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International Journal of Cancer Jun 2024The MRE11, RAD50, and NBN genes encode the MRN complex sensing DNA breaks and directing their repair. While carriers of biallelic germline pathogenic variants (gPV)...
The MRE11, RAD50, and NBN genes encode the MRN complex sensing DNA breaks and directing their repair. While carriers of biallelic germline pathogenic variants (gPV) develop rare chromosomal instability syndromes, the cancer risk in heterozygotes remains controversial. We performed a systematic review and meta-analysis of 53 studies in patients with different cancer diagnoses to better understand the cancer risk. We found an increased risk (odds ratio, 95% confidence interval) for gPV carriers in NBN for melanoma (7.14; 3.30-15.43), pancreatic cancer (4.03; 2.14-7.58), hematological tumors (3.42; 1.14-10.22), and prostate cancer (2.44, 1.84-3.24), but a low risk for breast cancer (1.29; 1.00-1.66) and an insignificant risk for ovarian cancer (1.53; 0.76-3.09). We found no increased breast cancer risk in carriers of gPV in RAD50 (0.93; 0.74-1.16; except of c.687del carriers) and MRE11 (0.87; 0.66-1.13). The secondary burden analysis compared the frequencies of gPV in MRN genes in patients from 150 studies with those in the gnomAD database. In NBN gPV carriers, this analysis additionally showed a high risk for brain tumors (5.06; 2.39-9.52), a low risk for colorectal (1.64; 1.26-2.10) and hepatobiliary (2.16; 1.02-4.06) cancers, and no risk for endometrial, and gastric cancer. The secondary burden analysis showed also a moderate risk for ovarian cancer (3.00; 1.27-6.08) in MRE11 gPV carriers, and no risk for ovarian and hepatobiliary cancers in RAD50 gPV carriers. These findings provide a robust clinical evidence of cancer risks to guide personalized clinical management in heterozygous carriers of gPV in the MRE11, RAD50, and NBN genes.
PubMed: 38924040
DOI: 10.1002/ijc.35066 -
Transplantation Reviews (Orlando, Fla.) Jun 2024Pancreatic islet transplantation for type 1 diabetes mellitus (T1DM) is efficacious in supressing severe hypoglycaemic episodes (SHE) and restoring glycaemic regulation,... (Review)
Review
BACKGROUND
Pancreatic islet transplantation for type 1 diabetes mellitus (T1DM) is efficacious in supressing severe hypoglycaemic episodes (SHE) and restoring glycaemic regulation, which are both pivotal in increasing health-related quality of life (HRQoL). Therefore, a systematic assessment of reports detailing HRQoL outcomes is warranted to better understand the benefits of islet transplantation. To this end, we performed a systematic review of the literature to assess the impact of islet transplantation on HRQoL in individuals with T1DM, whether as a standalone procedure (ITA) or following renal transplantation (IAK).
METHOD
All studies providing a quantitative assessment of HRQoL following ITA or IAK were included. Selected studies had to meet the following criteria: they had to (i) involve adult recipients of islet grafts for T1DM, (ii) use either generic or disease-specific QoL assessment tools, (iii) provide a comparative analysis of QoL metrics between the pre- and post-transplantation state or between the post-transplantation state and other pre-transplant patients or the general population.
RESULTS
Seven studies that met the inclusion criteria provided data on 205 subjects. In the included studies, HRQoL was measured using both generic instruments, such as the 36-item Short Form Health Survey (SF-36) and the Health Status Questionnaire (HSQ) 2.0, and disease-specific instruments, such as the Diabetes Distress Scale (DDS), the Diabetes Quality of Life Questionnaire, and the Hypoglycaemia Fear Survey (HFS). These instruments cover physical, mental, social, or functional health dimensions. We found that pancreatic islet transplantation was associated with improvements in all HRQoL dimensions compared with the pre-transplant baseline.
