Mutations and amplification of oncogenes in endometrial cancer

Alterations in oncogenes are critical steps in the development of endometrial cancer. To investigate the potential clinical relevance of the amplification of the oncogenes c-erbB2, c-myc, and int-2 and the mutation of K-ras in endometrial cancer, 112 tumors were examined using PCR-based fluorescent DNA technology. Amplification of the three oncogenes and the mutation of K-ras were correlated with age, tumor size, lymph node status, metastases, stage, histological types, grade, steroid hormone receptor expression (estrogen receptor, ER; progesterone receptor, PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy. Oncogene amplification of c-erbB2 was detected in 18.9%, of c-myc in 2.7% and of int-2 in 4.2%, and K-ras mutation in 11.6%. No significant correlations could be detected between amplification of c-erbB2 and any of the other parameters. Mutation of K-ras is associated with positive expression of PgR. This might indicate that mutation and activation of K-ras are involved in the development of hormonal independence in endometrial cancer

State-of-the-Art Treatment and Novel Agents in Local and Distant Recurrences of Cervical Cancer

Depending on the stage at initial presentation, cervical cancer will recur in 25-61% of women. Typical manifestations of recurrent cervical cancer include the central pelvis and the pelvic side walls as well as retroperitoneal lymph node basins in the pelvis and the para-aortic region, and - more rarely - supraclavicular lymph nodes. There are no typical symptoms of recurrent cervical cancer. Women with suspected recurrence after cervical cancer based on gynecological examination or organ-specific symptoms must undergo imaging studies and - if technically feasible - biopsy with histological verification, especially in cases of distant metastases, in order to rule out a second primary. Radiotherapy-naïve women should be treated with salvage radiochemotherapy with curative intention. For women with previous radiotherapy, surgery in the form of hysterectomy, local resection, or pelvic exenteration is the treatment of choice. Pelvic exenteration can lead to cure in selected patients, but at the price of a high rate of complications and significant morbidity and mortality. If complete surgical resection is not feasible or if the woman is not a candidate for surgery, chemotherapy with palliative intent should be offered. Patients with recurrent disease outside the pelvis are candidates for systemic chemotherapy. Several agents have shown to be active in this situation, either in single-agent or combination regimens. Platinum-containing regimens have a superior efficacy over non-platinum regimens and bevacizumab may be added to chemotherapy

The role of peroxisome proliferator-activated receptors in endometriosis

Endometriosis constitutes the most common cause of chronic pelvic pain in female patients and is associated with infertility. Although there is no known cause for the disease, it is a heritable condition that is determined by numerous genetic, epigenetic, and environmental aspects. Peroxisome proliferator-activated receptors (PPARs) represent nuclear receptor proteins that control gene expression. By using the MEDLINE and LIVIVO databases we conducted a literature review in order to look into the role of PPARs in the endometriosis pathophysiology and succeeded in revealing 36 pertinent publications between 2001 and 2022. In regards to PPAR expression in endometriosis, PPARγ seems to represent the most studied PPAR isoform in endometriosis and to influence various pathways involved in the disease onset and progression. It's interesting to note that diverse treatment agents targeting the PPAR system have been identified as innovative, effective therapeutic alternatives in the context of endometriosis treatment. In conclusion, PPARs appear to contribute an important role in both endometriosis pathophysiology and therapy

Villoglandular adenocarcinoma of the uterine cervix: a systematic review and meta-analysis

Purpose Villoglandular adenocarcinoma (VGA) of the uterine cervix has been classified as a rare subtype of cervical adenocarcinoma with good prognosis. A conservative surgical approach is considered feasible. The main risk factor is the presence of other histologic types of cancer. In this largest systematic review to date, we assess oncological outcomes associated with conservative therapy compared to those associated with invasive management in the treatment of stage Ia and Ib1 VGA. Methods Case series and case reports identified by searching the PubMed database were eligible for inclusion in this review (stage Ia–Ib1). Results A total of 271 patients were included in our literature review. 54 (20%) patients were treated by “conservative management” (conization, simple hysterectomy, and trachelectomy) and 217 (80%) by “invasive management” (radical hysterectomy ± radiation, hysterectomy, and radiation). Recurrences of disease (RODs) were found in the conservative group in two (4%) cases and in the invasive group in nine (4%) cases. There was no significant difference in disease-free survival (DFS) according to conservative or invasive treatment (p = 0.75). The histology of VGA may be complex with underlying usual adenocarcinoma (UAC) combined with VGA. Conclusion The excellent prognosis of pure VGA and the young age of the patients may justify the management of this tumor using a less radical procedure. The histological diagnosis of VGA is a challenge, and pretreatment should not be based solely on a simple punch biopsy but rather a conization with wide tumor-free margins

