M.L. Sprague

Uterine viability in the baboon after ligation of uterine vasculature: a pilot study to assess alternative perfusion and venous return for uterine transplantation

OBJECTIVE To assess, in two separate groups of baboons, uterine viability after ligation of the uterine veins and uterine viability after ligation of both the uterine arteries and veins, respectively. DESIGN Prospective, observational study. SETTING Baboon breeding colony. ANIMAL(S) Six naïve female Papio hamadryas baboons with indicators of normal reproductive function. INTERVENTION(S) Three baboons underwent surgical interruption of the uterine veins bilaterally, and three baboons underwent surgical interruption of the uterine arteries and the uterine veins bilaterally. All baboons also underwent colpotomy, cervico-vaginal reanastomosis, and intraoperative near-infrared fluorescence imaging after vessel ligation. In the postoperative period, transabdominal sonography, vaginoscopy, and endocervical biopsy were performed on all animals. MAIN OUTCOME MEASURE(S) Postoperative uterine and ovarian viability. RESULT(S) Near-infrared imaging confirmed intraoperative perfusion of the uterus and cervico-vaginal anastomosis in all cases. In all subjects, sonography revealed normal uteri, and vaginoscopy revealed well-healed anastomoses. Endocervical biopsies (five of six) demonstrated pathologically normal endocervical tissue without evidence of necrosis. Cyclical sex skin turgescence and menstruation were unanimously observed. CONCLUSION(S) Disruption of bilateral uterine vessels does not affect uterine or ovarian viability in the baboon. Bilateral uterine artery and vein ligation furthers development of a minimally invasive approach to donor hysterectomy.

Utility of indocyanine green (ICG) intra-operative angiography to determine uterine vascular perfusion at the time of radical trachelectomy

OBJECTIVES The aim of our study was to measure and analyze uterine perfusion utilizing laser angiography with ICG during uterine artery sparing and non-sparing radical trachelectomy. METHODS Data were collected from all patients diagnosed with early-stage cervical cancer that underwent laser angiography with ICG during open or laparoscopic radical trachelectomy from June 2012 to December 2015. Regression analysis was use to determine the p values and R-squares on fluorescence, surgical time, hospital stay, age and BMI; a p-value<0.05 was considered statistically significant. RESULTS A total of 20 patients met the inclusion criteria and were included in this study. Ten patients underwent uterine artery-sparing surgery, and ten patients underwent uterine artery non-sparing surgery. The most frequent stage for the entire cohort was IA2 (55%), and the most common histologic subtype was squamous cell carcinoma (49%). Lymph-vascular invasion was noted in 30% of the patients. There was no statistical significance difference in the mean ICG fundal fluorescence intensity between the uterine artery-sparing group 162.5 (range, 137-188) and the uterine artery non-sparing group 160.5 (range, 135-186), p=0.22. In both groups, 100% of the patients regained their menstrual function by postoperative week 8. A total of 4 (40%) pregnancies have occurred in the uterine artery-sparing group and 3 (30%) in the non-uterine artery-sparing group. CONCLUSIONS Based on our real-time intraoperative angiography observations, there is no need to preserve the uterine artery during radical trachelectomy to maintain uterine viability.

Livebirth and utero-placental insufficiency in Papio hamadryas baboons with uterus angiosome perfused by bilateral utero-ovarian microsurgical anastomoses alone

