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Iranian Biomedical Journal Nov 2021Lung injury is common in coronavirus disease 2019 (COVID-19) patients. The severity of lung injury appears to be reflected in serum Krebs von den Lungen-6 (KL-6), a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lung injury is common in coronavirus disease 2019 (COVID-19) patients. The severity of lung injury appears to be reflected in serum Krebs von den Lungen-6 (KL-6), a glycoprotein expressed on type II alveolar epithelium. This study aims to assess the role of serum KL-6 in reflecting the severity of lung injury in COVID-19 patients.
METHODS
A systematic search was conducted in Scopus, PubMed, Wiley Online Library, and ProQuest. Articles were screened based on several eligibility criteria and assessed for study quality using Newcastle-Ottawa Scale.
RESULTS
This systematic review included four studies involving a total of 151 adult COVID-19 patients. Pooled analysis revealed that serum KL-6 was significantly higher in severe patients (SMD = 1.16; 95% CI = 0.69–1.63) with moderately high pooled sensitivity (79%; 95% CI = 61–91%) and specificity (86%; 95% CI = 72–95%).
CONCLUSION
High serum KL-6 may depict more severe lung injury in COVID-19 patients with moderately high sensitivity and specificity.
Topics: Biomarkers; COVID-19; Humans; Lung Injury; Mucin-1; Sensitivity and Specificity; Severity of Illness Index
PubMed: 34641641
DOI: 10.52547/ibj.25.6.381 -
International Journal of Molecular... Sep 2021The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells,...
The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells, including epithelial cells, fibroblasts, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, basophils, eosinophils, mucin, and lysozyme. Neutrophil infiltration and degranulation occur on the ocular surface. Degranulation, neutrophil extracellular traps formation, called NETosis, and autophagy in neutrophils are involved in the pathogenesis of ocular surface diseases. It is necessary to understand the role of neutrophils on the ocular surface. Furthermore, there is a need for research on therapeutic agents targeting neutrophils and neutrophil extracellular trap formation for ocular surface diseases.
Topics: Cell Degranulation; Cornea; Extracellular Traps; Eye Diseases; Humans; Neutrophil Infiltration; Neutrophils
PubMed: 34638724
DOI: 10.3390/ijms221910386 -
European Journal of Surgical Oncology :... Mar 2022It is unclear whether patients with intraductal papillary mucinous neoplasia harbor a higher risk of developing extrapancreatic malignancies. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is unclear whether patients with intraductal papillary mucinous neoplasia harbor a higher risk of developing extrapancreatic malignancies.
AIMS
We performed a pooled estimate of the incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasia, with a particular focus on the comparison to the general population.
METHODS
Computerized bibliographic search of main databases was performed through February 2021. The primary endpoint was the pooled incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasms. Additional outcome was the comparison between intraductal papillary mucinous neoplasia patients and the general population, expressed in terms of standardized incidence ratio along with 95% confidence intervals.
RESULTS
Eighteen studies with 8709 patients were included. The pooled rate of metachronous extrapancreatic malignancies was 10 (6-13)/1000 persons-year. No difference was observed according to intraductal papillary mucinous neoplasia histology and sex, whereas a significantly superior incidence of extrapancreatic malignancies was observed in patients with main-duct (36.7%, 25.4%-48%) as compared to branch-duct intraductal papillary mucinous neoplasia (26.2%, 17.6%-34.8%; p = 0.03). Pooled standardized incidence ratio comparing expected rates in the general population was 1.01 (0.79-1.29); no difference was observed concerning rates of metachronous gastric cancer (standardized incidence ratio 1.60, 0.72-3.54) and colorectal cancer (1.29, 0.92-1.18), whereas biliary cancer was observed more frequently in intraductal papillary mucinous neoplasia patients (2.29, 1.07-4.93).
CONCLUSION
Patients with intraductal papillary mucinous neoplasia harbor an overall rate of extrapancreatic malignancies as high as 27.3%. The rate of metachronous extrapancreatic malignancies is not superior to the general population.
