BACKGROUND: Pulmonary hernia is a rare condition characterized by the protrusion of lung tissue through a chest wall defect. Trauma and thoracic surgery are the most common causes of acquired lung hernias. We present an unusual case of (sequential) bilateral lung herniation with parenchymal infarction after bilateral lobar lung transplantation. CASE PRESENTATION: A 50-year-old female, wait-listed as high-urgency candidate, with a body mass index (BMI) of 29 kg/m2 underwent a bilateral lobar lung transplantation for pulmonary fibrosis through a clamshell thoracotomy approach. Due to a size mismatch, stapler resection of the segment 3 and the middle lobe of the right lung, as well as an upper left lobectomy was required. The chest was closed with 3 braided non-absorbable pericostal sutures on each side. Sternal osteosynthesis was performed with a titanium sternal splint along with 7 self-tapping screws with a length of 18 mm. On the posttransplant day (PTD) 18, patient's clinical condition deteriorated. Physical examination didn't reveal any palpable subcutaneous chest resistance. However, a computed tomography (CT) scan showed a herniation of the segment 6 of the right lung. During acute surgical revision, perioperative finding revealed posterior pericostal suture failure. Therefore, a stapler resection was performed due to the infarction of the herniated segment. On the PTD 36, herniation of the left lung parenchyma was detected by acute CT scan. The protruding vital parenchyma was surgically repositioned without necessity of resection. Two posterior pericostal sutures were broken, and distal part of sternal splint detached. Thoracotomy was closed using 5 braided non-absorbable sutures. Sternum was re-osteosynthesized with the STRATOS™ system. After 3 months of intensive postoperative care, the patient was transferred to the rehabilitation department. She was discharged on the PTD 99. After 20 months of follow-up, lung function remains stable without the need for oxygen support. CONCLUSION: Clamshell incision remains ultimate approach in thoracic surgery. However, pulmonary herniation after clamshell thoracotomy is a rare complication and may manifest as acute respiratory distress syndrome with an inflammatory response. In these cases, CT scan should be always considered, even if no palpable pathology of chest is present.
- Klíčová slova
- Clamshell thoracotomy, Lung hernia, Lung transplantation,
- MeSH
- hernie * etiologie MeSH
- infarkt etiologie chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- operace kýly metody škodlivé účinky MeSH
- plíce diagnostické zobrazování MeSH
- plicní nemoci chirurgie etiologie MeSH
- počítačová rentgenová tomografie MeSH
- pooperační komplikace chirurgie MeSH
- torakotomie * metody MeSH
- transplantace plic * škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Scoliotic deformity represents a serious spinal disorder that influences the locomotive and cardiopulmonary systems. Some patients with severe scoliosis and end-stage lung disease are therefore denied lung transplantation. In patients with scoliosis considering lung transplantation, size match, straight back syndrome, delayed chest closure and bronchial stenosis are key issues clinicians should evaluate. Therefore, it is vital to determine donor-recipient size matches very precisely. Chest opening is a routine intraoperative primary therapeutic procedure after lung transplantation in unstable patients with oversized transplanted lungs. Postoperative bronchial stenosis occurs predominantly on the right side and is usually handled through interventional bronchoscopy and the insertion of stents. This report describes the complex case of a patient with scoliosis who underwent lobar transplantation in our center.
