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Introduction After puberty, at least 10% of all women and girls suffer from endometriosis. Surgery is useful for both the diagnosis and therapy. To date, quality indicators for the surgical treatment of endometriosis are lacking. QS ENDO aims to record the quality of care provided in the DACH region and to introduce quality indicators for the diagnosis and treatment of endometriosis. In the first phase of the study, QS ENDO real, the reality of care was recorded using a questionnaire. The second phase, QS ENDO pilot, investigated the treatment of patients who underwent surgery in certified endometriosis centers in a defined time-period. Material and Methods The surgical data of 10 patients from each of the 44 endometriosis centers in the DACH region was recorded using an online tool. Collected data included the approach used, the endometriosis phenotype, a description of the surgical site, resection status, histological confirmation, the use of a classification, and any complications. All operations were carried out in October 2016 as the defined time-period. The surgical approaches used were compared with the recommendations in the current guidelines. Results The data of 435 patients with a median age of 34 years were evaluated. 315 (72.4%) were nulliparous. 120 patients had given birth to at least one child and 42.5% (51) of them had delivered their child by caesarean section. About 50% of all patients also had deep infiltrating endometriosis in addition to ovarian endometriosis, and the median NAS score was 7.5. With regards to the surgical treatment, endometriomas were completely resected in 81% (94) of patients. 87.3% of patients underwent resection of peritoneal endometriosis. Forty-one patients had a hysterectomy, with a total hysterectomy carried out in 26 (63.4%) and a supracervical hysterectomy in 15 (36.6%) patients. Of the 59 patients with bowel endometriosis, half had segmental resection and half had shaving of the anterior rectal wall. Complications requiring revision occurred in 0.9% of cases. Conclusion The surgical procedures carried out in the certified endometriosis centers of the DACH region are largely in line with the recommendations for appropriate surgical approaches in the current standard guidelines., Competing Interests: Conflict of Interest/Interessenkonflikt The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Introduction Endometriosis significantly reduces patients' quality of life and is additionally a burden on healthcare and social security systems. There are currently no quality indicators for the treatment of endometriosis. The care of patients with endometriosis must be considered inadequate. QS ENDO aims to record the quality of care available in the DACH region and to introduce quality indicators for the diagnosis and treatment of endometriosis as part of providing quality assurance in endometriosis care. The first phase, QS ENDO Real, recorded the reality of current care using a questionnaire. The second phase, QS ENDO Pilot, investigated the treatment of 435 patients who underwent surgical treatment within a defined one month period in certified endometriosis centers. Material and Methods An online tool was used to gather information about 9 points which covered both prior patient history and the process of clinical diagnosis. Surgery reports were reviewed to obtain information about the surgical approach, the investigated sites, findings of any histological examinations, the use of classification systems, and information about resection status. Results 85.3% of patients were asked all 4 questions about their prior medical history. All 5 diagnostic steps were carried out in 34.5% of patients. The 3 areas needed to describe potential sites of disease were recorded in 67.1% of patients. Samples for histological examination were taken in 84.1% of patients. The endometriosis stage was classified in 94.7% of surgeries. A combination of the rASRM and the ENZIAN classifications, which is needed for complex cases, was used in 46.1% of patients. Complete resection was achieved in 81.6% of surgical procedures. Conclusion For the first time, the quality of care in certified endometriosis centers has been recorded using QS ENDO Pilot. Despite the high certification standards, a substantial number of required indicators were omitted., Competing Interests: Conflict of Interest/Interessenkonflikt The authors declare that they have no conflict of interest./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Advances in preoperative diagnostics as well as in surgical techniques for the treatment of endometriosis, especially for deep endometriosis, call for a classification system, that includes all aspects of the disease such as peritoneal endometriosis, ovarian endometriosis, deep endometriosis, and secondary adhesions. The widely accepted revised American Society for Reproductive Medicine classification (rASRM) has certain limitations because of its incomplete description of deep endometriosis. In contrast, the Enzian classification, which has been implemented in the last decade, has proved to be the most suitable tool for staging deep endometriosis, but does not include peritoneal or ovarian disease or adhesions. To overcome these limitations, a comprehensive classification system for complete mapping of endometriosis, including anatomical location, size of the lesions, adhesions and degree of involvement of the adjacent organs, that can be used with both diagnostic and surgical methods, has been created through a consensus process and will be described in detail-the #Enzian classification., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Endometriosis affects a significant number of young premenopausal women. Quite apart from the medical challenges, endometriosis is a relevant burden for healthcare and social security systems. Standardized quality indicators for the treatment of endometriosis have not previously been systematically verified. The three-stage study QS ENDO was initiated to record and improve the reality and quality of care. One of its aims is to create quality indicators for the diagnosis and treatment of endometriosis. For the first stage of QS ENDO Real, letters were sent to all 1014 gynecological departments in the German-speaking area of Europe (the DACH region) which included a questionnaire as a means of surveying the current state of care. A total of 296 (29.2%) of the centers which received the questionnaire participated in the survey. The subsequent evaluation of the completed questionnaires showed that the majority of patients with endometriosis (around 60%, based on estimates from the data) are not treated in hospitals which have been certified by the SEF. The guidelines recommend the use of specific classification systems (rASRM, ENZIAN) but, depending on the level of care offered by the hospital, only around 44.4 to 66.4% of departments used the rASRM score and only 27% of hospitals used the ENZIAN classification system to describe deep-infiltrating endometriosis. When taking patients' medical history, some centers (6.6 - 17.9%) considered questions about leading symptoms such as dyschezia, dysuria and dyspareunia to be unimportant. QS ENDO Real has made it possible, for the first time, to get an overview of the reality of care provided to patients with endometriosis in the German-speaking areas of Europe. The findings indicate that several of the measures recommended in international guidelines as the gold standard of care are only used to treat some of the patients. In this respect, more efforts will be needed to provide more advanced training. The approach used for treatment must be guideline-based, also in not-certified centers, to improve the quality of care in the treatment of patients with endometriosis., Competing Interests: Conflict of Interest/Interessenkonflikt No conflicts of interest reported. Several authors are leaders of SEF-certified Endometriosis centers. Klaus Bühler, Karl-Werner Schweppe and Martin Sillem are members of the SEF board./Kein Interessenkonflikt angegeben. Einige der Autoren sind Leiter SEF-zertifizierter Endometriosezentren. Klaus Bühler, Karl-Werner Schweppe und Martin Sillem sind Mitglieder des SEF-Vorstandes.

