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Pancreatic Neoplasms: HELP
Articles by Caroline S. Verbeke
Based on 18 articles published since 2010
(Why 18 articles?)
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Between 2010 and 2020, Caroline S. Verbeke wrote the following 18 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Editorial Resection margins in pancreatic cancer: are we entering a new era? 2014

Verbeke, Caroline S. ·Division of Pathology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden. ·HPB (Oxford) · Pubmed #24329942.

ABSTRACT: -- No abstract --

2 Review Resection margins in pancreatic cancer. 2013

Verbeke, Caroline S. ·Division of Pathology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden. caroline.verbeke@ki.se ·Surg Clin North Am · Pubmed #23632150.

ABSTRACT: Controversy regarding various aspects of microscopic margin involvement (R1) in pancreatic cancer has resulted in conflicting published data on the R1 rate and the prognostic significance of margin involvement. This article discusses the current lack of consensus regarding the definition and diagnostic criteria of R1 resection, the terminology for the various surgical margins, and the pathology grossing technique. Recent developments in pathology examination that allow a more accurate margin assessment are described. Furthermore, the need of a quality assurance system that ensures robustness and comparability of data on resection margins in pancreatic cancer is highlighted.

3 Review Pancreatic lesions in von Hippel-Lindau disease? A systematic review and meta-synthesis of the literature. 2012

Charlesworth, Michael / Verbeke, Caroline S / Falk, Gavin A / Walsh, Matthew / Smith, Andrew M / Morris-Stiff, Gareth. ·Pancreatic Surgery Unit, St. James's University Hospital, Beckett Street, Leeds, LS9 7TF, England, UK. ·J Gastrointest Surg · Pubmed #22370733.

ABSTRACT: BACKGROUND: von Hippel-Lindau (vHL) disease is a rare condition that leads to characteristic lesions within many different body systems. Pancreatic manifestations of vHL cover a wide spectrum of pathologies, and thus, accurate characterization and management is critical. METHODS: A comprehensive and systematic text word and MeSH search of the medical literature was performed to identify studies where information regarding the prevalence, clinical characteristics, and management recommendations could be extracted. RESULTS: Eleven studies were identified but 2 studies utilized the same data set. Of the 10 remaining studies, a total of 1,442 patients with vHL were available for analysis. Four hundred and twenty patients were examined for any type of pancreatic lesion, 362 for simple cysts or serous cystadenomas (SCAs), and 1,442 for neuroendocrine tumors (NETs). Of the 420 assessed for any pancreatic manifestation of vHL, 252 (60%) had a pancreatic lesion identified. Simple cysts that present as the sole manifestation of pancreatic disease were common and found in 169 of 362 (47%) patients. These are usually asymptomatic and do not normally require intervention. SCAs were reported in 39 of 362 (11%) patients and followed a similar benign course; resection is acceptable in symptomatic patients. NETs were identified in 211 of 1,442 (15%) patients, and 27 of 1,442 (2%) lesions behaved malignantly. Management of NETs depends on size, doubling time, and underlying genetics. Renal cell carcinoma is a characteristic in vHL, but there were no cases of pancreatic metastases identified from the included studies. Adenocarcinomas of the pancreas are not pathogenically linked to vHL. CONCLUSIONS: This review highlights the wide spectrum and high prevalence of pancreatic lesions in vHL. Simple cysts and SCAs are benign, but NETs require careful observation due to their malignant potential.

4 Clinical Trial Highly Accurate Identification of Cystic Precursor Lesions of Pancreatic Cancer Through Targeted Mass Spectrometry: A Phase IIc Diagnostic Study. 2018

Jabbar, Karolina S / Arike, Liisa / Verbeke, Caroline S / Sadik, Riadh / Hansson, Gunnar C. ·Karolina S. Jabbar, Liisa Arike, and Gunnar C. Hansson, University of Gothenburg · Karolina S. Jabbar and Riadh Sadik, Sahlgrenska University Hospital, Gothenburg, Sweden · and Caroline S. Verbeke, University of Oslo, Oslo, Norway. ·J Clin Oncol · Pubmed #29166170.

