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Pancreatic Neoplasms: HELP
Articles by Thomas Hank
Based on 8 articles published since 2010
(Why 8 articles?)
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Between 2010 and 2020, T. Hank wrote the following 8 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Conversion Surgery for Advanced Pancreatic Cancer. 2019

Hank, Thomas / Strobel, Oliver. ·Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. ·J Clin Med · Pubmed #31718103.

ABSTRACT: While primarily unresectable locally advanced pancreatic cancer (LAPC) used to be an indication for palliative therapy, a strategy of neoadjuvant therapy (NAT) and conversion surgery is being increasingly used after more effective chemotherapy regimens have become available for pancreatic ductal adenocarcinoma. While high-level evidence from prospective studies is still sparse, several large retrospective studies have recently reported their experience with NAT and conversion surgery for LAPC. This review aims to provide a current overview about different NAT regimens, conversion rates, survival outcomes and determinants of post-resection outcomes, as well as surgical strategies in the context of conversion surgery after NAT. FOLFIRINOX is the predominant regimen used and associated with the highest reported conversion rates. Conversion rates considerably vary between less than 5% and more than half of the study population with heterogeneous long-term outcomes, owing to a lack of intention-to-treat analyses in most studies and a high heterogeneity in resectability criteria, treatment strategies, and reporting among studies. Since radiological criteria of local resectability are no longer applicable after NAT, patients without progressive disease should undergo surgical exploration. Surgery after NAT has to be aimed at local radicality around the peripancreatic vessels and should be performed in expert centers. Future studies in this rapidly evolving field need to be prospective, analyze intention-to-treat populations, report stringent and objective inclusion criteria and criteria for resection. Innovative regimens for NAT in combination with a radical surgical approach hold high promise for patients with LAPC in the future.

2 Review Local radicality and survival outcome of pancreatic cancer surgery. 2019

Niesen, Willem / Hank, Thomas / Büchler, Markus / Strobel, Oliver. ·Department of General, Visceral and Transplantation Surgery Heidelberg University Hospital Heidelberg Germany. ·Ann Gastroenterol Surg · Pubmed #31549006.

ABSTRACT: Pancreatic cancer remains a therapeutic challenge. Surgical resection in combination with systemic chemotherapy is the only option promising long-term survival and potential cure. However, only about 20% of patients are diagnosed with tumors that are still in a resectable stage. Even after potentially curative resection and modern regimens for adjuvant chemotherapy, the majority of patients develop local and systemic recurrence resulting in median overall survival times of 28-54 months. The predominance of systemic recurrence and its impact on survival may lead to the assumption that surgical radicality and local control play only minor roles in the treatment of pancreatic cancer. This review provides an overview of the recent literature on surgical radicality and survival outcome in pancreatic cancer. The current evidence on the extent of lymphadenectomy, the prognostic impact of the extent of lymph node involvement, and the impact of the resection margin status on postresection survival are reviewed. Data from recent studies performed in the context of modern surgery and adjuvant therapy provide good evidence of a considerable impact of local radicality on survival after pancreatic cancer surgery. Surgical techniques that have been developed to refine oncological resections and to increase local control as well as resectability are highlighted. These techniques include artery-first approaches, level-3 dissection with removal of the periarterial nerve plexus, the triangle operation, and extended resections. Local radicality and quality of surgical resection remain among the most important parameters that determine the chances for survival in patients with non-metastatic pancreatic cancer.

3 Article Diabetes mellitus is associated with unfavorable pathologic features, increased postoperative mortality, and worse long-term survival in resected pancreatic cancer. 2020

Hank, Thomas / Sandini, Marta / Qadan, Motaz / Weniger, Maximilian / Ciprani, Debora / Li, Annie / Ferrone, Cristina R / Warshaw, Andrew L / Lillemoe, Keith D / Fernández-Del Castillo, Carlos. ·Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: CFernandez@mgh.harvard.edu. ·Pancreatology · Pubmed #31706821.

