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Clinical Epigenetics Jun 2024Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a... (Review)
Review
BACKGROUND
Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a pivotal role in immune surveillance, orchestrating the recognition and elimination of tumor cells by the immune system. However, the intricate regulation of MHC gene expression is susceptible to dynamic epigenetic modification, which can influence functionality and pathological outcomes.
MAIN BODY
By understanding the epigenetic alterations that drive MHC downregulation, insights are gained into the molecular mechanisms underlying immune escape, tumor progression, and immunotherapy resistance. This systematic review examines the current literature on epigenetic mechanisms that contribute to MHC deregulation in esophageal, gastric, pancreatic, hepatic and colorectal malignancies. Potential clinical implications are discussed of targeting aberrant epigenetic modifications to restore MHC expression and 0 the effectiveness of immunotherapeutic interventions.
CONCLUSION
The integration of epigenetic-targeted therapies with immunotherapies holds great potential for improving clinical outcomes in patients with gastrointestinal malignancies and represents a compelling avenue for future research and therapeutic development.
Topics: Humans; Gastrointestinal Neoplasms; Epigenesis, Genetic; Major Histocompatibility Complex; Gene Expression Regulation, Neoplastic; Immunotherapy; DNA Methylation; Tumor Escape
PubMed: 38915093
DOI: 10.1186/s13148-024-01698-8 -
International Journal of Surgery... Dec 2023
Meta-Analysis
Comment on 'Effect of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on survival and recurrence rates in advanced gastric cancer - a systematic review and meta-analysis'.
Topics: Humans; Hyperthermic Intraperitoneal Chemotherapy; Stomach Neoplasms; Combined Modality Therapy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37678282
DOI: 10.1097/JS9.0000000000000679 -
BMC Cancer Feb 2024Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients. In this meta-analysis, we aimed to assess the outcome of temozolomide, alone or in combination with other anticancer medications in patients with advanced pNET.
METHODS
Online databases of PubMed, Web of Science, Embase, the Cochrane Library, and ClinicalTrials.gov were searched systematically for clinical trials that reported the efficacy and safety of temozolomide in patients with advanced pNET. Random-effect model was utilized to estimate pooled rates of outcomes based on Response Evaluation Criteria in Solid Tumors criteria, biochemical response, and adverse events (AEs).
RESULTS
A total of 14 studies, providing details of 441 individuals with advanced pNET, were included. The quantitative analyses showed a pooled objective response rate (ORR) of 41.2% (95% confidence interval, CI, of 32.4%-50.6%), disease control rate (DCR) of 85.3% (95% CI of 74.9%-91.9%), and a more than 50% decrease from baseline chromogranin A levels of 44.9% (95% CI of 31.6%-49.0%). Regarding safety, the results showed that the pooled rates of nonserious AEs and serious AEs were 93.8% (95% CI of 88.3%-96.8%) and 23.7% (95% CI of 12.0%-41.5%), respectively. The main severe AEs encompassed hematological toxicities.
CONCLUSIONS
In conclusion, our meta-analysis suggests that treatment with temozolomide, either as a monotherapy or in combination with other anticancer treatments might be an effective and relatively safe option for patients with advanced locally unresectable and metastatic pNET. However, additional clinical trials are required to further strengthen these findings. This study has been registered in PROSPERO (CRD42023409280).
Topics: Humans; Temozolomide; Neuroendocrine Tumors; Response Evaluation Criteria in Solid Tumors; Pancreatic Neoplasms; Neuroectodermal Tumors, Primitive
PubMed: 38347461
DOI: 10.1186/s12885-024-11926-2 -
Journal of Clinical Medicine Jan 2024Patients who undergo resection for non-invasive IPMN are at risk for long-term recurrence. Further evidence is needed to identify evidence-based surveillance strategies... (Review)
Review
Patients who undergo resection for non-invasive IPMN are at risk for long-term recurrence. Further evidence is needed to identify evidence-based surveillance strategies based on the risk of recurrence. We performed a systematic review of the current literature regarding recurrence patterns following resection of non-invasive IPMN to summarize evidence-based recommendations for surveillance. Among the 61 studies reviewed, a total of 8779 patients underwent resection for non-invasive IPMN. The pooled overall median follow-up time was 49.5 months (IQR: 38.5-57.7) and ranged between 14.1 months and 114 months. The overall median recurrence rate for patients with resected non-invasive IPMN was 8.8% (IQR: 5.0, 15.6) and ranged from 0% to 27.6%. Among the 33 studies reporting the time to recurrence, the overall median time to recurrence was 24 months (IQR: 17, 46). Existing literature on recurrence rates and post-resection surveillance strategies for patients with resected non-invasive IPMN varies greatly. Patients with resected non-invasive IPMN appear to be at risk for long-term recurrence and should undergo routine surveillance.
