Treatment Responses in Histologic Versus Molecular Diagnoses of Lung Rejection.

Histologic evaluation of allograft biopsies after lung transplantation has several limitations, suggesting that molecular assessment using tissue transcriptomics could improve biopsy interpretation. This single-center, retrospective cohort study evaluated discrepancies between the histology of transbronchial biopsies (TBBs) with no rejection (NR) and T-cell mediated rejection (TCMR) by molecular diagnosis. The accuracy of diagnosis was assessed based on response to treatment. 54 TBBs from Prague Lung Transplant Program obtained between December 2015 and January 2020 were included. Patients with acute cellular rejection (ACR) grade ≥ 1 by histology received anti-rejection treatment. Response to therapy was defined as an increase in FEV1 of ≥ 10% 4 weeks post-biopsy compared to the pre-biopsy value. Among the 54 analyzed TBBs, 25 (46%) were concordant with histology, while 29 (54%) showed discrepancies. ACR grade 0 was found in 12 TBBs (22%) and grade A1 ≥ 1 in 42 TBBs (78%). Treatment response was present in 14% in the NR group and in 50% in the TCMR group (p = 0.024). Our findings suggest that low-grade acute cellular rejection is less likely to be associated with molecular TCMR, which might better identify lung transplant recipients who benefit from therapy.

Robotic pulmonary segmentectomy, initial experience in the Czech Republic.

INTRODUCTION: The initiation of lung cancer screening in Czechia and diagnosis in earlier stages has been reflected by an increasing demand for anatomical lung segmentectomy. The purpose of this study was to describe early results of the first robotic-assisted thoracoscopic segmentectomies performed in the country. METHODS: Our institution has performed 151 robotic anatomical lung resections since the initiation of the screening program in August 2020, which enabled us to attain the status of a proctoring and case observation centre. The robotic segmentectomy program was initiated after completing 70 robotic lobectomies. We performed a retrospective analysis of the results of our first 20 patients indicated for robotic segmentectomy. RESULTS: Median age of the patients was 60, with 11 females and 7 males. The most common indications included primary lung malignancy (n=13), pulmonary metastasis (n=2) and benign lesions (n=3). We performed 11 simple segmentectomies, 6 complex (S2, S3, S1a+2, S10 on the right) and one right S6 segmentectomy with bronchoplasty. The mean number of harvested lymph nodes for NSCLC was 20, the mean blood loss was 25 mL (from 10 mL to 100 mL), and the mean operative time was 200 minutes. All resection margins were tumour-free. There was no conversion to thoracotomy. Two patients were excluded as they required conversion to robotic lobectomy given that their lesions were localized close to the intersegmental plane. One complication (recurrent laryngeal nerve paralysis) occurred in 1 patient. Mean chest tube duration was 1.9 days and length of stay 3.9 days. CONCLUSION: Our experience suggests that implementation of the robotic segmentectomy program after completion of the robotic learning curve provides promising outcomes. Robotic technology and preoperative planning facilitate this technically demanding procedure especially when bronchoplasty is required.

Biportal robotic pulmonary lobectomy, initial experience - case report.

INTRODUCTION: Thanks to perfect visualization and high maneuverability of instruments, the robotic technique is a preferable type of lung resection, even though the number of required incisions is usually higher compared to the video-assisted approach. This case report presents our initial experience with the reduced-port approach in performing robotic biportal lobectomy. CASE REPORT: The 72-years-old female, examined for hemoptysis, was diagnosed with a carcinoid tumor of the left lower lobe bronchus based on bronchoscopy. The patient underwent a biportal fully robotic left lower lobectomy. The time of operation was 235 minutes, longer compared to the average time of multiportal procedures, i.e. 190±52 minutes, and the blood loss of 100 mL was higher compared to 43±54 mL. The patient was discharged without complications on the third postoperative day. Histological analysis confirmed the diagnosis of a typical carcinoid with tumor free margins and seven tumor free lymph nodes. The patient continues to be followed at the Department of Pneumology, showing no signs of disease recurrence for eight months. CONCLUSION: The robotic biportal approach offers a reduction in chest wall traumatization while maintaining oncological radicality. Although this approach is safe and feasible, limitations in instrument movements necessitate specific training.

