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Purpose To investigate the oncologic and reproductive outcome of a conservative treatment with progestin agents in early-stage grade 1 endometrial cancer (G1EC), grade 2 endometrial cancer (G2EC) or complex atypical hyperplasia (CAH) in young premenopausal women. Methods Women treated for early-stage endometrial cancer or atypical hyperplasia of the endometrium with a conservative therapy between 2006 and 2018 were enrolled in this retrospective analysis. Progestin agents were orally administered on a daily basis for 3 months for at least one cycle. Endometrial tissue was obtained by hysteroscopy and Dilatation & Curettage (D&C) being performed before and after end of treatment. Therapeutic response was assessed by pathological examination. Results A total of 14 patients were included. After treatment with progestin agents, 11 of these patients initially showed a complete or partial response. Three patients with early-stage endometrial cancer did not respond. Of the three patients with initially diagnosed atypical hyperplasia, none showed any remaining disease later. Of the eight patients with initially diagnosed endometrial cancer, who had responded to first treatment, three patients were re-diagnosed with endometrial cancer later. One patient with initial endometrial cancer became pregnant but aborted in the 10th week. Conclusion Due to its good efficacy, progestin agents offer a feasible therapeutic option in the fertility-preserving treatment of early-stage endometrial cancer in young premenopausal women. However, recurrence rate remains high. Therefore, a close follow-up is mandatory, also in responders. Patients should be informed of limitations and risks of conservative treatment. Yet after completion of family planning, hysterectomy should be performed.

Purpose Surgery and radiotherapy as part of breast cancer treatment can lead to lymphoedema of the upper extremities (breast cancer-related lymphoedema = BCRL) and reduce the quality of life (health-related quality of life = HRQoL). The aim of the present study was to investigate the influence of paddling in a dragon boat (PP), on HRQoL and BCRL in breast cancer survivors (BCS). Methods Between April and October 2017, a prospective case-control study evaluated the effects of PP compared to a control group. In the paddle group (n = 28), weekly arm circumference measurements were taken at four defined anatomic areas of the arm before and after training; in the control group (n = 70) the measurements were taken once a month. At the beginning and end of the study, questionnaires from both groups (SF 36, EORTC QLQ-C30) were evaluated to understand the differences in HRQoL. Results The paddle group started with a higher HRQoL compared to in the control group. Most interesting, whether the affected or unaffected arm, whether before or after training - the arm circumference decreased over time in the paddling group. A pre-existing lymphoedema was not negatively influenced by paddling. In the paddle group the physical health was constant over the season, while the physical health of the control group decreased significantly over time. Conclusion PP in a dragon boat does not lead to the development or worsening of pre-existing lymphoedema due to breast cancer therapy and seems to have a positive effect on the quality of life.

Background:Endometrial cancer ranges among the most common gynecologic cancers worldwide. As the incidence of causing risk factors increases it is also becoming more prevalent in younger, premenopausal women who havent´ completed family planning yet. Our study aimed to investigate the oncologic and reproductive outcome of a conservative treatment with progestin agents in early stage grade 1 endometrial cancer (G1EC), grade 2 endometrial cancer (G2EC) or complex atypical hyperplasia (CAH) in young premenopausal women. Methods:Women treated for early stage endometrial cancer or atypical hyperplasia of the endometrium with a conservative therapy between 2006 and 2018 were enrolled in this retrospective analysis. Progestin agents were orally administered on a daily basis for 3 months for at least one cycle. Endometrial tissue was obtained by hysteroscopy and Dilatation & Curettage (D&C) being performed before and after end of treatment. Therapeutic response was assessed by pathological examination.Results:A total of 14 patients were included. After treatment with progestin agents, 11 of these patients initially showed a complete or partial response. Three patients with early stage endometrial cancer did not respond. Of the three patients with initially diagnosed atypical hyperplasia, none showed any remaining disease later. Of the 8 patients with initially diagnosed endometrial cancer, who had responded to first treatment, 3 patients were re-diagnosed with endometrial cancer later. One patient with initial endometrial cancer became pregnant but aborted in the 10th week. Conclusion:Due to its good efficacy progestin agents offer a feasible therapeutic option in the fertility preserving treatment of early stage endometrial cancer in young premenopausal women. However, recurrence rate remains high in early stage endometrial cancer. Therefore, a close follow-up is mandatory, also in responders. Patients should be informed of limitations and risks of conservative treatment. Yet after completion of family planning, hysterectomy should be performed.

