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| 6. |
- Omazic, B., et al.
(författare)
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A Preliminary Report : Radical Surgery and Stem Cell Transplantation for the Treatment of Patients with Pancreatic Cancer
- 2017
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Ingår i: Journal of immunotherapy (1997). - : Lippincott Williams and Wilkins. - 1524-9557 .- 1537-4513. ; 40:4, s. 132-139
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Tidskriftsartikel (refereegranskat)abstract
- We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A∗01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT. Both TAAs were highly expressed in the original tumor tissue suggesting that HSCT promoted a clinically relevant, long-lasting cellular immune response. In contrast to untreated controls, who succumbed to progressive disease, both patients are tumor-free 9 years after diagnosis. Radical surgery combined with HSCT may cure pancreatic adenocarcinoma and change the cellular immune repertoire capable of responding to clinically and biologically relevant TAAs.
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- Valente, Roberto, et al.
(författare)
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Lumen apposing metal stents vs double pigtail plastic stents for the drainage of pancreatic walled-off necrosis
- 2024
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Ingår i: Minerva gastroenterology. - : Edizioni Minerva Medica. - 2724-5365. ; 70:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Few studies compared lumen-apposing metal stents (LAMS) and standard double pigtail plastic stents (PS) for the endoscopic drainage of pancreatic walled-off necrosis (WON). Albeit sometimes large, previously described cohorts display considerable heterogeneity and often pooled together data from several centers, involving multiple operators and techniques. Moreover, they often lack a control group for the comparison of outcomes.AIM: to compare clinical efficacy and safety of PS versus LAMS for the endoscopic drainage of infected WON.METHODS: Single-centre, 1:1 case-control study. We compared patients undergoing endoscopic drainages of infected WON through LAMS (cases) or PS (controls). The primary endpoint was the clinical efficacy (resolution of the WON/sepsis), the secondary endpoint was safety (procedure-related complications).RESULTS: Thirty patients were enrolled between 2011 and 2017. Cases and controls were homogeneous in terms of etiology and clinical characteristics. 93% of cases and 86.7% of controls were clinically successfully treated, with no significant differences in rates of post-operative infections, bleedings and stent migrations (respectively 13.3% vs 21.4%; p=0.65; 13.3% vs 0%; p=0.48; 13.3% vs 7.1%; p=1.00). No difference was shown regarding the need for additional percutaneous or surgical treatments (33.3% vs 13.3%; p=0.39). Cases, however, displayed a significantly prolonged mean hospital stay (90.2 days vs 18.5 days; p<0.01) and a higher mean number of endoscopic procedures per patient (4.8 vs 1.5; p<0.01).CONCLUSIONS: PS might be not inferior to LAMS for the treatment WONs. Further prospective RCT is needed to compare clinical efficacy and safety in the two groups.
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| 14. |
- Vitaloni, M, et al.
(författare)
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Pancreatic Cancer From the Patient Perspective: The Time to Act is Now
- 2022
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Ingår i: Journal of patient experience. - : SAGE Publications. - 2374-3735 .- 2374-3743. ; 9, s. 23743735221112633-
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is a disease requiring urgent attention from governments and policymakers. Recently, a state of emergency has been declared for this cancer—being the fourth most common cause of cancer deaths in the European Union, it has the lowest survival rate of all common cancers. One of the major reasons pancreatic cancer is associated with such poor outcomes is because it is usually diagnosed at a late stage. Also, investment in research for effective targeted therapies is lacking. This is the perspective of a white paper developed by Digestive Cancers Europe, an umbrella organisation representing European patient organisations. It has been developed after consultation with pancreatic cancer patients, representatives of cancer patient organisations and leading pancreatic cancer healthcare professionals. The purpose of the paper is to highlight the key urgent unmet needs in pancreatic cancer from the patient perspective, ultimately with a view to improve patient care and outcomes in this very challenging disease.
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| 15. |
- Arnelo, Urban, et al.
