bims-mesote Biomed News
on Mesothelioma
Issue of 2022–11–27
eleven papers selected by
Laura Mannarino, Humanitas Research
  1. Managing Malignant Pleural Mesothelioma in the Age of Personalized Medicine: Where Are We and What Is Still Missing?
  2. A Pilot Mixed-Methods Study of Malignant Pleural Mesothelioma Symptoms.
  3. Isolated BAP1 Genomic Alteration in Malignant Pleural Mesothelioma Predicts Distinct Immunogenicity with Implications for Immunotherapeutic Response.
  4. Haemorrhagic Brain Metastasis From Malignant Pleural Mesothelioma: A Rare Case.
  5. The Effects of Preserving the Diaphragm on Early and Late Outcome of Lung-Sparing Radical Surgery for Malignant Pleural Mesothelioma.
  6. Diagnosis of malignant pleural disease: Ultrasound as "a detective probe".
  7. Usefulness of malignant pleural effusion for early cytological diagnosis of mesothelioma in situ: A case report.
  8. Pericardial Mesothelioma, a Disease for Brave Hearts.
  9. Effects of Photon Radiation on DNA Damage, Cell Proliferation, Cell Survival, and Apoptosis of Murine and Human Mesothelioma Cell Lines.
  10. Histopathological and immunohistochemical features of 14 peritoneal mesotheliomas with clinical outcomes and recent updates.
  11. Sarcomatoid mesothelioma: unusual findings and literature review.
  1. Cancers (Basel). 2022 Nov 11. pii: 5540. [Epub ahead of print]14(22):
    Managing Malignant Pleural Mesothelioma in the Age of Personalized Medicine: Where Are We and What Is Still Missing?
    Giulia Maria Stella, Chandra Bortolotto.
      Malignant Mesothelioma (MM) is an aggressive neoplasm of the pleural mesothelium, less frequently peritoneal and exceptionally of the vaginal tunic of the testicle and pericardium [...].
    DOI:  https://doi.org/10.3390/cancers14225540
  2. Oncol Nurs Forum. 2022 Oct 20. 49(6): 615-623
    A Pilot Mixed-Methods Study of Malignant Pleural Mesothelioma Symptoms.
    Suzanne L Walker, Victoria Vaughan Dickson, Pamela Z Cacchione.
       OBJECTIVES: To describe symptoms of malignant pleural mesothelioma (MPM), a rare cancer associated with a poor prognosis and significant symptoms, via a pilot mixed-methods study, because it is unclear whether MPM symptom assessment tools accurately characterize these symptoms.
    SAMPLE & SETTING: Participants with MPM were recruited from a large northeastern U.S. academic medical center with an interprofessional MPM program.
    METHODS & VARIABLES: A mixed-methods pilot approach was employed using the Lung Cancer Symptom Scale for Mesothelioma (LCSS-Meso) to quantitatively describe MPM symptoms and semistructured interviews to qualitatively capture these symptoms.
    RESULTS: Seven participants with MPM completed the LCSS-Meso and qualitative interviews. The five symptoms evaluated by the LCSS-Meso were confirmed as symptoms of MPM in participant interviews. However, the presence and severity of some symptoms were either under- or overestimated by the scale. Two additional symptoms, distress and sleep disturbance, also emerged from the qualitative interviews.
    IMPLICATIONS FOR NURSING: Nurses caring for people with MPM should have a thorough understanding of common symptoms, but they must also explore additional symptoms that are meaningful to each patient.
    Keywords:  LCSS-Meso; malignant pleual mesothelioma; mixed methods; symptoms
    DOI:  https://doi.org/10.1188/22.ONF.615-623
  3. Cancers (Basel). 2022 Nov 16. pii: 5626. [Epub ahead of print]14(22):
    Isolated BAP1 Genomic Alteration in Malignant Pleural Mesothelioma Predicts Distinct Immunogenicity with Implications for Immunotherapeutic Response.
    Hatice Ulku Osmanbeyoglu, Drake Palmer, April Sagan, Eleonora Sementino, Michael J Becich, Joseph R Testa.
      Malignant pleural mesothelioma (MPM), an aggressive cancer of the mesothelial cells lining the pleural cavity, lacks effective treatments. Multiple somatic mutations and copy number losses in tumor suppressor genes (TSGs) BAP1, CDKN2A/B, and NF2 are frequently associated with MPM. The impact of single versus multiple genomic alterations of TSG on MPM biology, the immune tumor microenvironment, clinical outcomes, and treatment responses are unknown. Tumors with genomic alterations in BAP1 alone were associated with a longer overall patient survival rate compared to tumors with CDKN2A/B and/or NF2 alterations with or without BAP1 and formed a distinct immunogenic subtype with altered transcription factor and pathway activity patterns. CDKN2A/B genomic alterations consistently contributed to an adverse clinical outcome. Since the genomic alterations of only BAP1 was associated with the PD-1 therapy response signature and higher LAG3 and VISTA gene expression, it might be a candidate marker for immune checkpoint blockade therapy. Our results on the impact of TSG genotypes on MPM and the correlations between TSG alterations and molecular pathways provide a foundation for developing individualized MPM therapies.
