Grundlegende Prinzipien und zukünftige Aspekte der Thermofusion und Elektrokoagultion - Experimentelle Studie in in-vitro und in-vivo Tiermodellen sowie in humanen Modellen

Bipolar vessel sealing and electrosurgery in general is pivotal in surgical and especially minimally-invasive surgical hemostasis. However, quality of vessel sealing is only suboptimal and major coaptive desiccation parameters have yet to be investigated in depth. Moreover, the potentially hazardous capacity of electrosurgery to induce both post-operative adhesions and thermal complications such as tissue necrosis has not been looked into in detail hitherto. In order to (1) optimize bipolar vessel sealing, to (2) better understand the biothermomechanics of thermal fusion, to (3) analyze the relationship between electrocoagulation and adhesion formation and to (4) develop a human in-vivo in-situ model for quantifying electrosurgery-induced thermal tissue effects and thermal tissue damage, the following studies were conducted. It was found that in an isolated porcine renal artery model, self-regulating modulation of energy-based vessel coagulation achieved superior thermal fusion of vascular tissue than CPC. This promising novel technique should therefore be further analyzed to determine its in-vivo efficacy in long-term studies. Moreover it was ascertained that compressive pressure during coaptation determines the seal quality. Upper and lower pressure boundaries for safe coaptation exist for both arteries and veins. Vessel sealing by thermal conduction without electrical current effects is possible but represents a less effective method for coaptation. These findings have implications for the rational design of new electrosurgical instruments. With regards to the adhesiogenic potential of bipolar tissue desiccation, we conclude that superficial trauma limited mostly to the parietal peritoneum may be a neglible factor in adhesion formation in this model. This appears to be irrespective of the mode of trauma. However, additional trauma to the underlying tissues, either by deeper electrocoagulation or suturing, lead to significantly increased adhesion formation. These data also show that there is a spectrum of electrocoagulation trauma at the lower end of which there is little adhesion formation. Finally, the new purpose-designed in-vivo in-situ model allows standardized, reproducible, quantitative assessment of electrocoagulation-induced thermal effects and damage in human tissue. It will likely provide further insight into the underlying biothermomechanics and may prove useful in the development of safety guidelines for laparoscopic electrosurgery.Bipolar vessel sealing and electrosurgery in general is pivotal in surgical and especially minimally-invasive surgical hemostasis. However, quality of vessel sealing is only suboptimal and major coaptive desiccation parameters have yet to be investigated in depth. Moreover, the potentially hazardous capacity of electrosurgery to induce both post-operative adhesions and thermal complications such as tissue necrosis has not been looked into in detail hitherto. In order to (1) optimize bipolar vessel sealing, to (2) better understand the biothermomechanics of thermal fusion, to (3) analyze the relationship between electrocoagulation and adhesion formation and to (4) develop a human in-vivo in-situ model for quantifying electrosurgery-induced thermal tissue effects and thermal tissue damage, the following studies were conducted. It was found that in an isolated porcine renal artery model, self-regulating modulation of energy-based vessel coagulation achieved superior thermal fusion of vascular tissue than CPC. This promising novel technique should therefore be further analyzed to determine its in-vivo efficacy in long-term studies. Moreover it was ascertained that compressive pressure during coaptation determines the seal quality. Upper and lower pressure boundaries for safe coaptation exist for both arteries and veins. Vessel sealing by thermal conduction without electrical current effects is possible but represents a less effective method for coaptation. These findings have implications for the rational design of new electrosurgical instruments. With regards to the adhesiogenic potential of bipolar tissue desiccation, we conclude that superficial trauma limited mostly to the parietal peritoneum may be a neglible factor in adhesion formation in this model. This appears to be irrespective of the mode of trauma. However, additional trauma to the underlying tissues, either by deeper electrocoagulation or suturing, lead to significantly increased adhesion formation. These data also show that there is a spectrum of electrocoagulation trauma at the lower end of which there is little adhesion formation. Finally, the new purpose-designed in-vivo in-situ model allows standardized, reproducible, quantitative assessment of electrocoagulation-induced thermal effects and damage in human tissue. It will likely provide further insight into the underlying biothermomechanics and may prove useful in the development of safety guidelines for laparoscopic electrosurgery

