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BMC Gastroenterology Dec 2023Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a precancerous lesion of pancreatic malignancy. This study aimed to evaluate associations between acute pancreatitis (AP) and histologic subtypes of IPMN.
METHODS
In the clinical study, patients with IPMN confirmed by surgical resection specimens at our institute between 2009 and 2021 were eligible for inclusion. Associations and predictive accuracy of AP on the presence of HGD were determined by logistic regressions. In addition, a systematic review and meta-analysis was conducted through literatures upon search in PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CKNI), and Wanfang database, up to June, 2023. Pooled effects of the associations between AP and HGD and intestinal epithelial subtype subtype, shown as odds ratios (ORs) with 95% confidence intervals (CIs), were calculated using random effects model.
RESULTS
The retrospective cohort study included 47 patients (32 males, 15 females) diagnosed with IPMN at our center between 2009 and 2021, including 11 cases with AP (median 62 years) and 36 cases (median 64.5 years) without. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AP in predicting HGD were 78.7%, 57.1%, 82.5%, 36.4%, and 91.7%, respectively. Univariate logistic regression analysis showed that AP group had greater odds of presence of HGD (OR: 6.29,95% CI: 1.14-34.57) than non-AP group. Meta-analysis of five case-control studies in the literature included 930 patients and showed that AP-IPMN patients had higher odds for HGD (OR: 2.13, 95% CI 1.38-3.29) and intestinal epithelial subtype (OR: 5.38, 95% CI: 3.50-8.27) compared to non-AP IPMN.
CONCLUSIONS
AP is predictive of malignancy in patients with IPMN.
Topics: Male; Female; Humans; Carcinoma, Pancreatic Ductal; Pancreatitis; Retrospective Studies; Acute Disease; Pancreatic Intraductal Neoplasms; Adenocarcinoma, Mucinous; Pancreatic Neoplasms
PubMed: 38041073
DOI: 10.1186/s12876-023-02972-4 -
European Journal of Surgical Oncology :... Oct 2022Postoperative adjuvant chemotherapy followed surgery is the standard management for localized advanced colorectal carcinoma (CRC). Mucinous adenocarcinoma (MAC) is a... (Meta-Analysis)
Meta-Analysis Review
Mucinous histology is associated with poor prognosis in locally advanced colorectal adenocarcinoma treated with postoperative first-line adjuvant chemotherapy: A systematic review and meta-analysis.
PURPOSE
Postoperative adjuvant chemotherapy followed surgery is the standard management for localized advanced colorectal carcinoma (CRC). Mucinous adenocarcinoma (MAC) is a peculiar histological subtype of CRC, but the prognosis of MAC patients is controversial. The objective of this study is to assess the implication of MAC in survival of patients treated with surgery and firs-line adjuvant chemotherapy.
METHODS
Studies describing outcomes for advanced MAC and non-specific adenocarcinoma (AC) of CRC patients treated with first-line postoperative adjuvant chemotherapy followed surgery were searched in PubMed, Embase, Medline, EBSCO, Wiley, and Cochrane Library (January 1963-August 2021). Hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) for MAC to AC were extracted. Random-effects model was used for calculating the pooled HRs and 95% confidence interval (CI).
RESULTS
This meta-analysis is comprised of 8 studies involving a total of 124,303 CRC patients treated with first-line adjuvant chemotherapy followed surgery. The pooled HR for MAC was 1.23 (95% CI, 1.07-1.41, p < 0.01, I = 80%), and the DFS (HR, 2.95, 95% CI, 1.22-7.14) of MAC patients were significantly poorer than AC patients. Similar results were also observed in stage III and FOLFOX regimen subgroups.
CONCLUSION
MAC was a risk factor for prognosis of localized advanced CRC patients treated with postoperative first-line adjuvant chemotherapy. Thus, the role of first-line adjuvant chemotherapy regimens should be further studied in these MAC patients.
Topics: Humans; Colorectal Neoplasms; Adenocarcinoma; Chemotherapy, Adjuvant; Adenocarcinoma, Mucinous; Prognosis
PubMed: 35768312
DOI: 10.1016/j.ejso.2022.06.024 -
Cancers Apr 2021Intraductal papillary mucinous neoplasms (IPMN) are common but difficult to manage since accurate tools for diagnosing malignancy are unavailable. This study tests the... (Review)
Review
Ductal Dilatation of ≥5 mm in Intraductal Papillary Mucinous Neoplasm Should Trigger the Consideration for Pancreatectomy: A Meta-Analysis and Systematic Review of Resected Cases.