ABSTRACT: BACKGROUND: The risk of pancreatic ductal adenocarcinoma (PDAC) is increased in patients with diabetes mellitus (DM), particularly in those with new-onset DM. However, the impact of DM on outcomes following pancreatic surgery is not fully understood. We sought to explore the effects of DM on post-resection outcomes in patients undergoing either upfront resection or following neoadjuvant treatment (NAT). METHODS: Resections for PDAC between 2007 and 2016 were identified from a prospectively-maintained database. Data on demographics, pathology, and perioperative outcomes were compared between patients with or without DM. Survival analysis was performed using Kaplan-Meier curves and adjusted for confounders by a Cox-proportional hazards model. RESULTS: 662 patients were identified, of whom 277 (41.8%) had DM. Diabetics were more likely to be male, had higher BMI, and higher ASA-scores. At pathology, DM was associated with larger tumors (30 vs. 26 mm; p = 0.041), higher rates of lymph-node involvement (69% vs. 59%; p = 0.031) and perineural invasion (88% vs. 82%; p = 0.026). Despite having similar rates of complications, diabetics experienced higher 30-day mortality (3.2% vs. 0.8%; p = 0.019). Median overall survival was worse in diabetic patients (18 vs. 34 months; p < 0.001); this effect was more pronounced in patients with NAT (18 vs. 54 months; p < 0.001). At multivariate analysis, DM was confirmed as an independent predictor of post-resection survival. CONCLUSION: DM is a common comorbidity in PDAC and is associated with unfavorable pathology, as well as worse postoperative and oncologic outcomes. The blunted effect on survival is more pronounced in patients who undergo resection following NAT.

4 Article Validation of at least 1 mm as cut-off for resection margins for pancreatic adenocarcinoma of the body and tail. 2018

Hank, T / Hinz, U / Tarantino, I / Kaiser, J / Niesen, W / Bergmann, F / Hackert, T / Büchler, M W / Strobel, O. ·Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Institute of Pathology, University of Heidelberg, Heidelberg, Germany. ·Br J Surg · Pubmed #29738626.

ABSTRACT: BACKGROUND: The definition of resection margin (R) status in pancreatic cancer is under debate. Although a margin of at least 1 mm is an independent predictor of survival after resection for pancreatic head cancer, its relevance to pancreatic body and tail cancers remains unclear. This study aimed to validate R status based on a 1-mm tumour-free margin as a prognostic factor for resected adenocarcinoma involving the pancreatic body and tail. METHODS: Patients who underwent distal or total pancreatectomy for adenocarcinomas of the pancreatic body and tail between January 2006 and December 2014 were identified from a prospective database. Resection margins were evaluated using a predefined cut-off of 1 mm. Rates of R0, R1 with invasion within 1 mm of the margin (R1 less than 1 mm), and R1 with direct invasion of the resection margin (R1 direct) were determined, and overall survival in each group assessed by Kaplan-Meier analysis. Univariable and multivariable Cox regression analyses were performed to identify predictors of survival. RESULTS: R0 resection was achieved in 107 (23·5 per cent) and R1 in 348 (76·5 per cent) of 455 patients. Among R1 resections, invasion within 1 mm of the margin was found in 104 (22·9 per cent) and direct invasion in 244 (53·6 per cent). The R0 rate was 28·9 per cent after distal and 18·6 per cent after total pancreatectomy. In the total cohort, median survival times for patients with R0, R1 (less than 1 mm) and R1 (direct) status were 62·4, 24·6 and 17·2 months respectively, with 5-year survival rates of 52·6, 16·8 and 13·0 per cent (P < 0·001). In patients who received adjuvant chemotherapy, respective median survival times were 68·6, 32·8 and 21·4 months, with 5-year survival rates of 56, 22 and 16·0 per cent (P < 0·001). In multivariable analysis, R status was independently associated with survival. CONCLUSION: A cut-off of at least 1 mm for evaluation of resection margins is an independent determinant of survival after resection of adenocarcinomas of the pancreatic body and tail.

5 Article Genome-wide genetic and epigenetic analyses of pancreatic acinar cell carcinomas reveal aberrations in genome stability. 2017

Jäkel, Cornelia / Bergmann, Frank / Toth, Reka / Assenov, Yassen / van der Duin, Daniel / Strobel, Oliver / Hank, Thomas / Klöppel, Günter / Dorrell, Craig / Grompe, Markus / Moss, Joshua / Dor, Yuval / Schirmacher, Peter / Plass, Christoph / Popanda, Odilia / Schmezer, Peter. ·Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. · Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. · Department of General and Visceral Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. · Institute of Pathology, Technical University Munich, Trogerstr. 18, 81675, Munich, Germany. · Department of Pediatrics, Papé Family Pediatric Research Institute, Oregon Stem Cell Center, Oregon Health and Science University, Portland, OR, 97239, USA. · Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, 9112102, Jerusalem, Israel. · Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. p.schmezer@dkfz.de. ·Nat Commun · Pubmed #29109526.

