younger than 70 years [8.9 (8.7) vs 18.8 (25.5) days, P = 0.048]. Overall, all patients irrespective of age were highly satisfied with the procedure. There was no difference between young and elderly patients for disease-free survival (P = 0.99). Conclusions Patient’s age did not influence minor postoperative morbidity or overall satisfaction after robotic assisted surgery for endometrial cancer. Elderly patients had more major postoperative morbidity but resumed activities quicker than younger patients.

FOXP3+ regulatory T-cells are abundant in vulvar Paget's disease and are associated with recurrence

OBJECTIVEnTo characterize clinical features of vulvar Pagets disease, and examine the quantity of immunosuppressive regulatory T-cells in vulvar Pagets tissue.nnnMETHODSnVulvar Pagets cases from 1992 to 2007 from two institutions were identified by pathology database search. Regulatory T-cells were identified with FOXP3 immunohistochemistry and quantified at the dermal-epidermal junction using image analysis software. Thirteen non-neoplastic inflammatory cases were stained for comparison.nnnRESULTSnCases included 33 women treated for primary vulvar Pagets, and 7 referred at recurrence. Of the 24 primary cases with greater than 5 months follow-up, recurrence was documented in 12/24(50%). Eight women (20%) recurred multiple times, but no recurrences were invasive. Significantly more patients with positive margins developed recurrent disease (82% vs 23%, p=0.01). Secondary neoplasms occurred in 10/40(25%). FOXP3+ cells at the dermal-epidermal junction were quantified in 29 primary and 13 recurrent tissue samples. FOXP3+ cells were absent in surrounding normal vulvar skin. FOXP3+ cells averaged 66/HPF in primary vulvar Pagets and 66/HPF in recurrent Pagets, compared to 22/HPF in non-neoplastic inflammatory cases (p=0.0003, p=0.001). Primary cases with positive surgical margins had more FOXP3+ cells than those with negative margins (85 vs 49, p=0.01). Recurrent cases with positive margins had more FOXP3+ cells than negative cases (84 vs 33, p=0.06). FOXP3 levels in primary specimens were higher in cases which recurred (78 vs 35, p=0.02).nnnCONCLUSIONSnIncreased regulatory T-cells may be associated with more extensive cases of vulvar Pagets disease that result in positive surgical margins and are associated with recurrence of disease, suggesting immunosuppression as a key factor.

Advancing surgical simulation in gynecologic oncology: robotic dissection of a novel pelvic lymphadenectomy model.

Introduction Pelvic lymphadenectomy is a key component of the surgical treatment of several gynecologic cancers and involves mastery of complex anatomic relationships. Our aim was to demonstrate that the anatomy relevant to robotic pelvic lymphadenectomy can be modeled using low-cost techniques, thereby enabling simulation focused on surgical dissection, a task that integrates technical skills and anatomic knowledge. Methods A model of pelvic lymphadenectomy was constructed through experimentation with several different materials and a number of prototypes. In the final version, blood vessels were simulated by rubber tubing stented with wire and lymph nodes by cotton balls. Adipose and areolar tissue were simulated by a gelatin solution poured into the model and then allowed to cool and semisolidify. Three gynecologic oncologists and 2 gynecologic oncology fellows dissected the model using the surgical robot (da Vinci Surgical System) and completed a structured questionnaire. Five additional gynecologic oncologists assessed the model at a national conference. Results The model received high ratings for face and content validity. Median ratings were almost all 4 of 5 or higher (range, 3–5). Participants who dissected the model (n = 5) unanimously rated it as “useful for training throughout residency and fellowship.” Conclusions A novel low-cost inanimate model of pelvic lymphadenectomy has been developed and rated highly for face and content validity. This model may permit more regular simulation sessions compared with alternatives such as cadaveric dissection and animal laboratories, thereby complementing them and facilitating distributed practice.