Ovarian Tissue Transplantation: Experience From Germany and Worldwide Efficacy

Extraction of ovarian tissue prior to oncologic therapy and subsequent transplantation is being performed increasingly often to preserve fertility in women. The procedure can be performed at any time of the cycle and, therefore, generally does not lead to any delay in oncological therapy. Success rates with transplantation of cryopreserved ovarian tissue have reached promising levels. More than 130 live births have been reported worldwide with the aid of cryopreserved ovarian tissue and the estimated birth rate is currently approximately 30%. In Germany, Austria, and Switzerland, the FertiPROTEKT consortium has successfully achieved 21 pregnancies and 17 deliveries generated after 95 ovarian tissue transplantations by 2015, one of the largest case series worldwide confirming that ovarian tissue cryopreservation and transplantation are successful. Approximately, more than 400 ovarian tissue cryopreservation procedures are performed each year in the FertiPROTEKT consortium, and the request and operations for ovarian tissue transplantation have increased in recent years. Therefore, recommendations for managing transplantation of ovarian tissue to German-speaking reproductive medicine centers were developed. In this overview, these recommendations and our experience in ovarian tissue transplantation are presented and discussed with international procedures

Implementation and update of guideline-derived quality indicators for cervical cancer in gynecological cancer centers certified by the German Cancer Society (DKG)

Purpose In 2008, the first gynecological cancer centres were certified by the German Cancer Society (DKG). Guideline-based quality Indicators (QIs) are a core element of the certification process. These QI are defined to assess the quality of care within the centres and can serve to measure the implementation of guideline recommendation. This article aims to give an overview of the developing and updating process of guideline based-QIs for women with cervical cancer and presents the QI results from the certified gynaecological cancer centres. Methods The QIs are derived in a multiple step review process and then implemented in the certification data sheet of the certified centres. The first set of QIs created in 2014 was revised in the update process of the S3-Guideline in 2020. QIs are based on strong recommendations of the evidence-based “Guideline for patients with Cervical Carcinoma” (registry-number: 032/033OL). Results In total, there are nine guideline-based QIs for cervical cancer. Four QIs are part of the certification process. In the treatment year 2020, 3.522 cases of cervical cancer were treated in 169 centers. The target values for the four QIs were met in at least 95% of the certified centers. In the guideline update in 2020, a new QI was added to the set of QIs “Complete pathological report on conization findings” and the QI “Exenteration” was removed. Conclusions QIs derived from strong recommendations of a guideline are an important tool to make essential parts of patient’s care measurable and enable the centers to draw consequences in process optimization. Over the years, the number of certified centers has grown, and the quality was improved. The certification systems is under constant revision to further improve patient’s care in the future, based on the results of the QI re-evaluation.Open Access funding enabled and organized by Projekt DEAL.Friedrich-Alexander-Universität Erlangen-Nürnberg (1041

Analysis and classification of oncology activities on the way to workflow based single source documentation in clinical information systems

BACKGROUND: Today, cancer documentation is still a tedious task involving many different information systems even within a single institution and it is rarely supported by appropriate documentation workflows. METHODS: In a comprehensive 14 step analysis we compiled diagnostic and therapeutic pathways for 13 cancer entities using a mixed approach of document analysis, workflow analysis, expert interviews, workflow modelling and feedback loops. These pathways were stepwise classified and categorized to create a final set of grouped pathways and workflows including electronic documentation forms. RESULTS: A total of 73 workflows for the 13 entities based on 82 paper documentation forms additionally to computer based documentation systems were compiled in a 724 page document comprising 130 figures, 94 tables and 23 tumour classifications as well as 12 follow-up tables. Stepwise classification made it possible to derive grouped diagnostic and therapeutic pathways for the three major classes - solid entities with surgical therapy - solid entities with surgical and additional therapeutic activities and - non-solid entities. For these classes it was possible to deduct common documentation workflows to support workflow-guided single-source documentation. CONCLUSIONS: Clinical documentation activities within a Comprehensive Cancer Center can likely be realized in a set of three documentation workflows with conditional branching in a modern workflow supporting clinical information system