ABSTRACT: Pancreatic acinar cell carcinoma (ACC) is an aggressive exocrine tumor with largely unknown biology. Here, to identify potential targets for personalized treatment, we perform integrative genome-wide and epigenome-wide analyses. The results show frequently aberrant DNA methylation, abundant chromosomal amplifications and deletions, and mutational signatures suggesting defective DNA repair. In contrast to pancreatic ductal adenocarcinoma, no recurrent point mutations are detected. The tumor suppressors ID3, ARID1A, APC, and CDKN2A are frequently impaired also on the protein level and thus potentially affect ACC tumorigenesis. Consequently, this work identifies promising therapeutic targets in ACC for drugs recently approved for precision cancer therapy.

6 Article Pancreatic Cancer Surgery: The New R-status Counts. 2017

Strobel, Oliver / Hank, Thomas / Hinz, Ulf / Bergmann, Frank / Schneider, Lutz / Springfeld, Christoph / Jäger, Dirk / Schirmacher, Peter / Hackert, Thilo / Büchler, Markus W. ·*Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany †Institute of Pathology Heidelberg, Heidelberg, Germany ‡National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany. ·Ann Surg · Pubmed #27918310.

ABSTRACT: OBJECTIVE: To assess the relevance of resection margin status for survival outcome after resection and adjuvant therapy for pancreatic cancer. BACKGROUND: The definitions for R0 and R1 margin status after resection for pancreatic cancer are controversial. The strict definition of R0 requiring a 1 mm tumor-free margin is not commonly accepted. Reported R0/R1 rates and associated survival are highly heterogeneous. METHODS: A standardized protocol with rigorous assessment of circumferential margins and the R0 definition with a 1 mm free margin were introduced into clinical routine in 2005. From a prospective database, patients undergoing pancreatoduodenectomy for pancreatic adenocarcinoma between January 1, 2006 and December 12, 2012 were identified. The rates of R0 (≥1 mm margin), R1 (<1 mm clearance), and R1 (direct margin involvement) status and associated survival were assessed by uni- and multivariable analyses. RESULTS: Of 561 patients included, 112 patients (20.0%) had R0 and 449 patients (80.0%) had R1 resections, including 123 (21.9%) R1 (≤1 mm) and 326 (58.1%) R1 (direct) resections. A total of 438 (85.9%) received adjuvant therapy. With R0, R1 (<1 mm), and R1 (direct) status the median survival times and 5-year survival rates were 41.6, 27.5, and 23.4 months; and 37.7%, 30.1%, and 20.3%, respectively (P < 0.0001). By multivariable analysis, margin status was confirmed to be independently associated with survival. CONCLUSIONS: In the context of adjuvant therapy, the resection margin status remains an important independent determinant of postresection survival. R0/R1 resection rates and associated survival vary significantly with the definitions used. An international consensus is urgently needed to achieve comparability with respect to studies and protocols on patients with adjuvant therapy.

7 Article Relevance of Sp Binding Site Polymorphism in WWOX for Treatment Outcome in Pancreatic Cancer. 2016

Schirmer, Markus A / Lüske, Claudia M / Roppel, Sebastian / Schaudinn, Alexander / Zimmer, Christian / Pflüger, Ruben / Haubrock, Martin / Rapp, Jacobe / Güngör, Cenap / Bockhorn, Maximilian / Hackert, Thilo / Hank, Thomas / Strobel, Oliver / Werner, Jens / Izbicki, Jakob R / Johnsen, Steven A / Gaedcke, Jochen / Brockmöller, Jürgen / Ghadimi, B Michael. ·Affiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany · Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI) · Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW). ·J Natl Cancer Inst · Pubmed #26857392.

