Doubling down on the future of gynecologic oncology: The SGO future of the profession summit report.

The original vision of the field of gynecologic oncology was to establish a multidisciplinary approach to the management of patients with gynecologic cancers. Fifty years later, scientific advances have markedly changed the overall practice of gynecologic oncology, but the profession continues to struggle to define its value-financial and otherwise. These issues were examined in full at the Society of Gynecologic Oncology (SGO) Future of the Profession Summit and the purpose of this document is to summarize the discussion, share the group's perceived strengths, weaknesses, opportunities, and threats (SWOT) for gynecologic oncologists, further educate members and others within the patient care team about the unique role of gynecologic oncologists, and plan future steps in the short- and long- term to preserve the subspecialty's critical mission of providing comprehensive, longitudinal care for people with gynecologic cancers.

Ex vivo culture of mouse skin activates an interleukin 1 alpha-dependent inflammatory response.

Ex vivo culture of mouse and human skin causes an inflammatory response characterized by production of multiple cytokines. We used ex vivo culture of mouse tail skin specimens to investigate mechanisms of this skin culture-induced inflammatory response. Multiplex assays revealed production of interleukin 1 alpha (IL-1α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), chemokine C-X-C motif ligand 1 (CXCL1), granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during skin culture, and quantitative PCR revealed transcripts for these proteins were also increased. Ex vivo cultures of skin from myeloid differentiation primary response 88 deficient mice (Myd88-/- ) demonstrated significantly reduced expression of transcripts for the aforementioned cytokines. The same result was observed with skin from interleukin 1 receptor type 1 deficient mice (Il1r1-/- ). These data suggested the IL-1R1/MyD88 axis is required for the skin culture-induced inflammatory response and led us to investigate the role of IL-1α and IL-1ß (the ligands for IL-1R1) in this process. Addition of IL-1α neutralizing antibody to skin cultures significantly reduced expression of Cxcl1, Il6 and Csf3. IL-1ß neutralization did not reduce levels of these transcripts. These studies suggest that IL-1α promotes the skin the culture-induced inflammatory response.

Unprecedented multiphonon vibronic transitions of erbium ions on copper nanoparticle-containing tellurite glasses.

Erbium-doped tellurite glass containing copper nanoparticles showed multi-band emission of one particular transition (4I9/2→4I15/2, at 980 nm) due to electron-lattice coupling. The present study reports the vibronic transitions of intraconfigurational 4fn transitions of Er3+ ions in a tellurite host matrix at room temperature for the first time. The mechanisms of multiphoton transitions and the effect of laser heating are discussed here. This unprecedented behavior enables the design of a plethora of different applications spanning from tunable emission in the near infrared, such as lasers for bioimaging and biomedical fields, to energy conversion by thermophotovoltaic conversion of thermal radiation.

Mucin 5B, carbonic anhydrase 9 and claudin 18 are potential theranostic markers of gallbladder carcinoma.

AIMS: Gallbladder cancer (GBC) is an aggressive tumour that is usually diagnosed at advanced stages and is characterised by a poor prognosis. Using public data of normal human tissues, we found that mRNA and protein levels of mucin 5B (MUC5B) and carbonic anhydrase 9 (CA9) were highly increased in gallbladder tissues. In addition, previous evidence has shown that claudin 18 (CLDN18) protein expression is higher in GBC. The aim of this study was to perform an analysis of these cell surface proteins during the histological progression of GBC in order to identify their theranostic potential. METHODS AND RESULTS: MUC5B expression, CA9 expression and CLDN18 expression were examined by immunohistochemistry in a series of 179 chronic cholecystitis (including 16 metaplastic tissues), 15 dysplasia and 217 GBC samples by the use of tissue microarray analysis. A composite staining score was calculated from staining intensity and percentage of positive cells. Immunohistochemical analysis showed high expression of MUC5B and CA9 among normal epithelium, metaplastic tissues, and dysplastic tissues. However, expression of both proteins was observed in roughly 50% of GBC samples. In contrast, CLDN18 was absent in normal epithelium, but its expression was higher in metaplastic cells. Among GBC cases, approximately half showed high CLDN18 expression. No associations were found between MUC5B, CA9 and CLDN18 expression and any clinicopathological features. CONCLUSIONS: CLDN18 is a new metaplasia marker in gallbladder tissues, and is conserved in approximately half of GBC cases. MUC5B and CA9 are highly conserved during GBC histological progression. The three markers are potential theranostic markers, in particular CA9 and CLDN18, for which there are already targeted therapies available.

