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La Medicina Del Lavoro Oct 2023Per- and poly-fluoroalkyl substances (PFASs) are a large, complex group of synthetic chemicals humans can be exposed to from occupational or environmental sources. In... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Per- and poly-fluoroalkyl substances (PFASs) are a large, complex group of synthetic chemicals humans can be exposed to from occupational or environmental sources. In this systematic review and meta-analysis, we examined the association between PFAS exposure, particularly Perfluorooctanoic Acid (PFOA), and Perfluorooctane Sulfonic Acid (PFOS), and risk of kidney, liver, and testicular cancer.
METHODS
We systematically searched PubMed to identify cohort and case-control studies reported after the Monograph of the International Agency for Research on Cancer and the Toxicological Profile of the Agency for Toxic Substances and Disease Registry. We assessed the quality of the studies by using a modified version of the Newcastle-Ottawa Scale (NOS). Forest relative risk (RR) plots were constructed for liver, kidney, and testicular cancer. We conducted stratified analyses by geographic region, study design, quality score, outcome, years of publication, exposure source, and PFAS type. A random-effects model was used to address heterogeneity between studies.
RESULTS
Fifteen studies, including ten cohort studies, three case-control studies nested in a cohort, and two case-control studies were included after removing duplicate and irrelevant reports. We found an association between overall PFAS exposure and the risk of kidney cancers (RR=1.18, 95% CI =1.05-1.32; I =52.8%, 11 studies). Also, we showed an association between high-level exposure to PFAS and kidney cancer (RR=1.74, 95% CI =1.23-2.47; p=0.005) and testicular cancer (RR=2.22, 95% CI =1.12-4.39; p=0.057). There was no association with liver cancer. We found no heterogeneity by geographical region, PFAS type, study design, outcome, quality score, year of publication, or exposure source. Only two studies reported results among women.
CONCLUSIONS
We detected an association between overall PFAS exposure and kidney cancer and high doses of PFAS with testicular cancer. However, bias and confounding cannot be excluded, precluding a conclusion in terms of causality.
Topics: Female; Humans; Male; Testicular Neoplasms; Kidney; Liver; Kidney Neoplasms; Carcinoma, Renal Cell; Fluorocarbons
PubMed: 37878255
DOI: 10.23749/mdl.v114i5.15065 -
Cells Oct 2023Circulating tumour DNA (ctDNA) is a potential biomarker that could contribute to more judicious patient selection for personalised treatment. This review and... (Meta-Analysis)
Meta-Analysis Review
Circulating tumour DNA (ctDNA) is a potential biomarker that could contribute to more judicious patient selection for personalised treatment. This review and meta-analysis gives an overview of the current knowledge in the literature investigating the value of ctDNA in patients with colorectal liver metastases (CRLM). A systematic search was conducted in electronic databases for studies published prior to the 26th of May 2023. Studies investigating the association between ctDNA and oncological outcomes in patients undergoing curative-intent local therapy for CRLM were included. Meta-analyses were performed to pool hazard ratios (HR) for the recurrence-free survival (RFS) and overall survival (OS). A total of eleven studies were included and nine were eligible for meta-analyses. Patients with detectable ctDNA after surgery experienced a significantly higher chance of recurrence (HR 3.12, 95% CI 2.27-4.28, < 0.000010) and shorter OS (HR 5.04, 95% CI 2.53-10.04, < 0.00001) compared to patients without detectable ctDNA. A similar association for recurrence was found in patients with detectable ctDNA after the completion of adjuvant therapy (HR 6.39, 95% CI 2.13-19.17, < 0.0009). The meta-analyses revealed no association between detectable ctDNA before surgery and the RFS and OS. These meta-analyses demonstrate the strong association between detectable ctDNA after treatment and oncological outcomes in CRLM patients.
Topics: Humans; Circulating Tumor DNA; Biomarkers; Combined Modality Therapy; Liver Neoplasms; Colorectal Neoplasms
PubMed: 37947598
DOI: 10.3390/cells12212520 -
Frontiers in Immunology 2023Cancer is a major global health concern, and immune checkpoint inhibitors (ICIs) offer a promising treatment option for cancer patients. However, the efficacy of ICIs...
INTRODUCTION
Cancer is a major global health concern, and immune checkpoint inhibitors (ICIs) offer a promising treatment option for cancer patients. However, the efficacy of ICIs can be influenced by various factors, including the use of concomitant medications.
