Medicine

About the journal

Publisher: Lippincott Williams & Wilkins
Published: 1922 to the present, United States
Language: English
ISSN: 0025-7974 (print), 1536-5964 (electronic)
Its record in the NLM Catalog

2020s

Contributions of smoking behaviour to lung cancer subtypes: A two-sample Mendelian randomization study. M.A. Jareebi, A.Y. Alqassim. 2026;105(42):e51170. PubMed · Publisher · Free full text

Abstract

Smoking is an established cause of lung cancer (LC), but the relative causal contributions of whether a person ever smokes and how heavily they smoke across histological subtypes remain uncertain. This study investigated the causal effects of smoking status and smoking intensity on major LC subtypes. Two-sample Mendelian randomization (MR) was performed. Genetic instruments were drawn from the GWAS and Sequencing Consortium of Alcohol and Nicotine Use: 85 variants for smoking status, a binary trait contrasting ever with never smokers, and 23 variants for smoking intensity, a continuous trait measuring cigarettes smoked per day. Outcomes were 5 LC phenotypes from FinnGen: non-small cell LC (1627 cases), adenocarcinoma (571), squamous cell carcinoma (365), small cell LC (179), and mesothelioma (133). Inverse-variance weighted regression with multiplicative random effects was the primary estimator, with weighted median, weighted mode, and MR-Egger as sensitivity analyses. Benjamini-Hochberg correction was applied across all ten tests. Analyses used R 4.2.3 with TwoSampleMR 0.7.9. Smoking intensity was causally associated with all 4 smoking-related subtypes: squamous cell carcinoma (odds ratio [OR]: 5.95 per standard deviation increase, 95% confidence interval [CI]: 3.12-11.37), small cell LC (OR: 4.43, 95% CI: 1.60-12.32), non-small cell LC (OR: 3.45, 95% CI: 2.30-5.18), and adenocarcinoma (OR: 2.66, 95% CI: 1.40-5.06). All 4 survived correction for multiple testing and were reproduced by the weighted median and weighted mode estimators. Smoking status showed positive point estimates for all 4 subtypes (OR: 1.40-1.61) but reached only nominal significance for non-small cell LC (OR: 1.51, 95% CI: 1.04-2.19, P = .030), which did not survive correction and was not reproduced by other estimators. Neither exposure was associated with mesothelioma. Smoking intensity shows robust causal effects on all smoking-related LC subtypes, whereas the evidence for smoking status is directionally consistent but considerably weaker. The null finding for mesothelioma, a cancer principally caused by asbestos, supports the specificity of the instruments. These results indicate that reducing consumption among established smokers warrants emphasis alongside preventing uptake.

Copyright © 2026 the Author(s). Published by Wolters Kluwer Health, LLC.
Interaction between ENPP1 and homologous recombination deficiency defines distinct pan-cancer signatures: A retrospective observational study. Y.M. Kim, S.H. Lee, W. Na, et al. 2026;105(1):e47164. PubMed · Publisher · Free full text

Abstract

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), 1st identified in breast cancer and subsequently in multiple other cancer types, is an innate immune checkpoint regulator that recently emerged as a promising biomarker and therapeutic target. Homologous recombination deficiency (HRD) has gained clinical relevance with therapeutic vulnerability, particularly in breast and ovarian cancers. Despite the increasing significance of ENPP1 and HRD in cancer biology and treatment, their potential relationships have not yet been comprehensively investigated. We analyzed the relationship between ENPP1 expression and HRD score across the Cancer Genome Atlas pan-cancer and individual tumor types using the Pearson and Spearman correlations. To account for heterogeneity, pan-cancer samples were clustered using linear regression into 3 groups based on Bayesian Information Criterion. Differential expression, functional enrichment, and survival analyses were performed for these clusters at both the pan-cancer and representative tumor type levels. Although the pan-cancer relationship between ENPP1 expression and HRD score was heterogeneous, significant correlations were observed in 11 tumor types. Linear regression-based clustering resolved this heterogeneity into 3 functionally and clinically distinct groups: Cluster 1 was characterized by proliferation programs; Cluster 2 by extracellular matrix remodeling, differentiation, and immune response; and Cluster 3, by metabolic reprogramming. Clinically, Cluster 3 was associated with better survival than Clusters 1 and 2 in a pan-cancer analysis (P < .0001). At the individual tumor type level, these global cluster features were further modified in tissue-specific contexts, reflecting local microenvironment adaptation. Significant survival differences were observed in patients with adrenocortical carcinoma, chromophobe renal cell carcinoma, low grade glioma, and mesothelioma, further underscoring the tissue-specific modification of global cluster features. Our comprehensive pan-cancer analysis revealed the intrinsic heterogeneity of ENPP1 expression and HRD score, which may arise from complex and dynamic interactions with diverse cancer hallmarks, including proliferation, extracellular matrix remodeling, immune response, and metabolic reprogramming, and can be generalized into 3 clusters with distinct molecular and clinical characteristics. At the individual tumor type level, these global cluster features were further modified to adapt to a tissue-specific microenvironment, manifesting distinct tissue-specific patterns. Collectively, these findings provide a foundation for refining biomarker-driven precision medicine strategies for diverse tumor types.

Copyright © 2026 the Author(s). Published by Wolters Kluwer Health, Inc.
Bidirectional Mendelian randomization and potential mechanistic insights into the causal relationship between gut microbiota and malignant mesothelioma. Y. Zhou, H. Zhu, L. Zhao, et al. 2025;104(17):e42245. PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is a rare but aggressive cancer originating from mesothelial cells, which presents significant challenges to patients' physical and psychological well-being. The gut-lung axis underscores the connection between gut microbiota and respiratory diseases, with emerging evidence suggesting a strong association between gut microbiota and the development of MM. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between gut microbiota and MM, while also exploring the underlying mechanisms through bioinformatics approaches. Gut microbiota summary data were obtained from the MiBioGen consortium, while MM data were sourced from the FinnGen R11 dataset. Causality was examined using the inverse variance weighted method as the primary analysis. Additional methods, including the weighted median, simple mode, MR-Egger, and weighted mode, were also employed. The robustness of the findings was validated through sensitivity analyses, and reverse causality was considered to further strengthen the MR results. Moreover, bioinformatics analyses were conducted on genetic loci associated with both gut microbiota and MM to explore potential underlying mechanisms. Our study suggests that genetically predicted increases in class.Bacilli, family.Rikenellaceae, genus.Clostridium innocuum group, and order.Lactobacillales were suggestively associated with a higher risk of MM, whereas increases in genus.Ruminococcaceae UCG004, genus.Flavonifractor, phylum.Firmicutes, genus.Anaerofilum, genus.Clostridium sensu stricto 1, and genus.Lactobacillus appeared to confer protective effects. Bioinformatics analysis indicated that differentially expressed genes near loci associated with gut microbiota might affect MM by modulating pathways and the tumor microenvironment. The results of this study point to a potential genetic predisposition linking gut microbiota to MM. Further experimental validation is crucial to confirm these candidate microbes, establish causality, and elucidate the underlying mechanisms.

Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.
Pan-cancer analysis shows that TRIP13 as a potential prognostic and immunotherapeutic biomarker for multiple cancer types including LIHC and LUAD. C. Li, Z. Zhou, Y. Liu, et al. 2025;104(22):e42588. PubMed · Publisher · Free full text

Abstract

Growing evidence indicates that thyroid hormone receptor interactor 13 (TRIP13) plays an oncogenic role in various malignancies. Pan-cancer analysis was performed to elucidate the prognostic value and oncogenic role of TRIP13, and detect TRIP13 expression levels in diverse cancer types. We found that TRIP13 was overexpressed in multiple tumors. Subsequently, we explored the relationship between TRIP13 expression-associated alterations and clinical prognosis, DNA methylation, immune cell infiltration, immune checkpoints, tumor mutational burden, microsatellite instability, and drug sensitivity. Gene set enrichment analysis was utilized to explore the molecular mechanism of TRIP13. A nomogram was developed to predict the impact of TRIP13 expression on an liver hepatocellular carcinoma prognosis. The miRDB database was used to predict miRNA targets for TRIP13. The results indicated that TRIP13 overexpression was associated with a poor overall survival, disease-specific survival, and progression-free interval in various cancer types. The mutation frequency of TRIP13 was the highest in individuals with lung squamous cell carcinoma. TRIP13 expression levels were negatively associated with immunocyte infiltration, immune scores, tumor mutational burden, microsatellite instability, and DNA methylation in certain cancers, and positively correlated with the expression of at least 5 immune checkpoint-related genes in bladder carcinoma, breast cancer, kidney clear cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, mesothelioma, and thyroid cancer. In addition, we discovered that TRIP13 participated in the cell cycle during Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis for most cancers. The areas under the curve for the 1-, 3-, and 5-year survival rates in the nomogram exceeded 0.6, indicating that the model has good predictive performance, and was validated using samples obtained from liver hepatocellular carcinoma patients. We also found that miR-656-3p tends to bind to TRIP13 mRNA and regulate TRIP13 expression. Additionally, we identified 26 drugs sensitive to tumors with high TRIP13 expression levels from the CTRP and GDSC databases. Finally, the promoting effect of TRIP13 on lung cancer was verified, the results demonstrating TRIP13 could accelerate lung cancer cell proliferation, migration, and invasion. Collectively, our findings suggest that TRIP13 may act as a potential prognostic marker and novel target for cancer therapy.

Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.
The application value of HRCT quantitative analysis in early pneumoconiosis and concomitant diseases. X. Hu, X.D. Liu, T. Gao, et al. 2025;104(18):e42374. PubMed · Publisher · Free full text

Abstract

This study aims to investigate the differential capabilities of high-resolution computed tomography (HRCT) and digital radiography (DR) in detecting small opacity characteristics and distribution patterns in pneumoconiosis, while evaluating HRCT's potential for early diagnosis of disease-associated complications. A retrospective evaluation was conducted on the HRCT and DR imaging findings of 206 dust-exposed workers. Quantitative CT assessment was carried out for emphysema and diffuse coniofibrosis. The density of mediastinal lymph nodes and the number of calcified lymph nodes were counted, and pleural plaques were graded. Moreover, the detection rates of small opacities and pneumoconiosis complications were compared between the 2 methods. Results demonstrated HRCT's superior capability to DR in detecting small opacities, characterizing their distribution patterns, and identifying complications. Significant positive correlations emerged between CT-based complication scores and pneumoconiosis staging. The findings indicate that HRCT enhances early detection of small opacities and enables quantitative assessment of comorbid pathologies, providing critical insights for timely clinical intervention and therapeutic management in early-stage pneumoconiosis patients.

Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.
Well-differentiated papillary mesothelial tumor of the peritoneum in a young woman: A case report with molecular insights. R. Xu, S. Xu, X. Wang, et al. 2025;104(48):e46241. Case report PubMed · Publisher · Free full text

Abstract

Rationale: Well-differentiated papillary mesothelial tumor (WDPMT) is an uncommon, slow-growing neoplasm that is often an incidental finding in the peritoneum of women of reproductive age. It can be misdiagnosed as malignant mesothelioma on routine histology, potentially leading to unnecessary aggressive therapy. The role of modern molecular techniques in resolving this diagnostic dilemma and guiding conservative management warrants emphasis.

Patient Concerns: A 32-year-old woman presented with vague abdominal discomfort. Imaging revealed bilateral ovarian cysts and significant pelvic free fluid.

Diagnoses: Laparoscopy identified multiple small peritoneal nodules. Initial frozen-section histology suggested malignant mesothelioma. Definitive diagnosis of WDPMT was established through comprehensive immunohistochemistry (retained BAP1 expression) and next-generation sequencing, which revealed a low tumor mutational burden and a pathogenic GPR124 mutation. This genetic profile distinct from malignant mesothelioma.

Interventions: After definitive diagnosis and thorough counseling, the patient opted against cytoreductive surgery or systemic therapy. A strategy of active surveillance with serial imaging and tumor marker assessment was implemented.

Outcomes: The patient remained asymptomatic with no evidence of disease recurrence or progression 24 months after diagnosis.

Lessons: This case highlights that a definitive distinction between WDPMT and malignant mesothelioma is paramount, as it dictates a radically different management strategy. Integration of immunohistochemistry (particularly BAP1) and molecular profiling is essential for accurate diagnosis and can prevent overtreatment. For appropriately selected patients with WDPMT, conservative management with active surveillance represents a safe and effective approach, underscoring the value of precision medicine in guiding patient-centric care.

Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.
Diagnosis and treatment of malignant retroperitoneal mesothelioma: A case report. F. Tang, Y. Cui, Y. Gao. 2024;103(17):e37985. Case report PubMed · Publisher · Free full text

Abstract

Rationale: Malignant peritoneal mesothelioma (MPM) is a rare clinical disease. Although there are several reports describing intraperitoneal mesothelioma of the lung, liver, and intestine, retroperitoneal mesothelioma is, to our knowledge, very rare and rarely reported. In recent years, our best clinical protocols for the treatment and diagnosis of retroperitoneal mesothelioma have not been proven and the diagnosis and treatment are challenging.

Patient Concerns: A 37-year-old Chinese woman complained of bilateral low back pain for a month, with obvious symptoms of low back pain on the left side. To treat low back pain, retroperitoneal masses were found during physical examination. The patient consulted a urological specialist for further treatment.

Diagnosis: After the operation, pathological biopsy confirmed retroperitoneal epithelioid diffuse mesothelioma.

Interventions: After exclusion of surgical contraindications, the patient underwent laparoscopic retroperitoneal lesion resection under tracheal intubation and general anesthesia, and the operation was successful.

Outcomes: On the tenth day after surgery, the patient vital signs were stable, and he was discharged.

Lessons: Patients with malignant peritoneal mesothelioma may have no typical clinical symptoms, and the diagnosis is based on pathological and immunohistochemical examination. In selected patients, surgical cell reduction and intraoperative intraperitoneal heat chemotherapy have become the first choice of treatment, which can achieve ideal therapeutic effects and prolong survival.

Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
Pancancer analysis of the interactions between CTNNB1 and infiltrating immune cell populations. X. Xu, A. Yang, Y. Han, et al. 2024;103(44):e40186. PubMed · Publisher · Free full text

Abstract

Recently, evidence has indicated that CTNNB1 is important in a variety of malignancies. However, how CTNNB1 interacts with immune cell infiltration remains to be further investigated. In this study, we focused on the correlations between CTNNB1 and tumorigenesis, tumor progression, mutation, phosphorylation, and prognosis via gene expression profiling interaction analysis; TIMER 2.0, cBioPortal, GTEx, CPTAC, and GEPIA2 database analyses; and R software. CTNNB1 mutations are most found in uterine endometrioid carcinoma and hepatocellular carcinoma. However, no CTNNB1 mutations were found to be associated with a poor prognosis. In addition, CTNNB1 DNA methylation levels were higher in normal tissues than in tumor tissues in cancer except for breast invasive carcinoma, which had higher methylation levels in tumor tissues. The phosphorylation level of the S675 and S191 sites of CTNNB1 was greater in the primary tumor tissues in the clear cell renal cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, pancreatic adenocarcinoma, and breast cancer datasets but not in the glioblastoma multiform dataset. As for, with respect to immune infiltration, CD8 + T-cell infiltration was negatively correlated with the expression of CTNNB1 in thymoma and uterine corpus endometrial carcinoma. The CTNNB1 level was found to be positively associated with the infiltration index of the corresponding fibroblasts in the TCGA tumors of colon adenocarcinoma, human papillomavirus-negative head and neck squamous cell carcinoma, mesothelioma, testicular germ cell tumor, and thymoma. We also identified the top CTNNB1-correlated genes in the TCGA projects and analyzed the expression correlation between CTNNB1 and selected target genes, including PPP4R2, RHOA, and SPRED1. Additionally, pathway enrichment suggested that NUMB is involved in the Wnt pathway. This study highlights the predictive role of CTNNB1 across cancers, suggesting that CTNNB1 might serve as a potential biomarker for the diagnosis and prognosis evaluation of various malignant tumors.

Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
Clinical predictors and outcomes of non-expandable lung following percutaneous catheter drainage in lung cancer patients with malignant pleural effusion. C.H. Kim, J.E. Park, J.G. Cha, et al. 2023;102(26):e34134. PubMed · Publisher · Free full text

Abstract

Non-expandable lung (NEL) often occurs during pleural fluid drainage in patients with malignant pleural effusion (MPE). However, data regarding the predictors and prognostic impact of NEL on primary lung cancer patients with MPE receiving pleural fluid drainage, compared to malignant pleural mesothelioma (MPM), are limited. This study was aimed to investigate the clinical characteristics of lung cancer patients with MPE developing NEL following ultrasonography (USG)-guided percutaneous catheter drainage (PCD) and compare the clinical outcomes between those with and without NEL. Clinical, laboratory, pleural fluid, and radiologic data and survival outcomes of lung cancer patients with MPE undergoing USG-guided PCD were retrospectively reviewed and compared between those with and without NEL. Among 121 primary lung cancer patients with MPE undergoing PCD, NEL occurred in 25 (21%). Higher pleural fluid lactate dehydrogenase (LDH) levels and presence of endobronchial lesions were associated with development of NEL. The median time to catheter removal was significantly extended in those with NEL compared to those without (P = .014). NEL was significantly associated with poor survival outcome in lung cancer patients with MPE undergoing PCD, along with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS), the presence of distant metastasis, higher serum C-reactive protein (CRP) levels, and not receiving chemotherapy. NEL developed in one-fifth of lung cancer patients undergoing PCD for MPE and was associated with high pleural fluid LDH levels and the presence of endobronchial lesions. NEL may negatively affect overall survival in lung cancer patients with MPE receiving PCD.

Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.
Comprehensive bioinformatics analysis of the role of VWF in the tumor microenvironment of malignant mesothelioma. J. Weng, J. Chen. 2023;102(41):e35579. PubMed · Publisher · Free full text

Abstract

To explore the influence and effect of tumor microenvironment on the development of malignant mesothelioma using machine learning methods. 87 open cases were downloaded from the Cancer Genome Atlas database including transcriptome data, clinical data, and mutation data. The immune, stromal, and estimate scores were calculated for each case by using the ESTIMATE algorithm, and then the cases were grouped according to high and low stromal scores to predict all-cause survival in malignant mesothelioma cases. Their mutation data were analyzed to reveal the differences in mutated genes between the 2 groups, and then the von Willebrand factor (VWF) and FCRL3 genes were identified according to the intersection of DEGs and high-frequency mutated genes. Lastly, the correlation between VWF and the immune checkpoint of 22 kinds of immune cells was analyzed by using the CIBERSORT package of R software. A significant difference was found in the survival time of patients between the high and low stromal score groups. High expression of the VWF gene was negatively correlated with the prognosis of malignant mesothelioma, and the expression of VWF was positively correlated with naive B cells and activated CD4 memory T cells and negatively correlated with NK cells. The results revealed that high expression of VWF may involve in the development of malignant mesothelioma, and the anti-CTLA4 immune checkpoint treatment may have certain efficacy.

Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.
Diagnostic value of pleural fluid SMRP, CA125, MMP-7, and MMP-9 in malignant pleural effusion. G. Han, J. Li, X. Liu, et al. 2023;102(4):e32759. PubMed · Publisher · Free full text

Abstract

This study aimed to investigate the clinical value of mesothelin soluble related peptide (SMRP), cancer antigen 125 (CA125), matrix metalloproteinase-7 (MMP-7), and matrix metalloproteinase-9 (MMP-9) in benign and malignant pleural exudative effusion. A total of 105 adult patients with pleural exudative effusion admitted in our hospital from December 2019 to December 2020 were selected. Patients were divided into the benign group (n = 60) and the malignant group (n = 45) according to their condition. The levels of SMRP, CA125, MMP-7, and MMP-9 in the pleural effusion were determined by enzyme linked immunosorbent assay. Receiver operating characteristic curves were used to analyze the individual and combined predictive value of SMRP, MMP-7, MMP-9, and CA125 levels. In the malignant group, the SMRP, CA125, MMP-7, and MMP-9 levels were all significantly higher than those in benign group (P = .01). The detection efficiency of the 4 indicators in the combined diagnosis were higher than that of single index and combination of any 2 indices. There was a moderate positive correlation between SMRP and CA125 and MMP-7 in malignant pleural effusion. The correlation between MMP-7 and MMP-9 was moderately positive. The diagnostic efficacy of SMRP combined with CA125, MMP-7, and MMP-9 in pleural effusion for malignant pleural effusion and BPE are better than single index, which has certain clinical values for the selection of early intervention scheme for BPE patients.

Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.
Intraoperative nociception and postoperative inflammation associated with the suppression of major complications due to thoracic epidural block after pleurectomy/decortication for malignant pleural mesothelioma under general anesthesia: A retrospective observational study. Y. Hamanaka, W. Ueda, K. Taki, et al. 2023;102(35):e34832. PubMed · Publisher · Free full text

Abstract

A recent study showed that thoracic epidural block (TEB) suppressed the occurrence of major complications after pleurectomy/decortication (P/D) for malignant pleural mesothelioma (MPM) under general anesthesia. To investigate the mechanisms underlying the correlation, both acute inflammatory status and intraoperative nociception were evaluated in the present study. In a single-institutional observational study, consecutive adult patients undergoing P/D were enrolled from March 2019 to April 2022. Perioperative acute inflammatory status was evaluated using differential White blood cell (WBC) counts and serum concentration of C-reactive protein (CRP) both before and after the surgery on postoperative day (POD) 1. The averaged value of nociceptive response index during surgery (mean NR) was obtained to evaluate the level of intraoperative nociception. Multivariable logistic regression analysis was performed to determine the association between perioperative variables and major complications Postoperative major postoperative complication was defined as Clavien-Dindo grades ≥ III. We conducted this study with 97 patients. After logistic regression analysis showed that general anesthesia without TEB was a sole risk factor for major complications, patients were divided into 2 groups: general anesthesia with and without TEB. The incidence of major complications was significantly lower in patients with TEB (33.3%, n = 33) than in those without TEB (64.1%, n = 64, P < .01). Although there was no significant difference in the CRP level between 2 groups, the lymphocyte-to-monocyte ratio (LMR) on POD 1 in patients with TEB was significantly higher than that in patients without TEB (P = .04). The mean NR was significantly lower in patients with TEB than that in those without TEB (P = .02). Both lower mean NR during surgery and higher LMR on POD 1 are likely associated the suppression of major complications due to TEB after P/D under general anesthesia. Decreases in the postoperative acute inflammatory response, caused by the reduction of intraoperative nociception due to TEB, may help suppress major complications after P/D.

Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.
Metachronous double primary malignant tumors with nasopharyngeal carcinoma and diffuse malignant peritoneal mesothelioma accompanied with paraneoplastic syndromes treated with nivolumab: A case report. L.K. Tang, Z.K. Li, Y.L. Xiang, et al. 2023;102(30):e34349. Case report PubMed · Publisher · Free full text

Abstract

Rationale: Multiple primary malignant tumors are rare and challenging to diagnose. Diffuse malignant peritoneal mesothelioma (DMPM) originate from the peritoneum, which lacks specific clinical manifestations and is difficult to diagnose, with a short survival about 10 to 13 months for inoperable ones. This is the first report of metachronous double primary malignant tumors in nasopharyngeal carcinoma and DMPM accompanied with paraneoplastic syndromes.

Patient Concerns: A 61-year-old man presented with abdominal discomfort with a history of nasopharyngeal carcinoma 5 years ago.

Diagnoses: The diagnosis of DMPM was finally confirmed by laparoscopic mesenteric biopsies. Paraneoplastic syndromes including increased platelets were present when diagnosis, followed by increased neutrophils after disease progression.

Interventions: Due to intolerable for surgery, he was treated with pemetrexed combined with nivolumab, intraperitoneal infusion of nivolumab, radiotherapy, anlotinib and maintenance treatment of nivolumab.

Outcomes: Progression-free survival in first line is 12 months, overall survival is 23 months.

Lessons: This indicate that comprehensive treatment including immunotherapy may be helpful for inoperable DMPM patients with nasopharyngeal carcinoma accompanied with paraneoplastic syndromes.

Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.
A comprehensive investigation on pan-cancer impacts of constitutive centromere associated network gene family by integrating multi-omics data: A CONSORT-compliant article. H. Su, Y. Fan, Z. Wang, et al. 2022;101(7):e28821. PubMed · Publisher · Free full text

Abstract

Background: The constitutive centromere associated network (CCAN) complex played a critical role in connecting the centromere with the mitotic spindle during mitosis and meiosis. Many studies have indicated that CCAN is related to the tumorigenesis and cancer development. Nonetheless, the overview of CCAN gene family in pan-cancer remain incompletely understood.

Methods: We performed a comprehensive investigation on pan-cancer impacts of CCAN by integrating multi-omics data. We comprehensively investigated the expression profile, kyoto encyclopedia of genes and genomes (kegg) pathway, mutation, copy number variation, tumor microenvironment, immune cells infiltration, and drug sensitivity of CCAN in pan-cancer. MRNA expression profiles were collected from the cancer genome atlas, oncomine and ccle, the differential expression and various relevance analysis were performed with R or Perl.

Results: The results showed that the expression of CCAN was different in 33 tumors. Intriguingly, the poor survival in adrenocortical carcinoma, cholangiocarcinoma, kidney chromophobe, mesothelioma, kidney renal clear cell carcinoma, brain lower grade glioma, pheochromocytoma and paraganglioma, prostate adenocarcinoma, thyroid carcinoma, uveal melanoma was most likely related to the kegg single transduction pathway including one carbon pool by folate, proteasome, arachidonic acid metabolism and so on. CENPC, ITGB3BP, APITD1, CENPU, and CENPW were more involved in tumor microenvironment, which more likely related to NK cells resting, T cells follicular helper, T cells CD8, neutrophils, macrophages M0, T cells CD4 memory activated. The relationship of CCAN expression with drug sensitivity showed that chelerythrine, nelarabine, and hydroxyurea maybe be potential drugs.

Conclusions: This multidimensional study provides a valuable resource to assist mechanism research and clinical utility about CCAN.

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.
Diagnostic method for malignant pleural effusion distinguishing malignant mesothelioma from lung cancer using pleural carcinoembryonic antigen and hyaluronic acid levels. T. Saraya, K. Ohkuma, M. Fujiwara, et al. 2022;101(1):e28517. PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is difficult to diagnose because of the lack of parenchymal opacities, often revealing minimal or absent pleural thickening. Furthermore, pleural effusion has diverse differential diagnoses, including malignancies, infections, as well as collagen vascular and other benign diseases. In general practice, lung cancer (LC) is the most common malignancy causing pleural effusion; therefore, a simple method using pleural diagnostic markers to differentiate between LC and mesothelioma is crucial.We retrospectively reviewed the data of 530 adult patients diagnosed with pleural effusion between January 2010 and December 2020 in an outpatient or inpatient setting. Patients with pathologically diagnosed MM or LC with cytologically positive (class IV or V) pleural effusion were analyzed, and the characteristics of these 2 diseases were compared.During the study period, 27 patients diagnosed with MM and 100 patients diagnosed with LC were enrolled. Receiver operating characteristic curve analysis demonstrated that pleural carcinoembryonic antigen (CEA) and hyaluronic acid (HA) could discriminate MM from LC with an area under the curve of 0.925 (95% confidence interval [CI]: 0.879-0.972, P < .001) and 0.815 (95% CI: 0.686-0.943, P < .001), respectively. To diagnose MM, the accuracy of pleural HA >30,000 ng/mL revealed a sensitivity of 75.0%, specificity of 72.6%, and odds ratio of 7.94 (95% CI: 2.5-25.2, P = .001); pleural CEA <6.0 ng/mL revealed a sensitivity of 95.2%, specificity of 84.9%, smaller negative likelihood ratio of 0.06, and odds ratio of 112.5% (95% CI: 14.4-878.1, P < .001). Multiple logistic regression analysis revealed that these 2 parameters could discriminate MM from LC, with a hazard ratio of 23.6 (95% CI: 2.437-228.1, P = .006) and 252.3 (95% Cl: 16.4-3888.1, P < .001), respectively, and their combination had a high specificity of 98.3%.Pleural CEA (≥6.0 ng/mL) can rule out MM with a high degree of certainty, and the positive results for combination of pleural CEA <6.0 ng/mL and HA >30,000 ng/mL can confirm MM with high specificity, prior to cytological or pathological examinations.