CONCLUSIONS
Our systematic review demonstrates that islet transplantation significantly enhances quality of life in individuals with T1DM who are experiencing SHE. To our knowledge, this is the most extensive systematic review conducted to date, evaluating the impact of islet transplantation on HRQoL.
PubMed: 38917621
DOI: 10.1016/j.trre.2024.100870 -
Techniques in Coloproctology Jun 2024Anastomotic leakage (AL) represents a major complication after rectal low anterior resection (LAR). Transanal drainage tube (TDT) placement offers a potential strategy... (Meta-Analysis)
Meta-Analysis
Updated evidence of the effectiveness and safety of transanal drainage tube for the prevention of anastomotic leakage after rectal low anterior resection: a systematic review and meta-analysis.
BACKGROUNDS
Anastomotic leakage (AL) represents a major complication after rectal low anterior resection (LAR). Transanal drainage tube (TDT) placement offers a potential strategy for AL prevention; however, its efficacy and safety remain contentious.
METHODS
A systematic review and meta-analysis were used to evaluate the influence of TDT subsequent to LAR as part of the revision of the surgical site infection prevention guidelines of the Japanese Society of Surgical Infectious Diseases (PROSPERO registration; CRD42023476655). We searched each database, and included randomized controlled trials (RCTs) and observational studies (OBSs) comparing TDT and non-TDT outcomes. The main outcome was AL. Data were independently extracted by three authors and random-effects models were implemented.
RESULTS
A total of three RCTs and 18 OBSs were included. RCTs reported no significant difference in AL rate between the TDT and non-TDT groups [relative risk (RR): 0.69, 95% confidence interval (CI) 0.42-1.15]. OBSs reported that TDT reduced AL risk [odds ratio (OR): 0.45, 95% CI 0.31-0.64]. In the subgroup excluding diverting stoma (DS), TDT significantly lowered the AL rate in RCTs (RR: 0.57, 95% CI 0.33-0.99) and OBSs (OR: 0.41, 95% CI 0.27-0.62). Reoperation rates were significantly lower in the TDT without DS groups in both RCTs (RR: 0.26, 95% CI 0.07-0.94) and OBSs (OR: 0.40, 95% CI 0.24-0.66). TDT groups exhibited a higher anastomotic bleeding rate only in RCTs (RR: 4.28, 95% CI 2.14-8.54), while shorter hospital stays were observed in RCTs [standard mean difference (SMD): -0.44, 95% CI -0.65 to -0.23] and OBSs (SMD: -0.54, 95% CI -0.97 to -0.11) compared with the non-TDT group.
CONCLUSIONS
A universal TDT placement cannot be recommended for all rectal LAR patients. Some patients may benefit from TDT, such as patients without DS creation. Further investigation is necessary to identify the specific beneficiaries.
Topics: Humans; Anastomotic Leak; Drainage; Proctectomy; Randomized Controlled Trials as Topic; Rectum; Anal Canal; Rectal Neoplasms; Treatment Outcome; Female; Male; Observational Studies as Topic; Middle Aged
PubMed: 38916755
DOI: 10.1007/s10151-024-02942-2 -
Supportive Care in Cancer : Official... Jun 2024To evaluate the quality of guidelines on the pancreatic perioperative enhanced recovery after surgery both domestically and internationally, providing reference and... (Review)
Review
PURPOSE
To evaluate the quality of guidelines on the pancreatic perioperative enhanced recovery after surgery both domestically and internationally, providing reference and reference for clinical practice.
METHODS
Systemically retrieved in the guideline websites, professional association websites and databases, such as up to date, BMJ Best Practice, PubMed, Embase, The Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang Data, China Science and Technology Journal Database(VIP), China Biology Medicine disc (CBMdisc), Medlive, Guidelines International Network(GIN), National Guideline Clearinghouse(NGC), National Institute for Health and Care Excellence(NICE), Registered Nurses Association of Ontario(RNAO), Scottish Intercollegiate Guidelines Network(SIGN), Joanna Briggs Institute Library(JBI), including guidelines and expert consensus on enhanced postsurgical recovery in pancreatic surgery published as of December 20, 2023. The Appraisal of Guidelines for Research and Evaluation II(AGREE II) tool was applied to evaluate the quality of the guidelines by four assessors.