(författare)
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Intraoperative pancreatoscopy can improve the detection of skip lesions during surgery for intraductal papillary mucinous neoplasia : a pilot study
- 2023
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Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 23:6, s. 704-711
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Intraoperative pancreatoscopy is a promising procedure that might guide surgical resection for suspected main duct (MD) and mixed type (MT) intraductal papillary mucinous neoplasms (IPMNs). The aim of the present study was to assess the diagnostic yield and clinical impact of intraoperative pancreatoscopy in patients operated on for MD and MT-IPMNs.Methods: This is a retrospective cohort study. Patients undergoing surgery for suspected MD or MT-IPMN underwent intraoperative pancreatoscopy and frozen section analysis. In all patients who required extended resection due to pancreatoscopic findings, we compared the final histology with the results of the intraoperative frozen section analysis.Results: In total, 46 patients, 48% females, mean age (range) 67 years (45–82 years) underwent intraoperative pancreatoscopy. No mortality or procedure related complications were observed. Pancreatoscopy changed the operative course in 30 patients (65%), leading to extended resections in 20 patients (43%) and to parenchyma sparing procedures in 10 patients (22%). Analyzing the group of patients who underwent extended resections, 7 (35%) displayed lesions that needed further surgical treatment (six high grade dysplasia and one with G1 pancreatic neuroendocrine tumor) and among those 7, just 1 (14%) would have been detected exclusively with histological frozen section analysis of the transection margin. The combination of both pancreatoscopy and frozen section analysis lead to 86% sensitivity and 92% specificity for the detection of pathological tissue in the remnant pancreas.Conclusion: Intraoperative pancreatoscopy is a safe and feasible procedure and might allow the detection of skip lesions during surgery for suspect MD-involving IPMNs.
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- El-Heliebi, Amin, et al.
(författare)
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In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells
- 2018
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 64:3, s. 536-546
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs. Here, we report an approach that adds AR-V7 or KRAS status to CTC enumeration, compatible with multiple CTC-isolation platforms.METHODS: We studied 3 independent CTC-isolation devices (CellCollector, Parsortix, CellSearch) for the evaluation of AR-V7 or KRAS status of CTCs with in situ padlock probe technology. Padlock probes allow highly specific detection and visualization of transcripts on a cellular level. We applied padlock probes for detecting AR-V7, androgen receptor full length (AR-FL), and prostate-specific antigen (PSA) in CRPC and KRAS wildtype (wt) and mutant (mut) transcripts in PaCa in CTCs from 46 patients.RESULTS: In situ analysis showed that 71% (22 of 31) of CRPC patients had detectable AR-V7 expression ranging from low to high expression [1-76 rolling circle products (RCPs)/CTC]. In PaCa patients, 40% (6 of 15) had KRAS mut expressing CTCs with 1 to 8 RCPs/CTC. In situ padlock probe analysis revealed CTCs with no detectable cytokeratin expression but positivity for AR-V7 or KRAS mut transcripts.CONCLUSIONS: Padlock probe technology enables quantification of AR-V7, AR-FL, PSA, and KRAS mut/wt transcripts in CTCs. The technology is easily applicable in routine laboratories and compatible with multiple CTC-isolation devices.
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| 20. |
- Haraldsson, E, et al.
(författare)
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Endoscopic classification of the papilla of Vater. Results of an inter- and intraobserver agreement study
- 2017
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Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 5:4, s. 504-510
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many endoscopists acknowledge that the appearance of the papilla of Vater seems to affect biliary cannulation. To assess the association between the macroscopic appearance of the papilla and biliary cannulation and other related clinical issues, a system is needed to define the appearance of the papilla. Objective: The purpose of this study was to validate an endoscopic classification of the papilla of Vater by assessing the interobserver and intraobserver agreements among endoscopist with varying experience. Methods: An endoscopic classification, based on pictures captured from 140 different papillae, containing four types of papillae was proposed. The four types are (a) Type 1: regular papilla, no distinctive features, ‘classic appearance’; (b) Type 2: small papilla, often flat, with a diameter ≤ 3 mm (approximately 9 Fr); (c) Type 3: protruding or pendulous papilla, a papilla that is standing out, protruding or bulging into the duodenal lumen or sometimes hanging down, pendulous with the orifice oriented caudally; and (d) Type 4: creased or ridged papilla, where the ductal mucosa seems to extend distally, rather out of the papillary orifice, either on a ridge or in a crease. To assess the level of interobserver agreement, a web-based survey was sent out to 18 endoscopists, containing 50 sets of still images of the papilla, distributed between the four different types. Three months later a follow-up survey, with images from the first survey was sent to the same endoscopists. Results: Interobserver agreement was substantial (κ = 0.62, 95% confidence interval (CI) 0.58–0.65) and were similar for both experts and non-experts. The intraobserver agreement assessed with the second survey was also substantial (κ = 0.66, 95% CI 0.59–0.72). Conclusion: The proposed endoscopic classification of the papilla of Vater seems to be easy to use, irrespective of the level of experience of the endoscopist. It carries a substantial inter- and intraobserver agreement and now the clinical relevance of the four different papilla types awaits to be determined.
