Lung Mass Research Articles

NEUROLOGIC COMPLICATION IN LUNG ADENOCARCINOMA EFGR MUTATION WITH A CONSOLIDATION-TO-TUMOR-RATIO (CTR) >75%

Lung adenocarcinoma (LAC) accounts for a large proportion of lung cancer subtypes and causes various neurologic complications. This calls for extensive use of CT scans for detecting lung cancer which contains ground glass opacity (GGO). A Consolidation-to-tumor-ratio (CTR) >75% has a worse prognosis in LAC. A male 50-years-old came with paraplegia, complaining suddenly that his legs could not be moved. The patient performed a spine MRI with the result indicating a spinal metastatic process. Furthermore, the Chest X-ray only showed consolidation in the right paracardial area but the chest CT confirmed as lung mass followed by histopathology examination result of LAC with EFGR mutation. After three months, the patient also had multiple cerebral infarcts. We reported one case of LAC EFGR mutation with a CTR of 83%. higher CTR has more invasive adenocarcinomas and also correlated with immunosuppressive conditions compared with a low CTR. The patient was diagnosed lately after a complication of spinal compression. The other neurological complication is multiple cerebral infarcts. The pathogenesis of cancer-associated stroke has not been fully clarified. The pathophysiological mechanisms of these cerebrovascular complications are multifactorial. Other biological markers may also be of interest, including high levels of C-reactive protein (CRP), high levels of fibrinogen, decreased hemoglobin, and hypoalbuminemia. Retrospective studies on acute stroke detected significantly higher levels of fibrinogen and CRP in patients with cryptogenic stroke and occult malignancy. LAC with a CTR >75% is more invasive due to neurologic complications such as spinal metastases and stroke infarction. Keywords: Lung adenocarcinoma, CTR, Stroke, Metastase

Ovarian myeloid sarcoma with concurrent acute myeloid leukemia- A case report

Myeloid sarcoma is a rare extramedullary tumor of immature myeloid cells that can be composed of cells showing granulocytic or monocytic differentiation. It is frequently detected as masses in subcutaneous soft tissue, bone, skin, GIT, reproductive organs, CNS, heart, lungs, kidney and breast. We report a pediatric case of myeloid sarcoma presenting with bilateral ovarian masses.A 12 years old female presented with complaints of fever, lethargy, decreased appetite and easy fatiguability. Patient further developed swelling and pain in large joints along with slurring of speech and difficulty in swallowing. Examination revealed polyserositis along with hepatosplenomegaly. ANA IFA profile was positive. CECT abdomen showed heterogeneous lesions in bilateral adnexae along with a few enlarged matted lymph nodes in left para-aortic region (?Neoplastic/ ?Histiocytosis/ ?EM hematopoiesis). GBP was suggestive of leucoerythroblastic reaction. BM study with flowcytometry was suggestive of Acute myeloid leukemia with monocytic differentiation. Biopsy from both adnexae showed features consistent with poorly differentiated malignancy, favour haematolymphoid neoplasm. Immunophenotyping by IHC showed the cells to be positive for CD45 (dim), MPO & CD117, thus establishing diagnosis of Myeloid sarcoma, both ovaries.Myeloid sarcoma is uncommon ovarian neoplasm and the clinical presentation may be with or without acute leukemia / MPN. Immunohistochemistry and ancillary studies are necessary to recognize this entity.

Karsinoma Sel Skuamosa Paru Kanan Dengan PPOK Dan Atelektasis Paru Kiri

Lung cancer is one of the most common causes of death today. One case of right lung squamous cell carcinoma with COPD and atelectasis has been reported in a 44 year old male patient. Based on the history, the patient said he had experienced chest pain for 1 week before entering the hospital and had a cough without phlegm or blood. Physical examination revealed dull chest wall percussion at the apex of the right lung and dullness in the left lung field, vesicular breathing sounds in both lung fields and rhonchi in the left lung field. The results of the supporting examination found a mass in the left lung on a chest x-ray and a bronchoscopy examination found a right lung tumor (type?) T3N1M0 Stage IIIA and the results of the anatomical pathology examination showed a picture of non-small cell carcinoma type squamous cell carcinoma. Patients are treated with chemotherapy and symptomatic therapy.