METHODS
We searched databases (PubMed, Embase, Cochrane Library, Web of Science) for systematic reviews and meta-analyses for systematic reviews and meta-analyses on the impact of concomitant medications on ICIs efficacy, published from inception to January 1, 2023. We evaluated the methodological quality of the included meta-analyses, and re-synthesized data using a random-effects model and evidence stratification.
RESULTS
We included 23 publications, comprising 11 concomitant medications and 112 associations. Class II-IV evidence suggested that antibiotics have a negative impact on ICIs efficacy. However, ICIs efficacy against melanoma, hepatocellular carcinoma, and esophageal squamous cell carcinoma was not affected, this effect was related to the exposure window (class IV). Class III evidence suggested that proton pump inhibitors have a negative impact on ICIs efficacy; nevertheless, the efficacy against melanoma and renal cell carcinoma was not affected, and the effect was related to exposure before the initiation of ICIs therapy (class II). Although class II/III evidence suggested that steroids have a negative impact, this effect was not observed when used for non-cancer indications and immune-related adverse events (class IV). Class IV evidence suggested that opioids reduce ICIs efficacy, whereas statins and probiotics may improve ICIs efficacy. ICIs efficacy was not affected by histamine 2 receptor antagonists, aspirin, metformin, β-blockers, and nonsteroidal anti-inflammatory agents.
CONCLUSION
Current evidence suggests that the use of antibiotics, PPIs, steroids, and opioids has a negative impact on the efficacy of ICIs. However, this effect may vary depending on the type of tumor, the timing of exposure, and the intended application. Weak evidence suggests that statins and probiotics may enhance the efficacy of ICIs. Aspirin, metformin, β-blockers, and NSAIDs do not appear to affect the efficacy of ICIs. However, caution is advised in interpreting these results due to methodological limitations.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO,identifier, CRD42022328681.
Topics: Humans; Analgesics, Opioid; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Esophageal Neoplasms; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immune Checkpoint Inhibitors; Kidney Neoplasms; Liver Neoplasms; Melanoma; Metformin; Steroids; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 37841249
DOI: 10.3389/fimmu.2023.1218386 -
Clinical Gastroenterology and... Sep 2023Although approximately 40% of patients with nonalcoholic fatty liver disease (NAFLD) are nonobese or lean, little is known about the long-term clinical outcomes of lean... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Although approximately 40% of patients with nonalcoholic fatty liver disease (NAFLD) are nonobese or lean, little is known about the long-term clinical outcomes of lean NAFLD. We aimed to estimate the risk of mortality and adverse liver-related events in patients with lean NAFLD compared with those with non-lean NAFLD.
METHODS
We searched the PubMed, Embase, and Cochrane Library databases through May 2022 for articles reporting mortality and/or development of cirrhosis among lean and non-lean NAFLD patients. The relative risks (RRs) of all-cause mortality, cardiovascular mortality, liver-related mortality, and occurrence of decompensated cirrhosis or hepatocellular carcinoma were pooled using the random-effects model. We also performed subgroup analysis according to characteristics of the study population, methods of NAFLD diagnosis, study design, study region, and length of follow-up.
RESULTS
We analyzed 10 cohort studies involving 109,151 NAFLD patients. Patients with lean NAFLD had comparable risks for all-cause mortality (RR, 1.09; 95% confidence interval [CI], 0.66-1.90), cardiovascular mortality (RR, 1.12; 95% CI, 0.66-1.90), and adverse liver events including decompensated cirrhosis and hepatocellular carcinoma (RR, 0.81; 95% CI, 0.50-1.30). However, the risk of liver-related mortality was higher in patients with lean than non-lean NAFLD (RR, 1.88; 95% CI, 1.02-3.45).
CONCLUSIONS
This study highlights a higher risk of liver-related mortality in patients with lean NAFLD than those with non-lean NAFLD. This finding indicates that further understanding of the pathophysiology, risk factors of adverse outcomes, and genetic and ethnic variabilities of lean NAFLD phenotype is warranted for individualized treatment strategies in lean NAFLD patients.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Carcinoma, Hepatocellular; Liver Neoplasms; Cardiovascular Diseases
PubMed: 36442727
DOI: 10.1016/j.cgh.2022.11.019 -
Health Technology Assessment... Dec 2023A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and preserved liver function.
OBJECTIVE
To review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm).