ABSTRACT: BACKGROUND: A genome-wide association study (GWAS) suggested inherited genetic single-nucleotide polymorphisms (SNPs) affecting overall survival (OS) in advanced pancreatic cancer. To identify robust clinical biomarkers, we tested the strongest reported candidate loci in an independent patient cohort, assessed cellular drug sensitivity, and evaluated molecular effects. METHODS: This study comprised 381 patients with histologically verified pancreatic ductal adenocarcinoma treated with gemcitabine-based chemotherapy. The primary outcome was the relationship between germline polymorphisms and OS. Functional assays addressed pharmacological dose-response effects in lymphoblastoid cell lines (LCLs) and pancreatic cancer cell lines (including upon RNAi), gene expression analyses, and allele-specific transcription factor binding. All statistical tests were two-sided. RESULTS: The A allele (26% in Caucasians) at SNP rs11644322 in the putative tumor suppressor gene WWOX conferred worse prognosis. Median OS was 14 months (95% confidence interval [CI] = 12 to 15 months), 13 months (95% CI = 11 to 15 months), and nine months (95% CI = 7 to 12 months) for the GG, GA, and AA genotypes, respectively (P trend < .001 for trend in univariate log-rank assuming a codominant mode of inheritance; advanced disease subgroup P trend < .001). Mean OS was 25 months (95% CI = 21 to 29 months), 19 months (95% CI = 15 to 22 months), and 13 months (95% CI = 10 to 16 months), respectively. This effect held true after adjustment for age, performance status according to Eastern Cooperative Oncology Group classification, TNM, grading, and resection status and was comparable with the strongest established prognostic factors in multivariable analysis. Consistently, reduced responsiveness to gemcitabine, but not 5-fluorouracil, along with lower WWOX expression was demonstrated in LCLs harboring the AA genotype. Likewise, RNAi-mediated WWOX knockdown in pancreatic cancer cells confirmed differential cytostatic drug sensitivity. In electrophoretic mobility shift assays, the A allele exhibited weaker binding of Sp family members Sp1/Sp3. CONCLUSIONS: WWOX rs11644322 represents a major predictive factor in gemcitabine-treated pancreatic cancer. Decreased WWOX expression may interfere with gemcitabine sensitivity, and allele-specific binding at rs11644332 might be a causative molecular mechanism behind the observed clinical associations.

8 Article Pancreatic adenocarcinoma: number of positive nodes allows to distinguish several N categories. 2015

Strobel, Oliver / Hinz, Ulf / Gluth, Alexander / Hank, Thomas / Hackert, Thilo / Bergmann, Frank / Werner, Jens / Büchler, Markus W. ·*Department of Surgery †Division of Biostatistics; and ‡Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; and §Department of Surgery, Ludwig-Maximilians University, Munich, Germany. ·Ann Surg · Pubmed #24979603.

ABSTRACT: OBJECTIVE: To determine the prognostic value of PLN and LNR based on a large series with standardized lymphadenectomy and pathological workup. BACKGROUND: Lymph node (LN) involvement is a major prognostic factor in pancreatic adenocarcinoma. However, the distinction N0/N1 is not sufficient to accurately predict prognosis. To improve prognostic accuracy in N1 tumors, different LN parameters have been tested. Previous studies were based on series with variable numbers of examined lymph nodes (ELN) and came to inconsistent conclusions as to the value of the number of positive lymph nodes (PLN) and the lymph node ratio (LNR). METHODS: 811 patients who underwent pancreatoduodenectomy for pancreatic adenocarcinoma between October 2001 and June 2012 were identified from a prospective database. Clinicopathological parameters included LN status (N0/N1), ELN, PLN, and LNR. Univariate and multivariate survival analyses were performed. RESULTS: The median number of ELN was 24 (interquartile range: 18-32). By univariate analysis, both PLN and LNR were significantly associated with survival in N1 tumors. However, by multivariate analysis, only the number of PLN was confirmed as independent predictor of survival. Median survival in patients with only 1 PLN was 31.1 months and comparable to the survival in N0 (33.2 months). With increasing numbers of PLN median survival significantly decreased (2-3 PLN: 26.1 months, 4-7 PLN: 21.9 months, ≥8 PLN: 18.3 months, P < 0.0001). CONCLUSIONS: This study demonstrates that, based on high numbers of ELN, PLN is superior to LNR in predicting survival and allows to distinguish several N-categories that improve prognostic accuracy in LN-positive resectable pancreatic adenocarcinoma.