ObjectiveIn cancer patients, the pathology report serves as an important basis for treatment. Therefore, a correct cancer diagnosis is crucial, and diagnostic discrepancies may be of clinical relevance. It was the aim of this study to perform a specialized histopathology review and to investigate potential clinical implications of expert second opinion pathology in endometrial cancer.MethodsPatients treated for endometrial carcinoma at the Tübingen University Women's hospital between 2003 and 2013 were identified. Original pathology reports were reviewed, and contributing pathologists were asked to submit original slides and paraffin blocks. Case review was subsequently performed by 3 pathologists specialized in gynecological pathology who were blinded for clinical information. For histological typing, the World Health Organization 2014 classification was used, grading and staging were performed according to International Federation of Gynecology and Obstetrics 2009. Risk assignment was performed based on the 2013 European Society for Medical Oncology clinical practice guidelines.ResultsIn 565 of 745 cases, which had originally been diagnosed as endometrial carcinoma, archival histological slides and blocks were available. In 55 (9.7%) of 565 cases, a major diagnostic discrepancy of potential clinical relevance was found after expert review. In 38 of these 55 cases, the diagnostic discrepancy was related to tumor type (n = 24), grade (n = 10) or myoinvasion (n = 4). In 17 cases, the diagnosis of endometrial carcinoma could not be confirmed (atypical hyperplasia, n = 10; endometrial carcinosarcoma, n = 4; neuroendocrine carcinoma, n = 1; leiomyosarcoma, n = 1; atypical polypoid adenomyoma, n = 1). Minor discrepancies not changing risk classification were also noted in 214 (37.9%) of 565, most frequently for grade within the low-grade (G1/G2) category (n = 184).ConclusionsA retrospective gynecopathological case review was shown to reveal limited but significant discrepancies in histological diagnoses as well as typing and grading of endometrial carcinomas, some directly impacting clinical management. Second opinion pathology therefore not only helps to improve the quality of translational research study cohorts but might also help to optimize patient care in difficult cases.

BACKGROUND/AIM Only 30-50% of patients with sentinel lymph node (SLN) metastases present with further axillary lymph node metastases. Therefore, up to 70% of patients with positive SLN are overtreated by axillary dissection (AD) and may suffer from complications such as sensory disturbances or lymphedema. According to the current S3 guidelines, AD can be avoided in patients with a T1/T2 tumor if breast-conserving surgery with subsequent tangential irradiation is performed and no more than two SLNs are affected. Additionally, use of nomograms, that predict the probability of non-sentinel lymph node (NSLN) metastases, is recommended. Therefore, models for the prediction of NSLN metastases in our defined population were constructed and compared with the published nomograms. PATIENTS AND METHODS In a retrospective study, 2,146 primary breast cancer patients, who underwent SLN biopsy at the University Women's Hospital in Tuebingen, were evaluated by dividing the patient group in a training and validation collective (TC or VC). Using the SLN-positive TC patients, three models for the prediction of the likelihood of NSLN metastases were adapted and were then validated using the SLN-positive VC patients. In addition, the predictive power of nomograms from Memorial Sloan Kettering Cancer Center (MSKCC), Stanford, and the Cambridge model were compared with regard to our patient collective. RESULTS A total of 2,146 patients were included in the study. Of these, 470 patients had positive SLN, 295 consisted the training collective and 175 consisted the validation collective. In a regression model, three variants - with 11, 6 and 2 variables - were developed for the prediction of NSLN metastases in our defined population and compared to the most frequently used nomograms. Our variants with 11 and with 6 variables were proven to be a particularly suitable model and showed similarly good results as the published MSKCC nomogram. CONCLUSION Our developed nomograms may be used as a prediction tool for NSLN metastases after positive SLN.