    Keywords:  BAP1; malignant pleural mesothelioma; tumor suppressor gene loss
    DOI:  https://doi.org/10.3390/cancers14225626
  4. Cureus. 2022 Oct;14(10): e30345
    Haemorrhagic Brain Metastasis From Malignant Pleural Mesothelioma: A Rare Case.
    Cleofina Furtado, Sachin Srivastava, Sanjeev Nayak, Changrez Jadun, Zafar Hashim.
      Malignant pleural mesothelioma (MPM) typically has a short median survival of only a few months from diagnosis, with death usually due to thoracic disease. This has led to the belief in the past that mesothelioma rarely has distant metastasis, with cerebral metastasis accounting for only 3%. The multiple cases of brain metastasis from MPM recorded so far were discovered after death at autopsy. This report describes a rare case of known malignant mesothelioma with distant haemorrhagic metastasis to the brain, reviews current literature about its metastatic potential to the brain and discusses prognosis and management. We also review the imaging evaluation in known MPM patients with suspected intracranial involvement and describe typical imaging findings of parenchymal brain metastasis on computed tomography (CT) and magnetic resonance imaging (MRI).
    Keywords:  cerebral; computed tomography (ct); haemorrhagic; malignant pleural mesothelioma (mpm); metastasis
    DOI:  https://doi.org/10.7759/cureus.30345
  5. J Clin Med. 2022 Nov 19. pii: 6839. [Epub ahead of print]11(22):
    The Effects of Preserving the Diaphragm on Early and Late Outcome of Lung-Sparing Radical Surgery for Malignant Pleural Mesothelioma.
    Michelle Lee, Luigi Ventura, Ralitsa Baranowski, Joanne Hargrave, David Waller.
       BACKGROUND: The accepted aim of radical surgery for malignant pleural mesothelioma (MPM) is the achievement of macroscopic complete resection (MCR) whilst reducing perioperative morbidity by preserving normal tissue. Whilst preservation of the lung by pleurectomy/decortication (PD) has become widely utilised, there remains debate regarding the management of the diaphragm. Muscle-sparing complete excision of the diaphragmatic pleura is technically challenging; thus, surgeons may proceed to extended PD with phrenectomy and possible increased morbidity or to preserve the diaphragmatic pleura at the expense of MCR with potential survival deficit. We aimed to evaluate the effects of an intentional change in protocol to diaphragm-sparing PD whilst maintaining MCR as the treatment of choice for MPM.
    METHODS: In a series of 136 patients (111M:25F, median age 68(63-73) years) undergoing radical surgery for MPM, we identified 28 patients (22M:6F, median age 67(60-71) years) in whom MCR was achieved without phrenectomy (PD group). We compared their perioperative outcomes and survival with a historical control group of 18 patients (18M:0F, median age 69(57-78) years) in whom MCR had been achieved with phrenectomy (EPD group) but in whom there was no histological evidence of diaphragm muscle invasion and who, in retrospect, could have undergone muscle-sparing MCR if this procedure had been attempted.
    RESULTS: There was no significant intergroup difference in demographics or tumour cell type; the majority of both groups were found to be epithelial (PD 85.7%, EPD 77.8%). The EPD group was found to be more locally advanced (T3 55.56%) than the PD group (T1 46.43%) (p = 0.03). All the following parameters were significantly reduced after PD compared to EPD: operative time (188 vs. 220 min, p = 0.007); duration of air leak (5 vs. 10 days, p = 0.001), duration of inotrope (p = 0.009) and post-operative hospital stay (8 vs. 13 days, p = 0.034). There were no significant differences (p = 0.123) in overall survival (OS) between the two groups, but the median survival in the PD group had not been reached at a median follow up of 33.9 (24.2-46) months.
    CONCLUSIONS: A surgical strategy of attempting to spare the diaphragm whilst still achieving MCR wherever possible is justified by improved perioperative outcomes without compromising OS.
    Keywords:  diaphragm; pleural mesothelioma; pleurectomy decortication
    DOI:  https://doi.org/10.3390/jcm11226839
  6. Thorac Cancer. 2022 Nov 22.
    Diagnosis of malignant pleural disease: Ultrasound as "a detective probe".
    Gaetana Messina, Mary Bove, Giovanni Natale, Vincenzo Di Filippo, Giorgia Opromolla, Anna Rainone, Beatrice Leonardi, Mario Martone, Alfonso Fiorelli, Giovanni Vicidomini, Mario Santini, Andrea Ronchi, Eva Massimilla, Carminia Maria Della Corte, Mario Pirozzi, Marianna Caterino, Fortunato Ciardiello, Morena Fasano.