Intraductal papillary mucinous neoplasms (IPMN) are common but difficult to manage since accurate tools for diagnosing malignancy are unavailable. This study tests the diagnostic value of the main pancreatic duct (MPD) diameter for detecting IPMN malignancy using a meta-analysis of published data of resected IPMNs. Collected from a comprehensive literature search, the articles included in this analysis must report malignancy cases (high-grade dysplasia (HGD) and invasive carcinoma (IC)) and MPD diameter so that two MPD cut-offs could be created. The sensitivity, specificity, and odds ratios of the two cutoffs for predicting malignancy were calculated. A review of 1493 articles yielded 20 retrospective studies with 3982 resected cases. A cutoff of ≥5 mm is more sensitive than the ≥10 mm cutoff and has pooled sensitivity of 72.20% and 75.60% for classification of HGD and IC, respectively. Both MPD cutoffs of ≥5 mm and ≥10 mm were associated with malignancy (OR = 4.36 (95% CI: 2.82, 6.75) vs. OR = 3.18 (95% CI: 2.25, 4.49), respectively). The odds of HGD and IC for patients with MPD ≥5 mm were 5.66 (95% CI: 3.02, 10.62) and 7.40 (95% CI: 4.95, 11.06), respectively. OR of HGD and IC for MPD ≥10 mm cutoff were 4.36 (95% CI: 3.20, 5.93) and 4.75 (95% CI: 2.39, 9.45), respectively. IPMN with MPD of >5 mm could very likely be malignant. In selected IPMN patients, pancreatectomy should be considered when MPD is >5 mm.
PubMed: 33922344
DOI: 10.3390/cancers13092031 -
The Cochrane Database of Systematic... Sep 2018This is the second update of the review first published in the Cochrane Library (2010, Issue 2) and later updated (2014, Issue 9).Despite advances in chemotherapy, the... (Review)
Review
BACKGROUND
This is the second update of the review first published in the Cochrane Library (2010, Issue 2) and later updated (2014, Issue 9).Despite advances in chemotherapy, the prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce tumour antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer.
OBJECTIVES
Primary objective• To assess the clinical efficacy of antigen-specific active immunotherapy for the treatment of ovarian cancer as evaluated by tumour response measured by Response Evaluation Criteria In Solid Tumors (RECIST) and/or cancer antigen (CA)-125 levels, response to post-immunotherapy treatment, and survival differences◦ In addition, we recorded the numbers of observed antigen-specific humoral and cellular responsesSecondary objective• To establish which combinations of immunotherapeutic strategies with tumour antigens provide the best immunological and clinical results SEARCH METHODS: For the previous version of this review, we performed a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL; 2009, Issue 3), in the Cochrane Library, the Cochrane Gynaecological Cancer Group Specialised Register, MEDLINE and Embase databases, and clinicaltrials.gov (1966 to July 2009). We also conducted handsearches of the proceedings of relevant annual meetings (1996 to July 2009).For the first update of this review, we extended the searches to October 2013, and for this update, we extended the searches to July 2017.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs), as well as non-randomised studies (NRSs), that included participants with epithelial ovarian cancer, irrespective of disease stage, who were treated with antigen-specific active immunotherapy, irrespective of type of vaccine, antigen used, adjuvant used, route of vaccination, treatment schedule, and reported clinical or immunological outcomes.
DATA COLLECTION AND ANALYSIS
Two reviews authors independently extracted the data. We evaluated the risk of bias for RCTs according to standard methodological procedures expected by Cochrane, and for NRSs by using a selection of quality domains deemed best applicable to the NRS.
