Review of sustainable practices for the gynecology operating room.

PURPOSE OF REVIEW: Climate change has immediate impacts on women's health. Hospitals and operating rooms are large contributors to greenhouse gas (GHG) emissions and waste. This article will review current green initiatives designed to minimize environmental impact in the operating room and highlight areas for future improvement. RECENT FINDINGS: From a materials perspective, reusable goods result in less GHG emissions while being just as efficacious, well tolerated, and easy to use. Materials should be opened judiciously, only as necessary. Processing regulated medical waste produces greater GHG emissions, so waste should be properly sorted, and items which are not biohazard waste should be processed separately. Choosing appropriate anesthesia and utilizing an 'off' setting, in which operating rooms are shut down when not in use, can also drastically decrease the environmental impact of surgery. Further research is needed to determine effective implementation in hospitals. SUMMARY: This article summarizes current attempts to make operating rooms more sustainable. Many practices result in a decreased carbon footprint and cost savings without adversely affecting patient outcomes. Gynecologic surgeons and the hospitals in which they practice need to focus on implementing these changes in a timely fashion.

Retrieval of Intra-abdominal Fetal Scalp Electrode 4 Years After Cesarean Birth.

BACKGROUND: Fetal scalp electrodes are used routinely for intrapartum fetal heart rate monitoring. The electrode is typically removed from the newborn's scalp immediately after vaginal delivery. However, there is no guidance on the timing of fetal scalp electrode removal in the event of an unplanned cesarean delivery. CASE: A 43-year-old woman with a prior cesarean delivery presented for gynecologic care with the chief symptom of chronic abdominal pain for 2 years. Imaging revealed a retained fetal scalp electrode in the abdominal cavity. The patient underwent an uncomplicated surgical extraction of the retained item, and her symptoms resolved. CONCLUSION: A standardized protocol to manage and account for fetal scalp electrodes during an unplanned cesarean delivery is an important patient-safety measure to prevent surgical retention of fetal scalp electrodes.

Factors that Lengthen Patient Hospitalizations Following Laparoscopic Hysterectomy.

OBJECTIVE: To establish descriptive observations associated with prolonged hospitalization after laparoscopic hysterectomy prior to the implementation of a department-wide Enhanced Recovery After Surgery protocol. METHODS: A retrospective cohort study at three academic affiliated hospitals in the southeastern United States was conducted evaluating length of hospitalization by patient, surgical, and physician factors for 384 patients who underwent total laparoscopic hysterectomy, laparoscopic assisted vaginal hysterectomy, and robotic assisted total laparoscopic hysterectomy for benign conditions by general and subspecialized gynecologists from 2010 to 2015. RESULTS: Among 384 patients, 19.5% experienced prolonged hospitalization, defined as greater than one day. After adjusting for covariates, robotic assisted total laparoscopic hysterectomy (aOR 3.13), dietary restrictions on postoperative day 1 (aOR 4.42), postoperative nausea or vomiting (aOR 2.01), and postoperative complications (aOR 3.58) were associated with prolonged hospitalization. CONCLUSION: Data from this study were collected prior to implementation of department-wide enhanced recovery after surgery protocols and highlights areas for improvement. Implementation of specific aspects of these protocols, including aggressive prevention of postoperative nausea and vomiting and early feeding, are easily made changes which may help to effectively decrease length of stay after laparoscopic hysterectomy. Patient and provider education on enhanced recovery protocols is also key to reducing length of stay.

Laser Angiography to Assess the Vaginal Cuff During Robotic Hysterectomy.