To investigate in a large cohort of young university women whether different progestins and different ethinyl estradiol (EE) dosages in oral hormonal contraceptives (OHCs) adversely affect sexual function.Female medical students from German, Austrian, and Swiss universities (14/1/1) completed an anonymous online questionnaire comprising the 19 Female Sexual Function Index (FSFI) questions and 17 additional questions concerning demographics, lifestyle, sexual activity, and contraceptive use. OHCs were categorized by EE dose (≤20,20 to ≤30, and30 µg) and partially androgenic or antiandrogenic progestins. FSFI scores were analyzed by contraceptive method using descriptive statistics and standard nonparametric tests.We analyzed 2612 questionnaires submitted by respondents aged ≤30 years [mean age (SD) 23.5 (2.5) years]. Of 2126 contraceptive users, 1535 (72.2 %) used OHCs. Median FSFI total scores (ranges) were 28.2 (2.0-36.0) for all respondents. Median FSFI was significantly lower in non-users (24.4) versus users (28.7) of contraception (p 0.001). Stratified analysis showed that 279/486 (57.4 %) respondents using no contraceptives, 563/1535 (36.7 %) using OHCs, 71/227 (31.3 %) using non-oral hormonal contraceptives, and 96/351 (27.4 %) using non-hormonal contraceptives were at risk for female sexual dysfunction (FSFI total score26.55). FSFI scores for the three EE dosage categories and progestin components did not differ significantly.For OHCs, the FSFI score was lower than for other contraceptives but there was no significant association with EE dose or progestins, possibly due to small sample sizes. Further research needs to clarify the role of OHCs in female sexual function.

Several classification systems for female genital tract anomalies exist but are of limited use in clinical practice. We, therefore, assessed the applicability and ease of use of the new ESHRE/ESGE classification, using only patient records. This retrospective, single-center, proof-of-principle study systematically analyzed the surgical reports and other hospital records of 920 inpatients and outpatients treated for confirmed female genital tract congenital malformations at a major German university hospital during 2003–2013. Using only this information, a non-expert (medical student) assigned patients to an ESHRE/ESGE class, rating ease of classification based on the time and the number of additional medical records required. Results were verified by an expert gynecologist, who also classified any malformations previously left unclassified. Data analysis used descriptive statistics. The non-expert successfully classified 859/920 patients (93.4%), rating classification as “easy” for 836/859 (90.9%) and “moderately difficult” for 23/859 (2.5%) patients. The expert gynecologist successfully classified 60 (60/920, 6.5%) of the remaining 61 patients rated as “difficult” by the non-expert, but was unable to accurately subclassify 1 patient (1/920, 0.1%) because the operative report lacked the relevant details. 251/920 (27.3%) patients had associated non-Mullerian anomalies, most frequently renal (20.9%) and skeletal (9.1%) malformations. The ESHRE/ESGE classification provides a generally applicable, comprehensive, and adequately specific classification of female genital tract congenital malformations. It offers an efficient basis for communication between non-experts and experts in the field and is, therefore, useful in clinical management and treatment planning.

Objective The main objectives of our study were to demonstrate that laparoscopic supracervical hysterectomy (LSH) or total laparoscopic hysterectomy (TLH) can be performed safely even in patients with a uterine weight ≥ 500 g, to analyze the rate of conversions to laparotomy due to uterine size and to estimate the incidence and type of intraoperative and long-term postoperative complications. Study Design Retrospective open, single-center, comparative interventional study of LSH and TLH. Results The present study comprised a total of 138 patients that underwent laparoscopic hysterectomy with a uterine weight ≥ 500 g; 109 patients (79.0 %) underwent LSH and 29 patients (21.0 %) underwent TLH. Median uterine weight across the entire cohort was 602 g, with the largest uterus weighing 1860 g. A total of 24 cases (17.4 %) among the 138 hysterectomies were converted to a laparotomy due to lack of adequate intraabdominal space and size of the uterus. Mean uterine weight of the patients in the LSH group that underwent conversion was 883 g (SD 380 g, n = 13) and 757 g (SD 371 g, n = 11) in the TLH group. The rate of conversion to laparotomy due to the uterine weight was significantly lower in the LSH group (11.9 %) compared to the TLH group (37.9 %) (p = 0.002). Intraoperative complications requiring laparotomy for other reasons but uterine size occurred in 6 patients of the study cohort (6/138; 4.3 %). Long-term postoperative complications occurred in 2 patients (2/138, 1.4 %), both patients from LSH group had to be re-operated on due to adhesions. Conclusions Our study adds further insight in the limited data set of laparoscopic hysterectomy for increased uterine weight and shows that LSH and TLH are safe and feasible even in patients with very large uteri (≥ 500 g).

