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Journal of Clinical Medicine May 2023Pulmonary carcinoids (PCs) are part of a spectrum of well-differentiated neuroendocrine neoplasms (NENs) and are classified as typical carcinoid (TC) and atypical... (Review)
Review
Pulmonary carcinoids (PCs) are part of a spectrum of well-differentiated neuroendocrine neoplasms (NENs) and are classified as typical carcinoid (TC) and atypical carcinoid (AC). TC differ from AC not only for its histopathological features but also for its "functional imaging pattern" and prognosis. ACs are more undifferentiated and characterized by higher aggressiveness. Positron emission tomography/computed tomography (PET/CT) with somatostatin analogs (SSA) labeled with Gallium-68 (Ga-DOTA-TOC, Ga-DOTA-NOC, Ga-DOTA-TATE) has widely replaced conventional imaging with gamma camera using In- or Tc-labelled compounds and represents now the gold standard for diagnosis and management of NENs. In this setting, as already described for gastro-entero-pancreatic NENs, F-Fluorodeoxiglucose ([F]FDG) in addition to Ga-SSA can play an important role in clinical practice, particularly for ACs that show a more aggressive behavior compared to TCs. The aim of this systematic review is to analyze all original studies collected from the PubMed and Scopus databases regarding PCs in which both Ga-SSA PET/CT and [F]FDG PET/CT were performed in order to evaluate the clinical impact of each imaging modality. The following keywords were used for the research: "F, Ga and (bronchial carcinoid or carcinoid lung)". A total of 57 papers were found, of which 17 were duplicates, 8 were reviews, 10 were case reports, and 1 was an editorial. Of the remaining 21 papers, 12 were ineligible because they did not focus on PC or did not compare Ga-SSA and [F]FDG. We finally retrieved and analyzed nine papers (245 patients with TCs and 110 patients with ACs), and the results highlight the importance of the combined use of Ga-SSA and [F]FDG PET/CT for the correct management of these neoplasms.
PubMed: 37297914
DOI: 10.3390/jcm12113719 -
Frontiers in Immunology 2023Identification of modulators of the immune response with inhibitory properties that could be susceptible for therapeutic intervention is a key goal in cancer research.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Identification of modulators of the immune response with inhibitory properties that could be susceptible for therapeutic intervention is a key goal in cancer research. An example is the human leukocyte antigen G (HLA-G), a nonclassical major histocompatibility complex (MHC) class I molecule, involved in cancer progression.
METHODS
In this article we performed a systematic review and meta-analysis on the association between HLA-G expression and outcome in solid tumors. This study was performed in accordance with PRISMA guidelines and registered in PROSPERO.
RESULTS
A total of 25 studies met the inclusion criteria. These studies comprised data from 4871 patients reporting overall survival (OS), and 961 patients, reporting disease free survival (DFS). HLA-G expression was associated with worse OS (HR 2.09, 95% CI = 1.67 to 2.63; P < .001), that was higher in gastric (HR = 3.40; 95% CI = 1.64 to 7.03), pancreatic (HR = 1.72; 95% CI = 0.79 to 3.74) and colorectal (HR = 1.55; 95% CI = 1.16 to 2.07) cancer. No significant differences were observed between the most commonly utilized antibody (4H84) and other methods of detection. HLA-G expression was associated with DFS which approached but did not meet statistical significance.
DISCUSSION
In summary, we describe the first meta-analysis associating HLA-G expression and worse survival in a variety of solid tumors.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022311973.
Topics: Humans; Disease-Free Survival; HLA-G Antigens; Neoplasms; Prognosis; Progression-Free Survival
PubMed: 37275862
DOI: 10.3389/fimmu.2023.1165813 -
World Journal of Surgical Oncology Jun 2023The role of prophylactic drainage (PD) in gastrectomy for gastric cancer (GC) is not well-established. The purpose of this study is to compare the perioperative outcomes... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of prophylactic drainage (PD) in gastrectomy for gastric cancer (GC) is not well-established. The purpose of this study is to compare the perioperative outcomes between the PD and non-drainage (ND) in GC patients undergoing gastrectomy.
METHODS
A systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure was performed up to December 2022. All eligible randomized controlled trials (RCTs) and observational studies were included and meta-analyzed separately. The registration number of this protocol is PROSPERO CRD42022371102.