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| 21. |
- He, Fei, et al.
(författare)
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FPR2 Shapes an Immune-Excluded Pancreatic Tumor Microenvironment and Drives T-cell Exhaustion in a Sex-Dependent Manner
- 2023
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Ingår i: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:10, s. 1628-1645
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Tidskriftsartikel (refereegranskat)abstract
- Sex-driven immune differences can affect tumor progression and the landscape of the tumor microenvironment. Deeper understanding of these differences in males and females can inform patient selection to improve sex-optimized immunotherapy treatments. In this study, single-cell RNA sequencing and protein analyses uncovered a subpopulation of myeloid cells in pancreatic lesions associated with an immune-excluded tumor phenotype and effector T-cell exhaustion exclusively in females. This myeloid subpopulation was positively correlated with poor survival and genetic signatures of M2-like macrophages and T-cell exhaustion in females. The G-protein coupled receptor formyl peptide receptor 2 (FPR2) mediated these immunosuppressive effects. In vitro, treatment of myeloid cells with a specific FPR2 antagonist prevented exhaustion and enhanced cytotoxicity of effector cells. Proteomic analysis revealed high expression of immunosuppressive secretory proteins PGE2 and galectin-9, enriched integrin pathway, and reduced proinflammatory signals like TNFα and IFNγ in female M2-like macrophages upon FPR2 agonist treatment. In addition, myeloid cells treated with FPR2 agonists induced TIM3 and PD-1 expression only in female T cells. Treatment with anti-TIM3 antibodies reversed T-cell exhaustion and stimulated their ability to infiltrate and kill pancreatic spheroids. In vivo, progression of syngeneic pancreatic tumors was significantly suppressed in FPR2 knockout (KO) female mice compared with wild-type (WT) female mice and to WT and FPR2 KO male mice. In female mice, inoculation of tumors with FPR2 KO macrophages significantly reduced tumor growth compared with WT macrophages. Overall, this study identified an immunosuppressive function of FPR2 in females, highlighting a potential sex-specific precision immunotherapy strategy.
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| 22. |
- Klatte, DCF, et al.
(författare)
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Hereditary pancreatic cancer
- 2022
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Ingår i: Best practice & research. Clinical gastroenterology. - : Elsevier BV. - 1532-1916 .- 1521-6918. ; 58-59, s. 101783-
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Tidskriftsartikel (refereegranskat)
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| 24. |
- Löhr, J. -M, et al.
(författare)
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Nanoparticles for cancer therapy
- 2017
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Ingår i: Läkartidningen. - : Swedish Medical Association. - 0023-7205 .- 1652-7518. ; 114:27-29
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles carry a big promise in oncology, for diagnosis/imaging, therapy, or both (theragnostics). As common in medical history, there is a huge gap between the exciting experimental possibilities and data and clinical studies making use of it. Of the cell-containing nanoparticles, only one formulation using gene-directed enzyme prodrug therapy (GDEPT) with CYP2B1 and ifosfamide was used in early clinical studies. Of the cellfree nanoparticles, some drug-releasing (doxorubicin) ones are in clinical use for trans-arterial chemoembolization (TACE) in liver tumors and metastasis. Using liposomes, both paclitaxel and irinotecan have been used in pancreatic cancer as the model indication. Nanoparticle-albumin-bound paclitaxel (NAB-paclitaxel) has also been developed and is now registered as a drug for first-line therapy of pancreatic cancer, as is the liposomal irinotecan. The novel nanoparticle formulations carry a big promise for even better performance, both in diagnosis and therapy; however, few of these has entered the clinic as of today.