The aim of this study is to systematically investigate under standardized experimental conditions the effects of instrument contamination and wear on the quality of bipolar vessel sealing (BVS) achieved using a reusable instrument.The study was designed as a prospective, randomized, and controlled in vitro study and conducted in an academic research environment. Reusable bipolar coagulation forceps (BiClamp® 200 C, ERBE Elektromedizin) were used to apply sealing pressures of 300-1,100 mN/mm(2) to 239 renal arteries from commercially slaughtered female pigs (Swabian-Hall Swine). Forceps jaws were coated with porcine blood, blood and collagen, or blood, collagen, and fat to simulate instrument contamination with biological material during surgery. Clinical wear was mimicked by sandpaper abrasion. The main outcome measures were seal success (resistance to 250 mmHg intraluminal pressure for 2 min) and seal stability (burst pressure).Sealing pressure had a significant impact, with 800 mN/mm(2) producing the best sealing results. Seal success increased with total energy applied to the tissue, a higher maximum temperature, and longer coagulation as indicated by desiccation time. Experimental contamination had no significant impact on seal success and only a limited effect on seal stability. Similarly, abrasive wear also had no significant effect on either seal quality or seal strength.The impact of bipolar forceps contamination and wear on seal success and quality was negligible in our in vitro model. To achieve high-quality seals, it is essential to use adequate sealing pressures. Our findings could have direct implications for the design and clinical handling of BVS instruments.

Low- and intermediate-risk endometrial carcinomas have an excellent prognosis. Nonetheless, a small subgroup of such patients will experience unexpected relapse. Recently L1CAM was suggested to be a strong prognosticator in endometrial carcinoma. The focus of our study was on low- and intermediate-risk disease, where no or only limited adjuvant treatment is recommended according to current guidelines.Endometrial carcinomas of low, intermediate and high-intermediate risk according to published 2016 consensus guidelines were identified. The study was limited to cases with previous central pathology review focusing on histotype, depth of myometrial invasion, presence of lymphovascular space invasion (LVSI) and MELF pattern of invasion. Standard L1CAM immunohistochemistry was performed. Disease-specific uni- and multivariate survival analyses were calculated.A total of 344 cases were available for immunohistochemistry (low-risk: n = 250; intermediate-risk: n = 67; high-intermediate-risk: n = 27). L1CAM positivity rates were: 29/344 (8.4 %; all cases), 18/250 (7.2 %; low-risk), 6/67 (9.0 %; intermediate-risk) and 5/27 (18.5 %; high-intermediate-risk). Expression of L1CAM was independent of LVSI and MELF. L1CAM was a significant independent prognosticator for disease-specific survival with a hazard ratio of 5.98 [CI 1.50-22.14, p = 0.012]. Adverse prognostic significance of L1CAM positivity was maintained after low-risk subgroup analysis (5-year disease-specific survival rates 71.8 vs. 100 %, p 0.0001). All four tumour-related deaths in the subgroup of low-risk disease occurred in patients with L1CAM-positive tumours.The current definition of "low-risk" in endometrial carcinoma should be amended. "Low-risk carcinomas" should be limited to L1CAM-negative tumours. L1CAM status will play a key role in future algorithms to tailor adjuvant treatment and patient follow-up strategies.