PubMed: 38337524
DOI: 10.3390/jcm13030830 -
Journal of the ASEAN Federation of... 2024Insulinoma is one of the causes of recurrent hypoglycemia, one of the chief complaints for emergency department admission. The gold standard in diagnosing insulinoma is... (Review)
Review
BACKGROUND
Insulinoma is one of the causes of recurrent hypoglycemia, one of the chief complaints for emergency department admission. The gold standard in diagnosing insulinoma is a 72-hour fasting test which is inconvenient and inefficient as it requires hospitalization. Research has found that measurement of insulin and C-peptide during OGTT may help diagnose insulinoma. We aimed to assess the diagnostic value of OGTT in diagnosing insulinoma.
METHODOLOGY
The literature search was conducted on 19 August 2022 using several databases (MEDLINE, Scopus, Embase, and ScienceDirect). All studies that measured OGTT as diagnostic tools in diagnosing insulinoma and 72-hour fasting test as reference standard were included. The quality assessment of the selected studies was based on the Centre of Evidence-Based Medicine University of Oxford and the Quality Assessment of Diagnostic Accuracy-2 tool (QUADAS-2). Analysis of the included studies was performed qualitatively. This study was registered on PROSPERO (CRD42022360205).
RESULTS
A total of two case-control studies (106 patients) were included, which were at risk of bias and low concern of applicability. Both studies demonstrated that the combination of insulin and C-peptide levels measured during OGTT had high specificity, sensitivity, positive predictive value, and negative predictive value in diagnosing insulinoma compared to the reference standard. A logistic regression model of 8.305 - (0.441 × insulin 2-h/0-h) - (1.679 × C-peptide 1-h/0-h) >0.351 has the highest diagnostic value in one study (AUC 0.97, Sensitivity 86.5%, Specificity 95.2%, PPV 94.1, NPV 88.9).
CONCLUSION
The measurement of 0-h and 2-h insulin and C-peptide levels during 2-h OGTT was found in two small case-control studies with a total of 106 patients to have good sensitivity and specificity. However, due to these limitations, future research is still needed to validate the potential use of OGTT for the diagnosis of insulinoma.
Topics: Humans; C-Peptide; Insulinoma; Glucose Tolerance Test; Pancreatic Neoplasms; Insulin; Sensitivity and Specificity; Insulin Secretion
PubMed: 38863915
DOI: 10.15605/jafes.039.01.16 -
International Journal of Surgery... Jan 2024Hilar cholangiocarcinoma (HCCA) is widely considered to have a poor prognosis. In particular, combined caudate lobe resection (CLR) as a strategy for radical resection...
Hilar cholangiocarcinoma (HCCA) is widely considered to have a poor prognosis. In particular, combined caudate lobe resection (CLR) as a strategy for radical resection in HCCA is important for improving the R0 resection rate. However, the criteria for R0 resection, necessity of CLR, optimal extent of hepatic resection, and surgical approach are still controversial. This review aimed to summarize the findings and discuss the controversies surrounding CLR. Numerous clinical studies have shown that combined CLR treatment for HCCA improves the R0 resection rate and postoperative survival time. Whether surgery for Bismuth type I or II is combined with CLR depends on the pathological type. Considering the anatomical factors, total rather than partial CLR is recommended to achieve a higher R0 resection rate. In the resection of HCCA, a proximal ductal margin greater than or equal to 10 mm should be achieved to obtain a survival benefit. Although there is no obvious boundary between the right side (especially the paracaval portion) and the right posterior lobe of the liver, Peng's resection line can serve as a reference marker for right-sided resection. Laparoscopic resection of the caudate lobe may be safer, more convenient, accurate, and minimally invasive than open surgery, but it needs to be completed by experienced laparoscopic doctors.
Topics: Humans; Klatskin Tumor; Cholangiocarcinoma; Hepatectomy; Bile Duct Neoplasms; Liver; Bile Ducts, Intrahepatic; Treatment Outcome; Retrospective Studies
PubMed: 37738006
DOI: 10.1097/JS9.0000000000000795 -
World Journal of Gastroenterology Mar 2024Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer; however, the superiority of neoadjuvant chemotherapy (nCT) or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer; however, the superiority of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) is unclear. Therefore, a discussion of these two modalities is necessary.
AIM
To investigate the benefits and complications of neoadjuvant modalities.
METHODS
To address this concern, predefined criteria were established using the PICO protocol. Two independent authors performed comprehensive searches using predetermined keywords. Statistical analyses were performed to identify significant differences between groups. Potential publication bias was visualized using funnel plots. The quality of the data was evaluated using the Risk of Bias Tool 2 (RoB2) and the GRADE approach.
