The need for cardiac surgery differential tariffs in Israel at the era of aging population and emerging technology: Importance of procedure type and patient complexity as assessed by EuroSCORE.

BACKGROUND: Reimbursement for cardiac surgical procedures in Israel is uniform and does not account for diversity in costs of various procedures or for diversity in patient mix. In an era of new and costly technology coupled with higher risk patients needing more complex surgery, these tariffs may not adequately reflect the true financial burden on the caregivers. In the present study we attempt to determine whether case mix and complexity of procedures significantly affect cost to justify differential tariffs. METHODS: We included all patients undergoing cardiac surgery at Shaare Zedek Medical Center between the years 1993-2016. Patients were stratified according to (1) type of surgery and (2) clinical profile as reflected by the predicted operative risk according to the European System for Cardiac Operative Risk Evaluation (EuroSCORE). Approximate cost of each group of patients was estimated by the average number of days in the Intensive Care Unit and days in the postoperative ward multiplied by the respective daily costs as determined by the Ministry of Health. We then added the fixed cost of the components used in the operating room (manpower and disposables). The final estimated cost (the outcome variable) was then evaluated as it relates to type of surgery and clinical profile. ANOVA was used to analyze cost variability between groups, and backward regression analysis to determine the respective effect of the abovementioned variables on cost. Because of non-normal distribution, both costs and lengths of stay were Log-transformed. RESULTS: Altogether there were 5496 patients: 3863, 836, 685 and 112 in the isolated CABG, CABG + valve, 1 valve and 2 valves replacement groups. By ANOVA, the costs in all EuroSCORE subgroups were significantly different from each other, increasing with increased EuroSCORE subgroup. Cost was also significantly different among procedure groups, increasing from simple CABG to single valve surgery to CABG + valve surgery to 2-valve surgery. In backward stepwise multiple regression analysis, both type of procedure and EuroSCORE group significantly impacted cost. ICU stay and Ward stay were significantly but weakly related while EuroSCORE subgroup was highly predictive of both ICU stay and ward stay. CONCLUSIONS: The cost of performing heart surgery today is directly influenced by both patient profile as well as type of surgery, both of which can be quantified. Modern day technology is costly yet has become mandatory. Thus reimbursement for heart surgery should be based on differential criteria, namely clinical risk profile as well as type of surgery. Our results suggest an urgent need for design and implementation of a differential tariff model in the Israeli reimbursement system. We suggest that a model using a fixed, average price according to the type of procedure costs, in addition to a variable hospitalization cost (ICU + ward) determined by the patient EuroSCORE or EuroSCORE subgroup should enable an equitable reimbursement to hospitals, based on their case mix.

PD-L1 receptor expression in vulvar carcinomas is HPV-independent.

PD-L1 (programmed cell death 1 ligand) is expressed on many cancer cells and prevents tumor cell death by blocking T cell activity. PD-L1 overexpression has been reported in squamous cell carcinomas of head and neck and lung cancer. To better understand the role of PD-L1 expression in vulvar cancer, we analyzed PD-L1 expression by immunohistochemistry in 55 well-characterized squamous cell carcinomas of vulva. PD-L1 was found in 72.7% of tumors. 27.3% of vulvar carcinomas showed moderate or strong PD-L1 expression. PD-L1 expression was correlated with low tumor stage (p < 0.05). There was no association to other clinicopathological parameters, HPV status, and overall survival of vulvar carcinoma patients. In conclusion, PD-L1 overexpression is detectable in a substantial proportion of vulvar carcinomas in all stages independent of HPV and may be a suitable therapeutic target in these cancers.

Correction to: The use of PIPAC (pressurized intraperitoneal aerosol chemotherapy) in gynecological oncology: a statement by the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Kommission Ovar, AGO Study Group, North-Eastern German Society of Gynaecologic Oncology (NOGGO), AGO Austria and AGO Switzerland.

The title of the article has been published incorrectly. The correct title is given below.

