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World Journal of Gastroenterology Jun 2022Given the low survival rate in pancreatic cancer, new therapeutic techniques have been explored, especially for unresectable or borderline resectable disease. Endoscopic...
BACKGROUND
Given the low survival rate in pancreatic cancer, new therapeutic techniques have been explored, especially for unresectable or borderline resectable disease. Endoscopic ultrasound (EUS) provides real-time imaging and minimally invasive access for local and targeted injection of anti-tumor agents directly into the pancreatic tumor. Limited studies have been reported using this technique for the treatment of pancreatic ductal adenocarcinoma (PDAC).
AIM
To evaluate the progress made with EUS-guided injectable therapies in the treatment of PDAC.
METHODS
All original articles published in English until July 15, 2021, were retrieved a library-assisted literature search from Ovid Evidence-Based Medicine Reviews and Scopus databases. Reference lists were reviewed to identify additional relevant articles. Prospective clinical studies evaluating the use of EUS-guided injectable therapies in PDAC were included. Studies primarily directed at non-EUS injectable therapies and other malignancies were excluded. Retrieved manuscripts were reviewed descriptively with on critical appraisal of published studies based on their methods and outcome measures such as safety, feasibility, and effectiveness in terms of tumor response and survival. Heterogeneity in data outcomes and therapeutic techniques limited the ability to perform comparative statistical analysis.
RESULTS
A total of thirteen articles (503 patients) were found eligible for inclusion. The EUS-injectable therapies used were heterogeneous among the studies consisting of immunotherapy ( = 5) in 59 patients, chemotherapy ( = 1) in 36 patients, and viral and other biological therapies ( = 7) in 408 patients. Eleven of the studies reviewed were single armed while two were double armed with one randomized trial and one non-randomized comparative study. Overall, the included studies demonstrated EUS-guided injectable therapies to be safe and feasible with different agents as monotherapy or in conjunction with other modalities. Promising results were also observed regarding their efficacy and survival parameters in patients with PDAC.
CONCLUSION
EUS-guided injectable therapies, including immunotherapy, chemotherapy, and viral or other biological therapies have shown minimal adverse events and potential efficacy in the treatment of PDAC. Comparative studies, including controlled trials, are required to confirm these results in order to offer novel EUS-based treatment options for patients with PDAC.
Topics: Adenocarcinoma; Carcinoma, Pancreatic Ductal; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Pancreatic Neoplasms; Prospective Studies
PubMed: 35800184
DOI: 10.3748/wjg.v28.i21.2383 -
The Cochrane Database of Systematic... Jan 2022Pancreatic cancer remains one of the five leading causes of cancer deaths in industrialised nations. For adenocarcinomas in the head of the gland and premalignant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic cancer remains one of the five leading causes of cancer deaths in industrialised nations. For adenocarcinomas in the head of the gland and premalignant lesions, partial pancreaticoduodenectomy represents the standard treatment for resectable tumours. The gastro- or duodenojejunostomy after partial pancreaticoduodenectomy can be reestablished via either an antecolic or retrocolic route. The debate about the more favourable technique for bowel reconstruction is ongoing.
OBJECTIVES
To compare the effectiveness and safety of antecolic and retrocolic gastro- or duodenojejunostomy after partial pancreaticoduodenectomy.
SEARCH METHODS
In this updated version, we conducted a systematic literature search up to 6 July 2021 to identify all randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library 2021, Issue 6, MEDLINE (1946 to 6 July 2021), and Embase (1974 to 6 July 2021). We applied no language restrictions. We handsearched reference lists of identified trials to identify further relevant trials, and searched the trial registries clinicaltrials.govand World Health Organization International Clinical Trials Registry Platform for ongoing trials.
SELECTION CRITERIA
We considered all RCTs comparing antecolic with retrocolic reconstruction of bowel continuity after partial pancreaticoduodenectomy for any given indication to be eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the identified references and extracted data from the included trials. The same two review authors independently assessed risk of bias of included trials, according to standard Cochrane methodology. We used a random-effects model to pool the results of the individual trials in a meta-analysis. We used odds ratios (OR) to compare binary outcomes and mean differences (MD) for continuous outcomes.