The first lung retransplantation with “ECMO bridge” in the Czech Republic - case report.

During the last 23 years of the National Lung Transplant Program in the Czech Republic, more than 500 lung transplantations, 4 retransplantations and one lobar retransplantation have been performed. We present the case report of a female patient with cystic fibrosis who underwent her first bilateral lung transplantation in January 2020. Due to a chronic lung allograft dysfunction, the patient required ECMO support and retransplantation. For the first time in the Czech Republic, a lung retransplantation with “ECMO bridge to (re)transplantation” preoperative support was performed in April 2021. The patient was discharged 39 days after retransplantation in a stable condition. At the day 90 follow-up visit, the patient was in a generally good condition with satisfying spirometric functions.

Video-assisted and robotic-assisted thoracoscopic pulmonary lobectomies, our experience.

INTRODUCTION: The use of video-assisted (VATS) and robotic-assisted (RATS) thoracoscopic surgery for anatomical pulmonary resections has been rapidly increasing. This study aimed to analyze our results of minimal invasive lobectomies to safely introduce these techniques to our practice. METHODS: Starting these new programs we followed the recommended steps including case observations and a proctoring. We retrospectively analyzed the data of our 7-year experience with VATS lobectomies and 1-year experience with RATS lobectomies. RESULTS: 128 minimal invasive lobectomies were performed between 4/2015 and 4/2021 in our center. The mean age of our patients was 64.7±10.5 years; 61 (47.7%) were women and 67 (52.3%) were men. Pulmonary malignancy was the main indication in 116 (90.6%) patients, including 2 patients with localized small cell lung cancer (SCLC). In 12 (9.4%) cases we operated for bronchiectasis and benign lung lesions. Stage I lung cancer was found in 57 (66.3%), stage II in 22 (25.6%) and stage III in 7 (8.1%) patients. We performed 110 VATS and 18 RATS lobectomies with a clear shift from triportal VATS to uniportal VATS and RATS in the last years. The mean operative time was 166±55.5 minutes and a conversion was approached in 8 (6.2%) cases (4 bleedings - less than 300 ml in all cases, 3 oncological cases, 1 case for a technical reason). The median postoperative length of stay was 4 days. CONCLUSION: VATS and RATS lobectomy has become a standard approach for early stages of lung cancer. Respecting the rules of introducing VATS and RATS including proctoring offers safety without any negative impact on survival or oncological radicality.

Starting the first robotic lobectomy program in the Eastern Europe during Coronavirus disease-2019 pandemic.

BACKGROUND: We report our experience in starting RATS (robotic-assisted thoracic surgery) lobectomy program during COVID-19 pandemic. METHODS: Data from 20 consecutive cases undergoing RATS lobectomy between August 2020 and April 2021 were prospectively accumulated into our database. RESULTS: The mean operational time was 235±69 minutes (median 210, range 175 to 370). Conversion-to-open rate was 5 %. One patient was converted to an open procedure during surgery due to surgical bleeding. One patient (5 %), with sever chronic obstructive pulmonary disease (COPD), had prolonged air leak with chest drainage 11 days and conservative treatment. Morbidity rate was 10 % (2 patients). Estimated costs of RATS lobectomy in our department were $9,590 (range $8,250-$12,730). 30-days mortality was 0%. CONCLUSIONS: Safe robotic surgery is based not only on improved robotic equipment, but also on good technical skills and medical knowledge. It requires training of the entire operating room team. The learning curve is steep, involving port placement, use of the correct robotic arms, availability of the proper instrumentation, and proper patient positioning (Tab. 2, Ref. 28).

Malignancy after lung transplantation.

