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BMC Cancer Aug 2023Patients with advanced pancreatic cancer have a poor prognosis and high burden of cancer-related symptoms. It is necessary to assess the trade-off of clinical benefits...
BACKGROUND
Patients with advanced pancreatic cancer have a poor prognosis and high burden of cancer-related symptoms. It is necessary to assess the trade-off of clinical benefits and possible harms of treatments with anticancer drugs (TAD). This systematic review aims to compare the effectiveness of TAD versus supportive care or no treatment, considering all patient-important outcomes.
METHODS
We searched PubMed, Embase, Cochrane Library, and Epistemonikos. Two reviewers performed selection, data extraction and risk of bias assessment. We assessed certainty of the evidence using the GRADE approach.
RESULTS
We included 14 randomised controlled trials. Chemotherapy may result in a slight increase in overall survival (MD: 2.97 months (95%CI 1.23, 4.70)) and fewer hospital days (MD: -6.7 (-8.3, -5.1)), however, the evidence is very uncertain about its effect on symptoms, quality of life, functional status, and adverse events. Targeted/biological therapy may result in little to no difference in overall survival and a slight increment in progression-free survival (HR: 0.83 (95%CI 0.63, 1.10)), but probably results in more adverse events (RR: 5.54 (95%CI 1.24, 23.97)). The evidence is very uncertain about the effect of immunotherapy in overall survival and functional status.
CONCLUSIONS
The evidence is very uncertain about whether the benefits of using treatment with anticancer drugs outweigh their risks for patients with advanced pancreatic cancer. This uncertainty is further highlighted when considering immunotherapy or a second line of chemotherapy and thus, best supportive care would be an appropriate alternative. Future studies should assess their impact on all patient-important outcomes to inform patients in setting their goals of care.
Topics: Humans; Quality of Life; Antineoplastic Agents; Pancreatic Neoplasms; Immunotherapy
PubMed: 37573294
DOI: 10.1186/s12885-023-11207-4 -
HPB : the Official Journal of the... Mar 2020Minimally invasive pancreaticoduodenectomy (MIPD) is a demanding surgical procedure, thus explaining its slow expansion and limited popularity amongst... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Minimally invasive pancreaticoduodenectomy (MIPD) is a demanding surgical procedure, thus explaining its slow expansion and limited popularity amongst Hepato-Pancreatico-Biliary (HPB) surgeons. However, three main advantages of robotic assisted pancreaticoduodenectomy (PD) including improved dexterity, 3D vision less surgical fatigue, may overcome some of the hurdles and ultimately lead to a wider adoption. This systematic review and network meta-analysis aims to evaluate the current literature on open and MIPD.
METHODS
A systematic literature search was conducted for studies reporting robotic, laparoscopic and open surgery for PD. Network meta-analysis of intraoperative (operating time, blood loss, transfusion rate), postoperative (overall and major complications, pancreatic fistula, delayed gastric emptying, length of hospital stay) and oncological outcomes (R0 resection, lymphadenectomy) were performed.
RESULTS
Sixty-one studies including 62,529 patients were included in the network meta-analysis, of which 3% (n = 2131) were totally robotic (TR) and 10% (n = 6514) were totally laparoscopic (TL). There were no significant differences between surgical techniques for major complications, overall and grade B/C fistula, biliary leak, mortality and R0 resections. Transfusion rates were significantly lower in TR compared to TL and open. Operative time for TR was longer compared with open and TL. Both TL and TR were associated with significantly lower rates of wound infections, pulmonary complications, shorter length of stay and higher lymph nodes examined when compared to open. TR was associated with significantly lower conversion rates than TL.
CONCLUSION
In summary, this network meta-analysis highlights the variability in techniques within MIPD and compares other variations to the conventional open PD. Current evidence appears to demonstrate MIPD, both laparoscopic and robotic techniques are associated with improved rates of surgical site infections, pulmonary complications, and a shorter hospital stay, with no compromise in oncological outcomes for cancer resections.
Topics: Humans; Laparoscopy; Network Meta-Analysis; Pancreatic Neoplasms; Pancreaticoduodenectomy; Robotic Surgical Procedures
PubMed: 31676255
DOI: 10.1016/j.hpb.2019.09.016 -
Journal of Clinical Oncology : Official... Aug 2021To analyze the prevalence of homologous recombination deficiency (HRD) in patients with pancreatic ductal adenocarcinoma (PDAC). (Meta-Analysis)
Meta-Analysis
PURPOSE
To analyze the prevalence of homologous recombination deficiency (HRD) in patients with pancreatic ductal adenocarcinoma (PDAC).