RESULTS
This study included seven guidelines, all of which were rated as Grade B in terms of quality, with ICC coefficients ranging from 0.752 to 0.884, indicating a high level of consistency.
CONCLUSION
When formulating guidelines in the future, it is recommended to use AGREE II as a reference, emphasizing the standardization of the guideline development process and methods, fully considering patients' values and preferences, focusing on the applicability of the guidelines, and striving to create high-quality evidence-based recommendations.
Topics: Humans; Practice Guidelines as Topic; Enhanced Recovery After Surgery; Perioperative Care; Pancreas
PubMed: 38916656
DOI: 10.1007/s00520-024-08641-w -
Annals of Hepato-biliary-pancreatic... Jun 2024To compare the procedural outcomes of minimally invasive and open central pancreatectomy. A systematic review in compliance with PRISMA statement standards was conducted... (Review)
Review
To compare the procedural outcomes of minimally invasive and open central pancreatectomy. A systematic review in compliance with PRISMA statement standards was conducted to identify and analyze studies comparing the procedural outcomes of minimally invasive (laparoscopic or robotic) central pancreatectomy with the open approach. Random effects modeling using intention to treat data, and individual patient as unit of analysis, was used for analyses. Seven comparative studies including 289 patients were included. The two groups were comparable in terms of baseline characteristics. The minimally invasive approach was associated with less intraoperative blood loss (mean difference [MD]: -153.13 mL, = 0.0004); however, this did not translate into less need for blood transfusion (odds ratio [OR]: 0.30, = 0.06). The minimally invasive approach resulted in less grade B-C postoperative pancreatic fistula (OR: 0.54, = 0.03); this did not remain consistent through sensitivity analyses. There was no difference between the two approaches in operative time (MD: 60.17 minutes, = 0.31), Clavien-Dindo ≥ 3 complications (OR: 1.11, = 0.78), postoperative mortality (risk difference: -0.00, = 0.81), and length of stay in hospital (MD: -3.77 days, = 0.08). Minimally invasive central pancreatectomy may be as safe as the open approach; however, whether it confers advantage over the open approach remains the subject of debate. Type 2 error is a possibility, hence adequately powered studies are required for definite conclusions; future studies may use our data for power analysis.
PubMed: 38915256
DOI: 10.14701/ahbps.24-093 -
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 -
Frontiers in Endocrinology 2024Hypertriglyceridemia (HTG) is a complex disorder caused by genetic and environmental factors that frequently results from loss-of-function variants in the gene encoding...
INTRODUCTION
Hypertriglyceridemia (HTG) is a complex disorder caused by genetic and environmental factors that frequently results from loss-of-function variants in the gene encoding lipoprotein lipase (LPL). Heterozygous patients have a range of symptoms, while homozygous LPL deficiency presents with severe symptoms including acute pancreatitis, xanthomas, and lipemia retinalis.
METHODS
We described the clinical characteristics of three Slovenian patients (an 8-year-old female, an 18-year-old man, and a 57-year-old female) and one Pakistani patient (a 59-year-old male) with LPL deficiency. We performed next-generation sequencing (NGS) targeting all coding exons and intron-exon boundaries of the gene, and Sanger sequencing for variant confirmation. In addition, we performed a systematic literature review of all cases with three identified variants and described their clinical characteristics.
RESULTS
Two Slovenian patients with a heterozygous pathogenic variant NM_000237.3:c.984G>T (p.Met328Ile) were diagnosed within the first three years of life and had triglyceride (TG) values of 16 and 20 mmol/L. An asymptomatic Pakistani patient with TG values of 36.8 mmol/L until the age of 44 years, was identified as heterozygous for a pathogenic variant NM_000237.3:c.724G>A (p.Asp242Asn). His TG levels dropped to 12.7 mmol/L on dietary modifications and by using fibrates. A Slovenian patient who first suffered from pancreatitis at the age of 18 years with a TG value of 34 mmol/L was found to be homozygous for NM_000237.3:c.337T>C (p.Trp113Arg).
