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World Journal of Gastroenterology Jul 2015To analyze the benefits and harms of pancreatic cancer screening in familial high-risk individuals (HRIs). (Review)
Review
AIM
To analyze the benefits and harms of pancreatic cancer screening in familial high-risk individuals (HRIs).
METHODS
Studies were identified by searching PubMed, EBSCO, ClinicalTrials.gov and the Cochrane database from database inception to June 2014. We also obtained papers from the reference lists of pertinent studies and systematic reviews. English-language trials and observational studies were searched. The key words used as search terms were "screening" and "surveillance". Cost-effectiveness, diagnostic rate, survival rate, mortality and adverse events were the outcomes of interest. Age, sex, lifestyle and other confounding factors were also considered. However, anticipating only a few of these studies, we also included observational studies with or without control groups. We also included studies concerning the anxiety associated with pancreatic cancer risk and other psychological changes in familial HRIs. We extracted details on study design, objectives, population characteristics, inclusion criteria, year of enrollment, method of screening, adjusted and unadjusted mortality, cost-effectiveness and adverse events from the included studies. Studies were assessed using the Reporting of Observational studies in Epidemiology (STROBE) checklist.
RESULTS
Sixteen studies on pancreatic cancer screening were included. Five studies included control groups, nine were observational studies without control groups, and the other two studies investigated the worry associated with pancreatic cancer risk. We found that pancreatic cancer screening resulted in a high curative resection rate (60% vs 25%, P = 0.011), longer median survival time (14.5 mo vs 4 mo, P < 0.001), and higher 3-year survival rate (20% vs 15.0%, P = 0.624). We also found that familial HRIs had a higher diagnostic rate of pancreatic tumors than controls (34% vs 7.2%, P < 0.001). In patients who underwent regular physical examinations, more stage I pancreatic cancers were observed (19% vs 2.6%, P = 0.001). In addition, endoscopic ultrasonography, which was the main means of detection, diagnosed 64.3% of pancreatic cancers. In comparison, endoscopic retrograde cannulation of the pancreas, magnetic resonance imaging, and computed tomography diagnosed 28.6%, 42.9%, and 21.4%, respectively. For mass lesions, instant surgery was recommended because of the beneficial effects of post-operative chemotherapy. However, in patients with intraductal papillary mucinous neoplasms, we did not find a significant difference in outcome between surgery and follow-up without treatment. Moreover, pancreatic cancer screening in familial HRIs had a greater perceived risk of pancreatic cancer (P < 0.0001), higher levels of anxiety regarding pancreatic cancer (P < 0.0001), and increased economic burden.
CONCLUSION
Pancreatic cancer screening in familial HRIs is associated with a higher detection rate and longer survival, although screening may influence psychological function and increase the economic burden.
Topics: Biomarkers, Tumor; Diagnostic Imaging; Early Detection of Cancer; Genetic Predisposition to Disease; Genetic Testing; Heredity; Humans; Neoplasm Staging; Pancreatic Neoplasms; Pedigree; Phenotype; Predictive Value of Tests; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 26229410
DOI: 10.3748/wjg.v21.i28.8678 -
Langenbeck's Archives of Surgery Jan 2023Granular cell tumours (GCTs) of the pancreas are mostly benign and exceptionally rare, with no unique identifying radiological features. Following a case discussion of a... (Meta-Analysis)
Meta-Analysis
PURPOSE
Granular cell tumours (GCTs) of the pancreas are mostly benign and exceptionally rare, with no unique identifying radiological features. Following a case discussion of a patient with GCT, a comprehensive review of available literature was conducted to identify the common diagnostic features associated with GCT.
METHODS
Following a case report identified in our institution, a systematic review was conducted by two authors in accordance with Preferred Reporting Items for Systematic review and Meta-Analysis protocols (PRISMA) guidelines. Databases MEDLINE, EMBASE, Scopus, World of Science, and grey literature were searched on August 2021. Inclusion criteria were histopathology diagnosed granular cell tumour of the pancreas.
