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Annals of Medicine Dec 2023We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy.
MATERIALS AND METHODS
We systematically searched three databases (PubMed, Web of Science and Embase) up to 20 February 2023. Extracting the effect size and 95% confidence intervals for overall survival (OS), progression-free survival (PFS) and the objective response rate (ORR).
RESULTS
A total of 65 articles were included. We identified the following factors that benefit ICI therapy: smoking status (PFS: 0.72 [0.62, 0.84], < .001), chemotherapy (PFS: 0.68 [0.58, 0.79], < .001), expression of programmed cell death ligand 1(PD-L1) (≥1%, ≥5%, or ≥10%) (≥1%: 0.76 [0.71,0.82], < .001; ≥5%: 0.62 [0.52, 0.74], < .001; ≥10%: 0.42 [0.30, 0.59], < .001). We also identified three adverse factors: epidermal growth factor receptor mutations (OS: 1.57 [1.06, 2.32], = .02), with liver metastases (OS: 1.16 [1.02,1.32], = .02) and antibiotics (OS: 3.13 [1.25,7.84], < .001; PFS: 2.54 [1.38, 4.68], = .003).
CONCLUSION
The results of this umbrella meta-analysis first supported pre-existing understandings of the relationship between beneficial and adverse factors with the efficacy of ICI therapy. In addition, the overexpression of PD-L1 may adversely affect patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; B7-H1 Antigen; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Randomized Controlled Trials as Topic
PubMed: 37212453
DOI: 10.1080/07853890.2023.2215543 -
Frontiers in Immunology 2023Our study represents the first meta-analysis conducted to evaluate the prognostic utility of the baseline prognostic nutritional index (PNI) in patients with... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Our study represents the first meta-analysis conducted to evaluate the prognostic utility of the baseline prognostic nutritional index (PNI) in patients with gastrointestinal cancer (GIC) who received immune checkpoint inhibitor (ICI) therapy.
METHODS
We searched PubMed, the Cochrane Library, EMBASE, and Google Scholar until April 23, 2023, to obtain relevant articles for this study. Our analysis examined several clinical outcomes, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR).
RESULTS
In this analysis, a total of 17 articles with 2883 patients were included. Our pooled results indicated that patients with high PNI levels had longer OS (HR: 0.530, 95% CI: 0.456-0.616, < 0.001) and PFS (HR: 0.740, 95% CI: 0.649-0.844, < 0.001), as well as higher ORR (OR: 1.622, 95% CI: 1.251-2.103, < 0.004) and DCR (OR: 1.846, 95% CI: 1.428-2.388, < 0.001). Subgroup analysis showed that PNI cutoff values of 40 to 45 showed greater predictive potential. Subgroup analysis also confirmed that the above findings still hold true in patients with esophageal cancer, gastric cancer, and hepatocellular carcinomas.
CONCLUSION
The PNI were reliable predictors of outcomes in GIC patients treated with ICIs.
Topics: Humans; Immune Checkpoint Inhibitors; Nutrition Assessment; Prognosis; Gastrointestinal Neoplasms; Liver Neoplasms; Biomarkers
PubMed: 37545502
DOI: 10.3389/fimmu.2023.1219929 -
Alimentary Pharmacology & Therapeutics May 2024The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may eventually lead to cirrhosis and hepatocellular carcinoma (HCC). These are important causes of morbidity and mortality in these patients. We performed a systematic review and meta-analysis to assess the incidence of cirrhosis and HCC in Fontan patients and stratify it based on time since surgery.
METHODS
A literature search of seven databases identified 1158 records. Studies reporting the number of cirrhosis and HCC cases in Fontan patients and time since Fontan surgery were included. In the cirrhosis cohort, we included only those studies where all patients underwent liver biopsy.
RESULTS
A total of 23 studies were included: 12 and 13 studies in the cirrhosis and HCC cohorts, respectively, with two studies included in both cohorts. The incidence of cirrhosis was 0.97 per 100 patient-years (95% CI 0.57-1.63), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 1.61 per 100 patient-years (95% CI 1.24-2.08) and 32.2% (95% CI 25.8%-39.4%), respectively. The incidence of HCC was 0.12 per 100 patient-years (95% CI 0.07-0.21), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 0.20 per 100 patient-years (95% CI 0.12-0.35) and 3.9% (95% CI 2.2%-6.8%), respectively. Only about 70% of patients with HCC (20/28) had underlying cirrhosis.
CONCLUSION
The incidence of cirrhosis and HCC increases over time, especially at ≥20 years post Fontan surgery. Studies are needed to further identify at-risk patients in order to streamline surveillance for these highly morbid conditions.