The use of PIPAC (pressurized intraperitoneal aerosol chemotherapy) in gynecological oncology: a statement by the "Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR)", the Swiss and Austrian AGO, and the North-Eastern German Society of Gynaecologic Oncology.

BACKGROUND: Ovarian, tubal, and peritoneal carcinomas primarily affect the peritoneal cavity, and they are typically diagnosed at an advanced tumor stage (Foley, Rauh-Hain, del Carmen in Oncology (Williston Park) 27:288-294, 2013). In the course of primary surgery, postoperative tumor residuals are, apart from the tumor stage, the strongest independent factors of prognosis (du Bois, Reuss, Pujade-Lauraine, Harter, Ray-Coquard, Pfisterer in Cancer 115:1234-1244, 2009). Due to improved surgical techniques, including the use of multi-visceral procedures, macroscopic tumor clearance can be achieved in oncological centers, in most cases (Harter, Muallem, Buhrmann et al in Gynecol Oncol 121:615-619, 2011). However, to date, it has not been shown that peritoneal carcinomatosis is, per se, an independent factor of prognosis or that it excludes the achievement of tumor clearance. Several studies have shown that a preceding drug therapy in peritoneal carcinomatosis could positively influence the overall prognosis (Trimbos, Trimbos, Vergote et al in J Natl Cancer Inst 95:105-112, 2003). In relapses of ovarian carcinoma, studies have shown that peritoneal carcinomatosis is a negative predictor of complete tumor resection; however, when it is possible to resect the tumor completely, peritoneal carcinomatosis does not play a role in the prognosis (Harter, Hahmann, Lueck et al in Ann Surg Oncol 16:1324-1330, 2009). RESULTS: PIPAC is a highly experimental method for treating patients with ovarian, tubal, and peritoneal cancer. To date, only three studies have investigated a total of 184 patients with peritoneal carcinomatosis (Grass, Vuagniaux, Teixeira-Farinha, Lehmann, Demartines, Hubner in Br J Surg 104:669-678, 2017). Only some of those studies were phase I/II studies that included PIPAC for patients with different indications and different cancer entities. It is important to keep in mind that the PIPAC approach is associated with relatively high toxicity. To date, no systematic dose-finding studies have been reported. Moreover, no studies have reported improvements in progression-free or overall survival associated with PIPAC therapy. CONCLUSIONS: Randomized phase III studies are required to evaluate the effect of this therapy compared to other standard treatments (sequential or simultaneous applications with systemic chemotherapy). In cases of ovarian, tubal, and peritoneal cancer, PIPAC should not be performed outside the framework of prospective, controlled studies.

Gota úrica visceral em bobo-pequeno (Puffinus puffinus) no sul do Brasil / Visceral gout uric in manx shearwater (Puffinus puffinus) in Southern of Brazil

A gota úrica visceral é uma doença que acomete répteis, aves e mamíferos. Caracteriza-se por depósitos de cristais de urato e ácido úrico em diferentes órgãos da região visceral. O objetivo deste trabalho foi relatar um caso de gota úrica visceral em um indivíduo de bobo-pequeno (Puffinus puffinus) encontrado morto no litoral norte de Santa Catarina, sul do Brasil. No período de 20 de agosto de 2015 a 20 de abril de 2016, as praias dos municípios de Araquari, Barra do Sul, São Francisco do Sul e Itapoá foram monitoradas diariamente para o registro e a recuperação de tetrápodes marinhos mortos, incluindo aves marinhas. Foram encontrados e necropsiados 84 indivíduos. Um deles apresentou o pericárdio aderido ao miocárdio e com a coloração esbranquiçada. Os rins, o fígado e os pulmões continham inúmeros pontos esbranquiçados. A ocorrência dessa patologia na espécie foi de 1,19%. Trata-se do primeiro relato de bobo-pequeno com gota úrica visceral encontrado no Brasil.(AU)