INTRODUCTION: Lung transplantation has become a successful life-saving treatment for patients with end-stage pulmonary disorders. Long-term survival outcomes after lung transplantation have been improving with increasing experience. Malignancies occupy the third position among the causes of death, particularly between years 5 to 10 from lung transplantation. The risk factors include predominantly high doses of immunosuppressive therapy, older age, infections caused by oncogenic viruses and smoking history. METHODS: We retrospectively evaluated all patients undergoing lung transplantation between 2010 and 2019. The aim of this study was to analyze the incidence, type and location of tumors, time from detection, survival time and cause of death in patients with malignant tumors after lung transplantation. RESULTS: In total, 308 lung transplantations were performed at the 3rd Department of Surgery of the 1st Faculty of Medicine, Charles University and University Faculty Hospital in Motol between 2010 and 2019. Posttransplant malignancy was diagnosed in 32 patients; a tumor was detected in the explanted lung in 5 patients. Lung cancer was the most frequent tumor in our study and was found in 13 patients (37%); 6 patients (17%) had a nonmelanoma skin cancer; and posttransplant proliferative disease developed in 4 patients (12.5%). The incidence rate of other types of malignancy was low. Mean of survival after diagnosis was 152 days. CONCLUSION: Life time administration of immunosuppressive therapy in lung transplanted patients plays a key role in the prevention of rejection but on the other hand it represents a risk factor for cancer development. Oncological management of posttransplant cancer is based on reduction of immunosuppressive therapy, combined with surgical resection of solid organ tumors and other types of cancer therapy. Oncology screening tests should be done regularly as a method of prevention, and for an early detection of any tumor.

[Ruptures of the diaphragm]. / Ruptury bránice.

INTRODUCTION: The diaphragm is a flat muscle that divides the thoracic and abdominal cavities, and it is one of the most important muscles involved in respiration. Traumas of the diaphragm include its rupture caused by an external force, resulting in blunt or penetrating injuries. Diaphragmatic rupture is associated with the risk of a prolapse (i.e. not a typical hernia) of abdominal organs into the pleural cavity. The rupture may occur due to a blunt injury of the chest or abdomen, or due to penetrating injuries (gunshots, stab wounds, foreign bodies) in the lower part of the chest and epigastrium. Ruptures never heal spontaneously and always require suture of the diaphragmatic defect. Most acute rupture cases are managed using laparotomy; thoracotomy is preferred for lately recognised ruptures to facilitate the removal of adhesions in the thoracic cavity developed between the diaphragmatic defect and a lung. Thirty one patients with diaphragmatic rupture were operated at the 3rd Department of Surgery of the 1st Faculty of Medicine, Charles University and University Hospital Motol between 2006 and 2016. Acute rupture was present in 60% of the cases and chronic in 40%. Right-sided rupture was found in 20% and left-sided in 80%. CONCLUSION: The authors describe surgical treatment of diaphragmatic ruptures. They recommend an early surgical treatment if diaphragmatic rupture is recognized. Generally, the prognosis of the patients depends on availability of professional health care; ideally, these patients should be treated at specialised traumacentres with specialists for abdominal and thoracic surgery. The authors advise against establishing injudicious thoracic drainage in cases where diaphragmatic rupture with herniation of abdominal organs into the thorax may be present.Key words: polytrauma - acute rupture of diaphragm - chronic rupture - suture - patch.

[Development of tracheal resection technique - our experience]. / Vývoj techniky resekcí trachey - nase zkusenosti.