ABSTRACT: Purpose Pancreatic cystic lesions are common incidental findings on imaging, but up to half may be forerunners of pancreatic cancer. Therefore, accurate differential diagnosis is crucial for correct patient management. Unfortunately, currently available diagnostic methods cannot robustly identify premalignant and malignant pancreatic cystic lesions. Methods Cyst fluid samples obtained by routine endoscopic ultrasound-guided aspiration were used for the analyses. In a cohort of 24 patients, eight biomarker candidates for malignant potential and high-grade dysplasia/cancer were identified by an explorative proteomic approach. Subsequently, a quantitative analysis, using 30 heavy-labeled peptides from the biomarkers and parallel reaction monitoring mass spectrometry, was devised, tested in a training cohort of 80, and prospectively evaluated in a validation cohort of 68 patients. End points were surgical pathology diagnosis/clinical follow-up. Diagnostic assessments were blinded to mass spectrometry results. Results The optimal set of markers for detecting malignant potential was a panel of peptides from mucin-5AC and mucin-2, which could discriminate premalignant/malignant lesions from benign with an accuracy of 97% (95% CI, 89% to 99%) in the validation cohort. This result compared favorably with the accuracy of standard analyses: cyst fluid carcinoembryonic antigen (61%; 95% CI, 46% to 74%; P < .001) and cytology (84%; 95% CI, 71% to 92%; P = .02). A combination of proteins mucin-5AC and prostate stem-cell antigen could identify high-grade dysplasia/cancer with an accuracy of 96% (95% CI, 90% to 99%), and detected 95% of malignant/severely dysplastic lesions, compared with 35% and 50% for carcinoembryonic antigen and cytology ( P < .001 and P = .003, respectively). Conclusion Targeted mass spectrometry analysis of just three cyst fluid biomarkers provides highly accurate identification and assessment of cystic precursors to pancreatic adenocarcinoma. Additional studies should determine whether the method can facilitate timely cancer diagnosis, successful intervention, and prevention.

5 Article Immunohistochemical profiling of liver metastases and matched-pair analysis in patients with metastatic pancreatic ductal adenocarcinoma. 2019

Held, Thomas / Verbeke, Caroline S / Strobel, Oliver / Rutkowski, Wiktor / Villard, Christina / Moro, Carlos Fernández / Del Chiaro, Marco / Büchler, Markus / Heuchel, Rainer / Löhr, Matthias. ·Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany; National Center for Tumor Diseases (NCT), Heidelberg, Germany; Pancreas Cancer Research Lab, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden. Electronic address: thomas.held@med.uni-heidelberg.de. · Department of Pathology, Karolinska University Hospital, Stockholm, Sweden; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: c.s.verbeke@medisin.uio.no. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: oliver.strobel@med.uni-heidelberg.de. · Pancreas Cancer Research Lab, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden. Electronic address: wiktor.rutkowski@stud.ki.se. · Department of Cancer, Karolinska University Hospital, Stockholm, Sweden. Electronic address: christina.villard@sll.se. · Department of Pathology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: carlos.fernandez.moro@ki.se. · Department of Cancer, Karolinska University Hospital, Stockholm, Sweden. Electronic address: marco.del.chiaro@ki.se. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: markus.buechler@med.uni-heidelberg.de. · Pancreas Cancer Research Lab, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden. Electronic address: rainer.heuchel@ki.se. · Pancreas Cancer Research Lab, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden; Department of Cancer, Karolinska University Hospital, Stockholm, Sweden. Electronic address: matthias.lohr@ki.se. ·Pancreatology · Pubmed #31542399.

ABSTRACT: BACKGROUND: The purpose of the current study was to investigate the immunohistochemical (IHC) profile of liver metastases (LM) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Expression of 15 IHC markers in liver biopsies from 77 patients with PDAC, who were diagnosed between 2010 and 2014, were evaluated. In a separate subgroup analysis (n = 12), paired samples (LM and primary tumor) from the same patient were investigated for IHC profile differences. RESULTS: LM samples were classified as pancreatobiliary-type (PB-type) in 72 patients (93.5%), intestinal-type (INT-type) in four patients (5.2%), and squamous in one patient (1.3%). There was no significant difference in overall survival (OS) between LM of the PB-type or INT-type (p = 0.097). In a multivariate analysis, age <70 years (p = 0.047), absence of SMAD4 mutation (p = 0.026), absence of CDX2 expression (p = 0.003), and well to moderate differentiation were significant prognostic factors for better OS in patients with LM (p = 0.031). Analysis of paired tissue samples from LM and the primary tumor revealed a difference in CDX2 (50% increase, p = 0.125) and SMAD4 (33% loss of SMAD4, p = 0.375). CONCLUSIONS: CDX2 expression and SMAD4 mutation indicate a poor outcome in patients with LM of PDAC. Matched-pair analysis revealed differences in distinct IHC marker expression.

6 Article Secretion of fibronectin by human pancreatic stellate cells promotes chemoresistance to gemcitabine in pancreatic cancer cells. 2019

Amrutkar, Manoj / Aasrum, Monica / Verbeke, Caroline S / Gladhaug, Ivar P. ·Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, Blindern, 0316, Oslo, Norway. manoj.amrutkar@medisin.uio.no. · Department of Hepato-Pancreato-Biliary Surgery, Institute of Clinical Medicine, University of Oslo, PO Box 1171, Blindern, 0318, Oslo, Norway. manoj.amrutkar@medisin.uio.no. · Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, Blindern, 0316, Oslo, Norway. · Department of Pathology, Institute of Clinical Medicine, University of Oslo, Blindern, 0316, Oslo, Norway. · Department of Pathology, Oslo University Hospital Rikshospitalet, Nydalen, 0424, Oslo, Norway. · Department of Hepato-Pancreato-Biliary Surgery, Institute of Clinical Medicine, University of Oslo, PO Box 1171, Blindern, 0318, Oslo, Norway. · Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital Rikshospitalet, Nydalen, 0424, Oslo, Norway. ·BMC Cancer · Pubmed #31208372.