- Klíčová slova
- Bronchial stenosis, Delayed chest closure, Lung transplantation, Scoliosis, Straight back syndrome,
- MeSH
- bronchiální nemoci * chirurgie MeSH
- lidé MeSH
- skolióza * chirurgie MeSH
- stenóza chirurgie MeSH
- sternum chirurgie MeSH
- transplantace plic * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
INTRODUCTION: Compared with traditional static ice storage, controlled hypothermic storage (CHS) at 4-10°C may attenuate cold-induced lung injury between procurement and implantation. In this study, we describe the first European lung transplant (LTx) experience with a portable CHS device. METHODS: A prospective observational study was conducted of all consecutively performed LTx following CHS (11 November 2022 and 31 January 2024) at two European high-volume centers. The LUNGguard device was used for CHS. The preservation details, total ischemic time, and early postoperative outcomes are described. The data are presented as median (range: minimum-maximum) values. RESULTS: A total of 36 patients underwent LTx (i.e., 33 bilateral, 2 single LTx, and 1 lobar). The median age was 61 (15-68) years; 58% of the patients were male; 28% of the transplantations had high-urgency status; and 22% were indicated as donation after circulatory death. In 47% of the patients, extracorporeal membrane oxygenation (ECMO) was used for perioperative support. The indications for using the CHS device were overnight bridging (n = 26), remote procurement (n = 4), rescue allocation (n = 2), logistics (n = 2), feasibility (n = 1), and extended-criteria donor (n = 1). The CHS temperature was 6.5°C (3.7°C-9.3°C). The preservation times were 11 h 18 (2 h 42-17 h 9) and 13 h 40 (4 h 5-19 h 36) for the first and second implanted lungs, respectively, whereas the total ischemic times were 13 h 38 (4 h 51-19 h 44) and 15 h 41 (5 h 54-22 h 48), respectively. The primary graft dysfunction grade 3 (PGD3) incidence rates were 33.3% within 72 h and 2.8% at 72 h. Intensive care unit stay was 8 (4-62) days, and the hospital stay was 28 (13-87) days. At the last follow-up [139 (7-446) days], three patients were still hospitalized. One patient died on postoperative day 7 due to ECMO failure. In-hospital Clavien-Dindo complications of 3b were observed in six (17%) patients, and 4a in seven (19%). CONCLUSION: CHS seems safe and feasible despite the high-risk recipient and donor profiles, as well as extended preservation times. PGD3 at 72 h was observed in 2.8% of the patients. This technology could postpone LTx to daytime working hours. Larger cohorts and longer-term outcomes are required to confirm these observations.
- Klíčová slova
- controlled hypothermic storage, lung preservation, overnight bridging, preservation temperature, preservation time, primary graft dysfunction, total ischemic time,
- Publikační typ
- časopisecké články MeSH
Background: Ivacaftor is a modern drug used in the treatment of cystic fibrosis. It is highly lipophilic and exhibits a strong positive food effect. These characteristics can be potentially connected to a pronounced lymphatic transport after oral administration. Methods: A series of studies was conducted to describe the basic pharmacokinetic parameters of ivacaftor in jugular vein cannulated rats when dosed in two distinct formulations: an aqueous suspension and an oil solution. Additionally, an anesthetized mesenteric lymph duct cannulated rat model was studied to precisely assess the extent of lymphatic transport. Results: Mean ± SD ivacaftor oral bioavailability was 18.4 ± 3.2% and 16.2 ± 7.8%, respectively, when administered as an aqueous suspension and an oil solution. The relative contribution of the lymphatic transport to the overall bioavailability was 5.91 ± 1.61% and 4.35 ± 1.84%, respectively. Conclusion: Lymphatic transport plays only a minor role in the process of ivacaftor intestinal absorption, and other factors are, therefore, responsible for its pronounced positive food effect.
- Klíčová slova
- bioavailability, intestinal absorption, ivacaftor, lymphatic transport, pharmacokintetics,
- Publikační typ
- časopisecké články MeSH
Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease with unknown cause. It mainly affects joints and, without proper treatment, negatively impacts their movement, causes painful deformities, and reduces the patients' quality of life. Current treatment options consist of various types of disease-modifying antirheumatic drugs (DMARDs), however 20-30% of patients are partially resistant to them. Therefore, development of new drugs is necessary. Possible option are compounds exhibiting their action via endocannabinoid system, which plays an important role in pain and inflammation modulation. One such compound - cannabidiol (CBD) has already been shown to attenuate synovitis in animal model of RA in in vivo studies. However, it has low bioavailability due to its low water solubility and lipophilicity. This issue can be addressed by preparation of a lipid containing formulation targeting lymphatic system, another route of absorption in the body. Materials and Methods: CBD-containing emulsion was prepared by high-shear homogenization and its droplet size distribution was analysed by optical microscopy. The relative oral bioavailability compared to oil solution as well as total availability of CBD were assessed in a cross-over study in rats and absorption of CBD via lymphatic system was observed. The effect of CBD on the animal model of RA was determined. Results: Compared to oil solution, the emulsion exhibited higher absolute oral bioavailability. Significant lymphatic transport of CBD was observed in all formulations and the concentrations in lymph were calculated. The therapeutic effect of CBD on RA was confirmed as an improvement in clinical symptoms as well as morphological signs of disease activity were observed during the study. Conclusion: In this work, we prepared a simple stable emulsion formulation, determined the pharmacokinetic parameters of CBD and calculated its absolute bioavailability in rats. Moreover, we successfully tested the pharmaceutical application of such a formulation and demonstrated the positive effect of CBD in an animal model of RA.