MAIN RESULTS
Of a total of 287 citations identified by the systematic literature search, we included eight randomised controlled trials (reported in 11 publications), with a total of 818 participants. There was high risk of bias in all of the trials in regard to blinding of participants and/or outcome assessors and unclear risk for selective reporting in six of the trials. There was little or no difference in the frequency of delayed gastric emptying (OR 0.67; 95% confidence interval (CI) 0.41 to 1.09; eight trials, 818 participants, low-certainty evidence) with relevant heterogeneity between trials (I=40%). There was little or no difference in postoperative mortality (risk difference (RD) -0.00; 95% CI -0.02 to 0.01; eight trials, 818 participants, high-certainty evidence); postoperative pancreatic fistula (OR 1.01; 95% CI 0.73 to 1.40; eight trials, 818 participants, low-certainty evidence); postoperative haemorrhage (OR 0.87; 95% CI 0.47 to 1.59; six trials, 742 participants, low-certainty evidence); intra-abdominal abscess (OR 1.11; 95% CI 0.71 to 1.74; seven trials, 788 participants, low-certainty evidence); bile leakage (OR 0.82; 95% CI 0.35 to 1.91; seven trials, 606 participants, low-certainty evidence); reoperation rate (OR 0.68; 95% CI 0.34 to 1.36; five trials, 682 participants, low-certainty evidence); and length of hospital stay (MD -0.21; 95% CI -1.41 to 0.99; eight trials, 818 participants, low-certainty evidence). Only one trial reported quality of life, on a subgroup of 73 participants, also without a relevant difference between the two groups at any time point. The overall certainty of the evidence was low to moderate, due to some degree of heterogeneity, inconsistency and risk of bias in the included trials.
AUTHORS' CONCLUSIONS
There was low- to moderate-certainty evidence suggesting that antecolic reconstruction after partial pancreaticoduodenectomy results in little to no difference in morbidity, mortality, length of hospital stay, or quality of life. Due to heterogeneity in definitions of the endpoints between trials, and differences in postoperative management, future research should be based on clearly defined endpoints and standardised perioperative management, to potentially elucidate differences between these two procedures. Novel strategies should be evaluated for prophylaxis and treatment of common complications, such as delayed gastric emptying.
Topics: Humans; Length of Stay; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications
PubMed: 35014692
DOI: 10.1002/14651858.CD011862.pub3 -
Gut Jan 2021Recently, tumours with microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) have gained considerable interest due to the success of immunotherapy in... (Comparative Study)
Comparative Study
OBJECTIVE
Recently, tumours with microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) have gained considerable interest due to the success of immunotherapy in this molecular setting. Here, we aim to clarify clinical-pathological and/or molecular features of this tumour subgroup through a systematic review coupled with a comparative analysis with existing databases, also providing indications for a correct approach to the clinical identification of MSI/dMMR pancreatic ductal adenocarcinoma (PDAC).
DESIGN
PubMed, SCOPUS and Embase were searched for studies reporting data on MSI/dMMR in PDAC up to 30 November 2019. Histological and molecular data of MSI/dMMR PDAC were compared with non-MSI/dMMR PDAC and with PDAC reference cohorts (including SEER database and The Cancer Genome Atlas Research Network - TCGA project).
RESULTS
Overall, 34 studies with 8323 patients with PDAC were included in the systematic review. MSI/dMMR demonstrated a very low prevalence in PDAC (around 1%-2%). Compared with conventional PDAC, MSI/dMMR PDAC resulted strongly associated with medullary and mucinous/colloid histology (p<0.01) and with a / wild-type molecular background (p<0.01), with more common genes mutations. Data on survival are still unclear.
CONCLUSION
PDAC showing typical medullary or mucinous/colloid histology should be routinely examined for MSI/dMMR status using specific tests (immunohistochemistry, followed by MSI-PCR in cases with doubtful results). Next-generation sequencing (NGS) should be adopted either where there is limited tissue or as part of NGS tumour profiling in the context of precision oncology, acknowledging that conventional histology of PDAC may rarely harbour MSI/dMMR.
Topics: Carcinoma, Pancreatic Ductal; Databases, Factual; Humans; Microsatellite Instability; Pancreatic Neoplasms
PubMed: 32350089
DOI: 10.1136/gutjnl-2020-320726 -
Annals of Oncology : Official Journal... May 2020Aspirin has been associated with a reduced risk of colorectal cancer, and possibly of a few other digestive tract cancers. The quantification of risk reduction and the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aspirin has been associated with a reduced risk of colorectal cancer, and possibly of a few other digestive tract cancers. The quantification of risk reduction and the optimal dose and duration of aspirin use for the prevention of colorectal and other digestive tract cancers remains unclear.
METHODS
To provide an up-to-date quantification of this association, we conducted a systematic review and meta-analysis of all observational studies on aspirin and cancers of the digestive tract sites published through March 2019. We estimated the pooled relative risk (RR) of cancer for regular aspirin use versus non-use using random-effects models, and, whenever data were available, we investigated the dose- and duration-risk relations.