BACKGROUND AND OBJECTIVES: Vaginal cuff dehiscence may be a vascular-mediated event, and reports show a higher incidence after robot-assisted total laparoscopic hysterectomy (RATLH), when compared with other surgical routes. This study was conducted to determine the feasibility of using laser angiography to assess vaginal cuff perfusion during RATLH. METHODS: This was a pilot feasibility trial incorporating 20 women who underwent RATLH for benign disease. Colpotomy was made with ultrasonic or monopolar instruments, whereas barbed or nonbarbed suture was used for cuff closure. Time of instrument activation during colpotomy was recorded. Images were captured of vaginal cuff perfusion before and after cuff closure. Reviewers evaluated these images and determined areas of adequate cuff perfusion. RESULTS: Indocyanine green (ICG) was visible at the vaginal cuff in all participants. Optimal dosage was determined to be 7.5 mg of ICG per intravenous dose. Mean time to appearance for ICG was 18.4 ± 7.3 s (mean ± SD) before closure and 19.0 ± 8.7 s after closure. No significant difference (P = .19) was noted in judged perfusion in open cuffs after colpotomy with a monopolar (48.9 ± 26.0%; mean ± SD) or ultrasonic (40.2 ± 14.1%) device. No difference was seen after cuff closure (P = .36) when a monopolar (70.9 ± 21.1%) or ultrasonic (70.5 ± 20.5%) device was used. The use of barbed (74.1 ± 20.1%) or nonbarbed (66.4 ± 20.9%) sutures did not significantly affect estimated closed cuff perfusion (P = .19). Decreased cuff perfusion was observed with longer instrument activation times in open cuffs (R2 = 0.3175). CONCLUSION: Laser angiography during RATLH allows visualization of vascular perfusion of the vaginal cuff. The technology remains limited by the lack of quantifiable fluorescence and knowledge of clinically significant levels of fluorescence.

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.

Sterility of Selected Operative Sites During Total Laparoscopic Hysterectomy.

STUDY OBJECTIVE: To describe the type and quantity of bacteria found intraoperatively on the abdomen, vagina, surgical gloves, instrument tips, and uterus at distinct time points during total laparoscopic hysterectomy (TLH). DESIGN: Observational study (Canadian Task Force classification III). SETTING: Academic affiliated hospital. PATIENTS: Thirty-one women undergoing TLH for benign indications in 2016. INTERVENTIONS: After antibiotic prophylaxis and chlorhexidine preparation, swabs were collected from the vaginal fornices and abdomen. During subsequent TLH, additional swabs were collected from the following sites: surgeon's gloves after placement of the uterine manipulator, tips of instruments used to close the vaginal cuff, uterine fundus after extraction, and surgeon's gloves after removal of the uterus. A calibrated loop was used to inoculate each specimen onto 5% blood and chocolate agars for growth of aerobes and onto Brucella blood, phenylethyl alcohol, kanamycin vancomycin, and Bacteroides bile esculin agars for growth of anaerobes. Manual colony counts were tabulated for all positive cultures and reported in colony-forming units per milliliter (CFU/mL). MEASUREMENTS AND MAIN RESULTS: Anaerobic growth was not seen on the instrument tips, in the vagina, or on the abdomen of any patient. Aerobic bacterial growth was not seen in the vagina of any patient. On the surgeon's gloves after uterine manipulator placement, no patients demonstrated sufficient bacterial growth to potentially cause surgical site infection (≥5000 CFU/mL). On the surgeon's gloves following uterine extraction, 1 patient demonstrated sufficient growth to potentially cause infection. None of the patients developed surgical site infections postoperatively. CONCLUSION: Cultures from multiple operative sites yielded bacterial growth, but the bacterial concentrations did not exceed the threshold for infection in 98.9% of cultures. Given absent growth from vaginal cultures and rare growth from abdominal cultures, chlorhexidine gluconate 4% is considered an appropriate surgical preparation for use in laparoscopic hysterectomy.

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.

Laser Angiography with Indocyanine Green to Assess Vaginal Cuff Perfusion during Total Laparoscopic Hysterectomy: A Pilot Study.