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| 26. |
- Löhr, M., et al.
(författare)
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Nanotekniken kan revolutionera behandlingen av cancer - Ger nya möjligheter att målstyra läkemedel, men flera stora utmaningar återstår att tackla
- 2017
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 114, s. 27-29
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles for cancer therapy Nanoparticles carry a big promise in oncology, for diagnosis/imaging, therapy, or both (theragnostics). As common in medical history, there is a huge gap between the exciting experimental possibilities and data and clinical studies making use of it. Of the cell-containing nanoparticles, only one formulation using gene-directed enzyme prodrug therapy (GDEPT) with CYP2B1 and ifosfamide was used in early clinical studies. Of the cell-free nanoparticles, some drug-releasing (doxorubicin) ones are in clinical use for trans-arterial chemo-embolization (TACE) in liver tumors and metastasis. Using liposomes, both paclitaxel and irinotecan have been used in pancreatic cancer as the model indication. Nanoparticle-albumin-bound paclitaxel (NAB-paclitaxel) has also been developed and is now registered as a drug for first-line therapy of pancreatic cancer, as is the liposomal irinotecan. The novel nanoparticle formulations carry a big promise for even better performance, both in diagnosis and therapy; however, few of these has entered the clinic as of today.
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| 30. |
- Pozzi Mucelli, Raffaella M., et al.
(författare)
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Branch-duct intraductal papillary mucinous neoplasm (IPMN) : Are cyst volumetry and other novel imaging features able to improve malignancy prediction compared to well-established resection criteria?
- 2022
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Ingår i: European Radiology. - : Springer Science+Business Media B.V.. - 0938-7994 .- 1432-1084. ; 32:8, s. 5144-5155
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Current guidelines base the management of intraductal papillary mucinous neoplasms (IPMN) on several well-established resection criteria (RC), including cyst size. However, malignancy may occur in small cysts. Since branch-duct (BD) IPMN are not perfect spheres, volumetric and morphologic analysis might better correlate with mucin production and grade of dysplasia. Nonetheless, their role in malignancy (high-grade dysplasia/invasive cancer) prediction has been poorly investigated. Previous studies evaluating RC also included patients with solid-mass-forming pancreatic cancer (PC), which may affect the RC yield. This study aimed to assess the role of volume, morphology, and other well-established RC in malignancy prediction in patients with BD- and mixed-type IPMN after excluding solid masses.Methods: Retrospective ethical review-board-approved study of 106 patients (2008–2019) with histopathological diagnosis of BD- and mixed-type IPMN (without solid masses) and preoperative MRI available. Standard imaging and clinical features were collected, and the novel imaging features cyst-volume and elongation value [EV = 1 − (width/length)] calculated on T2-weighted images. Logistic regression analysis was performed. Statistical significance set at two-tails, p < 0.05.Results: Neither volume (odds ratio (OR) = 1.01, 95% CI: 0.99–1.02, p = 0.12) nor EV (OR = 0.38, 95% CI: 0.02–5.93, p = 0.49) was associated with malignancy. Contrast-enhancing mural nodules (MN), main pancreatic duct (MPD) ≥ 5 mm, and elevated carbohydrate antigen (CA) 19-9 serum levels (> 37 μmol/L) were associated with malignancy (MN OR: 4.32, 95% CI: 1.18–15.76, p = 0.02; MPD ≥ 5 mm OR: 4.2, 95% CI: 1.34–13.1, p = 0.01; CA19-9 OR: 6.72; 95% CI: 1.89 – 23.89, p = 0.003).Conclusions: Volume and elongation value cannot predict malignancy in BD- and/or mixed-type IPMN. Mural nodules, MPD ≥ 5 mm and elevated CA19-9 serum levels are associated with higher malignancy risk even after the exclusion of solid masses. Key Points: • Novel and well-established resection criteria for IPMN have been evaluated after excluding solid masses. • BD-IPMN volume and elongation value cannot predict malignancy. • Main pancreatic duct ≥ 5 mm, mural nodules, and elevated carbohydrate antigen 19-9 levels are associated with malignancy.