MATERIALS AND METHODS
We conducted a systematic review and meta-analysis of the prevalence of HRD in PDAC from PubMed, Scopus, and Cochrane Library databases, and online cancer genomic data sets. The main outcome was pooled prevalence of somatic and germline mutations in the better characterized HRD genes (, , , , , , , and the genes). The secondary outcomes were prevalence of germline mutations overall, and in sporadic and familial cases; prevalence of germline mutations in Ashkenazi Jewish (AJ); and prevalence of HRD based on other definitions (ie, alterations in other genes, genomic scars, and mutational signatures). Random-effects modeling with the Freeman-Tukey transformation was used for the analyses. PROSPERO registration number: (CRD42020190813).
RESULTS
Sixty studies with 21,842 participants were included in the systematic review and 57 in the meta-analysis. Prevalence of germline and somatic mutations was : 0.9%, : 3.5%, : 0.2%, : 2.2%, : 0.3%, : 0.5%, : 0.0%, and : 0.1%. Prevalence of germline mutations was : 0.9% (2.4% in AJ), : 3.8% (8.2% in AJ), : 0.2%, : 2%, : 0.3%, and : 0.4%. No significant differences between sporadic and familial cases were identified. HRD prevalence ranged between 14.5%-16.5% through targeted next-generation sequencing and 24%-44% through whole-genome or whole-exome sequencing allowing complementary genomic analysis, including genomic scars and other signatures (surrogate markers of HRD).
CONCLUSION
Surrogate readouts of HRD identify a greater proportion of patients with HRD than analyses limited to gene-level approaches. There is a clear need to harmonize HRD definitions and to validate the optimal biomarker for treatment selection. Universal HRD screening including integrated somatic and germline analysis should be offered to all patients with PDAC.
Topics: Adenocarcinoma; Carcinoma, Pancreatic Ductal; Homologous Recombination; Humans; Prevalence
PubMed: 34197182
DOI: 10.1200/JCO.20.03238 -
International Journal of Surgery... May 2022Pancreaticoduodenectomy (PD) is a challenging procedure with peri-operative complications. Robotic surgery offers improved dexterity, visibility, and accessibility.... (Review)
Review
BACKGROUND
Pancreaticoduodenectomy (PD) is a challenging procedure with peri-operative complications. Robotic surgery offers improved dexterity, visibility, and accessibility. Recently, many centres have reported improved clinical outcomes for robotic PD. We reviewed the safety and efficacy of robotic PD in comparison to open PD using 'Therapeutic Index' (TI).
METHODS
A systematic review of the literature was conducted in various databases. Articles published between January 2010 and March 2021 reporting totally-robotic and open PD were included, according to the PRISMA and AMSTAR-2 guidelines. The Cochrane tool was used for risk of bias assessment. We compared 30-day mortality rates (MR), lymphadenectomy rates (LR), R0 resection rates (RRR) and therapeutic index (TI). STATA 16.1 was used for statistical analysis.
RESULTS
The four studies that met inclusion criteria included 5090 PDs, out of which 617 were totally-robotic (RPD) and 4473 were open (OPD). Variance ratio tests demonstrated a)Higher TI for RPD versus OPD (1807.42 vs 1723.37, p = 0.86), b)Significantly smaller MR (2.50 vs 19.00, p = 0.0004), c)Significantly lower RRR (130.50 vs 939.25, p = 0.00) and d)No significant difference in LR between RPD and OPD (35.63 vs 38.25, p = 0.81). Meta-regression analysis showed a significantly higher TI coefficient of RPD than OPD (0.66 vs -0.40, p = 0.08, α = 0.1).
CONCLUSION
Our study suggests that robotic PD is safe and not inferior to open PD and our analysis RPD demonstrated a higher therapeutic index than OPD. Randomised controlled trials are required to establish the efficacy of robotic PD. Also, standardisation of reporting mortality, survival and oncological outcomes is needed for the effective calculation of TI.