Adenocarcinoma de pulmón en felinos

Lung adenocarcinoma in felines is a lung neoplasm commonly described among the primary lung carcinomas reported in the species. Primary lung neoplasms in felines are rare, have characteristics of malignancy and tend to metastasize to intrathoracic and extrathoracic organs. Elderly cats are commonly more affected, with no predisposition by sex or breed, although the Persian breed has been reported in the literature. In veterinary medicine, metastasis to the digits, called digit-pulmonary syndrome, has been described as a condition that exclusively affects this species. Specific clinical signs are generally a dry, non-productive cough, dyspnea, tachypnea and intolerance to exercise, while non-specific systemic signs are related to the organ involved and, when present, are associated with paraneoplastic syndrome. Cats with primary lung neoplasia may be asymptomatic and primary lung disease presents as an incidental finding. The initial diagnosis may be based on a chest radiographic study, with the aim of detecting lung masses and metastases. Computed tomography has shown to be more sensitive and detect lymphadenopathy more efficiently than conventional radiography. Histopathological evaluation has proven to be the gold standard for the definitive diagnosis of primary lung neoplasms in felines. Post-mortem examination allows macroscopic evaluation of the lesion and allows for the identification of changes in other organs. Adjuvant chemotherapy treatment and surgical resection of well-differentiated lung neoplasms can offer longer survival compared to individuals diagnosed with poorly differentiated neoplasms and metastases present in other locations. The prognosis is mostly unfavorable, usually leaving only palliative care, aiming at analgesia and patient comfort.

Intrapulmonary schwannoma presenting as an asymptomatic lung mass: a case report

BackgroundSchwannomas are solitary well-circumscribed encapsulated benign tumors that exhibit Schwann cell differentiation, and arise directly from myelinated peripheral or central nerves. Although they are usually asymptomatic and found incidentally, schwannomas can cause symptoms due to compression of nearby structures which, depending on the location, can make clinical presentations widely variable. Despite their rarity, schwannomas have been documented in a number of locations including the limbs, cerebellopontine angle, posterior mediastinum, and, far more infrequently, the lungs.Case presentationIn this article, we report an incidental finding of an intrapulmonary schwannoma in a 59-year-old Pakistani woman who was grossly asymptomatic upon presentation to the cardiothoracic surgery clinic. An [18F]fluorodeoxyglucose positron emission tomography/computed tomography scan revealed a lobulated soft-tissue lesion measuring 23 mm × 23 mm in the lower lobe of the right lung. A computed tomography-guided core biopsy of the mass was performed, which revealed a benign spindle cell lesion based on histopathological examination and immunohistochemical staining. The mass was surgically resected via a right lower lobectomy, and subsequently confirmed to be an encapsulated neoplastic lesion composed of well-differentiated Schwann cells. There were no short- or long-term complications, morbidities, or recurrences based on 1-year follow-up.ConclusionThis report underscores the predominantly asymptomatic nature of schwannomas and reemphasizes the efficacy of surgical resection as a safe and curative procedure for a tumor of this nature. Albeit very rare, intrapulmonary schwannomas can be considered a differential diagnosis when encountering solitary asymptomatic pulmonary nodules or masses.

Pulmonary actinomycosis mimicking lung cancer – a case report

We present a case of a 55-year-old female patient admitted to the Thoracic Surgery Center for the treatment of a solid left lung mass of unknown aetiology. The patient was transported from another hospital, and the main reason for the patient’s referral to the Thoracic Surgery Center was recurrent haemoptysis and pulmonary haemorrhages. A chest X-ray in the posteroanterior projection showed no changes that could indicate the cause of the patient’s symptoms. In the course of diagnosis, a positron emission tomography combined with computed tomography scan was performed, in which an area of pathological radiotracer uptake was detected in the X segment of the left lung, with transverse dimensions of 6 × 6.5 cm, suggesting left lung cancer. Lower left lung lobectomy was performed, along with mediastinal lymphadenectomy. Final diagnosis was reached by histopathological examination of the resected tissues – the image corresponded to pulmonary actinomycosis.