Topics: Adenocarcinoma, Mucinous; Carcinoma, Pancreatic Ductal; Carcinoma, Papillary; Humans; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms
PubMed: 34620511
DOI: 10.1016/j.ejso.2021.09.018 -
World Journal of Surgery Jan 2022The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus surgery alone and to identify pathologic features that may predict survival benefit from adjuvant chemotherapy.
METHOD
A systematic search of MEDLINE, PubMed, Scopus, and EMBASE was performed using the PRISMA framework. Studies comparing adjuvant chemotherapy and surgery alone for patients with IIPMNs were included. Primary endpoint was overall survival (OS). A narrative synthesis was performed to identify pathologic features that predicted survival benefits from adjuvant chemotherapy.
RESULTS
Eleven studies and 3393 patients with IIPMNs were included in the meta-analysis. Adjuvant chemotherapy significantly reduced the risk of death in the overall cohort (HR 0.57, 95% CI 0.38-0.87, p = 0.009) and node-positive patients (HR 0.29, 95% CI 0.13-0.64, p = 0.002). Weighted median survival difference between adjuvant chemotherapy and surgery alone in node-positive patients was 11.6 months (95% CI 3.83-19.38, p = 0.003) favouring chemotherapy. Adjuvant chemotherapy had no impact on OS in node-negative patients (HR 0.53, 95% CI 0.20-1.43, p = 0.209). High heterogeneity (I > 75%) was observed in pooled estimates of hazard ratios. Improved OS following adjuvant chemotherapy was reported for patients with stage III/IV disease, tumour size > 2 cm, node-positive status, grade 3 tumour differentiation, positive margin status, tubular carcinoma subtype, and presence of perineural or lymphovascular invasion.
CONCLUSION
Adjuvant chemotherapy was associated with improved OS in node-positive IIPMNs. However, the findings were limited by marked heterogeneity. Future large multicentre prospective studies are needed to confirm these findings and explore additional predictors of improved OS to guide patient selection for adjuvant chemotherapy.
Topics: Chemotherapy, Adjuvant; Cohort Studies; Humans; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms
PubMed: 34545418
DOI: 10.1007/s00268-021-06309-8 -
Modern Pathology : An Official Journal... Jan 2022The literature is highly conflicted on what percentage of pancreatic ductal adenocarcinomas (PDACs) arise in association with intraductal papillary mucinous neoplasms... (Comparative Study)
Comparative Study
Pancreatic ductal adenocarcinomas associated with intraductal papillary mucinous neoplasms (IPMNs) versus pseudo-IPMNs: relative frequency, clinicopathologic characteristics and differential diagnosis.
The literature is highly conflicted on what percentage of pancreatic ductal adenocarcinomas (PDACs) arise in association with intraductal papillary mucinous neoplasms (IPMNs). Some studies have claimed that even small (Sendai-negative) IPMNs frequently lead to PDAC. Recently, more refined pathologic definitions for mucin-lined cysts were provided in consensus manuscripts, but so far there is no systematic analysis regarding the frequency and clinicopathologic characteristics of IPMN-mimickers, i.e., pseudo-IPMNs. In this study, as the first step in establishing frequency, we performed a systematic review of the pathologic findings in 501 consecutive ordinary PDACs, which disclosed that 10% of PDACs had associated cysts ≥1 cm. While 31 (6.2%) of these were IPMN or mucinous cystic neoplasm (MCN), 19 (3.8%) were other cyst types that mimicked IPMN (pseudo-IPMNs) per recent WHO/consensus criteria. As the second step of the study, we performed a comparative clinicopathologic analysis by also including our entire surgical pathology/consultation databases that was comprised of 60 IPMN-associated PDACs, 30 MCN-associated PDACs and 40 pseudo-IPMN-associated PDACs. We found that 84% of true IPMNs were pre-operatively recognized, whereas IPMN was considered in differential diagnosis