False Negative Urine Pregnancy Testing with Complete Molar Pregnancy: An Example of the Hook Effect.

INTRODUCTION: Gestational trophoblastic disease (GTD) encompasses a group of tumors derived from trophoblasts, which normally form the placenta during pregnancy. Human chorionic gonadotropin (hCG) is a glycoprotein composed of an alpha subunit identical to that of thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Detection of beta-hCG is achievable in both urine and serum samples, proving useful for the detection of normal pregnancy and GTD. However, in the presence of very high levels of beta-hCG, a false negative result may be obtained due to a phenomenon called the "hook effect" or "prozone phenomenon." In certain circumstances, trophoblastic tumors can produce very high levels of beta-hCG, causing misleading results on urine pregnancy testing. CASE PRESENTATION: A 49-year-old Caucasian female with past medical history pertinent for deep vein thrombosis, ovarian cysts, and osteopenia presented to her internist with report of irregular uterine bleeding for the preceding three months, accompanied by complaints of abdominal bloating, night sweats, and constipation. The patient stated she had completed two negative qualitative urine pregnancy tests and had been seen by both gynecology and gastroenterology, with recommendations to start supplemental estrogen for her symptoms and begin additional fiber intake for irritable bowel syndrome, respectively. Despite negative urine beta-hCG, a quantitative serum beta-hCG was obtained and revealed a level greater than 200,000 international units (IU). The patient was referred to gynecologic oncology and an open abdominal hysterectomy with preservation of her ovaries was performed. Histopathologic examination showed a complete hydatiform mole with no evidence of invasion. CONCLUSION: The case highlights the importance of clinical judgment in modern medicine, where biochemical methods and imaging modalities have become main stays in diagnosis. As mentioned, there are ways to reduce the incidence of the hook effect, but with added time and cost. Clinicians need to consider the possibility of the hook effect for instances where the clinical picture points to a disease entity despite negative test results. Delaying diagnoses, as illustrated with GTD, has the potential to cause significant morbidity and mortality.

Long-term primary culture of a clear cell ovarian carcinoma reveals an epithelial-mesenchymal cooperative interaction.

BACKGROUND: We studied a primary culture developed from a biopsy of a clear cell carcinoma of the ovary (O-CCC) by (a) assessing its capacity to retain in vitro pathological features of the tumor of origin; (b) characterizing the main cells released from the complex mass without forced purification of any particular cellular entity; and (c) investigating its long-term proliferative capacity. METHODS: A primary cell culture was developed from a pelvic mass diagnosed as an O-CCC. The morphological analysis of the cell culture was carried out by phase contrast microscopy. Markers of epithelial, mesenchymal, and tumor initiating cells were evaluated by immunocytochemistry. Cell proliferation was studied by detection of bromodeoxyuridine (BrdU) incorporated into newly synthesized DNA. As a biomarker of O-CCC, we assessed the expression of hepatocyte nuclear factor (HNF) 1ß. RESULTS: We show that cells with epithelial morphological features express E-cadherin and expand with time in culture, a fact that the incorporation of BrdU confirms. Cells with mesenchymal-like characteristics that express the mesenchymal marker vimentin, however, allocate to the edges of the epithelial compartment. Moreover, we found that some cells with epithelial features also expressed vimentin. At the beginning of incubation, over 60 % of primary cells expressed the O-CCC marker HNF1ß; such percentage declined upon passaging. We show that epithelial not mesenchymal cells undergo DNA replication, and that few cells in both epithelial and mesenchymal compartments express the stem-like tumor antigen CD133. CONCLUSIONS: We provide proof-of-principle that cells separated in bulk from a biopsy of an O-CCC can be maintained in culture for several months, and that two consistent cellular compartments-one epithelial that retains the O-CCC marker HNF1ß, and another mesenchymal-persist, and seem to have a cooperative interaction leading to the multiplication of epithelial cells within a mesenchymal cellular environment.

