Introduction: Mediastinoscopy is considered essential in staging of lung cancer and evaluation of mediastinal lymphadenopathy and masses. This facility has only recently been available at our center. ...We review our initial experience and analyse its safety and utility in our setting.
Methods: Retrospective analysis of data of all patients who underwent cervical mediastinoscopy at Manmohan Cardio-thoracic Vascular and Transplant Center (MCVTC) was done. Demographic, clinical and perioperative data were recorded. Concordance of pre and post-operative diagnosis was studied.
Results: Between January 2012 and April 2014, 24 patients underwent mediastinoscopy. The age ranged from 28-75 years (mean = 43.12 ± 15.14). Females outnumbered males (M: F = 3:5). Mediastinoscopy was done for staging of lung cancer in six patients and for assessment of mediastinal lymphadenopathy in 18 patients. One patient had a minor preoperative bleeding. One patient developed surgical site infection. The post-operative stay ranged from 1-4 days (mean = 2.15 ± 0.75). Concordance of pre and postoperative diagnosis was seen in 14 (58%) patients. Amongst the five patients pre-operatively thought to have tubercular mediastinal lymphadenopathy; Tuberculosis was confirmed in only three. Only one of six patients in whom mediastinoscopy was done as a staging procedure in lung cancer was found to have malignant spread in the sampled nodes.
Conclusion: Mediastinoscopy is safe and efficacious in diagnosing mediastinal lymphadenopathy. It should be routinely considered in staging of NSCLC and evaluation of enlarged mediastinal nodes.
Malignant pleural mesothelioma is an aggressive malignancy with limited systemic therapy options. Promising results have been reported with use of anti–programmed cell death 1 therapy; however, its ...benefits appear to be confined to a subgroup of patients. Microsatellite instability (MSI) results from the inactivation of DNA mismatch repair genes and results in a high tumor mutational burden, a phenomenon that has not been seen with mesothelioma. MSI and protein absence have been shown to correlate in colorectal cancer, such that most centers have adopted immunohistochemistry (IHC) to screen for MSI-high colorectal cancers. We profiled a large cohort of patients with mesothelioma to determine the rate of negative IHC staining results the four common mismatch repair proteins.
A tissue microarray comprising 335 patients with malignant pleural mesothelioma were used. IHC for the four common mismatch repair proteins (mutL homolog 1; PMS1 homolog 2, mismatch repair system component; mutS homolog 2; and mutS homolog 6) was performed. Programmed death ligand 1 IHC staining with the E1L3N clone was also performed. DNA was isolated from IHC equivocal samples and analyzed for microsatellite instability by using the Promega MSI Analysis System (version 1.2, Promega, Madison, WI).
Of the patients profiled, 329 had intact mismatch repair proteins by IHC. Six samples with IHC testing results indicating absent mismatch repair protein were analyzed for MSI and confirmed to be negative. Of the six IHC-negative samples, five were negative for programmed death ligand 1 staining and one sample had more than 5% staining.
In this large retrospective series, we were unable to identify any patients with malignant pleural mesothelioma with microsatellite instability. Response to anti–programmed cell death 1–based immunotherapy may be driven by other mechanisms.
•Agents targeting angiogenic pathways such as bevacizumab have demonstrated efficacy in mesothelioma. An analysis of the combination of stromal and vascular biomarkers is relevant to the use of ...multi-angiokinase targets of PDGF, FGF and VEGF in malignant mesothelioma to help determine their prognostic implications.•High CD31 was an independent poor prognostic factor and high PDGF-CC expression was associated with poor survival in mesothelioma.•There was a high incidence of positive VEGF and FGFR IHC in the large mesothelioma cohort but no significant correlation between prognosis and immune expression was found.
Malignant mesothelioma (MM) is an aggressive malignancy of the pleura and other mesothelial membranes. Agents targeting vascular endothelial growth factor (VEGF) such as bevacizumab; and multi-kinase inhibitors such as nintedanib angiokinase inhibitor of VEGF, platelet-derived growth factor (PDGF) receptor and fibroblast growth factor receptor (FGFR) have recently demonstrated efficacy in MM.
Tissue microarrays (TMAs) were created from formalin-fixed, paraffin-embedded tissue samples obtained from 326 patients with MM who were treated surgically. PDGF-CC, FGFR-1, VEGF and CD31 expression were analysed by immunohistochemical (IHC) staining. The H-score method assigned a score of 0–300 to each sample, based on the percentage of cells stained at different intensities. CD31 was evaluated via Chalkley’s method to evaluate microvessel density. We evaluated the association between expression of the biomarkers, clinicopathological factors and outcomes, in patients with MM.
CD31 high (≥5) was seen in only 31/302 (10.3%) irrespective of histology. PDGF-CC high (≥150) was seen in 203 /310 (65%) of all samples. VEGF high (≥80) was seen in 219/322 (68%) of all MM with 143/209 (68%) of epithelioid histology. FGFR-1 high (≥40) was seen in 127/310 (41%) of all MM. There was no association of VEGF and FGFR-1 IHC with survival nor differences between histological subtypes.