RESULTS
Overall, 7 RCTs (783 patients) and 14 observational studies (4359 patients) were ultimately included. Data from RCTs indicated that patients in the ND group had a lower total complications rate (OR = 0.68; 95%CI:0.47-0.98; P = 0.04; I = 0%), earlier time to soft diet (MD = - 0.27; 95%CI: - 0.55 to 0.00; P = 0.05; I = 0%) and shorter length of hospital stay (MD = - 0.98; 95%CI: - 1.71 to - 0.26; P = 0.007; I = 40%). While other outcomes including anastomotic leakage, duodenal stump leakage, pancreatic leakage, intra-abdominal abscess, surgical-site infection, pulmonary infection, need for additional drainage, reoperation rate, readmission rate, and mortality were not significantly different between the two groups. Meta-analyses on observational studies showed good agreement with the pooled results from RCTs, with higher statistical power.
CONCLUSION
The present meta-analysis suggests that routine use of PD may not be necessary and even harmful in GC patients following gastrectomy. However, well-designed RCTs with risk-stratified randomization are still needed to validate the results of our study.
Topics: Humans; Stomach Neoplasms; Randomized Controlled Trials as Topic; Gastrectomy; Drainage; Anastomotic Leak; Postoperative Complications
PubMed: 37270519
DOI: 10.1186/s12957-023-03054-1 -
BJS Open May 2023Pancreatic cancer has one of the worst prognoses of all cancers. Patients with locally advanced pancreatic cancer have a 12.7-20.2 per cent chance of receiving curative...
INTRODUCTION
Pancreatic cancer has one of the worst prognoses of all cancers. Patients with locally advanced pancreatic cancer have a 12.7-20.2 per cent chance of receiving curative surgery after induction systemic chemotherapy. Intratumoral injection therapies have been studied as complementary treatment options for improved local tumour control. The aim of this systematic review was to provide an overview of intratumoral injection therapies, their safety, and oncological outcome in patients with locally advanced pancreatic cancer.
METHODS
A literature search was conducted in PubMed, Embase and the Cochrane Library for articles written in English up to 28 November 2022. All study designs involving at least five patients with locally advanced pancreatic cancer who were treated with an intratumoral injection therapy were included. Critical appraisal of the included studies was performed using the Newcastle-Ottawa scale.
RESULTS
After evaluation of the 1680 articles yielded by the systematic search, 52 studies treating 1843 patients were included. Included intratumoral injection treatment modalities comprised iodine-125 (125I) seed brachytherapy (32 studies, 1283 patients), phosphorus-32 (32P) microbrachytherapy (5 studies, 133 patients), palladium-103 (103Pd) seed brachytherapy (2 studies, 26 patients), immunotherapy (9 studies, 330 patients), and chemotherapy (4 studies, 71 patients). Overall survival ranged between 7.0 and 16.0 months for 125I, 5.2 and 15.5 months for 32P, 6.9 and 10.0 months for 103Pd, 5.8 and 13.8 months for immunotherapy, and 9.0 and 16.2 months for chemotherapy. Severe complication (greater than or equal to grade III complications using Clavien-Dindo classification) rates were 6.2 per cent for 125I, 49.2 per cent for 32P, 15 per cent for 103Pd, 57.9 per cent for immunotherapy, and 0 per cent for chemotherapy.
CONCLUSION
Five intratumoral injection therapies are described and an overview is reported. Some intratumoral injection therapies for patients with locally advanced pancreatic cancer seem safe, although 32P microbrachytherapy and immunotherapy require additional evidence. Currently available data are insufficient to provide firm conclusions regarding the added value to survival. The potential advantage of intratumoral injection therapies complementary to conventional care should be studied in well designed RCTs.
Topics: Humans; Iodine Radioisotopes; Palladium; Injections, Intralesional; Pancreatic Neoplasms
PubMed: 37254902
DOI: 10.1093/bjsopen/zrad052 -
International Journal of Radiation... Dec 2023Evidence of a volume-outcome association in cancer surgery has shaped the centralization of cancer services; however, it is unknown whether a similar association exists... (Meta-Analysis)
Meta-Analysis
PURPOSE
Evidence of a volume-outcome association in cancer surgery has shaped the centralization of cancer services; however, it is unknown whether a similar association exists for radiation therapy. The objective of this study was to determine the association between radiation therapy treatment volume and patient outcomes.
METHODS AND MATERIALS
This systematic review and meta-analysis included studies that compared outcomes of patients who underwent definitive radiation therapy at high-volume radiation therapy facilities (HVRFs) versus low-volume facilities (LVRFs). The systematic review used Ovid MEDLINE and Embase. For the meta-analysis, a random effects model was used. Absolute effects and hazard ratios (HRs) were used to compare patient outcomes.