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Nine databases (March 2021), two trial registries (April 2021) and reference lists of relevant systematic reviews.
REVIEW METHODS
Eligible studies were randomised controlled trials of ablative and non-surgical therapies, versus any comparator, for small hepatocellular carcinoma. Randomised controlled trials were quality assessed using the Cochrane Risk of Bias 2 tool and mapped. The comparative effectiveness of therapies was assessed using network meta-analysis. A threshold analysis was used to identify which comparisons were sensitive to potential changes in the evidence. Where comparisons based on randomised controlled trial evidence were not robust or no randomised controlled trials were identified, a targeted systematic review of non-randomised, prospective comparative studies provided additional data for repeat network meta-analysis and threshold analysis. The feasibility of undertaking economic modelling was explored. A workshop with patients and clinicians was held to discuss the findings and identify key priorities for future research.
RESULTS
Thirty-seven randomised controlled trials (with over 3700 relevant patients) were included in the review. The majority were conducted in China or Japan and most had a high risk of bias or some risk of bias concerns. The results of the network meta-analysis were uncertain for most comparisons. There was evidence that percutaneous ethanol injection is inferior to radiofrequency ablation for overall survival (hazard ratio 1.45, 95% credible interval 1.16 to 1.82), progression-free survival (hazard ratio 1.36, 95% credible interval 1.11 to 1.67), overall recurrence (relative risk 1.19, 95% credible interval 1.02 to 1.39) and local recurrence (relative risk 1.80, 95% credible interval 1.19 to 2.71). Percutaneous acid injection was also inferior to radiofrequency ablation for progression-free survival (hazard ratio 1.63, 95% credible interval 1.05 to 2.51). Threshold analysis showed that further evidence could plausibly change the result for some comparisons. Fourteen eligible non-randomised studies were identified ( ≥ 2316); twelve had a high risk of bias so were not included in updated network meta-analyses. Additional non-randomised data, made available by a clinical advisor, were also included ( = 303). There remained a high level of uncertainty in treatment rankings after the network meta-analyses were updated. However, the updated analyses suggested that microwave ablation and resection are superior to percutaneous ethanol injection and percutaneous acid injection for some outcomes. Further research on stereotactic ablative radiotherapy was recommended at the workshop, although it is only appropriate for certain patient subgroups, limiting opportunities for adequately powered trials.
LIMITATIONS
Many studies were small and of poor quality. No comparative studies were found for some therapies.
CONCLUSIONS
The existing evidence base has limitations; the uptake of specific ablative therapies in the United Kingdom appears to be based more on technological advancements and ease of use than strong evidence of clinical effectiveness. However, there is evidence that percutaneous ethanol injection and percutaneous acid injection are inferior to radiofrequency ablation, microwave ablation and resection.
STUDY REGISTRATION
PROSPERO CRD42020221357.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (NIHR award ref: NIHR131224) and is published in full in ; Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Carcinoma, Hepatocellular; Ethanol; Liver Neoplasms; Network Meta-Analysis; Prospective Studies; Randomized Controlled Trials as Topic; Ablation Techniques
PubMed: 38149643
DOI: 10.3310/GK5221 -
Pituitary Oct 2023Pituitary carcinomas are a rare entity that respond poorly to multimodal therapy. Patients follow a variable disease course that remains ill-defined.
PURPOSE
Pituitary carcinomas are a rare entity that respond poorly to multimodal therapy. Patients follow a variable disease course that remains ill-defined.
METHODS
We present an institutional case series of patients treated for pituitary carcinomas over a 30-year period from 1992 to 2022. A systematic review was conducted to identify prior case series of patients with pituitary carcinomas.
RESULTS
Fourteen patients with a mean age at pituitary carcinoma diagnosis of 52.5 years (standard deviation [SD] 19.4) met inclusion criteria. All 14 patients had tumor subtypes confirmed by immunohistochemistry and hormone testing, with the most common being ACTH-producing pituitary adenomas (n = 12). Patients had a median progression-free survival (PFS) of 1.4 years (range 0.7-10.0) and a median overall survival (OS) of 8.4 years (range 2.3-24.0) from pituitary adenoma diagnosis. Median PFS and OS were 0.6 years (range 0.0-2.2) and 1.5 years (range 0.1-9.6) respectively upon development of metastases. Most patients (n = 12) had locally invasive disease to the cavernous sinus, dorsum sellae dura, or sphenoid sinus prior to metastasis. Common sites of metastasis included the central nervous system, liver, lung, and bone. In a pooled analysis including additional cases from the literature, treatment of metastases with chemotherapy or a combination of radiation therapy and chemotherapy significantly prolonged PFS (p = 0.02), while failing to significantly improve OS (p = 0.14).