Visceral gout uric is a disease that affects reptiles, birds and mammals. It is characterized by urate crystal deposits and uric acid in different organs of visceral region. The objective of this study was to report a case of visceral urica drop in a manx shearwater individual (Puffinus puffinus) found dead on the north coast of Santa Catarina, Southern Brazil. In the period from 20 August 2015 and 20 April 2016, beaches in the municipalities of Araquari, Barra do Sul, São Francisco do Sul and Itapoá, were monitored daily for the registration and recovery of dead marine tetrapods, including seabirds. Eighty-four were found and necropsied. One of them was whitish in color and had the pericardium adhered to the myocardium. The kidneys, liver and lungs contained numerous whitish dots. The occurrence of this disease in the species was 1.19%. This is the first manx shearwater report with visceral urica drop found in Brazil.(AU)

Systematic review of the efficacy and safety of biological therapy for inflammatory conditions in HIV-infected individuals.

Biologic therapies are injectable immunomodulatory agents directed against specific immune cell or chemical targets. They have transformed the lives of HIV-uninfected individuals with severe inflammatory conditions including psoriasis, rheumatoid arthritis, and ulcerative colitis. The perceived increased infection risk associated with these agents means that HIV-infected individuals have not been included in randomised control trials of these drugs. The literature for use of biologic therapies in HIV-infected populations is limited to case reports and case series. There are additional data on use of rituximab, a monoclonal antibody against B lymphocytes, in the setting of HIV-associated haematological malignancy. We performed a systematic review of efficacy and safety of biologic therapy for inflammatory conditions in HIV-infected individuals. Our systematic review identified 37 treatment episodes with six different biologic agents encompassing 10 different inflammatory conditions. Broadly, efficacy of the agents studied was comparable to reports from HIV-uninfected patients. Both infectious and non-infectious sequelae were also comparable with trial data from HIV-uninfected patients. HIV control, even for the minority of individuals not receiving anti-retroviral therapy (ART) at the time of biologic therapy, was not adversely affected. However, detail was limited concerning ART regimens and both immunological and virological parameters of follow-up. Overall available literature is of very low quality and likely subject to publication bias of successful cases. Firm conclusions are not possible regarding the efficacy and safety of biologic agents in HIV-infected individuals; however, there appear to be sufficient data to warrant inclusion of individuals with well-controlled HIV in future trial studies.

Comparison of quartz vials with polypropylene vials for rapid cryopreservation of human ovarian tissue.

BACKGROUND: Because higher survival of follicles during the freezing/thawing procedure improves the quality of cryopreserved tissue reimplanted after oncological therapies, defining an optimal method for human ovarian tissue cryopreservation remains a major issue in this field. One option to improve the cryopreservation procedure is to use better materials, i.e., vials with better conductivity. The aim of this study was to compare polypropylene (PP) with quartz vials. Between September 2012 and January 2013, eight patients were recruited. The ovarian cortex was cut into 3 slices, assigned randomly to a fresh and a cryopreserved group in PP (method B) or quartz vials (method C). Histological and immunohistochemical (IHC) analysis were used. For IHC three antibodies were analyzed: Ki67 (proliferation index), Bcl2 (anti apoptotic index) and Hsp70 (stress index). RESULTS: The majority of GCs showed positive staining for Bcl2 in both cryopreservation device, with higher expression in group C than in group B. Oocytes and their nuclei showed intense positive staining for ki67 in both methods B and C, and also a patch positive stromal cells staining for Ki67. Expression of hsp70 was not increased after cryopreservation. CONCLUSIONS: Cryopreservation using quartz vials led to larger numbers of good follicles while maintaining consistent preservation for stromal cells and vessels.

Statement of the AGO Kommission Ovar, AGO Study Group, NOGGO, AGO Austria and AGO Switzerland Regarding the Use of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer.

The AGO Kommission Ovar already published a statement in 2013, warning about the uncritical use of hyperthermic intraperitoneal chemotherapy (HIPEC) outside controlled studies. This statement has now been updated after the most recent literature was reviewed by AGO Kommission Ovar, the AGO Study Group, NOGGO, AGO Austria and AGO Switzerland. The authors conclude that HIPEC remains experimental. Its use is not recommended and should be rejected outside of prospective controlled trials.