Teleoncology for gynecologic cancers.

Teleoncology describes cancer care provided remotely to improve access to care in rural or underserved areas. In the United States, 14.8 million women live more than 50 miles away from the closest gynecologic oncologist; 4.3 million women live more than 100 miles distant. Teleoncology may therefore partially relieve the geographic barriers to high-quality gynecologic cancer care these women experience. Little has been published on the feasibility of remote provision of high-quality care for gynecologic cancers, perhaps owing to the particular difficulties inherent in remote management of patients who may require both medical and surgical intervention. In this article, we review the data supporting the use of telemedicine in the treatment of cancer patients with a specific focus on applicability to management of gynecologic malignancies. We further add our group's experience with the treatment of rural, underserved gynecologic cancer patients. We believe that development of teleoncologic systems is critical to ensure that all women have access to high-quality gynecologic cancer care, regardless of where they reside.

Quantification of whey in fluid milk using confocal Raman microscopy and artificial neural network.

In this work, we assessed the use of confocal Raman microscopy and artificial neural network as a practical method to assess and quantify adulteration of fluid milk by addition of whey. Milk samples with added whey (from 0 to 100%) were prepared, simulating different levels of fraudulent adulteration. All analyses were carried out by direct inspection at the light microscope after depositing drops from each sample on a microscope slide and drying them at room temperature. No pre- or posttreatment (e.g., sample preparation or spectral correction) was required in the analyses. Quantitative determination of adulteration was performed through a feed-forward artificial neural network (ANN). Different ANN configurations were evaluated based on their coefficient of determination (R2) and root mean square error values, which were criteria for selecting the best predictor model. In the selected model, we observed that data from both training and validation subsets presented R2>99.99%, indicating that the combination of confocal Raman microscopy and ANN is a rapid, simple, and efficient method to quantify milk adulteration by whey. Because sample preparation and postprocessing of spectra were not required, the method has potential applications in health surveillance and food quality monitoring.

A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube.

OBJECTIVE: To determine the safety and efficacy of the novel combination of docetaxel, oxaliplatin, and bevacizumab as first-line treatment of advanced cancer of the ovary, peritoneum or fallopian tube after initial debulking surgery. METHODS: Eligible patients (stage IB-IV) were treated with 6 cycles of oxaliplatin (85 mg/m(2)), docetaxel (75 mg/m(2)), and bevacizumab (15 mg/kg) every 3 weeks, followed by single-agent bevacizumab 15 mg/kg every 3 weeks to complete one year of therapy. The primary endpoint was 12-month progression-free survival (PFS). RESULTS: A total of 132 patients (80 with measurable disease at baseline; 52 with non-measurable, evaluable disease at baseline) enrolled and received study treatment. At diagnosis, 76.5% of patients had stage III disease and 20% had stage IV. 62.9% were optimally cytoreduced. The most common grade 3/4 adverse events were neutropenia (42.4%), leukopenia (13.6%), hypertension (8.3%), fatigue (6.1%), and nausea (6.1%). One patient (0.8%) had a fatal gastrointestinal perforation. The best overall confirmed response rate (complete response+partial response [measurable disease subgroup]) was 58.6% (95% CI 49%, 67%). CA-125 response rates for the measurable and non-measurable disease subgroups were 83.0% and 81.5%, respectively. The 12-month PFS rate for the measurable disease subgroup was 65.7% (95% CI 53.4%, 76.7%); median PFS was 16.3 (95% CI 12.6, 19.6) months. Median overall survival was 47.3 (95% CI 34.1, upper limit not applicable) months. CONCLUSIONS: This novel treatment regimen may provide a promising therapeutic approach for women with ovarian, primary peritoneal, or fallopian tube carcinoma. No unanticipated safety concerns were identified.

Is bilateral lymphadenectomy for midline squamous carcinoma of the vulva always necessary? An analysis from Gynecologic Oncology Group (GOG) 173.

