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Purpose Colposcopy-guided punch biopsy is a cornerstone method for diagnosing vulvar diseases. The aim of this study was to evaluate the concordance rate of clinical findings in vulvar diseases during examinations, in comparison with colposcopy-directed punch biopsy. We also developed a new classification to simplify the categorization of vulvoscopic findings. Methods The concordance rate of the clinical findings was compared with the final histology results from punch biopsies. The data were collected between January 2014 and May 2017 at the Erlangen University Hospital. Results A total of 482 colposcopy-directed punch biopsies of the vulva were obtained in 420 women. The overall concordance rate of the clinical findings in comparison with the histological vulvar punch-biopsy findings was 53.9% for all entities — benign lesions, lichen, low- and high-grade squamous intraepithelial lesions (LSIL/HSILs), and vulvar carcinoma. The concordance rate for detecting LSILs was 64.3% (45/70). The concordance rate for detecting HSILs was 62.3% and for Vulvar carcinoma 65.2%. Conclusions Punch biopsy of suspicious lesions continues to be a cornerstone in diagnosing HSILs and carcinoma of the vulva. Careful work-up of the vulva is recommended when patients have symptoms such as pruritus or pain. The new classification is more specific for diagnosing lesions in the vulva.

The purpose of this study was to determine and compare the gape angles (temporomandibular joint range of motion with mouth opening) of conscious and anesthetized domestic felines and to compare gape angles with and without evidence of oral pain. This prospective study evaluated the gape angle of 58 domestic felines. The cats were grouped into painful ( n = 33) and nonpainful cohorts ( n = 25) and gape angles were compared during conscious and anesthetized conditions. Gape angles were determined based on measurements of the maximal interincisal distance and lengths of the mandible and maxilla followed by calculation of the law of cosines. The mean feline gape angle (standard deviation) was determined to be 45.3° (8.6°) and 50.8° (6.2°) for conscious and anesthetized felines respectively. There was no significant difference between painful and non-painful feline gape angles during conscious ( P = .613) or anesthetized ( P = .605) evaluations. There was a significant difference between anesthetized and conscious gape angles ( P

Postmenopausal hormone therapy (HT) is known to affect the development of hormone-dependent endometrial carcinoma (type I EC). Several studies on breast and ovarian carcinoma have shown that HT influences the molecular profile and prognostic behavior of these tumors. This study aimed to investigate the influence of prior HT and other risk factors on the prognosis in a cohort of patients with invasive endometrial carcinoma (EC). Among 525 patients diagnosed with EC between 1987 and 2010, 426 postmenopausal patients were identified. Information regarding HT was available in 287 of these patients, 78 of whom had a history of HT and 209 of whom did not. Both overall survival (OS) and progression-free survival (PFS) were analyzed. In addition to OS and PFS, risk factors such as age at diagnosis, postmenopausal HT, body mass index (BMI), diabetes mellitus, tumor stage, EC type (I or II), and recurrences were analyzed. Relative to HT alone, women with EC and a history of HT had a longer survival than those with no HT. However, the Cox proportional hazards model showed that it was not HT itself, but rather other characteristics in the HT group that were causally associated with longer survival. Age (the older, the worse) and tumor stage (the higher, the worse) were significant influences on overall survival. Patients with HT also had lower BMIs, less diabetes, more type I EC, and fewer recurrences in comparison with the non-HT group. With regard to the PFS, it made no difference whether the patient was receiving HT.

The current cervical cancer screening program in Germany recommends that the results showing suspected HPV infection should be further examined in specialized colposcopy units. This study aimed to correlate externally documented Pap smear results with in-house colposcopy-guided Pap cytology results and compare colposcopy-guided biopsy and postoperative histopathology results. Clinical data were analyzed from 3627 examinations in 2844 patients who visited a university certified dysplasia unit from 2014 to 2017; 2212 patients underwent complete assessments, including Pap smear, colposcopy, HPV testing, colposcopy-guided biopsy, and/or surgery. The results were analyzed descriptively. External and in-house Pap results were consistent in 1054 ofthe 2212 patients (47.65%). Referral cytology showed a higher grade than in-house in 456 (20.61%) and a lower grade in 702 (31.74%). Using the histopathological findings as the gold standard, overdiagnosis in the referral cytology was noted in 180 patients (13.19%), underdiagnosis in 263 (19.27%), and concordant findings in 922 (67.55%). For in-house cytology, overdiagnosis was found in 133 patients (10.74%), underdiagnosis in 192 (15.51%), and accurate diagnosis with congruent cytology and histopathology findings in 913 (73.75%). The rate of detection of cervical abnormalities differs significantly depending on whether the examination is performed routinely or in specialized units. Colposcopy-guided Pap smears correlate significantly better with histology than referral cytology results without colposcopic guidance. More severe lesions were also detected more accurately.