STUDY QUESTION Can the baboon uterus support a gestation to livebirth with an angiosome using microsurgically anastomosed utero-ovarian vessels and lacking uterine arteries and veins? SUMMARY ANSWER Our angiosome model allows healthy livebirth albeit with risk of fetal growth restriction and stillbirth. WHAT IS KNOWN ALREADY Uterine transplant can provide livebirth in humans, but requires a living donor to undergo a prolonged laparotomy for hysterectomy. In an attempt to avoid the time-consuming dissection of the uterine vein, our group has previously shown maintenance of baboon uterine menstrual function after ligation of the uterine vein and after ligation of both the uterine artery and uterine vein. STUDY DESIGN, SIZE, DURATION In a 19-month timespan, three baboons underwent laparotomy to surgically alter uterine perfusion, and pregnancy outcomes were monitored after spontaneous mating in a breeding colony. PARTICIPANTS/MATERIALS, SETTING, METHODS Three nulligravid female Papio hamadryas baboons in a breeding colony underwent laparotomy to ligate uterine arteries and veins along with colpotomy and cervico-vaginal anastomosis. During the same surgery, the utero-ovarian arteries and veins were microsurgically transected and re-anastomosed to themselves. Intraoperative organ perfusion was confirmed with laser angiography. After a recovery period, monitoring of menstrual cycling via menstrual blood flow and sex-skin cycling occurred, as well as uterine viability via sonography and cervical biopsy. Each baboon was released to the breeding colony for spontaneous mating and pregnancies dated by menstrual calendar and compared with early ultrasound. Delivery outcomes were monitored in each including neonate weight and placental pathology. In the event of a stillbirth, the animal was returned to the breeding colony for repeat mating attempts. After achieving a livebirth, the maternal baboon was removed from the study. MAIN RESULTS AND THE ROLE OF CHANCE Each baboon in the trial underwent successful surgery with all uteri demonstrating viability and return of menstrual function within 10 weeks of surgery. Pregnancies occurred within two menstrual cycles in breeding colony. Baboons one and two initially had vaginal breech stillbirths, both with appearance of placental insufficiency, and one with fetal growth restriction. Baboon three underwent scheduled cesarean delivery resulting in a normally grown livebirth. Baboon one had a subsequent pregnancy resulting in a livebirth via cesarean delivery. LIMITATIONS, REASONS FOR CAUTION Stillbirth in two of four gestations, and fetal growth restriction in one of four, are the largest concerns in our perfusion model. It remains uncertain whether the stillbirths resulted from placental insufficiency, or birth trauma from breech deliveries. WIDER IMPLICATIONS OF THE FINDINGS The success of two livebirths warrants further attempts at improving consistency of our proposed uterine angiosome. This may allow living uterine donors to undergo less-invasive and shorter donor hysterectomy procedures. STUDY FUNDING/COMPETING INTEREST(S) The study had no external sponsors, and was supported by the Cleveland Clinic Foundation. Some equipment was loaned without cost to the research team including a laser angiography system courtesy of Novadaq Technologies, Inc. (Missaugua, ON, Canada) and a surgical microscope courtesy of DB Surgical (Coral Springs, FL, USA). B.B., K.A., M.S., K.R., M.M., P.F.E., A.T. and T.F. have no conflicts of interest. M.L.S. and S.Z. report activity as consultants for Medtronic-Covidien, and S.Z. also is a consultant to Applied Medical.

Anatomy of the Internal Iliac Vein: Implications for Uterine Transplant

STUDY OBJECTIVE Uterine transplantation has proven feasible since the first live birth reported in 2014. To enable attachment of the uterus in the recipient, long vascular pedicles of the uterine and internal iliac vessels were obtained during donor hysterectomy, which required a prolonged laparotomy to the living donors. To assist further attempts at uterine transplantation, our video serves to review literature reports of internal iliac vein anatomy and demonstrate a laparoscopic dissection of cadaver pelvic vascular anatomy. DESIGN Observational (Canadian Task Force Classification III). SETTING Academic anatomic laboratory. Institutional Review Board ruled that approval was not required for this study. INTERVENTION Literature review and laparoscopic dissection of cadaveric pelvic vasculature, focusing on the internal iliac vein. MEASUREMENTS AND MAIN RESULTS Although the internal iliac artery tends to have minimal anatomic variation, its counterpart, the internal iliac vein, shows much variation in published studies [1,2]. Relative to the internal iliac artery, the vein can lie medially or laterally. Normal anatomy is defined as some by meeting 2 criteria: bilateral common iliac vein formed by ipsilateral external and internal iliac vein at a low position and bilateral common iliac vein joining to form a right-sided inferior vena cava [2]. Reports show 79.1% of people have normal internal iliac vein anatomy by these criteria [2]. The cadaver dissection revealed internal iliac vein anatomy meeting criteria for normal anatomy. CONCLUSION Understanding the complexity and variations of internal iliac vein anatomy can assist future trials of uterine transplantation.

