PD-L1 Expression of Lung Cancer Cells, Unlike Infiltrating Immune Cells, Is Stable and Unaffected by Therapy During Brain Metastasis.

BACKGROUND: Approximately 50% of brain metastases originate from non-small-cell lung cancer. The median survival of patients with brain metastases is 1 month without treatment. Novel immunotherapeutic strategies, such as those targeting the programmed death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) axis, are promising in patients with advanced systemic disease but are often preferentially administered to patients with tumors showing PD-L1 positivity. PATIENTS AND METHODS: Surgically resected paired primary lung adenocarcinoma and brain metastasis samples of 61 patients were analyzed. We compared the paired samples regarding the amount of peritumoral and stromal mononuclear infiltration, PD-L1 expression of tumor and immune cells, and PD-1 expression of immune cells. We investigated the effect of radiotherapy, chemotherapy, and steroid therapy on PD-L1 expression in brain metastases. RESULTS: There was significant positive correlation regarding the PD-L1 expression of tumor cells between the paired primary lung adenocarcinoma and brain metastatic samples with the use of different cutoff levels (1%, 5%, 50%). We found no impact of chemotherapy or steroid therapy on the changes of PD-L1 expression of tumor cells between the 2 sites. There is no or only limited concordance of the proportion of PD-1- or PD-L1-positive tumor-associated immune cells between the paired tumor samples, which suggests that brain metastases develop their own immune environment. CONCLUSION: We observed a strong correlation of PD-L1 positive tumor cells between primary lung adenocarcinoma cases and their corresponding brain metastases, which is not significantly influenced by chemotherapy or steroid therapy.

[Unusually late presentation esophageal perforations and ruptures]. / Nagy idoveszteséggel felismert nyelocso-perforációk és -rupturák.

The aim of this study is to present the treatment modalities of unusual late esophageal perforations and ruptures. The reason for diagnostic delay was misinterpretation of pleural collection, overlooked sclerotherapy, foreign body extraction, and delayed recognition of the true origin of empyema after pneumonectomy. In all instances of transthoracic reinforced or temporary excluded primary repair were successful. In a 6- week-old iatrogenic perforation with localised empyema, Urschel-Ergin type exclusion with tube thoracostomy and lavage was used. In a 13-day-old rupture, and in a late postpulmonectomy perforation, Johnson type exclusion, decortication, and/or fenestration and second-stage colonic or Roux-en-Y by-pass were carried out. One patient was lost in deep sepsis for a delayed recognised transfixion esophageal injury. It is never too late to attempt to repair and salvage a perforated or ruptured healthy esophagus.

[Physiologic type reconstruction in upper gastrointestinal caustic strictures]. / A nyelés képességének helyreállítása lúgivás utáni nyelocsoszukületben.

The authors discuss their experience in the surgical treatment of caustic stenosis in the upper gastrointestinal tract. They present operative solutions using isoperistaltic transverse colonic segment in oesophageal stenosis caused by gastric outlet obstruction, or when these two presented together. Further indications for the above were bronchial or tracheo-oesophageal fistulas and oesophageal perforation. Late adaptation of the colonic grafts were measured by radiokinematography and histochemistry. The overall morbidity was 4.9%. Postoperative salivary fistulas closed spontaneously. Late postoperative complications (13.5%) were treated successfully. The multihaustral motility of the graft prevented the reflux, while the altered mucopolysaccharides of the colonic mucosa prevented the ulcer formation. Orv Hetil. 2019; 160(16): 613-618.

[Treatment of adult intrapulmonary sequestration with video-assisted thoracoscopic lobectomy]. / Felnottkori intrapulmonalis sequestratio kezelése videothoracoscopos lobectomiával.

INTRODUCTION: Surgical removal is the gold standard method for the treatment of pulmonary sequestration (PS); nowadays, video-assisted thoracoscopic lobectomy (VATS) is more frequently applied in the surgical treatment of malignant pulmonary tumours and appears to be suitable also in case of benign pulmonary diseases. We are the first in Hungary, who report three, radiologically identified intralobar PS treated with VATS. METHOD: Surgeries were performed in general anaesthesia with double-lumen separated ventilation in lateral decubitus position through two ports (1.5 cm camera port and 5-6 cm axillary working port, protected by a plastic ring). Results and cases: Two of the patients presented with the symptoms of haemoptysis and pneumonia, and the third patient after radiological screening (one 37 years old woman and 2 men, 39 and 46 years old). The nutritive artery was identified on the CT scans in all cases. We removed the right lower lobe in two cases and the left lower lobe in one case without major complications. CONCLUSION: We recommend the video-thoracoscopic lobectomy for the treatment of PS as a suitable treatment option.

[Doege-Potter syndrome with giant malignant solitary fibrous tumour of the pleura]. / Doege­Potter-szindróma a mellhártya óriás malignus szoliter fibrosus tumorával.