The main part of cytosolic protein degradation depends on the ubiquitin-proteasome system. Proteasomes degrade their substrates into small peptide fragments, some of which are translocated into the endoplasmatic reticulum and loaded onto MHC class I molecules, which are then transported to the cell surface for inspection by CTL. A reliable prediction of proteasomal cleavages in a given protein for the identification of CTL epitopes would benefit immensely from additional cleavage data for the training of prediction algorithms. To increase the knowledge about proteasomal specificity and to gain more insight into the relation of proteasomal activity and susceptibility to prion disease, we digested sheep prion protein with human constitutive and immuno-20S proteasomes. All fragments generated in the digest were quantified. Our results underline the different cleavage specificities of constitutive and immunoproteasomes and provide data for the training of prediction programs for proteasomal cleavages. Furthermore, the kinetic analysis of proteasomal digestion of two different alleles of prion protein shows that even small changes in a protein sequence can affect the overall efficiency of proteasomal processing and thus provides more insight into the possible molecular background of allelic variations and the pathogenicity of prion proteins.

To compare patient-reported quality-of-life and sexual function outcomes in women after laparoscopic supracervical hysterectomy (LSH) or total laparoscopic hysterectomy (TLH) for benign uterine disease. Out of a cohort of 1,952 patients from a previous implementation study of LSH and TLH, 1,886 patients who had not undergone intraoperative conversion to laparotomy or were ineligible for other reasons were invited by mail to participate in this prospective, questionnaire-based follow-up study. Of the 915/1,952 (48.5 %) survey respondents included in the analysis, 788 (86.1 %) and 127 (13.9 %) had undergone LSH or TLH, respectively. Women undergoing LSH reported significantly lower pain levels (p = 0.037) and faster partial (p = 0.015) and complete (p

Background To prospectively assess circulating tumor cell (CTC) status at baseline (CTCBL) and after one cycle of a new line of systemic therapy (CTC1C), and changes from CTCBL to CTC1C (CTC kinetics, CTCKIN) for their utility in predicting response, progression-free (PFS) and overall survival (OS) in metastatic breast cancer (MBC). Methods CTCBL and CTC1C status was determined as negative (-) or positive (+) for

We investigate very simple individual based models with movement, alignment and attraction rules. They can be formulated as dimer or generalised cellular automata. We distinguish decision and averaging models. In both classes movement and alignment can be achieved quite easily. We could produce a schooling-like behaviour with the combination of movement, alignment and attraction only in averaging models.

Objective: Currently available monopolar loop electrodes are difficult to handle in laparoscopic supracervical hysterectomy (LSH) and are entirely disposable devices, generating additional operating costs. The aim of this interventional study was the comparison of the efficiency and safety of cervical detachment with a newly developed monopolar loop electrode (SupraLoop™) with a conventional method of cervical detachment in LSH. Material and Methods: Our study sample included 1598 patients; 1070 patients that underwent LSH with cervical detachment using the monopolar SupraLoop™ (study group) and 528 patients that underwent LSH with cervical detachment using the monopolar needle (control group). We also assessed cervical detachment time and total device application and cutting time in a subgroup of 49 patients (23 patients from the study group and 26 patients from the control group). Results: Total operation time for LSH was significantly shorter among SupraLoop™ patients (93 ± 41 minutes) when compared to patients in whom cervical detachment was performed with the needle (105 ± 44 minutes) (p

A statistical-mechanical model for the propagation of a space-dependent epidemic is suggested based on the following assumptions. (1) The population is made up of three types of individuals, susceptibles, infectives and recovered. The total population size is constant and confined in a given region of d s -dimensional Euclidean space ( d s = 1, 2, 3). (2) An infected individual has a constant probability of recovery and an immune recovered individual has a constant probability of resensibilization. (3) Any infected individual from a given neighborhood of a susceptible individual has a probability p ( r ) of transmitting the disease which depends on the distance r between the two individuals. (4) The individuals migrate from one position to another with a rate depending on the displacement vector between the two positions. A statistical-mechanical description of the epidemic spreading is given in terms of a set of grand canonical probability densities for the positions and states of the individuals. An exact nonlinear evolution equation is derived for these probability densities and a self-consistent procedure of solving it is suggested. An explicit computation is presented for the case of very fast migration based on the adiabatic elimination of the coordinates of the individuals. An eikonal approximation for the fluctuations of the different types of individuals irrespective of their positions is developed in the limit of very large systems with constant total population density resulting in a Hamilton-Jacobi equation for the logarithm of the probability density of the proportions of susceptibles, infective and recovered. The deterministic equations of the process are identified with the evolution equations for the most probable fluctuation paths. If the individuals are confined at discrete positions in space this approach leads to the ordinary differential equation description of cellular automata epidemics presented in the literature. A continuous space alternative description is also presented. It is shown that the logarithm of the probability density of population fluctuations is a Liapunov function for the deterministic evolution equations. This Liapunov function is used for developing a generalized thermodynamic formalism of the epidemic process similar to the thermodynamic and stochastic theory of Ross, Hunt and Hunt from nonequilibrium thermodynamics of transport processes and reaction-diffusion systems.