       BACKGROUND: Malignant pleural mesothelioma (MPM) is an invasive, aggressive pleural tumor with a predominantly local spread. The objective of this study was to assess thoracic ultrasound (TUS) as an imaging modality with high sensitivity for the identification of malignant pleural involvement and in order to guide pleural biopsies.
    METHODS: In this retrospective single-center study between January 2018 and June 2022, 51 consecutive patients with impassable circumferential pleural thickening underwent TUS at the Thoracic Surgery Unit of the Vanvitelli University of Naples. Pleural biopsies were performed, and then large and multiple samples were sent to the pathological anatomy for histological examination.
    RESULTS: In all patients who underwent ultrasound examination, we chose the optimal point of entry to perform pleural biopsies and selected the areas of greater thickening without pleural effusion. No patient had any complications. No drainage tubes were placed after the pleural biopsies and no pneumothorax was present during the following days of hospitalization. The patients were discharged on the second postoperative day.
    CONCLUSION: With TUS the precise pleural thickening localization, local infiltration, mass extent, its nature (solid, cystic or complex) and ultrasound features can be easily defined. Furthermore, ultrasound is more economical than computed tomography and avoids the risks associated with radiation. Thoracic ultrasound is an important component of the diagnostic procedure in detecting a safe entry site for biopsies of MPMs.
    Keywords:  malignant pleural mesothelioma; pleural biopsies; probe; thoracic ultrasound
    DOI:  https://doi.org/10.1111/1759-7714.14735
  7. Oncol Lett. 2022 Dec;24(6): 440
    Usefulness of malignant pleural effusion for early cytological diagnosis of mesothelioma in situ: A case report.
    Yuki Yabuuchi, Kenzo Hiroshima, Hisayuki Oshima, Jun Kanazawa, Kenji Hayashihara, Takayuki Nakagawa, Masaki Shimanouchi, Shingo Usui, Shuji Oh-Ishi, Takefumi Saito, Nobuyuki Hizawa, Yuko Minami.
      Mesothelioma in situ (MIS) is defined as a preinvasive mesothelioma that forms a single layer of mild atypical mesothelial cells lining on the serosa surface of pleura. The atypical mesothelial cells present loss of BRCA-1 associated protein-1 (BAP-1) and/or methylthioadenosine phosphorylase as examined by immunohistochemistry (IHC) and/or homozygous deletion of cyclin-dependent kinase inhibitor 2A/p16 as examined by fluorescence in situ hybridization. It is difficult to diagnose because of the unremarkable clinical findings except for pleural effusion. The present report describes a case in which MIS was diagnosed at the time of sampling due to the presence of clearly malignant mesothelial cells in the pleural fluid. In 2016, a 74-year-old man with a history of past exposure to asbestos was admitted to Ibaraki Higashi National Hospital (Tokai-mura, Japan) with dyspnea. Chest CT indicated only right pleural effusion. Malignant mesothelial cells were suspected in a cell block made using pleural effusion; therefore, right pleural biopsy was performed. Pathologically, there was proliferation of mesothelial cells with mild atypia that formed a single-flat layer on the pleural surface; however, there was no invasion. Furthermore, IHC revealed loss of BAP-1 in cells from the biopsied pleura and pleural effusion. MIS was suspected at the time; however, the patient arbitrarily quit his medical check-ups. After 44 months, the patient was readmitted to our hospital complaining of dyspnea. CT indicated a large right pleural mass. A specimen of the mass obtained via CT-guided needle biopsy revealed malignant mesothelioma. The patient continued to deteriorate and eventually died. This case indicated that pleural effusion could be used to demonstrate overtly malignant mesothelial cells and diagnose MIS at the time of sampling. To the best of our knowledge, this is first report of MIS with overtly malignant mesothelial cells in pleural effusion. Pleural effusion may serve an important role in MIS diagnosis.
    Keywords:  BAP-1; atypical cells; cell block; first obtained pleural fluid; malignant mesothelial cells
    DOI:  https://doi.org/10.3892/ol.2022.13560
  8. J Thorac Oncol. 2022 Dec;pii: S1556-0864(22)01824-X. [Epub ahead of print]17(12): 1333-1334
    Pericardial Mesothelioma, a Disease for Brave Hearts.
    Federica Grosso, Luigi Cerbone, Giulia Pasello.
      
    DOI:  https://doi.org/10.1016/j.jtho.2022.09.224
  9. Adv Radiat Oncol. 2022 Nov-Dec;7(6):7(6): 101013
    Effects of Photon Radiation on DNA Damage, Cell Proliferation, Cell Survival, and Apoptosis of Murine and Human Mesothelioma Cell Lines.