Peculiarities of bioaccumulation and toxic effects produced by copper oxide (ii) nanoparti-cles on the respiratory organs under inhalation exposure as opposed to their micro-sized chemical analogue: assessment for prevention purposes

At present, it is quite relevant to get better insight into parameters and peculiarities of deleterious effects produced by copper oxide nanoparticles (CuO NPs) on the respiratory organs under inhalation exposure. This will help develop more effective prevention measures. The aim of this study was to assess peculiarities of bioaccumulation and toxic effects produced by CuO NPs on the respiratory organs as opposed to their micro-sized analogue in experimental modeling of inhalation exposure for prevention purposes. We established physical properties of the tested materials. Experimental studies were accomplished on Wistar rats. The experimental animals underwent a single 4-hour inhalation exposure to a concentration of ~4 mg/m3; a subchronic inhalation exposure to a concentration of 1.2–1.4 mg/m3; a single intratracheal exposure to a dose of 0.005 grams per one rat. We examined peculiarities of NPs bioaccumulation, their influence on the cellular population of the bronchoalveolar lavage fluid (BALF), development of pathomorphological disorders in tissues, and the lung mass in comparison with the micro-sized analogue. CuO NPs, as opposed to their micro-sized analogue, are smaller in size, have smaller hydrodynamic diameters, greater specific surface area and greater total pore volume; these properties determine their greater permeability. Bioaccumulation in the lungs, which was identified for NPs and MPs, is comparable under a single inhalation exposure. Under chronic exposure, NPs tend to bioaccumulate more intensively. A single intratracheal exposure induces more apparent changes in the BALF cellular population. Exposure to NPs causes emphysema, edema, and erythrocyte exudation in the lungs whereas these effects are not identified under exposure to MPs. Therefore, CuO NPs tend to accumulate more intensively and have more deleterious toxic effects on the respiratory organs (the lungs) than their micro-sized chemical analogue under a single intratracheal exposure (0.005 grams per one rat) and subchronic inhalation exposure (1.2 mg/m3). The study results should be considered when developing activities aimed at preventing negative health outcomes in the respiratory organs under inhalation exposure to the analyzed nanomaterial.

Physiological and Morphometric Differences in Resident Moderate-Altitude vs. Sea-Level Mice.

INTRODUCTION: High-altitude [>2400 m (7874 ft)] acclimatization has been well studied with physiological adaptations like reductions in body weight and exercise capacity. However, despite the significance of moderate altitude [MA, 1524-2438 m (5000-8000 ft)], acclimatization at this elevation is not well described. We aimed to investigate differences in mice reared at MA compared to sea level (SL). We hypothesized that MA mice would be smaller and leaner and voluntarily run less than SL mice.METHODS: C57BL/6 mice reared for at least three generations in Laramie, WY [2194 m (7198 ft), MA], were compared to C57BL/6J mice from Bar Harbor, ME [20 m (66 ft), SL]. We quantified body composition and exercise outputs as well as cardiopulmonary morphometrics. Subsets of MA and SL mice were analyzed to determine differences in neuronal activation after exercise.RESULTS: When body weight was normalized to tibia length, SL animals weighed 1.30 g ⋅ mm-1 while MA mice weighed 1.13 g · mm-1. Total fat % and trunk fat % were higher in MA mice with values of 41% and 39%, respectively, compared to SL mice with values of 28% and 26%, respectively. However, no differences were noted in leg fat %. MA animals had higher heart mass (119 mg) and lower lung mass (160 mg) compared to SL mice heart mass (100 mg) and lung mass (177 mg). MA mice engaged in about 40% less voluntary wheel-running activity than SL animals.DISCUSSION: Physiological differences are apparent between MA and SL mice, prompting a need to further understand larger scale implications of residence at moderate altitude.O'Connor AE, Hatzenbiler DM, Flom LT, Bobadilla A-C, Bruns DR, Schmitt EE. Physiological and morphometric differences in resident moderate-altitude vs. sea-level mice. Aerosp Med Hum Perform. 2023; 94(12):887-893.

