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European Journal of Radiology Open Dec 2023Intraductal papillary mucinous neoplasm of the bile ducts (IPMN-B) is a true pre-cancerous lesion, which shares common features with pancreatic IPMN (IPMN-P). While... (Review)
Review
RATIONALE AND OBJECTIVES
Intraductal papillary mucinous neoplasm of the bile ducts (IPMN-B) is a true pre-cancerous lesion, which shares common features with pancreatic IPMN (IPMN-P). While IPMN-P is a well described entity for which guidelines were formulated and revised, IPMN-B is a poorly described entity.We carried out a systematic review to evaluate the existing literature, emphasizing the role of MRI in IPMN-B depiction.
MATERIALS AND METHODS
PubMed database was used to identify original studies and case series that reported MR Imaging features of IPMN-B. The search keywords were "IPMN OR intraductal papillary mucinous neoplasm OR IPNB OR intraductal papillary neoplasm of the bile duct AND Biliary OR biliary cancer OR hepatic cystic lesions". Risk of bias and applicability were evaluated using the QUADAS-2 tool.
RESULTS
884 Records were Identified through database searching. 12 studies satisfied the inclusion criteria, resulting in MR features of 288 patients. All the studies were retrospective. Classic features of IPMN-B are under-described. Few studies note worrisome features, concerning for an underlying malignancy. 50 % of the studies had a high risk of bias and concerns regarding applicability.
CONCLUSIONS
The MRI features of IPMN-B are not well elaborated and need to be further studied. Worrisome features and guidelines regarding reporting the imaging findings should be established and published. Radiologists should be aware of IPMN-B, since malignancy diagnosis in an early stage will yield improved prognosis.
PubMed: 37609049
DOI: 10.1016/j.ejro.2023.100515 -
The Israel Medical Association Journal... Jun 2023Mucins, heavily glycosylated glycoproteins, are synthesized by mucosal surfaces and play an important role in healthy and malignant states. Changes in mucin synthesis,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mucins, heavily glycosylated glycoproteins, are synthesized by mucosal surfaces and play an important role in healthy and malignant states. Changes in mucin synthesis, expression, and secretion may be a primary event or may be secondary to inflammation and carcinogenesis.
OBJECTIVES
To assess current knowledge of mucin expression in the small bowel of celiac disease (CD) patients and to determine possible associations between mucin profile and gluten-free diet.
METHODS
Medical literature searches of articles in English were conducted using the terms mucin and celiac. Observational studies were included. Pooled odds ratios and 95% confidence intervals were calculated.
RESULTS
Of 31 articles initially generated by a literature search, 4 observational studies that fulfilled the inclusion criteria remained eligible for meta-analysis. These studies included 182 patients and 148 controls from four countries (Finland, Japan, Sweden, United States). Mucin expression was significantly increased in small bowel mucosa of CD patients than in normal small bowel mucosa (odds ratio [OR] 7.974, 95% confidence interval [95%CI] (1.599-39.763), P = 0.011] (random-effect model). Heterogeneity was significant: Q = 35.743, df (Q) = 7, P < 0.0001, I2 = 80.416%. ORs for MUC2 and MUC5AC expression in the small bowel mucosa of untreated CD patients were 8.837, 95%CI 0.222-352.283, P = 0.247 and 21.429, 95%CI 3.883-118.255, P < 0.0001, respectively.
CONCLUSIONS
Expression of certain mucin genes in the small bowel mucosa of CD patients is increased and may serve as a diagnostic tool and assist in surveillance programs.
Topics: Humans; Mucins; Celiac Disease; Intestine, Small; Abdomen; Diet, Gluten-Free
PubMed: 37381936
DOI: No ID Found -
JAMA Network Open Jun 2023Randomized clinical trials examining the effectiveness of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer predominantly included patients with high-grade... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Randomized clinical trials examining the effectiveness of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer predominantly included patients with high-grade serous carcinomas. The use and outcomes of NACT in less common epithelial carcinomas are understudied.
OBJECTIVE
To investigate the uptake and survival outcomes in treatment with NACT for less common histologic subtypes of epithelial ovarian cancer.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective cohort study and systematic literature review with meta-analysis was conducted using the National Cancer Database from 2006 to 2017 and the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2006 to 2019. Data analysis was performed from July 2022 to April 2023. The evaluation included patients with stage III to IV ovarian cancer with clear cell, mucinous, or low-grade serous histologic subtypes who received multimodal treatment with surgery and chemotherapy.