Topics: Humans; Pancreatectomy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Retrospective Studies; Robotic Surgical Procedures; Therapeutic Index
PubMed: 35487420
DOI: 10.1016/j.ijsu.2022.106633 -
Journal of Nuclear Medicine : Official... Jun 2016Neuroendocrine tumors (NETs) are uncommon tumors with increasing incidence and prevalence. Current reports suggest that (68)Ga-DOTATATE PET/CT imaging improves diagnosis... (Comparative Study)
Comparative Study Meta-Analysis Review
68Ga-DOTATATE Compared with 111In-DTPA-Octreotide and Conventional Imaging for Pulmonary and Gastroenteropancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis.
UNLABELLED
Neuroendocrine tumors (NETs) are uncommon tumors with increasing incidence and prevalence. Current reports suggest that (68)Ga-DOTATATE PET/CT imaging improves diagnosis and staging of NETs compared with (111)In-DTPA-octreotide and conventional imaging. We performed a systematic review of (68)Ga-DOTATATE for safety and efficacy compared with octreotide and conventional imaging to determine whether available evidence supports U.S. Food and Drug Administration approval.
METHODS
Medline, EMBASE, Web of Science, and Cochrane Reviews electronic databases were searched from January 1999 to September 2015. Results were restricted to human studies comparing diagnostic accuracy of (68)Ga-DOTATATE with octreotide or conventional imaging for pulmonary or gastroenteropancreatic NET and for human studies reporting safety/toxicity for (68)Ga-DOTATATE with 10 subjects or more thought to have NETs. Direct communication with corresponding authors was attempted to obtain missing information. Abstracts meeting eligibility criteria were collected by a research librarian and assembled for reviewers; 2 reviewers independently determined whether or not to include each abstract. If either reviewer chose inclusion, the abstract was accepted for review.
RESULTS
Database and bibliography searches yielded 2,479 articles, of which 42 were eligible. Three studies compared the 2 radiopharmaceuticals in the same patient, finding (68)Ga-DOTATATE to be more sensitive than octreotide. Nine studies compared (68)Ga-DOTATATE with conventional imaging. (68)Ga-DOTATATE estimated sensitivity, 90.9% (95% confidence interval, 81.4%-96.4%), and specificity, 90.6% (95% confidence interval, 77.8%-96.1%), were high. Five studies were retained for safety reporting only. Report of harm possibly related to (68)Ga-DOTATATE was rare (6 of 974), and no study reported major toxicity or safety issues.
CONCLUSION
No direct comparison of octreotide and (68)Ga-DOTATATE imaging for diagnosis and staging in an unbiased population of NETs has been published. Available information in the peer-reviewed literature regarding diagnostic efficacy and safety supports the use of (68)Ga-DOTATATE for imaging of NETs where it is available.
Topics: Humans; Intestinal Neoplasms; Lung Neoplasms; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Pentetic Acid; Positron Emission Tomography Computed Tomography; Stomach Neoplasms
PubMed: 26769864
DOI: 10.2967/jnumed.115.165803 -
BMC Gastroenterology Feb 2023We aim to evaluate the relationship between the use of metformin and the risk of pancreatic cancer in type 2 diabetes patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aim to evaluate the relationship between the use of metformin and the risk of pancreatic cancer in type 2 diabetes patients.
METHOD
We systematically searched the observational studies on PubMed, Embase, Web of Science, Cochrane Library, clinicalrials.gov, and CNKI databases, extracted relevant data, combined the OR value and 95% CI using the random effect model, and conducted a sensitivity analysis, subgroup analysis, and meta-regression to evaluate the size and stability of this relationship.
RESULT
Twenty-nine studies from twenty-four articles met our inclusion criteria, including more than 2 million subjects. Overall analysis showed that compared with no use of metformin, the use of metformin could reduce the risk of pancreatic cancer in patients with type 2 diabetes (OR = 0.82, 95% CI (0.69, 0.98)). Subgroup analysis showed that compared with the use of hypoglycemic drugs, the use of metformin could reduce the risk of pancreatic cancer in patients with type 2 diabetes (OR = 0.79, 95% CI (0.66, 0.94)). However, compared with no drugs or only diet therapy, metformin users might increase the risk of pancreatic cancer (OR = 2.19, 95% CI (1.08, 4.44)). Sensitivity analysis confirmed the stability of the study, and there was no significant publication bias.