- Klíčová slova
- bioavailability, cannabidiol, emulsion, in vivo study, lymphatic absorption, rheumatoid arthritis,
- MeSH
- aplikace orální MeSH
- bolest farmakoterapie MeSH
- emulze MeSH
- kanabidiol * farmakologie chemie MeSH
- klinické křížové studie MeSH
- krysa rodu Rattus MeSH
- kvalita života MeSH
- revmatoidní artritida * farmakoterapie MeSH
- voda MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- emulze MeSH
- kanabidiol * MeSH
- voda MeSH
The aim of this prospective study was to evaluate the pharmacokinetics of ganciclovir in lung transplant recipients, to explore its covariates, and to propose an individualized dosing regimen. Ganciclovir was administered according to the protocol in a standardized intravenous dose of 5 mg/kg twice daily. Serum ganciclovir concentrations were monitored as a trough and at 3 and 5 h after dosing. Individual ganciclovir pharmacokinetic parameters were calculated in a two-compartmental pharmacokinetic model, while regression models were used to explore the covariates. Optimal loading and maintenance doses were calculated for each patient. In lung transplant recipients (n = 40), the median (IQR) ganciclovir total volume of distribution and clearance values were 0.65 (0.52-0.73) L/kg and 0.088 (0.059-0.118) L/h/kg, respectively. We observed medium-to-high inter-individual but negligible intra-individual variability in ganciclovir pharmacokinetics. The volume of distribution of ganciclovir was best predicted by height, while clearance was predicted by glomerular filtration rate. Bodyweight-normalized clearance was significantly higher in patients with cystic fibrosis, while distribution half-life was reduced in this subgroup. On the basis of the observed relationships, practical nomograms for individualized ganciclovir dosing were proposed. The dosing of ganciclovir in patients with cystic fibrosis requires special caution, as their daily maintenance dose should be increased by approximately 50%.
- Klíčová slova
- covariates, cystic fibrosis, ganciclovir, lung transplant recipients, therapeutic drug monitoring,
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND PURPOSE: Lymphatic transport of drugs after oral administration is an important mechanism for absorption of highly lipophilic compounds. Direct measurement in lymph duct cannulated animals is the gold standard method, but non-invasive cycloheximide chylomicron flow blocking method has gained popularity recently. However, concerns about its reliability have been raised. The aim of this work was to investigate the validity of cycloheximide chylomicron flow blocking method for the evaluation of lymphatic transport using model compounds with high to very high lipophilicity, that is, abiraterone and cinacalcet. EXPERIMENTAL APPROACH: Series of pharmacokinetic studies were conducted with abiraterone acetate and cinacalcet hydrochloride after enteral/intravenous administration to intact, lymph duct cannulated and/or cycloheximide pre-treated rats. KEY RESULTS: Mean total absolute oral bioavailability of abiraterone and cinacalcet was 7.0% and 28.7%, respectively. There was a large and significant overestimation of the lymphatic transport extent by the cycloheximide method. Mean relative lymphatic bioavailability of abiraterone and cinacalcet in cycloheximide method was 28-fold and 3-fold higher than in cannulation method, respectively. CONCLUSION AND IMPLICATIONS: Cycloheximide chylomicron flow blocking method did not provide reliable results on lymphatic absorption and substantially overestimated lymphatic transport for both molecules, that is, abiraterone and cinacalcet. This non-invasive method should not be used for the assessment of lymphatic transport and previously obtained data should be critically revised.