RESULTS
Ten articles, including 1928 patients, were included for the analysis. Significant difference was detected in pathological complete response (pCR) [ < 0.001; odds ratio (OR): 0.27; 95%CI: 0.16-0.46], 30-d mortality ( = 0.015; OR: 0.4; 95%CI: 0.22-0.71) favoring the nCRT, and renal failure ( = 0.039; OR: 1.04; 95%CI: 0.66-1.64) favoring the nCT. No significant differences were observed in terms of survival, local or distal recurrence, or other clinical or surgical complications. The result of RoB2 was moderate, and that of the GRADE approach was low or very low in almost all cases.
CONCLUSION
Although nCRT may have a higher pCR rate, it does not translate to greater long-term survival. Moreover, nCRT is associated with higher 30-d mortality, although the specific cause for postoperative complications could not be identified. In the case of nCT, toxic side effects are suspected, which can reduce the quality of life. Given the quality of available studies, further randomized trials are required.
Topics: Humans; Neoadjuvant Therapy; Quality of Life; Adenocarcinoma; Chemoradiotherapy; Esophageal Neoplasms
PubMed: 38617451
DOI: 10.3748/wjg.v30.i11.1621 -
Experimental and Therapeutic Medicine Mar 2024Hepatocellular carcinoma (HCC) remains an important complication in patients with chronic hepatitis B (CHB). An association between the presence of metabolic...
Effect of metabolic dysfunction‑associated fatty liver disease on the risk of hepatocellular carcinoma in patients with chronic hepatitis B: A systematic review and meta‑analysis.
Hepatocellular carcinoma (HCC) remains an important complication in patients with chronic hepatitis B (CHB). An association between the presence of metabolic dysfunction-associated fatty liver disease (MAFLD) and an increased HCC risk in patients with CHB may exist; however, the exact nature of this possible association remains unclear. The present study conducted a comprehensive meta-analysis by pooling data from 18 studies encompassing 23,927 participants. The odds ratios (ORs) were calculated using a random-effects inverse-variance model, and heterogeneity was assessed using Cochran's Q test and the I² statistic. In addition, subgroup analyses were performed on the basis of geographical region, study design and follow-up length. Publication bias and meta-regression were also assessed. The overall pooled OR for the association between MAFLD and HCC risk in patients with CHB was 1.053 (95% CI, 0.704-1.576), which suggested a lack of association. Heterogeneity was observed across studies. Subgroup analyses demonstrated a potentially protective effect for MAFLD on the risk of HCC in patients in Asian countries (OR, 0.783; 95% CI, 0.568-1.080) and the opposite effect in other regions (OR, 4.380; 95% CI, 2.440-7.864). Analysis of the prospective cohort studies suggested a significant protective effect for MAFLD (OR, 0.479; 95% CI, 0.365-0.629), while analysis of retrospective cohorts did not. The publication bias assessment was inconclusive and the meta-regression failed to identify heterogeneity sources. The association between MAFLD and HCC risk in patients with CHB appeared to be multifactorial and may vary on the basis of geographical region and study design. While the exact mechanisms remain elusive, the potential protective effect demonstrated in certain subgroups warrants further investigation.
PubMed: 38356666
DOI: 10.3892/etm.2024.12387 -
Cirugia Y Cirujanos 2024The effect of a pre-operative biliary stent on complications after pancreaticoduodenectomy (PD) remains controversial. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The effect of a pre-operative biliary stent on complications after pancreaticoduodenectomy (PD) remains controversial.
MATERIALS AND METHOD
We conducted a meta-analysis according to the preferred reporting items for systematic reviews and meta-analyses guidelines, and PubMed, Web of Science Knowledge, and Ovid's databases were searched by the end of February 2023. 35 retrospective studies and 2 randomized controlled trials with a total of 12641 patients were included.
RESULTS
The overall complication rate of the pre-operative biliary drainage (PBD) group was significantly higher than the no-PBD group (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.22-1.74; p < 0.0001), the incidence of post-operative delayed gastric emptying was increased in patients with PBD compared those with early surgery (OR 1.21, 95% CI: 1.02-1.43; p = 0.03), and there was a significant increase in post-operative wound infections in patients receiving PBD with an OR of 2.2 (95% CI: 1.76-2.76; p < 0.00001).
CONCLUSIONS
PBD has no beneficial effect on post-operative outcomes. The increase in post-operative overall complications and wound infections urges the exact indications for PBD and against routine pre-operative biliary decompression, especially for patients with total bilirubin < 250 umol/L waiting for PD.
Topics: Humans; Drainage; Pancreaticoduodenectomy; Preoperative Care; Postoperative Complications; Stents; Surgical Wound Infection; Randomized Controlled Trials as Topic; Gastric Emptying; Ampulla of Vater; Pancreatic Neoplasms; Common Bile Duct Neoplasms
PubMed: 38862121
DOI: 10.24875/CIRU.23000318 -
Asian Journal of Surgery Dec 2023
Meta-Analysis
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Radiofrequency Ablation; Catheter Ablation; Treatment Outcome; Neoplasm Recurrence, Local
PubMed: 37739899
DOI: 10.1016/j.asjsur.2023.08.221