Most endometrial cancers are detected early and have a good prognosis, while some endometrial cancers are highly invasive, metastasize early, and respond suboptimally to therapy. Currently, ...appropriate model systems to study the aggressive nature of these tumors are lacking. The objective of this study was to establish a mouse xenograft model of endometrial tumors derived from patients in order to study the biological aggressive characteristics that underlie invasion and metastasis.
Endometrial tumor tissue fragments (1.5 mm × 1.5 mm) from patients undergoing surgery, were transplanted under the renal capsule of NOD scid gamma mice. After 6-8 weeks, tumors were excised and serially transplanted into additional mice for propagation. Immunohistochemical analysis of the tumors was done for various tumor markers.
Four cases of different subtypes of endometrial cancer were grown and propagated in mice. Three of the four tumor cases invaded into the kidneys and to adjacent organs. While all tumors exhibited minimal to no staining for estrogen receptor α, progesterone receptor staining was observed for tumor grafts. In addition, levels and localization of E-cadherin, cytokeratin and vimentin varied depending on subtype. Finally, all tumor xenografts stained positively for urokinase plasminogen activator while 3 tumor xenografts, which showed invasive characteristics, stained positively for urokinase plasminogen activator receptor.
Endometrial tumors transplanted under the renal capsule exhibit growth, invasion and local spread. These tumors can be propagated and used to study aggressive endometrial cancer.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • At high hCG levels in molar pregnancies, a “hook effect” can cause an artificially negative value. • Delay in diagnosis of a molar pregnancy due to the “hook effect” can lead to severe ...complications. • Suspicion of a molar pregnancy should be communicated so a diluted sample is used to quantify hCG.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Regional recurrence of endometrial cancer is a challenging yet potentially curable group of patients without defined standard of care. Our aim is to determine optimal methods of salvage therapy for ...regionally recurrent endometrial cancer.
Twenty-two cases of nodal, pelvic, or peritoneal cavity recurrences of endometrial cancer were identified from a single institution database. Univariable Cox proportional hazards models were used to estimate the risk of a second recurrence or death. Kaplan-Meier plots were used to estimate the probability of progression free survival and overall survival among patients in three cohorts: Multimodality therapy (surgery, chemotherapy, and external beam radiotherapy EBRT +/− vaginal brachytherapy), non-surgery (chemotherapy or EBRT, or both), and surgery cohort (surgery +/− chemotherapy OR EBRT).
Thirteen recurrences (59%) were regional including the pelvic and paraaortic nodes, while nine recurrences (41%) were abdominal. For the entire cohort, the probability of progression free survival at 2 years was 51% (95% CI, 26% - 72%). The 2-year probability of progression free survival was 62% in the multimodality cohort, 40% in the non-surgery cohort, and 38% in the surgery cohort. The 2-year probability of overall survival was 69% (95% CI, 38% - 86%) across our population. At 40 months of follow up, the only living patients belonged to the multimodality cohort.
We found no significant association of a definitive salvage regimen for recurrent endometrial cancer of the pelvis and peritoneal cavity. Aggressive use of multimodality therapy with surgery followed by tumor-directed radiotherapy and chemotherapy offers potentially curative therapy for these patients.
•Multimodality therapy results in fewer recurrences (31%) than surgery alone (50%) or non-surgery regimens (60%).•Multimodality therapy offers favorable progression free survival with 62% of patients disease free at 24 months.•Multimodality therapy can result in cure in patients with isolated recurrences to the pelvis and peritoneal cavity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUND:More than 50% of obstetric patients with sickle cell disease will have a pain crisis during pregnancy, and the management of these cases can be challenging.
CASE:A 20-year-old African ...American with sickle cell disease presented at 29 4/7 weeks of gestation with severe, debilitating leg and back pain. Large doses of intravenous narcotics did not result in significant pain relief, so a lumbar epidural was placed. This resulted in complete pain relief within several minutes. The patientʼs symptoms resolved over several days and after a short course of narcotics she was discharged to home, and the remainder of her pregnancy was uncomplicated.
CONCLUSION:Epidural anesthesia should be considered as a potentially effective treatment for a severe sickle cell crisis in obstetric patients.
Epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and heregulin-beta1 (HRG-beta1), can modulate the expression and activity of the estrogen receptor-alpha (ER-alpha) via the ...phosphatidylinositol 3-kinase (PI 3-K)/Akt pathway in the ER-alpha-positive breast cancer cell line, MCF-7. Estradiol can also rapidly activate PI 3-K/Akt in these cells (nongenomic effect). The recent study examines whether Akt is involved in the ER-alpha regulation by estradiol (genomic effect). Stable transfection of parental MCF-7 cells with a dominant-negative Akt mutant, as well as the PI 3-K inhibitors wortmannin and LY 294,002, blocked the effect of estradiol on ER-alpha expression and activity by 70-80 and 55-63%, respectively. Stable transfection of MCF-7 cells with a constitutively active Akt mimicked the effect of estradiol. The changes in ER-alpha expression and activity were abrogated in response to estradiol by an arginine to cysteine mutation in the pleckstrin homology (PH) domain of Akt (R25C), suggesting the involvement of this amino acid in the interaction between Akt and ER-alpha. Experiments employing selective ErbB inhibitors demonstrate that the effect of estradiol on ER-alpha expression and activity is mediated by ErbB2 and not by EGFR. Moreover, anchorage-dependent and -independent growth assays, cell cycle and membrane ruffling analyses showed that Akt exerts estrogen-like activity on cell growth and membrane ruffling and that a selective ErbB2 inhibitor, but not anti-ErbB2 antibodies directed to the extracellular domain, can block these effects. In the presence of constitutively active Akt, tamoxifen only partially inhibits cell growth. In contrast, in cells stably transfected with either a dominant-negative Akt or with R25C-Akt, as well as in parental cells in the presence of a selective ErbB2 inhibitor, the effect of estradiol on anchorage-dependent and -independent cell growth was inhibited by 50-75 and 100%, respectively. Dominant-negative Akt inhibited membrane ruffling by 54%; however, R25C-Akt did not have any effect, suggesting that kinase activity plays an important role in this process. Scatchard analysis demonstrated a 67% reduction in estrogen-binding capacity in cells transfected with constitutively active Akt. No change in binding affinity of estradiol to the receptor was observed upon transfection with either Akt mutant. Taken together, our results suggest that estradiol treatment results in binding to membrane ER-alpha and interaction with a heterodimer containing ErbB2, leading to tyrosine phosphorylation. This results in the activation of PI 3-K and Akt. Akt, in turn, may interact with nuclear ER-alpha, altering its expression and activity.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Our objectives were to compare the utility of learning a suturing task on the virtual reality da Vinci Skills Simulator versus the da Vinci Surgical System dry laboratory platform and to assess user ...satisfaction among novice robotic surgeons.
Medical trainees were enrolled prospectively; one group trained on the virtual reality simulator, and the other group trained on the da Vinci dry laboratory platform. Trainees received pretesting and post-testing on the dry laboratory platform. Participants then completed an anonymous online user experience and satisfaction survey.
We enrolled 20 participants. Mean pretest completion times did not significantly differ between the 2 groups. Training with either platform was associated with a similar decrease in mean time to completion (simulator platform group, 64.9 seconds P = .04; dry laboratory platform group, 63.9 seconds P < .01). Most participants (58%) preferred the virtual reality platform. The majority found the training "definitely useful" in improving robotic surgical skills (mean, 4.6) and would attend future training sessions (mean, 4.5).
Training on the virtual reality robotic simulator or the dry laboratory robotic surgery platform resulted in significant improvements in time to completion and economy of motion for novice robotic surgeons. Although there was a perception that both simulators improved performance, there was a preference for the virtual reality simulator. Benefits unique to the simulator platform include autonomy of use, computerized performance feedback, and ease of setup. These features may facilitate more efficient and sophisticated simulation training above that of the conventional dry laboratory platform, without loss of efficacy.