Richter syndrome (RS) of chronic lymphocytic leukemia (CLL) is typically chemoresistant, with a poor prognosis. We hypothesized that the oral Bcl-2 inhibitor venetoclax could sensitize RS to chemoimmunotherapy and improve outcomes. We conducted a single-arm, investigator-sponsored, phase 2 trial of venetoclax plus dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (VR-EPOCH) to determine the rate of complete response (CR). Patients received R-EPOCH for 1 cycle, then after count recovery, accelerated daily venetoclax ramp-up to 400 mg, then VR-EPOCH for up to 5 more 21-day cycles. Responders received venetoclax maintenance or cellular therapy off-study. Twenty-six patients were treated, and 13 of 26 (50%) achieved CR, with 11 achieving undetectable bone marrow minimal residual disease for CLL. Three additional patients achieved partial response (overall response rate, 62%). Median progression-free survival was 10.1 months, and median overall survival was 19.6 months. Hematologic toxicity included grade ≥3 neutropenia (65%) and thrombocytopenia (50%), with febrile neutropenia in 38%. No patients experienced tumor lysis syndrome with daily venetoclax ramp-up. VR-EPOCH is active in RS, with deeper, more durable responses than historical regimens. Toxicities from intensive chemoimmunotherapy and venetoclax were observed. Our data suggest that studies comparing venetoclax with chemoimmunotherapy to chemoimmunotherapy alone are warranted. This trial was registered at www.clinicaltrials.gov as #NCT03054896.

Malignancies of the vagina are rare, but colposcopy-directed biopsies play a major role in detecting vaginal intraepithelial lesions. Data of accuracy in detecting neoplasia of the vagina are very rare compared to accuracy in detecting cervical neoplasia. The aim of this study was to evaluate the accuracy of colposcopy-directed biopsy in comparison with clinical findings of the examiner. The accuracy of colposcopy-directed biopsy was compared with the clinical finding in relation to the patient’s age and the examiner’s level of training. This was done in combination with PAP-smear, HPV-test results, and the history of other malignancies of the lower genital tract. The data were collected between January 2014 and February 2018 at the certified Dysplasia Unit of the University Hospital Erlangen. In total, 253 biopsies from 253 women from the vagina were obtained. The overall accuracy of biopsy in comparison with clinical finding was 52.17% for all entities—benign lesions, low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), and vaginal carcinoma. The accuracy for detecting HSIL was 82.46% (47/57), with an underdiagnosis rate of 15.79% and an overdiagnosis rate of 1.79%. With a sensitivity of over 80%, colposcopy-directed biopsy plays an important role in detecting vaginal–HSIL. A highly experienced practitioner is increasing the sensitivity in detecting vaginal–HSIL. Careful examination is required in women with a history of HSIL of the lower genital tract or with simultaneous neoplasia because they are of greater risk of developing vaginal malignancies. The combination of careful clinical work up, PAP-smear, HPV-testing, and colposcopy-guided biopsy is crucial in detecting vaginal–HSIL.