ABSTRACT: BACKGROUND: Gemcitabine remains a cornerstone in chemotherapy of pancreatic ductal adenocarcinoma (PDAC) despite suboptimal clinical effects that are partly due to the development of chemoresistance. Pancreatic stellate cells (PSCs) of the tumor stroma are known to interact with pancreatic cancer cells (PCCs) and influence the progression of PDAC through a complex network of signaling molecules that involve extracellular matrix (ECM) proteins. To understand tumor-stroma interactions regulating chemosensitivity, the role of PSC-secreted fibronectin (FN) in the development of gemcitabine resistance in PDAC was examined. METHODS: PSC cultures obtained from ten different human PDAC tumors were co-cultured with PCC lines (AsPC-1, BxPC-3, Capan-2, HPAF-II, MIA PaCa-2, PANC-1 and SW-1990) either directly, or indirectly via incubation with PSC-conditioned medium (PSC-CM). Gemcitabine dose response cytotoxicity was determined using MTT based cell viability assays. Protein expression was assessed by western blotting and immunofluorescence. PSC-CM secretome analysis was performed by proteomics-based LC-MS/MS, and FN content in PSC-CM was determined with ELISA. Radiolabeled gemcitabine was used to determine the capacity of PCCs to uptake the drug. RESULTS: In both direct and indirect co-culture, PSCs induced varying degrees of resistance to the cytotoxic effects of gemcitabine among all cancer cell lines examined. A variable degree of increased phosphorylation of ERK1/2 was observed across all PCC lines upon incubation with PSC-CM, while activation of AKT was not detected. Secretome analysis of PSC-CM identified 796 different proteins, including several ECM-related proteins such as FN and collagens. Soluble FN content in PSC-CM was detected in the range 175-350 ng/ml. Neither FN nor PSC-CM showed any effect on PCC uptake capacity of gemcitabine. PCCs grown on FN-coated surface displayed higher resistance to gemcitabine compared to cells grown on non-coated surface. Furthermore, a FN inhibitor, synthetic Arg-Gly-Asp-Ser (RGDS) peptide significantly inhibited PSC-CM-induced chemoresistance in PCCs via downregulation of ERK1/2 phosphorylation. CONCLUSIONS: The findings of this study suggest that FN secreted by PSCs in the ECM plays a key role in the development of resistance to gemcitabine via activation of ERK1/2. FN-blocking agents added to gemcitabine-based chemotherapy might counteract chemoresistance in PDAC and provide better clinical outcomes.

7 Article Commonly Used Pancreatic Stellate Cell Cultures Differ Phenotypically and in Their Interactions with Pancreatic Cancer Cells. 2019

Lenggenhager, Daniela / Amrutkar, Manoj / Sántha, Petra / Aasrum, Monica / Löhr, Johannes-Matthias / Gladhaug, Ivar P / Verbeke, Caroline S. ·Department of Pathology, Institute of Clinical Medicine, University of Oslo, Blindern, 0316 Oslo, Norway. Daniela.Lenggenhager@usz.ch. · Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, Blindern, 0316 Oslo, Norway. Daniela.Lenggenhager@usz.ch. · Department of Pathology and Molecular Pathology, University Hospital Zürich, University of Zürich, Schmelzbergstrasse 12, 8091 Zürich, Switzerland. Daniela.Lenggenhager@usz.ch. · Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, Blindern, 0316 Oslo, Norway. manoj.amrutkar@medisin.uio.no. · Department of Hepato-Pancreato-Biliary Surgery, Institute of Clinical Medicine, University of Oslo, P.O. Box 1171 Blindern, 0318 Oslo, Norway. manoj.amrutkar@medisin.uio.no. · Department of Pathology, Oslo University Hospital Rikshospitalet, Nydalen, 0424 Oslo, Norway. petra.santha@medisin.uio.no. · Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, Blindern, 0316 Oslo, Norway. monica.aasrum@medisin.uio.no. · Department of Clinical Science, Intervention and Technology, Karolinska Institutet, K 53, 141 86 Stockholm, Sweden. matthias.lohr@ki.se. · Department of Hepato-Pancreato-Biliary Surgery, Institute of Clinical Medicine, University of Oslo, P.O. Box 1171 Blindern, 0318 Oslo, Norway. i.p.gladhaug@medisin.uio.no. · Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital Rikshospitalet, Nydalen, 0424 Oslo, Norway. i.p.gladhaug@medisin.uio.no. · Department of Pathology, Institute of Clinical Medicine, University of Oslo, Blindern, 0316 Oslo, Norway. c.s.verbeke@medisin.uio.no. · Department of Pathology, Oslo University Hospital Rikshospitalet, Nydalen, 0424 Oslo, Norway. c.s.verbeke@medisin.uio.no. ·Cells · Pubmed #30621293.