CONCLUSIONS
Patients with LPL deficiency had high TG levels at diagnosis. Homozygous patients had worse outcomes. Good diet and medication compliance can reduce severity.
Topics: Humans; Male; Female; Slovenia; Adolescent; Middle Aged; Lipoprotein Lipase; Child; Pakistan; Hyperlipoproteinemia Type I; Mutation
PubMed: 38911039
DOI: 10.3389/fendo.2024.1387419 -
American Journal of Obstetrics and... Jun 2024To investigate the association between actual and planned modes of delivery, neonatal mortality, and short-term outcomes among preterm pregnancies ≤32 weeks of gestation. (Review)
Review
Cesarean delivery is associated with lower neonatal mortality among breech pregnancies - a systematic review and meta-analysis of preterm deliveries ≤32 weeks of gestation.
OBJECTIVE
To investigate the association between actual and planned modes of delivery, neonatal mortality, and short-term outcomes among preterm pregnancies ≤32 weeks of gestation.
DATA SOURCES
A systematic literature search was conducted in three main databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to November 16, 2022. The protocol was registered in advance in the International Prospective Register of Systematic Reviews (CRD42022377870).
STUDY ELIGIBILITY CRITERIA
Eligible studies examined pregnancies ≤ 32nd gestational week. All infants received active care, and the outcomes were reported separately by different modes of delivery. Singleton and twin pregnancies at vertex and breech presentations were included. Studies that included pregnancies complicated with preeclampsia and abruptio placentae were excluded. Primary outcomes were neonatal mortality and intraventricular hemorrhage.
STUDY APPRAISAL AND SYNTHESIS METHODS
Articles were selected by title, abstract, and full text, and disagreements were resolved by consensus. Random effects model-based odds ratios with corresponding 95% confidence intervals were calculated for dichotomous outcomes. ROBINS-I was used to assess the risk of bias.
RESULTS
A total of nineteen observational studies were included involving a total of 16,042 preterm infants in this systematic review and meta-analysis. Actual cesarean delivery improves survival (odds ratio, 0.62; 95% confidence interval, 0.42 to 0.9) and decreases the incidence of intraventricular hemorrhage (odds ratio, 0.70; confidence interval, 0.57 to 0.85) compared to vaginal delivery. Planned cesarean delivery does not improve the survival of very and extremely preterm infants compared to vaginal delivery (odds ratio, 0.87; 95% confidence interval, 0.53 to 1.44). Subset analysis found significantly lower odds of death for singleton breech preterm deliveries born by both planned (odds ratio, 0.56; 95% confidence interval, 0.32 to 0.98) and actual (odds ratio, 0.34; 95% confidence interval, 0.13 to 0.88) cesarean delivery.
CONCLUSION
Cesarean delivery should be the mode of delivery for preterm ≤32 weeks of gestation breech births due to the higher mortality in preterm infants born via vaginal delivery.
PubMed: 38908650
DOI: 10.1016/j.ajog.2024.06.015 -
European Journal of Clinical... Jun 2024This meta-analysis was dedicated to evaluating the effectiveness and safety of Atezolizumab plus Bevacizumab (Atez/Bev) and Lenvatinib (LEN) as first-line systematic... (Review)
Review
BACKGROUND
This meta-analysis was dedicated to evaluating the effectiveness and safety of Atezolizumab plus Bevacizumab (Atez/Bev) and Lenvatinib (LEN) as first-line systematic therapy for unresectable hepatocellular carcinoma (u-HCC).