Assessment and refinement of intra-bone marrow transplantation in mice.

Intra-bone marrow transplantation (IBMT) may improve the seeding efficiency of transplanted hematopoietic stem cells compared to the routinely used intravenous injection. Current IBMT protocols are optimized for ease of use and to improve experimental results. However, there have been no investigations to assess the impact of IBMT on animal welfare. Here, we report the results of pain assessment after IBMT and the effects of refinements to the current standard procedure. IBMT was performed in either the tibia or the femur of a recipient mouse under general anesthesia. Impact was determined using clinical scoring of different parameters (lameness, grip capacity, body weight loss, footprint analysis), behavioural tests (burrowing, open-field), monitoring of stress hormones and post-mortem histology. The results revealed that IBMT definitely induces severe post-operative distress. Although IBMT in the tibia is technically easier, the degree of impairment and the distress observed were consistently higher than for transplantation in the femur. A refinement for IBMT in the tibia was achieved by using 30- instead of 26-gauge needles and by sparing the patellar tendon. Consequently, for IBMT, we recommend either using the femur, or if the tibia is required due to its better feasibility, using our refined protocol. Furthermore, IBMT should definitely be limited to one leg per animal.

A mixed methods epidemiological investigation of preventable deaths among U.S. Army soldiers assigned to a rehabilitative warrior transition unit.

BACKGROUND: The prevalence of medical risk factors for suicide (e.g., mental disorders, severe disability, social disruption) may be higher among WTs compared to traditional Army units. Likewise, the extent to which traditional factors that protect soldiers from developing serious mental disorders (e.g., social support, unit cohesion, leadership) are present among soldiers assigned to the WTU is unclear. OBJECTIVES: An epidemiological consultation (EPICON) was conducted in 2010 to assess potential causes for a perceived high rate of suicides and preventable deaths in U.S. Army Warrior Transition Units (WTUs) and to identify potential improvements to the system of care. METHODS OF STUDY: The EPICON focused on: (1) risk factors for suicide/preventable deaths; (2) chronic pain management; (3) utilization of and access to WTU medical and behavioral health (BH) services; and (4) the impact of the WTU environment on mission focus and warrior disposition. BH history was examined for soldiers who died by suicide or preventable death while assigned to the WTU (index cases) and a representative comparison group of non-index case soldiers. Surveys and focus groups were conducted at four WTUs with Warriors in Transition (WTs) and key support staff. RESULTS: The use of psychotropic and/or CNS depressant medications, prevalence of BH diagnoses and substance use disorders, polypharmacy, alcohol use, and a high cumulative number of stressors were identified as important risk factors for preventable deaths in the WTC. Areas of potential improvement to the system of care included addressing negative perceptions of the WTU environment, lack of social support, barriers to accessing BH services and issues related to coordination of care. CONCLUSIONS: There was no one single risk factor found to be associated with an increased likelihood of preventable deaths within the WTU. The unique design and operation of the WTUs as environments focused on treatment and rehabilitation provide both benefits and challenges to recovery and risk mitigation.

Activation of TLR-4 to produce tumour necrosis factor-α in neuropathic pain caused by paclitaxel.