ABSTRACT: Activated pancreatic stellate cells (PSCs) play a central role in the tumor stroma of pancreatic ductal adenocarcinoma (PDAC). Given the limited availability of patient-derived PSCs from PDAC, immortalized PSC cell lines of murine and human origin have been established; however, it is not elucidated whether differences in species, organ disease status, donor age, and immortalization alter the PSC phenotype and behavior compared to that of patient-derived primary PSC cultures. Therefore, a panel of commonly used PSC cultures was examined for important phenotypical and functional features: three primary cultures from human PDAC, one primary from normal human pancreas, and three immortalized (one from human, two from murine pancreas). Growth rate was considerably lower in primary PSCs from human PDAC. Basal collagen synthesis varied between the PSC cultures, and TGF-β stimulation increased collagen synthesis only in non-immortalized cultures. Differences in secretome composition were observed along with a divergence in the DNA synthesis, migration, and response to gemcitabine of PDAC cell lines that were grown in conditioned medium from the various PSC cultures. The findings reveal considerable differences in features and functions that are key to PSCs and in the interactions with PDAC. These observations may be relevant to researchers when selecting the most appropriate PSC culture for their experiments.

8 Article Pancreatectomy with arterial resection is superior to palliation in patients with borderline resectable or locally advanced pancreatic cancer. 2019

Del Chiaro, Marco / Rangelova, Elena / Halimi, Asif / Ateeb, Zeeshan / Scandavini, Chiara / Valente, Roberto / Segersvärd, Ralf / Arnelo, Urban / Verbeke, Caroline S. ·Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute at Center for Digestive Diseases, Karolinska University Hospital, K53, 14186, Stockholm, Sweden. Electronic address: marco.del.chiaro@ki.se. · Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute at Center for Digestive Diseases, Karolinska University Hospital, K53, 14186, Stockholm, Sweden. · Department of Pathology & Cytology, Karolinska University Hospital, Stockholm, Sweden; Institute of Clinical Medicine, Oslo University, Norway. ·HPB (Oxford) · Pubmed #30093144.

ABSTRACT: BACKGROUND: Few studies have investigated the outcome of pancreatectomy associated with artery resection (PAR). METHODS: Retrospective analysis of a cohort of operated borderline or locally advanced pancreatic cancer patients with surgically confirmed arterial involvement. Short and long-term outcome were analyzed and compared in patients who underwent PAR (Group 1) and palliative surgery (Group 2). RESULTS: Of 73 patients who underwent surgical exploration with intent of resection, 34 underwent PAR (±venous resection) (Group 1) and 39 underwent palliation (Group 2). 23 patients (67.7%) in Group 1 underwent combined artery-vein resection (AVR). Operation time was longer and blood loss higher in group 1 compared to group 2. There were no differences in post-operative mortality (2.9% vs 2.6%, p = 0.9) and post-operative surgical complications (38.2% vs 25.6%, p = 0.2). The 1, 3 and 5 years survival in Group 1 was superior to Group 2 (63.7%, 23.4% and Q3 23.4% vs 41.7%, 3.2% and 0, p = 0.003). CONCLUSION: PAR seems to be safe and feasible in well selected patients and associated with an advantage of survival compared to palliation, in patients affected by locally advanced pancreatic cancer.

9 Article Portal vein reconstruction using primary anastomosis or venous interposition allograft in pancreatic surgery. 2018

Kleive, Dyre / Berstad, Audun Elnaes / Sahakyan, Mushegh A / Verbeke, Caroline S / Naper, Christian / Haugvik, Sven Petter / Gladhaug, Ivar P / Line, Pål-Dag / Labori, Knut Jørgen. ·Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: dyrkle@ous-hf.no. · Department of Radiology, Oslo University Hospital, Oslo, Norway. · Institute of Clinical Medicine, University of Oslo, Oslo, Norway; The Intervention Centre, Oslo University Hospital, Oslo, Norway. · Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Pathology, Oslo University Hospital, Oslo, Norway. · Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway. · Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway; Department of Surgery, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway. · Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway. · Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway. ·J Vasc Surg Venous Lymphat Disord · Pubmed #29128301.