INTRODUCTION: Tracheal resections are very frequent interventions on the trachea in general. In borderline cases where the tracheal resection length is too high, the situation can be resolved by inserting a stent or Montgomerys T cannula. Tracheal stenoses are of benign origin in 94%, and malignant in 6% of cases. We present a summary of tracheal resection interventions for the last 21 years. METHOD: 235 tracheal resections were performed at the authors institution in 1993-2013. In total 221 benign stenosis cases (85 % developed after tracheostomy, 15% developed after intubation) and 14 malignant cases were treated. The patients were divided into two groups: A resection in years 19932002 and B - resection in years 20032013. The comparison of these two time periods is presented with focus on surgical procedures development and recommendations based on experienced complications. RESULTS: Restenosis (early or late) is the most common complication during the process of tracheal resection treatment. Tiny fistulas in the suture can be diagnosed easily by minor air leaking and are treated conservatively without intervention. Fortunately, suture insufficiency is relatively rare. In some cases the restenoses can be resected or treated by stent application or by Montgomerys T-cannula application. Complications were observed in 2% of the treated patients, which is a number presented also by international studies. CONCLUSION: Tracheal resection is definitely an optimal solution for patients suffering from tracheal stenosis. As presented in our study, in the hands of experienced thoracic surgeons tracheal resections is a safe and final solution of tracheal stenosis. KEY WORDS: trachea - stenosis resection.

[The first lung re-transplantation in the Czech Republic]. / První retransplantace plic v Ceské republice.

Nowadays, lung re-transplantation is an acceptable method of treatment in patients with graft failure after lung transplantation. During the 15-year duration of the lung transplant program in the Czech Republic, the first re-transplantation was performed on 1. 8. 2012. This article presents the case report of a female patient with lymphangioleiomyomatosis who underwent single lung transplantation on the left side on 4. 10. 1998. Over 12 years, based on bronchiolitis obliterans syndrome, she developed chronic respiratory insufficiency again. The patient was re-listed on the waiting list and on 1. 8. 2012, successful single-lung transplantation on the right side was performed.Key words: lung re-transplantation bronchiolitis obliterans syndrome organ allocation.

Canine osteosarcoma cells exhibit resistance to aurora kinase inhibitors.

We evaluated the effect of Aurora kinase inhibitors AZD1152 and VX680 on canine osteosarcoma cells. Cytotoxicity was seen in all four cell lines; however, half-maximal inhibitory concentrations were significantly higher than in human leukaemia and canine lymphoma cells. AZD1152 reduced Aurora kinase B phosphorylation, indicating resistance was not because of failure of target recognition. Efflux mediated by ABCB1 and ABCG2 transporters is one known mechanism of resistance against these drugs and verapamil enhanced AZD1152-induced apoptosis; however, these transporters were only expressed by a small percentage of cells in each line and the effects of verapamil were modest, suggesting other mechanisms contribute to resistance. Our results indicate that canine osteosarcoma cells are resistant to Aurora kinase inhibitors and suggest that these compounds are unlikely to be useful as single agents for this disease. Further investigation of these resistance mechanisms and the potential utility of Aurora kinase inhibitors in multi-agent protocols is warranted.

[Thoracic sarcoma, is indication for surgery sensible? case reports]. / Sarkomy hrudníku, má operacní indikace smysl? soubor kazuistik.

Sarcomas form a heterogenous group of diseases. They often affect young patients and their prognosis is uncertain. The only hope for curative treatment of these patients is a surgical R0 resection. Chemotherapy is only indicated for certain types of sarcomas and is often only recommended as part of clinical trials. The article describes 4 different case reports of patients with sarcomas and reflects on the justification of indicating surgical treatment. resection.

[Lung transplantation]. / Transplantace plic.

Lung transplantation is an effective life-saving therapy for the treatment of a variety of end-stage lung diseases. However, the application of lung transplantation is hindered by multiple factors such as the shortage of organ donors, early graft failure, infection, and chronic graft dysfunction. A novel strategy for donor lung preservation--ex-vivo lung perfusion (EVLP)--that keeps the organ at physiological protective conditions, has shown great promise to increase lung utilization by reassessing, treating, and repairing injured donor lungs prior to transplantation. Infections are a major cause of early morbidity and mortality after lung transplantation. Because of the potential association of infections such as respiratory viral infections and gram-negative bacterial infections with bronchiolitis obliterans syndrome, prompt attention to these pathogens is critical. Despite marked improvements in early survival, long-term outcome after lung transplantation is still threatened by bronchiolitis obliterans syndrome. The program of lung transplantation in Czech Republic was started in University Hospital Motol in Prague in 1997. Nowadays in Czech Republic is performed about 20 transplants every year with results comparable to other advanced centers. Until September 2011, 175 transplants were carried out in Czech Republic.