Topics: Child; Humans; Carcinoma, Hepatocellular; Incidence; Liver Neoplasms; Fontan Procedure; Liver Cirrhosis; Risk Factors
PubMed: 38497159
DOI: 10.1111/apt.17952 -
Clinical and Molecular Hepatology Apr 2024Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events. (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events.
METHODS
We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events.
RESULTS
19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05).
CONCLUSION
People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.
Topics: Adult; Humans; Middle Aged; Non-alcoholic Fatty Liver Disease; Incidence; Carcinoma, Hepatocellular; Metabolic Syndrome; Liver Neoplasms; Liver Cirrhosis; Fibrosis; Hypertension; Cardiovascular Diseases
PubMed: 38281814
DOI: 10.3350/cmh.2023.0485 -
Clinics and Research in Hepatology and... Aug 2023To study the efficacy of microwave ablation (MWA) and radiofrequency ablation (RFA) for colorectal liver metastases (CRLM) by meta-analysis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To study the efficacy of microwave ablation (MWA) and radiofrequency ablation (RFA) for colorectal liver metastases (CRLM) by meta-analysis.
METHODS
PubMed, Web of Science, Embase, CNKI and the Cochrane Library were searched from the establishment to May 2023, and studies that report outcomes with comparison between MWA and RFA in CRLM treatment were selected by inclusion and exclusion criteria. Furthermore, the perioperative and survival data were statistically summarized and analyzed by Review Manager 5.4.
RESULTS
Five studies (MWA: 316 patients; RFA: 332 patients) were evaluated. The results of meta-analysis showed that local tumor progression in MWA group was significantly lower than that in RFA group (P < 0.05). The1-year and 2-year disease-free survival (DFS) of the MWA group was significantly better than that of the RFA group with HR of 1.77 (95% CI: 1.04-3.02; P = 0.04) and1.60 (95% CI: 1.09-2.35; P = 0.02), respectively.
CONCLUSION
The local tumor progression and 1-year and 2-year DFS of MWA were superior to RFA. The included articles were retrospective, offering low-quality evidence and limited conclusions.
Topics: Humans; Retrospective Studies; Microwaves; Treatment Outcome; Radiofrequency Ablation; Liver Neoplasms; Colorectal Neoplasms; Catheter Ablation; Carcinoma, Hepatocellular
PubMed: 37479137
DOI: 10.1016/j.clinre.2023.102182 -
BMC Cancer Aug 2023The association between gastrointestinal cancer and types of meat consumption, including red meat, processed meat, or a combination of both, remains disputable.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The association between gastrointestinal cancer and types of meat consumption, including red meat, processed meat, or a combination of both, remains disputable. Therefore, we performed a systematic review and meta-analysis of prospective cohort studies to estimate the association between meat consumption and gastrointestinal cancer risk.
METHODS
PubMed, EmBase, and the Cochrane library databases were searched systematically for eligible studies that investigated the relation between meat consumption and the risk of developing gastrointestinal cancers, including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), colon cancer (CC), rectal cancer (RC), pancreatic cancer (PC), and hepatocellular carcinoma (HCC) throughout February, 2023. The pooled relative risk (RR) with 95% confidence interval (CI) was assigned as an effect estimate and calculated using a random-effects model with inverse variance weighting.
RESULTS
Forty cohorts comprising 3,780,590 individuals were selected for the final quantitative analysis. The summary results indicated that a higher red meat consumption was associated with an increased risk of CRC (RR: 1.09; 95% CI: 1.02-1.16; P = 0.007) and CC (RR: 1.13; 95% CI: 1.03-1.25; P = 0.011). Moreover, a higher processed meat consumption was associated with an increased risk of CRC (RR: 1.19; 95% CI: 1.13-1.26; P < 0.001), CC (RR: 1.24; 95% CI: 1.13-1.26; P < 0.001), and RC (RR: 1.24; 95% CI: 1.08-1.42; P = 0.002). Furthermore, a higher total consumption of red and processed meat was associated with an increased risk of CRC (RR: 1.13; 95% CI: 1.06-1.20; P < 0.001), CC (RR: 1.17; 95% CI: 1.04-1.33; P = 0.012), and RC (RR: 1.20; 95% CI: 1.04-1.39; P = 0.016). Finally, the strength of higher consumption of total red and processed meat with the risk of GC, and higher consumption of red meat with the risk of RC in subgroup of high adjusted level was lower than subgroup of moderate adjusted level, while the strength of higher consumption of processed meat with the risk of RC and HCC in subgroup of follow-up ≥ 10.0 years was higher than subgroup of follow-up < 10.0 years.