ABSTRACT: OBJECTIVE: Superior mesenteric vein/portal vein (SMV/PV) resection and reconstruction during pancreatic surgery are increasingly common. Several reconstruction techniques exist. The aim of this study was to evaluate characteristics of patients and clinical outcomes for SMV/PV reconstruction using interposed cold-stored cadaveric venous allograft (AG+) or primary end-to-end anastomosis (AG-) after segmental vein resections during pancreatic surgery. METHODS: All patients undergoing pancreatic surgery with SMV/PV resection and reconstruction from 2006 to 2015 were identified. Clinical and histopathologic outcomes as well as preoperative and postoperative radiologic findings were assessed. RESULTS: A total of 171 patients were identified. The study included 42 and 71 patients reconstructed with AG+ and AG-, respectively. Patients in the AG+ group had longer mean operative time (506 minutes [standard deviation, 83 minutes] for AG+ vs 420 minutes [standard deviation, 91 minutes] for AG-; P < .01) and more intraoperative bleeding (median, 1000 mL [interquartile range (IQR), 650-2200 mL] for AG+ vs 600 mL [IQR, 300-1000 mL] for AG-; P < .01). Neoadjuvant therapy was administered more frequently for patients in the AG+ group (23.8% vs 8.5%; P = .02). Patients with AG+ had a longer length of tumor-vein involvement (median, 2.4 cm [IQR, 1.6-3.0 cm] for AG+ vs 1.8 cm [IQR, 1.2-2.4 cm] for AG-; P = .01), and a higher number of patients had a tumor-vein interface >180 degrees (35.7% for AG+ vs 21.1% for AG-; P = .02). There was no difference in number of patients with major complications (42.9% for AG+ vs 36.6% for AG-; P = .51) or early failure at the reconstruction site (9.5% for AG+ vs 8.5% for AG-; P = 1). A subgroup analysis of 10 patients in the AG+ group revealed the presence of donor-specific antibodies in all patients. CONCLUSIONS: The short-term outcome of SMV/PV reconstruction with interposed cold-stored cadaveric venous allografts is comparable to that of reconstruction with primary end-to-end anastomosis. Graft rejection could be a contributing factor to severe stenosis in patients reconstructed with allograft.

10 Article Can standardized pathology examination increase the lymph node yield following laparoscopic distal pancreatectomy for ductal adenocarcinoma? 2018

Sahakyan, Mushegh A / Haugvik, Sven P / Røsok, Bård I / Kazaryan, Airazat M / Ignjatovic, Dejan / Buanes, Trond / Labori, Knut J / Verbeke, Caroline S / Edwin, Bjørn. ·The Intervention Centre, Rikshospitalet, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Norway. Electronic address: sahakyan.mushegh@gmail.com. · Department of Surgery, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway; Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, Oslo, Norway. · Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, Oslo, Norway. · The Intervention Centre, Rikshospitalet, Oslo University Hospital, Oslo, Norway; Department of Digestive Surgery, Akershus University Hospital, University of Oslo, Lørenskog, Norway. · Institute of Clinical Medicine, University of Oslo, Norway; Department of Digestive Surgery, Akershus University Hospital, University of Oslo, Lørenskog, Norway. · Institute of Clinical Medicine, University of Oslo, Norway; Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, Oslo, Norway. · Institute of Clinical Medicine, University of Oslo, Norway; Department of Pathology, Rikshospitalet, Oslo University Hospital, Oslo, Norway. · The Intervention Centre, Rikshospitalet, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Norway; Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, Oslo, Norway. ·HPB (Oxford) · Pubmed #28943397.

ABSTRACT: BACKGROUND: Lymph node yield (LNY) is an indicator of oncological adequacy of surgery in patients with pancreatic ductal adenocarcinoma (PDAC). Our hypothesis is that standardized pathology examination (SPE) aimed at accurate staging can increase the LNY without changing surgical technique. METHODS: After the introduction of SPE for distal pancreatosplenectomy specimens at Oslo University Hospital, prospective data were collected on patients with PDAC undergoing laparoscopic distal pancreatosplenectomy (LDP). Their data were compared with retrospective data from specimens examined in a non-standardized way (NSPE). RESULTS: SPE and NSPE were applied to 20 and 33 specimens, respectively. SPE was associated with a higher LNY and a higher median number of positive lymph nodes (PLN) in the specimen (18 vs 7, P = 0.001 and 4 vs 1, P = 0.005, respectively). In the stepwise regression model, SPE and younger age resulted in an increased LNY. In the logistic regression model, increased LNY and larger tumor size positively correlated with the presence of PLN. CONCLUSION: SPE of distal pancreatosplenectomy specimens is associated with higher LNY in patients with PDAC, which increases the likelihood of detecting PLN and reduces the risk of understaging. These findings also indicate that the LDP technique provides an adequate LNY in patients with PDAC.