Оценка особенностей бионакопления и токсического действия наночастиц оксида меди (ii) на органы дыхания при ингаляционном поступлении в организм в сравнении с микроразмерным химическим аналогом для задач профилактики

At present, it is quite relevant to get better insight into parameters and peculiarities of deleterious effects produced by copper oxide nanoparticles (CuO NPs) on the respiratory organs under inhalation exposure. This will help develop more effective prevention measures. The aim of this study was to assess peculiarities of bioaccumulation and toxic effects produced by CuO NPs on the respiratory organs as opposed to their micro-sized analogue in experimental modeling of inhalation exposure for prevention purposes. We established physical properties of the tested materials. Experimental studies were accomplished on Wistar rats. The experimental animals underwent a single 4-hour inhalation exposure to a concentration of ~4 mg/m3; a subchronic inhalation exposure to a concentration of 1.2–1.4 mg/m3; a single intratracheal exposure to a dose of 0.005 grams per one rat. We examined peculiarities of NPs bioaccumulation, their influence on the cellular population of the bronchoalveolar lavage fluid (BALF), development of pathomorphological disorders in tissues, and the lung mass in comparison with the micro-sized analogue. CuO NPs, as opposed to their micro-sized analogue, are smaller in size, have smaller hydrodynamic diameters, greater specific surface area and greater total pore volume; these properties determine their greater permeability. Bioaccumulation in the lungs, which was identified for NPs and MPs, is comparable under a single inhalation exposure. Under chronic exposure, NPs tend to bioaccumulate more intensively. A single intratracheal exposure induces more apparent changes in the BALF cellular population. Exposure to NPs causes emphysema, edema, and erythrocyte exudation in the lungs whereas these effects are not identified under exposure to MPs. Therefore, CuO NPs tend to accumulate more intensively and have more deleterious toxic effects on the respiratory organs (the lungs) than their micro-sized chemical analogue under a single intratracheal exposure (0.005 grams per one rat) and subchronic inhalation exposure (1.2 mg/m3). The study results should be considered when developing activities aimed at preventing negative health outcomes in the respiratory organs under inhalation exposure to the analyzed nanomaterial.

SFM Fetal Therapy Practice Guidelines: Open Fetal Surgery

AbstractOpen fetal surgery allows for surgical intervention on the fetus while maintaining placental perfusion, with the objective of prolonging intrauterine gestation as long as feasible after an operation. Fetal spina bifida utero repair, congenital diaphragmatic hernia, lower urinary tract obstruction/bladder outlet obstruction, and fetal lung masses are the pathologies that can be treated with open fetal surgery. With the availability of minimally invasive techniques, the open technique is not the primary choice of treatment; however, it is prominently used for meningomyelocele repair.

Dual-Layer Spectral CT as Innovative Imaging Guidance in Lung Biopsies: Could Color-Coded Z-Effective Images Allow More Diagnostic Samplings and Biomarkers Information?

The aim of the study was to try to obtain more information on diagnostic samplings and biomarkers using dual-layer spectral CT in lung biopsies. Lung biopsies were performed by merging images obtained with CBCT with those from spectral CT to use them as functional guidance, experimenting with double sampling to determine the difference between the area with a higher Z-effective number and that with a lower Z-effective number. Ten patients with large lung lesions on spectral CT were selected and underwent percutaneous transthoracic lung mass biopsy. Technical success was calculated. The percentage of neoplastic, inflammatory, fibrotic, necrotic cells, or non-neoplastic lung parenchyma was reported. The possibility of carrying out immunohistochemical or molecular biology investigations was analyzed. All lesions were results malignant in 10/10 samples in the Zmax areas; in the Zmin areas, malignant cells were found in 7/10 samples. Technical success was achieved in 100% of cases for Zmax sampling and in 70% for Zmin sampling (p-value: 0.2105). The biomolecular profile was detected in 9/10 (90%) cases in Zmax areas, while in 4/10 (40%) cases in Zmin areas (p-value: 0.0573). The advantage of Z-effective imaging would be to identify a region of the lesion that is highly vascularized and probably richer in neoplastic cells, thus decreasing the risk of obtaining a non-diagnostic biopsy sample.

Clinical Utility of Chest Sonography in Chronic Obstructive Pulmonary Disease Patients Focusing on Diaphragmatic Measurements.