STUDY OBJECTIVE: To determine feasibility of using laser angiography with indocyanine green (ICG) to assess vaginal cuff vascular perfusion during total laparoscopic hysterectomy (TLH). DESIGN: Pilot feasibility trial (Canadian Task Force classification II-2). SETTING: Academic-affiliated hospital. PATIENTS: Twenty women undergoing TLH for benign disease. INTERVENTIONS: Participants underwent 1:1 randomization of energy method used for colpotomy (ultrasonic vs monopolar) and vaginal cuff closure suture (barbed vs nonbarbed). After intravenous administration of ICG, laser angiography was used to capture images of the vaginal cuff before and after closure. Three reviewers analyzed fluorescent images of vaginal cuffs to determine percent of cuff perimeter with adequate perfusion when open and length of vaginal cuff adequately perfused when closed. MEASUREMENTS AND MAIN RESULTS: ICG fluorescence was visible at the vaginal cuff in all participants. Mean time to appearance of ICG in the pelvis after administration was 19.8 ± 6.8 seconds (mean ± SD) preclosure, and 26.0 ± 22.2 seconds postclosure. With ultrasonic energy 67.5% ± 17.4% of open cuff perimeter and 74.4% ± 20.5% of closed cuff length were adequately perfused, whereas with monopolar energy use 59.1% ± 17.4% of the open cuff perimeter and 66.3% ± 15.4% of closed cuff length were adequately perfused. Cuffs closed with barbed suture showed adequate perfusion along 71.5% ± 15.1% of the length, whereas those closed with nonbarbed suture showed 68.9% ± 20.9% adequate perfusion. When normalized to cervical cup circumference, ultrasonic energy required 1.0 ± .2 s/mm, whereas monopolar energy required .8 ± .3 s/mm (p = .162). Linear regression showed no association of normalized time of energy activation to percentage of perimeter of open cuff (R2 = .007) or length of closed cuff (R2 = .005) with adequate perfusion. No complications related to intravenous ICG administration occurred. CONCLUSION: Laser angiography with ICG allows evaluation of vascular perfusion at the vaginal cuff during TLH. This technique may facilitate future prospective studies examining causes for vaginal cuff dehiscence, a complication with potential for severe morbidity.

Correlation between CYP1A1 transcript, protein level, enzyme activity and DNA adduct formation in normal human mammary epithelial cell strains exposed to benzo[a]pyrene.

The polycyclic aromatic hydrocarbon (PAH) benzo(a)pyrene (BP) is thought to bind covalently to DNA, through metabolism by cytochrome P450 1A1 (CYP1A1) and CYP1B1, and other enzymes, to form r7, t8, t9-trihydroxy-c-10-(N(2)-deoxyguanosyl)-7,8,9,10-tetrahydro-benzo[a]-pyrene (BPdG). Evaluation of RNA expression data, to understand the contribution of different metabolic enzymes to BPdG formation, is typically presented as fold-change observed upon BP exposure, leaving the actual number of RNA transcripts unknown. Here, we have quantified RNA copies/ng cDNA (RNA cpn) for CYP1A1 and CYP1B1, as well as NAD(P)H: quinone oxidoreductase 1 (NQO1), which may reduce formation of BPdG adducts, using primary normal human mammary epithelial cell (NHMEC) strains, and the MCF-7 breast cancer cell line. In unexposed NHMECs, basal RNA cpn values were 58-836 for CYP1A1, 336-5587 for CYP1B1 and 5943-40112 for NQO1. In cells exposed to 4.0 µM BP for 12h, RNA cpn values were 251-13234 for CYP1A1, 4133-57078 for CYP1B1 and 4456-55887 for NQO1. There were 3.5 (mean, range 0.2-15.8) BPdG adducts/10(8) nucleotides in the NHMECs (n = 16), and 790 in the MCF-7s. In the NHMECs, BP-induced CYP1A1 RNA cpn was highly associated with BPdG (P = 0.002), but CYP1B1 and NQO1 were not. Western blots of four NHMEC strains, chosen for different levels of BPdG adducts, showed a linear correlation between BPdG and CYP1A1, but not CYP1B1 or NQO1. Ethoxyresorufin-O-deethylase (EROD) activity, which measures CYP1A1 and CYP1B1 together, correlated with BPdG, but NQO1 activity did not. Despite more numerous levels of CYP1B1 and NQO1 RNA cpn in unexposed and BP-exposed NHMECs and MCF-7cells, BPdG formation was only correlated with induction of CYP1A1 RNA cpn. The higher level of BPdG in MCF-7 cells, compared to NHMECs, may have been due to a much increased induction of CYP1A1 and EROD. Overall, BPdG correlation was observed with CYP1A1 protein and CYP1A1/1B1 enzyme activity, but not with CYP1B1 or NQO1 protein, or NQO1 enzyme activity.