RESULTS
The search identified 20 studies assessing the association between radiation therapy volume and patient outcomes. Seven of the studies looked at head and neck cancers (HNCs). The remaining studies covered cervical (4), prostate (4), bladder (3), lung (2), anal (2), esophageal (1), brain (2), liver (1), and pancreatic cancer (1). The meta-analysis demonstrated that HVRFs were associated with a lower chance of death compared with LVRFs (pooled HR, 0.90; 95% CI, 0.87- 0.94). HNCs had the strongest evidence of a volume-outcome association for both nasopharyngeal cancer (pooled HR, 0.74; 95% CI, 0.62-0.89) and nonnasopharyngeal HNC subsites (pooled HR, 0.80; 95% CI, 0.75-0.84), followed by prostate cancer (pooled HR, 0.92; 95% CI, 0.86-0.98). The remaining cancer types showed weak evidence of an association. The results also demonstrate that some centers defined as HVRFs are undertaking very few procedures per annum (<5 radiation therapy cases per year).
CONCLUSIONS
An association between radiation therapy treatment volume and patient outcomes exists for most cancer types. Centralization of radiation therapy services should be considered for cancer types with the strongest volume-outcome association, but the effect on equitable access to services needs to be explicitly considered.
Topics: Male; Humans; Nasopharyngeal Neoplasms; Head and Neck Neoplasms; Prostatic Neoplasms
PubMed: 37227363
DOI: 10.1016/j.ijrobp.2023.02.048 -
Health Technology Assessment... May 2023Early evidence suggests that using radiofrequency ablation as an adjunct to standard care (i.e. endoscopic retrograde cholangiopancreatography with stenting) may improve... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early evidence suggests that using radiofrequency ablation as an adjunct to standard care (i.e. endoscopic retrograde cholangiopancreatography with stenting) may improve outcomes in patients with malignant biliary obstruction.
OBJECTIVES
To assess the clinical effectiveness, cost-effectiveness and potential risks of endoscopic bipolar radiofrequency ablation for malignant biliary obstruction, and the value of future research.
DATA SOURCES
Seven bibliographic databases, three websites and seven trials registers were searched from 2008 until 21 January 2021.
REVIEW METHODS
The study inclusion criteria were as follows: patients with biliary obstruction caused by any form of unresectable malignancy; the intervention was reported as an endoscopic biliary radiofrequency ablation to ablate malignant tissue that obstructs the bile or pancreatic ducts, either to fit a stent (primary radiofrequency ablation) or to clear an obstructed stent (secondary radiofrequency ablation); the primary outcomes were survival, quality of life or procedure-related adverse events; and the study design was a controlled study, an observational study or a case report. Risk of bias was assessed using Cochrane tools. The primary analysis was meta-analysis of the hazard ratio of mortality. Subgroup analyses were planned according to the type of probe, the type of stent (i.e. metal or plastic) and cancer type. A de novo Markov model was developed to model cost and quality-of-life outcomes associated with radiofrequency ablation in patients with primary advanced bile duct cancer. Insufficient data were available for pancreatic cancer and secondary bile duct cancer. An NHS and Personal Social Services perspective was adopted for the analysis. A probabilistic analysis was conducted to estimate the incremental cost-effectiveness ratio for radiofrequency ablation and the probability that radiofrequency ablation was cost-effective at different thresholds. The population expected value of perfect information was estimated in total and for the effectiveness parameters.
RESULTS
Sixty-eight studies (1742 patients) were included in the systematic review. Four studies (336 participants) were combined in a meta-analysis, which showed that the pooled hazard ratio for mortality following primary radiofrequency ablation compared with a stent-only control was 0.34 (95% confidence interval 0.21 to 0.55). Little evidence relating to the impact on quality of life was found. There was no evidence to suggest an increased risk of cholangitis or pancreatitis, but radiofrequency ablation may be associated with an increase in cholecystitis. The results of the cost-effectiveness analysis were that the costs of radiofrequency ablation was £2659 and radiofrequency ablation produced 0.18 quality-adjusted life-years, which was more than no radiofrequency ablation on average. With an incremental cost-effectiveness ratio of £14,392 per quality-adjusted life-year, radiofrequency ablation was likely to be cost-effective at a threshold of £20,000 per quality-adjusted life-year across most scenario analyses, with moderate uncertainty. The source of the vast majority of decision uncertainty lay in the effect of radiofrequency ablation on stent patency.
LIMITATIONS
Only 6 of 18 comparative studies contributed to the survival meta-analysis, and few data were found concerning secondary radiofrequency ablation. The economic model and cost-effectiveness meta-analysis required simplification because of data limitations. Inconsistencies in standard reporting and study design were noted.