There are many methods of evaluating diaphragmatic function, including trans-diaphragmatic pressure measurements, which are considered the key rule of diagnosis. We studied the clinical usefulness of chest ultrasonography in evaluating stable chronic obstructive pulmonary disease (COPD) patients and those in exacerbation, focusing on diaphragmatic measurements and their correlation with spirometry and other clinical parameters. In a prospective case-control study, we enrolled 100 COPD patients divided into 40 stable COPD patients and 60 patients with exacerbation. The analysis included 20 age-matched controls. In addition to the clinical assessment of the study population, radiological evaluation included chest radiographs and chest computed tomography. Transthoracic ultrasonography (TUS) was performed for all included subjects. Multiple A lines (more than 3) were more frequent in COPD exacerbation than in stable patients, as was the case for B-lines. TUS significantly showed high specificity, negative predictive value, positive predictive value, and accuracy in detecting pleural effusion, consolidation, pneumothorax, and lung mass. Diaphragmatic measurements were significantly lower among stable COPD subjects than healthy controls. Diaphragmatic thickness and excursion displayed a significant negative correlation with body mass index and the dyspnea scale, and a positive correlation with spirometry measures. Patients in Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D showed lower diaphragmatic measurements (thickness and excursion). The TUS of COPD patients both in stable and exacerbated conditions and the assessment of diaphragm excursion and thickness by TUS in COPD patients and their correlations to disease-related factors proved informative and paved the way for the better management of COPD patients.

Lung and Systemic Mass Shadows due to Methotrexate-associated Lymphoproliferative Disease with Pulmonary Aspergillosis Diagnosed by Multiple Approaches: A Case Report

Lung and Systemic Mass Shadows due to Methotrexate-associated Lymphoproliferative Disease with Pulmonary Aspergillosis Diagnosed by Multiple Approaches: A Case Report

Macro-Vitamin B12 as Cause of Falsely Elevated Cobalamin Levels.

High blood concentrations of vitamin B12 are often caused by over-supplementation. However, there are instances in which augmented vitamin B12 levels are seen in the absence of supplements. Macro-vitamin B12 is an underrated cause of supra-physiological cobalamin plasma levels. A 70-year-old man was referred to an ambulatory internal medicine centre because of high vitamin B12 levels yet he denied taking supplements. An X-ray showed a tumour in the right upper lobe of the lung, which triggered further examinations. An MRI scan of the brain came back normal as well as a CT scan of the abdomen, and colonoscopy. The pulmonologist requested a PET-CT scan, which showed an isolated 18-FDG uptake in the area of the lung mass that was detected earlier. The patient underwent surgery with adjuvant cis-platinum and gemcitabine and is still making good progress. The vitamin B12 levels persisted after successful treatment of lung adenocarcinoma; determination of vitamin B12 after PEG (polyethylene glycol) precipitation showed normal concentrations. A high vitamin B12 plasma concentration in the absence of vitamin supplementation can be a daunting diagnostic problem for the internist, as there are several possible underlying causes. In this case the diagnosis of lung carcinoma was made, the patient was treated appropriately, yet this pathology had no correlation with the cobalamin levels. A high vitamin B12 concentration can be the impetus of thorough medical inquiries. Internists should be careful not to forget macro-vitamin B12 as a possible source of falsely elevated vitamin B12 values. When encountering an otherwise unexplainable B12 hypervitaminosis, the diagnosis of macro-vitamin B12 should be taken into account to avoid unnecessary extensive medical examinations.PEG precipitation can distinguish between a 'real' high vitamin B12 and macro-vitamin B12.A high vitamin B12 concentration is no guarantee for adequate cobalamin storage. In case of suspicion, a vitamin B12 measurement after PEG precipitation should be considered.