RESULTS
A 37-year-old male presented with 1 month of abdominal pain and an MRI demonstrating a dilated main pancreatic duct, distal parenchymal atrophy, but no focal lesion. Repeat MRI at 6 months re-demonstrated similar findings and subsequent endoscopic ultrasound was suspicious for main duct IPMN. Following multidisciplinary team discussion, a spleen-preserving distal pancreatectomy was performed. Histopathology demonstrated granular cell tumour with cells diffusely positive for S100 and no malignant transformation. 11 case reports were identified in the literature with diagnosis confirmed on tissue histopathology based on positive immunohistochemical staining for S-100 protein. Eight patients presented with gastrointestinal symptoms with abdominal pain the main presenting complaint (50%). 10 patients underwent CT with portal venous contrast and all underwent endoscopic examination. Imaging findings were similar in five studies for EUS which demonstrated a hypoechoic lesion with homogenous appearance. On non-contrast CT GCT was iso-enhancing, and with portal venous contrast demonstrated hypo-enhancement that gradually enhanced on late phases. Pre-operative diagnosis of pancreatic carcinoma was described in six cases based on imaging and biopsy, resulting in progression to surgical resection. Nine patients were managed surgically and no complications identified on follow-up (6-52 months).
CONCLUSION
The currently proposed management pathway includes EUS with biopsy and CT, and surgical resection recommended due to malignancy risk. Improved sample collection with EUS-FNA and microscopic assessment utilising S-100 immunohistochemistry may improve pre-operative diagnosis. Limitations include rare numbers in reported literature and short follow-up not allowing an assessment of GCT's natural history and malignancy risk. Additional cases would expand the current dataset of GCTs of the pancreas, so that surgical resection may be avoided in the future.
Topics: Male; Humans; Adult; Granular Cell Tumor; Pancreas; Pancreatic Neoplasms; Endosonography; Abdominal Pain
PubMed: 36694023
DOI: 10.1007/s00423-023-02761-3 -
HPB : the Official Journal of the... Aug 2022Surgery for patients with pancreatic cancer carries a high risk of major post-operative complications and only marginally improves overall survival. This review aims to... (Review)
Review
BACKGROUND
Surgery for patients with pancreatic cancer carries a high risk of major post-operative complications and only marginally improves overall survival. This review aims to assess the impact of surgical resection on health-related quality of life (HRQOL) of pancreatic cancer patients.
METHODS
A systematic review of the literature was performed according to the PRISMA guidelines. All studies assessing QOL using validated questionnaires in pancreatic cancer patients undergoing surgical resection were included.
RESULTS
Twenty-two studies were assessed. Patients reported a decrease in physical, social and global scales within the first 3 months after surgery. These values showed improvement and were comparable to baseline values by 6 months. Recovery in emotional functioning towards baseline figures was demonstrated in the first 3 months post-operatively. Symptom scales including pain, fatigue and diarrhoea deteriorated after surgery, but reverted to baseline after 3-6 months.
CONCLUSIONS
Surgical resection for pancreatic cancer has short-term negative impact on QOL. In the longer term, this will improve and eventually recover to baseline values after 6 months. Knowledge on the impact of surgery on QOL of pancreatic cancer patients is necessary to facilitate decision-making and tailoring of surgical techniques to the individual patient.
Topics: Humans; Pancreatic Neoplasms; Prospective Studies; Quality of Life; Surveys and Questionnaires
PubMed: 35304039
DOI: 10.1016/j.hpb.2022.02.013 -
Journal of Gastrointestinal Cancer Jun 2023Pancreatic cancer is characterized by its high mortality, usually attributed to its diagnosis in already advanced stages. This article aims at presenting an overview of... (Review)
Review
PURPOSE
Pancreatic cancer is characterized by its high mortality, usually attributed to its diagnosis in already advanced stages. This article aims at presenting an overview of the economic burden of pancreatic cancer in Europe.