11 Article Bioinformatory-assisted analysis of next-generation sequencing data for precision medicine in pancreatic cancer. 2017

Malgerud, Linnéa / Lindberg, Johan / Wirta, Valtteri / Gustafsson-Liljefors, Maria / Karimi, Masoud / Moro, Carlos Fernández / Stecker, Katrin / Picker, Alexander / Huelsewig, Carolin / Stein, Martin / Bohnert, Regina / Del Chiaro, Marco / Haas, Stephan L / Heuchel, Rainer L / Permert, Johan / Maeurer, Markus J / Brock, Stephan / Verbeke, Caroline S / Engstrand, Lars / Jackson, David B / Grönberg, Henrik / Löhr, Johannes Matthias. ·Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden. · Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden. · Department of Medical Epidemiology & Biostatistics (MEB), Karolinska Institutet, Stockholm, Sweden. · Science for Life Laboratory, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden. · Department of Oncology at Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden. · Department of Pathology, Karolinska University Hospital, Stockholm, Sweden. · Molecular Health GmbH, Heidelberg, Germany. · Innovation Office, Karolinska University Hospital, Stockholm, Sweden. · Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden. ·Mol Oncol · Pubmed #28675654.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a tumor with an extremely poor prognosis, predominantly as a result of chemotherapy resistance and numerous somatic mutations. Consequently, PDAC is a prime candidate for the use of sequencing to identify causative mutations, facilitating subsequent administration of targeted therapy. In a feasibility study, we retrospectively assessed the therapeutic recommendations of a novel, evidence-based software that analyzes next-generation sequencing (NGS) data using a large panel of pharmacogenomic biomarkers for efficacy and toxicity. Tissue from 14 patients with PDAC was sequenced using NGS with a 620 gene panel. FASTQ files were fed into treatmentmap. The results were compared with chemotherapy in the patients, including all side effects. No changes in therapy were made. Known driver mutations for PDAC were confirmed (e.g. KRAS, TP53). Software analysis revealed positive biomarkers for predicted effective and ineffective treatments in all patients. At least one biomarker associated with increased toxicity could be detected in all patients. Patients had been receiving one of the currently approved chemotherapy agents. In two patients, toxicity could have been correctly predicted by the software analysis. The results suggest that NGS, in combination with an evidence-based software, could be conducted within a 2-week period, thus being feasible for clinical routine. Therapy recommendations were principally off-label use. Based on the predominant KRAS mutations, other drugs were predicted to be ineffective. The pharmacogenomic biomarkers indicative of increased toxicity could be retrospectively linked to reported negative side effects in the respective patients. Finally, the occurrence of somatic and germline mutations in cancer syndrome-associated genes is noteworthy, despite a high frequency of these particular variants in the background population. These results suggest software-analysis of NGS data provides evidence-based information on effective, ineffective and toxic drugs, potentially forming the basis for precision cancer medicine in PDAC.

12 Article Outcome of probe-based confocal laser endomicroscopy (pCLE) during endoscopic retrograde cholangiopancreatography: A single-center prospective study in 45 patients. 2015

Löhr, Johannes-Matthias / Lönnebro, Ragnar / Stigliano, Serena / Haas, Stephan L / Swahn, Fredrik / Enochsson, Lars / Noel, Rozh / Segersvärd, Ralf / Del Chiaro, Marco / Verbeke, Caroline S / Arnelo, Urban. ·Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden. · Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden ; Department of Gastroenterology, La Sapienza University, Rome, Italy. ·United European Gastroenterol J · Pubmed #26668748.

ABSTRACT: BACKGROUND: Diagnosis of pre-malignant and malignant lesions in the bile duct and the pancreas is sometimes cumbersome. This applies in particular to intraductal papillary mucinous neoplasia (IPMN) and bile duct strictures in primary sclerosing cholangitis (PSC). AIMS: To evaluate in a prospective cohort study the sensitivity and specificity of probe-based confocal laser microscopy (pCLE) during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: We performed pCLE together with mother-baby endoscopy (SpyGlass) during 50 ERCP sessions in 45 patients. The Miami and Paris criteria were applied. Clinical diagnosis via imaging was compared to pCLE and the final pathological diagnosis from surgically-resected, biopsy, or cytology specimens. Patients were followed up for at least 1 year. RESULTS: We were able to perform pCLE in all patients. Prior to endoscopy, the diagnosis was benign in 23 patients and undetermined (suspicious) in 16 patients, while six patients had an unequivocal diagnosis of malignancy. Sensitivity was 91% and specificity 52%. The positive (PPV) and negative predictive value (NPV) was 82% and 100%, respectively. Apart from mild post-ERCP pancreatitis in two patients, no complications occurred. CONCLUSIONS: Our study showed that pCLE is a safe, expert endoscopic method with high technical feasibility, high sensitivity and high NPV. It provided diagnostic information that can be helpful for decisions on patient management, especially in the case of IPMN and unclear pancreatic lesions, in individuals whom are at increased risk for pancreatic cancer.

13 Article Short-term Results of a Magnetic Resonance Imaging-Based Swedish Screening Program for Individuals at Risk for Pancreatic Cancer. 2015

Del Chiaro, Marco / Verbeke, Caroline S / Kartalis, Nikolaos / Pozzi Mucelli, Raffaella / Gustafsson, Peter / Hansson, Johan / Haas, Stephan L / Segersvärd, Ralf / Andren-Sandberg, Åke / Löhr, J-Matthias. ·Division of Surgery, Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden. · Division of Pathology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden. · Division of Radiology, Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden. · Department of Clinical Genetics, Karolinska Institute, Stockholm, Sweden. · Department of Onco-Pathology, Karolinska Institute, Stockholm, Sweden. · Department of Medicine, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden. ·JAMA Surg · Pubmed #25853369.