Primary Pulmonary Diffuse Large B-Cell Lymphoma - a Rare Case Report

Background: Diffuse large B cell lymphoma (DLBCL) is an aggressive hematological malignancy, and a common histological form of non-Hodgkin's lymphoma. However, its extra-nodal presentation is seen in 30-40% of cases with involvement of gastrointestinal tract, skin, testes, adrenals and bone. ( Lugogo NL et al., 2006) A pulmonary manifestation is an extremely rare entity. We present an atypical case of DLBCL presenting as pleuritic chest pain with imaging consistent with bilateral pulmonary nodules suggestive of metastasis. Case description: A healthy 87 year old male former smoker with a history of type 2 diabetes mellitus, hypertension presented to the emergency department with pleuritic chest pain. There was no associated cough, shortness of breath, palpitations, nausea, dizziness or diaphoresis. No recent infections or B symptoms. He had a good appetite. He had prostate cancer 20 years ago and had a radical prostatectomy. Upon presentation, work up showed mild anemia (Hb 11.1 g/dL). Cardiac work up for chest pain was unremarkable. Chest X-Ray revealed mass like opacities in each lung with largest in left mid lung measuring up to 6 cm. CT chest with IV contrast revealed multiple lung nodules bilaterally with 2 largest in left upper lobe measuring 5.6 x 3.7 cm and 5.7 x 3.3 cm. Multiple other small nodules are present in both lung fields consistent with diffuse lung metastasis. No lymphadenopathy was noted. (Image 1) PET CT scan was significant for bilateral FDG avid lung lesions. No evidence of other FDG avid disease. CT guided biopsy of the left lung mass surprisingly revealed diffuse large B cell non-Hodgkin's lymphoma, non-germinal center type. (Image 1) Immuno-histochemistry showed atypical lymphocytes positively stained with CD20, BCL6, BCL2, PAX5 and MUM1. C-myc had 50% positivity. Ki67 had 90% proliferative index. FISH analysis was negative for MYC, BCL2 and BCL6; hence there was no double hit lymphoma detected. According to Lunago classification, patient had advanced stage disease with IPI (prognosis index) of 2. His ECOG PS score was 0. He was initiated on R-Pola-CHP. Given his age, Cyclophosphamide and Adriamycin doses were reduced as done with R-mini CHOP. Vincristine was avoided given neurotoxicity. Discussion: Primary pulmonary B-cell lymphomas (PP-BCLs) represent less than 3-4% of all extra-nodal NHL. They primarily affect the lung without evidence of extrapulmonary disease at the time of diagnosis. PP-DLBCL accounts for only 10% cases of PP-BCLs. ( Sanguedolce et al., 2021) Most cases have atypical presentation. Likewise, in our patient, he manifested with atypical chest pain without any B symptoms. Radiographic imaging can show variable findings of consolidation, single/multiple nodules, reticular interstitial infiltrate or bilateral ground glass opacities. In view of the insidious onset and lack of specificity in clinical symptoms, primary pulmonary lymphomas are frequently misdiagnosed as refractory pneumonia, lung abscess, asthma, primary lung cancer, or lung metastasis. ( Liu et al., 2020) Patients with DLBCL are typically treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). However, with this regimen, only 60% of patients are cured and the rest might relapse. In the POLARIX phase 3 trial, polatuzumab vedotin (a monoclonal antibody to CD79b ubiquitously expressed on B cells) combined with R-CHP significantly improved 2 year progression-free survival compared to the routine R-CHOP therapy in previously untreated DLBCL patients. ( Tilly et al., 2022) Given our patient's advanced stage disease, he was initiated on the Pola-R-CHP regimen. Doses of cyclophosphamide and doxorubicin were reduced as per the R-mini CHOP dose-reduced regimen for a physically fit elderly individual. Patient continues on therapy at the time of this abstract. In conclusion, primary pulmonary DLBCL is a rare entity with only a few case reports in literature. It should be considered in patients presenting with large pulmonary masses, mimicking metastatic disease.

Preliminary Results of Phase 2 Open Label Study of Lorlatinib Monotherapy in Relapsed/Refractory ALK + Lymphomas Previously Treated with Other Tyrosine Kinase Inhibitors