OBJECTIVE: To determine which patients with near midline lesions may safely undergo unilateral groin dissection based on clinical exam and lymphoscintigraphy (LSG) results. METHODS: Patients participating in GOG-173 underwent sentinel lymph node (SLN) localization with blue dye, and radiocolloid with optional LSG before definitive inguinal-femoral lymphadenectomy (LND). This analysis interrogates the reliability of LSG alone relative to primary tumor location in those patients who had an interpretable LSG and at least one SLN identified. Primary tumor location was categorized as lateral (>2cm from midline), midline, or lateral ambiguous (LA) if located within 2cm, but not involving the midline. RESULTS: Two-hundred-thirty-four patients met eligibility criteria. Sixty-four had lateral lesions, and underwent unilateral LND. All patients with LA (N=65) and midline (N=105) tumors underwent bilateral LND. Bilateral drainage by LSG was identified in 14/64 (22%) patients with lateral tumors, 38/65 (58%) with LA tumors and in 73/105 (70%) with midline tumors. At mapping, no SLNs were found in contralateral groins among those patients with LA and midline tumors who had unilateral-only LSGs. However, in these patients groin metastases were found in 4/32 patients with midline tumors undergoing contralateral dissection; none were found in 27 patients with LA tumors. CONCLUSION: The likelihood of detectable bilateral drainage using preoperative LSG decreases as a function of distance from midline. Patients with LA primaries and unilateral drainage on LSG may safely undergo unilateral SLN.

Circumscribed Palmar Hypokeratosis With Superimposed Actinic Keratosis.

A man in his late 70s with a history of psoriasis and non-melanoma skin cancer presented with a progressive rash on his right thenar eminence. He first noticed it about one year ago. He denied any pruritus in the affected region but did note some overlying skin breakdown. He had used topical betamethasone and calcipotriene cream in the past with minimal improvement. Physical examination revealed a pink atrophic plaque with linear hyperkeratotic borders and central fissuring on the right thenar eminence extending into the first webspace. A shave biopsy revealed hypokeratosis with a rim of surrounding hyperkeratosis and associated parakeratosis, basal keratinocyte atypia, and lichenoid inflammation. These histopathological features were consistent with circumscribed palmar hypokeratosis and central actinic keratosis. Circumscribed palmar hypokeratosis is often considered a benign entity, but there have been reports suggesting an association with premalignancy. The decision was made to treat with 5-fluorouracil and calcipotriene cream twice daily for six weeks. At his two-month follow-up, he endorsed a robust reaction, which was further suggestive of premalignant change. He had a near-complete resolution of the rash. This case features circumscribed palmar hypokeratosis and suggests a novel treatment option for patients who develop concomitant actinic keratosis.

Zn[Formula: see text]Ni[Formula: see text]Te semiconductor nanocrystals in transparent glass for optoelectronic device applications.