CONCLUSION
Pituitary carcinomas are highly recurrent, heterogenous tumors with variable responses to treatment. Multidisciplinary management with an experienced neuro-endocrine and neuro-oncology team is needed given the unrelenting nature of this disease.
Topics: Humans; Pituitary Neoplasms; Neoplasm Recurrence, Local; Adenoma; ACTH-Secreting Pituitary Adenoma; Pituitary Gland
PubMed: 37523025
DOI: 10.1007/s11102-023-01341-4 -
Cancer Epidemiology, Biomarkers &... Jul 2023Sex hormones may influence the development of gastrointestinal cancer, but evidence is inconsistent. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sex hormones may influence the development of gastrointestinal cancer, but evidence is inconsistent.
METHODS
We systematically searched MEDLINE and Embase databases to identify prospective studies examining associations between prediagnostic circulating levels of sex hormones and risk of five gastrointestinal cancers: esophageal, gastric, liver, pancreatic, and colorectal cancer. Pooled ORs and 95% confidence intervals (95% CI) were calculated using random-effects models.
RESULTS
Among 16,879 identified studies, 29 were included (11 cohort, 15 nested case-control, and three case-cohort studies). Comparing the highest versus lowest tertiles, levels of most sex hormones were not associated with the studied tumors. Higher levels of sex hormone binding globulin (SHBG) were associated with increased risk of gastric cancer (OR = 1.35; 95% CI, 1.06-1.72), but such associations were restricted in men only (OR = 1.43; 95% CI, 1.10-1.85) when stratified by sex. Higher SHBG levels were associated with increased risk of liver cancer (OR = 2.07; 95% CI, 1.40-3.06). Higher testosterone levels were associated with increased risk of liver cancer overall (OR = 2.10; 95% CI, 1.48-2.96), particularly in men (OR = 2.63; 95% CI, 1.65-4.18), Asian populations (OR = 3.27; 95% CI, 1.57-6.83), and in hepatitis B surface antigen-positive individuals (OR = 3.90; 95% CI, 1.43-10.64). Higher levels of SHBG and testosterone were associated with decreased risk of colorectal cancer in men (OR = 0.89; 95% CI, 0.80-0.98 and OR = 0.88; 95% CI, 0.80-0.97, respectively) but not in women.
CONCLUSIONS
Circulating levels of SHBG and testosterone may influence the risk of gastric, liver, and colorectal cancer.
IMPACT
Further clarifying the role of sex hormones in the development of gastrointestinal cancer may unravel future novel targets for prevention and treatment.
Topics: Male; Humans; Female; Prospective Studies; Risk Factors; Gonadal Steroid Hormones; Testosterone; Gastrointestinal Neoplasms; Liver Neoplasms; Colorectal Neoplasms; Sex Hormone-Binding Globulin; Estradiol
PubMed: 37104672
DOI: 10.1158/1055-9965.EPI-23-0039 -
Hepatology (Baltimore, Md.) May 2024Studies have suggested that patients with chronic hepatitis B, either co- or superinfected, have more aggressive liver disease progression than those with the HDV. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Studies have suggested that patients with chronic hepatitis B, either co- or superinfected, have more aggressive liver disease progression than those with the HDV. This systematic literature review and meta-analysis examined whether HDV RNA status is associated with increased risk of advanced liver disease events in patients who are HBsAg and HDV antibody positive.
APPROACH AND RESULTS
A total of 12 publications were included. Relative rates of progression to advanced liver disease event for HDV RNA+/detectable versus HDV RNA-/undetectable were extracted for analysis. Reported OR and HRs with 95% CI were pooled using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. The presence of HDV RNA+ was associated with an increased risk of any advanced liver disease event [random effect (95% CI): risk ratio: 1.48 (0.93, 2.33); HR: 2.62 (1.55, 4.44)]. When compared to the patients with HDV RNA- status, HDV RNA+ was associated with a significantly higher risk of progressing to compensated cirrhosis [risk ratio: 1.74 (1.24, 2.45)] decompensated cirrhosis [HR: 3.82 (1.60, 9.10)], HCC [HR: 2.97 (1.87, 4.70)], liver transplantation [HR: 7.07 (1.61, 30.99)], and liver-related mortality [HR: 3.78 (2.18, 6.56)].