EXPOSURES
Exposure assignment per the sequence of treatment: primary debulking surgery (PDS) followed by chemotherapy (PDS group) or NACT followed by interval surgery (NACT group).
MAIN OUTCOMES AND MEASURES
Temporal trends and characteristics of NACT use were assessed using multivariable analysis, and overall survival (OS) was assessed with the inverse probability of treatment weighting propensity score.
RESULTS
A total of 3880 patients were examined in the National Cancer Database including 1829 women (median age, 56 [IQR, 49-63] years) with clear cell, 1156 women (median age, 53 [IQR, 42-64] years) with low-grade serous, and 895 women (median age, 57 [IQR, 48-66] years) with mucinous carcinomas. NACT use increased in patients with clear cell (from 10.2% to 16.2%, 58.8% relative increase; P < .001 for trend) or low-grade serous (from 7.7% to 14.2%, 84.4% relative increase; P = .007 for trend) carcinoma during the study period. This association remained consistent in multivariable analysis. NACT use also increased, but nonsignificantly, in mucinous carcinomas (from 8.6% to 13.9%, 61.6% relative increase; P = .07 for trend). Across the 3 histologic subtypes, older age and stage IV disease were independently associated with NACT use. In a propensity score-weighted model, the NACT and PDS groups had comparable OS for clear cell (4-year rates, 31.4% vs 37.7%; hazard ratio [HR], 1.12; 95% CI, 0.95-1.33) and mucinous (27.0% vs 26.7%; HR, 0.90; 95% CI, 0.68-1.19) carcinomas. For patients with low-grade serous carcinoma, NACT was associated with decreased OS compared with PDS (4-year rates, 56.4% vs 81.0%; HR, 2.12; 95% CI, 1.55-2.90). Increasing NACT use and histologic subtype-specific survival association were also found in the Surveillance, Epidemiology, and End Results Program cohort (n = 1447). A meta-analysis of 4 studies, including the current study, observed similar OS associations for clear cell (HR, 1.13; 95% CI, 0.96-1.34; 2 studies), mucinous (HR, 0.93; 95% CI, 0.71-1.21; 2 studies), and low-grade serous (HR, 2.11; 95% CI, 1.63-2.74; 3 studies) carcinomas.
CONCLUSIONS AND RELEVANCE
Despite the lack of data on outcomes of NACT among patients with less common carcinomas, this study noted that NACT use for advanced disease has gradually increased in the US. Primary chemotherapy for advanced-stage, low-grade serous ovarian cancer may be associated with worse survival compared with PDS.
Topics: Female; Humans; Middle Aged; Adenocarcinoma, Mucinous; Carcinoma, Ovarian Epithelial; Chemotherapy, Adjuvant; Cystadenocarcinoma, Serous; Neoadjuvant Therapy; Neoplasm Staging; Ovarian Neoplasms; Peritoneal Neoplasms; Retrospective Studies; Adult; Aged
PubMed: 37326992
DOI: 10.1001/jamanetworkopen.2023.18602 -
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 Allergy 2023Epigenetics facilitates insights on the impact of host environment on the genesis of chronic rhinosinusitis (CRS) through modulations of host gene expression and... (Review)
Review
BACKGROUND
Epigenetics facilitates insights on the impact of host environment on the genesis of chronic rhinosinusitis (CRS) through modulations of host gene expression and activity. Epigenetic mechanisms such as DNA methylation cause reversible but heritable changes in gene expression over generations of progeny, without altering the DNA base-pair sequences. These studies offer a critical understanding of the environment-induced changes that result in host predisposition to disease and may help in developing novel biomarkers and therapeutics. The goal of this systematic review is to summarize the current evidence on epigenetics of CRS with a focus on chronic rhinosinusitis with nasal polyps (CRSwNP) and highlight gaps that merit further research.
METHODS
A systematic review of the English language literature was performed to identify investigations related to epigenetic studies in subjects with CRS.