Single-Source Tumor Documentation – Reusing Oncology Data for Different Purposes

We present a path towards single-source tumor documentation established at the Comprehensive Cancer Center Erlangen-Nürnberg (CCC-EN). Our goal was to derive data for cancer quality assurance and certification, cancer registry documentation and cancer research directly from routine care documentation. Therefore, clinical documentation activities were analyzed and a cancer data superset, containing these required elements, was developed. This superset was then split into appropriate clinical documentation packages, and the existing information technology infrastructure was analyzed and adapted to accommodate those documentation packages. A clinical documentation package is the amount of cancer-relevant data that can be captured within a clinical encounter. This grouping of data enables integration into existing clinical documentation workflows. We present examples in which single-source tumor documentation has been successfully established at the CCC-EN. The resulting cancer documentation reference model is described and its transferability to other institutions discussed.Wir stellen dar, wie am Comprehensive Cancer Center Erlangen-Nürnberg (CCC-EN) eine Single-Source-Tumordokumentation umgesetzt wurde. Dabei ist es unser Ziel, Daten für Qualitätssicherungsverfahren, Zertifizierungen, Krebsregistrierung und Krebsforschung direkt aus den Daten der klinischen Routinedokumentation abzuleiten. Hierfür wurden medizinische Dokumentationsaktivitäten analysiert und ein übergreifender Datensatz entwickelt, welcher die Anforderungen der klinischen Dokumentation, Qualitätssicherung, Krebsregistrierung und Krebsforschung abdeckt. Anschließend wurde dieser Datensatz in entsprechende klinische Dokumentationspakete aufgesplittet sowie die bestehende IT-Infrastruktur analysiert und so angepasst, dass diese Dokumentationspakete korrekt abgebildet und deren Daten per Schnittstelle übertragen werden können. Ein klinisches Dokumentationspaket ist eine Sammlung von Daten, die komplett während eines klinischen Arbeitsschritts erhoben werden können. Diese Gruppierung der Daten stellt die Integrationsfähigkeit in bestehende klinische Dokumentationsabläufe sicher. Wir zeigen Beispiele, wie unser Modell einer Single-Source-Tumordokumentation erfolgreich am CCC-EN umgesetzt wurde. Schließlich wird das resultierende Tumordokumentations-Referenzmodell dargestellt und seine Übertragbarkeit auf andere Institutionen diskutiert

Implementation of quality indicators for vulvar cancer in gynaecological cancer centres certified by the German Cancer Society (DKG)

Purpose In 2018, the first guideline-based quality indicators (QI) for vulvar cancer were implemented in the data-sheets of certified gynaecological cancer centres. The certification process includes guideline-based QIs as a fundamental component. These indicators are specifically designed to evaluate the level of care provided within the centres. This article aims to give an overview of the developing process of guideline based-QIs for women with vulvar cancer and presents the QIs results from the certified gynaecological cancer centres. Methods The QIs were derived in a standardized multiple step process during the update of the 2015 S2k guideline “Diagnosis, Therapy, and Follow-Up Care of Vulvar Cancer and its Precursors” (registry-number: no. 015/059) and are based on strong recommendations. Results In total, there are eight guideline-based QIs for vulvar cancer. Four QIs are part of the certification process. In the treatment year 2021, 2.466 cases of vulvar cancer were treated in 177 centres. The target values in the centres for pathology reports on tumour resection and lymphadenectomy as well as sentinel lymph nodes have increased since the beginning of the certification process and have been above 90% over the past three treatment years (2019–2021). Discussion QIs based on strong guideline recommendations, play a crucial role in measuring and allowing to quantify essential aspects of patient care. By utilizing QIs, centres are able to identify areas for process optimization and draw informed conclusions. Over the years the quality of treatment of vulvar cancer patients measured by the QIs was improved. The certification system is continuously reviewed to enhance patient care even further by using the outcomes from QIs revaluation