RESULTS
Regular aspirin use is associated with a reduced risk of colorectal cancer [RR = 0.73, 95% confidence interval (CI) = 0.69-0.78, 45 studies], squamous-cell esophageal cancer (RR = 0.67, 95% CI = 0.57-0.79, 13 studies), adenocarcinoma of the esophagus and gastric cardia (RR = 0.61, 95% CI = 0.49-0.77, 10 studies), stomach cancer (RR = 0.64, 95% CI = 0.51-0.82, 14 studies), hepato-biliary tract cancer (RR = 0.62, 95% CI = 0.44-0.86, five studies), and pancreatic cancer (RR = 0.78, 95% CI = 0.68-0.89, 15 studies), but not of head and neck cancer (RR = 0.94, 95% CI = 0.76-1.16, 10 studies). The associations are somewhat stronger in case-control than in cohort and nested case-control studies and are characterized by some between-study heterogeneity. Risk estimates are consistent across sex, geographical areas, and other selected covariates. For colorectal cancer, an aspirin dose between 75 and 100 mg/day conveys a risk reduction of 10%, and a dose of 325 mg/day of 35%. For all neoplasms, except head and neck cancer, inverse duration-risk relations with aspirin use are found.
CONCLUSION
The present comprehensive meta-analysis supports and further quantifies the inverse association between regular aspirin use and the risk of colorectal and other digestive tract cancers, including some rare ones. The favorable effect of aspirin increases with longer duration of use, and, for colorectal cancer, with increasing dose.
Topics: Aspirin; Cohort Studies; Colorectal Neoplasms; Gastrointestinal Neoplasms; Humans
PubMed: 32272209
DOI: 10.1016/j.annonc.2020.02.012 -
Langenbeck's Archives of Surgery May 2021The clinical significance of indeterminate pulmonary nodules (IPN) in patients with resectable pancreatic adenocarcinoma (PDAC) is unknown. The rate of detection on IPN... (Review)
Review
BACKGROUND
The clinical significance of indeterminate pulmonary nodules (IPN) in patients with resectable pancreatic adenocarcinoma (PDAC) is unknown. The rate of detection on IPN has risen due to enhanced staging investigations to determine resectability. IPNs detected on preoperative imaging represent a clinical dilemma and complicate decision-making. Currently, there are no recommendations on the management of IPN. This review provides a comprehensive overview of the current knowledge on the natural history of IPN detected among patients with resectable PDAC.
METHODS
A systematic review based on a search in Medline and Embase databases was performed. All clinical studies evaluating the significance of IPN in patients with resectable PDAC were included. PRISMA guidelines were followed.
RESULTS
Five studies met the inclusion criteria. The total patient population was 761. The prevalence of IPN reported ranged from 18 to 71%. The median follow-up duration was 17 months. The median overall survival was 19 months. Patients with pre-operative IPN which subsequently progressed to clinically recognizable pulmonary metastases, ranged from 1.5 to 16%. Four studies found that there was no significant difference in median overall survival in patients with or without IPNs.
CONCLUSION
This is a first review on the significance of IPN in patients with resectable PDAC. The preoperative presence of IPN does not demonstrate an association with overall survival after surgery. The identification of IPN is a significant finding however it should not preclude patients with resectable PDAC from undergoing curative resection.
Topics: Adenocarcinoma; Humans; Lung Neoplasms; Multiple Pulmonary Nodules; Pancreatic Neoplasms
PubMed: 33392814
DOI: 10.1007/s00423-020-02049-w -
Journal of Clinical Medicine Dec 2023Pancreatic cancer is notorious for its aggressive nature and low survival rate, with less than 10% of patients surviving beyond five years. Early detection is difficult,... (Review)
Review
BACKGROUND
Pancreatic cancer is notorious for its aggressive nature and low survival rate, with less than 10% of patients surviving beyond five years. Early detection is difficult, but skin metastases can be a rare but significant indicator. This systematic review focuses on the epidemiology, clinical features, and histology of skin metastases from pancreatic cancer to determine their importance in early diagnosis and overall management of the disease.
MATERIALS AND METHODS
Following PRISMA guidelines, we conducted an exhaustive search of MEDLINE/PubMed, EMBASE, and SCOPUS databases up to June 2023, using specific keywords. Four independent investigators screened the studies using predefined criteria, and two investigators checked the accuracy and consistency of the data extraction. We assessed the quality of the trials using adapted criteria from the Joanna Briggs Institute. A narrative synthesis rather than a meta-analysis was chosen because of the different study designs.