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.
Factors affecting the life expectancy in malignant pleural mesothelioma: Our 10 years of studies and experience. F. Cimen, Y. Agackiran, S. Düzgün, et al. 2022;101(39):e30711. PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. In our study, we aimed to investigate the specific clinical, laboratory, and radiological features of the tumor and the prognostic effect of SUVmax (maximum standardized uptake values) according to PET/CT (positron emission tomography). Demographic, therapeutic, clinical, and survival information of patients diagnosed with histologically-validated pleural mesothelioma in our hospital between January 2010 to December 2019 will be retrospectively scanned from the hospital records. A total of 116 patients, 61 men (52.6%), and 55 women (47.4%), were analyzed. Thirty five patients (30.2%) were over the age of 65. Percentage of patients over 65 years of age, neutrophil count, and PET SUV Max values, asbestos exposure and pleural thickening rate were significantly higher in the deceased patients' group than in the living patients' group (P = .042, P = .039, P = .002, P = .004, P = .037). T stage (tumor stage), N stage (lymph nodes stage), metastasis stage, and Grade distribution were significantly higher in the deceased patients' group than in the living patients' group (P < .000, P < .000, P = .003, P < .000). The rates of chemotherapy and surgical treatment, right lung location, and epithelioid pathology were significantly lower in the deceased patients' group compared to the living patients' group (P = .016, P = .030, P = .018, P = .008). The mean follow-up time was 13 months. Key determinants of survival in MPM include age, male gender, neutrophil increase, pleural thickening, high PET SUV max values, stage, histological type, asbestos exposure, and treatment regimen.

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.
Tislelizumab combined with anlotinib in the second-line treatment of malignant pleural mesothelioma. D. Zhang, J. Liang, Y. Lv, et al. 2022;101(52):e32459. Case report PubMed · Publisher · Free full text

Abstract

Rationale: Malignant pleural mesothelioma (MPM) is a malevolent tumor originated from pleura and often leads to poor prognosis. Chemotherapy of pemetrexed and cisplatin combined with antiangiogenic therapy of bevacizumab is recommended as the first-line regimen by guidelines. However, there are few sustainable second-line anti-tumor theraies that bring distinct survival benefit after the occurrence of drug resistance as the reported mPFS (median progression-free survival) scarcely exceeds 6 months. Immune checkpoint inhibitors are extensively investigated in pan-cancer, and dual immunotherapy has been listed in the first-line recommendation of MPM in several guidelines, while MPM patients benefit modestly from immune checkpoint inhibitors combination or monotherapy in second-line practice.

Patient Concerns And Diagnosis: We report a 59-year-old male patient who was diagnosed with unresectable MPM in April 2021.

Interventions: He received firstly pemetrexed combined with platinum and bevacizumab, which barely curbed disease progression; When the first line treatment failed, he was switched to tislelizumab combined with anlotinib.

Outcomes: Tislelizumab combined with anlotinib significantly relieved his clinical symptoms, and imaging examination further validated the improvement. Until present, the second-line treatment PFS is more than 10 months.

Lessons: The case firstly demonstrated the efficacy of tislelizumab combined with anlotinib in the second-line management of MPM. Thus, immunotherapy combined with small-molecule multi-target anti-angiogenic medication may be alternative for the second-line schemes of MPM.

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.
Ultrasonographic misdiagnosis of multicystic mesothelioma of the omentum: A case report. Y. Diao, L. Chen, Z. Liu. 2022;101(36):e30441. Case report PubMed · Publisher · Free full text

Abstract

Rationale: Multicystic Mesothelioma (MM) is very rare and preoperative diagnosis is difficult.

Patient Concerns: We report a case of a 34-year-old man with solid abdominal cystic echo mass. Physical examination showed that the patient had a flat and soft abdomen without tenderness or rebound pain, no fluid wave tremor, and no obvious abdominal mass was touched. The patient complained of repeated abdominal distention with nausea for 5 days. Sonographic examination suspected pseudomyxoma peritoneum.

Diagnosis: Conventional ultrasound examination showed a cystic solid echo mass in the right abdominal cavity of the patient, with uneven internal echo and honeycomb change, and clear boundary with surrounding organs. Color Doppler suggested that the blood flow in the mass was not obvious. Contrast-enhanced computed tomography of the abdomen revealed hypodensity foci in hepatic and renal crypts and right paracolic sulcus.

Interventions: Laparoscopic resection of the mass was performed, and the postoperative pathological findings were polycystic mesothelioma (greater omentum).

Outcomes: After mass resection, all laboratory tests and abdominal ultrasound were normal, and abdominal distension and nausea disappeared.

Lessons: Improved ultrasound diagnosis of MM is useful for clinical decision-making.

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.
Can YKL-40 be used as a biomarker for interstitial lung disease?: A systematic review and meta-analysis. X. Tong, Y. Ma, T. Liu, et al. 2021;100(17):e25631. Meta-analysis · Systematic review PubMed · Publisher · Free full text

Abstract

Background: Interstitial lung disease (ILD) has a poor prognosis and lacks specific biomarkers for early diagnosis, assessment of disease severity, and prognosis. YKL-40 levels were found to be elevated in patients with ILD, but these results are inconsistent. Therefore, we conducted a systematic review and meta-analysis to accurately study the relation between YKL-40 and ILD.

Methods: We performed a systematic literature search in many databases (PubMed, Embase, the China National Knowledge Infrastructure, and Wanfang databases) and commercial Internet search engines to identify studies involving the role of YKL-40 in patients with ILD. The weighted mean difference with its 95% confidence interval were used to investigate the effect sizes. If obvious heterogeneity was found in the meta-analysis, the level of YKL-40 was directly compared by the Mann-Whitney test.

Results: Sixteen eligible articles were finally identified. The results showed that the serum YKL-40 levels of patients with idiopathic pulmonary fibrosis, connective tissue-related ILD, sarcoidosis, cryptogenic tissue pneumonia, asbestosis-ILD, and idiopathic nonspecific interstitial pneumonia were higher than those in controls, but there was no increase in patients with pulmonary alveolar proteinosis. We also found that there are certain differences in the serum YKL-40 levels in patients with different types of ILD. The results showed that the bronchoalveolar lavage fluid YKL-40 levels of patients with idiopathic pulmonary fibrosis were significantly higher than that in controls. A systematic review indicated that there were correlations between the serum YKL-40 levels and lung function in patients with different ILD. In addition, YKL-40 may be used as a valuable biomarker for survival, with risk ratios ranging from 1.006 to 10.9.

Conclusions: This study suggests that YKL-40 may be a useful biomarker for the diagnosis and prognosis of ILD.

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.
Clinicopathological characteristics of primary peritoneal epithelioid mesothelioma of clear cell type: A case report. X.M. Du, Y.P. Wei, Y. Gao, et al. 2021;100(12):e25264. Case report PubMed · Publisher · Free full text

Abstract

Rationale: Primary peritoneal epithelioid mesothelioma of clear cell type is an extremely rare entity composed of clear cytoplasm. It is challenging to diagnose because of the morphological resemblance to clear cell tumor.

Patients Concerns: A 69-year-old male patient had swollen lymph nodes in the right inguinal region for 7 months and was constipated for 1 month.

Diagnosis: The patient was diagnosed as peritoneal epithelioid mesothelioma of clear cell type based on computed tomography scan, pathology, immunohistochemistry, special staining and whole-exome sequencing. This patient harbored VHL gene alteration in exon 1 and homologous recombination defect (with a score of 45). This finding indicated that this patient might be sensitive to platinum-based therapy and Poly ADP-ribose Polymerase (PARP) inhibitor. This patient carried no microsatellite instability, a low level of tumor mutation burden, and a high extent of intratumoral heterogeneity. Eighteen neoantigens were detected.

Interventions: The patient received surgery-based multidisciplinary treatment by integrating cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). HIPEC was administered with docetaxel 120 mg plus cisplatin 120 mg, at 43°C, for 60 minutes. After operation, the patient received intravenous (IV) chemotherapy with docetaxel 60 mg, pemetrexed 750 mg and cisplatin 100 mg, and then intraperitoneal (IP) chemotherapy with docetaxel 40 mg. The patient received interventional therapy of hepatic artery embolization for 5 times.

Outcomes: Regular follow-up was performed until Oct 14, 2020. The patient died 31.6 months later owing to incomplete intestinal obstruction.

Lessons: Primary peritoneal epithelioid mesothelioma of clear cell type needs to be differentiated from a variety of clear cell tumors. This disease is characterized by specific genetic alteration. Whole-exome sequencing contributes to guide individualized therapy. CRS-HIPEC helps achieve long-term overall survival.

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.
Pulmonary sarcomatoid carcinoma mimicking pleural mesothelioma: A case report. L. Wang, J. Zhang, X. Chen, et al. 2021;100(45):e27813. Case report PubMed · Publisher · Free full text

Abstract

Introduction: Pulmonary sarcomatoid carcinoma (PSC) is an extremely rare biphasic tumor characterized by a mixture of malignant epithelial and mesenchymal cells. Owing to the rarity, as well as the lack of typical manifestations and imaging signs, the rate of misdiagnosis is high. Herein, we present a case of PSC misdiagnosed as pleural mesothelioma in a 59-year-old man.