There was a non-significant trend towards poorer survival in epithelioid tumours with increased PDGF-CC expression (OS 18.5 vs 13.2 months; HR 0.7928; 95% CI 0.5958 to 1.055, P = 0.1110). High CD31 score was associated with significantly poorer survival (OS 12 vs 8.6 months; HR 0.48; 95% CI 0.2873 to 0.7941, P = 0.0044). Of the 31 patients with high CD31 scores; 23/31 (74%) were also high for PDGF-CC and 20/31 (64%) with high VEGF scores. CD31 was found to be an independent prognostic factor in multivariate analysis (HR 1.540; 95% CI 1.018 to 2.330; p = 0.041).
High CD31 was an independent poor prognostic factor and high PDGF-CC expression was associated with poor survival in MM. Abrogating these pathways may have prognostic implications.
Introduction: Empyema thoracis is an uncommon complication of childhood pneumonias but a common problem faced by a thoracic surgeon. Its management is still controversial, with a range of treatment ...options available and evolving gradually towards adoption of video-assisted thoracoscopic surgery (VATS) as the most commonly practiced one.
Aim: The aim of this study was to review our experience in pediatric empyema thoracis.
Methods: It was a retrospective review of the prospectively recorded data, spanning a period of 18 months in the Department of Cardio-Thoracic and Vascular Surgery in Manmohan Cardio-Thoracic Vascular and Transplant Center.
Results: A total of 40 consecutive patients, 29 males and 11 females, aged 15 years or less were operated upon for a diagnosis of empyema thoracis made based on clinical, radiological and laboratory evidence. All of them were referred patients, mostly from pediatricians. VATS was undertaken in 36 of them, the remaining four treated by open approach. Deloculation sufficed in majority (26/40; 65%) of the patients which mostly (23/26; 90%) had either acute or subacute presentation. Decortication was required in 35% (14/40) of the patients. However, all of the patients but one had a successful outcome in terms of lung expansion, sterilization of the pleural cavity and absence of recurrence. There was no operative mortality.
Conclusion: Surgical management of pediatric thoracic empyema is feasible and safe with favorable outcome. VATS is gradually becoming the more favored modality of operative management.
Despite having one of the lowest survival rates of all cancers, there have been no new approved treatments for malignant pleural mesothelioma (MPM) in over a decade. Standard-of-care treatment relies ...on Cisplatin plus Pemetrexed chemotherapy. Here, we tested a suite of BH3-mimetic drugs targeting BCL-2 pro-survival proteins of the intrinsic apoptotic pathway. We found BCL-XL is the dominant pro-survival protein in a panel of cell lines in vitro, though potent, synergistic cell killing occurred with MCL-1 co-targeting. This correlates with high-level expression of BCL-XL and MCL-1 in cell lines and a large cohort of patient tumour samples. BCL-XL inhibition combined with Cisplatin also enhanced cell killing. In vivo BCL-XL inhibition was as effective as Cisplatin, and the combination enhanced tumour growth control and survival. Genetic ablation of MCL-1 also enhanced the effects of BCL-XL inhibitors, in vivo. Combined, these data provide a compelling rationale for the clinical investigation of BH3-mimetics targeting BCL-XL in MPM.
Malignant pleural mesothelioma (MPM) is an aggressive, almost universally fatal cancer with limited therapeutic options. Despite efforts, a real breakthrough in treatment and outcomes has been ...elusive. Pleural effusion with significant breathlessness and pain is the most typical presentation of individuals with MPM. Although thoracentesis provides relief of breathlessness, most such pleural effusions recur rapidly, and a definitive procedure is often required to prevent a recurrence. Unfortunately, the optimal treatment modality for individuals with recurrent MPM-related effusion is unclear, and considerable variation exists in practice. In addition, non-expandable lung is common in pleural effusions due to MPM and makes effective palliation of symptoms more difficult. This review delves into the latest advances in the available management options (both surgical and non-surgical) for dealing with pleural effusion and non-expandable lung related to MPM. We discuss factors that determine the choice of definitive procedures that need to be tailored to the individual patient.
Large spontaneous lung hernia—a case report Devan Nair, Hareshdeva; Thapa, Bibhusal; Bhagwat, Krishna
Journal of surgical case reports,
12/2023, Volume:
2023, Issue:
12
Journal Article
Peer reviewed
Open access
Abstract
Intercostal lung hernias can be results of trauma or surgery. True spontaneous lung hernias thought to be a result of sudden acute increase in intrathoracic pressures are extremely rare. ...Only 51 cases have been reported in literature over the past four-and-half decades. We report a case of spontaneous chest wall posterior-lateral lung herniation that developed in a 73-year-old following severe coughing and straining during an episode of lower respiratory tract infection. Herein we present the unusual findings in the case and outline the pathophysiology of the problem and management options available.
Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented ...in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.
Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting ...response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment. We propose a standardized methodology to assess TILs in solid tumors on hematoxylin and eosin sections, in both primary and metastatic settings, based on the International Immuno-Oncology Biomarker Working Group guidelines for TIL assessment in invasive breast carcinoma. A review of the literature regarding the value of TIL assessment in different solid tumor types follows in part 2. The method we propose is reproducible, affordable, easily applied, and has demonstrated prognostic and predictive significance in invasive breast carcinoma. This standardized methodology may be used as a reference against which other methods are compared, and should be evaluated for clinical validity and utility. Standardization of TIL assessment will help to improve consistency and reproducibility in this field, enrich both the quality and quantity of comparable evidence, and help to thoroughly evaluate the utility of TILs assessment in this era of immunotherapy.
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