METHODS
A systematic literature review was conducted. It made use of the search engines EconLit, Google Scholar, PubMed and Web of Science, and retrieved articles published after December 31st, 1992, and before April 1st, 2020. Study characteristics and cost information were extracted. Cost per patient and cost per patient per month (PPM) were calculated, and drivers of estimate heterogeneity was analysed. Results were converted into 2019 Euros.
RESULTS
The literature review yielded 26 studies on the economic burden attributable to pancreatic cancer in Europe. Cost per patient was on average 40,357 euros (median 15,991), while figures PPM were on average 3,656 euros (median 1,536). Indirect costs were found to be on average 154,257 euros per patient or 14,568 euros PPM, while direct costs 20,108 euros per patient and 2,004 euros PPM. Nevertheless, variation on cost estimations was large and driven by study methodology, patient sample characteristics, such as type of tumour and cancer stage and cost components included in analyses, such as type of procedure.
CONCLUSION
Pancreatic cancer direct costs PPM are in the upper bound relative to other cancer types; however, direct per patient costs are likely to be lower because of shorter survival. Indirect costs are substantial, mainly attributed to high mortality.
Topics: Humans; Financial Stress; Europe; Pancreatic Neoplasms; Cost of Illness
PubMed: 35474568
DOI: 10.1007/s12029-022-00821-3 -
Pancreatology : Official Journal of the... Sep 2019Intraductal oncocytic papillary neoplasm of the pancreas (IOPN-P) is a rare subtype of intraductal papillary mucinous neoplasm (IPMN). This study was performed to...
BACKGROUND
Intraductal oncocytic papillary neoplasm of the pancreas (IOPN-P) is a rare subtype of intraductal papillary mucinous neoplasm (IPMN). This study was performed to summarize the clinicopathological features and management of IOPN-P.
METHODS
English-language articles were searched from MEDLINE and EMBASE from the first report of IOPN-P in 1996 until 1 May 2019 following the methodology in the PRISMA guidelines.
RESULTS
In total, 66 patients from 24 full articles were included in the final data analysis. The patients' average age was 61 years, and the male/female ratio was 1. Most lesions were large (average size, 5.50 cm), located in the pancreatic head, and found either incidentally or by uncharacteristic abdominal symptoms. IOPN-P was usually a cystic and solid lesion with or without mural nodules on radiological examination. A definitive diagnosis was often acquired from fine needle aspiration biopsy or postoperative pathology. All tumors were diagnosed as carcinoma in situ or minimally invasive carcinoma, necessitating surgical resection. The prognosis of IOPN-P was better than that of other IPMN subtypes, even when metastasis occurred. Recurrence after surgical resection of IOPN-P was rare.
CONCLUSIONS
IOPN-P is rare among IPMN subtypes with unique pathological characteristics. Because of the nontypical symptoms and radiological findings, a definitive preoperative diagnosis usually depends on multimodal examinations. Management and surveillance of IOPN-P after surgical resection should be differentiated from those of other pancreatic benign cystic lesions because of its relative malignancy, but IOPN-P should also be differentiated from other IPMN subtypes and malignant cystic tumors because of its favorable prognosis.
Topics: Carcinoma, Pancreatic Ductal; Humans; Pancreatic Neoplasms; Papilloma, Intraductal; Prognosis; Treatment Outcome
PubMed: 31375434
DOI: 10.1016/j.pan.2019.07.040 -
Journal of Gastrointestinal Cancer Mar 2024T cell exhaustion and activation markers are helpful in determining the therapies and predicting the overall survival in pancreatic cancer (PC) patients. (Review)
Review
BACKGROUND
T cell exhaustion and activation markers are helpful in determining the therapies and predicting the overall survival in pancreatic cancer (PC) patients.
PURPOSE
In this systematic review, we have addressed two questions, how do these markers differ in their expression levels in PC patients and healthy individual and correlating the expression level of these markers with the cancer stage.