METHODS
The prospective protocol for this study was registered with the PROSPERO (Registration number: CRD42022356874). Literature searches were conducted in PubMed, EMBASE database Cochrane Library, and Web Science to determine all clinical controlled studies that reported Atez/Bev and LEN for treating u-HCC. We. evaluated as primary end-point overall survival (OS) and progression-free survival (PFS), as well as other outcomes such as tumor response and adverse events (AEs).Quality assessment and data extraction of studies were conducted independently by three reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software.
RESULTS
12 retrospective cohort studies (RCSs) involving a total of 4948 patients were finally included. The results showed that compared with LEN, Atez/Bev can improve the patient's PFS (HR = 0.80, 95% CI: 0.72 ~ 0.88; p < 0.0001) and reduce the rate of overall AEs (OR = 0.46 95% CI: 0.38 ~ 0.55, p < 0.00001) and grade ≥ 3 AEs (OR = 0.43; 95% CI: 0.36 ~ 0.51, p < 0.00001), while there is no difference between OS and treatment responses rate (objective response rate, disease control rate, complete response, partial response, progressive disease, and stable disease) between two groups. In addition, the subgroup analysis shows that Atez/Bev can promote the OS of patients with viral hepatitis. (HR = 0.79, 95% CI: 0.67 ~ 0.95; p = 0.01), while LEN has an advantage in improving OS in patients with Child-Pugh grade B liver function (HR = 1.98, 95% CI: 1.50 ~ 2.63; p < 0.00001).
CONCLUSION
Current evidence shows that compared with LEN, Atez/Bev has more advantages in PFS and safety in treating u-HCC and can improve the OS of patients with viral. LEN has advantages in improving the OS of patients with grade B liver function. However, more multicenter randomized controlled experiments are needed in the future to verify our results.
PubMed: 38907884
DOI: 10.1007/s00228-024-03718-1 -
European Radiology Jun 2024Recent studies have shown the potential of fibroblast activating protein inhibitor (FAPI) PET imaging for pancreatic cancer assessment.
BACKGROUND
Recent studies have shown the potential of fibroblast activating protein inhibitor (FAPI) PET imaging for pancreatic cancer assessment.
PURPOSE
This article is dedicated to comparing the diagnostic efficacy of FAPI PET and [F]fluorodeoxyglucose (FDG) PET in the evaluation of primary tumors, lymph nodes, and distant metastases in pancreatic cancer.
METHODS
In this review, we conducted a systematic search of studies published in PubMed and Web of Science databases up to September 18, 2023. All included studies used radionuclide labeled FAPI and FDG as PET diagnostic tracers to evaluate their applicability in patients with pancreatic cancer.
RESULTS
The FAPI PET imaging group showed significantly higher sensitivity in the detection of primary lesions (1.000, [95% CI: 0.999-1.000]), lymph node metastases (0.624 [95% CI: 0.391-0.834]) and distant metastatic (0.965 [95% CI: 0.804-1.000]) in pancreatic cancer compared to the FDG PET imaging group (0.889 [95% CI: 0.788-0.966], 0.373 [95% CI: 0.163-0.606] and 0.889 [95% CI: 0.689-0.999], respectively). Furthermore, the maximum standardized uptake value (SUVmax) in FAPI PET imaging is significantly higher than that in FDG imaging for primary lesions (mean difference (MD) = 7.51, 95% CI: 5.34-9.67).
CONCLUSION
Compared with [F]FDG PET/CT, FAPI PET imaging showed higher sensitivity, SUVmax. This method can be effectively utilized for the evaluation of pancreatic cancer.
CLINICAL RELEVANCE STATEMENT
Fibroblast activating protein inhibitor PET may be a better alternative to [F]FDG in evaluating primary pancreatic cancer, lymph node metastases, and distant metastases.
KEY POINTS
Fibroblast activating protein inhibitor (FAPI) PET is compared with FDG PET for evaluating pancreatic cancer. Multiple radiolabeled FAPI variants have shown promising results in the diagnosis of pancreatic cancer. FAPI PET imaging effectively helps clinicians diagnose and stage pancreatic cancer.
PubMed: 38907099
DOI: 10.1007/s00330-024-10843-z