BACKGROUND: Neuropathic pain is a common complication of treatment with the anti-neoplastic drug paclitaxel. Animal studies suggest neuroinflammation and transient receptor potential channels TRPA1 and TRPV4 are involved in the pathogenesis of pain in this condition. However, how neuroinflammation and TRPA1 and TRPV4 are linked to cause pain in paclitaxel-treated animals is not known. METHODS: Paclitaxel-induced pain was modelled by IP injection of paclitaxel (16 mg/kg) once a week for 5 weeks. The role of toll-like receptor 4 (TLR-4) in tumour necrosis factor-α (TNF-α) production and the effect of TNF-α on the expression of TRPA1 and TRPV4 were evaluated in vitro and in vivo. TNF-α signalling in dorsal root ganglion (DRG) was blocked by expressing soluble TNF receptor I (TNFsR) from a herpes simplex virus (HSV)-based vector (vTNFsR). RESULTS: Paclitaxel treatment increased the expression and release of TNF-α in satellite glial cells and increased the expression of TRPA1 and TRPV4 in DRG neurons in animals. In vitro, paclitaxel enhanced the expression and release of TNF-α in enriched primary satellite glial cells, an effect that was blocked by an inhibitor of TLR-4. Direct application of TNF-α to primary DRG neurons in culture up-regulated the expression of TRPA1 and TRPV4. In vivo, vector-mediated TNFsR release from DRG neurons reduced paclitaxel-induced up-regulation of TRPA1 and TRPV4 expression and prevented paclitaxel-induced pain. CONCLUSION: These results suggest that paclitaxel activation of TLR-4 to cause release of TNF-α from satellite glial cells increases the expression of TRPA1 and TRPV4 in DRG neurons to cause neuropathic pain.

Frequency and risk factors of lower limb lymphedema following lymphadenectomy in patients with gynecological malignancies.

OBJECTIVE: Lower limb lymphedema (LLL) is a major cause of morbidity in patients with gynecological malignancies after surgical treatment involving lymph node (LN) dissection. The aim of this study was to estimate the prevalence of LLL in such patients and detect risk factors for its occurrence. MATERIALS AND METHODS: A retrospective analysis of all patients undergoing lymphadenectomy in newly-diagnosed gynecological malignancies at the University Hospital of Zurich between 2000 and 2007 was performed. Data from 313 patients were collected. Twenty patients with pre-existing edema or missing information were excluded before analysis. Time-to-LLL was estimated using the Kaplan-Meier estimate and potential risk factors were evaluated by a Cox regression model. RESULTS: Estimated prevalence of LLL one year after surgery was 32%, increasing to 58% eight years after surgery. Median time to diagnosis of LLL was 5.2 years. The number of removed lymph nodes was significantly associated with time-to-LLL. Diagnosis of postoperative lymphocysts and local infections were accompanied by a significantly elevated risk for the development of LLL. Furthermore, time-to-LLL decreased with a higher body mass index (BMI) of the patient. In contrast, chemo- and radiotherapy, age, positive LNs, site of lymphadenectomy, and type of cancer were not observed to be associated with the occurrence of LLL. CONCLUSIONS: LLL is a frequent postoperative complication in patients undergoing lymphadenectomy for gynecological malignancies. It is thus imperative to sufficiently educate patients about the risk and symptoms of LLL prior to surgery. The data clearly show an association between time-to-LLL and number of dissected LNs, stressing the need to prospectively analyze the prevalence of LLL and carefully plan LN sampling as increasing knowledge is gained regarding the therapeutic benefit of sentinel and systemic lymphadenectomy in patients with different stages of gynecological malignancies.

Does increased tumor burden of sentinel nodes in breast cancer affect detection procedure?

Numerous studies have shown that sentinel lymph node biopsy (SLN) has a high level of detection sensitivity. Successful detection procedure depends on the amount of radioactivity and accumulation of blue dye in the SN. Our aim was to relate the differences observed in intraoperative SN presentation to tumor burden, characteristics of the primary tumor and patient attributes. Our retrospective analysis included 369 patients undergoing SLN in the Department of Gynecology of the University Hospital of Zurich within five years. Data was collected from the patients (age, BMI), the primary tumor (size, grading, hormone receptors, HER2 status) and the SNs removed (counts per second [cps], blue dye, size of nodular metastasis, extracapsular involvement, number of SNs excised). Because patients typically had more than one SN, a linear mixed-effects model was used to account for the clustering within one patient. SNs presented with significantly lower radioactivity in elderly (-1.8%/year, p < 0.001) and obese patients (-3.9%/kg/m2, p = 0.006) as well as in G3 primary tumors (p = 0.002). Radiocolloid accumulation decreased with increasing metastasis size (-6.1%/mm, p = 0.006). In conclusion the detection procedure of SNs is mainly affected by the patient's age and BMI and by nodular metastasis' size. Phagocytotic activity in the lymph node may increase radiotracer accumulation, showing the highest tracer signals in micrometastatic SNs. In large SN metastasis the lymph flow appears obstructed, reducing the axillary drainage and therefore making detection procedure difficult.