Patient Concerns: A 59-year-old man presented with recurrent coughing, fever, and chest pain.

Diagnosis: Chest computed tomography showed 2 large and dense masses involving the inferior lobes of right lung, along with slight irregular pleural thickening and a small amount of effusion.

Interventions: Chest computed tomography-guided tumor biopsy was performed. PSC was confirmed based on histopathology and immunohistochemistry. The patient refused treatment due to economic reasons.

Outcomes: The patient developed adrenal, multiple lung and brain metastasis. The overall survival time was 11 months.

Conclusions: PSC, despite its rarity, should be considered in the differential diagnosis of lung cancer. Besides, biopsy, histopathology, and specific immunohistochemical staining of larger tissue specimens can be contributing to the accurate diagnosis of PSC.

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.
Squamous cell carcinoma of the tongue with cardiac metastasis on 18F-FDG PET/CT: A case report and literature review. P. Delabie, D. Evrard, I. Zouhry, et al. 2021;100(15):e25529. Case report · Review PubMed · Publisher · Free full text

Abstract

Introduction: The most common malignancies metastasizing to the heart are cancers of the lung, breast, mesothelioma, melanoma, leukemia, and lymphoma. Cardiac metastasis from a tongue cancer is a rare finding and only a few cases have been reported previously in the literature. In this case report and literature review, we discuss the main clinical features of patients with cardiac metastases secondary to a tongue cancer and imaging modalities performed, especially the 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT).

Patient Concerns: This is a case of a 39-year-old woman who in April 2018 was diagnosed with an invasive well differentiated squamous cell carcinoma of the movable tongue. She underwent a left hemiglossectomy followed by a revision of hemiglossectomy and ipsilateral selective neck lymph nodes dissection levels II to III because of pathological margins. An early inoperable clinical recurrence was diagnosed and she received radiochemotherapy with good clinical and metabolic response. She remained asymptomatic thereafter.

Diagnosis: In January 2020, a pre-scheduled 18F-FDG PET/CT showed a diffuse cardiac involvement. In February 2020, a biopsy of the lesion revealed a metastatic squamous cell carcinoma.

Interventions: She was deemed to not be a cardiac surgical candidate and treated by palliative chemotherapy: taxol-carboplatin associated with cetuximab then cetuximab alone because of adverse effects. A re-evaluation imaging performed in April 2020 evidenced a progression of the cardiac involvement, which led to switch chemotherapy by immunotherapy with nivolumab.

Outcomes: This patient had a very poor prognosis and succumbed to major heart failure 4 months after the diagnosis of cardiac metastasis.

Conclusion: In this case report, 18F-FDG PET/CT proved to be useful in detecting cardiac metastasis and changed the therapeutic management of the patient. It suggests that patients with tongue malignancies in a context of poor initial prognosis should be followed-up early by 18F-FDG PET/CT with HFLC diet to facilitate detection of recurrence.

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.
Cisplatin plus pemetrexed therapy and subsequent immune checkpoint inhibitor administration for malignant peritoneal mesothelioma without pleural lesions: Case report. H. Ikushima, T. Sakatani, S. Ohara, et al. 2020;99(22):e19956. Case report PubMed · Publisher · Free full text

Abstract

Rationale: Malignant peritoneal mesothelioma is a rare tumor with a poor prognosis and has no recommended therapy after first-line pemetrexed and platinum-based chemotherapy. Moreover, effects of immune checkpoint inhibitors on peritoneal mesothelioma remains to be elucidated. We herein report the case of a 75-year-old man with peritoneal mesothelioma treated with cisplatin plus pemetrexed and subsequent nivolumab.

Patient Concerns: A 75-year-old man was referred to our hospital due to lower abdominal pain.

Diagnosis: Positron emission tomography-computed tomography (CT) showed the accumulation of fluorodeoxyglucose in an intraperitoneal mass. A histological examination of a laparoscopic biopsy specimen revealed malignant peritoneal mesothelioma.

Interventions: After 4 cycles of cisplatin plus pemetrexed and 13 subsequent cycles of pemetrexed maintenance therapy showed beneficial responses until CT revealed liver metastasis. Nivolumab was then administered as the second-line therapy.

Outcomes: After 3 cycles of biweekly nivolumab administration, he developed severe abdominal distention. CT revealed an intraperitoneal mass growing much more rapidly than ever, indicating hyperprogressive disease after nivolumab treatment. He ultimately died 51 days after the initial nivolumab administration.

Lessons: To our knowledge, this is the first report of hyperprogressive disease in a case of peritoneal mesothelioma after nivolumab treatment. While immune checkpoint inhibitors may be promising therapeutic strategies for treating malignant peritoneal mesothelioma, careful monitoring must be practiced with their application.
Does exposure to asbestos cause prostate cancer? A systematic literature review and meta-analysis: Retraction. 2020;99(44):e23097. PubMed · Publisher · Free full text

2010s

A novel diagnostic method for distinguishing parapneumonic effusion and empyema from other diseases by using the pleural lactate dehydrogenase to adenosine deaminase ratio and carcinoembryonic antigen levels. T. Saraya, K. Ohkuma, T. Koide, et al. 2019;98(13):e15003. PubMed · Publisher · Free full text

Abstract

Pleural effusions are a common medical problem not only for pulmonologists but also for general physicians, often needing thoracentesis for a definite diagnosis. However, thoracentesis cannot always reveal malignant cells or microbiological evidence.In this context, we prospectively enrolled a total of 289 patients with pleural effusions due to diverse etiologies: parapneumonic effusion (PPE) (63), empyema (22), tuberculous pleural effusion (TBPE) (54), malignant pleural effusion (MPE) (140), or chronic renal failure (CRF)/congestive heart failure (CHF) (10). The MPE group consisted of lung cancer (adenocarcinoma, n = 90; squamous cell carcinoma, n = 5; small cell carcinoma, n = 4), malignant lymphoma (n = 17), malignant mesothelioma (n = 11), malignant melanoma (n = 3), and metastasis from other organs (n = 10).This study demonstrated that the pleural lactate dehydrogenase (LDH)to adenosine deaminase (ADA) ratios differed significantly between patients with CHF/CRF, MPE, TBPE, empyema, and PPE. We discovered a simple method to differentiate pleural diseases based on the pleural LDH to ADA ratio and carcinoembryonic antigen (CEA). A pleural LDH to ADA ratio greater than 15.5 and a pleural CEA level of less than 5 ng/mL is indicative of PPE or empyema rather than TBPE, MPE, or transudative pleural effusion (CRF, CHF).This method has a sensitivity of 62.0%, a specificity of 91.0%, and an area under the receiver operating characteristic curve of 0.765 (95% confidence interval [CI]: 0678-0.852, P < .001), odds ratio of 16.6 (95% CI: 7.28-37.8, P < .001), a positive likelihood ratio (LR) of 6.8, and a negative LR of 0.02.
Biomarkers for detecting malignant pleural mesothelioma: Protocol for a reanalysis of published data based on systematic reviews of diagnostic test accuracy. X. Zan, Y. Wang, J. Shi, et al. 2019;98(24):e16028. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a highly invasive tumor caused primarily by asbestos exposure. In recent decades, the incidence of MPM has shown an increasing trend, posing a great threat to human health. Although there is currently no effective way to treat MPM, patients can survive for more than 5 years if the tumor is removed early. Several systematic reviews (SRs) have evaluated the diagnostic value of biomarkers for diagnosing MPM. However, no studies have been conducted to analyze the quality of these SRs and it remains unclear which biomarker is the excellent diagnostic test. This study aims to assess the methodological quality of the SRs and reanalyze the published data based on SRs to find the optimal biomarker for the early diagnosis of MPM.

Methods: A systematic search will be performed in PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science to identify SRs reporting value of biomarkers for detecting MPM. We will evaluate the risk of bias of the included SRs according to the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. Standard pairwise meta-analysis and adjusted indirect comparison will be used to compare the diagnostic value of different biomarkers.

Results: The results of this study will be submitted to a peer-reviewed journal for publication.

Conclusion: This study will reanalyze the published data based on SRs to find a biomarker with the superior diagnostic performance for the diagnosis of MPM.

Ethics And Dissemination: Ethics approval and patient consent are not required as this study is an overview based on published systematic reviews.

Prospero Registration Number: CRD42019125880.
Diagnostic value of soluble mesothelin-related peptides in pleural effusion for malignant pleural mesothelioma: An updated meta-analysis. R. Gao, F. Wang, Z. Wang, et al. 2019;98(14):e14979. Meta-analysis · Systematic review PubMed · Publisher · Free full text

Abstract

Background: Soluble mesothelin-related peptide (SMRP) is a widely studied tumor marker for diagnosing malignant pleural mesothelioma (MPM). This study discussed the diagnostic value of SMRPs in pleural effusion (PE) for MPM.

Methods: Medline, Embase, Web of Science, and Cochrane library system were systematically searched on the data of SMRPs in PE for MPM diagnosis. Pooled diagnostic sensitivity, specificity, and symmetric receiver operating characteristic curve were calculated.