METHODS
The systematic review was registered with Prospective Register of Systematic Reviews (PROSPERO) with registration number "CRD42022246780." All the included articles were obtained from three databases, PubMed, MEDLINE, and Cochrane, published from January 2010 to 26th May 2022. Two independent reviewers followed the PRISM protocol and reviewed and extracted data from the included articles.
RESULTS
PD-1 and CTLA-4 were the most studied markers in this field. A clear elevation in the expression of PD-1, CTLA-4, TIM-3, LAG-3, and TIGIT was found in most of the studies. CD69, CD25, and HLA-DR expression was found to be upregulated after chemotherapy and immunotherapy. CD25 was the only marker analyzed against cancer progression, in a single study. No study compared the expression of exhaustion and activation markers (except CD69) with the cancer progression of the tumor stage.
CONCLUSION
Since the exhaustion markers are upregulated in patients, single or multiple markers can be targeted in immunotherapies. Knowledge of the dynamics of these markers at various cancer stages will help in determining the right immunotherapy for pancreatic cancer patients. Stage-wise comparison could also be made possible by developing in vitro models.
Topics: Humans; Pancreatic Neoplasms; Biomarkers, Tumor; T-Lymphocytes; CTLA-4 Antigen; Lymphocyte Activation; T-Cell Exhaustion
PubMed: 37672169
DOI: 10.1007/s12029-023-00965-w -
Cancer Medicine Jun 2017There is a strong rationale and many theoretical advantages for neoadjuvant therapy in pancreatic cancer (PC). However, study results have varied significantly. In this... (Meta-Analysis)
Meta-Analysis Review
There is a strong rationale and many theoretical advantages for neoadjuvant therapy in pancreatic cancer (PC). However, study results have varied significantly. In this study, a systematic review and meta-analysis of prospective studies were performed in order to evaluate safety and effectiveness of neoadjuvant therapy in PC. Thirty-nine studies were selected (n = 1458 patients), with 14 studies focusing on patients with resectable disease (group 1), and 19 studies focusing on patients with borderline resectable and locally advanced disease (group 2). Neoadjuvant chemotherapy was administered in 97.4% of the studies, in which 76.9% was given radiotherapy and 74.4% administered with chemoradiation. The complete and partial response rate was 3.8% and 20.9%. The incidence of grade 3/4 toxicity was 11.3%. The overall resection rate after neoadjuvant therapy was 57.7% (group 1: 73.0%, group 2: 40.2%). The R0 resection rate was 84.2% (group 1: 88.2%, group 2: 79.4%). The overall survival for all patients was 16.79 months (resected 24.24, unresected 9.81; group 1: 17.76, group 2: 16.20). Our results demonstrate that neoadjuvant therapy has not been proven to be beneficial and should be considered with caution in patients with resectable PC. Patients with borderline resectable or locally advanced disease may benefit from neoadjuvant therapy, but further research is needed.
Topics: Antineoplastic Agents; Humans; Morbidity; Neoadjuvant Therapy; Pancreatic Neoplasms; Prospective Studies; Treatment Outcome
PubMed: 28544758
DOI: 10.1002/cam4.1071 -
Artificial Intelligence for the Prediction and Early Diagnosis of Pancreatic Cancer: Scoping Review.Journal of Medical Internet Research Mar 2023Pancreatic cancer is the 12th most common cancer worldwide, with an overall survival rate of 4.9%. Early diagnosis of pancreatic cancer is essential for timely treatment... (Review)
Review
BACKGROUND
Pancreatic cancer is the 12th most common cancer worldwide, with an overall survival rate of 4.9%. Early diagnosis of pancreatic cancer is essential for timely treatment and survival. Artificial intelligence (AI) provides advanced models and algorithms for better diagnosis of pancreatic cancer.
OBJECTIVE
This study aims to explore AI models used for the prediction and early diagnosis of pancreatic cancers as reported in the literature.