Li-Fraumeni syndrome (LFS) is a rare autosomal dominant inherited disorder associated with the occurrence of a wide spectrum of early-onset malignancies, the most prevalent being breast cancer and sarcoma. The presence of TP53 germline mutations in the majority of LFS patients suggests a genetic basis for the cancer predisposition. No special recommendations for the treatment of LFS patients have been made to date, except that of minimizing radiation. We hypothesized that TP53 germline mutations may be associated not only with cancer predisposition, but also with lack of response to chemo- and radiotherapy. Here, we present an Austrian LFS family whose members were intensively treated with chemo- and radiotherapy due to cancers that occurred at a predominantly young age, including eight breast cancers in six patients. Material from seven family members was screened for p53 mutation by Sanger sequencing and immunohistochemistry. A rare missense mutation in the tetramerization domain of exon 10 of the TP53 gene was found to segregate with malignant disease in this family. Lack of response to various chemotherapies and radiotherapy could be ascertained by histopathology of surgical specimens after neoadjuvant treatment, by cancer relapse occurring while receiving adjuvant systemic treatment and by the occurrence of second primaries in areas of adjuvant radiation. Our observations suggest that current standards of cancer treatment may not be valid for patients with LFS. In patients with TP53 germline mutation, cytotoxic treatment may bear not only the risk of tumor induction but also the risk of treatment failure.

Background: Germ-line mutations in mismatch repair genes are associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, which is characterized by susceptibility to cancer of the colon, endometrium, small bowel or urothelium at an unusually young age and with a high degree of penetration in all generations., Material and Methods: One hundred and nine individuals from 46 Austrian families who fulfilled the Amsterdam criteria (n = 29) or at least one of the Bethesda guidelines (n = 17) were analyzed for mutations in MLH1 and MSH2. Microsatellite instability was determined in the tumors of index persons and affected relatives., Results and Conclusion: High-grade instability was present in 60.6% of the tumor samples from index patients. Twenty-three germ-line DNA sequence variants in 24/46 families and four somatic mutations in three tumors were detected in MLH1 and MSH2. Fifteen mutations are novel. None of the newly identified germ-line variants was found in 100 alleles of healthy control individuals. We were able to characterize two intronic variants (MLH1 c.589-10T>A; MSH2 c.367-1G>A) with regard to their effect on mRNA. Both created new splice sites that replaced the regular ones. Germ-line mutations occurred in 44.8% of the families fulfilling the Amsterdam criteria and in 35.3% of the Bethesda patients. The detection of a pathogenic mutation was strongly correlated with microsatellite instability in the tumor DNA (p=0.007). This study is the first comprehensive report of mutations in mismatch repair genes in Austrian patients with HNPCC.