Vaginal cuff dehiscence following hysterectomy

Vaginal cuff dehiscence is a rare complication following total hysterectomy with an overall incidence generally estimated to be less than 1 %. The severity of vaginal cuff dehiscence ranges from mild separation to intestinal evisceration, a surgical emergency. Characteristics such as obesity and vaginal atrophy may predispose patients to vaginal cuff dehiscence. Additionally, factors such as the surgical approaches for hysterectomy and cuff closure likewise impact a patient’s overall risk for vaginal cuff dehiscence. Pelvic surgeons must be mindful of the signs of vaginal cuff dehiscence and prepared to efficiently address this potentially life-threatening surgical emergency.

Fallopian tube perfusion in ex-vivo and in-vivo laparoscopic hysterectomy specimens: potential application for uterine transplantation

STUDY QUESTION Is there perfusion to the fallopian tubes in ex-vivo and in-vivo uteri at the time of total laparoscopic hysterectomy (TLH), as observed using laser angiography with indocyanine green (ICG)? SUMMARY ANSWER The fallopian tubes may have perfusion from the utero-ovarian vasculature alone. WHAT IS KNOWN ALREADY The fallopian tubes are perfused by the uterine and utero-ovarian vessels. Perfusion can be measured using laser angiography with ICG. STUDY DESIGN, SIZE, DURATION This prospective pilot cohort study included 15 women, ages 32-59 years old, who underwent TLH with bilateral salpingectomy for benign indications. PARTICIPANTS/MATERIALS, SETTING, METHODS In five participants, TLH was performed and the utero-ovarian artery was cannulated ex vivo and injected with ICG. The other 10 participants underwent the in-vivo protocol. The mesosalpinx and uterine vessels were transected in the partial protocol. Colpotomy was also performed in the complete protocol. All fallopian tubes were imaged using laser angiography with ICG. The relative fluorescence and the fluorescence intensity ratio (length of fluorescent fallopian tube/total length of fallopian tube) of the fallopian tubes were measured in the ex-vivo and in-vivo protocols, respectively. MAIN RESULTS AND THE ROLE OF CHANCE Ex vivo, the fimbria of the ipsilateral fallopian tube had 47% median relative fluorescence as compared to the contralateral fallopian tube, which had 2.4% median relative fluorescence. In vivo, the post-ICG fluorescence intensity ratios were 0.61 ± 0.40 for the partial protocol, and 0.78 ± 0.30 for the complete protocol, with mean differences of 0.37 (95% CI: 0.23-0.50, P < .0001) and 0.22 (95% CI: 0.12-0.31, P < 0.0001), respectively, between the pre-procedure and the post-ICG fluorescence intensity ratios. Greater than 0.75 fluorescence intensity ratios (i.e. >75% tubal length fluorescence) was seen in 60% of fallopian tubes. LIMITATIONS, REASONS FOR CAUTION This is a pilot study with a small sample size and pathologic uteri, which would not be appropriate for uterine transplantation. No conclusions can be made regarding the functionality of the fallopian tubes. WIDER IMPLICATIONS OF THE FINDINGS The fallopian tubes may have perfusion with the utero-ovarian vasculature alone, potentially allowing for future animal studies regarding tubal viability in recipients of uterine-tubal transplants. If successful, human uterine-tubal transplantation may allow for spontaneous conception rather than IVF. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used. S.F., P.F.P., K.A.S. and R.F. have no conflicts of interest to report. M.L.S. is an educational consultant for Medtronic (Dublin, Republic of Ireland) and Applied Medical (Rancho Santa Margarita, CA, USA), as well as a stockholder for SynDaver Labs (Tampa, FL, USA). S.E.Z. is an educational consultant for Applied Medical (Rancho Santa Margarita, CA, USA) and is on the advisory board for AbbVie Inc. (Chicago, IL, USA). TRIAL REGISTRATION NUMBER Not applicable.

Management, Prevention, and Sequelae of Adhesions in Women Undergoing Laparoscopic Gynecologic Surgery: a Systematic Review