- Klíčová slova
- abiraterone, bioavailability, biodistribution, cinacalcet, lymph duct cannulation, pharmacokinetics,
- MeSH
- aplikace orální MeSH
- biologická dostupnost MeSH
- biologický transport MeSH
- chylomikrony * metabolismus MeSH
- cykloheximid farmakologie MeSH
- intestinální absorpce * MeSH
- krysa rodu Rattus MeSH
- léčivé přípravky MeSH
- reprodukovatelnost výsledků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chylomikrony * MeSH
- cykloheximid MeSH
- léčivé přípravky MeSH
BACKGROUND: Spitzoid melanocytic lesions represent a heterogeneous group of proliferations with ambiguous and overlapping terminology. The exact distinction of a Spitz nevus from a Spitzoid melanoma can be very difficult or, in some cases, impossible. Among the Spitzoid lesions, there is a lesion termed an atypical Spitz tumour (AST) that has intermediate histopathologic features between those of a Spitz nevus and a Spitzoid melanoma and thus uncertain malignant potential. There are several rare cases of patients with a Spitzoid melanoma initially misdiagnosed as a Spitz nevus or an AST with fatal consequences. It is, therefore, advised to perform a molecular characterization in cases where uncertain skin lesions are presented, as it may provide extended set of information with a possible impact on the treatment options. Furthermore, preventive measures, such as regular physical and skin examinations, as well as thorough scheduling of individual follow-up visits, are essential in patients with potentially malignant skin nevi. CASE REPORT: We report a case of a young adult female with a history of AST excision with a negative sentinel lymph node biopsy (SLNB) and insufficient follow-up. Four years after the primary dermatological diagnosis, she presented with a giant tumour in the right hemithorax. Radical en bloc resection of the tumour with right pneumonectomy and resection of the pericardium with reconstruction of the pericardium using mesh was performed. A definitive histopathological examination revealed a metastatic melanoma. The association of the previously diagnosed AST and subsequent appearance of melanoma metastases led to a retrospective re-evaluation of the initial lesion. The suspected diagnosis of Spitzoid melanoma, however, was not confirmed. Moreover, the molecular examination revealed a major discordance between the initial lesion and the lung tumour, which most likely excluded the possible association of the lung metastasis with the initial skin lesion. The initial skin lesion was a BRAF-mutant melanoma with Spitzoid features and termed as AST, while the giant lung metastasis was NRAS-mutant melanoma. The subsequent postoperative course was complicated by the appearance of brain metastases that were stereotactically irradiated. Nevertheless, despite complex specialised medical care, the patient's clinical condition rapidly deteriorated. By this time, no active oncological treatment was possible. The patient was delegated to local hospice for palliative care six months after the surgery and died three weeks later. CONCLUSIONS: Our patient was surgically treated at the age of 20 for AST and died four years later of metastatic NRAS-mutant melanoma most likely of different occult origin. Molecular characterization, as well as the close clinical follow-up should be always precisely performed in patients with uncertain skin lesions, such as AST.
- Klíčová slova
- Atypical spitz tumour, Case report, Conventional melanoma, Metastasis, Molecular analysis, Spitz nevus, Spitzoid melanoma,
- MeSH
- epiteloidní a vřetenobuněčný névus genetika patologie MeSH
- GTP-fosfohydrolasy genetika MeSH
- lidé MeSH
- maligní melanom kůže MeSH
- melanom genetika sekundární MeSH
- membránové proteiny genetika MeSH
- mladý dospělý MeSH
- mnohočetné primární nádory genetika patologie MeSH
- mutace MeSH
- nádory kůže genetika patologie sekundární MeSH
- nádory plic sekundární MeSH
- protoonkogenní proteiny B-Raf genetika MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- BRAF protein, human MeSH Prohlížeč
- GTP-fosfohydrolasy MeSH
- membránové proteiny MeSH
- NRAS protein, human MeSH Prohlížeč
- protoonkogenní proteiny B-Raf MeSH
INTRODUCTION: Lung cancer is the leading cause of cancer mortality worldwide; therefore, understanding the biological or clinical role of tumor-associated antigens and autoantibodies is of eminent interest for designing antitumor immunotherapeutic strategies. METHODS: Here we prospectively analyzed the serum frequencies of New York esophageal squamous cell carcinoma 1 (NY-ESO-1), human epidermal growth factor 2/neu, and melanoma-associated antigen A4 (MAGE-A4) antibodies and expression of the corresponding antigens in tumors of 121 patients with NSCLC undergoing an operation without prior neoadjuvant chemotherapy and compared them with those in 57 control age-matched patients with no history of a malignant disease. RESULTS: We found that only antibodies specific for NY-ESO-1 (19.8% [n = 24 of 121]) were significantly increased in the group of patients with NSCLC compared with in the controls. NY-ESO-1 seropositivity was significantly positively associated with an active smoking history in patients with NSCLC but not in smokers from the control group. In tumors, the frequency of NY-ESO-1 mRNA expression was 6.3% (in four of 64 patients), the frequency of human epidermal growth factor 2/neu (HER 2/neu) expression was 11.9% (five of 42), and the frequency of MAGE-A4 expression was 35.1% (20 of 57). MAGE-A4 expression in tumors correlated with smoking status and male sex in patients with NSCLC. Patients with squamous cell carcinoma displayed higher expression of NY-ESO-1 and MAGE-A4 in tumors than did patients with adenocarcinoma. On the other hand, 94.7% of nonsmoking patients in our study had adenocarcinoma (of whom 73.7% were women). CONCLUSION: These results confirm the reported high immunogenicity of NY-ESO-1 and suggest that a smoking-induced chronic inflammatory state might potentiate the development of NY-ESO-1-specific immune responses. Moreover, smoking might contribute to the expression of other cancer/testis antigens such as MAGE-A4 at early stages of NSCLC development.