In breast cancer patients receiving adjuvant tamoxifen after unilateral treatment, contralateral breast cancer (CBC) is extremely rare. As a result, only limited data are available on the hormone receptor status of CBCs evolving in tamoxifen-treated patients. The aim of our investigation was to evaluate the pattern of hormone receptor status of CBCs in patients treated with adjuvant tamoxifen at our institution. Material was collected from 35 patients. We have found that 27 of the 35 patients included into our investigation developed an estrogen receptor (ER)-positive CBC despite adjuvant tamoxifen. Seven ER-positive CBCs occurred after tamoxifen had been discontinued, and 20 patients developed an ER-positive CBC while receiving tamoxifen. Notably, 80% of these CBCs displayed moderate-to-strong levels of ER. In our opinion, the selection of ER-negative CBCs, which has previously been implicated to be the pivotal mechanism of tumor escape of CBCs evolving in tamoxifen-treated patients, is only one mechanism of tumor escape in patients receiving antiestrogen treatment. The emergence of ER-positive CBCs in the majority of tamoxifen-treated patients suggests that alternative escape mechanisms may be equally relevant. These include the emergence of ER-positive CBCs that display tamoxifen-dependent growth properties, the selection of CBCs that are tamoxifen resistant because of ER mutations with altered ER function, and, finally, the selection of ER-positive CBCs that overexpress c-erbB2.

Objective: To evaluate and compare the predictive power of p53 gene analysis versus p53 immunohistochemical staining in terms of response to preoperative short-term radiotherapy using 25 Gy in operable rectal cancer., Summary Background Data: Recent studies show that p53 may be a determinant of radiosensitivity being required for induction of apoptosis in case of radiation-induced DNA damage., Methods: Preirradiation biopsy samples of 64 patients with rectal carcinoma were analyzed. Genetic alterations of the p53 gene were detected by complete direct sequencing of exons 2 to 10. Expression of the nuclear phosphoprotein p53 was assessed by immunohistochemical staining. Results were correlated with histopathology of resected specimens and follow-up data, respectively., Results: Mutations of the p53 gene were present in 45% of tumors. Patients with a normal p53 gene had a significant survival advantage. Comparing pre- and postradiotherapy T category, a reduction was seen in patients with normal p53 genotype only. A mutant p53 genotype was highly specific in indicating stable disease concerning T category after irradiation. Protein overexpression was detected in 61%. Overexpression of the p53 protein was not related to survival or response. The concordance between immunohistochemistry and sequencing was only 0.51., Conclusions: The authors show that downstaging after short-term radiation may occur but is seen in tumors with normal p53 gene only. Moreover, p53 genotype but not p53 immunohistochemistry is predictive for response to preoperative short-term radiotherapy and patient survival.

Previous cancer in one breast is a strong known risk factor for cancer in the contralateral breast. Differences in tumor histology and nuclear grading are applied to distinguish between a metastatic spread and a second primary cancer, although cancers of the breast often share the same histological features. Comparison of genetic alterations in paired tumors may provide the most reliable approach for discerning clonal relationships, hence uncovering the presence or absence of multiple primary cancers. We compared tumors from 33 patients with cancer in both breasts for mutations in the p53 gene. With this molecular approach, we were able to define the relationship within paired tumors in 13 patients. The paired tumors of two patients shared the same mutation, revealing the second lesion in one case as a contralateral metachronous lymph node metastasis appearing 29 months after first surgery, and in the other as a spread to the opposite breast. In 11 patients, mutations were either discordant or solely present in one of the lesions, confirming the diagnosis of bilateral breast cancer. Histopathological evaluation had failed to provide firm diagnosis in nine out of 11 instances on account of concordances in pathological parameters such as histological type and grading. In our study, we could show that bilateral breast malignancies most frequently represent two primary breast cancers. We could also demonstrate that contralateral breast cancer spread does occur. Standard pathological assessment allowed a firm diagnosis only in the presence of different histological types.

The value of p53 to predict the cytotoxic effect of two commonly used chemotherapy regimens was assessed in patients with advanced breast cancer. Response to a DNA-damaging combination therapy [fluorouracil, epirubicin, cyclophosphamide (FEC] considered to induce p53-dependent apoptosis was compared with a microtubule stabilizing therapy (paclitaxel) expected to be independent of p53 function. The p53 status of the patients' breast tumors was assessed using both immunohistochemistry (IHC) and direct sequencing of the entire p53 gene. p53 findings were correlated with treatment response, and linkage between p53 function and cellular response was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. In a series of 67 breast tumors, 19% had TP53 gene mutations, 40% had a positive p53 IHC, and 12% had both. In the FEC group, treatment failure was related to both the presence of TP53 gene mutations (P = 0.0029) and a positive IHC (P < 0.0001). Apoptosis was almost exclusively found in tumors having normal p53 in both parameters (P < 0.0001). In the paclitaxel group, treatment response was neither related to apoptosis nor to normal p53. Combination of sequencing and IHC results revealed a significant association between abnormal p53 and response to paclitaxel (P = 0.011). We found TP53 mutations, as well as p53 protein overexpression, to be associated with response to chemotherapy. Whereas clinical response to FEC was found to be dependent on normal p53, the cytotoxicity of paclitaxel was related to defective p53. The efficiency of paclitaxel during mitosis might be supported by lack of G1 arrest due to p53 deficiency. Therefore, patients with p53-deficient tumors may benefit from paclitaxel.