Depression and anxiety in women with malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST): an analysis of the AGO-CORSETT database.

INTRODUCTION: The intention of this study was to evaluate the level of anxiety and depression of malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST) survivors and to identify possible alterable cofactors. METHODS: CORSETT was an observational, multicenter, mixed retrospective/prospective cohort study of the AGO Studygroup. Women who had been diagnosed with MOGCTs and SCSTs between 2001 and 2011 were asked to complete the Hospital Anxiety and Depression Scale (HADS) to evaluate distress. Predictors of distress (type of surgery, chemotherapy, time since diagnosis, recurrence, second tumor, pain) were investigated using multivariate linear regression analysis. RESULTS: 150 MOGCT and SCST patients with confirmed histological diagnosis completed the questionnaire median seven years after diagnosis. They had a HADS total score ≥ 13 indicating severe mental distress in 34% of cases. Patients after fertility-conserving surgery had lower probability of severe mental distress than those without fertility-conserving treatment (ß = - 3.1, p = 0.04). Pain was associated with the level of distress in uni- and multivariate analysis (coef 0.1, p < 0.01, coef. Beta 0.5). DISCUSSION: Severe mental distress was frequent in patients with MOGCT and SCST and the level of pain was associated with the level of distress. Fertility conserving therapy, however, was associated with less mental distress. Screening and treatment of pain and depression is required to improve mental well-being in survivors of MOGCT and SCST.

Biomarker-based early detection of epithelial ovarian cancer based on a five-protein signature in patient's plasma - a prospective trial.

BACKGROUND: Trial on five plasma biomarkers (CA125, HE4, OPN, leptin, prolactin) and their possible role in differentiating benign from malignant ovarian tumors. METHODS: In this unicentric prospective trial preoperative blood samples of 43 women with ovarian masses determined for ovarian surgery were analyzed. 25 patients had pathologically confirmed benign, 18 malignant ovarian tumors. Blood plasma was analyzed for CA125, HE4, OPN, leptin, prolactin and MIF by multiplex immunoassay analysis. Each single protein and a logistical regression model including all the listed proteins were tested as preoperative predictive marker for suspect ovarian masses. RESULTS: Plasma CA125 was confirmed as a highly accurate tumor marker in ovarian cancer. HE4, OPN, leptin and prolactin plasma levels differed significantly between benign and malignant ovarian masses. With a logistical regression model a formula including CA125, HE4, OPN, leptin and prolactin was developed to predict malignant ovarian tumors. With a discriminatory AUC of 0.96 it showed to be a highly sensitive and specific diagnostic test for a malignant ovarian tumor. CONCLUSIONS: The calculated formula with the combination of CA125, HE4, OPN, leptin and prolactin plasma levels surpasses each single marker in its diagnostic value to discriminate between benign and malignant ovarian tumors. The formula, applied to our patient population was highly accurate but should be validated in a larger cohort. TRIAL REGISTRATION: Clinical Trials.gov under NCT01763125 , registered Jan. 8, 2013.

A pilot study of an HbA1c chairside screening protocol for diabetes in patients with chronic periodontitis: the dental hygienist's role.