Update Mammakarzinom 2018 (Teil 1) – primäres Mammakarzinom und Biomarker

This summary provides an overview of how new therapies or new aspects of established therapies relate to the latest findings. Neoadjuvant therapy, local therapy, new aspects of systemic therapy, and prognostic and predictive factors are presented. In the neoadjuvant setting, the association between pathological complete response (pCR) and prognosis is still of interest as is the identification of new molecular predictors for new therapies such as CDK4/6 inhibitors. As regards surgical treatment, the target is still to reduce the aggressiveness of surgery. To achieve this, a better understanding particularly of ductal carcinoma in situ is required. With regard to systemic therapy, more data on the best combinations and therapy sequences for existing therapies is available. Finally, the use of prognostic and predictive factors may help to avoid overtreatment and ensure that patients only receive therapies which have been shown to be effective for their specific condition and have fewer side effects.In dieser Übersichtsarbeit wird dargestellt, wie neue Therapien oder neue Aspekte etablierter Therapien in Zusammenhang mit neuesten, aktuellen Erkenntnissen stehen. Neoadjuvanz, Lokaltherapie, neue Aspekte der Systemtherapie und Prognose- sowie Prädiktivfaktoren werden beleuchtet. In der Neoadjuvanz ist nach wie vor der Zusammenhang zwischen pCR und Prognose von Interesse, ebenso wie neue molekulare Prädiktoren für neue Therapien wie CDK4/6-Inhibitoren zu identifizieren. Bei der operativen Behandlung wird weiter nach einer Reduktion der Aggressivität gestrebt. Insbesondere das duktale Carcinoma in situ muss dafür noch besser verstanden werden. Bei den Systemtherapien wächst die Datenlage zum Verständnis der besten Kombinationen und Therapieabläufe für bestehende Therapieverfahren. Letztendlich muss mithilfe von Prognose- und Prädiktivfaktoren vermieden werden, dass Übertherapien stattfinden und nur die Patientin spezifische Therapien erhält, welche bei dieser individuellen Patientin eine nachgewiesene Wirksamkeit mit wenig Nebenwirkungen haben

Update Mammakarzinom 2018 (Teil 1) – primäres Mammakarzinom und Biomarker

This summary provides an overview of how new therapies or new aspects of established therapies relate to the latest findings. Neoadjuvant therapy, local therapy, new aspects of systemic therapy, and prognostic and predictive factors are presented. In the neoadjuvant setting, the association between pathological complete response (pCR) and prognosis is still of interest as is the identification of new molecular predictors for new therapies such as CDK4/6 inhibitors. As regards surgical treatment, the target is still to reduce the aggressiveness of surgery. To achieve this, a better understanding particularly of ductal carcinoma in situ is required. With regard to systemic therapy, more data on the best combinations and therapy sequences for existing therapies is available. Finally, the use of prognostic and predictive factors may help to avoid overtreatment and ensure that patients only receive therapies which have been shown to be effective for their specific condition and have fewer side effects.In dieser Übersichtsarbeit wird dargestellt, wie neue Therapien oder neue Aspekte etablierter Therapien in Zusammenhang mit neuesten, aktuellen Erkenntnissen stehen. Neoadjuvanz, Lokaltherapie, neue Aspekte der Systemtherapie und Prognose- sowie Prädiktivfaktoren werden beleuchtet. In der Neoadjuvanz ist nach wie vor der Zusammenhang zwischen pCR und Prognose von Interesse, ebenso wie neue molekulare Prädiktoren für neue Therapien wie CDK4/6-Inhibitoren zu identifizieren. Bei der operativen Behandlung wird weiter nach einer Reduktion der Aggressivität gestrebt. Insbesondere das duktale Carcinoma in situ muss dafür noch besser verstanden werden. Bei den Systemtherapien wächst die Datenlage zum Verständnis der besten Kombinationen und Therapieabläufe für bestehende Therapieverfahren. Letztendlich muss mithilfe von Prognose- und Prädiktivfaktoren vermieden werden, dass Übertherapien stattfinden und nur die Patientin spezifische Therapien erhält, welche bei dieser individuellen Patientin eine nachgewiesene Wirksamkeit mit wenig Nebenwirkungen haben

Heregulin (HRG) assessment for clinical trial eligibility testing in a molecular registry (PRAEGNANT) in Germany

Background: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry. Methods:Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor–positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria. Results: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive. Conclusion: Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials. Trial registration: Clinicaltrials, NCT02338167, Registered 14 January 2015 - retrospectively registered

13th St. Gallen International Breast Cancer Conference 2013 : Primary Therapy of Early Breast Cancer Evidence, Controversies, Consensus - Opinion of a German Team of Experts (Zurich 2013)

The International Consensus Conference on the treatment of primary breast cancer takes place every two years in St. Gallen, Switzerland.The panel in St. Gallen is composed of international experts from different countries. From a German perspective, it seems reasonable to interpret the voting results in the light of AGO-recommendations and S3-guidelines for everyday practice in Germany. Consequently, a team of eight breast cancer experts, of whom two are members of the international St. Gallen panel, commented on the voting results of the St. Gallen Consensus Conference (2013). The main topics at this year’s St. Gallen conference were surgical issues of the breast and axilla, radio-therapeutic and systemic treatment options, and the clinical relevance of tumour biology. The clinical utility of multigene assays for supporting individual treatment decisions was also intensively discussed