    Synat Keam, Kelly M MacKinnon, Rebecca A D'Alonzo, Suki Gill, Martin A Ebert, Anna K Nowak, Alistair M Cook.
       Purpose: To characterize the cellular responses of murine and human mesothelioma cell lines to different doses of photon radiation with a long-term aim of optimizing a clinically relevant in vivo model in which to study the interaction of radiation therapy and immunotherapy combinations.
    Methods and Materials: Two murine mesothelioma cell lines (AB1 and AE17) and 3 human cell lines (BYE, MC, and JU) were used in the study. Cells were treated with increasing doses of photon radiation. DNA damage, DNA repair, cell proliferation, and apoptosis at different time points after irradiation were quantified by flow cytometry, and cell survival probability was examined using clonogenic survival assay.
    Results: DNA damage increased with escalating dose in all cell lines. Evident G2/M arrest and reduced cell proliferation were observed after irradiation with 8 Gy. DNA repair was uniformly less efficient at higher compared with lower radiation-fraction doses. The apoptosis dose response varied between cell lines, with greater apoptosis observed at 16 Gy with human BYE and murine AB1 cell lines but less for other studied cell lines, regardless of dose and time. The α/β ratio from the cell survival fraction of human mesothelioma cell lines was smaller than from murine ones, suggesting human cell lines in our study were more sensitive to a change of dose per fraction than were murine mesothelioma cell lines. However, in all studied cell lines, colony formation was completely inhibited at 8 Gy.
    Conclusions: A threshold dose of 8 Gy appeared to be appropriate for hypofractionated radiation therapy. However, the radiation therapy doses between 4 and 8 Gy remain to be systematically analyzed. These observations provide an accurate picture of the in vitro response of mesothelioma cell lines to photon irradiation and characterize the heterogeneity between human and murine cell lines. This information may guide in vivo experiments and the strengths and limitations of extrapolation from murine experimentation to potential human translation.
    DOI:  https://doi.org/10.1016/j.adro.2022.101013
  10. J Cancer Res Ther. 2022 Oct-Dec;18(6):18(6): 1683-1691
    Histopathological and immunohistochemical features of 14 peritoneal mesotheliomas with clinical outcomes and recent updates.
    Srushti Karmarkar, Bharat Rekhi, Kedar K Deodhar, Santosh Menon.
       Background: Malignant peritoneal mesotheliomas (MPMs) are rare tumors with overlapping clinical and histopathological features, especially with epithelial ovarian carcinomas (EOCs). There is no substantial documentation on these rare tumors from our country.
    Objective: To study the clinicopathological features including immunohistochemical (IHC) profile and clinical outcomes of 14 MPMs, diagnosed at our institution.
    Materials and Methods: This was a retrospective study, wherein 14 cases of MPM, occurring in female patients, diagnosed at our institution, between January 2008 and May 2019 were included, after a critical review.
    Results: Median age was 54.5 years. Most patients presented with ascites, omental nodularity, and fat stranding. Microscopically, most cases (11, 78.6%) displayed epithelioid morphology, followed by biphasic pattern (2, 14.3%) and a single case of well-differentiated MPM. IHC, diagnostic sensitivity and specificity of calretinin were 100% (13/13) and 85.7%; of HBME1 were 100% (5/5) and 100%; and of podoplanin (D2-40) were 60% (2/5) and 100%. Other positively expressed immunomarkers were epithelial membrane antigen (n = 2/5, 40%), cytokeratin 5/6 (n = 4/4, 100%), and WT1 (n = 9/10, 90%). Most patients (5/12, 41.7%) were treated with chemotherapy. The 3-year disease-free and overall survival rates were 25.7% and 54%, respectively, including improved survival trend in patients with epithelioid type of MPMs.
    Conclusion: MPMs are diagnosed with a combination of clinicopathological features and optimal IHC markers. Their differentiation from EOCs and other metastatic carcinomas is imperative in view of significant treatment implications.
    Keywords:  Calretinin; D2–40; peritoneal malignancy; peritoneal mesothelioma; rare gynecologic malignancies
    DOI:  https://doi.org/10.4103/jcrt.JCRT_1292_20
  11. J Surg Case Rep. 2022 Nov;2022(11): rjac512
    Sarcomatoid mesothelioma: unusual findings and literature review.
    Brittni Clopton, Winnie Long, Monica Santos, Armand Asarian, Romulo Genato, Philip Xiao.
      Sarcomatoid mesothelioma is an aggressive disease secondary to its propensity to undergo rapid growth, show inconsistent expression of tumor markers and invade surrounding tissues. Therefore, there are numerous obstacles that clinical researchers face as they look for new methods to diagnose and treat the malignancy. We present a case of sarcomatoid mesothelioma, originally thought to be metastasis from renal cell carcinoma.
    DOI:  https://doi.org/10.1093/jscr/rjac512
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