Laparoscopic sentinel lymph node mapping with indocyanine green in endometrial cancer: surgeon's learning curve (cumulative sum analysis).

OBJECTIVES: To evaluate surgeons' learning curves for laparoscopic sentinel lymph node biopsy in endometrial cancer. METHODS: A prospective observational study was performed at the Oncogynecology Center, Lithuanian University of Health Sciences Hospital, from March 2018 to October 2022. Participating surgeons had no previous experience of laparoscopic sentinel lymph node biopsy with indocyanine green tracer. Cumulative sum analysis was used to create learning curves for the performance of eight surgeons, based on a specific result over a time period. Two different cumulative sum plots were made for each surgeon: successful bilateral sentinel lymph node mapping and removal of sentinel lymph node specimens containing actual lymphatic tissue. RESULTS: 190 patients were included. The overall rate of sentinel lymph node mapping was 89.5%: successful bilateral mapping was achieved in 134 (70.5%) patients, while in 36 (19%) patients sentinel lymph nodes were mapped unilaterally. The bilateral detection rate significantly improved in later study periods (from 59.3% in the first year to 85.0% in the last year; p=0.03). Analysis of the performance of the surgeons for bilateral sentinel lymph node mapping showed that the cumulative sum plot crossed the H0 limit line after 13 consecutive successful bilateral sentinel lymph node biopsies, indicating an acceptable level of competence to achieve the bilateral detection rate of at least 75%. This was accomplished by only one surgeon after 30 surgeries. Analysis of the performance of the surgeons for identification and removal of specimens containing histologically confirmed lymphatic tissue showed that the cumulative sum plots crossed the H0 limit line after six consecutive successful sentinel lymph node removals. This was accomplished by most of the surgeons (5 of 8). CONCLUSION: At least 30 procedures of indocyanine green traced laparoscopic sentinel lymph node biopsy were needed to reach an acceptable level of competence for a bilateral sentinel lymph node detection rate of at least 75%. TRIAL REGISTRATION NUMBER: ACTRN12619000979156.

The Feasibility of Sentinel Lymph-Node, Mapped with Indocyanine Green, Biopsy in Endometrial Cancer Patients: A Prospective Study.

Background and objectives. Systematic pelvic lymphadenectomy (LND) is an essential part of lymph-node status evaluation in endometrial cancer (EC) patients to tailor the adjuvant treatment. However, it is associated with the post-operative lymphatic complications and does not improve the outcomes of the disease. Indocyanine green (ICG) mapped sentinel lymph-node biopsy (SLB) has recently been introduced into the clinical practice as an alternative for the surgical lymph-node evaluation in EC patients with the potential to decrease LND related complications. The aim of our study was to evaluate the feasibility of ICG mapped SLB in low, intermediate, and high-risk EC patients in a center with no previous experience on endoscopic SLB procedure. Materials and Methods: The prospective study was performed. 170 patients with histologically confirmed EC were included. Sentinel lymph-nodes (SLs) were mapped with ICG dye and removed ahead of the total laparoscopic hysterectomy. Low-risk patients received only SLB, while SLB and LND were performed for intermediate and high-risk patients. Results: The overall detection rate of SLs was 88.8%. Bilateral mapping was achieved in 68.2% of the patients. The overall detection rate for low-risk patients was 93.7%, 85.0% for the intermediate-risk group, and 100% for high-risk patients (p = 0.232). The most common anatomical sites of SLs were the external iliac (45.8% on the right and 46.6% on the left) and obturator regions (20.9% and 25.6%, respectively). Positive lymph-nodes were found in 8 (4.7%) patients. The sensitivity of SLB was 75.0% and negative predictive value (NPV)-97.2%. Conclusions: Even in the center with no previous experience, sentinel lymph-node biopsy using ICG mapping is feasible. However, the favorable outcomes might be associated with the learning process of newly established method.

Obstetric and intensive-care strategies in a high-risk pregnancy with critical respiratory failure due to COVID-19: A case report.