Results: Thirteen studies fulfilled the inclusion criteria and a total of 3359 cases including 759 MPM cases, 1061 non-MM (malignant mesothelioma) malignant PE, and 1539 benign PE were brought into this meta-analysis. The pooled results of SMRPs in PE for diagnosing MPM were as follows: sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.68 (95% confidence interval [CI]: 0.64-0.72), 0.91 (95% CI: 0.86-0.94), 7.8 (95% CI: 5.0-12.0), 0.35 (95% CI: 0.31-0.40), and 22 (95% CI: 14-35), respectively. The area under the summary receiver operating characteristic curves (AUC) was 0.75 (95% CI: 0.72-0.80). Subgroup analyzes revealed that the AUC of cohort group using histological diagnosis could be improved to 0.86 (95% CI: 0.83, 0.89). The Deek's funnel plot asymmetry test showed no publication bias.

Conclusion: Although the sensitivity of SMRPs was low, PE-SMRPs can be a good indicator of the existence of MPM.
Retracted. Does exposure to asbestos cause prostate cancer? A systematic literature review and meta-analysis. R. Peng, F. Fang, Z. Chen, et al. 2019;98(3):e14108. Meta-analysis · Systematic review PubMed · Publisher · Free full text

Abstract

Objective: The relationship between asbestos and prostate cancer (PCa) is not well understood due to small number of cases. This study aimed to determine the incidence and mortality of PCa among workers or residents exposed to asbestos based on a systematic review and meta-analysis METHODS: All published studies citing the standardized mortality ratio (SMR) or standardized incidence ratio (SIR) of PCa in workers or residents exposed to asbestos were collected by conducting a search on PubMed, EMBASE, Cochrane Library, and Web of Science before April 2018. Standardized mortality rate for PCa with its 95% confidence interval (CI) was pooled using a fixed-/random-effect model in STATA (Version14.0). This study is registered with PROSPERO, number CRD42018095195.

Results: A total of 17 independent studies were included for the analysis. The overall pooled SMR of PCa was 1.22, with a 95% CI of 1.13 to 1.32, with no heterogeneity across the studies (I = 18.8%, P = .234). Subgroup analysis shows that exposure to crocidolite, cement, studies conducted in Europe and Oceania, and long study follow-up (≥25 years) all contribute to significantly higher SMR, and we found no evidence of publication bias (Begg test P value = .592, Egger test P value = .874).

Conclusions: This meta-analysis suggested that exposed to asbestos might be associated with an increased risk of PCa. High-exposure level of asbestos could contribute to significantly higher risk of PCa mortality.
Hamartoma of mature cardiomyocytes in right atrium: A case report and literature review. X. Zhou, Y. Zhou, Y. Zhaoshun, et al. 2019;98(31):e16640. Case report PubMed · Publisher · Free full text

Abstract

Rationale: Tumors in the heart are rare. Myxomas, rhabdomyomas, and fibromas are the most common benign cardiac tumors. Hamartoma of mature cardiomyocytes (HMCM) is another benign cardiac tumor, are very rare and have only been reported in a few literatures.

Patient Concerns: We report a case of 41-year-old male who suffered short of breath for 3 years, and lower limbs edema for 2 years.

Diagnoses: Transthoracic echocardiogram (TTE) and cardiac magnetic resonance (CMR) showed a large amount of pericardial effusion and confirmed a mass of 18 × 14 mm on the superior vena cava near the outer edge of right atrium. The patient was first diagnosed as pleural mesothelioma. Surgery was performed to relieve the symptoms and confirm diagnoses. However, during surgery, we found the right atrium is apparently thicken with rough and uneven surface. Histology of right atrium mass indicated it as hamartoma of mature cardiomyocytes.

Intervention: We resected the thicken atrial wall completely, reconstructed right atrium with bovine pericardial patch, and resected the pericardium.

Outcomes: Patient was discharged 9 days after surgery, and remained asymptomatic during 9 months follow up.

Lessons: Hamartoma of mature cardomyocytes is a rare benign cardiac tumor. There were 26 cases reported until now. The conclusive diagnosis depends on pathological sections. For patients with symptoms, surgery is an effective treatment for HMCM.
Pleural small cell carcinoma with massive pleural effusion: A case report. J.G. Jang, M.H. Jang, J.H. Ahn. 2019;98(48):e18251. Case report PubMed · Publisher · Free full text

Abstract

Rationale: Small cell carcinoma (SCC) occurs mostly in the lung, and small cell lung cancer accounts for 13% of newly diagnosed lung cancers. Only 2.5% of SCC occurs in extrapulmonary sites, and SCC of pleural origin is especially very uncommon.

Patient Concerns: An 85-year-old man presenting with progressive dyspnea for more than 7 days.

Diagnoses: Computed tomography scan of the chest showed massive pleural effusion and diffuse nodular thickening of the pleura on the right chest. Sonography-guided needle biopsy of the pleural mass was performed and histologic and immunohistochemical findings revealed SCC. Since no parenchymal lung lesion was observed, the patient was finally diagnosed with SCC of the pleura (SCCP).

Interventions: Due to the patient's old age and poor performance status, chemotherapy was not performed and only drainage of pleural effusion was conducted for symptom relief.

Outcomes: Dyspnea improved after pleural effusion drainage. The patient was discharged and transferred to a local medical center for hospice care.

Lessons: Although primary SCCP is extremely rare, SCCP should also be considered as well as mesothelioma in case of presence of a pleural-based mass with massive pleural effusion.
Primary malignant mesothelioma of the diaphragm with liver invasion: A case report and review of literature. W.J. Huang, Z.H. Li, Z. Wang, et al. 2019;98(15):e15147. Case report · Review PubMed · Publisher · Free full text

Abstract

Rationale: Malignant mesothelioma is a malignant tumor with poor prognosis, which usually originates in the pleura, peritoneum, and pericardial cavity. Mesotheliomas that originate from the diaphragm are very rare. Here, we report a case of primary malignant mesothelioma of the diaphragm with liver invasion.

Patient Concerns: A 66-year-old woman was admitted to our hospital because of a "liver space-occupying lesion," without any special clinical symptoms. Imaging examinations suggested a cystic-solid mixed lesion in the right lobe of the liver.

Diagnosis: The tumor was diagnosed as epithelioid mesothelioma of the diaphragm with liver invasion.

Intervention: The patient underwent abdominal surgery in our hospital to remove the diaphragmatic mass, liver mass, and part of the diaphragm.

Outcomes: The postoperative course was uneventful.

Lessons: Primary diaphragmatic malignant mesothelioma is very rare and may involve liver or lung tissue and be mistaken for liver or lung tumor. Accurate diagnosis depends on careful pathological examination. Immunohistochemical staining is very useful to distinguish this tumor from other liver or diaphragmatic tumors.
Synchronous occurrence of benign mesothelioma and adenomatoid tumor of uterus: A case report and review of literature. P.R. Shen, J. Cen, X.Q. Qian, et al. 2019;98(20):e15746. Case report · Review PubMed · Publisher · Free full text

Abstract

Introduction: Synchronous occurrence of benign cystic mesothelioma and adenomatoid tumor of uterus (UAT) are very rare and few cases have been published in the English literature. They are easily misdiagnosed as malignant by clinicians, due to the lack of reports.

Patient Concerns: A case of benign mesothelial combined with uterus adenomatoid tumor (UAT) in a 48-year-old Chinese woman was reported. Our patient presented with abdominal pain and surgery showed a large subserous mass (12.0 × 11.4 × 9.8 cm) combined with a small intramural solid nodule (2.0 × 1.0 × 1.0 cm), and multiple minute neoplastic growth on the ovary.

Diagnosis: Due to the patient's symptoms, pathological findings, she was diagnosed with synchronous occurrence of benign mesothelioma and UAT.

Interventions: We treated her with a total hysterectomy and bilateral adnexectomy.

Outcomes: The patient is now in stable condition, without any signs of recurrence during 1 year of follow-up.

Lessons: Most mesotheliomas are malignant, synchronous occurrence of benign mesothelioma and UAT are extremely rare. And they are often misdiagnosed as malignancy by clinicians. Our case report can improve the awareness of the disease and avoid excessive treatment.
Apatinib for salvage treatment of advanced malignant pleural mesothelioma: A case report. Z. Du, Y. Yu, D. Wu, et al. 2018;97(45):e13105. Case report PubMed · Publisher · Free full text

Abstract

Rationale: Malignant Pleural Mesothelioma (MPM) is rare cancer and has a poor prognosis with resistance to chemotherapy or radiotherapy. Until now there is no standard third-line treatment for patients who have failed second-line therapy.

Patient Concerns: A 58-year-old non-smoking female peasant of ethnic Han was admitted to the oncology department of the 363 Hospital with a primary complaint of chest tightness and breathlessness from 3 months ago.

Diagnoses: Positron emission tomography-computed tomography (PET/CT) examination showed "dirty" pleural and parietal pleural involvement as well as mediastinal and pulmonary hilar lymph node enlargement. Finally, cancer cells were seen after repeated pleural effusion cell examination. Immunohistochemistry confirmed epithelioid of pleural mesothelioma.

Interventions: Apatinib as a third-line treatment after failure from pemetrexed/cisplatin (PC) as the first-line chemotherapy and gemcitabine/cisplatin (GP) as the second-line chemotherapy. At first, 250 mg/day was given and 1 week later, the dose was increased to 500 mg/day.

Outcomes: A 5-month progression-free survival was achieved and toxicity included severe hand-foot syndrome, mild proteinuria, and hypertension.