Background Daysy is a fertility monitor that uses the fertility awareness method by tracking and analyzing the individual menstrual cycle. In addition, Daysy can be connected to the application DaysyView to transfer stored personal data from Daysy to a smartphone or tablet (IOS, Android). This combination is interesting because as it is shown in various studies, the use of apps is increasing patients´ focus on their disease or their health behavior. The aim of this study was to investigate if by the additional use of an App and thereby improved usability of the medical device, it is possible to enhance the typical-use related as well as the method-related pregnancy rates. Result In the resultant group of 125 women (2076 cycles in total), 2 women indicated that they had been unintentionally pregnant during the use of the device, giving a typical-use related Pearl-Index of 1.3. Counting only the pregnancies which occurred as a result of unprotected intercourse during the infertile (green) phase, we found 1 pregnancy, giving a method-related Pearl-Index of 0.6. Calculating the pregnancy rate resulting from continuous use and unprotected intercourse exclusively on green days, gives a perfect-use Pearl-Index of 0.8. Conclusion It seems that combining a specific biosensor-embedded device (Daysy), which gives the method a very high repeatable accuracy, and a mobile application (DaysyView) which leads to higher user engagement, results in higher overall usability of the method.

Mit einer Inzidenz von 5,8/100 000 Frauen/Jahr ist das Vulvakarzinom das vierthäufigste Genitalkarzinom der Frau. Meist werden Vulvakarzinome in einem frühen Stadium diagnostiziert. Häufigstes Symptom ist der therapieresistente Pruritus, perineale Schmerzen und/oder beim Sitzen, Dysurie und Brennen. Bei der klinischen Inspektion sollte das komplette äußere Genitale mit Vagina, Perineum, Anus sowie die Zervix inspiziert werden. Liegt eine VIN1, LSIL (vulväre intraepitheliale Neoplasie Grad 1, low-grade squamous intraepithelial lesion) ohne Symptome vor, sind regelmäßige Kontrollen ausreichend. Bei symptomatischer LSIL, HPV-assoziierter VIN2 oder VIN3 (vulväre intraepitheliale Neoplasie Grad 2 oder 3, high-grade squamous intraepithelial lesion) kann eine Laserevaporisation erfolgen. Eine komplette Vulvektomie sollte nur bei multizentrischen Tumoren erfolgen. Eine systematische Lymphonodektomie ist ab Stadium T1b mit Infiltrationstiefe > 1 mm empfohlen. Eine adjuvante Radiotherapie der Primärtumorregion sollte bei non-in-sano-Situation durchgeführt werden, falls eine Nachresektion aus funktionellen Gründen oder Patientenwunsch nicht möglich ist. Eine lebenslange Nachsorge ist notwendig, denn jede dritte Patientin mit Vulvakarzinom erleidet ein Rezidiv. Als Therapie des Lokalrezidivs ohne Beteiligung von Anus, Urethra oder Lymphknoten sollte eine operative Resektion mit R0-Situation angestrebt werden.

Postmenopausal hormone therapy (HT) is known to affect the development of hormone-dependent endometrial carcinoma (type I EC). Several studies on breast and ovarian carcinoma have shown that HT influences the molecular profile and prognostic behavior of these tumors. This study aimed to investigate the influence of prior HT and other risk factors on the prognosis in a cohort of patients with invasive endometrial carcinoma (EC).Among 525 patients diagnosed with EC between 1987 and 2010, 426 postmenopausal patients were identified. Information regarding HT was available in 287 of these patients, 78 of whom had a history of HT and 209 of whom did not. Both overall survival (OS) and progression-free survival (PFS) were analyzed. In addition to OS and PFS, risk factors such as age at diagnosis, postmenopausal HT, body mass index (BMI), diabetes mellitus, tumor stage, EC type (I or II), and recurrences were analyzed.Relative to HT alone, women with EC and a history of HT had a longer survival than those with no HT. However, the Cox proportional hazards model showed that it was not HT itself, but rather other characteristics in the HT group that were causally associated with longer survival.Age (the older, the worse) and tumor stage (the higher, the worse) were significant influences on overall survival. Patients with HT also had lower BMIs, less diabetes, more type I EC, and fewer recurrences in comparison with the non-HT group. With regard to the PFS, it made no difference whether the patient was receiving HT.