OBJECTIVE: To assess effectiveness, convenience and cost of point-of-care diabetes screenings performed by a dental hygienist for patients with periodontitis, using a diabetes risk questionnaire, periodontal findings and a glycosylated haemoglobin (HbA1c) analyser. METHODS: A purposive sample of 50 participants with periodontitis, never diagnosed with diabetes, reporting ≥one diabetes risk factor, were administered an HbA1c test. Spearman's correlation measured relationships between HbA1c and diabetes risk test scores, numbers of missing teeth, percentage of deep pockets ≥5 mm and percentage of bleeding sites (BOP). Cost and time were assessed. Analyses used 0.05 alpha levels. RESULTS: Thirty-two per cent (n = 16) of participants presented HbA1c values indicating prediabetes; one HbA1c value indicated type 2 diabetes, totalling 34% (N = 17). No relationships existed between HbA1c values and diabetes risk scores (rs = 0.153; P = 0.144), numbers of missing teeth (r = 0.190; P = 0.093), percentage of deep pockets (rs = -0.048; P = 0.370) or percentage of BOP sites (rs = 0.066, P = 0.324). Direct cost for each HbA1c was $9US, excluding follow-up medical diagnosis. Mean screening time including patient education was 14 min (SD = 6.2). Fifty-three per cent (n = 9 of 17) of participants with elevated HbA1c values contacted their primary healthcare provider within 2 weeks as recommended. CONCLUSION: Point-of-care HbA1c screenings by dental hygienists were effective and convenient for identifying undiagnosed prediabetes and provide opportunity for interprofessional patient care; cost or lack of dental insurance may inhibit implementation. Identification of patients at risk for diabetes requires further evaluation.

Index-matched IWKB method for the measurement of spatially varying refractive index profiles within thin-film photovoltaics.

In many thin-film photovoltaic devices, the photoactive layer has a spatially varying refractive index in the substrate-normal direction, but measurement of this variation with high spatial resolution is difficult due to the thinness of these layers (typically 200 nm for organic photovoltaics). We demonstrate a new method for reconstructing the depth-dependent refractive-index profile with high spatial resolution (~10 nm at a wavelength of 500 nm) in thin (200 nm) photoactive layers by depositing a relatively thick index-matched layer (1-10 µm) adjacent to the photoactive layer and applying the Inverse Wentzel-Kramers-Brillouin (IWKB) method. This novel technique, which we refer to as index-matched IWKB (IM-IWKB), is applicable to any thin film, including the photoactive layers of a broad range of thin-film photovoltaics.

The need for accredited training in gynaecological oncology: a report from the European Network of Young Gynaecological Oncologists (ENYGO).

BACKGROUND: Primary data on training experiences of European gynaecological oncology trainees are lacking. This study aims to evaluate trainee profile, satisfaction and factors affecting the training experience in gynaecological oncology in Europe. PATIENTS AND METHODS: A web-based anonymous survey sent to ENYGO members/trainees in July 2011. It included sociodemographic information and a 22-item (1-5 Likert scale) questionnaire evaluating training experience in gynaecological oncology. Chi-square tests were used for evaluating the independence of categorical variables and t-test (parametric)/Mann-Whitney (non-parametric) tests for differences between two independent groups on continuous data. Cluster analysis was used to identify groupings in multivariate data and Cronbach's-alpha for questionnaire reliability. A multivariable linear regression model was used to assess the effect of variables on training satisfaction. RESULTS: One hundred and nineteen gynaecological-oncology trainees from 31 countries responded. The mean age was 37.4 (S.D, 5.3) years and 55.5% were in accredited training posts. Two clusters identified in the cohort (Calinski-Harabasz, CH = 47.35) differed mainly by accredited training (P = 0.003). The training-satisfaction score (TSS) had high reliability (Cronbach's alpha, 0.951) and was significantly associated with accredited posts (P < 0.0005), years of training (P = 0.001) and salary (P = 0.002). The TSS was independent of age (P = 0.360), working hours (P = 0.620), overtime-pay (P = 0.318), annual leave (P = 0.933), gender (P = 0.545) and marital status (P = 0.731). Accredited programme trainees scored significantly higher than others in 17 of 22 aspects of training. The areas of greater need included advanced laparoscopic/urological/colorectal surgery, radiation oncology, palliative-care, cancer genetics and research opportunities. CONCLUSIONS: Our data demonstrate the importance of accredited training and the need for harmonisation of gynaecological oncology training within Europe.

Video-assisted thoracic surgery (VATS) evaluation of intrathoracic disease in patients with FIGO III and IV stage ovarian cancer.