Indications and long-term clinical outcomes in 282 patients with pelvic exenteration for advanced or recurrent cervical cancer.

OBJECTIVE: The aim of this study was to summarize the clinical experience at our clinic with pelvic exenteration as a treatment for cervical cancer with special regard to the indications and outcomes of specific patient groups. METHODS: Medical records of 282 women who underwent pelvic exenteration to treat cervical cancer were analyzed. RESULTS: In total, 70 patients (25%) underwent primary exenteration, and 212 (75%) underwent secondary exenteration. Exenteration was anterior for 14 (5%) patients, posterior for 6 (2%) and total for 262 (93%). The overall survival (OS) of the 282 patients was 41% at 5 years and 37% at 10 years. The disease-free survival at 5 years was 61%. For 133 patients for whom pelvic exenteration was a curative procedure, the OS was 64% at 5 years and 57% at 10 years. For cases of pelvic exenteration as a palliative intervention, the OS was 19% at 5 years and 18% at 10 years. No difference was seen in the OS at 5 years between patients who received primary and secondary operations. No significant difference in the OS was found regardless of whether the patients had positive pelvic lymph nodes, whereas in cases of paraaortic lymph node metastasis, the OS was significantly lower. Out of all of the procedures, 139 (49%) involved no perioperative or postoperative complications. One major complication was reported for 72 (26%) patients, two complications occurred for 42 patients (15%) and more than three complications were noted for 29 (10%) patients. CONCLUSION: Pelvic exenteration is an effective technique with a high percentage of long-term survivors. To the best of our knowledge, our study involves the largest published number of patients treated with pelvic exenteration for a single gynecological cancer and shows that previous contraindications for pelvic exenteration, such as lymph node metastasis (especially when confined to the pelvic lymph nodes), older age or palliative intent, should be reconsidered.

Transgene-mediated expression of tumor necrosis factor soluble receptor attenuates morphine tolerance in rats.

Opiate/narcotic analgesics are the most effective treatments for chronic severe pain, but their clinical utility is often hampered by the development of analgesic tolerance. Recent evidence suggests chronic morphine may activate glial cells to release proinflammatory cytokines. In this study, we used herpes simplex virus (HSV) vector-based gene transfer to dorsal root ganglion to produce a local release of p55 tumor necrosis factor (TNF) soluble receptor in the spinal cord in rats with morphine tolerance. Subcutaneous inoculation of HSV vectors expressing p55 TNF soluble receptor into the plantar surface of the hindpaws enhanced the antinociceptive effect of acute morphine in rats. Subcutaneous inoculation of those vectors into hindpaws also delayed the development of chronic morphine tolerance in rats. TNF soluble receptor expressed by HSV vector reduced gene transcription of spinal TNFα and interleukin-1ß (IL-1ß) induced by repeated morphine. Furthermore, we found that TNF soluble receptor mediated by HSV reversed the upregulation of protein level of TNFα and IL-1ß and phosphorylation of p38 mitogen-activated protein kinase induced by repeated morphine. These results support the concept that proinflammatory cytokines may have an important role in the pathogenesis induced by morphine. This study provides a novel approach to treating morphine tolerance.

Prolonged regulatable expression of EPO from an HSV vector using the LAP2 promoter element.