of 33% of pseudo-IPMNs. Of the 40 pseudo-IPMNs, there were 15 secondary duct ectasias; 6 large-duct-type PDACs; 5 pseudocysts; 5 cystic tumor necrosis; 4 simple mucinous cysts; 3 groove pancreatitis-associated paraduodenal wall cysts; and 2 congenital cysts. Microscopically, pseudo-IPMNs had at least partial mucinous-lining mimicking IPMN but had smaller cystic (mean = 1.9 cm) and larger PDAC (mean = 3.8 cm) components compared to true IPMNs (cyst = 5.7 cm; PDAC = 2.0 cm). In summary, in this pathologically verified analysis that utilized refined criteria, 10% of PDACs were discovered to have cysts ≥1 cm, about two-thirds of which were IPMN/MCN but about one-third were pseudo-IPMNs. True IPMNs underlying the PDACs are often large and are already diagnosed pre-operatively as having an IPMN component, whereas only a third of the pseudo-IPMNs receive IPMN diagnosis by imaging and their cysts are smaller. At the histopathologic level, pseudo-IPMNs are highly prone to misdiagnosis as IPMN, which presumably accounts for much higher association of IPMNs with PDAC as reported in some studies. The subtle but salient characteristics of pseudo-IPMNs elucidated in this study should be combined with careful radiological/clinical correlation in order to exclude pseudo-IPMNs.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Carcinoma, Pancreatic Ductal; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms
PubMed: 34518632
DOI: 10.1038/s41379-021-00902-x -
Annals of Gastroenterology 2021The American Gastroenterological Association recommends endoscopic ultrasound (EUS) for evaluating pancreatic cystic lesions (PCL) with ≥2 high-risk features (HRF),...
BACKGROUND
The American Gastroenterological Association recommends endoscopic ultrasound (EUS) for evaluating pancreatic cystic lesions (PCL) with ≥2 high-risk features (HRF), whereas the American College of Gastroenterology recommends EUS for ≥1 HRF. This systematic review and meta-analysis compared the diagnostic accuracy of using ≥1 vs. ≥2 HRF for assessing the risk of advanced neoplasia (AN) and performing EUS in PCL.
METHODS
An electronic database search was performed for eligible studies. AN was defined as pancreatic adenocarcinoma, intraductal papillary mucinous neoplasm or mucinous cystadenoma with high-grade dysplasia, pancreatic intraepithelial neoplasia and pancreatic neuroendocrine tumors. HRF included cyst size ≥3 cm, solid component, and dilated pancreatic duct ≥5 mm. The primary outcome was the sensitivity and specificity of using ≥1 vs. ≥2 HRF as an indication for EUS to detect AN in PCL.
RESULTS
Of 38 studies initially screened, 8 were included in the final analysis. Seven studies assessed the accuracy of ≥2 HRF and 4 studies assessed ≥1 HRF. The pooled sensitivity, specificity, positive and negative predictive values of EUS for detecting AN were 41.7% (95% confidence interval 19.5-67.8%), 90.8% (81.9-95.5%), 30.4% (19.4-44.2%) and 94.3% (89.6-97.0%) with ≥2HRFs, and 77.1% (66.1-85.3%), 72.7% (50.4-87.5%), 17.95% (10.3-29.4%), 98.1% (90.8-99.6%), respectively, with ≥1 HRF.
CONCLUSION
Performing EUS for PCL with ≥1 HRF could offer greater sensitivity in detecting AN compared to ≥2 HRF, with a similar negative predictive value.
PubMed: 34475747
DOI: 10.20524/aog.2021.0630 -
BJS Open Jul 2021Mucinous appendiceal neoplasms with peritoneal dissemination (PD) show a wide spectrum of clinical behaviour. Histological grade has been correlated with prognosis, but...
BACKGROUND
Mucinous appendiceal neoplasms with peritoneal dissemination (PD) show a wide spectrum of clinical behaviour. Histological grade has been correlated with prognosis, but no universally accepted histological grading has been established. The aim of this systematic review was to provide historical insight to understand current grading classifications, basic histopathological features of each category, and to define which classification correlates best with prognosis.