RESULTS
The review identified 65 studies. These have focused on DNA methylation and non-coding RNAs, with only a few on histone deacetylation, alternative polyadenylation, and chromatin accessibility. Studies include those investigating and changes or both. Studies also include animal models of CRS. Almost all have been conducted in Asia. The genome-wide studies of DNA methylation found differences in global methylation between CRSwNP and controls, while others specifically found significant differences in methylation of the CpG sites of the thymic stromal lymphopoietin (), , and . In addition, DNA methyltransferase inhibitors and histone deacetylase inhibitors were studied as potential therapeutic agents. Majority of the studies investigating non-coding RNAs focused on micro-RNAs (miRNA) and found differences in global expression of miRNA levels. These studies also revealed some previously known as well as novel targets and pathways such as tumor necrosis factor alpha, TGF beta-1, IL-10, , aryl hydrocarbon receptor, PI3K/AKT pathway, mucin secretion, and vascular permeability. Overall, the studies have found a dysregulation in pathways/genes involving inflammation, immune regulation, tissue remodeling, structural proteins, mucin secretion, arachidonic acid metabolism, and transcription.
CONCLUSIONS
Epigenetic studies in CRS subjects suggest that there is likely a major impact of the environment. However, these are association studies and do not directly imply pathogenesis. Longitudinal studies in geographically and racially diverse population cohorts are necessary to quantify genetic vs. environmental risks for CRSwNP and CRS without nasal polyps and assess heritability risk, as well as develop novel biomarkers and therapeutic agents.
PubMed: 37284022
DOI: 10.3389/falgy.2023.1165271 -
European Urology Jul 2023The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for...
Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.
CONTEXT
The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed.
OBJECTIVE
To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent.
EVIDENCE ACQUISITION
A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021.
EVIDENCE SYNTHESIS
We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy.
CONCLUSIONS
Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers.
PATIENT SUMMARY
We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact.
Topics: Humans; Male; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms
PubMed: 37117107
DOI: 10.1016/j.eururo.2023.03.014 -
HPB : the Official Journal of the... Jul 2023Mucinous Cystic Neoplasms (MCN) of the pancreas are premalignant cysts for which current guidelines support pancreatic resection. The primary aim of this systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mucinous Cystic Neoplasms (MCN) of the pancreas are premalignant cysts for which current guidelines support pancreatic resection. The primary aim of this systematic review and meta-analysis is to define the pooled rate of malignancy for MCN.
METHODS
A systematic review of eligible studies published between 2000 and 2021 was performed on PubMed and Embase. Primary outcome was rate of malignancy. Data regarding high-risk features, including cyst size and mural nodules, were collected and analyzed.
RESULTS
A total of 40 studies and 3292 patients with resected MCN were included in the final analysis. The pooled rate of malignancy was 16.1% (95%CI 13.1-19.0). The rate of malignant MCN in studies published before 2012 was significantly higher than that of studies published after recent guidelines were published (21.0% vs 14.9%, p < 0.001). Malignant MCN were larger than benign (mean difference 25.9 mm 95%CI 14.50-37.43, p < 0.001) with a direct correlation between size and presence of malignant MCN (R2 = 0.28, p = 0.020). A SROC identified a threshold of 65 mm to be associated with the diagnosis of malignant MCN. Presence of mural nodules was associated with the diagnosis of a malignant MCN (OR = 4.34, 95%CI 3.00-6.29, p < 0.001).
CONCLUSION
Whereas guidelines recommend resection of all MCN, the rate of malignancy in resected MCN is 16%, implying that surveillance has a role in most cases, and that surgical selection criteria are warranted. Size and presence of mural nodules are significantly associated with an increased risk of malignant degeneration, small MCN and without mural nodules can be considered for surveillance.
Topics: Humans; Pancreatic Neoplasms; Pancreas; Neoplasms, Cystic, Mucinous, and Serous; Precancerous Conditions; Risk Factors; Retrospective Studies
PubMed: 37003852
DOI: 10.1016/j.hpb.2023.03.001 -
Cancer Metastasis Reviews Mar 2023Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low... (Review)
Review
Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low as 48%. PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples. The secondary aim was to identify whether genetic marks could be used to predict patient survival. Ovid EMBASE, Ovid MEDLINE, PubMed, and Web of Science were searched to identify studies investigating the genetic profile of histologically-confirmed human PMP or AMN samples. We review findings of 46 studies totalling 2181 tumour samples. The most frequently identified somatic gene mutations in patients with PMP included KRAS (38-100%), GNAS (17-100%), and TP53 (5-23%); however, there were conflicting results of their effect on survival. Three studies identified molecular subtypes based on gene expression profiles classifying patients into oncogene-enriched, immune-enriched, and mixed molecular subtypes with prognostic value. This review summarises the current literature surrounding genetic aberrations in PMP and AMNs and their potential utility for targeted therapy. Given the recent advances in clinical trials to directly target KRAS and GNAS mutations in other cancers, we propose a rationale to explore these mutations in future pre-clinical studies in PMP with a view for a future clinical trial.