ABSTRACT: IMPORTANCE: Pancreatic cancer is the fourth leading cause of cancer-related death in Western countries. In approximately 10% of all patients with pancreatic cancer, it is possible to define a positive family history for pancreatic cancer or for one of the other related genetic syndromes. A screening program for individuals at risk is recommended; however, surveillance modalities have not been defined yet. OBJECTIVE: To analyze the short-term results of a prospective clinical surveillance program for individuals at risk for pancreatic cancer using a noninvasive magnetic resonance imaging (MRI)-based screening protocol. DESIGN, SETTING AND PARTICIPANTS: A prospective observational study of all patients with a genetic risk for developing pancreatic cancer who were referred to Karolinska University Hospital between January 1, 2010, and January 31, 2013, using an MRI-based surveillance program. All patients were investigated for the most common genetic mutations associated with pancreatic cancer. EXPOSURE: A noninvasive MRI-based screening protocol. MAIN OUTCOMES AND MEASURES: The ability of MRI to identify potential precancerous or early cancers in individuals at risk for pancreatic cancer. RESULTS: Forty patients (24 women and 16 men) were enrolled. The mean age was 49.9 years. The mean length of follow-up was 12.9 months. The numbers of relatives affected by pancreatic cancer were 5 in 2 patients (5%), 4 in 5 patients (12.5%), 3 in 17 patients (42.5%), 2 in 14 patients (35%), and 1 in 2 patients (5%). In 4 patients (10%), a p16 mutation was found; in 3, a BRCA2 mutation (7.5%); and in 1, a BRCA1 mutation (2.5%). In 16 patients (40%), MRI revealed a pancreatic lesion: intraductal papillary mucinous neoplasia (14 patients, 35%) and pancreatic ductal adenocarcinoma (2 patients, 5%). One patient had a synchronous intraductal papillary mucinous neoplasia and pancreatic ductal adenocarcinoma. Five patients (12.5%) required surgery (3 for pancreatic ductal adenocarcinoma and 2 for intraductal papillary mucinous neoplasia), while the remaining 35 are under continued surveillance. CONCLUSIONS AND RELEVANCE: During a median follow-up of approximately 1 year, pancreatic lesions were detected in 40% of the patients, of whom 5 underwent surgery. Although the study time was relatively short, the surveillance program in individuals at risk seems to be effective.

14 Article Single-operator pancreatoscopy is helpful in the evaluation of suspected intraductal papillary mucinous neoplasms (IPMN). 2014

Arnelo, Urban / Siiki, Antti / Swahn, Fredrik / Segersvärd, Ralf / Enochsson, Lars / del Chiaro, Marco / Lundell, Lars / Verbeke, Caroline S / Löhr, J-Matthias. ·Centre for Digestive Diseases, Karolinska University Hospital and Division of Surgery, CLINTEC, Karolinska Institute, Stockholm, Sweden. Electronic address: urban.arnelo@ki.se. · Centre for Digestive Diseases, Karolinska University Hospital and Division of Surgery, CLINTEC, Karolinska Institute, Stockholm, Sweden; Dept. of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland. · Centre for Digestive Diseases, Karolinska University Hospital and Division of Surgery, CLINTEC, Karolinska Institute, Stockholm, Sweden. · Division of Pathology, Dept. of Laboratory Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden. ·Pancreatology · Pubmed #25287157.

ABSTRACT: BACKGROUND AND OBJECTIVE: Even when advanced cross-sectional imaging modalities have been employed, endoscopic evaluation of intraductal papillary mucinous neoplasms (IPMN) is often required in order to assess the final character and extent of lesions. The current study addresses the use of SpyGlass single-operator peroral pancreatoscopy in suspected IPMN. DESIGN: A prospective, non-randomized exploratory cohort study. SETTING: Single-center. PATIENTS AND INTERVENTION: A prospective study-cohort of 44 consecutive patients in a single tertiary referral center who underwent ERCP and peroral pancreatoscopy, was prospectively collected between July 2007 and March 2013 because of a radiological signs of IPMN. These IPMN-findings were discovered incidentally in 44% of the cases. MAIN OUTCOME MEASUREMENTS: Diagnostic accuracy (specificity & sensitivity) and complications. RESULTS: The targeted region of the pancreatic duct was reached with the SpyGlass system in 41 patients (median age 65 years, 41% female). Three patients were excluded from analysis because of failed deep cannulation of the pancreatic duct. Brush cytology was taken in 88% and direct biopsies in 41%. IPMN with intermediate or high-grade dysplasia was the main final diagnosis (76%) in 22 patients who had surgery. Out of the 17 patients with a final diagnosis of MD-IPMN, 76% were correctly identified by pancreatoscopy. Of the 9 patients with a final diagnosis of BD-IPMN, the pancreatoscopy identified 78% of the cases correctly.The incidence of post-ERCP pancreatitis was 17%. Pancreatoscopy was found to have provided additional diagnostic information in the vast majority of the cases and to affect clinical decision-making in 76%. LIMITATIONS: Single-center study. CONCLUSIONS: Single-operator peroral pancreatoscopy contributed to the clinical evaluation of IPMN lesions and influenced decision-making concerning their clinical management. The problem of post-procedural pancreatitis needs further attention.