The current cervical cancer screening program in Germany recommends that the results showing suspected HPV infection should be further examined in specialized colposcopy units. This study aimed to correlate externally documented Pap smear results with in-house colposcopy-guided Pap cytology results and compare colposcopy-guided biopsy and postoperative histopathology results.Clinical data were analyzed from 3627 examinations in 2844 patients who visited a university certified dysplasia unit from 2014 to 2017; 2212 patients underwent complete assessments, including Pap smear, colposcopy, HPV testing, colposcopy-guided biopsy, and/or surgery. The results were analyzed descriptively.External and in-house Pap results were consistent in 1054 ofthe 2212 patients (47.65%). Referral cytology showed a higher grade than in-house in 456 (20.61%) and a lower grade in 702 (31.74%). Using the histopathological findings as the gold standard, overdiagnosis in the referral cytology was noted in 180 patients (13.19%), underdiagnosis in 263 (19.27%), and concordant findings in 922 (67.55%). For in-house cytology, overdiagnosis was found in 133 patients (10.74%), underdiagnosis in 192 (15.51%), and accurate diagnosis with congruent cytology and histopathology findings in 913 (73.75%).The rate of detection of cervical abnormalities differs significantly depending on whether the examination is performed routinely or in specialized units. Colposcopy-guided Pap smears correlate significantly better with histology than referral cytology results without colposcopic guidance. More severe lesions were also detected more accurately.

BackgroundDisease-related symptoms impair the quality of life of patients with chronic lymphocytic leukaemia (CLL) who do not require systemic therapy. Available therapies are not specifically aimed at symptom control. Because stimulation of the B-cell receptor activates JAK2 in CLL cells and the JAK2 inhibitor ruxolitinib improves symptoms in patients with myelofibrosis, we postulated that ruxolitinib would improve disease-related symptoms in patients with CLL. We did a phase 2 trial of ruxolitinib to test this hypothesis.MethodsSymptomatic patients with CLL who did not require systemic therapy were enrolled at MD Anderson Cancer Center (Houston, TX, USA) between Sept 15, 2014, and Sept 20, 2015. Participants were given 10 mg ruxolitinib orally twice a day. Scores on the Brief Fatigue Inventory (BFI), CLL module of the MD Anderson Symptom Inventory (MDASI) and symptom-associated interference in daily activities, were assessed before treatment and after 3 months. This trial is ongoing and is registered at ClinicalTrials.gov (NCT02131584).Findings41 patients (25 previously untreated for CLL and 16 previously treated) were enrolled. At 3 months, the mean percentage change from baseline in BFI score was 44·3% (SD 35·0, p

Aktuell findet ein Paradigmenwandel in der Therapie des Zervixkarzinoms statt. Grundlage hierfur ist ein interdisziplinares Therapiekonzept mit dem Ziel einer unimodalen Therapiestrategie. Das bedeutet, entweder moglichst nur Operation oder nur Radio(chemo)therapie. Eine sequenzielle Abfolge sollte vermieden werden. Hierzu ist eine exakte praoperative Risikoanalyse notwendig, um interdisziplinar mittels Klinik, Pathologie und Bildgebung das Tumorstadium der Patientin zu definieren und mittels des operativen Stagings zu komplettieren. Weitere neue Entwicklungen zeigen sich auf dem Gebiet der primaren Pravention des Zervixkarzinoms mit dem neu am Markt zur Verfugung stehenden Neunfachimpfstoff mit erweitertem Humanpapillomvirus(HPV)-Typen-Spektrum sowie im Bereich der sekundaren Pravention mit der Diskussion um die Etablierung eines HPV-basierten Screeningprogramms.