METHODS
MEDLINE and the Cochrane Library were searched for studies that reported survival across different pathological grades in patients with mucinous neoplasm of the appendix with PD treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. PRISMA guidelines were followed.
RESULTS
Thirty-eight studies were included. Ronnett's classification was the most common (9 studies). Classifications proposed by the Peritoneal Surface Oncology Group International (PSOGI) (6 studies) and the seventh or eighth edition of the AJCC (7 studies) are gaining in popularity. Nine studies supported a two-tier, 12 a three-tier, and two a four-tier classification system. Three studies demonstrated that acellular mucin had a better prognosis than low-grade pseudomyxoma peritonei in the PSOGI classification or M1bG1 in the eighth edition of the AJCC classification. Four studies demonstrated that the presence of signet ring cells was associated with a worse outcome than high-grade pseudomyxoma peritonei in the PSOGI classification and M1bG2 in the eighth edition of the AJCC.
CONCLUSION
There is a great need for a common language in describing mucinous neoplasms of the appendix with PD. Evolution in terminology as a result of pathological insight turns the four-tiered PSOGI classification system into a coherent classification option.
Topics: Appendiceal Neoplasms; Appendix; Cytoreduction Surgical Procedures; Humans; Peritoneal Neoplasms; Pseudomyxoma Peritonei
PubMed: 34355239
DOI: 10.1093/bjsopen/zrab059 -
Journal of Cancer Research and Clinical... Jun 2022Abscess or fistula of the anal region is an uncommon presentation of malignancy. Under the assumption of a benign condition, diagnostics is often delayed, resulting in...
Non-mucinous adenocarcinomas and squamous cell carcinomas of the anal region masquerading as abscess or fistula: a retrospective analysis and systematic review of literature.
PURPOSE
Abscess or fistula of the anal region is an uncommon presentation of malignancy. Under the assumption of a benign condition, diagnostics is often delayed, resulting in advanced tumour stages at first diagnosis. Due to the case rarity, treatment guidelines for cancers of anorectal region masquerading as abscess or fistula are missing.
METHODS
We analysed all patients presenting with an abscess or fistula of the anal region in our department between January 2004 and August 2020. The malignancies were included to our study to acquire data on clinical presentation, treatment and outcome. Furthermore, a systematic review to present adenocarcinomas and squamous cell carcinomas associated to an abscess or fistula was performed.
RESULTS
0.5% of the patients treated for an abscess or fistula of the anal region met the selection criteria. Mean time from the onset of symptoms to diagnosis of malignancy was 100 days. Histology revealed adenocarcinoma and squamous cell carcinoma each in two patients. All patients had locally advanced tumours without distant metastases, in two cases with regional lymph-node metastases. Neoadjuvant chemoradiation was applied in two patients. All patients underwent abdomino-perineal resection of the rectum. The overall outcome reveals a recurrence-free survival of 4.5 and 3 years for two patients. Further two patients died within 5 months after the primary resection.
CONCLUSION
Advanced carcinomas of the anorectal region may masquerade as abscess or fistula, cause diagnostic problems and delay oncologic treatment. However, even in these very advanced situations, surgical therapy with curative intent should be attempted.
Topics: Abscess; Adenocarcinoma; Carcinoma, Squamous Cell; Fistula; Humans; Rectum; Retrospective Studies
PubMed: 34338860
DOI: 10.1007/s00432-021-03747-8 -
BMC Gastroenterology Jul 2021Approximately 5.0-24.2% of colorectal cancers (CRCs) have inactivating mutations in SMAD4, making it one of the frequently mutated genes in CRC. We thus carried out a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Approximately 5.0-24.2% of colorectal cancers (CRCs) have inactivating mutations in SMAD4, making it one of the frequently mutated genes in CRC. We thus carried out a comprehensive system review and meta-analysis investigating the prognostic significance and clinicopathological features of SMAD4 gene mutation in CRC patients.
METHODS
A detailed literature search was conducted in PubMed, Web of Science and Embase databases to study the relationship between SMAD4 mutations and the demographic and clinicopathological characteristics in CRC patients. The hazard ratios (HRs) with 95% confidence intervals (CI) were used to evaluate the effect of SMAD4 mutations on overall survival (OS) and progression-free survival (PFS)/recurrence-free survival (RFS).