Lung transplantation in cystic fibrosis patients in the Czech Republic: initial single-center experience.

BACKGROUND: Lung transplantation is a well established treatment for advanced lung diseases. METHODS: We compared the clinical results of patients with cystic fibrosis (CF) entered into the waiting list with those of patients after lung transplantation. RESULTS: Among 36 patients with CF on the waiting list, 23 underwent lung transplantation, 8 died, 3 are still on the waiting list, and 2 were excluded from the waiting list. The median waiting list time of 0.48 years (range, 0.03-2.37) was insignificantly longer for patients who died compared with transplanted patients (0.97 vs 0.44 years). Mortality of waiting-list patients was 25.8%. The median survival of transplant patients of 7.48 years (range 0.00-10.85 years) was significantly lower among patients who were colonized (BCC) versus those who were not Burkholderia cepacia complex (0.19 vs 7.48 years; P = .041). The 1-, 3-, and 5-year patient survivals after lung transplantation were 72.9, 54.4, and 54.4, respectively. CONCLUSION: The results of patients with cystic fibrosis on the waiting list versus after lung transplantation in our center were similar to those reported in the literature. We confirmed a less favorable prognosis of BCC-colonized patients.

[Surgical-anatomical study as a part of operative treatment of primary hyperparathyroidism]. / Chirurgicko-anatomická studie jako soucást problematiky operacního resení primární hyperparatyreózy.

Surgical- anatomical studies improve experience of a surgeon and technique of the parathyroids preparation. The authors conducted a study aimed at standardization of the parathyroidectomy procedure and collection of the parathyroids from cadaverous donors for allotransplantation. The total of 101 cadavers (51 females, 50 males) were sectioned. Parathyroid regions were closely preparated, the glands were collected and histologically verified. Anatomical differences of this region were recorded. The parathyroid tissue was confirmed microscopically in 75%. Mostly, the parathyroids were mistaken for lymphonodes, a thyroid or thymus tissue. Location of inferior parathyroids was more variable (28% of inferior parathyroids is located within the thymus tissue), compared to the superior ones. Based on the study, systematic anatomical preparation in the cervical region, including a. thyroidea inferior and n. laryngeus recurrens and around the thymus cervical procesi is recommended in parathyroid procedures, where preoperative location examinations were inconclusive. Complete thymectomy with exenteration of the anterior mediastinal adipose tissue is fundamental for preparations in the mediastinum.

Assessment of serum ionized magnesium levels in healthy volunteers, in patients with coronary artery disease and/or hypertension and in hypertension alone.

We examined ionized magnesium concentration by blood analysis in patients with hypertonia arterialis, ischemic heart diseases, both of them and in a control group. Slighty lower mean serum ionized magnesium concentration was found in the study group hypertonia arterialis when compared to the control group. In patients both group "B" with coronary artery diseases and group "C" with hypertonia arterialis + ischemic heart diseases, mean serum ionized magnesium concentrations were higher then in the control group, the differences were statistically significant.

Surgical contribution to the management of primary hyperparathyroidism.

Surgical management of primary hyperparathyroidism is a very effective method. The target is to cure primary hyperparathyroidism and to reach normal calcium levels. This results in an improvement of health condition and resolution or at least moderation of symptoms. Complications are infrequent and mortality is very low. Surgical management is definite, safe and effective. Authors of this article address the diagnosis of primary hyperparathyroidism, clarify bone, metabolic and biochemical syndromes and present series of 151 patients that have been operated on at the 3rd Department of Surgery of the Motol University Hospital, Prague, with the diagnosis of primary hyperparathyroidism. The survey is focused on the primary hyperparathyroidism concomitant diseases and on the possible sequelae in the postoperative period.