Topics: Humans; Pseudomyxoma Peritonei; Peritoneal Neoplasms; Appendiceal Neoplasms; Genetic Profile; Proto-Oncogene Proteins p21(ras)
PubMed: 36723696
DOI: 10.1007/s10555-023-10088-0 -
American Journal of Transplantation :... Mar 2023Solid organ transplantation (SOT) recipients are known to carry an increased risk of malignancy because of long-term immunosuppression. However, the progression of...
Solid organ transplantation (SOT) recipients are known to carry an increased risk of malignancy because of long-term immunosuppression. However, the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN) in this population remains unclear. We performed a systematic review by searching PubMed, Embase, Scopus, and Google Scholar. All studies containing IPMNs in solid organ transplantation recipients were screened. We included 11 studies in our final analysis, totaling 274 patients with IPMNs of the 8213 SOT recipients. The prevalence from 8 studies was 4.7% (95% CI 2.4%-7.7%) in a random-effects model with median study periods of 24 to 220 months. The median rate for all progressions from 10 studies was 20% (range, 0%-88%) within 13 to 41 months of the median follow-up time. By utilizing the results of 3 case-control studies, the relative risk from a random-effects model for progression (worrisome features and high-risk stigmata) of IPMNs was 0.39 (95% CI 0.12-1.31). No adenocarcinoma derived from IPMN was reported in the included studies. Overall, this study indicates that the progression of pretransplant IPMN does not increase drastically compared with the general nontransplant population. However, considering the limited literature, further studies are required for confirmation.
Topics: Humans; Pancreatic Intraductal Neoplasms; Carcinoma, Pancreatic Ductal; Prevalence; Retrospective Studies; Adenocarcinoma, Mucinous; Pancreatic Neoplasms; Pancreas; Organ Transplantation
PubMed: 36695699
DOI: 10.1016/j.ajt.2022.11.024 -
Infection and Drug Resistance 2022Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main... (Review)
Review
Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main role in inflammatory cytokine responses. Similarly, alveolar macrophages produce IFN-β, IFN-α, TNF-α, IL-6, CXCL10, and CCL3, while alternatively activated macrophages differentiate at the late phase, and require IL-13 or IL-4 cytokines. Furthermore, activated NKT cells secrete IL-13 and IL-4 that cause lung epithelial, endothelial and fibroblasts to secrete eotaxin that enhances the recruitment of eosinophil to the lung. CD8 and CD4T cells infection by the virus decreases the IFN-γ and IL-2 production. Despite this, both are involved in terminating virus replication. CD8T cells produce a larger amount of IFN-γ than CD4T cells, and CD8T cells activated under type 2 conditions produce IL-4, down regulating CD8 expression, granzyme and IFN-γ production. Antiviral inhibitors inhibit biological functions of viral proteins. Some of them directly target the virus replication machinery and are effective at later stages of infection; while others inhibit F protein dependent fusion and syncytium formation. TMC353121 reduces inflammatory cytokines, TNF-α, IL-6, and IL-1β and chemokines, KC, IP-10, MCP and MIP1-α. EDP-938 inhibits viral nucleoprotein (N), while GRP-156784 blocks the activity of respiratory syncytial virus ribonucleic acid (RNA) polymerase. PC786 inhibits non-structural protein 1 (NS-1) gene, RANTES transcripts, virus-induced CCL5, IL-6, and mucin increase. In general, it is an immune reaction that is blamed for the disease severity and pathogenesis in respiratory syncytial virus infection. Anti-viral inhibitors not only inhibit viral entry and replication, but also may reduce inflammatory cytokines and chemokines. Many respiratory syncytial virus inhibitors are proposed; however, only palivizumab and ribavirin are approved for prophylaxis and treatment, respectively. Hence, this review is focused on immunity cell responses to respiratory syncytial virus and the role of antiviral inhibitors.
PubMed: 36540102
DOI: 10.2147/IDR.S387479