MAIN RESULTS
We included 67 studies (representing 3632 women with epithelial ovarian cancer). The most striking observations of this review address the lack of uniformity in conduct and reporting of early-phase immunotherapy studies. Response definitions show substantial variation between trials, which makes comparison of trial results unreliable. Information on adverse events is frequently limited. Furthermore, reports of both RCTs and NRSs frequently lack the relevant information necessary for risk of bias assessment. Therefore, we cannot rule out serious biases in most of the included trials. However, selection, attrition, and selective reporting biases are likely to have affected the studies included in this review. GRADE ratings were high only for survival; for other primary outcomes, GRADE ratings were very low.The largest body of evidence is currently available for CA-125-targeted antibody therapy (17 studies, 2347 participants; very low-certainty evidence). Non-randomised studies of CA-125-targeted antibody therapy suggest improved survival among humoral and/or cellular responders, with only moderate adverse events. However, four large randomised placebo-controlled trials did not show any clinical benefit, despite induction of immune responses in approximately 60% of participants. Time to relapse with CA-125 monoclonal antibody versus placebo, respectively, ranged from 10.3 to 18.9 months versus 10.3 to 13 months (six RCTs, 1882 participants; high-certainty evidence). Only one RCT provided data on overall survival, reporting rates of 80% in both treatment and placebo groups (three RCTs, 1062 participants; high-certainty evidence). Other small studies targeting many different tumour antigens have presented promising immunological results. As these strategies have not yet been tested in RCTs, no reliable inferences about clinical efficacy can be made. Given the promising immunological results and the limited side effects and toxicity reported, exploration of clinical efficacy in large well-designed RCTs may be worthwhile.
AUTHORS' CONCLUSIONS
We conclude that despite promising immunological responses, no clinically effective antigen-specific active immunotherapy is yet available for ovarian cancer. Results should be interpreted cautiously, as review authors found a significant dearth of relevant information for assessment of risk of bias in both RCTs and NRSs.
Topics: CA-125 Antigen; Female; Humans; Immunotherapy, Active; Neoplasm Recurrence, Local; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms
PubMed: 30199097
DOI: 10.1002/14651858.CD007287.pub4 -
International Journal of Surgery... Jul 2023The best approach for treating benign or low-grade malignant lesions localized in the pancreatic neck or body remains debatable. Conventional pancreatoduodenectomy and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The best approach for treating benign or low-grade malignant lesions localized in the pancreatic neck or body remains debatable. Conventional pancreatoduodenectomy and distal pancreatectomy (DP) are associated with a risk of impairment of pancreatic function at long-term follow-up. With advances in technology and surgical skills, the use of central pancreatectomy (CP) has gradually increased.
OBJECTIVES
The objective was to compare the safety, feasibility, and short-term and long-term clinical benefits of CP and DP in matched cases.
METHODS
The PubMed, MEDLINE, Web of Science, Cochrane, and EMBASE databases were systematically searched to identify studies published from database inception to February 2022 that compared CP and DP. This meta-analysis was performed using R software.
RESULTS
Twenty-six studies matched the selection criteria, including 774 CP and 1713 DP cases. CP was significantly associated with longer operative time ( P <0.0001), less blood loss ( P <0.01), overall and clinically relevant pancreatic fistula ( P <0.0001), postoperative hemorrhage ( P <0.0001), reoperation ( P =0.0196), delayed gastric emptying ( P =0.0096), increased hospital stay ( P =0.0002), intra-abdominal abscess or effusion ( P =0.0161), higher morbidity ( P <0.0001) and severe morbidity ( P <0.0001) but with a significantly lower incidence of overall endocrine and exocrine insufficiency ( P <0.01), and new-onset and worsening diabetes mellitus ( P <0.0001) than DP.
CONCLUSIONS
CP should be considered as an alternative to DP in selected cases such as without pancreatic disease, length of the residual distal pancreas is more than 5 cm, branch-duct intraductal papillary mucinous neoplasms, and a low risk of postoperative pancreatic fistula after adequate evaluation.