[Regulation of natriuresis in diabetic nephropathy]. / Regulacja natriurezy w nefropatii cukrzycowej.

The aim of this study was to determine the influence of metabolic control of diabetes on natriuresis, the effect of natriuretic peptides and renal kallikrein on the kidney and the participation of proximal and distal tubules in natriuresis. The study was done in 41 individuals: 27 IDDM patients and 14 healthy controls. The patients were on insulin only, had normal blood pressure, and were prescribed a standard diabetic diet without sodium or protein restriction. Diabetic patients were assigned to subgroups, depending on the stage of nephropathy and level of metabolic control. Urine collection was done three times daily in all participants. The first collection was done after 500 mg lithium carbonate (p.o.) and was followed by 10 mg amilorid (Midamor, Thomas Morson Pharmaceuticals). The third collection of urine was used to evaluate excretion of cGMP. In addition to sodium, lithium, potassium and creatinine clearances, excretion of renal kallikrein, and levels of microalbuminuria, fructosamine and glycated hemoglobin were also determined. Lithium clearance was used to evaluate tubular sodium transport. The influence of diuretic peptides--ANP and urodilatin, on natriuresis was reflected by urinary cGMP excretion. Function of the kallikrein-kinin system was studied on the basis of excretion of kallikrein. Amilorid was used to test the effect of blocking amiloride-sensitive sodium channels in distal tubules on natriuresis (Tab. 1). A statistically significant decrease in mean lithium clearance was observed in IDDM patients as compared to healthy controls. Creatinine clearance was the same in both groups (Tab. 2). Lower lithium clearance was observed in the subgroup of diabetic patients with "silent" nephropathy. Diabetic patients with "silent" and early nephropathy had significantly higher levels of fractional sodium reabsorption in the proximal tubule when compared with controls (Tab. 3). Moreover, lower daily excretion of kallikrein was observed in patients with stage II nephropathy in comparison to the control group (Tab. 4). Amilorid uptake had no influence on urinary kallikrein. However, natriuresis after amilorid was significantly higher in diabetic patients than in controls. In conclusion, reabsorption in the proximal tubule is increased in patients with "silent" diabetic nephropathy, as revealed by decreased lithium clearance and unchanged creatinine clearance. Hyperactivity of the proximal tubule in stage II and III of diabetic nephropathy results in increased sodium reabsorption in the proximal tubule, as reflected by the increase in fractional sodium reabsorption in this tubule. Amilorid, a distal tubule blocker, reduces distal tubule activity independently of urinary kallikrein excretion. Elevated natriuresis was observed after amilorid without any change in urinary kallikrein excretion.

[The level of calcium, magnesium, zinc and copper in blood serum in children and young people between 5 and 18 years of age]. / Poziom wapnia, magnezu, cynku i miedzi w surowicy krwi u dzieci i mlodziezy w wieku 5-18 lat.

The blood serum of 420 children and young people between 5 and 18 years of age was examined to appoint the content of calcium, magnesium, zinc and copper in it. The examination was realized by AAS method. The calcium level was from 54.16 mg/l to 594.28 mg/l; an average was 148.66 +/- 64.61 mg/l. The magnesium level was from 7.78 mg/l to 66.26 mg/l; an average was 21.84 +/- 6.36 and was higher than data in literary output for children from other regions of Poland. The zinc level was from 0.19 mg/l to 2.94 mg/l, on an average 0.92 +/- 0.30 mg/l. The copper level was from 0.23 mg/l to 2.56 mg/l; average was 1.03 +/- 0.34 mg/l. The almost shortages in these bioelements were in children between 10 and 14, the least shortages were in children between 5 and 9. There were most of all children with high zinc level in blood serum in 10-14 years old group.