METHODS
A scoping review was conducted and reported in line with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. PubMed, Google Scholar, Science Direct, BioRXiv, and MedRxiv were explored to identify relevant articles. Study selection and data extraction were independently conducted by 2 reviewers. Data extracted from the included studies were synthesized narratively.
RESULTS
Of the 1185 publications, 30 studies were included in the scoping review. The included articles reported the use of AI for 6 different purposes. Of these included articles, AI techniques were mostly used for the diagnosis of pancreatic cancer (14/30, 47%). Radiological images (14/30, 47%) were the most frequently used data in the included articles. Most of the included articles used data sets with a size of <1000 samples (11/30, 37%). Deep learning models were the most prominent branch of AI used for pancreatic cancer diagnosis in the studies, and the convolutional neural network was the most used algorithm (18/30, 60%). Six validation approaches were used in the included studies, of which the most frequently used approaches were k-fold cross-validation (10/30, 33%) and external validation (10/30, 33%). A higher level of accuracy (99%) was found in studies that used support vector machine, decision trees, and k-means clustering algorithms.
CONCLUSIONS
This review presents an overview of studies based on AI models and algorithms used to predict and diagnose pancreatic cancer patients. AI is expected to play a vital role in advancing pancreatic cancer prediction and diagnosis. Further research is required to provide data that support clinical decisions in health care.
Topics: Humans; Artificial Intelligence; Early Detection of Cancer; Pancreatic Neoplasms; Algorithms
PubMed: 37000507
DOI: 10.2196/44248 -
The Cochrane Database of Systematic... Mar 2018Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options. Over the past few decades, many anti-cancer therapies have been tested in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options. Over the past few decades, many anti-cancer therapies have been tested in the locally advanced and metastatic setting, with mixed results. This review attempts to synthesise all the randomised data available to help better inform patient and clinician decision-making when dealing with this difficult disease.
OBJECTIVES
To assess the effect of chemotherapy, radiotherapy or both for first-line treatment of advanced pancreatic cancer. Our primary outcome was overall survival, while secondary outcomes include progression-free survival, grade 3/4 adverse events, therapy response and quality of life.
SEARCH METHODS
We searched for published and unpublished studies in CENTRAL (searched 14 June 2017), Embase (1980 to 14 June 2017), MEDLINE (1946 to 14 June 2017) and CANCERLIT (1999 to 2002) databases. We also handsearched all relevant conference abstracts published up until 14 June 2017.
SELECTION CRITERIA
All randomised studies assessing overall survival outcomes in patients with advanced pancreatic ductal adenocarcinoma. Chemotherapy and radiotherapy, alone or in combination, were the eligible treatments.
DATA COLLECTION AND ANALYSIS
Two review authors independently analysed studies, and a third settled any disputes. We extracted data on overall survival (OS), progression-free survival (PFS), response rates, adverse events (AEs) and quality of life (QoL), and we assessed risk of bias for each study.