CONCLUSIONS
The patients with HDV RNA+ status have a significantly greater risk of liver disease progression than the patients who are HDV RNA-. These findings highlight the need for improved HDV screening and linkage to treatment to reduce the risk of liver-related morbidity and mortality.
Topics: Humans; Hepatitis Delta Virus; Carcinoma, Hepatocellular; Liver Neoplasms; Hepatitis B Surface Antigens; Liver Cirrhosis; Morbidity; RNA, Viral; Disease Progression; Hepatitis B virus
PubMed: 37870278
DOI: 10.1097/HEP.0000000000000642 -
Surgical Oncology Dec 2023Surgical resection is the cornerstone of treatment for metastatic colorectal cancer (CRC) and offers the best chance at long-term survival. Unfortunately, most patients... (Review)
Review
Surgical resection is the cornerstone of treatment for metastatic colorectal cancer (CRC) and offers the best chance at long-term survival. Unfortunately, most patients do not present with resectable metastatic disease and, among patients who do undergo curative-intent resection, many will develop recurrence. In turn, patients require a multi-disciplinary treatment approach with a combination of chemotherapy, surgery, radiation, and/or liver directed therapies that is guided by patient disease burden and clinical status. The development of targeted therapies has led to varying success in other cancers and has emerged as a treatment option for patients with metastatic CRC. While cytotoxic chemotherapy aims to kill cells as they replicate, targeted therapies are directed at biologic features of cancers, like angiogenesis or immune checkpoints. Targeted therapy can facilitate a more treatment tailored approach to the unique genomic alterations of the tumor and hopefully deliver more personalized therapy. We herein provide a systematic review of approved targeted therapies and immune checkpoint inhibitors for metastatic CRC and provide an overview of the current literature.
Topics: Humans; Immune Checkpoint Inhibitors; Rectal Neoplasms; Colonic Neoplasms; Immunotherapy; Colorectal Neoplasms
PubMed: 37742544
DOI: 10.1016/j.suronc.2023.101993 -
Cells Aug 2023Immunotherapy has recently been incorporated into the spectrum of biliary tract cancer (BTC) treatment. The identification of predictive response biomarkers is essential... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immunotherapy has recently been incorporated into the spectrum of biliary tract cancer (BTC) treatment. The identification of predictive response biomarkers is essential in order to identify those patients who may benefit most from this novel treatment option. Here, we propose a systematic literature review and a meta-analysis of PD-1, PD-L1, and other immune-related biomarker expression levels in patients with BTC.
METHODS
Prisma guidelines were followed for this systematic review and meta-analysis. Eligible studies were searched on PubMed. Studies published between 2017 and 2022, reporting data on PD-1/PD-L1 expression and other immune-related biomarkers in patients with BTC, were considered eligible.
RESULTS
A total of 61 eligible studies were identified. Despite the great heterogeneity between 39 studies reporting data on PD-L1 expression, we found a mean PD-L1 expression percentage (by choosing the lowest cut-off per study) of 25.6% (95% CI 21.0 to 30.3) in BTCs. The mean expression percentages of PD-L1 were 27.3%, 21.3%, and 27.4% in intrahepatic cholangiocarcinomas (iCCAs-15 studies), perihilar-distal CCAs (p/dCCAs-7 studies), and gallbladder cancer (GBC-5 studies), respectively. Furthermore, 4.6% (95% CI 2.38 to 6.97) and 2.5% (95% CI 1.75 to 3.34) of BTCs could be classified as TMB-H and MSI/MMRd tumors, respectively.
CONCLUSION
From our analysis, PD-L1 expression was found to occur approximately in 26% of BTC patients, with minimal differences based on anatomical location. TMB-H and MSI molecular phenotypes occurred less frequently. We still lack a reliable biomarker, especially in patients with mismatch-proficient tumors, and we must need to make an effort to conceive new prospective biomarker discovery studies.
Topics: Humans; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Biliary Tract Neoplasms; Immunotherapy; Biomarkers; Bile Duct Neoplasms; Bile Ducts, Intrahepatic
PubMed: 37626908
DOI: 10.3390/cells12162098