Topics: Humans; Pancreatectomy; Pancreatic Fistula; Retrospective Studies; Pancreas; Pancreatic Neoplasms; Postoperative Complications
PubMed: 37300889
DOI: 10.1097/JS9.0000000000000326 -
Frontiers in Immunology 2022Lung cancer is a disease with remarkable heterogeneity. A deep understanding of the tumor microenvironment (TME) offers potential therapeutic strategies against this... (Review)
Review
Lung cancer is a disease with remarkable heterogeneity. A deep understanding of the tumor microenvironment (TME) offers potential therapeutic strategies against this malignant disease. More and more attention has been paid to the roles of macrophages in the TME. This article briefly summarizes the origin of macrophages, the mutual regulation between anti-tumoral immunity and pro-tumoral statuses derived from macrophage polarization, and the therapeutic opportunities targeting alternately activated macrophages (AAM)-type macrophage polarization. Among them, cellular components including T cells, as well as acellular components represented by IL-4 and IL-13 are key regulators driving the polarization of AAM macrophages. Novel treatments targeting macrophage-associated mechanisms are mainly divided into small molecule inhibitors, monoclonal antibodies, and other therapies to re-acclimate AMM macrophages. Finally, we paid special attention to an immunosuppressive subgroup of macrophages with T cell immunoglobulin and mucin domain-3 (TIM-3) expression. Based on cellular interactions with cancer cells, TIM3+ macrophages facilitate the proliferation and progression of cancer cells, yet this process exposes targets blocking the ligand-receptor recognition. To sum up, this is a systematic review on the mechanism of tumor-associated macrophages (TAM) polarization, therapeutic strategies and the biological functions of Tim-3 positive macrophages that aims to provide new insights into the pathogenesis and treatment of lung cancer.
Topics: Humans; Hepatitis A Virus Cellular Receptor 2; Lung Neoplasms; Macrophages; Tumor Microenvironment; Tumor-Associated Macrophages
PubMed: 36439090
DOI: 10.3389/fimmu.2022.1007812 -
Digestive Diseases and Sciences Oct 2010Preoperative diagnosis of malignancy in pancreatic cystic lesions (PCLs) remains challenging. Most non-mucinous cystic lesions (NMCLs) are benign, but mucinous cystic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preoperative diagnosis of malignancy in pancreatic cystic lesions (PCLs) remains challenging. Most non-mucinous cystic lesions (NMCLs) are benign, but mucinous cystic lesions (MCLs) are more likely to be premalignant or malignant.
AIM
The aim of this study was to assess the sensitivity, specificity, and positive and negative likelihood ratios (LRs) of EUS-FNA-based cytology in differentiating MCLs from non-mucinous PCLs.
METHODS
We conducted a comprehensive search of MEDLINE, SCOPUS, Cochrane, and "CINAHL Plus" databases to identify studies, in which the results of EUS-FNA-based cytology of PCLs were compared with those of surgical biopsy or surgical excision histopathology. A DerSimonian-Laird random effect model was used to estimate the pooled sensitivity, specificity, and LRs, and a summary receiver-operating characteristic (SROC) curve was constructed.
RESULTS
We included 376 patients from 11 distinct studies who underwent EUS-FNA-based cytology and also had histopathological diagnosis. The pooled sensitivity and specificity in diagnosing MCLs were 0.63 (95% CI, 0.56-0.70) and 0.88 (95% CI, 0.83-0.93), respectively. The positive and negative LRs in diagnosing MCLs were 4.46 (95% CI, 1.21-16.43) and 0.46 (95% CI, 0.25-0.86), respectively. The area under the curve (AUC) was 0.89.
CONCLUSIONS
EUS-FNA-based cytology has overall low sensitivity but good specificity in differentiating MCLs from NMCLs. Further research is required to improve the overall sensitivity of EUS-FNA-based cytology to diagnose MCLs while evaluating PCL.
Topics: Adenocarcinoma, Mucinous; Biopsy, Fine-Needle; Endosonography; Humans; Pancreatic Cyst; Pancreatic Neoplasms; Precancerous Conditions
PubMed: 20694512
DOI: 10.1007/s10620-010-1361-8 -
Life Sciences in Space Research May 2024The space environment poses substantial challenges to human physiology, including potential disruptions in gastrointestinal health. Gut permeability has only recently... (Review)
Review
The space environment poses substantial challenges to human physiology, including potential disruptions in gastrointestinal health. Gut permeability has only recently become widely acknowledged for its potential to cause adverse effects on a systemic level, rendering it a critical factor to investigate in the context of spaceflight. Here, we propose that astronauts experience the onset of leaky gut during space missions supported by transcriptomic and metagenomic analysis of human and murine samples. A genetic map contributing to intestinal permeability was constructed from a systematic review of current literature. This was referenced against our re-analysis of three independent transcriptomic datasets which revealed significant changes in gene expression patterns associated with the gut barrier. Specifically, in astronauts during flight, we observed a substantial reduction in the expression genes that are crucial for intestinal barrier function, goblet cell development, gut microbiota modulation, and immune responses. Among rodent spaceflight studies, differential expression of cytokines, chemokines, and genes which regulate mucin production and post-translational modifications suggest a similar dysfunction of intestinal permeability. Metagenomic analysis of feces from two murine studies revealed a notable reduction probiotic, short chain fatty acid-producing bacteria and an increase in the Gram-negative pathogens, including Citrobacter rodentium, Enterobacter cloacea, Klebsiella aerogenes, and Proteus hauseri which promote LPS circulation, a recipe for barrier disruption and systemic inflammatory activation. These findings emphasize the critical need to understand the underlying mechanisms and develop interventions to maintain gastrointestinal health in space.