RESULTS
Ten studies enrolling 4394 patients were eligible for inclusion. Data on OS were available from 5 studies and data on PFS/RFS were available from 3 studies. Comparing SMAD4-mutated CRC patients with SMAD4 wild-type CRC patients, the summary HR for OS was 1.46 (95% CI 1.28-1.67, P = 0.001), the summary HR for PFS/RFS was 1.59 (95% CI 1.14-2.22, P = 0.006). In terms of clinicopathology parameters, 9 studies have data that can be extracted, SMAD4 mutations were associated with tumor location (odds ratio [OR] = 1.15, colon/rectum, 95% CI 1.01-1.31, P = 0.042), TNM stage (OR = 1.28, stage IV/I-III, 95% CI 1.03-1.58, P = 0.025), lymph node metastasis (OR = 1.42, N1 + N2/N0, 95% CI 1.20-1.67, P < 0.001), mucinous differentiation (OR = 2.23, 95% CI 1.85-2.70, P < 0.001) and rat sarcoma viral oncogene homolog (RAS) mutation status (OR = 2.13, 95% CI 1.37-3.34, P = 0.001). No connection was found with age, gender, tumor grade, microsatellite instability status and b-viral oncogene homolog B1 mutation status. Besides, publication bias was not observed in any study.
CONCLUSIONS
This meta-analysis suggests that SMAD4 mutation was associated with OS, PFS/RFS, and clinicopathological parameters, including tumor site, disease stage, RAS status, lymph node metastasis and mucinous differentiation. Our meta-analysis indicated that SMAD4 mutations could predict the poor prognosis and aggressive clinicopathological characteristics of CRC. More large-sample cohort studies are needed to confirm this conclusion. Since SMAD4 mutations are closely related to RAS mutations, their relationship warrants further investigation.
Topics: Biomarkers, Tumor; Colorectal Neoplasms; Humans; Microsatellite Instability; Mutation; Prognosis; Smad4 Protein
PubMed: 34301194
DOI: 10.1186/s12876-021-01864-9 -
Frontiers in Oncology 2021To assess the diagnostic accuracy of diffusion-weighted imaging (DWI) in predicting the malignant potential in patients with intraductal papillary mucinous neoplasms...
Diagnostic Performance of Diffusion-Weighted Imaging for Differentiating Malignant From Benign Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Systematic Review and Meta-Analysis.
OBJECTIVES
To assess the diagnostic accuracy of diffusion-weighted imaging (DWI) in predicting the malignant potential in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.
METHODS
A systematic search of articles investigating the diagnostic performance of DWI for prediction of malignant potential in IPMNs was conducted from PubMed, Embase, and Web of Science from January 1997 to 10 February 2020. QUADAS-2 tool was used to evaluate the study quality. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and their 95% confidence intervals (CIs) were calculated. The summary receiver operating characteristic (SROC) curve was then plotted, and meta-regression was also performed to explore the heterogeneity.
RESULTS
Five articles with 307 patients were included. The pooled sensitivity and specificity of DWI were 0.74 (95% CI: 0.65, 0.82) and 0.94 (95% CI: 0.78, 0.99), in evaluating the malignant potential of IPMNs. The PLR was 13.5 (95% CI: 3.1, 58.7), the NLR was 0.27 (95% CI: 0.20, 0.37), and DOR was 50.0 (95% CI: 11.0, 224.0). The area under the curve (AUC) of SROC curve was 0.84 (95% CI: 0.80, 0.87). The meta-regression showed that the slice thickness of DWI (p = 0.02) and DWI parameter (p= 0.01) were significant factors affecting the heterogeneity.
CONCLUSIONS
DWI is an effective modality for the differential diagnosis between benign and malignant IPMNs. The slice thickness of DWI and DWI parameter were the main factors influencing diagnostic specificity.
PubMed: 34290974
DOI: 10.3389/fonc.2021.637681