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| 31. |
- Påhlsson, H. I., et al.
(författare)
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Telemedicine : an important aid to perform high-quality endoscopic retrograde cholangiopancreatography in low-volume centers
- 2013
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Ingår i: Endoscopy. - : Georg Thieme Verlag KG. - 0013-726X .- 1438-8812. ; 45:5, s. 357-361
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Tidskriftsartikel (refereegranskat)abstract
- Background and study aims: The aim of this study was to investigate whether telemedicine can help to ensure high-quality endoscopic retrograde cholangiopancreatography (ERCP) in patients living in rural areas. The study was conducted by investigators from two centers: the Karolinska University Hospital, a high-volume center which provided the teleguided support, and the Visby District Hospital, a low-volume center. Patients and methods: From September 2010 to August 2011, 26 ERCP procedures performed at a district hospital were teleguided by an experienced endoscopist at the Karolinska University Hospital. To ensure patient data protection, all communication went through a network (Sjunet) that was separate from the Internet and open only to accredited users. The indications for ERCP were common bile duct stones (n=12), malignant strictures (n=12), and benign biliary strictures (n=2). In 15 cases, this was the patient's first ERCP procedure. Results: The common bile duct was successfully cannulated in all 26 teleguided procedures. The local endoscopist scored the teleguided support as crucial for the successful outcome in 8/26 cases, as an important factor in 8, and as being of less importance in the remaining 10. In the eight cases where the teleguided support was judged to be crucial, six subsequent percutaneous trans-hepatic cholangiography procedures and two repeat ERCPs were avoided. The overall cannulation rate at the district hospital improved from 85% to 99% after teleguided support was introduced. No procedure-related complications occurred. Conclusion: Distant guidance of advanced ERCP procedures in a low-volume center, through teleguided support from a high-volume center, has the potential to improve the quality of care, as reflected in high cannulation rates and the ability to complete the scheduled interventions.
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| 33. |
- Vu Trung, Kien, et al.
(författare)
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Endoscopic papillectomy for ampullary lesions of minor papilla
- 2024
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Ingår i: Gastrointestinal Endoscopy. - 0016-5107. ; 99:4, s. 587-595.e1
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Ampullary lesions (ALs) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla, but the role of EP for minor AL has not been accurately studied. Methods: We identified 20 patients with ALs of minor duodenal papilla in the multicentric database from the Endoscopic Papillectomy vs Surgical Ampullectomy vs Pancreatitcoduodenectomy for Ampullary Neoplasm study, which included 1422 EPs. We used propensity score matching (nearest-neighbor method) to match these cases with ALs of the major duodenal papilla based on age, sex, histologic subtype, and size of the lesion in a 1:2 ratio. Cohorts were compared by means of chi-square or Fisher exact test as well as Mann-Whitney U test. Results: Propensity score–based matching identified a cohort of 60 (minor papilla 20, major papilla 40) patients with similar baseline characteristics. The most common histologic subtype of lesions of minor papilla was an ampullary adenoma in 12 patients (3 low-grade dysplasia and 9 high-grade dysplasia). Five patients revealed nonneoplastic lesions. Invasive cancer (T1a), adenomyoma, and neuroendocrine neoplasia were each found in 1 case. The rate of complete resection, en-bloc resection, and recurrences were similar between the groups. There were no severe adverse events after EP of lesions of minor papilla. One patient had delayed bleeding that could be treated by endoscopic hemostasis, and 2 patients showed a recurrence in surveillance endoscopy after a median follow-up of 21 months (interquartile range, 12-50 months). Conclusions: EP is safe and effective in ALs of the minor duodenal papilla. Such lesions could be managed according to guidelines for EP of major duodenal papilla.
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| 34. |
- Vujasinovic, M, et al.
(författare)
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Autoimmune pancreatitis and micronutrients
- 2023
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Ingår i: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. - 1878-3562. ; 55:10, s. 1375-1381
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Tidskriftsartikel (refereegranskat)
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