Lessons: Apatinib may be a potential therapeutic drug for MPM, particularly as a third-line treatment in cases resistant to chemotherapeutic options.
Publication trend, resource utilization, and impact of the US National Cancer Database: A systematic review. C. Su, C. Peng, E. Agbodza, et al. 2018;97(9):e9823. Meta-analysis · Systematic review PubMed · Publisher · Free full text

Abstract

Background: The utilization and impact of the studies published using the National Cancer Database (NCDB) is currently unclear. In this study, we aim to characterize the published studies, and identify relatively unexplored areas for future investigations.

Methods: A literature search was performed using PubMed in January 2017 to identify all papers published using NCDB data. Characteristics of the publications were extracted. Citation frequencies were obtained through the Web of Science.

Results: Three hundred 2 articles written by 230 first authors met the inclusion criteria. The number of publications grew exponentially since 2013, with 108 articles published in 2016. Articles were published in 86 journals. The majority of the published papers focused on digestive system cancer, while bone and joints, eye and orbit, myeloma, mesothelioma, and Kaposi Sarcoma were never studied. Thirteen institutions in the United States were associated with more than 5 publications. The papers have been cited for a total of 9858 times since the publication of the first paper in 1992. Frequently appearing keywords congregated into 3 clusters: "demographics," "treatments and survival," and "statistical analysis method." Even though the main focuses of the articles captured a extremely wide range, they can be classified into 2 main categories: survival analysis and characterization. Other focuses include database(s) analysis and/or comparison, and hospital reporting.

Conclusion: The surging interest in the use of NCDB is accompanied by unequal utilization of resources by individuals and institutions. Certain areas were relatively understudied and should be further explored.
A CARE-compliant case report: Lung transplantation for a Chinese young man with idiopathic pleuroparenchymal fibroelastosis. H. Huang, R. Feng, S. Li, et al. 2017;96(19):e6900. Case report PubMed · Publisher · Free full text

Abstract

Rational: Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease that is characterized radiologically by apical pleural thickening and histologically by elastic fibrosis of the visceral pleura. Although PPFE cases have been reported occasionally since this disease was initially described, most such cases have involved secondary PPFE. Idiopathic PPFE (iPPFE) cases have been less thoroughly studied. There are no effective medications for patients with iPPFE.

Patient Concerns: A 34-year-old man with no asbestos or cigarette exposure was admitted to our ward due to worsening cough and exertional dyspnea for 10 years. He had a "flattened thoracic cage" and bibasilar inspiratory crackles without finger clubbing. A series of chest computed tomography scans during the preceding 10 years revealed the presence of gradual, exaggerated, upper lung-predominant, diffuse pleural thickening and dense subpleural opacification with traction bronchiectasis.

Diagnosis: He was performed with video-assisted thoracic surgical (VATS) lung biopsy. The pulmonary histopathologic examination showed thickened visceral pleura and prominent subpleural fibroelastosis, confirming the diagnosis of iPPFE.

Intervention: After the failure of treatment with prednisone plus cyclophosphamide and sequential pirfenidone administration, he was arranged with bilateral lung transplantation two years later.

Outcomes: The patient did not require supplemental oxygenation anymore after he recovered from lung transplantation.

Lessons: Bilateral lung transplantation might be tried for the end-stage iPPFE cases.
Cisplatin-induced sudden cardiac death with hemodynamic collapse: a severe adverse drug reaction: Case report. S. Abramavicius, M. Zemaitis, V. Pilvinis, et al. 2017;96(48):e8995. Case report PubMed · Publisher · Free full text

Abstract

Rationale: Cisplatin is responsible for a significant percentage of adverse drug reactions (ADRs) in oncology setting. A great proportion of cisplatin-induced severe adverse events are difficult to foresee, and giving premedication does not always prevent the occurrence of such events.

Patient Concerns: A 53-year-old woman with progressive T4 N0 M0 stage IV pleural mesothelioma experienced cardiac arrest with hemodynamic collapse after cisplatin and pemetrexed chemotherapy administration.

Diagnoses: Progressive pleural T4 N0 M0 stage IV mesothelioma of the right lung, primary arterial hypertension, and cardiac arrest with hemodynamic collapse.

Interventions: The cisplatin and pemetrexed chemotherapy was administered intravenously for progressive pleural T4 N0 M0 stage IV mesothelioma of the right lung. During infusion of cisplatin the patient developed cardiac arrest, and cardiopulmonary resuscitation was initiated.

Outcomes: The patient was treated in intensive care unit and recovered successfully. Further chemotherapy with cisplatin and pemetrexed was withheld due to this severe adverse reaction to cisplatin.

Lessons: Cisplatin therapy should be thoroughly monitored including electrolyte, especially magnesium levels. Absence of previous ADRs to cisplatin and premedication should not give false sense of security.
Secondary hypertrophic osteoarthropathy caused by non-pleural or pulmonary tumors. H.J. Meyer, L. Leifels, A.G. Bach, et al. 2017;96(36):e7985. PubMed · Publisher · Free full text

Abstract

Hypertrophic osteoarthropathy (HOA) is a rare paraneoplastic syndrome characterized by digital clubbing, periosteal reaction, polyarthralgia, arthritis, and synovitis. Herein, we report a case series of patients with secondary HOA caused by non-pleural or pulmonary tumors.The radiologic databases of 2 tertiary university hospitals were retrospectively screened for secondary HOA patients. In addition, a systemic review of the published case reports. Only HOA cases with non-pleural or pulmonary malignancies were involved into the study. HOA in primary pleural or pulmonary malignant or benign disorders, as well in inflammatory diseases were excluded. In all cases, plain radiography was performed and clinical signs were documented.In our databases, 6 patients with secondary HOA were identified. In addition, the systemic review yielded 24 eligible patients. The most prevalent primary tumors were nasopharyngeal carcinoma and esophageal cancer in 6 patients (20%), respectively. In 17 patients, (56.7%) HOA was associated with lung metastases, and in 10 patients (33.3%), no lung metastases were detected. In 14 patients (46.7%), HOA was symptomatically before a tumor diagnosis was made. Plain radiography displayed typically features with periostal enlargement in every case.This study is the first report about secondary HOA caused by non-pleural or pulmonary tumors. Various primary tumors were identified, including several rare tumors such as sarcomas. HOA is a rare disorder with typically radiologically findings, which is not only associated with lung cancer or pleural mesothelioma and can even occur in tumor patients without lung metastasis.
Identifying Thoracic Malignancies Through Pleural Fluid Biomarkers: A Predictive Multivariate Model. J.M. Porcel, A. Esquerda, M. Martínez-Alonso, et al. 2016;95(10):e3044. Randomized trial PubMed · Publisher · Free full text

Abstract

The diagnosis of malignant pleural effusions may be challenging when cytological examination of aspirated pleural fluid is equivocal or noncontributory. The purpose of this study was to identify protein candidate biomarkers differentially expressed in the pleural fluid of patients with mesothelioma, lung adenocarcinoma, lymphoma, and tuberculosis (TB).A multiplex protein biochip comprising 120 biomarkers was used to determine the pleural fluid protein profile of 29 mesotheliomas, 29 lung adenocarcinomas, 12 lymphomas, and 35 tuberculosis. The relative abundance of these predetermined biomarkers among groups served to establish the differential diagnosis of: malignant versus benign (TB) effusions, lung adenocarcinoma versus mesothelioma, and lymphoma versus TB. The selected putative markers were validated using widely available commercial techniques in an independent sample of 102 patients.Significant differences were found in the protein expressions of metalloproteinase-9 (MMP-9), cathepsin-B, C-reactive protein, and chondroitin sulfate between malignant and TB effusions. When integrated into a scoring model, these proteins yielded 85% sensitivity, 100% specificity, and an area under the curve (AUC) of 0.98 for labeling malignancy in the verification sample. For lung adenocarcinoma-mesothelioma discrimination, combining CA19-9, CA15-3, and kallikrein-12 had maximal discriminatory capacity (65% sensitivity, 100% specificity, AUC 0.94); figures which also refer to the validation set. Last, cathepsin-B in isolation was only moderately useful (sensitivity 89%, specificity 62%, AUC 0.75) in separating lymphomatous and TB effusions. However, this last differentiation improved significantly when cathepsin-B was used with respect to the patient's age (sensitivity 72%, specificity 100%, AUC 0.94).In conclusion, panels of 4 (i.e., MMP-9, cathepsin-B, C-reactive protein, chondroitin sulfate), or 3 (i.e., CA19-9, CA15-3, kallikrein-12) different protein biomarkers on pleural fluid samples are highly discriminative for signaling a malignant versus tuberculous effusion, or lung adenocarcinoma versus mesothelioma, respectively. Cathepsin-B could also be helpful in establishing the presence of a lymphomatous effusion versus that of TB, if the patient's age is simultaneously taken into consideration.
Pemetrexed Maintenance Therapy Following Bevacizumab-Containing First-Line Chemotherapy in Advanced Malignant Pleural Mesothelioma: A Case Report and Literatures Review. X.Q. Jing, L. Zhou, X.D. Sun, et al. 2016;95(14):e3351. Case report · Review PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a lethal disease with poor prognosis. The combination of cisplatin and pemetrexed has been confirmed as the standard of care for nonoperable MPM. Data have shown that the adoption of pemetrexed maintenance therapy (PMT) following first-line treatment appears extremely promising.We describe a 57-year-old man diagnosed as advanced MPM. We treated this patient with PMT after first-line cisplatin-based bevacizumab-containing chemotherapy and residual tumor disappeared after 6 course of PMT. A perfect response and a long progression-free survival (PFS) were reached with tumor mass disappearing and 14 months duration of PFS.This case suggests that adding bevacizumab to standard first-line chemotherapy is feasible and that PMT could be promising and useful for treating advanced MPM. We further entail a review of the literature on the first-line treatment, continuation maintenance therapy, switch maintenance therapy, and second-line treatment of patients with advanced MPM.
Pretreatment elevated serum lactate dehydrogenase as a significant prognostic factor in malignant mesothelioma: A meta-analysis. Y. Zhuo, L. Lin, S. Wei, et al. 2016;95(52):e5706. Meta-analysis PubMed · Publisher · Free full text

Abstract

Background: Lactate dehydrogenase (LDH) as a hypoxia-regulator plays a vital role in alternative metabolic pathways of cancer cells. Numerous studies have assessed the prognostic value of elevated pretreatment LDH in malignant mesothelioma (MM). However, the results have been largely inconsistent. Hence, the aim of current study was to investigate the prognostic value of pretreatment LDH levels in patients with MM by performing a meta-analysis of relevant studies.

