TY  - JOUR
A1  - Anger, Friedrich
A1  - Döring, Anna
A1  - van Dam, Jacob
A1  - Lock, Johann Frisco
A1  - Klein, Ingo
A1  - Bittrich, Max
A1  - Germer, Christoph-Thomas
A1  - Wiegering, Armin
A1  - Kunzmann, Volker
A1  - van Eijck, Casper
A1  - Löb, Stefan
T1  - Impact of Borderline Resectability in Pancreatic Head Cancer on Patient Survival: Biology Matters According to the New International Consensus Criteria
JF  - Annals of Surgical Oncology
N2  - Background
International consensus criteria (ICC) have redefined borderline resectability for pancreatic ductal adenocarcinoma (PDAC) according to three dimensions: anatomical (BR-A), biological (BR-B), and conditional (BR-C). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumour and vessels but that biological and conditional dimensions also are important.

Methods
Patients’ tumours were retrospectively defined borderline resectable according to ICC. The study cohort was grouped into either BR-A or BR-B and compared with patients considered primarily resectable (R). Differences in postoperative complications, pathological reports, overall (OS), and disease-free survival were assessed.

Results
A total of 345 patients underwent resection for PDAC. By applying ICC in routine preoperative assessment, 30 patients were classified as stage BR-A and 62 patients as stage BR-B. In total, 253 patients were considered R. The cohort did not contain BR-C patients. No differences in postoperative complications were detected. Median OS was significantly shorter in BR-A (15 months) and BR-B (12 months) compared with R (20 months) patients (BR-A vs. R: p = 0.09 and BR-B vs. R: p < 0.001). CA19-9, as the determining factor of BR-B patients, turned out to be an independent prognostic risk factor for OS.

Conclusions
Preoperative staging defining surgical resectability in PDAC according to ICC is crucial for patient survival. Patients with PDAC BR-B should be considered for multimodal neoadjuvant therapy even if considered anatomically resectable.
KW  - pancreatic head cancer
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235251
SN  - 1068-9265
VL  - 28
IS  - 4
ER  - 
TY  - JOUR
A1  - Anany, Mohamed A.
A1  - Kreckel, Jennifer
A1  - Füllsack, Simone
A1  - Rosenthal, Alevtina
A1  - Otto, Christoph
A1  - Siegmund, Daniela
A1  - Wajant, Harald
T1  - Soluble TNF-like weak inducer of apoptosis (TWEAK) enhances poly(I:C)-induced RIPK1-mediated necroptosis
JF  - Cell Death & Disease
N2  - TNF-like weak inducer of apoptosis (TWEAK) and inhibition of protein synthesis with cycloheximide (CHX) sensitize for poly(I:C)-induced cell death. Notably, although CHX preferentially enhanced poly(I:C)-induced apoptosis, TWEAK enhanced primarily poly(I:C)-induced necroptosis. Both sensitizers of poly(I:C)-induced cell death, however, showed no major effect on proinflammatory poly(I:C) signaling. Analysis of a panel of HeLa-RIPK3 variants lacking TRADD, RIPK1, FADD, or caspase-8 expression revealed furthermore similarities and differences in the way how poly(I:C)/TWEAK, TNF, and TRAIL utilize these molecules for signaling. RIPK1 turned out to be essential for poly(I:C)/TWEAK-induced caspase-8-mediated apoptosis but was dispensable for this response in TNF and TRAIL signaling. TRADD-RIPK1-double deficiency differentially affected poly(I:C)-triggered gene induction but abrogated gene induction by TNF completely. FADD deficiency abrogated TRAIL- but not TNF- and poly(I:C)-induced necroptosis, whereas TRADD elicited protective activity against all three death inducers. A general protective activity against poly(I:C)-, TRAIL-, and TNF-induced cell death was also observed in FLIPL and FLIPS transfectrants.
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221104
VL  - 9
ER  -