We previously reported regulated expression of erythropoietin (EPO) over 4 weeks in the peripheral nerve in vivo, using a herpes simplex virus (HSV)-based vector containing a Tet-on regulatable gene expression cassette. To create a vector that would be appropriate for the treatment of chronic neuropathy, we constructed a HSV vector with expression of EPO under the control of the Tet-on system in which the HSV latency-associated promoter 2 element was used to drive the expression of the Tet-on transactivator. EPO expression from the vector was tightly controlled by administration of doxycycline (DOX) in vitro. One month after inoculation of the vector to transduce dorsal root ganglion (DRG) in vivo, administration of DOX-containing chow-induced expression of EPO. Mice with streptozotocin-induced diabetes, inoculated with the vector, were protected against the development of neuropathy by continuous administration of DOX-containing chow over the course of 3 months. Identical results were achieved when DOX was administered every other week over 3 months of diabetes, but administration of DOX, 1 week out of 3, provided only partial protection against the development of neuropathy. Taken together, these results suggest such a vector is well suited for clinical trial for the treatment of chronic or subacutely developing neuropathy.

Inpatient and outpatient loop electrosurgery excision procedure for cervical intraepithelial neoplasia: a retrospective analysis.

PURPOSE: To determine whether the outpatient loop electrosurgical excision procedure (LEEP) conization (out-LEEP) is as effective and safe as inpatient LEEP conization (in-LEEP) with regard to the complete removal of cervical dysplasia, recurrence-free survival and post-operative morbidity. METHODS: 233 patients were included in this retrospective cohort study from January 2002 to December 2007. 181 had outpatient treatment and 52 inpatient treatment. We used Mann-Whitney U test, two-sided Fisher's exact test, Chi-square test, log rank test and Kaplan-Meier curve. RESULTS: Incomplete excision was found in 16/52 (30.8%) cases in the inpatient group and 46/181 (25.4%) in the outpatient group (P = 0.48). Six patients had post-operative complications: two cases of secondary haemorrhage in each group (in-LEEP 3.8%, out-LEEP 1.1%, P = 0.22) and two cases of cervical stenosis amongst inpatients (3.8%, P = 0.049). Alteration of specimen by thermal artifact were reported in 4/52 (7.7%) of in-LEEP cones and 10/181 (5.5%) of out-LEEP cones (P = 0.52). Measurements of cones in both groups were comparable with a mean depth of 9.35 mm (±5.5 mm) and 8.4 mm (±3.4 mm), respectively. CONCLUSION: Our results suggest that efficacy and safety of ambulatory LEEP conization is comparable as in inpatient procedure.

[Erythropoietinin oncologic therapy -- what so we know about the risks?]. / Erythropoietin in der Onkologischen Therapie - was Wissen wir über die Risiken?

Erythropoietin is a glycoprotein predominantly produced in the kidney. It is an essential regulator of erythropoiesis in the bone marrow. Although cancer-associated anemia is caused by multiple factors, recombinant erythropoietin (rhuEpo) was widely used to treat and prevent this condition. Several clinical studies showed that the use of rhuEpo results in an efficient reduction of red blood cell transfusions in cancer-associated anemia. However, over the past twenty years, Epo and its receptor EpoR were found to be expressed also outside the hematopoietic system and in malignant tumors. This led to a discussion concerning potential risks associated with the application of erythropoiesis-stimulating agents in oncology.

Development of glioblastoma cell lines expressing red fluorescence for non-invasive live imaging of intracranial tumors.

UNLABELLED: Glioblastoma (GBM) cell lines expressing red fluorescent proteins were evaluated as a tool for non-invasive imaging of orthotopic tumors. MATERIALS AND METHODS: mKate2- and mCherry-transduced U251MG GBM lines were sorted by flow cytometry. The growth rates and drug sensitivity of the resulting cell lines were compared to those of the parental line. Following orthotopic implantation, mKate2-expressing cells were detected using multispectral imaging. RESULTS: Flow cytometry-sorted fluorescent populations exhibiting growth curves that were comparable to those of the parental line were selected. mKate2-expressing cells were inoculated orthotopically and formed tumors which were visualized non-invasively, allowing monitoring of tumor growth over time and the assessment of tumor response to temozolomide drug treatment. CONCLUSION: The strategy reported here led to the successful development of GBM models expressing mKate2 or mCherry. The fluorescence signal intensity measured in the brain of live animals correlates with tumor size, thus providing a method to assess tumor progression and response to treatment.