OBJECTIVES: The aim of this study was to assess the influence of video-assisted thoracic surgery (VATS) on our treatment decisions in FIGO III and IV ovarian cancer patients. METHODS: Patients with ovarian cancer and suspected supra-diaphragmatic involvement (pleural effusions, pleural carcinomatosis, lung metastasis, or enlarged supra-diaphragmatic lymph nodes) at chest computer tomography (CT) scan underwent VATS with or without laparoscopy (LSC) to decide for primary cytoreduction or neoadjuvant chemotherapy. Operation time, VATS complications (intrapleural hematoma, secondary hemorrhage with intervention, pneumonia and empyema) and shift in the therapeutic strategy due to VATS were evaluated. RESULTS: 17 patients were included into this study (1 patient with FIGO stage IIIb, 1 with IIIc and 15 with stage IV). The median operation time for VATS only was 46.5 min (range: 20-50 min, n=3). Perioperatively, no complications occurred. After surgical staging, the tumor was confined to the abdomen in four patients in whom primary cytoreduction was attempted. All other 13 patients underwent neoadjuvant chemotherapy. VATS altered the therapeutic management in 6/17 ovarian cancer patients (3 times upstaging, 3 times downstaging). Negative predictive values (NPV) for local and diffuse pleural carcinomatosis ranged between 0.5 and 0.71. CONCLUSION: In this case series, VATS in addition to LSC showed negligible morbidity related to surgery and a short operation time. We were able to improve the accuracy of the FIGO staging and assessed operability more reliably in these patients than through imaging techniques alone.

Sentinel lymph node detection in patients with vulvar carcinoma; Feasibility of intra-operative mapping with technetium-99m-labeled nanocolloid.

AIMS: Sentinel lymph node (SLN) mapping appears to be feasible in patients with primary vulvar cancer. Previous protocols describe the injection of the technetium-99m-nanocolloid at least 3 h before surgery which involves two invasive procedures for the patient. In this study, we assessed the feasibility, safety, and accuracy of an intra-operative rather than preoperative SLN mapping in patients with primary vulvar cancer. METHODS: Patients with histologically confirmed squamous cell vulvar cancer and clinically FIGO stage Ib disease underwent intra-operative SLN mapping by intradermal injection of the nanocolloid around the tumor. SLN were identified and removed before a complete inguinofemoral lymphnode dissection was performed. Surgical and pathologic data on all patients were prospectively entered into a database. RESULTS: An SLN procedure was performed in 16 patients; 3 patients received unilateral lymphadenectomy, and 13 women underwent surgery on both groins. In all groins but 4 at least one SLN was clearly identified (detection rate 25/29, 86%). A median number of 2 SLN and 4 non-SLN per groin were removed. 3 of 16 patients (19%) had metastatic disease in the lymph nodes. There was no false negative SLN result. CONCLUSION: Intra-operative SLN detection seems feasible in patients with early stage vulvar cancer. More patients need to be enrolled in this ongoing study before this more convenient technique can be considered safe.

Stereoselective radical aryl migration from silicon to carbon.

Highly diastereoselective radical 1,5 phenyl migration reactions from silicon in diarylsilyl ethers to various C-centered radicals to form the corresponding 3-phenylated alcohols are described. Functionalized aryl groups can also be transferred. The effect of the variation of the attacking radical on the aryl transfer reaction is discussed. Best results are obtained for the phenyl migration to nucleophilic secondary alkyl radicals, where high yields (up to 81%) and high selectivities (up to 95% ds) have been obtained. The mechanism of the process is discussed and a model to explain the stereochemical outcome of the reaction is presented. Finally, stereoselective 1,4 aryl migration reactions from Si to C, including a new method for the alpha-arylation of esters, are presented.