Introduction: Both aggressive T and B cell lymphoma may harbour Anaplastic Lymphoma Kinase (ALK) translocations: ALK+ Anaplastic Large Cell lymphoma (ALCL) offer a good outcome with first line therapy with 5-year survival of 79%, but relapses occur in half of the patients (pts) and salvage therapy still represents a challenge for clinicians; ALK+ large B cell lymphoma (LBCL) are very rare cases but with dismal prognosis. In addition other hematologic neoplasms can be caused by ALK fusions. Crizotinib, an ALK/MET tyrosine kinase inhibitor (TKI), provides long-term response in up to 70% relapsed/refractory (R/R) ALK+ ALCL and can obtain a similar but less durable response rates in ALK+ LBCL. In both cases the loss of response to crizotinib is frequently a fatal event. Lorlatinib, a selective ALK and ROS1 TKI, demonstrated preclinical inhibition of all reported ALK kinase domain mutations responsible for resistance to Crizotinib. Methods: From 2019 to 2022 six relapsed/refractory ALK + neoplasm pts previously treated with at least one ALK-inhibitor were enrolled in a phase 2 open label monocentric study with lorlatinib monotherapy (EudraCT2016-003970-41): Three patients had diagnosis of ALK+ LBCL (# 1, 2, 3) and 2 (#5 and #6) had ALK+ ALCL. One patient (#4) with an ALK+ histiocytosis was also included. Median age was 22 years (range 19-57), Ratio M/F was 1, all pts were in stage IV. Median prior therapy lines was 3 (range 2-5); all pts previously received Crizotinib, two pts received also Alectinib and 1 Ceritinib as TKI treatment. Lorlatinib was administered daily at dose of 100 mg. Clinical, laboratory, radiological and molecular data were collected at screening and during scheduled follow-up. Response was evaluated with 18F-FDG PET/CT (and with contrast enhanced (ce) CT scan) according Lugano Classification, and with ALK RT-PCR on peripheral blood and bone marrow. Side effects were classified according to CTCAEv4.03. PFS and OS were determined from Lorlatinib start to relapse and/or death. The primary endpoint was the evaluation of ORR considering 18F-FDG PET/CT scan and ALK- RT-PCR. Secondary endpoints were: PFS, OS, toxicity, QoL. Results: ALK rearrangement fusion pattern was detected in 6/6 pts: 3 pts with LBCL harboured Clathrin-ALK (CTCL::ALK) rearrangement and 2 ALCL pts the ATIC::ALK fusion; the ALK+ histiocytosis patient harbored an EML4::ALK rearrangement. Median follow-up was 13.7 months (IQR 22-55). At month +1 (M1) 3/6 patients had complete response (CR) defined as complete metabolic and complete radiologic response (CMR/CR) according to PET/CT scans and ALK RT-PCR negativity. The remaining 3 pts had a partial response (PR), for an Overall Response Rate (ORR) of 100% (95%CI: 0.6-1.0). One pt is still on treatment and in CR at 45 months, receiving Lorlatinib 100 mg daily with neither toxicities nor need for Allogenic Stem Cell Transplantation (ASCT); 2 CR pts underwent ASCT after 1 month, resumed lorlatinib after ASCT and are still in CR. 2 pts with PR relapsed within month +3: one pt received salvage therapy without benefit, the other one underwent ASCT but progressed 3 months later. Both pts had ALK+ BCL with CTCL-ALK rearrangement. 1 pts in PR AT M1 (ALK+ istiocytosis) obtain CR at M3 after surgical resection of a residual lung mass and is still receiving Lorlatinib at month 36. Median PFS and OS were not reached: PFS at 6 and 12 months is 83% and 62% respectively; OS at 6 and 12 months is 83% and 55%. Safety: 2/6 pts had thrombocytopenia grade 1, whereas 3/6 pts showed grade I-II hypertriglyceridemia/hypercholesterolemia and muscle cramps. Conclusions: Lorlatinib represents a safe and effective salvage therapy for ALK+ Lymphoma patients failing first line TKI treatment. The obtainment of CR at M1 seems to represent a pivotal prognostic factor. Lorlatinib also offers a promising bridging regimen to salvage ASCT especially for ALK+ BCL patients, with high response rates and no additional toxicities, .