BACKGROUND: With the disease burden increasing daily, there is a lack of evidence regarding the impact of COVID-19 in pregnancy. Healthy pregnant women are still not regarded as a susceptible group despite physiological changes that make pregnant women more vulnerable to severe infection. However, high-risk pregnancies may be associated with severe COVID-19 disease with respiratory failure, as outlined in this report. We discuss the importance of timely delivery and antenatal steroid administration in a critically ill patient. CASE: A 27-year-old pregnant woman (gravida 2, para 1) with type I diabetes, morbid obesity, hypothyroidism and a previous Caesarean section presented with critical respiratory failure secondary to COVID-19 at 32 weeks of gestation. A preterm emergency Caesarean section was performed, after steroid treatment for foetal lung maturation. The patient benefited from prone positioning; however, transient acute renal injury, rhabdomyolysis and sepsis led to prolonged intensive care and mechanical ventilation for 30 days. The baby had an uncomplicated recovery. CONCLUSION: COVID-19 infection in high-risk pregnancies may result in severe maternal and neonatal outcomes such as critical respiratory failure requiring mechanical ventilation and premature termination of the pregnancy. Antenatal steroids may be of benefit for foetal lung maturation but should not delay delivery in severe cases.

Effects in postmenopausal women of estradiol and medroxyprogesterone alone and combined on resistance artery function and endothelial morphology and movement.

CONTEXT: Endothelial dysfunction in resistance arteries after menopause is important for the development of high blood pressure and cardiovascular disease. OBJECTIVES: Our objectives were to study the effects of different hormone replacement therapies on the function and morphology of isolated resistance arteries, and to look for their mechanistic basis. DESIGN AND SETTING: This was a randomized, placebo-controlled double-blind study in a University hospital, along with laboratory based studies. PATIENTS AND INTERVENTIONS: We isolated resistance arteries in sc biopsies from 55 postmenopausal women before and after 3-month therapy with estradiol (E2), medroxyprogesterone acetate (MPA), E2 plus MPA, or placebo. In addition, we studied isolated human endothelial cells. MAIN OUTCOME MEASURES AND RESULTS: Artery flow-mediated dilatation was augmented after treatment with E2 or E2 plus MPA, whereas MPA or placebo had no effect. Pressure-induced myogenic tone was reduced by E2 plus MPA, whereas it was unchanged in the other groups. Scanning microscopy showed that E2 improved endothelial cell morphology and decreased signs of endothelial apoptosis, but the addition of MPA impaired these events. E2, MPA, or the combination all increased the expression and phosphorylation of the actin-binding protein, moesin and of the focal adhesion complex controller, focal adhesion kinase, and induced the rearrangement of cytoskeletal actin and vinculin fibers. All treatments promoted endothelial cell horizontal migration, with E2 inducing the strongest effect. CONCLUSIONS: This study suggests that hormone replacement therapy with estrogens or in combination with MPA may benefit the function of resistance arteries and may preserve the morphological integrity of endothelial cells by regulatory actions on the cytoskeleton.

Comparison of adjuvant and neoadjuvant chemotherapy in the management of advanced ovarian cancer: a retrospective study of 574 patients.

BACKGROUND: There is a lack of clinical data on the validity of neoadjuvant chemotherapy in the treatment of ovarian cancer. The aim of this study was to compare the impact of the adjuvant and neoadjuvant chemotherapy regimens on the clinical outcomes in patients with advanced ovarian cancer. METHODS: We performed a retrospective analysis of 574 patients with advanced ovarian cancer admitted to four Lithuanian oncogynaecology departments during 1993-2000. The conventional combined treatment of cytoreductive surgery and platinum-based chemotherapy was applied to both the group that underwent neoadjuvant chemotherapy (n = 213) and to the control group (n = 361). The selection criterion for neoadjuvant chemotherapy was large extent of the disease. Overall and progression-free survival rates and survival medians were calculated using life tables and the Kaplan-Meier method. RESULTS: There was no difference in median overall survival between stage III patients treated with adjuvant chemotherapy and neoadjuvant chemotherapy (25.9 months vs. 29.3 months, p = 0.2508) and stage IV patients (15.4 months vs. 14.9 months, p = 0.6108). Similarly, there was no difference in median progression-free survival between stage III patients treated with adjuvant chemotherapy and neoadjuvant chemotherapy (15.7 months vs. 17.5 months, p = 0.1299) and stage IV patients (8.7 months vs. 8.2 months, p = 0.1817). There was no difference in the rate of the optimal cytoreductive surgery between patients who underwent the neoadjuvant chemotherapy and patients primarily treated with surgery (n = 134, 63% vs. n = 242, 67%, respectively). CONCLUSION: There was no difference in progression-free or overall survival and in the rate of optimal cytoreductive surgery between the neoadjuvant and adjuvant chemotherapy groups despite the fact that patients receiving neoadjuvant chemotherapy had a more extensive disease. Multivariate analysis failed to prove that neoadjuvant chemotherapy could be considered as an independent prognostic factor for survival, and the findings need to be investigated in the future prospective randomised studies.