Doping glass with semiconductors, particularly with nanostructured semiconductors, has attracted attention due to the large optical absorption cross-sections of the latter. Based on this property, Ni[Formula: see text] (5 wt%) doped phosphate glass and Zn[Formula: see text]Ni[Formula: see text]Te (x = 0.5, 1.0, 5.0 and 10.0 wt% of Ni[Formula: see text]) nanocrystals (NCs) doped phosphate glasses (GCs) were prepared by fusion method and subsequent heat treatment. Influence of Ni[Formula: see text] on structural, thermo-optical and third-order nonlinear optical properties have been analysed through various spectroscopic characterizations. The XRD pattern of the glass (G) exhibits the amorphous nature of the host material while GCs exhibit not only amorphous halo but also the presence of quantum dots (QDs) or nanocrystals (NCs) phases. TEM analysis of the studied GCs samples confirm the presence of quantum dots (QDs) and bulk NCs with an average diameter of approximately 4.2 [Formula: see text] 0.3 nm and 13.4 [Formula: see text] 0.2 nm, respectively. Several phosphate groups were observed and reported from Raman and FTIR-ATR spectra. The absorption band positions confirmed that Ni[Formula: see text] ions resemble to the octahedral symmetry. The intensity of absorption band around 1352 nm ([Formula: see text]T[Formula: see text](F) [Formula: see text] [Formula: see text]A[Formula: see text](F)) increased with the increase of Ni[Formula: see text] in GCs which is an indicative of the [Formula: see text]Ni[Formula: see text] coordination. The emission properties such as emission cross-sections ([Formula: see text]) full width at half maxima (FWHM) for the [Formula: see text]T[Formula: see text](D) [Formula: see text] [Formula: see text]T[Formula: see text](F) (visible) and [Formula: see text]A[Formula: see text](F) [Formula: see text] [Formula: see text]T[Formula: see text](F) (near-infrared) emission transitions were reported. Among the glass-containing semiconductor nanocrystals (GCs), the emission cross-sections in GC4 sample (x = 10% of Ni[Formula: see text]) are the largest for both the visible (11.88 [Formula: see text] 10[Formula: see text] cm[Formula: see text]) and infrared (0.98 [Formula: see text] 10[Formula: see text] cm[Formula: see text]) transitions. Thermal diffusivity (D), thermal conductivity (K) and temperature dependent optical path length change (ds/dT) were obtained through time-resolved thermal lens (TL) and thermal relaxation (TR) methods. The D and K parameters do not change significantly with increase of Ni[Formula: see text] ions (0.5-5%) in GCs. Nonlinear-refractive index and nonlinear absorption of the studied samples were also obtained using femtosecond Z-scan technique. The increase of nonlinear absorption coefficient ([Formula: see text]) is observed from GC2 (2.53 [Formula: see text] 10[Formula: see text] cm/W) to GC4 (7.98 [Formula: see text] 10[Formula: see text] cm/W). The GC4, sample with 10 wt% of Ni[Formula: see text], showed the lowest ds/dT (1.22 [Formula: see text] 10[Formula: see text] K[Formula: see text]) with good lasing (FOM and emission cross-sections) and nonlinear absorption properties suggesting that it can be a good candidate for visible-red emission light conversion in LED technology.

Synthesis and Antitumor Activity of Brominated-Ormeloxifene (Br-ORM) against Cervical Cancer.

Aberrant regulation of ß-catenin signaling is strongly linked with cancer proliferation, invasion, migration, and metastasis, thus, small molecules that can inhibit this pathway might have great clinical significance. Our molecular modeling studies suggest that ormeloxifene (ORM), a triphenylethylene molecule that docks with ß-catenin, and its brominated analogue (Br-ORM) bind more effectively with relatively less energy (-7.6 kcal/mol) to the active site of ß-catenin as compared to parent ORM. Herein, we report the synthesis and characterization of a Br-ORM by NMR and FTIR, as well as its anticancer activity in cervical cancer models. Br-ORM treatment effectively inhibited tumorigenic features (cell proliferation and colony-forming ability, etc.) and induced apoptotic death, as evident by pronounced PARP cleavage. Furthermore, Br-ORM treatment caused cell cycle arrest at the G1-S phase. Mechanistic investigation revealed that Br-ORM targets the key proteins involved in promoting epithelial-mesenchymal transition (EMT), as demonstrated by upregulation of E-cadherin and repression of N-cadherin, Vimentin, Snail, MMP-2, and MMP-9 expression. Br-ORM also represses the expression and nuclear subcellular localization of ß-catenin. Consequently, Br-ORM treatment effectively inhibited tumor growth in an orthotopic cervical cancer xenograft mouse model along with EMT associated changes as compared to vehicle control-treated mice. Altogether, experimental findings suggest that Br-ORM is a novel, promising ß-catenin inhibitor and therefore can be harnessed as a potent anticancer small molecule for cervical cancer treatment.

Functional neuronal circuits promote disease progression in cancer.

The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these nerves form functional connections. Consistent with this, electrophysiological analysis shows that malignancies harbor significantly higher electrical activity than benign disease or normal tissues. We also demonstrate pharmacologic silencing of tumoral electrical activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced electrical activity. These data suggest that intratumoral nerves remain functional at the tumor bed. Immunohistochemical staining demonstrates the presence of the neuropeptide, Substance P (SP), within the tumor space. We show that tumor cells express the SP receptor, NK1R, and that ligand/receptor engagement promotes cellular proliferation and migration. Our findings identify a mechanism whereby intratumoral nerves promote cancer progression.