CONCLUSIONS
Primary radiofrequency ablation increases survival and is likely to be cost-effective. The evidence for the impact of secondary radiofrequency ablation on survival and of quality of life is limited. There was a lack of robust clinical effectiveness data and, therefore, more information is needed for this indication.
FUTURE WORK
Future work investigating radiofrequency ablation must collect quality-of-life data. High-quality randomised controlled trials in secondary radiofrequency ablation are needed, with appropriate outcomes recorded.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42020170233.
FUNDING
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 27, No. 7. See the NIHR Journals Library website for further project information.
Topics: Humans; Bile Duct Neoplasms; Cholestasis; Cost-Benefit Analysis; Cost-Effectiveness Analysis; Observational Studies as Topic; Quality of Life
PubMed: 37212444
DOI: 10.3310/YYMN9802 -
Cancers Apr 2023To systematically review all studies comparing multi-agent to single-agent chemotherapy in the first and second-line setting for unresectable pancreatic adenocarcinoma,... (Review)
Review
PURPOSE
To systematically review all studies comparing multi-agent to single-agent chemotherapy in the first and second-line setting for unresectable pancreatic adenocarcinoma, so as to compare the outcomes of young and elderly patients.
METHODS
This review searched three databases for relevant studies. The inclusion criteria were diagnosis of locally advanced or metastatic pancreatic adenocarcinoma, comparison of an elderly versus young population, comparison of single-agent versus multi-agent chemotherapy, data on survival outcomes, and randomised controlled trials. The exclusion criteria were phase I trials, incomplete studies, retrospective analyses, systematic reviews, and case reports. A meta-analysis was performed on second-line chemotherapy in elderly patients.
RESULTS
Six articles were included in this systematic review. Three of these studies explored first-line treatment and three explored second-line treatment. In the subgroup analysis, the meta-analysis showed statistically improved overall survival for elderly patients receiving single-agent second-line treatment.
CONCLUSIONS
This systematic review confirmed that combination chemotherapy improved survival in the first-line treatment of advanced pancreatic adenocarcinoma, regardless of age. The benefit of combination chemotherapy in second-line studies for elderly patients with advanced pancreas cancer was less clear.
PubMed: 37190218
DOI: 10.3390/cancers15082289 -
The International Journal of Behavioral... May 2023Studies of the associations between soft drinks and the risk of cancer showed inconsistent results. No previous published systematic reviews and meta-analysis has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies of the associations between soft drinks and the risk of cancer showed inconsistent results. No previous published systematic reviews and meta-analysis has investigated a dose-response association between exposure dose and cancer risk or assessed the certainty of currently available evidence. Therefore, we aim to demonstrate the associations and assessed the certainty of the evidence to show our confidence in the associations.
METHODS
We searched Embase, PubMed, Web of Science, and the Cochrane Library from inception to Jun 2022, to include relevant prospective cohort studies. We used a restricted cubic spline model to conduct a dose-response meta-analysis and calculated the absolute effect estimates to present the results. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence.
RESULTS
Forty-two articles including on 37 cohorts enrolled 4,518,547 participants were included. With low certainty evidence, increased consumption of sugar-sweetened beverages (SSBs) per 250 mL/day was significantly associated with a 17% greater risk of breast cancer, a 10% greater risk of colorectal cancer, a 30% greater risk of biliary tract cancer, and a 10% greater risk of prostate cancer; increased consumption of artificially sweetened beverages (ASBs)re per 250 mL/day was significantly associated with a 16% greater risk of leukemia; increased consumption of 100% fruit juice per 250 mL/day was significantly associated with a 31% greater risk of overall cancer, 22% greater risk of melanoma, 2% greater risk of squamous cell carcinoma, and 29% greater risk of thyroid cancer. The associations with other specific cancer were no significant. We found linear dose-response associations between consumption of SSBs and the risk of breast and kidney cancer, and between consumption of ASBs and 100% fruit juices and the risk of pancreatic cancer.
CONCLUSIONS
An increment in consumption of SSBs of 250 mL/day was positively associated with increased risk of breast, colorectal, and biliary tract cancer. Fruit juices consumption was also positively associated with the risk of overall cancer, thyroid cancer, and melanoma. The magnitude of absolute effects, however, was small and mainly based on low or very low certainty of evidence. The association of ASBs consumption with specific cancer risk was uncertain.
TRIAL REGISTRATION
PROSPERO: CRD42020152223.