Small artery endothelial dysfunction in postmenopausal women: in vitro function, morphology, and modification by estrogen and selective estrogen receptor modulators.

OBJECTIVE: Our objective was to assess vascular endothelial function and morphology in resistance vasculature from healthy pre- and postmenopausal women in vitro and to determine potential mechanisms of vascular protection by estrogenic compounds. METHODS: Arteries (approximately 220 microm) were dissected from sc fat biopsies obtained from healthy premenopausal and postmenopausal women. Flow-mediated dilatation, agonist-induced endothelium-dependent and -independent relaxation, and myogenic responses to changes in intraluminal pressure were evaluated before and after incubation (3 h) with 17beta-estradiol, propyl pyrazole triol [a selective estrogen receptor-alpha (ERalpha) agonist], raloxifene (a second-generation selective ER modulator), and the phytoestrogen genistein, using pressure myography technique. In addition, endothelial morphology was assessed in arteries from pre- and postmenopausal women, and distribution of ERs within the artery wall from postmenopausal women was evaluated. RESULTS: Functional and morphological disturbances of endothelial function were observed in small arteries from postmenopausal women. Incubation with 17beta-estradiol improved postmenopausal resistance artery function, an effect mimicked by propyl pyrazole triol but not raloxifene or genistein. Immunohistochemical staining revealed similar expression of ERalpha and ERbeta in the smooth muscle of arteries from postmenopausal women; however, ERalpha was dominant in endothelium. CONCLUSIONS: The resistance arteries from postmenopausal women show functional and morphological abnormalities. ERalpha may contribute to vascular protection by estrogens in the peripheral resistance circulation in postmenopausal women. Selective ERalpha agonists warrant further investigation as therapeutic agents for prevention of cardiovascular disease in postmenopausal women.

Vascular endothelial growth factor induced functional and morphologic signs of endothelial dysfunction in isolated arteries from normal pregnant women.

OBJECTIVE: The purpose of this study was to determine the effects of vascular endothelial growth factor on basal tone, endothelium-dependent dilatation, permeability, and morphologic features of endothelium in isolated arteries from normal pregnant women. We hypothesized that vascular endothelial growth factor might induce signs of endothelial dysfunction. STUDY DESIGN: Arteries (approximately 200 microm) were dissected from subcutaneous fat biopsy specimens that were obtained at cesarean delivery and mounted on a pressure arteriograph. Changes in basal tone, dilatation to bradykinin (1 nmol/L to 3 micromol/L) before, during, and after 3 hours of incubation with vascular endothelial growth factor (0.5 or 1 nmol/L), vascular endothelial growth factor (0.5 nmol/L) plus bosentan (a nonselective endothelin receptor A and B antagonist, 1 micromol/L), or vehicle were compared. Scanning electron microscopy was applied for endothelial morphologic features. Permeability to Evans blue dye was evaluated in arteries after incubation with vascular endothelial growth factor, vascular endothelial growth factor plus angiopoietin-1, or vehicle, and in arteries that were obtained from women with preeclampsia. RESULTS: Basal tone was higher after 60 minutes of incubation with vascular endothelial growth factor (0.5 nmol/L) compared with vehicle (29% +/- 5% [n = 10] vs 10% +/- 4% [n = 7], P =.006). Combination of vascular endothelial growth factor with bosentan failed to increase the tone (n = 4). Bradykinin-mediated dilatation was impaired in arteries that were incubated with vascular endothelial growth factor 0.5 nmol/L (max dilatation: 287% +/- 16% vs 160% +/- 23% [n = 10], P =.0001) or vascular endothelial growth factor 1 nmol/L (max dilatation: 207% +/- 21% vs 88% +/- 4% [n = 3], P =.003). Bradykinin-mediated dilatation was similar after incubation with vehicle (n = 7) or the combination of vascular endothelial growth factor plus bosentan (n = 4). Evans blue dye staining was higher after incubation with vascular endothelial growth factor but was reversed by the addition of angiopoietin-1. Scanning electron microscopy demonstrated the development of intercellular gaps. CONCLUSION: Vascular endothelial growth factor impaired bradykinin-mediated dilatation and enhanced basal tone and permeability. This might indicate a potential role for vascular endothelial growth factor in the development of endothelial dysfunction in pregnancy. Angiopoietin-1 inhibited the vascular endothelial growth factor-induced vascular leakage, which may have therapeutic implications in preeclampsia.