Surgical adhesions can lead to significant consequences including abdominopelvic pain, bowel obstruction, subfertility, and subsequent surgery. Although laparoscopic surgery is associated with a decreased risk of adhesion formation, methods to further decrease adhesions are warranted. We systematically reviewed literature addressing the management, prevention, and sequelae of adhesions in women undergoing laparoscopic gynecologic surgery. We searched PubMed, EMBASE, EBSCOhost, and Cochrane Central Register of Controlled Trials and found 6566 records. The primary outcome was adhesion formation. The secondary outcomes were abdominopelvic pain, quality of life, subfertility, pregnancy, bowel obstruction, urinary symptoms, and subsequent surgery. After applying inclusion and exclusion criteria, 52 studies remained for qualitative synthesis. Risk of bias assessments were applied independently by 2 authors. There was evidence that Hyalobarrier Gel (Anika Therapeutics, Bedford, MA), HyaRegen NCH Gel (Bilar Medikal, Istanbul, Turkey), Oxiplex/AP Gel (Fziomed, Inc., San Luis Obispo, CA), SprayGel (Confluent Surgical Inc., Waltham, MA), and Beriplast (CSL Behring, LLCm King of Prussia, PA) all decrease the incidence of adhesions. Adept (Baxter, Deerfield, IL) significantly decreased de novo adhesion scores of the posterior uterus. Using an integrated treatment approach to pelvic pain significantly improved pain and quality of life compared with standard laparoscopic treatment. Lastly, Hyalobarrier Gel Endo (Anika Therapeutics, Bedford, MA) placement led to a higher pregnancy rate than no barrier usage. Our findings underscore the need for high-quality trials to evaluate the efficacy of surgical techniques, adhesion barriers, and other treatment modalities on the management and prevention of adhesions and their clinical sequelae. This review was registered on PROSPERO (ID = CRD42017068053).

Vaginal Cuff Dehiscence After Total Laparoscopic Hysterectomy

e broken barbed suA 45-year-old woman with abnormal uterine bleeding, endometriosis, history of diethylstilbestrol exposure in utero, and leiomyoma uteri underwent uncomplicated total laparoscopic hysterectomy. At 51 days after surgery, she presented with postcoital abdominal pain and watery vaginal discharge. Vaginal cuff dehiscence with a broken V-Loc suture, without evisceration, was noted (Fig. 1 and Fig. 2). The patient was taken to the operating room for surgical repair, during which interrupted 2-0 PDS stitches were placed vaginally in a figure-eight fashion. Vaginal cuff dehiscence is a rare but potentially morbid postoperative adverse event after total hysterectomy. The

Giant cystic degeneration of a uterine leiomyoma in a patient with autosomal dominant polycystic kidney disease

Objective To report the management of a large uterine leiomyoma with diffuse cystic degeneration in a patient with autosomal dominant polycystic kidney disease (ADPKD). Design Case Report. Setting Cleveland Clinic Florida, Department of Gynecology, Section of Minimally Invasive Gynecologic surgery, Weston Florida. Patient(s) A 52-year old woman with ADPKD with a large abdominal mass, abnormal uterine bleeding and symptomatic anemia. Imaging revealed a giant intramural cystic lesion of the uterus compressing the inferior vena cava. Intervention(s) Uterine artery embolization and blood transfusion followed by a computed tomography guided cyst aspiration were performed on admission to alleviate anemia and abdominal pain and distension. Total laparoscopic hysterectomy with bilateral salpingectomy was performed in an outpatient setting. Main Outcome Measure(s) Management of large cystic degeneration of leiomyoma. Results Normal recovery from definitive surgery. Surgical pathology confirmed a benign, cystically dilated leiomyoma. Conclusion This case demonstrates the management of giant intramural cyst lesion of the uterus using a minimally invasive surgical approach, as opposed to emergency surgery via laparotomy. Capsule Large uterine leiomyoma with diffuse cystic degeneration in a patient with autosomal dominant polycystic kidney disease, in which step-wise treatments allows successful minimally invasive hysterectomy.

Cystoscopic Evaluation of Ureteral Jets: Alternatives to Indigo Carmine

A 54-year-old Korean woman was referred to my department because PETCT scan showed a hypermetabolic spot on the aortocaval area. She underwent radical abdominal hysterectomy with bilateral salpingooophorectomy, appendectomy, and bilateral pelvic lymphadenectomy followed by concurrent chemo-radiation because of pelvic lymph node metastasis and parametrial involvement in other hospital a few years ago. We performed laparoscopic excision of para-aortic metastatic lymph nodes on Jul 16, 2013. The final histopathological report showed that aortocaval lymph node was metastatic squamous cell carcinoma which greatest size was 2.6cm with extranodal extension. Six of all retrocaval lymph node was metastatic squamous cell carcinoma. After surgery, she received adjuvant chemotherapy and she is healthy without evidence of disease recurrence.