Methods: A literature search for English language studies, which investigated the association of LDH levels with overall survival (OS) in malignant mesothelioma, was performed in the electronic databases, PubMed, Medline, Embase, and Web of Science. Pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated. Heterogeneity was assessed using Cochran Q and I statistics. Sensitivity analysis, meta-regression model, and subgroup analysis were performed to trace the source of heterogeneity, if applicable.

Results: A total of 9 studies with a combined study population of 1977 patients came within the purview of this meta analysis. Pooled HR for OS in patients with high LDH level was 1.68 (95% CI = 1.36-2.00). Significant heterogeneity was observed in the included studies (I = 54.1%, P = 0.026). Sensitivity analysis after sequential exclusion of 1 study at a time, and meta-regression with inclusion of 6 confounding factors failed to identify the source of heterogeneity. However, in the subgroup analysis, it was found that the publication of Nojiri et al was the origin of heterogeneity. When omitted the publication of Nojiri et al, the pooled HR of the rest 8 studies was 1.83 (95% CI = 1.45-2.20, I = 0.0%, P = 0.723). Egger test and funnel plots excluded the possibility of publication bias affecting the results of the current meta-analysis.

Conclusion: A negative association was observed between high LDH levels and poor overall survival in the current study. Our findings suggest that pretreatment LDH level could serve as a useful predictor of prognosis in patients with malignant mesothelioma.
Whole exome sequencing of independent lung adenocarcinoma, lung squamous cell carcinoma, and malignant peritoneal mesothelioma: A case report. I. Vanni, S. Coco, S. Bonfiglio, et al. 2016;95(48):e5447. Case report PubMed · Publisher · Free full text

Abstract

The presence of multiple primary tumors (MPT) in a single patient has been identified with an increasing frequency. A critical issue is to establish if the second tumor represents an independent primary cancer or a metastasis. Therefore, the assessment of MPT clonal origin might help understand the disease behavior and improve the management/prognosis of the patient.Herein, we report a 73-year-old male smoker who developed 2 primary lung cancers (adenocarcinoma and squamous cell carcinoma) and a malignant peritoneal mesothelioma (PM).Whole exome sequencing (WES) of the 3 tumors and of germline DNA was performed to determine the clonal origin and identify genetic cancer susceptibility.Both lung cancers were characterized by a high mutational rate with distinct mutational profiles and activation of tumor-specific pathways. Conversely, the PM harbored a relative low number of genetic variants and a novel mutation in the WT1 gene that might be involved in the carcinogenesis of nonasbestos-related mesothelioma. Finally, WES of the germinal DNA displayed several single nucleotide polymorphisms in DNA repair genes likely conferring higher cancer susceptibility.Overall, WES did not disclose any somatic genetic variant shared across the 3 tumors, suggesting their clonal independency; however, the carcinogenic effect of smoke combined with a deficiency in DNA repair genes and the patient advanced age might have been responsible for the MPT development. This case highlights the WES importance to define the clonal origin of MPT and susceptibility to cancer.
Diagnostic Ability of FDG-PET/CT in the Detection of Malignant Pleural Effusion. R. Nakajima, K. Abe, S. Sakai. 2015;94(29):e1010. PubMed · Publisher · Free full text

Abstract

We investigated the role of F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) for the differential diagnosis of malignant and benign pleural effusion. We studied 36 consecutive patients with histologically proven cancer (excluding malignant mesothelioma) who underwent FDG-PET/CT for suspected malignant pleural effusion. Fourteen patients had cytologically proven malignant pleural effusion and the other 22 patients had either negative cytology or clinical follow-up, which confirmed the benign etiology. We examined the maximum standardized uptake values (SUV max) of pleural effusion and the target-to-normal tissue ratio (TNR), calculated as the ratio of the pleural effusion SUV max to the SUV mean of the normal tissues (liver, spleen, 12th thoracic vertebrae [Th12], thoracic aorta, and spinalis muscle). We also examined the size and density (in Hounsfield units) of the pleural effusion and pleural abnormalities on CT images. TNR (Th12) and increased pleural FDG uptake compared to background blood pool were significantly more frequent in cases with malignant pleural effusion (P < 0.05 for both). The cutoff TNR (Th12) value of >0.95 was the most accurate; the sensitivity, specificity, and accuracy for this value were 93%, 68%, and 75%, respectively. FDG-PET/CT can be a useful method for the differential diagnosis of malignant and benign pleural effusion.

2000s

Idiopathic retroperitoneal fibrosis: prospective evaluation of incidence and clinicoradiologic presentation. E.F.H. van Bommel, I. Jansen, T.R. Hendriksz, et al. 2009;88(4):193-201. PubMed · Publisher

Abstract

Retroperitoneal fibrosis (RPF) is a rare disorder of unknown etiology. Its incidence is unknown, and the insidious and nonspecific nature of symptoms may contribute to considerable diagnostic delay. We conducted the current study to assess the incidence and clinicoradiologic characteristics of idiopathic RPF. For this, we evaluated prospectively 53 consecutive patients with a diagnosis of idiopathic RPF at our tertiary care referral center from April 1998 through January 2008.Calculated annual incidence of RPF was 1.3/100,000 inhabitants. Mean age was 64 +/- 11.1 (SD) yr; male-female ratio was 3.3:1.0. Median duration of symptoms was 6.0 mo (IQR 3.0-12.0). Abdominal, flank, and/or back pain and discomfort were the major symptoms, with visual analogue scale scores of 49 +/- 27.2 mm and 43 +/- 29.4 mm for pain and discomfort, respectively. Female patients had higher erythrocyte sedimentation rate (ESR), higher white blood cell count, and lower hemoglobin content than male patients at presentation. Computed tomography-documented maximal mass thickness amounted to 35 +/- 16.6 mm; craniocaudal length amounted to 137 +/- 48.8 mm. RPF mass extension up to or above the level of the renal vessels was noted in 3 patients (6%). Six patients (11%) presented with atypical RPF localization and/or bulky mass. Localized lymphadenopathy adjacent to the RPF mass was observed frequently (25%). Patients with hydronephrosis (56%) presented earlier than patients without hydronephrosis, with higher creatinine and greater mass thickness but similar pain severity. Patients were typically at high cardiovascular risk with increased-often aneurysmal-infrarenal aortic diameter (25.0 mm, IQR 22.0-30.0). RPF mass distribution was similar in patients with or without aneurysmal dilation. Occupational asbestos exposure (20%) and asbestos-related pleural changes (17%) were frequent among males. Previous or concurrent chronic inflammatory disease and/or autoimmune disease was noted in 8 patients (15%). Multivariate analysis revealed an independent association of ESR values with severity of pain and discomfort. Smoking was independently associated with infrarenal aortic diameter.In summary, annual RPF incidence is higher than previously assumed. Age at diagnosis and male-female ratio seem to have changed over time. RPF typically affects patients at high cardiovascular risk, including increased aortic diameter. Clinical presentation is influenced by sex, severity of inflammation and presence of hydronephrosis. Prolonged asbestos exposure and asbestos-related pleural changes were frequent among males. Localized lymphadenopathy adjacent to the RPF mass occurs frequently and should not confuse RPF diagnosis.
Retroperitoneal fibrosis: new insights into clinical presentation and diagnosis. A. Vaglio. 2009;88(4):208-210. Comment PubMed · Publisher

Summary

This commentary discussed two prospective studies of idiopathic retroperitoneal fibrosis (RPF) by van Bommel et al and Scheel et al, published in the same issue of Medicine. The author noted that earlier RPF research had been limited by the disease's rarity, the lack of diagnostic and classification criteria, and the inclusion of heterogeneous patient groups. He reported that the population-based Dutch study gave an annual incidence of idiopathic RPF of 1.3 × 10^-5 inhabitants, more than 10-fold higher than an earlier Finnish estimate based on hospital discharge data. Pain was the most common symptom in both cohorts, affecting more than 90% of patients. Atherosclerotic disease was present in 40% and 20% of the two cohorts. In van Bommel's series, 20% of patients had been exposed to asbestos, most with pleural plaques. In Scheel's cohort, 12.5% had potential occupational asbestos exposure. The author considered it appropriate to classify RPF in asbestos-exposed patients as idiopathic rather than secondary, because it is indistinguishable radiologically and histologically and no clear causal relationship has been shown. He also discussed the typical imaging findings, Scheel's proposed four-class scheme based on disease extent, and limitations of both studies. He concluded that the studies extended knowledge of RPF and paved the way for future large controlled studies.

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