15 Article Real-time assessment of tissue hypoxia in vivo with combined photoacoustics and high-frequency ultrasound. 2014

Gerling, Marco / Zhao, Ying / Nania, Salvatore / Norberg, K Jessica / Verbeke, Caroline S / Englert, Benjamin / Kuiper, Raoul V / Bergström, Asa / Hassan, Moustapha / Neesse, Albrecht / Löhr, J Matthias / Heuchel, Rainer L. ·1. Center of Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; · 2. StratCan Preclinical Cancer Test Facility, Karolinska Institutet, Stockholm, Sweden; ; 3. Pancreas Research Laboratory, CLINTEC, Karolinska Institutet, Stockholm, Sweden; · 3. Pancreas Research Laboratory, CLINTEC, Karolinska Institutet, Stockholm, Sweden; · 4. Division of Pathology, Karolinska Institutet, Stockholm, Sweden; · 6. Core Facility for Morphologic Phenotype Analysis, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden; · 5. Clinical Research Centre, Karolinska University Hospital-Huddinge, Stockholm, Sweden; · 7. Department of Gastroenterology, Endocrinology and Metabolism, Philipps University Marburg, Marburg, Germany. · 1. Center of Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; ; 3. Pancreas Research Laboratory, CLINTEC, Karolinska Institutet, Stockholm, Sweden; ·Theranostics · Pubmed #24723982.

ABSTRACT: PURPOSE: In preclinical cancer studies, non-invasive functional imaging has become an important tool to assess tumor development and therapeutic effects. Tumor hypoxia is closely associated with tumor aggressiveness and is therefore a key parameter to be monitored. Recently, photoacoustic (PA) imaging with inherently co-registered high-frequency ultrasound (US) has reached preclinical applicability, allowing parallel collection of anatomical and functional information. Dual-wavelength PA imaging can be used to quantify tissue oxygen saturation based on the absorbance spectrum differences between hemoglobin and deoxyhemoglobin. EXPERIMENTAL DESIGN: A new bi-modal PA/US system for small animal imaging was employed to test feasibility and reliability of dual-wavelength PA for measuring relative tissue oxygenation. Murine models of pancreatic and colon cancer were imaged, and differences in tissue oxygenation were compared to immunohistochemistry for hypoxia in the corresponding tissue regions. RESULTS: Functional studies proved feasibility and reliability of oxygenation detection in murine tissue in vivo. Tumor models exhibited different levels of hypoxia in localized regions, which positively correlated with immunohistochemical staining for hypoxia. Contrast-enhanced imaging yielded complementary information on tissue perfusion using the same system. CONCLUSION: Bimodal PA/US imaging can be utilized to reliably detect hypoxic tumor regions in murine tumor models, thus providing the possibility to collect anatomical and functional information on tumor growth and treatment response live in longitudinal preclinical studies.

16 Article Survey of UK histopathologists' approach to the reporting of resection specimens for carcinomas of the pancreatic head. 2013

Feakins, Roger / Campbell, Fiona / Verbeke, Caroline S. ·Department of Histopathology, Barts Health NHS Trust, Pathology and Pharmacy Building, Royal London Hospital, London, UK. ·J Clin Pathol · Pubmed #23580659.

ABSTRACT: To assess UK histopathologists' approach to reporting resection specimens for carcinomas of the pancreatic head. Questions were asked using an online survey service. The responses revealed considerable variation in dissection and sampling procedures, interpretation of histology, and the structure of services in the UK. Assessment of resection margins was a notable area of inconsistency. Information in guidelines and better support for some centres could help reduce the observed differences in practice.

17 Minor Information needs among patients and a surveillance strategy after surgery for pancreatic and periampullary cancer. 2015

Labori, Knut J / Verbeke, Caroline S / Gladhaug, Ivar P. ·Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway. uxknab@ous-hf.no. · Department of Pathology, Oslo University Hospital, Oslo, Norway. · Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway. ·HPB (Oxford) · Pubmed #25776256.

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18 Minor Survival after pancreaticoduodenectomy is not improved by extending resections to achieve negative margins. 2010

Verbeke, Caroline S / Smith, Andrew M. · ·Ann Surg · Pubmed #20224357.

ABSTRACT: -- No abstract --