Progressive mitochondrial compromise in brains and livers of primates exposed in utero to nucleoside reverse transcriptase inhibitors (NRTIs).

Mitochondrial compromise has been documented in infants born to women infected with the human immunodeficiency virus (HIV-1) who received nucleoside reverse transcriptase inhibitor (NRTI) therapy during pregnancy. To model these human exposures, we examined mitochondrial integrity at birth and 1 year in brain cortex and liver from offspring of retroviral-free Erythrocebus patas dams-administered human-equivalent NRTI doses for the last half (10 weeks) of gestation. Additional infants, followed for 1 year, were given the same drugs as their mothers for the first 6 weeks of life. Exposures included: no drug, Zidovudine (AZT), Lamivudine (3TC), AZT/3TC, AZT/Didanosine (ddI), and Stavudine (d4T)/3TC. In brain and liver, oxidative phosphorylation (OXPHOS) enzyme activities (complexes I, II, and IV) showed minimal differences between unexposed and NRTI-exposed offspring at both times. Brain and liver mitochondria from most NRTI-exposed patas, both at birth and 1 year of age, contained significant (p < 0.05) morphological damage observed by electron microscopy (EM), based on scoring of coded photomicrographs. Brain and liver mitochondrial DNA (mtDNA) levels in NRTI-exposed patas were depleted significantly in the 3TC and d4T/3TC groups at birth and were depleted significantly (p < 0.05) at 1 year in all NRTI-exposed groups. In 1-year-old infants exposed in utero to NRTIs, mtDNA depletion was 28.8-51.8% in brain and 37.4-56.5% in liver. These investigations suggest that some NRTI-exposed human infants may sustain similar mitochondrial compromise in brain and liver and should be followed long term for cognitive integrity and liver function.

Metabolism and pharmacokinetics of the combination Zidovudine plus Lamivudine in the adult Erythrocebus patas monkey determined by liquid chromatography-tandem mass spectrometric analysis.

Because of their similarity to humans, non-human primates constitute useful preclinical models in which to examine potential human drug toxicities. Antiretroviral nucleoside reverse transcriptase inhibitor (NRTI) toxicity is currently under investigation in Erythrocebus patas monkeys, and whereas NRTI pharmacokinetics have been studied in other monkey species, pharmacokinetics for Zidovudine plus Lamivudine (AZT/3TC) dosing have not been reported in the patas. Here we present 24 h serum pharmacokinetic parameters after a single oral exposure to the combination of AZT (40 mg) and 3TC (24 mg), doses equivalent to a human daily dose of Combivir. The patas (n=3) AZT/3TC pharmacokinetic profiles were similar to those seen in other primate species. Average maximum serum concentrations (Cmax) for AZT and 3TC were 2.35 and 2.65 microg/ml, respectively, and were observed at 0.83 h (Tmax). Cmax was 13.34 microg/ml for the AZT-glucuronide (AZT-G) and was 0.023 microg/ml for the potentially toxic minor metabolite 3'-amino-3'-deoxythymidine (AMT), both occurring at about 1 h after dosing. Similar elimination half-times, 0.70 and 0.68 h(-1), were found for AZT and AZT-G, respectively, while 3TC was eliminated about half as fast (0.33 h(-1)) resulting in AUC(0-infinity) values of 6.97 microg/ml h for 3TC, 2.99 microg/ml h for AZT, 20.5 microg/ml h for AZT-G and 0.002 for AMT 6.97 microg/ml h. This study shows similar metabolism and pharmacokinetics for oral administration of AZT/3TC in the adult patas monkey, other primate species and humans. The data validate the use of the patas monkey for studies of NRTI toxicity.