The treatment with trandolapril and losartan attenuates pressure and volume overload alternations of cardiac connexin-43 and extracellular matrix in Ren-2 transgenic rats

Heart failure (HF) is life-threatening disease due to electro-mechanical dysfunction associated with hemodynamic overload, while alterations of extracellular matrix (ECM) along with perturbed connexin-43 (Cx43) might be key factors involved. We aimed to explore a dual impact of pressure, and volume overload due to aorto-caval fistula (ACF) on Cx43 and ECM as well as effect of renin–angiotensin blockade. Hypertensive Ren-2 transgenic rats (TGR) and normotensive Hannover Sprague–Dawley rats (HSD) that underwent ACF were treated for 15-weeks with trandolapril or losartan. Blood serum and heart tissue samples of the right (RV) and left ventricles (LV) were used for analyses. ACF-HF increased RV, LV and lung mass in HSD and to lesser extent in TGR, while treatment attenuated it and normalized serum ANP, BNP-45 and TBARS. Cx43 protein and its ser368 variant along with PKCε were lower in TGR vs HSD and suppressed in both rat strains due to ACF but prevented more by trandolapril. Pro-hypertrophic PKCδ, collagen I and hydroxyproline were elevated in TGR and increased due to ACF in both rat strains. While SMAD2/3 and MMP2 levels were lower in TGR vs HSD and reduced due to ACF in both strains. Findings point out the strain-related differences in response to volume overload. Disorders of Cx43 and ECM signalling may contribute not only to HF but also to the formation of arrhythmogenic substrate. There is benefit of treatment with trandolapril and losartan indicating their pleiotropic anti-arrhythmic potential. It may provide novel input to therapy.

Diagnostic yield of endobronchial ultrasound and virtual CT navigational bronchoscopy for biopsy of pulmonary nodules, mediastinal lymph nodes, and thoracic tumors in children.

Endobronchial ultrasound-guided transbronchial biopsy and needle aspiration (EBUS-TBB/EBUS-TBNA) are first line investigative modalities for lung and mediastinal pathology in adults. We aimed to characterize and assess the diagnostic yield of EBUS and virtual CT navigation guided biopsies in children. This single center, retrospective cohort study included patients who underwent radial or linear EBUS procedures (+/- CT navigation) for biopsy of mediastinal lymph nodes, tumors, and pulmonary nodules. Demographic, procedural, and outcome were collected. Sixty procedures were performed in 56 patients aged 2-22 years of age between January 2015 and May 2023. The most common indications for biopsy were pulmonary nodules (45%) and hilar/mediastinal lymphadenopathy (33%). For cases in which a final diagnosis was ascertained by any means, the diagnostic yield for linear EBUS (mediastinal pathology) was 76% and the diagnostic yield from radial EBUS (pulmonary nodules and lung masses) was 85%. The most common diagnoses were infection (45%), malignancy (17%), and sarcoidosis (11%). Among patients in whom infection was the final diagnosis, a total of 31 pathogens were identified. Eighteen were identified on bronchoalveolar lavage and an additional 14 pathogens identified on EBUS-TBB, representing an increase of 77% (p < .005). The sensitivity, specificity, negative and positive predictive values for malignancy detection were 73%, 100%, 94%, and 100%, respectively. EBUS-TBB/TBNA is a safe and effective way to diagnose lung and mediastinal pathology in children. Pediatric interventional pulmonology is a growing field offering minimally-invasive diagnostic opportunities for children in whom more invasive procedures were previously the only option.

Lipoid pneumonia presenting as lung mass following accidental diesel ingestion: An interesting case

Lipoid pneumonia presenting as lung mass following accidental diesel ingestion: An interesting case

Concomitant minimally invasive surgery for tricuspid valve papillary fibroelastoma and right lung cancer in an elderly patient: a case report and review of the literature

BackgroundIt is very common for patients with newly diagnosed lung masses to have heart disease. However, papillary fibroelastomas (PFEs) of the tricuspid valve (TV) combined with lung cancer are rarely reported. It is thus unclear whether a two-stage surgery or concomitant surgery is optimal.Case presentationWe report the case of a 73-year-old Chinese male who was diagnosed with PFEs on the TV by transthoracic echocardiography (TTE) examination while being evaluated to undergo video-assisted thoracic surgery (VATS) for a right lower lung nodule. We resected both the PFEs and the lung nodule via right minithoracotomy. The surgery was uneventful, and histopathology reports confirmed PFEs of the TV and moderately to poorly differentiated squamous cell carcinoma. The patient recovered uneventfully, and there was no sign of tumor recurrence during 15 months of follow-up.ConclusionsWe suggest that after careful evaluation, concomitant minimally invasive radical resection of primary lung cancer after cardiac PFE removal is an acceptable and safe treatment strategy and should be performed as soon as possible.