A general method for constructing self-similar scalar fractal random fields is suggested based on the assumption that the fields are generated by a broad distribution of punctual sources. The method is illustrated by a problem of population biology, the evolution on a random fitness landscape. A random fitness landscape is constructed based on the following hypotheses. The landscape is defined by the dependence of a fitness variable φ on the state vector x of the individuals: φ = φ( x ) ; the corresponding hypersurface has a large number of local maxima characterized by a local probability law with variable parameters. These maxima are uniformly randomly distributed throughout the state space of the individuals. From generation to generation the heights and the shapes of these local maxima can change; this change is described in terms of two probabilities p and α that an individual modification occurs and that the process of variation as a whole stops, respectively. A general method for computing the stochastic properties of the evolutionary landscape is suggested based on the use of characteristic functionals. An explicit computation of the Fourier spectrum of the cumulants of the evolutionary landscape is performed in a limit of the thermodynamic type for which the number of maxima and the volume of the state space of the individuals tend to infinity but the density of maxima remains constant. It is shown that, although a typical realization of the evolutionary landscape is very rough, its average properties expressed by the Fourier spectrum of its cumulants are smooth and characterized by scaling laws of the power law type. The average landscape which is made up of the frozen contributions of the changes corresponding to different generations is flat, a result which is consistent with the Kimura's theory of molecular evolution. Some general implications of the suggested approach for the statistical physics of systems with random ultrametric topology are also investigated.

The possible occurrence of ergodic behavior for large times is investigated in the case of stationary random processes with memory. It is shown that for finite times the time average of a state function is generally a random variable and thus two types of cumulants can be introduced: for the time average and for the statistical ensemble, respectively. In the limit of infinite time a transition from the random to the deterministic behavior of the time average may occur, resulting in an ergodic behavior. The conditions of occurrence of this transition are investigated by analyzing the scaling behavior of the cumulants of the time average. A general approach for the computation of these cumulants is developed; explicit computations are presented both for short and long memory in the particular case of separable stationary processes for which the cumulants of a statistical ensemble can be factorized into products of functions depending on binary time differences. In both cases the ergodic behavior emerges for large times provided that the cumulants of a statistical ensemble decrease to zero as the time differences increase to infinity. The analysis leads to the surprising conclusion that the scaling behavior of the cumulants of the time average is relatively insensitive to the type of memory considered: both for short and long memory the cumulants of the time average obey inverse different from zero for large time differences, then the time averaage is random even as the length of the total time interval tends to infinity and the ergodic behavior no longer holds. The theory is applied to the study of long range correlations of nucleotide sequences in DNA; in this case the length t of a sequence of nucleotides plays the role of the time variable. A proportionality relationship is established between the cumulants of the pyrimidine excess in a sequence of length t and the cumulants of the time (length) average of the probability of occurrence of a pyrimidine. It is shown that the statistical analysis of the DNA data presented in the literature is consistent with the occurrence of the ergodic behavior for large lengths. The implications of the approach to the analysis of the large time behavior of stochastic cellular automata and of fractional Brownian motion are also investigated.