CONCLUSIONS
This study found that meat consumption was associated with an increased risk of CRC, CC, and RC, and dietary intervention could be considered an effective strategy in preventing CRC.
Topics: Humans; Carcinoma, Hepatocellular; Prospective Studies; Liver Neoplasms; Gastrointestinal Neoplasms; Stomach Neoplasms; Meat; Colonic Neoplasms
PubMed: 37612616
DOI: 10.1186/s12885-023-11218-1 -
Surgical Endoscopy Dec 2023Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the liver's two most common malignant neoplasms. Liver-directed therapies such as...
SAGES/AHPBA guidelines for the use of microwave and radiofrequency liver ablation for the surgical treatment of hepatocellular carcinoma or colorectal liver metastases less than 5 cm.
BACKGROUND
Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the liver's two most common malignant neoplasms. Liver-directed therapies such as ablation have become part of multidisciplinary therapies despite a paucity of data. Therefore, an expert panel was convened to develop evidence-based recommendations regarding the use of microwave ablation (MWA) and radiofrequency ablation (RFA) for HCC or CRLM less than 5 cm in diameter in patients ineligible for other therapies.
METHODS
A systematic review was conducted for six key questions (KQ) regarding MWA or RFA for solitary liver tumors in patients deemed poor candidates for first-line therapy. Subject experts used the GRADE methodology to formulate evidence-based recommendations and future research recommendations.
RESULTS
The panel addressed six KQs pertaining to MWA vs. RFA outcomes and laparoscopic vs. percutaneous MWA. The available evidence was poor quality and individual studies included both HCC and CRLM. Therefore, the six KQs were condensed into two, recognizing that these were two disparate tumor groups and this grouping was somewhat arbitrary. With this significant limitation, the panel suggested that in appropriately selected patients, either MWA or RFA can be safe and feasible. However, this recommendation must be implemented cautiously when simultaneously considering patients with two disparate tumor biologies. The limited data suggested that laparoscopic MWA of anatomically more difficult tumors has a compensatory higher morbidity profile compared to percutaneous MWA, while achieving similar overall 1-year survival. Thus, either approach can be appropriate depending on patient-specific factors (very low certainty of evidence).
CONCLUSION
Given the weak evidence, these guidelines provide modest guidance regarding liver ablative therapies for HCC and CRLM. Liver ablation is just one component of a multimodal approach and its use is currently limited to a highly selected population. The quality of the existing data is very low and therefore limits the strength of the guidelines.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Microwaves; Catheter Ablation; Treatment Outcome; Radiofrequency Ablation; Colorectal Neoplasms; Retrospective Studies
PubMed: 37957297
DOI: 10.1007/s00464-023-10468-1 -
United European Gastroenterology Journal Oct 2023Transjugular intrahepatic portosystemic shunts (TIPS) in patients with hepatocellular carcinoma (HCC) may improve access to curative therapies, treat portal hypertension...
BACKGROUND/AIMS
Transjugular intrahepatic portosystemic shunts (TIPS) in patients with hepatocellular carcinoma (HCC) may improve access to curative therapies, treat portal hypertension (PH)-related complications without worsening liver function, and increase overall survival. Data on the efficacy and safety of TIPS to treat PH complications in HCC patients, as well as the HCC treatment response, were evaluated.
METHODS
Studies reporting efficacy in controlling bleeding/ascites or response to HCC therapy, safety, and survival in patients with HCC and TIPS were searched systematically on PubMed and Embase. An extraction of articles using predefined data fields and quality indicators was used.
RESULTS
We selected 19 studies and found 937 patients treated for ascites/bleeding and 177 evaluating HCC treatment response. Over half were under 5 cm and solitary lesions, and most studies included tumours with portal vein thrombosis. Regarding PH studies, TIPS resolved bleeding/ascites in >60% of patients, more effective for bleeding. There were no lethal complications reported and procedural bleeding occurred in <5%. Hepatic encephalopathy occurred in 15%-30% within three months. In the HCC treatment-response studies, major complication rates were low with no mortality. In the studies that evaluated the response to transarterial chemoembolization, complete response rate of patients with TIPS varied from 16% to 75%. Liver transplantation rate varied from 8% to 80%, with >40% rate in half of the studies.
CONCLUSIONS
In the published studies, TIPS is effective in treating PH complications in patients with HCC. Prospective studies on TIPS placement in patients with HCC are urgently needed to evaluate the efficacy and safety of TIPS in this setting.