8004 Background: While therapeutic options for CLL have improved, patients (pts) who develop Richter’s Syndrome (RS) still have a poor prognosis. Chemoimmunotherapy regimens such as R-EPOCH lead to CR in about 20% of RS pts, but PFS/OS is typically < 6 mo. The oral Bcl-2 inhibitor venetoclax (ven) had a 43% single agent response rate in RS. Here, we report the results of a phase 2 study of VR-EPOCH in RS. Methods: This is a single-arm, phase 2, IST of VR-EPOCH for RS (NCT03054896) at 3 US sites. CLL pts with biopsy-confirmed DLBCL were treated with R-EPOCH for 1 cycle, then after count recovery underwent accelerated inpatient ven daily ramp-up (20/50/100/200/400 mg), then ven + R-EPOCH for up to 5 more 21d cycles (ven 400 mg qd, d1-10 each cycle). Responders went to alloHCT or to continuous daily ven 400 mg maintenance. Response evaluation by Lugano criteria with PET/CT. Results: As of the data cut on 2/3/2020, the study is fully enrolled with 27 pts. Median age: 63 yrs (range 49-77). CLL features: 26% del(17p); 44% complex karyotype; 48% IGHV unmutated; 41% TP53 and 15% NOTCH1 mutation. Median prior CLL treatments: 2 (range 0-5, prior ibrutinib [n = 8], ven [n = 2], and PI3Ki [n = 2]) with 6 untreated CLL pts. Median # ven + R-EPOCH cycles: 4 (range 0-6). 5 pts had dose de-escalation of R-EPOCH, 1 pt had dose escalation. ≥Gr 3 heme tox: neutropenia (58%), anemia (50%), thrombocytopenia (50%). ≥Gr 3 non-heme tox in > 15% of pts: febrile neutropenia (38%) and hypophosphatemia (23% each). No pts had TLS with daily ven ramp-up. Infections: pneumonia (n = 4), sepsis during C1 of R-EPOCH prior to starting ven (n = 3), enterocolitis (n = 3), sinusitis (n = 2), and 1 pt each with influenza A and norovirus. 10 pts have died, including 7 due to disease progression (2 during C1 before ven), and 1 each due to sepsis, sudden death, and GVHD post-alloHCT. In ITT analysis, 16 responded (ORR 59%); 13/27 (48%) had CR as best response, all with undetectable bone marrow MRD for CLL. Six pts were not evaluable for efficacy of the combo (5 had toxicity in C1 and never started ven, 1 withdrew after C1). In the 21 pts who started combo therapy, the ORR was 76%, CR rate 62%. Only 1 pt with CR has progressed. The pt on longest ven maintenance is in CR 2 years post chemo. 8 pts went to alloHCT, with pts still in CR now up to 2.5 yrs post-alloHCT. With a median follow-up of 9.3 mo (range 0.6-30), median PFS and OS are both 16.3 mo. Conclusions: VR-EPOCH is active for RS. Expected toxicities from intensive chemoimmunotherapy and ven were seen, but daily ven ramp-up was feasible. The 48% CR rate and median PFS of 16.3 mo are favorable in the context of historical results. Clinical trial information: NCT03054896 .

Colposcopy-directed biopsy is a cornerstone method for diagnosing cervical intraepithelial neoplasia. The aim of this study was to evaluate the accuracy of colposcopy-directed biopsy in comparison with definitive surgery. The accuracy of colposcopy-directed biopsy was compared with the final histology in relation to different types of transformation zone (TZ), the patient’s age, and the examiner’s level of training. The overall accuracy of biopsy in comparison with definitive surgery was 71.9% for all entities—benign lesions, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), and cervical carcinoma—with an underdiagnosis rate of 11.8% and an overdiagnosis rate of 16.5%. The accuracy for detecting HSIL was 88% (401/455), with an underdiagnosis rate of 10.5% and overdiagnosis rate of 1.3%. The accuracy rates for detecting HSIL in women with TZ 1, TZ 2, or TZ 3 were 92.2, 90.5, and 76.5%, respectively. The accuracy rates for detecting HSIL in the different age groups were 93.1% (age 0–34), 83.6% (age 34–55), and 80% (age 55 or older). A combination of the colposcopic findings, cytology, human papillomavirus testing, and colposcopy-directed biopsy is necessary for the correct diagnosis of HSIL. The accuracy rate depends on the TZ and the patient’s age. The examiner’s level of training does not have any substantial influence on the accuracy.

Background In March 2018, Dr. Martin C. Koch and colleagues published an analysis purporting to measure the effectiveness of the Daysy device and DaysyView app for the prevention of unintended pregnancy. Unfortunately, the analysis was flawed in multiple ways which render the estimates unreliable. Unreliable estimates of contraceptive effectiveness can endanger public health. Main body This commentary details multiple concerns pertaining to the collection and analysis of data in Koch et al. 2018. A key concern pertains to the inappropriate exclusion of all women with fewer than 13 cycles of use from the Pearl Index calculations, which has no basis in standard effectiveness calculations. Multiple additional methodological concerns, as well as prior attempts to directly convey concerns to the manufacturer regarding marketing materials based on prior inaccurate analyses, are also discussed. Conclusion The Koch et al. 2018 publication produced unreliable estimates of contraceptive effectiveness for the Daysy device and DaysyView app, which are likely substantially higher than the actual contraceptive effectiveness of the device and app. Those estimates are being used in marketing materials which may inappropriately inflate consumer confidence and leave consumers more vulnerable than expected to the risk of unintended pregnancy. Prior attempts to directly convey concerns to the manufacturer of this device were unsuccessful in preventing publication of subsequent inaccurate analyses. To protect public health, concerns with this analysis should be documented in the published literature, the Koch et al. 2018 analysis should be retracted, and marketing materials on contraceptive effectiveness should be subjected to appropriate oversight.