CONCLUSION
Compared with the no-use of metformin, metformin users with diabetes can reduce the risk of pancreatic cancer. More research is needed to prove it works.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Pancreatic Neoplasms
PubMed: 36829129
DOI: 10.1186/s12876-023-02671-0 -
The American Journal of Clinical... Feb 2009Habitual consumption of diets with a high glycemic index (GI) and a high glycemic load (GL) may influence cancer risk via hyperinsulinemia and the insulin-like growth... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Habitual consumption of diets with a high glycemic index (GI) and a high glycemic load (GL) may influence cancer risk via hyperinsulinemia and the insulin-like growth factor axis.
OBJECTIVE
The objective was to conduct a systematic review to assess the association between GI, GL, and risk of digestive tract cancers.
DESIGN
Medline and Embase were searched for relevant publications from inception to July 2008. When possible, adjusted results from a comparison of cancer risk of the highest compared with the lowest category of GI and GL intake were combined by using random-effects meta-analyses.
RESULTS
Cohort and case-control studies that examined the risk between GI or GL intake and colorectal cancer (n = 12) and adenomas (n = 2), pancreatic cancer (n = 6), gastric cancer (n = 2), and squamous-cell esophageal carcinoma (n = 1) were retrieved. Most case-control studies observed positive associations between GI and GL intake and these cancers. However, pooled cohort study results showed no associations between colorectal cancer risk and GI intake [relative risk (RR): 1.04; 95% CI: 0.92, 1.12; n = 7 studies] or GL intake (RR: 1.06; 95% CI: 0.95, 1.17; n = 8 studies). Furthermore, no significant associations were observed in meta-analyses of cohort study results of colorectal cancer subsites and GI and GL intake. Similarly, no significant associations emerged between pancreatic cancer risk and GI intake (RR: 0.99; 95% CI: 0.83, 1.19; n = 5 studies) or GL intake (RR: 1.01; 95% CI: 0.86, 1.19; n = 6 studies) in combined cohort studies.
CONCLUSIONS
The findings from our meta-analyses indicate that GI and GL intakes are not associated with risk of colorectal or pancreatic cancers. There were insufficient data available regarding other digestive tract cancers to make any conclusions about GI or GL intake and risk.
Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Case-Control Studies; Cohort Studies; Colorectal Neoplasms; Dietary Carbohydrates; Female; Gastrointestinal Neoplasms; Glycemic Index; Humans; Hyperinsulinism; Insulin; Male; Middle Aged; Pancreatic Neoplasms; Risk Factors; Stomach Neoplasms
PubMed: 19088152
DOI: 10.3945/ajcn.2008.26823 -
Journal of Gastrointestinal Surgery :... Dec 2021Radioguided surgery (RGS) for gastroenteropancreatic neuroendocrine tumours (GEP-NETs) has been suggested as a way to improve intraoperative lesion detection. This... (Review)
Review
BACKGROUND
Radioguided surgery (RGS) for gastroenteropancreatic neuroendocrine tumours (GEP-NETs) has been suggested as a way to improve intraoperative lesion detection. This systematic literature review of reports of the use of RGS for GEP-NETs was performed to determine if there is a benefit.
METHODS
A literature search was conducted using Google Scholar and PubMed, and snowballing from any relevant literature. Full-text studies were included if they were published in the English language and reported outcomes of RGS on human subjects with GEP-NETs. Qualitative data synthesis was performed.
RESULTS
Twenty-six papers including a total of 209 patients were included. The tracers used were predominantly indium-111 pentetreotide, gallium-68 DOTA-peptides, and technetium-99m EDDA/HYNIC-peptides. Heterogeneous protocols make comparisons difficult, but most papers reported a benefit from the use of RGS in tumours in the gastrointestinal tract; utility in localisation of pancreatic tumours was less clear. Time between tracer administration and operation varied: from 16 h to 8 days with indium-111, 0-24 h with technetium-99m, and 19-193 min with gallium-68. Eight teams reported the thresholding technique used for discrimination-four used a ratio, four statistical methods, and one looked at the sensitivity and specificity of different cut-offs. Six teams performed follow-up of 24 patients (three pancreas, eight gastrinoma, 13 gastrointestinal tract) for between 3 months and 3 years. Two patients relapsed (one pancreas, one gastrinoma) between 6 and 12 months post-surgery.
CONCLUSIONS
RGS appears to aid in localisation of gastrointestinal NETs, but the benefit is more equivocal in pancreatic NETs. Further work into outcomes is warranted.