Topics: Humans; Carcinoma, Hepatocellular; Portasystemic Shunt, Transjugular Intrahepatic; Liver Neoplasms; Ascites; Prospective Studies; Esophageal and Gastric Varices; Treatment Outcome; Chemoembolization, Therapeutic; Hypertension, Portal
PubMed: 37736854
DOI: 10.1002/ueg2.12454 -
European Review For Medical and... Dec 2023This study aimed to systematically review and quantitatively synthesize the existing evidence to better identify the high-risk population of hepatocellular carcinoma... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to systematically review and quantitatively synthesize the existing evidence to better identify the high-risk population of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease (NAFLD).
MATERIALS AND METHODS
We searched databases including MEDLINE, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov up to February 2023. The meta-analysis was performed using RevMan5.3 software, and we calculated the estimated combined effect using inverse variance weighting of OR. I2 statistics were used to quantify the inter-study heterogeneity. Funnel plots and Egger test were used to assess publication bias, and sensitivity analysis was carried out through the transformation effect model or the removal of literature one by one.
RESULTS
Finally, 29 articles were included in the study, which involved a total of 726,656 patients with NAFLD. A total of 15 major risk factors were evaluated. Statistically significant risk factors were: advanced liver fibrosis (OR=6.40), diabetes (OR=2.38), obesity (OR=1.46), hypertension (OR=1.75), older age (OR=3.57), male (OR=2.45), alcohol intake (OR=2.98), smoking (OR=1.44), PNPLA3 genotype variation (OR=1.76), elevated liver enzymes (OR=2.92), low platelet counts (OR=4.61), and low albumin levels (OR=2.11).
CONCLUSIONS
Our results showed that advanced liver fibrosis, diabetes, obesity, hypertension, older age, male, alcohol intake, smoking, PNPLA3 genotype variation, elevated liver enzymes, low platelet counts, and low albumin levels were all significant risk factors for HCC in NAFLD. However, dyslipidemia was not found to be a risk factor. Further exploration is needed to confirm whether Hispanic ethnicity and high ferritin levels are also risk factors.
Topics: Humans; Male; Albumins; Carcinoma, Hepatocellular; Diabetes Complications; Hypertension; Liver Cirrhosis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease; Obesity; Risk Factors; Female; Sex Factors
PubMed: 38164853
DOI: 10.26355/eurrev_202312_34788 -
Journal For Immunotherapy of Cancer Jan 2024Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can...
Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can overstimulate the patient's immune system, leading to potentially severe immune-related adverse events (irAEs), including hepatitis, colitis, pneumonitis and myocarditis. The initial mainstay of treatments includes the administration of corticosteroids. There is little evidence how to treat steroid-resistant (sr) irAEs. It is mainly based on small case series or single case reports. This systematic review summarizes available evidence about sr-irAEs. We conducted a systematic literature search in PubMed. Additionally, we included European Society for Medical Oncology, Society for Immunotherapy of Cancer, National Comprehensive Cancer Network and American Society of Clinical Oncology Guidelines for irAEs in our assessment. The study population of all selected publications had to include patients with cancer who developed hepatitis, colitis, pneumonitis or myocarditis during or after an immunotherapy treatment and for whom corticosteroid therapy was not sufficient. Our literature search was not restricted to any specific cancer diagnosis. Case reports were also included. There is limited data regarding life-threatening sr-irAEs of colon/liver/lung/heart and the majority of publications are single case reports. Most publications investigated sr colitis (n=26), followed by hepatitis (n=21), pneumonitis (n=17) and myocarditis (n=15). There is most data for mycophenolate mofetil (MMF) to treat sr hepatitis and for infliximab, followed by vedolizumab, to treat sr colitis. Regarding sr pneumonitis there is most data for MMF and intravenous immunoglobulins (IVIG) while data regarding infliximab are conflicting. In sr myocarditis, most evidence is available for the use of abatacept or anti-thymocyte globulin (ATG) (both with or without MMF) or ruxolitinib with abatacept. This review highlights the need for prompt recognition and treatment of sr hepatitis, colitis, pneumonitis and myocarditis. Guideline recommendations for sr situations are not defined precisely. Based on our search, we recommend-as first line treatment-(1) MMF for sr hepatitis, (2) infliximab for sr colitis, followed by vedolizumab, (3) MMF and IVIG for sr pneumonitis and (4) abatacept or ATG (both with or without MMF) or ruxolitinib with abatacept for sr myocarditis. These additional immunosuppressive agents should be initiated promptly if there is no sufficient response to corticosteroids within 3 days.
Topics: Humans; Abatacept; Adrenal Cortex Hormones; Colitis; Hepatitis; Immunoglobulins, Intravenous; Infliximab; Mycophenolic Acid; Myocarditis; Neoplasms; Nitriles; Pneumonia; Pyrazoles; Pyrimidines
PubMed: 38233099
DOI: 10.1136/jitc-2023-007409