Topics: Humans; Male; Beverages; Biliary Tract Neoplasms; Carbonated Beverages; Fruit and Vegetable Juices; Melanoma; Prospective Studies; Sweetening Agents
PubMed: 37189146
DOI: 10.1186/s12966-023-01459-5 -
International Journal of Molecular... Apr 2023Lymph node (LN) status is the most significant prognostic factor for invasive urothelial bladder cancer (UBC); however, the optimal extent of LN dissection (LND) is... (Meta-Analysis)
Meta-Analysis Review
Lymph node (LN) status is the most significant prognostic factor for invasive urothelial bladder cancer (UBC); however, the optimal extent of LN dissection (LND) is debated. We assessed circulating matrix metalloproteinase-7 (MMP-7) as a prognostic factor and decision-making marker for the extent of LND. Preoperative serum MMP-7 levels were determined in two independent UBC cohorts (n = 188; n = 68) and in one control cohort (n = 97) by using the ELISA method. A systematic review and meta-analysis on the prognostic role of circulating pretreatment MMP-7 levels were performed. Serum MMP-7 levels were higher in patients compared to controls ( < 0.001) with the highest levels in LN-positive cases. Half of LN-positive UBC patients had low MMP-7 levels, whereas the survival of LN-negative patients with high serum MMP-7 findings was poor. MMP-7 levels were independently associated with poor survival in both cohorts ( = 0.006, < 0.001). Accordingly, our systematic review of six eligible publications revealed a 2.5-fold higher mortality risk in patients with high MMP-7 levels. In conclusion, preoperative MMP-7 level is a validated and independent prognostic factor in urothelial cancer. It cannot be used to decide between regional or extended LND but may be useful in identifying LN-negative high-risk patients with potentially undetected metastases.
Topics: Humans; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Matrix Metalloproteinase 7; Prognosis; Cystectomy; Cohort Studies; Lymph Nodes
PubMed: 37175566
DOI: 10.3390/ijms24097859 -
BMJ Open May 2023Hepatectomy is the best treatment for patients with intrahepatic cholangiocarcinoma (ICC) at present, but there has been controversy about the width of surgical margins.... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Hepatectomy is the best treatment for patients with intrahepatic cholangiocarcinoma (ICC) at present, but there has been controversy about the width of surgical margins. In this study, we systematically investigated the effects of different surgical margin widths on the prognosis of patients with ICC undergoing hepatectomy.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
PubMed, Embase and Web of Science databases were systematically searched from inception to June 2022.
ELIGIBILITY CRITERIA
Cohort studies reported in English with patients who underwent negative marginal (R0) resection were included. The effects of surgical margin width on overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) in patients with ICC were assessed.
DATA EXTRACTION AND SYNTHESIS
Two investigators independently conducted literature screening and data extraction. Risk of bias was assessed using funnel plots and quality was assessed by the Newcastle-Ottawa Scale. Forest plots of HRs and their 95% CIs for outcome indicators were plotted. Heterogeneity was assessed and determined quantitatively using I, and the stability of the study results was evaluated using sensitivity analysis. Analyses were performed using Stata software.
RESULTS
Nine studies were included. With the wide margin group (≥10 mm) as the control, pooled HR of OS in the narrow margin group (<10 mm) was 1.54 (95% CI 1.34 to 1.77). HRs of OS in three subgroups where the margin was less than 5 mm ranged from 5 mm to 9 mm, or was less than 10 mm in length were 1.88 (1.45 to 2.42), 1.33 (1.03 to 1.72) and 1.49 (1.20 to 1.84), respectively. Pooled HR of DFS in the narrow margin group (<10 mm) was 1.51 (1.14 to 2.00). Pooled HR of RFS in the narrow margin group (<10 mm) was 1.35 (1.19 to 1.54). HRs of RFS in three subgroups where the margin was less than 5 mm ranged from 5 mm to 9 mm, or was less than 10 mm in length were 1.38 (1.07 to 1.78), 1.39 (1.11 to 1.74) and 1.30 (1.06 to 1.60), respectively. Neither lymph node lesions (HR 1.44, 95% CI 1.22 to 1.70) nor lymph node invasion (2.14, 1.39 to 3.28) was favourable for postoperative OS in patients with ICC. Lymph node metastasis (1.31, 1.09 to 1.57) was unfavourable for RFS in patients with ICC.
CONCLUSION
Patients with ICC who underwent curative hepatectomy with a negative margin ≥10 mm may have a long-term survival advantage, but lymph node dissection also needs to be considered. In addition, tumour-related pathological features need to be explored to see if they affect the surgical outcome of R0 margins.
Topics: Humans; Margins of Excision; Survival Rate; Bile Duct Neoplasms; Cholangiocarcinoma; Prognosis; Hepatectomy; Bile Ducts, Intrahepatic
PubMed: 37156579
DOI: 10.1136/bmjopen-2022-067222