To compare laparoscopic supracervical hysterectomy (LSH) with total laparoscopic hysterectomy (TLH) with regard to relevant surgical parameters and risk factors of conversion to laparotomy and complications. This prospective, open, single-center, interventional study included women with benign gynecologic disease who underwent standardized LSH or TLH. The techniques were compared for conversion rate and mean operating time, hemoglobin drop, hospital stay, and complication rates using descriptive statistics and standard non-parametric statistical tests. Risk factors of conversion and complications were identified by logistic regression analysis. During January 2003 to December 2010, 1,952 women [mean age (SD): 47.5 (7.2) years] underwent LSH [1,658 (84.9 %)] or TLH [294 (15.1 %)], mostly (>70 %) for uterine fibroids. Significant differences in surgical parameters were observed for conversion rate (LSH/TLH: 2.6/6.5 %), mean operating time [87 (34)/103 (36) min], hemoglobin drop [1.3 (0.8)/1.6 (1.0) g/dL], and hospital stay [4.3 (1.5)/4.9 (2.8) days]. Overall intraoperative (0.2/0.7 %) and long-term (>6 weeks) post-operative (0.8/1.7 %) complication rates did not differ significantly, but the short-term LSH complication rate was significantly lower (0.6 vs. 4.8 %). Spotting (LSH, 0.2 %) and vaginal cuff dehiscence (TLH, 0.7 %) were long-term method-specific complications. Logistic regression showed that uterine weight and extensive adhesiolysis were significant factors for conversion while previous surgery, age, and BMI were not. Major risk factors of short-term complications were age, procedure (LSH/TLH), and extensive adhesions. Both procedures proved effective and were well tolerated. LSH performed better than TLH regarding most outcome measures. LSH is associated with very low rates of re-operation and spotting.

PURPOSE To study the rate of multifocal electroretinographic (mfERG) response amplitude changes and their relation to other parameters of disease development in retinitis pigmentosa (RP). METHODS Twenty-three patients (9 men and 14 women) with clinically defined RP were included in the study. Disease progression was monitored during a period of up to 10 years by psychophysical techniques and Ganzfeld electroretinography. In addition, ERGs were recorded with a mfERG imaging system (VERIS; Electro-Diagnostic Imaging, Inc., Redwood City, CA). The black and white stimulus consisted of 61 hexagons covering a visual field of approximately 60 degrees x 55 degrees . Responses were analyzed according to concentric ring averages. RESULTS The progression of visual field loss for target III4e was approximately 14.5%. Using the same type of regression model, the yearly progression according to the mfERG values was found to be approximately 6% to 10% in the outer three rings. Visual acuity (median 0.8) correlated well with the amplitude of the central segment of the mfERGs, ring 5 amplitudes of the mfERG strongly correlated with the scotopic Ganzfeld ERG mixed cone-rod response amplitude. However, in advanced cases, reliable mfERG responses could still be recorded, even if the ISCEV scotopic Ganzfeld ERG was not reproducible. MfERG ring 5 amplitudes as well as the Ganzfeld ERG mixed cone-rod response amplitude showed only a mild correlation with visual field area. CONCLUSIONS The mfERG allows long-term follow-up of disease progression in retinitis pigmentosa. It does not replace, but complements psychophysical methods and could be used as an objective outcome measure in upcoming treatment studies involving patients with advanced retinal diseases.

Proteasomes are the main proteases responsible for cytosolic protein degradation and the production of major histocompatibility complex class I ligands. Incorporation of the interferon γ–inducible subunits low molecular weight protein (LMP)-2, LMP-7, and multicatalytic endopeptidase complex–like (MECL)-1 leads to the formation of immunoproteasomes which have been associated with more efficient class I antigen processing. Although differences in cleavage specificities of constitutive and immunoproteasomes have been observed frequently, cleavage motifs have not been described previously.We now report that cells expressing immunoproteasomes display a different peptide repertoire changing the overall cytotoxic T cell–specificity as indicated by the observation that LMP-7−/− mice react against cells of LMP-7 wild-type mice. Moreover, using the 436 amino acid protein enolase-1 as an unmodified model substrate in combination with a quantitative approach, we analyzed a large collection of peptides generated by either set of proteasomes. Inspection of the amino acids flanking proteasomal cleavage sites allowed the description of two different cleavage motifs. These motifs finally explain recent findings describing differential processing of epitopes by constitutive and immunoproteasomes and are important to the understanding of peripheral T cell tolerization/activation as well as for effective vaccine development.