Background Daysy is a fertility monitor that uses the fertility awareness method by tracking and analyzing the individual menstrual cycle. In addition, Daysy can be connected to the application DaysyView to transfer stored personal data from Daysy to a smartphone or tablet (IOS, Android). This combination is interesting because as it is shown in various studies, the use of apps is increasing patients´ focus on their disease or their health behavior. The aim of this study was to investigate if by the additional use of an App and thereby improved usability of the medical device, it is possible to enhance the typical-use related as well as the method-related pregnancy rates. Result In the resultant group of 125 women (2076 cycles in total), 2 women indicated that they had been unintentionally pregnant during the use of the device, giving a typical-use related Pearl-Index of 1.3. Counting only the pregnancies which occurred as a result of unprotected intercourse during the infertile (green) phase, we found 1 pregnancy, giving a method-related Pearl-Index of 0.6. Calculating the pregnancy rate resulting from continuous use and unprotected intercourse exclusively on green days, gives a perfect-use Pearl-Index of 0.8. Conclusion It seems that combining a specific biosensor-embedded device (Daysy), which gives the method a very high repeatable accuracy, and a mobile application (DaysyView) which leads to higher user engagement, results in higher overall usability of the method. Electronic supplementary material The online version of this article (10.1186/s12978-018-0479-6) contains supplementary material, which is available to authorized users.

Summary The prevalence of obesity is increasing in children and adolescents even in resource-poor countries. The study aimed to determine the prevalence of obesity in a group of Nigerian school children using triceps skin-fold thickness (SFT) and body mass index (BMI). The subjects were 1235 randomly selected primary and secondary Lagos school children aged 5–18 years, triceps SFT was measured with Harpenden® calipers and BMI calculated from weight and height. Using BMI, overweight and obesity were defined as values of 85th to 94th percentile for age and sex and ≥95th percentile, respectively. Using triceps SFT, obesity was defined as SFT > 85th percentile of the NHANES III study. Fifty-seven subjects (15 boys and 42 girls) had SFT > 85th percentile with a higher prevalence in girls than boys (6.4% vs. 2.6%, P = 0.001). The prevalence of BMI-defined overweight and obesity were also higher among girls (11.9% vs. 5.7%, P

Background: There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial. Methods: ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5–24.9 kg m−2), overweight (BMI=25–29.9 kg m−2), and obese (30 kg m−2) according to WHO criteria. Results: Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0·018) and a worse overall survival (OS; HR: 1·49; Cox P=0·052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0·24) and OS (HR: 0.99; Cox P=0·97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0·03) and a worse OS (1.47; Cox P=0·11) compared with normal weight patients. Conclusion: BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen.

Introduction: Endometriosis is a heterogeneous disease characterized by a range of different presentations. It is usually diagnosed when patients present with pain and/or infertility, but it has also been diagnosed in asymptomatic patients. Because of the different diagnostic approaches and diverse therapies, time to diagnosis can vary considerably and the definitive diagnosis may be delayed, with some cases not being diagnosed for several years. Endometriosis patients have many unmet needs. A systematic registration and follow-up of endometriosis patients could be useful to obtain an insight into the course of the disease. The validation of biomarkers could contribute to the development of diagnostic and predictive tests which could help select patients for surgical assessment earlier and offer better predictions about patients who might benefit from medical, surgical or other interventions. The aim is also to obtain a better understanding of the etiology, pathogenesis and progression of the disease. Material and Methods: To do this, an online multicenter documentation system was introduced to facilitate the establishment of a prospective multicenter case-control study, the IEEP (International Endometriosis Evaluation Program) study. We report here on the first 696 patients with endometriosis included in the program between June 2013 and June 2015. Results: A documentation system was created, and the structure and course of the study were mapped out with regard to data collection and the collection of biomaterials. Conclusion: The documentation system permits the history and clinical data of patients with endometriosis to be recorded. The IEEP combines this information with biomaterials and uses it for scientific studies. The recorded data can also be used to evaluate clinical quality control measures such as the certification parameters used by the EEL (European Endometriosis League) to assess certified endometriosis centers.