Synthesis of biaryls by intramolecular radical aryl migration from silicon to carbon

A new method for the preparation of biaryls via intramolecular 1,5 aryl migration reaction from silicon in silyl ethers to aryl radicals is presented. Various readily available diphenylsilyl ethers can be used as substrates in this reaction. Functionalized aryl groups can also be transferred. The analogous 1,4 aryl migration reaction is less efficient.

Anastomosis of bypass grafts using a low-powered CO2 laser.

The purpose of this study was to evaluate the feasibility of using a low-powered CO2 laser to perform end-to-side anastomoses of bypass grafts. The internal jugular veins of 13 domestic swine were removed and used as grafts to bypass their ligated carotid arteries. Each end of the vein graft was apposed to the artery with four to six temporary stay sutures, and a waveguide delivery CO2 laser with a power density of 900 mW/mm2 was used to perform the anastomoses, after which the sutures were removed. The animals were sacrificed postoperatively at five time intervals: 2 to 4 hours, 5 days, 1 month, 3 months, and 5 months. Of the 10 anastomoses studied at 2 to 4 hours, 70% were fully patent, none thrombosed, and 30% disrupted. Of the 16 anastomoses studied between 5 days and 5 months postoperatively, 88% were patent, 12% thrombosed, and none disrupted. None of the animals developed aneurysms at any stage of this investigation. Histologic analysis of acute studies revealed thermal damage such as charring of tissue, unraveling of the collagen fibrils, and the formation of microvacuoles. Within 3 months, the anastomotic sites showed localized healing with intimal fibromuscular proliferation and dense fibrous tissue. Good apposition of tissue was found to be of great importance in achieving patency of vessels in this procedure.

Restrictive cardiomyopathy with kappa light chain deposits in myocardium as a complication of multiple myeloma. Histochemical and electron microscopic observations.

kappa Light chain deposits occurring in myocardium as a complication of multiple myeloma were identified ultrastructurally and immunohistochemically in a right ventricular endomyocardial biopsy specimen from a patient who presented with clinical and hemodynamic findings of restrictive cardiomyopathy. These deposits were not evident on routine histopathologic examination; they were Congo red-negative and gave a positive immunoperoxidase reaction for kappa light chains and a negative reaction for lambda chains. They consisted of amorphous, electron-dense granules that formed discontinuous layers adjacent to the plasma membranes of cardiac myocytes, arteriolar endothelial and smooth-muscle cells, and neural elements. These observations underscore the need for critical study of endomyocardial biopsy specimens, using electron microscopy and immunohistochemical reagents, for the precise identification of protein components in tissue deposits in patients suspected of having cardiac amyloidosis or related disorders.

Microcystic adenoma (serous cystadenoma) of the pancreas. A study of 14 cases with immunohistochemical and electron-microscopic correlation.

Microcystic adenoma (serous cystadenoma) of the pancreas (MA) is an unusual benign tumor of uncertain histogenesis. We have studied 14 cases of MA from 11 women and three men. The average age at diagnosis was 64 years. Six tumors were discovered incidentally. Tumors varied from 2.5 to 12 cm in greatest dimension and all were multicystic; eight tumors were located in the pancreatic head, two in the body, and three in the tail. Each tumor was composed of variably sized cysts lined by simple cuboidal or flattened, focally glycogen-rich epithelium. The stroma was variably collagenized and showed highly vascularized, delicate to broad fibrous septae, which focally contained dystrophic calcification, cholesterol clefts, and hemosiderin. Immunohistochemical studies were performed on eight cases to determine the cell of origin. Epithelial membrane antigen and a low-molecular-weight keratin, detected by monoclonal antibodies PKK1 or AE1/AE3, were diffusely seen in tumor cells of all cases. Tumor cells were uniformly negative for carcinoembryonic antigen, chromogranin, insulin, glucagon, somatostatin, vasoactive intestinal peptide, pancreatic polypeptide, and a low-molecular-weight keratin detected by monoclonal antibody PKK2. Tumor cell antigen reactivity most resembled that seen in normal centroacinar and ductal cells. Electron microscopy of seven cases showed primitive tumor cells with irregularly spaced, short, blunt microvilli, luminal occluding junctions and belt desmosomes, bundles of filaments including dense bodies in both apical and basal cell cytoplasm, sparse organelles, and variable but often pronounced amounts of glycogen. These ultrastructural features most closely resembled the normal pancreatic centroacinar cell. Based on both immunohistochemical and ultrastructural features described above, we conclude that the centroacinar cell is the cell of origin of MA.