Erythrocebus patas monkey offspring exposed perinatally to NRTIs sustain skeletal muscle mitochondrial compromise at birth and at 1 year of age.

Antiretroviral nucleoside reverse transcriptase inhibitors (NRTIs), given to human immunodeficiency virus-1-infected pregnant women to prevent vertical viral transmission, have caused mitochondrial dysfunction in some human infants. Here, we examined mitochondrial integrity in skeletal muscle from offspring of pregnant retroviral-free Erythrocebus patas dams administered human-equivalent NRTI doses for the last 10 weeks of gestation or for 10 weeks of gestation and 6 weeks after birth. Exposures included no drug, Zidovudine (AZT), Lamivudine (3TC), AZT/3TC, AZT/Didanosine (ddI), and Stavudine (d4T)/3TC. Offspring were examined at birth (n=3 per group) and 1 year (n=4 per group, not including 3TC alone). Circulating levels of creatine kinase were elevated at 1 year in the d4T/3TC-exposed group. Measurement of oxidative phosphorylation enzyme activities (complexes I, II, and IV) revealed minimal NRTI-induced changes at birth and at 1 year. Histochemistry for complex IV activity showed abnormal staining with activity depletion at birth and 1 year in groups exposed to AZT alone and to the 2-NRTI combinations. Electron microscopy of skeletal muscle at birth and 1 year of age showed mild to severe mitochondrial damage in all the NRTI-exposed groups, with 3TC inducing mild damage and the 2-NRTI combinations inducing extensive damage. At birth, mitochondrial DNA (mtDNA) was depleted by approximately 50% in groups exposed to AZT alone and the 2-NRTI combinations. At 1 year, the mtDNA levels had increased but remained significantly below normal. Therefore, skeletal muscle mitochondrial compromise occurs at birth and persists at 1 year of age (46 weeks after the last NRTI exposure) in perinatally exposed young monkeys, suggesting that similar events may occur in NRTI-exposed human infants.

Morphological and molecular course of mitochondrial pathology in cultured human cells exposed long-term to Zidovudine.

Long-term use of antiretroviral nucleoside reverse transcriptase inhibitors (NRTIs) as therapy for human immunodeficiency virus-1 (HIV-1) infection is limited by mitochondrial toxicity. Here we document mitochondrial pathology during the long-term culture of human HeLa cells in the presence or absence of the NRTI Zidovudine(R) (AZT, 800 muM) for up to 77-passages (p), with samples taken at early (p5-p11), middle (p36 and p37), and late (p70-p77) passages. Samples were analyzed for changes in mitochondrial morphology, mitochondrial (mt)DNA quantity, nuclear and mitochondrial gene expression, and mitochondrial membrane potential. Mitochondria showed abnormal proliferation at p5 and abnormal morphology >/=p36. mtDNA quantity was increased at p5 and p11, and 65% depleted at p71. Hierarchical clustering of nuclear gene expression, examined at p37 by the NCI cDNA microarray in AZT-exposed cells, showed down-regulation of 13 out of 16 lipid-metabolizing genes, and up-regulation of most oxidative phosphorylation (OXPHOS) genes. OXPHOS genes encoded by mtDNA, examined at p5, p36, and p75 using the Mitochondrial Gene Mini Array, revealed up-regulation of genes coding for polypeptides of NADH dehydrogenase, ATP synthase, and cytochrome c oxidase. Mitochondrial membrane potential, monitored by JC1 staining, was elevated at p10 and p32, and essentially completely absent at p71. The data show that during chronic exposure of HeLa cells to AZT, a compensatory response was induced at the earlier passages (p5-p37), and by p71 there was widespread mitochondrial morphological damage, severe mtDNA depletion, and a substantial loss of mitochondrial membrane potential.