RESULTS
The final analysis included 57 patients with skin metastases from pancreatic cancer. Cutaneous metastases, although rare, presented with approximately equal gender distribution and a mean age of 63.4 years. Predominantly non-umbilical (77%), these metastases showed clinical diversity, ranging from asymptomatic nodules to painful or ulcerated lesions. Notably, skin metastases often preceded the diagnosis of primary pancreatic cancer (58%). Primary tumor characteristics revealed different localizations, with adenocarcinoma being the most prevalent histological type (77%). A significant association ( = 0.008) was observed between pancreatic tumor location and the timing of presentation of skin metastases. Tumors located in the body and tail of the pancreas were more likely to manifest skin metastases as an initial clinical manifestation (62.2%) than those in the head of the pancreas (20.8%).
CONCLUSIONS
In conclusion, although skin metastases are rare, they are important indicators of pancreatic cancer, highlighting the need for multidisciplinary healthcare collaboration and thorough skin examination. Recognizing them could lead to earlier diagnosis, which is crucial in a cancer with limited treatment options.
PubMed: 38202111
DOI: 10.3390/jcm13010104 -
Cancer Management and Research 2020Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies and a major health problem worldwide. There were no major advances in conventional... (Review)
Review
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies and a major health problem worldwide. There were no major advances in conventional treatments in inhibiting tumor progression and increasing patient survival time. In order to suppress mechanisms responsible for tumor cell development such as those with oncogenic roles, more advanced therapeutic strategies should be sought. One of the most important oncogenes of pancreatic cancer is the gene. The overexpression of can activate many tumorigenic processes such as cell proliferation and pancreatic cancer cell invasion. MiRNAs are important molecules that are confirmed by targeting mRNA transcripts to regulate the expression of the gene. Therefore, restoring -repressing miRNAs expression tends to be an effective method of treating MYC-driven cancers.
OBJECTIVE
The purpose of this study was to identify all validated microRNAs targeting expression to inhibit PDAC progression by conducting a systematic review.
METHODS
In this systematic review study, the papers published between 2000 and 2020 in major online scientific databases including PubMed, Scopus, and Web of Science were screened, following inclusion and exclusion criteria. We extracted all the experimental studies that showed miRNAs could target the expression of the MYC gene in PDAC.
RESULTS
Eight papers were selected from a total of 89 papers. We found that six miRNAs (Let-7a, miR-145, miR-34a, miR-375, miR-494, and miR-148a) among the selected studies were validated for targeting MYC gene and three of them confirmed Let-7a as a direct MYC expression regulator in PC cells. Finally, we summarized the latest shreds of evidence of experimentally validated miRNAs targeting the MYC gene with respect to PDAC's therapeutic potential.
CONCLUSION
Restoring the expression of -repressing miRNAs tends to be an effective way to treat -driven cancers such as PDAC. Several miRNAs have been proposed to target this oncogene via bioinformatics tools, but only a few have been experimentally validated for pancreatic cancer cells and models. Further studies should be conducted to find the interaction network of miRNA- to develop more successful therapeutic strategies for PC, using the synergistic effects of these miRNAs.
PubMed: 32308478
DOI: 10.2147/CMAR.S245872 -
The Journal of Pathology. Clinical... Mar 2021Immune cell infiltration has been identified as a prognostic biomarker in several cancers. However, no immune based biomarker has yet been validated for use in... (Meta-Analysis)
Meta-Analysis
Immune cell infiltration has been identified as a prognostic biomarker in several cancers. However, no immune based biomarker has yet been validated for use in pancreatic ductal adenocarcinoma (PDAC). We undertook a systematic review and meta-analysis of immune cell infiltration, measured by immunohistochemistry (IHC), as a prognostic biomarker in PDAC. All other IHC prognostic biomarkers in PDAC were also summarised. MEDLINE, EMBASE and Web of Science were searched between 1998 and 2018. Studies investigating IHC biomarkers and prognosis in PDAC were included. REMARK score and Newcastle-Ottawa scale were used for qualitative analysis. Random-effects meta-analyses were used to pool results, where possible. Twenty-six articles studied immune cell infiltration IHC biomarkers and PDAC prognosis. Meta-analysis found high infiltration with CD4 (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.51-0.83.) and CD8 (HR = 0.68, 95% CI = 0.55-0.84.) T-lymphocytes associated with better disease-free survival. Reduced overall survival was associated with high CD163 (HR = 1.62, 95% CI = 1.03-2.56). Infiltration of CD3, CD20, FoxP3 and CD68 cells, and PD-L1 expression was not prognostic. In total, 708 prognostic biomarkers were identified in 1101 studies. In summary, high CD4 and CD8 infiltration are associated with better disease-free survival in PDAC. Increased CD163 is adversely prognostic. Despite the publication of 708 IHC prognostic biomarkers in PDAC, none has been validated for clinical use. Further research should focus on reproducibility of prognostic biomarkers in PDAC in order to achieve this.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; B7-H1 Antigen; Biomarkers; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Carcinoma, Pancreatic Ductal; Disease-Free Survival; Humans; Immunohistochemistry; Pancreatic Neoplasms; Prognosis; Receptors, Cell Surface; Reproducibility of Results
PubMed: 33481339
DOI: 10.1002/cjp2.192 -
International Journal of Molecular... Mar 2021Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical...
Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo)adjuvant chemotherapy regimens. Early detection of PDAC may increase the overall survival. It is furthermore foreseen that precision medicine will provide improved prognostic stratification and prediction of therapeutic response. In this review, omics-based discovery efforts are presented that aim for novel diagnostic and prognostic biomarkers of PDAC. For this purpose, we systematically evaluated the literature published between 1999 and 2020 with a focus on protein- and protein-glycosylation biomarkers in pancreatic cancer patients. Besides genomic and transcriptomic approaches, mass spectrometry (MS)-based proteomics and glycomics of blood- and tissue-derived samples from PDAC patients have yielded new candidates with biomarker potential. However, for reasons discussed in this review, the validation and clinical translation of these candidate markers has not been successful. Consequently, there has been a change of mindset from initial efforts to identify new unimarkers into the current hypothesis that a combination of biomarkers better suits a diagnostic or prognostic panel. With continuing development of current research methods and available techniques combined with careful study designs, new biomarkers could contribute to improved detection, prognosis, and prediction of pancreatic cancer.
Topics: Biomarkers, Tumor; Body Fluids; Carcinoma, Pancreatic Ductal; Clinical Decision-Making; Diagnosis, Differential; Early Detection of Cancer; Glycomics; Glycoproteins; Humans; Mass Spectrometry; Neoplasm Proteins; Neoplastic Syndromes, Hereditary; Pancreatic Neoplasms; Pancreatitis, Chronic; Precancerous Conditions; Precision Medicine; Predictive Value of Tests; Prognosis; Proteomics; Reproducibility of Results; Risk Factors
PubMed: 33800786
DOI: 10.3390/ijms22052655 -
International Journal of Surgery... Jan 2024A greater than 1 mm tumour-free resection margin (R0 >1 mm) is a prognostic factor in upfront-resected pancreatic ductal adenocarcinoma. After neoadjuvant treatment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A greater than 1 mm tumour-free resection margin (R0 >1 mm) is a prognostic factor in upfront-resected pancreatic ductal adenocarcinoma. After neoadjuvant treatment (NAT); however, the prognostic impact of resection margin (R) status remains controversial.
METHODS
Randomised and non-randomised studies assessing the association of R status and survival in resected pancreatic ductal adenocarcinoma after NAT were sought by systematic searches of MEDLINE, Web of Science and CENTRAL. Hazard ratios (HR) and their corresponding 95% CI were collected to generate log HR using the inverse-variance method. Random-effects meta-analyses were performed and the results presented as weighted HR. Sensitivity and meta-regression analyses were conducted to account for different surgical procedures and varying length of follow-up, respectively.
RESULTS
Twenty-two studies with a total of 4929 patients were included. Based on univariable data, R0 greater than 1 mm was significantly associated with prolonged overall survival (OS) (HR 1.76, 95% CI 1.57-1.97; P<0.00001) and disease-free survival (DFS) (HR 1.66, 95% CI 1.39-1.97; P<0.00001). Using adjusted data, R0 greater than 1 mm was significantly associated with prolonged OS (HR 1.65, 95% CI 1.39-1.97; P<0.00001) and DFS (HR 1.76, 95% CI 1.30-2.39; P=0.0003). Results for R1 direct were comparable in the entire cohort; however, no prognostic impact was detected in sensitivity analysis including only partial pancreatoduodenectomies.
CONCLUSION
After NAT, a tumour-free margin greater than 1 mm is independently associated with improved OS as well as DFS in patients undergoing surgical resection for pancreatic cancer.
Topics: Humans; Prognosis; Margins of Excision; Neoadjuvant Therapy; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Retrospective Studies
PubMed: 38315795
DOI: 10.1097/JS9.0000000000000792