Chloroquine-induced cardiomyopathy.

Biventricular hypertrophy and failure developed in two patients during treatment of systemic lupus erythematosus with chloroquine phosphate. In both patients, morphologic analysis of the myocardium, obtained by a right ventricular endomyocardial biopsy in one patient and at autopsy in the other, revealed accumulations of electron-dense concentric and parallel lamellae and curvilinear bodies within cardiac myocytes. These deposits were similar to those reported in chloroquine-induced skeletal myopathy and were considered to represent evidence of chloroquine-induced cardiotoxicity rather than a cardiovascular manifestation of the underlying disease. Clinical awareness and an endomyocardial biopsy specimen are necessary for the appropriate diagnosis of chloroquine-induced cardiomyopathy.

Rare primary sarcomas of the heart.

Three patients with primary malignant cardiac neoplasms are described. All tumors were intracavitary myxomatous masses of the left atrium. Preoperative clinical diagnostic techniques did not indicate malignancy, but suggested mitral stenosis, cor triatriatum, and cardiac myxoma. Grossly, the tumors were sessile rather than pedunculated, and they invaded the underlying structures. Microscopically, although the tumors resembled benign cardiac myxomas, they exhibited mitotic activity and areas of necroses. Ultrastructural examination revealed a spectrum of differentiated mesenchymal cells that lacked the maturation features of cardiac myxoma cells. These gross, microscopic, and ultrastructural features, which suggested the tumors' malignant potential, should help in the early recognition and management of similar tumors.

Sarcomatous type of malignant mesothelioma.

Thirteen malignant mesotheliomas of a sarcomatous type were studied by light microscopy and ten were studied by electron microscopy. The histologic patterns varied from tumor to tumor, often resembling other soft tissue sarcomas. Electron microscopic observation showed most of the tumors to be composed of primitive cells. Despite their mesenchymal character, many tumors contained foci of rudimentary epithelial differentiation. It is concluded that both histologic types of malignant mesothelioma, the epithelial as well as the sarcomatous, originate from the same precursor cell at various points of its differentiation and reflect the range of maturation from the mesenchymal reserve cell to the epithelial mesothelial cell.

Multilocular cystic leiomyoma of the kidney.

A large, multilocular cystic mass from the kidney of a 26-year-old woman was examined by light microscopy and transmission electron microscopy. Ultrastructurally the cysts were shown to be lined by smooth muscle cells, giving evidence that the cysts originated in smooth muscle. Thus the tumor is considered to be a multilocular cystic leiomyoma, an apparently unique renal tumor.

Calcification in chronically-implanted blood pumps: experimental results and review of the literature.

Blood compatibility is a major objective in the development of long-term, implantable circulatory assist (left ventricular assist devices) and replacement (total artificial heart) devices. An important problem in experimental studies in animals has been the propensity for calcification to occur at the blood/material interface. Presented is a summary of our experience (27 studies) with blood pump calcification and a review of the current literature regarding this complication.

Persistent atrial paralysis: Case report with light microscopy and ultrastructural analyses.

Persistent atrial paralysis in a patient with complete heart block and mild mitral insufficiency is presented. Left atrial specimens obtained during implantation of a permanent cardiac pulse generator showed evidence of hypertrophy and fibrosis; subcellular degenerative changes ranged from near normal to irreversible, thus suggesting that atrial paralysis may be due to the replacement of normal atrial muscle with nonfunctional fibrous tissue.