Review Objective: To review the recent developments and published
literature on laparoendoscopic single-site (LESS) surgery in
gynaecology. Recent Findings: Minimally invasive surgery has become a
...standard of care for the treatment of many benign and malignant
gynaecological conditions. Recent advances in conventional laparoscopy
and robotic-assisted surgery have favorably impacted the entire
spectrum of gynaecological surgery. With the goal of improving
morbidity and cosmesis, continued efforts towards refinement of
laparoscopic techniques have lead to minimization of size and number of
ports required for these procedures. LESS surgery is a recently
proposed surgical term used to describe various techniques that aim at
performing laparoscopic surgery through a single, small-skin incision
concealed within the umbilicus. In the last 5 years, there has been a
surge in the developments in surgical technology and techniques for
LESS surgery, which have resulted in a significant increase in
utilisation of LESS across many surgical subspecialties. Recently
published outcomes data demonstrate feasibility, safety and
reproducibility for LESS in gynaecology. The contemporary LESS
literature, extent of gynaecological procedures utilising these
techniques and limitations of current technology will be reviewed in
this manuscript. Conclusions: LESS surgery represents the newest
frontier in minimally invasive surgery. Comparative data and
prospective trials are necessary in order to determine the clinical
impact of LESS in treatment of gynaecological conditions.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To determine whether the epidermal growth factor receptor 2 (ErbB2) and Akt1 can alter the in vivo growth of MCF-7 cells, parental cells or cells stably transfected with constitutively active Akt1 ...(myr-Akt1) or dominant-negative Akt1 mutants (K179M-Akt1 and R25C-Akt1) were implanted into athymic nude mice. Tumor growth was monitored in the presence or absence of the antiestrogen tamoxifen and the selective ErbB2 inhibitor, AG825. MCF-7 parental or empty vector transfected, cytomegalovirus (CMV) and myr-Akt1 cells formed tumors upon estradiol supplementation after 20–30 d (59-, 29-, and 17-fold increase in tumor volume, respectively). Tamoxifen and AG825 blocked the estradiol effect by 93 and 96% in MCF-7 xenografts, 88 and 81% in CMV xenografts, and 91% in myr-Akt1 xenografts. Furthermore, AG825 suppressed the growth of established tumors in CMV and myr-Akt1 inoculated animals by 68 and 75%, respectively, as compared with continued estrogen supplementation, suggesting a role for ErbB2. When K179M-Akt1 or R25C-Akt1 cells were injected into ovariectomized animals, tumor growth was reduced upon estradiol treatment by 95% and 98%, respectively, supporting a role for Akt1. In contrast to ovariectomized animals, in intact animals, myr-Akt1 cells could establish tumors without estradiol priming after 40–50 d (20-fold increase in tumor volume). Loss of Akt1 phosphorylation was associated with tumor growth inhibition. Immunohistochemical assays showed that in tumors from parental and CMV xenografts, estradiol decreased estrogen receptor-α expression and induced progesterone receptor expression and Akt phosphorylation, effects that were inhibited by tamoxifen, AG825, and R25C-Akt1 by 89, 82, and 77% for progesterone receptor expression and 48, 66, and 73% for pAkt expression, respectively. Cumulatively, our results suggest that Akt1 and ErbB2 are involved in in vivo tumorigenesis and modulation of estrogen receptor-α expression and activity.
Objective:
Here we present a pilot study investigating the prevalence of pelvic floor myofascial pain in patients presenting to an academic tertiary care gynecologic oncology clinic. We describe ...patients’ responses to a pain survey including the pain disability index.
Methods:
An IRB approved prospective survey and chart review was conducted. Patients underwent standard physical exam maneuvers for detection of pelvic floor myofascial pain. Consented patients completed a pain survey and pain disability index on presentation to clinic. Statistical analysis included Chi square test and Mann Whitney test.
Results:
Twenty-nine percent (45/155) of patients exhibited pelvic floor myofascial pain, while 71% (110/155) did not. Of those with malignancy, 28% (16/57) had pelvic floor myofascial pain and 72% (41/57) did not. Patients with pelvic floor myofascial pain had a significantly higher rating of “pain right now” (p = 0.001) and “usual level of pain during the past week” (p = 0.003) than those without such pain. Patients with pelvic floor myofascial pain had significantly greater disability in family/home responsibilities (p = 0.01), recreation (p = 0.001), social activity (p = 0.008), occupation (p = 0.015), sexual behavior (p = 0.025), and life support activities (p = 0.007) compared to those without pelvic floor myofascial pain.
Conclusion:
Pelvic floor myofascial pain affects 28% of patients with malignancy. Routine incorporation of a myofascial exam can identity those with such pain, which can lead to improved quality of life in gynecologic oncology patients with pelvic floor disorders.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
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