The development of an ultra-high-resolution high-dynamic-range infrared optical coherence tomography (OCT) imaging system is reported for the novel purpose of sub-surface inspection of silicon integrated-circuits. This approach utilises an almost octave-spanning supercontinuum source and a balanced-detection scheme in a time-domain OCT configuration to achieve an axial resolution of 2.5@mm in air, corresponding to ~700nm in silicon. Examples of substrate thickness profiling and device feature inspection capabilities for additional circuit navigation and characterisation are presented.

The relative magnitudes of the chemical shift differences (Deltadeltas) in the two diastereomers of menthyl esters of known chiral derivatizing agents (CDAs) were compared to those of the alpha-methoxy-alpha-trifluoromethyl-1-naphthylacetyl (MTN((1))A) analogues I. Discrimination of the terminal diastereotopic methyl resonances in esters of the homologous, symmetrical carbinols II was evaluated. Remarkably, the methyls differed in the MTN((1))A esters III even when n = 15; an unexpected crossover in the sign of the Deltadelta values was also observed.

BACKGROUND: Phyllodes tumour is a very rare fibroepithelial neoplasia of the female breast. As a consequence of its low worldwide incidence of 0.3–1% of female breast tumours, the diagnosis, treatment, and prognosis of this disease are largely speculative and unresolved. A nationwide multicentre analysis was carried out with the objective of describing the diagnostic and therapeutic methods currently used and assessing the prognosis of this rare disease. METHODS: From April 2000 to June 2001 a computer-assisted survey was carried out in 24 surgical and gynaecological departments in Austria. Using a data sheet, the departments collected information on phyllodes tumours treated until present, as well as the follow-up care, treatment, and the long-term results. RESULTS: Across Austria 85 cases of women with phyllodes tumour covering the period from January 1985 to December 2000 were included in this study. In 40 (47%) cases the tumour was localised in the left breast, in 37 (44%) cases it was in the right breast. The histological review of the surgical specimens found that 28 (33%) patients had a malignant phyllodes tumour. Eight (9%) cases were borderline and 46 (54%) benign. The mean follow-up time was 39 (11–85) months. Seven patients died during the study. CONCLUSIONS: Patients with borderline and benign lesions should also undergo regular follow-up. A breast-conserving operation with adequate excision margins should be the primary objective, since even malignant tumours seldomly metastasise.

Purpose Identification of prognostic factors for tumor recurrence in nephronsparing surgery and tumor progression after organ-preserving surgery. Material and methods From June 1989 to February 2003, 43 patients (47 nephron units) underwent organ-preserving surgery or the upper urinary tract because of urothelial carcinoma, with 26 (60.5 %) having an elective indication (healthy contralateral kidney). Results The mean follow-up was 39.2 months with a range of 10.6 to 168.3 months. Ipsilateral recurrences occurred in 13 (27.6 %) of reno-ureteral units. Recurrences were significantly more common for tumors located in the renal pelvis or opposite the ureteral origin (p = 0.018). Tumor progression occurred in 8 of 43 patients (18.6 %) and significantly correlated with the T- and G-stage of the primary tumor (p = 0.006 and p = 0.002). Of the 47 conservatively treated reno-ureteral units, 38 (80.8 %) could be preserved. Conclusion Organ-preserving resection of the urothelial carcinoma of the upper urinary tract is an alternative in some patients with well-differentiated superficial tumors. A follow-up for life and a good patient compliance are necessary. Tumors of the renal pelvis have a significantly higher recurrence rate than ureteral tumors. Poorly differentiated tumors should undergo organ-preserving surgery only if the goal is palliation and in patients with solitary kidney after intensive consultation about the high risk of invasive recurrences and the development of metastases.