Physical strain and urgent need for ergonomic training among gynecologic oncologists who perform minimally invasive surgery.

OBJECTIVES: There is limited data regarding physical strain and minimally invasive gynecologic surgery (MIS). We sought to evaluate ergonomic strain among gynecologic oncologists. METHODS: An online survey was sent to all physician members of the Society of Gynecologic Oncology in North America in 2010. The survey contained 42 questions and data was analyzed using univariate and bivariate analyses with summary statistics, t-tests, and chi-squared test. RESULTS: There were 260 respondents (31.2%) to the survey. Case mix was 26% benign and 64% oncologic surgery. Over 52% of respondents had been in practice for greater than 11 years and 52% practice in an academic setting. Physical discomfort related to MIS was reported in 88% (216/244) of surgeons with 52% reporting persistent pain. Increased pain symptoms were associated with surgeon's height, glove size, age and female gender. Patient body mass index (BMI) was associated with pain symptoms in surgeons performing conventional laparoscopic surgery, but not robotic surgery. To decrease pain, surgeons changed positions (78%), limited the number of cases per day (14%), spread cases throughout the week (6%), or limited the total number of cases (3%). Only 29% had received treatment at any time for pain symptoms. Treatment included physical therapy (59%), medical management (28%), surgery (13%), and time off (1%). Only 16% of those with pain symptoms had received formal ergonomic training. CONCLUSION: Physical strain rates of 88% are far greater than previously reported. Such prevalent occupational strain presents a growing problem in the face of increasing demand for MIS.

Near-infrared quantum cutting luminescence in Pr3+/Yb3+ doped lead bismuth borate glass.

In this paper, thermally stable lead-bismuth-borate glasses were doped with 0.5 mol% of Pr3+ ions at several concentration levels of Yb3+ ions. Structural characterizations were performed via Raman, differential scanning calorimetry, optical absorption and fluorescence spectra. The Judd-Ofelt intensity parameter, [Formula: see text], of Pr3+ doped glass was comparatively higher than those from reported ones, which reflects the increase of co-valency and asymmetry of chemical bonds in the local environment of Pr3+. Near-infrared emission in 900-2200 nm wavelength range was recorded through 443 nm blue laser pumping. Visible to near-IR quantum cutting and concentration quenching mechanisms were discussed to understand the luminescent behaviour. Intense IR emission ([Formula: see text] features generated by absorbing one visible photon leads to quantum efficiencies close to 128% in Pr3+/Yb3+ co-doped samples which may improve the solar spectrum absorption and accordingly, increase the efficiency of c-Si solar cells. Emission cross-section, lifetime, figure of merit and gain bandwidth corresponding to Pr3+: [Formula: see text] ([Formula: see text]m) were comparatively reported suggesting that the glass with molar composition 0.5Pr3+/0.1Yb3+ might be a potential candidate for [Formula: see text]m laser operation with low pump threshold.

Origin geographical classification of green coffee beans (Coffea a rabica L.) produced in different regions of the Minas Gerais state by FT-MIR and chemometric.

The present work was proposal the potential evaluation of Fourier-Transform Mid-Infrared (FT-MIR) associated with chemometric approach in green beans, in order to discriminate the origin of special Arabica coffees in a single state that has heterogeneous environments. Partial Least Squares Discriminant Analysis (PLS-DA) model presented as result: 3 latent variables, R 2 X (cum) = 0.892, R 2 Y (cum) = 0.659; Q 2 Y (cum) = 0.494, RMSEP = 0.182387, p-value CV-Anova = 0.009, 100% of both sensitivity and specificity and the prediction classification obtained was: 100, 83.33, 100, 83.33% for class 1, class 2, class 3 and class 4, respectively. These results can be considered adequate for the proposed hypothesis. The obtained results that the regions have markers such as trigonelline, chlorogenic and fatty acids, sensitive to absorption in the mid-infrared and that are able to determine the origin of green coffee beans of Arabica. Thus, the FT-MIR associated with chemometrics has the potential to employ speed, modernity and cost reduction in the certification of origin of coffees.