Topics: Humans; Intestinal Neoplasms; Neuroendocrine Tumors; Pancreatic Neoplasms; Stomach Neoplasms; Surgery, Computer-Assisted
PubMed: 34506015
DOI: 10.1007/s11605-021-05115-w -
Digestive Surgery 2017Survival rates after a total gastrectomy with adequate lymphadenectomy are improving, leading to a shift in outcomes of interest from survival to postoperative outcomes... (Review)
Review
BACKGROUND
Survival rates after a total gastrectomy with adequate lymphadenectomy are improving, leading to a shift in outcomes of interest from survival to postoperative outcomes and symptoms. In this systematic review, we investigate gastrointestinal symptoms that occur after a gastrectomy in relation to exocrine pancreatic insufficiency and the effect of pancreatic exocrine enzyme supplementation on these symptoms.
METHODS
Online databases PubMed, Embase, and Cochrane Library were systematically searched in accordance with the PRISMA guidelines. Studies that researched gastrointestinal symptoms, exocrine pancreatic function, and enzyme supplementation were identified and assessed.
RESULTS
The search resulted in a total of 1,023 articles after exclusion of duplicates. After performing a thorough assessment, 4 studies were included for systematic review. Exocrine pancreatic insufficiency was investigated by 2 studies; the results showed a significant decrease of total exocrine pancreatic function of up to 76%. The other 2 studies investigated the effect of pancreatic enzyme supplementation and found minor improvement in fecal consistency and a decrease in high-degree steatorrhea. No differences in individual symptom scores were reported.
CONCLUSION
Gastrointestinal symptoms such as steatorrhea, bloating, and dumping syndrome may be related to exocrine pancreatic function, initiated by total gastrectomy. Treatment with pancreatic enzymes had a minor positive effect on patients. It should be noted that these studies were of a small sample size and low quality. New and larger RCTs are necessary to either prove or disprove the benefit of pancreatic enzyme replacement therapy in the treatment of the gastrointestinal symptoms after total gastrectomy.
Topics: Dietary Supplements; Enzyme Therapy; Exocrine Pancreatic Insufficiency; Gastrectomy; Humans; Steatorrhea; Stomach Neoplasms
PubMed: 28315875
DOI: 10.1159/000454958 -
European Journal of Cancer (Oxford,... Feb 2024Emerging cancer trends suggest an increase in pancreatic cancer incidence in individuals younger than its typical age of onset, potentially reflecting changes in...
BACKGROUND
Emerging cancer trends suggest an increase in pancreatic cancer incidence in individuals younger than its typical age of onset, potentially reflecting changes in population exposures and lifestyles.
PATIENTS AND METHODS
We conducted a PRISMA-standard systematic literature review to identify non-heritable risk factors for early-onset pancreatic ductal adenocarcinoma (PDAC) (PROSPERO number: CRD42022299397). Systematic searches of MEDLINE and Embase bibliographic databases were performed (January 2022), and publications were screened against predetermined eligibility criteria; data were extracted using standardised data fields. The STROBE checklist was used to assess the completeness of reporting as a proxy for publication quality. Data were categorised by risk factor and analysed descriptively.
RESULTS
In total, 24 publications were included. All publications reported observational study data; thresholds for age group comparisons ranged between 40 and 65 years. Lifestyle factors investigated included smoking, alcohol consumption, obesity, physical inactivity, meat intake, socioeconomic status and geographical residence. Clinical factors investigated included pancreatitis, diabetes/insulin resistance, prior cancer and cancer stage at diagnosis, hepatitis B infection, metabolic syndrome and long-term proton pump inhibitor exposure. Publication STROBE scores were 6-21 (maximum, 22). Eight studies reported results adjusted for confounders. Potential non-heritable risk factors for early-onset PDAC that warrant further investigation included smoking, alcohol consumption, pancreatitis and hepatitis B infection.
CONCLUSION
Evidence for non-heritable risk factors for early-onset PDAC is heterogeneous, but four factors were identified that might aid the identification of at-risk individuals who may benefit from screening and risk reduction strategies.
Topics: Adult; Aged; Humans; Middle Aged; Carcinoma, Pancreatic Ductal; Hepatitis B; Observational Studies as Topic; Pancreatic Neoplasms; Pancreatitis; Risk Factors
PubMed: 38154392
DOI: 10.1016/j.ejca.2023.113471