Topics: Space Flight; Astronauts; Humans; Animals; Permeability; Gastrointestinal Microbiome; Mice; Transcriptome; Gastrointestinal Tract
PubMed: 38670644
DOI: 10.1016/j.lssr.2024.03.003 -
Digestive Diseases (Basel, Switzerland) 2021Mucus protects the epithelium against invaders and toxic materials. Sticky and thick mucus is characteristic of CF.
BACKGROUND
Mucus protects the epithelium against invaders and toxic materials. Sticky and thick mucus is characteristic of CF.
OBJECTIVE
The aim of this systematic review is to characterize the specific mucins secreted in the lung and intestinal tract of CF patients.
METHODS
A systematic literature search was conducted up to December 31, 2019. The following terms were used: "cystic fibrosis" AND "mucin." Case-control studies comparing mucin expression in CF patients to healthy controls were included.
RESULTS
We found 741 eligible studies, 694 studies were rejected because they were performed in animals and not in full text, and 32 studies were excluded being editorials, duplications, review articles, meta-analysis, or not in English. Fifteen studies were eligible for our study, including 150 CF patients compared to 82 healthy controls, all fulfilled the inclusion criteria. The main mucin types expressed in the sinus submucosal glands, sputum, tracheobronchial surface epithelium, and lung submucosal glands were MUC5AC and MUC5B. Increase in the number of sinusoidal submucosal glands and expression of MUC5B was found in CF patients, but no such difference from healthy controls was found for the number of goblet cells in the surface epithelium nor in the expression of -MUC5AC. The opposite was found in the tracheobronchial surface epithelium and in the lungs.
CONCLUSIONS
Increased expression of MUC5AC in the surface epithelium and of MUC5B in the subepithelial glands may be the result of higher secretion rate of mucin into the lumen of the respiratory tract, causing mucus plaque, infection, and inflammation.
Topics: Animals; Bodily Secretions; Case-Control Studies; Cystic Fibrosis; Gastrointestinal Tract; Humans; Lung; Mucin 5AC; Mucin-5B; Mucins
PubMed: 33049746
DOI: 10.1159/000512268 -
Viruses Mar 2022During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4... (Review)
Review
During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), T cell immunoglobulin and ITIM domain (TIGIT), lymphocyte-activation gene-3 (LAG-3), T cell immunoglobulin and mucin domain-3 (Tim-3), CD160, 2B4 (CD244), and V-domain Ig suppressor of T cell activation (VISTA), can lead to chronic T cell exhaustion. These ICs play predominant roles in regulating the progression of HIV/SIV infection by mediating T cell responses as well as enriching latent viral reservoirs. It has been demonstrated that enhanced expression of ICs on CD4 and CD8 T cells could inhibit cell proliferation and cytokine production. Overexpression of ICs on CD4 T cells could also format and prolong HIV/SIV persistence. IC blockers have shown promising clinical results in HIV therapy, implying that targeting ICs may optimize antiretroviral therapy in the context of HIV suppression. Here, we systematically review the expression profile, biological regulation, and therapeutic efficacy of targeted immune checkpoints in HIV/SIV infection.
Topics: Animals; CD8-Positive T-Lymphocytes; Disease Progression; HIV Infections; Humans; Immunoglobulins; Lymphocyte Activation; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus
PubMed: 35336991
DOI: 10.3390/v14030581