- Klíčová slova
- MAGE-A4 autoantibodies, NSCLC, NY-ESO-1, Smoking, Tumor antigens,
- MeSH
- adenokarcinom krev etiologie patologie MeSH
- antigeny nádorové krev imunologie MeSH
- dospělí MeSH
- kouření škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové proteiny krev imunologie MeSH
- nádorové biomarkery krev MeSH
- nádorové proteiny krev MeSH
- nádory plic krev etiologie patologie MeSH
- následné studie MeSH
- nemalobuněčný karcinom plic krev etiologie patologie MeSH
- prognóza MeSH
- prospektivní studie MeSH
- receptor erbB-2 krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocelulární karcinom krev etiologie patologie MeSH
- staging nádorů MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- antigeny nádorové MeSH
- CTAG1B protein, human MeSH Prohlížeč
- ERBB2 protein, human MeSH Prohlížeč
- MAGEA4 protein, human MeSH Prohlížeč
- membránové proteiny MeSH
- nádorové biomarkery MeSH
- nádorové proteiny MeSH
- receptor erbB-2 MeSH
Lung transplantation has become a standard therapeutic procedure for patients with end-stage pulmonary diseases in the Czech Republic. There were 246 lung transplantations performed from December 1997 to the end of November 2014 at the 3rd Department of Surgery, 1st Faculty of Medicine, Charles University in Prague and Motol University Hospital. The most common indications for transplantation were chronic obstructive pulmonary disease in 39.4 % of patients, idiopathic pulmonary fibrosis in 28.9 % of patients and cystic fibrosis in 19.1 % of patients. The trans-bronchial biopsy is important for monitoring patients after lung transplantation. The biopsy helps to detect acute cellular rejection, which was found within 63 % of our patients. Patients with the mild and moderate grade of acute cellular rejection got better after the anti-rejection therapy. The severe rejection in three patients led to the shock change in lung and to respiratory failure. Humoral rejection cannot be determined based on biopsy only - the capillaritis and the linear binding of C4d fraction of the complement to the capillaries are inconsistent findings and are not pathognomonic. The classification of chronic rejection, which corresponds to the bronchiolitis obliterans, is limited for the common absence of bronchioli in the biopsy. Therefore, bronchiolitis obliterans in our study group was detected in only 3.7 % of patients.Since the first transplantation, 109 of our patients have survived (44.3 %). After transplantation about 90 % of patients live one year, about 70.9 % of patients live 3 years and 69.1 % live 5 years. An autopsy at our department was performed in 79 cases. The most common causes of death were mycotic infections (aspergillosis, candidiasis), bacterial infections (Klebsiela, Pseudomonas aeruginosa, Burkholderia cepacia) followed by sepsis and viral infection (CMV, varicella zoster). At the autopsy, chronic rejection was found in 13 patients and it led to chronic respiratory failure, which was often complicated by an infection. The tumors as the cause of death were mostly generalized carcinomas.
- Klíčová slova
- lungs transplantation - acute rejection - humoral rejection - chronic rejection - infections - tumors.,
- MeSH
- biopsie MeSH
- lidé MeSH
- plíce patologie MeSH
- plicní nemoci chirurgie MeSH
- rejekce štěpu diagnóza epidemiologie MeSH
- transplantace plic mortalita statistika a číselné údaje MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