Endothelial dysfunction in uterine circulation in preeclampsia: can estrogens improve it?

OBJECTIVE: The purpose of this study was to evaluate whether a 3-hour incubation with 17beta-estradiol will enhance blood flow- and bradykinin-mediated dilatation and alter pressure-induced basal tone in myometrial resistance arteries from women with preeclampsia and to evaluate the role of nitric oxide in the responses that were observed. STUDY DESIGN: Blood flow- and bradykinin-mediated dilatation and responses to intraluminal pressure of 60 and 80 mm Hg were compared before and after 3 hours of incubation with 17beta-estradiol (10(-8) mol/L) in isolated myometrial arteries with the pressure myography technique. In separate experiments, the role of nitric oxide on 17beta-estradiol-induced responses was evaluated in the presence of the nitric oxide synthase inhibitor (10(-4) mol/L). Endothelial morphologic condition was evaluated by scanning electron microscopy. RESULTS: Incubation with 17beta-estradiol significantly improved blood flow-mediated dilatation compared with initial blood flow-mediated response in arteries from women with preeclampsia. This effect was nitric oxide mediated, because the nitric oxide synthase inhibitor abolished the response. Arteries from women with preeclampsia demonstrated impaired bradykinin-mediated dilatation compared with that obtained in arteries from normal pregnant women. The 17beta-estradiol had no effect on bradykinin-mediated dilatation in arteries from women with preeclampsia. The enhanced pressure-induced tone at 80 mm Hg compared with the tone that developed at 60 mm Hg in arteries from women with preeclampsia was reduced after incubation with 17beta-estradiol. This reduction was also nitric oxide mediated. Morphologic signs of endothelial dysfunction were evident in arteries from women with preeclampsia. CONCLUSION: The 17beta-estradiol improved impaired blood flow-mediated dilatation and reduced basal tone through a nitric oxide-mediated pathway in isolated myometrial arteries from women with preeclampsia.

Isolated microparticles, but not whole plasma, from women with preeclampsia impair endothelium-dependent relaxation in isolated myometrial arteries from healthy pregnant women.

OBJECTIVE: This study was performed to establish whether microparticles from plasma of women with preeclampsia cause endothelial dysfunction, as described for isolated myometrial arteries in preeclampsia. STUDY DESIGN: Myometrial arteries were isolated from biopsy specimens obtained at cesarean delivery from healthy pregnant women (n = 22) and mounted in a wire myograph. Bradykinin concentration-response curves were obtained before and after 1-hour incubation or after overnight incubation with one of the following preparations of plasma from individual women with preeclampsia (n = 16): Whole plasma, microparticle-free plasma, isolated microparticles resuspended in physiologic saline solution or physiologic saline solution. Overnight incubation was also performed with microparticles isolated from healthy pregnant women (n = 6). One-hour incubation was performed with 2% or 10% solution and overnight incubation with 5% solution. RESULTS: No effect of preeclamptic plasma, with or without microparticles, on bradykinin-mediated relaxation was observed. Overnight, but not 1-hour, incubation with preeclamptic microparticles caused abolishment of bradykinin-mediated relaxation in contrast to healthy pregnant microparticles (P <.005). CONCLUSION: Preeclamptic microparticles, but not healthy pregnant microparticles cause endothelial dysfunction in isolated myometrial arteries from healthy pregnant women after overnight incubation, whereas other preeclamptic plasma constituents protect the endothelium from this effect.