Die Rolle des Tumor Budding beim neoadjuvant therapierten Rektumkarzinom

ZIEL: Das Ziel dieser Arbeit bestand darin, die Rolle des Tumor Budding nach neoad-juvanter Radiochemotherapie bei Patienten mit Rektumkarzinom zu klären. Um Rück-schlüsse auf die Unterschiede zwischen der qualitativen Budding-Auswertung nach Ha-e und der quantitativen Budding-Auswertung nach Ueno zu ziehen, wurde ein und dieselbe Patientenkohorte auf beide Arten ausgewertet und die Ergebnisse miteinander verglichen. Ferner sollte die Rolle der Immunhistochemie (IHC) beleuchtet werden. METHODEN: Die Analyse umfasste die Daten von 124 Patienten mit neoadjuvant the-rapiertem Rektumkarzinom in den Stadien I bis IV, die zwischen 2002 und 2011 operiert worden waren. In den Resektaten wurden Budding und weitere klinisch-pathologische Parameter untersucht. Budding wurde je Auswertungsmethode sowohl in der Färbung mit Hämatoxylin&Eosin (H&E) als auch mit dem Anti-Zytokeratin-Antikörper AE1/AE3 ausgewertet. ERGEBNISSE: Im H&E waren nach der Methode von Hase 38,8% (n = 40) der Patienten budding-positiv, nach der Methode von Ueno 36,9% (n = 38). Für die Auswertung des Budding nach der Färbung mit dem Antikörper AE1/AE3 zeigte sich für beide Methoden eine Budding-Rate von 55,6% (n = 55). Unabhängig von der Methode oder der Färbung korrelierte Budding mit einem höheren ypT- und ypN-Status, einer geringeren Response gemessen anhand des Regressionsgrades nach Dworak und mit einem schlechteren Outcome im Follow-up wie dem Rezidiv oder dem Tod (p<0,05 jeweils). Im multivariaten Cox-Regressions-Modell blieb Budding als einziger Parameter für das Gesamtüberleben signifikant und übertraf damit sogar die ypT- und ypN-Klassifikation (Budding ausgewertet nach Hase im H&E: Hazard-Ratio (HR) 3,06 im 95%-Konfidenzintervall (95%-CI) 1,26–7,41, p=0,013 und in der IHC: HR 4,08, 95%-CI 1,30–12,78, p=0,016; Budding ausgewertet nach Ueno im H&E: HR 2,72, 95%-CI 1,15–6,44, p=0,023 und in der IHC: HR 5,19, 95%-CI 1,62–16,61, p=0,006). SCHLUSSFOLGERUNG: Budding ist ein starker prognostischer Faktor für das Überleben von Rektumkarzinom-Patienten nach neoadjuvanter Therapie. Beide Methoden sind in etwa gleich gut geeignet, um Budding auszuwerten und Patienten in prognostischrelevante Gruppen einzuteilen. Um eine Standardisierung zu erreichen, ist es dennoch empfehlenswert, zu einem Konsens bezüglich der besten Methode der Budding-Auswertung nach neoadjuvanter Therapie zu kommen. Die IHC trägt dazu bei, die prognostische Aussagekraft zu verbessern und sollte in komplizierten Fällen herange-zogen werden.AIM: The aim of this study was to clarify the role of tumor budding in rectal cancer after preoperative chemoradiotherapy. In order to draw conclusions about the differences between the qualitative budding evaluation according to Hase and the quantitative bud-ding evaluation according to Ueno, the same patient cohort was evaluated in both ways and the results were compared. Furthermore, the role of immunohistochemistry (IHC) will be highlighted. METHODS: A total of 124 patients with rectal cancer treated with neoadjuvant chemo-radiotherapy between 2002 and 2011 followed by surgery were included. All surgical specimens were evaluated for budding and other clinic-pathological features. Budding was evaluated on both haematoxylin and eosin (H&E) and immunhistochemical (IHC) stained slides with an anti-human cytokeratin antibody AE1/AE3. RESULTS: In the H&E-stained slides a budding rate of 38.8% (n = 40) for the Hase’s method and of 36.9% (n = 38) for Ueno’s method were observed. For IHC a budding rate of 55.6% (n = 55) was assessed for both methods. Irrespective of the method or staining used for the evaluation, budding was significantly associated with a higher ypT and ypN status, a lower response according to Dworak’s tumor regression grading sys-tem and with a worse outcome in follow-up like recurrence or death (p<0.05 each). In multivariate analyses, budding remained the only significant parameter for overall sur-vival and was even superior to the ypT and ypN status (budding evaluated with Hase’s method on H&E: hazard ratio (HR) 3.06, 95%-confidence interval (95%-CI) 1.26–7.41, p=0.013; on IHC: HR 4.08, 95%-CI 1.30–12.78, p=0.016; with Ueno’s method on H&E: HR 2.72, 95%-CI 1.15–6.44, p=0.023; on IHC: HR 5.19, 95%-CI 1.62–16.61, p=0.006). CONCLUSION: Budding is a strong prognostic factor of survival in rectal cancer pa-tients after neoadjuvant therapy. Both methods are equally well suited to evaluate bud-ding and to divide patients into prognostically relevant groups. In order to achieve a standardization, it is nevertheless recommended to reach a consensus on the best method for the evaluation of budding after neoadjuvant therapy. Immunostaining helps to improve the prognostic significance and can be used in difficult cases

Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy

BACKGROUND: Budding is a complementary prognostic factor for colorectal cancer. In this study, we aimed to clarify the role of tumor budding in rectal cancer patients after preoperative chemoradiotherapy. METHODS: A total of 124 patients with rectal cancer treated with neoadjuvant chemoradiotherapy and consecutive surgery were included. Surgical specimens were evaluated for budding and routine clinicopathological features. Budding was evaluated on hematoxylin and eosin (H&E)-stained slides and by cytokeratin immunohistochemical (IHC) staining. RESULTS: A budding rate of 36.9% (n = 38) by H&E and 55.6% (n = 55) by IHC was observed. Budding was significantly associated with a high ypT and ypN status, poor differentiation, and low degrees of tumor regression. Moreover, budding was strongly predictive of a worse patient outcome, as measured by tumor recurrence or death. In multivariate analyses, budding remained the only significant parameter for overall survival and was even superior to the ypT and ypN status (budding in H&E: hazard ratio (HR) 2.72, 95% confidence interval (95% CI) 1.15-6.44, p = 0.023; budding in IHC: HR 5.19, 95% CI 1.62-16.61, p = 0.006). CONCLUSION: Budding is a strong prognostic predictor of survival in rectal cancer patients after neoadjuvant therapy. A standardized evaluation of tumor budding after neoadjuvant therapy may thus aid in risk stratification and guide the clinical management of patients with rectal cancer. Immunostaining can help to enhance the diagnostic accuracy and prognostic significance

COVID-19: Autopsy findings in six patients between 26 and 46 years of age

Objectives: Studies on coronavirus disease 2019 (COVID-19) usually focus on middle-aged and older adults. However, younger patients may present with severe COVID-19 with potentially fatal outcomes. For optimized, more specialized therapeutic regimens in this particular patient group, a better understanding of the underlying pathomechanisms is of utmost importance. Methods: Our study investigated relevant, pre-existing medical conditions, clinical histories, and autopsy findings, together with SARS-CoV-2-RNA, determined by qPCR, and laboratory data in six COVID-19 decedents aged 50 years or younger, who were autopsied at the Charite University Hospital. Results: From a total of 76 COVID-19 patients who underwent an autopsy at our institution, six (7.9%) were 50 years old or younger. Most of these younger COVID-19 decedents presented with pre-existing medical conditions prior to SARS-CoV-2 infection. These included overweight and obesity, arterial hypertension, asthma, and obstructive sleep apnea, as well as graft-versus-host disease following cancer and bone marrow transplantation. Furthermore, clinical histories and autopsy results revealed a disproportionally high prevalence of thromboembolism and ischemic organ damage in this patient cohort. Histopathology and laboratory results indicated coagulopathies, signs of immune dysregulation, and liver damage. Conclusions: In conclusion, pre-existing health conditions may increase the risk of severe and fatal COVID-19 in younger patients, who may be especially prone to developing thromboembolic complications, immune dysregulation, and liver damage