Asymmetric aldol reactions were conducted with the titanium enolate of N(3)-hydrocinnamoyl-3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-one to afford aldol adducts 5a-j. The dominant product of the asymmetric aldol reaction was the non-Evans syn adduct as determined by (1)H NMR spectroscopy and X-ray crystallography. When evaluating the (1)H NMR spectra of adducts 5a-j, a highly shielded signal with an average chemical shift of 0.05 ppm was observed. This signal was readily determined to be the C(5)-methyl group of the oxadiazinone. It is presumed that the overall conformation adopted by the aldol adducts in solution places an aromatic ring of the N(3)-substituent in close proximity to the C(5)-methyl group. An investigation of this conformational preference is conducted employing (1)H NMR spectroscopy, X-ray crystallography, and computational methods.

Einleitung. Der arteriellen Verbindung zwischen Arteria mesenterica superior und Arteria mesenterica inferior kommt bei Eingriffen am Kolon sowie an der Aorta eine entscheidende Bedeutung zu.

In view of local recurrence rates of up to 50% after “curative” resection of rectal cancer, preoperative pelvic radiotherapy was introduced. 1–3 Short-term preoperative radiotherapy using 25 Gy resulted in significant improvement in overall survival, disease-free survival, and local control compared with surgery only and with postoperative radiotherapy. 4 In addition, the implementation of the technique of total mesorectal excision has been shown to be associated with a significant reduction in local recurrence rates. 5 Today the combination of both strategies is recommended as a standard procedure for treatment of locally advanced rectal cancer, although there is still no agreement as to the optimal intensity and sequencing of adjuvant treatment. 6 The effect of radiotherapy is based on induction of DNA damage. DNA damage is a well-known trigger for p53-dependent apoptosis induction. 7,8 The p53 gene is the most commonly mutated gene in cancer, with a prevalence of about 50% in rectal cancer. 9 Functional p53 has been shown to be crucial in determining the radiosensitivity of tumor cells. 10 The value of p53 to predict outcome of various anticancer treatments has been investigated in several studies. Data suggesting a correlation between response to (neo)adjuvant treatment and p53 status are inconsistent and differ among different cancers. Most data have been accrued from studies using immunohistochemical analysis to detect p53 protein overexpression, which is a possible but not exclusive determinant of mutation in the p53 gene. 11–14 Data on p53 gene analysis generated from sufficient numbers of patients to be correlated with clinical results are rare but appear to be more consistent regarding their relation to treatment response. 15–18 For colorectal cancer, p53 gene mutations have been reported to be associated with decreased survival. 19 Some studies report p53 protein overexpression to be a useful parameter for predicting tumor response to radiotherapy. 9,20 The aim of our study was to evaluate whether p53 genotype or p53 protein overexpression, or both, are predictive factors of tumor response to radiotherapy and outcome of patients with operable distal rectal cancer.

Three new cyclic heptapeptides, cyclomarins A−C (1−3), were isolated from extracts of a cultured marine bacterium collected in the vicinity of San Diego, CA. The major metabolite, cyclomarin A (1), contains three common and four unusual (or unique) amino acids. The structures of the new metabolites were determined using 1D and 2D NMR methods, and the stereochemistry was determined from an X-ray crystal structure of the diacetate derivative of 1. Cyclomarin A (1) displays significant antiinflammatory activity in both in vivo and in vitro assays.

Three novel sesterterpenes, neomangicols A−C (1−3) were isolated from the mycelial extract of a marine fungus belonging within the genus Fusarium. The carbon skeleton of the neomangicols is undescribed and constitutes a new class of C25 rearranged sesterterpenes. The structures of the new metabolites were determined by 1D and 2D NMR methods, and the absolute configuration of 3 was determined by Mosher ester analysis of a diacetonide derivative. The configurations of the three stereocenters in the side-chain were assigned on the basis of molecular modeling and NOESY NMR correlations observed for several diacetonide derivatives of 3. Neomangicols A and B are cytotoxic against HCT-116 human colon carcinoma in in vitro evaluation, while neomangicol B inhibits the growth of the Gram-positive bacterium Bacillus subtilus with a potency similar to that of the antibiotic gentamycin.