MAIN RESULTS
We included 42 studies addressing chemotherapy in 9463 patients with advanced pancreatic cancer. We did not identify any eligible studies on radiotherapy.We did not find any benefit for chemotherapy over best supportive care. However, two identified studies did not have sufficient data to be included in the analysis, and many of the chemotherapy regimens studied were outdated.Compared to gemcitabine alone, participants receiving 5FU had worse OS (HR 1.69, 95% CI 1.26 to 2.27, moderate-quality evidence), PFS (HR 1.47, 95% CI 1.12 to 1.92) and QoL. On the other hand, two studies showed FOLFIRINOX was better than gemcitabine for OS (HR 0.51 95% CI 0.43 to 0.60, moderate-quality evidence), PFS (HR 0.46, 95% CI 0.38 to 0.57) and response rates (RR 3.38, 95% CI 2.01 to 5.65), but it increased the rate of side effects. The studies evaluating CO-101, ZD9331 and exatecan did not show benefit or harm when compared with gemcitabine alone.Giving gemcitabine at a fixed dose rate improved OS (HR 0.79, 95% CI 0.66 to 0.94, high-quality evidence) but increased the rate of side effects when compared with bolus dosing.When comparing gemcitabine combinations to gemcitabine alone, gemcitabine plus platinum improved PFS (HR 0.80, 95% CI 0.68 to 0.95) and response rates (RR 1.48, 95% CI 1.11 to 1.98) but not OS (HR 0.94, 95% CI 0.81 to 1.08, low-quality evidence). The rate of side effects increased. Gemcitabine plus fluoropyrimidine improved OS (HR 0.88, 95% CI 0.81 to 0.95), PFS (HR 0.79, 95% CI 0.72 to 0.87) and response rates (RR 1.78, 95% CI 1.29 to 2.47, high-quality evidence), but it also increased side effects. Gemcitabine plus topoisomerase inhibitor did not improve survival outcomes but did increase toxicity. One study demonstrated that gemcitabine plus nab-paclitaxel improved OS (HR 0.72, 95% CI 0.62 to 0.84, high-quality evidence), PFS (HR 0.69, 95% CI 0.58 to 0.82) and response rates (RR 3.29, 95% CI 2.24 to 4.84) but increased side effects. Gemcitabine-containing multi-drug combinations (GEMOXEL or cisplatin/epirubicin/5FU/gemcitabine) improved OS (HR 0.55, 95% CI 0.39 to 0.79, low-quality evidence), PFS (HR 0.43, 95% CI 0.30 to 0.62) and QOL.We did not find any survival advantages when comparing 5FU combinations to 5FU alone.
AUTHORS' CONCLUSIONS
Combination chemotherapy has recently overtaken the long-standing gemcitabine as the standard of care. FOLFIRINOX and gemcitabine plus nab-paclitaxel are highly efficacious, but our analysis shows that other combination regimens also offer a benefit. Selection of the most appropriate chemotherapy for individual patients still remains difficult, with clinicopathological stratification remaining elusive. Biomarker development is essential to help rationalise treatment selection for patients.
Topics: Albumins; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Deoxycytidine; Epirubicin; Fluorouracil; Humans; Paclitaxel; Pancreatic Neoplasms; Pyrimidines; Randomized Controlled Trials as Topic; Treatment Outcome; Gemcitabine
PubMed: 29557103
DOI: 10.1002/14651858.CD011044.pub2 -
Langenbeck's Archives of Surgery Dec 2019Central pancreatectomy (CP) is the alternative to distal pancreatectomy (DP) for specific pathologies of the mid-pancreas. However, the benefits of CP over DP remain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Central pancreatectomy (CP) is the alternative to distal pancreatectomy (DP) for specific pathologies of the mid-pancreas. However, the benefits of CP over DP remain controversial. This study aims to compare the two procedures by conducting a meta-analysis of all published papers.
METHODS
A systematic search of original studies comparing CP vs. DP was performed using PubMed, Scopus, and Cochrane Library databases up to June 2018. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist was followed.
RESULTS
Twenty-one studies were included (596 patients with CP and 1070 patients with DP). Compared to DP, CP was associated with significantly higher rates of overall and severe morbidity (p < 0.0001), overall and clinically relevant pancreatic fistula (p < 0.0001), postoperative hemorrhage (p = 0.02), but with significantly lower incidences of new-onset (p < 0.0001) and worsening diabetes mellitus (p = 0.004). Furthermore, significantly longer length of hospital stay (p < 0.0001) was observed for CP patients.
CONCLUSIONS
CP is superior to DP regarding the preservation of pancreatic functions, but at the expense of significantly higher complication rates and longer hospital stay. Proper selection of patients is of utmost importance to maximize the benefits and mitigate the risks of CP.
Topics: Disease-Free Survival; Female; Humans; Laparoscopy; Length of Stay; Male; Neoplasm Invasiveness; Neoplasm Staging; Open Abdomen Techniques; Operative Time; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Patient Selection; Postoperative Complications; Prognosis; Risk Assessment; Survival Analysis
PubMed: 31641855
DOI: 10.1007/s00423-019-01829-3