Infrequent solitary fibrous tumours of the pleura are associated with hypoglycaemia only in a few percent of the cases; this condition is called Doege-Potter syndrome, named after its first descriptors. Our 63 years old male patient has previously undergone clinical treatment for intrathoracic fluid accumulation on the left side caused by a giant tumour-like mass in the lower left lobe detected by CT scan. In the course of further investigations performed due to increasing load-induced dyspnoea, lung core biopsy verified low grade sarcoma in the tumour. Tumour board suggested surgery. The patient was transferred from the intensive care unit into the operation theater due to increasing dyspnoea and repeated hypoglycaemic periods in rapidly worsening general condition. Pneumonectomy and removal of the tumour was performed on the left side. Histology showed solitary fibrous tumour of the pleura corresponding to Doege-Potter syndrome. The patient was discharged without complications and underwent adjuvant chemotherapy due to pleural dissemination of the tumour observed intraoperatively. One year after surgery the patient underwent surgical removal of a locally recurrent tumour. In spite of repeated chemotherapy local and multiplex contralateral pulmonary progression was observed. Three-year survival was noted from the time of the first surgery. Orv Hetil. 2018; 159(41): 149-153.

[Risk stratification before thoracic surgery, perioperative pulmonary rehabilitation]. / A mellkassebészeti mutéti teherbíró képesség megítélése, perioperatív légzésrehabilitáció.

INTRODUCTION: Besides the oncology and operative surgical technics, functional aspects influence the operability of lung cancer. Preoperative risk stratification, evaluation of postoperative complications needs to be considered. AIM: To review international literature and experiences of our institute. METHOD: We focused the literature of risk stratification of thoracic surgery. Lung function, lung mechanics, chest kinematics, exercise physiology were considered. Effectiveness of pulmonary rehabilitation for cardiovascular system, lung mechanics, muscles, exercise capacity and quality of life were evaluated. Laboratory parameters, comorbidities, obesity, cachexia, smoking cessation were considered. RESULTS: Elevated blood sugar, kidney function, reduced albumin level increased the risk. COPD, sleep apnoea, heart failure, obesity and cachexia influences the outcome. Smoking cessation may reduce postoperative complications. Controlled breathing technics, chest wall mobilization, training have favourable effects. Psychosocial support and dietetics are important. CONCLUSIONS: Risk stratification is supported by laboratory parameters, lung function, oxygen uptake and comorbidities. Pulmonary rehabilitation can improve functionality and quality of life. Orv Hetil. 2017; 158(50): 1989-1997.

A transhiatalis sebészet járatlan ösvényei.

Right-sided spontaneous oesophageal rupture developed two days after left pneumonectomy and vomiting. In this extremely rare emergency, we used a transhiatal approach for primary repair of the rupture, combined with right-sided pleural and mediastinal drainage, gastrostomy and feeding jejunostomy. The seven-day barium meal showed healing of the rupture. It was mandatory that contamination of the pneumonectomized left thoracic cavity during rupture closure as well as a contralateral thoracotomy with its respiratory consequences had to be avoided by all means. Reconstruction and reinforcement (with omentum) of the oesophageal wall was achieved without difficulties, but we did not mobilize the oesophagus to avoid rupture of the left-sided mediastinal pleura. After massive haematamesis, a 68-year-old man was admitted for a huge (8×5 cm) mass in the lower-posterior mediastinum at the right side of the vertebra, seen on CT scan. On the barium meal incarcerated hiatal hernia, secondary short oesophagus and intramediastinally penetrating high lesser curvature ulcer was discovered. To reduce the magnitude of intervention one-stage transhiatal approach was decided. Through enlarged hiatus, dissection of incarcerated and firmly adherent hiatal hernia and of the short oesophagus was done. The following step was the removal of an encapsulated, huge lipomatosus mass from the posterior mediastinum, extending high from behind the vertebra, arising from the lesser curvature of the stomach. The lesser curvature ulcer was excised - sutured and a Toupet type (270 posterior) fundoplication was finally carried out. The follow-up was free from recurrence. This experience suggests that for some particular lower posterior mediastinal or esophageal problems, transhiatal access seems to be a useful alternative of traditional mediastinal approaches.

A pleura óriás fibrosus tumora légzési elégtelenséggel szövodve.

Surgery of mostly benign giant tumours involving large part of the chest is a special surgical challenge. The problems comprise difficulties of surgical technique, management of the narcosis and postoperative intensive care. An additional peculiarity of our case is the extreme confliction of the otherwise presumably evident indication for surgery. Our 64-years-old male patient has been suffering from increasing dyspnoea on exercise for one and a half years. A chest X-ray performed for other reasons demonstrated a large, expansive structural change in the right thoracic cavity. Lung biopsy performed as part of respiratory investigations, which showed a solitaire fibrous tumour of the pleura. Oncological consultation suggested consideration of surgery. The general condition of the patient worsened rapidly in the course of preassessment; he had to be admitted to ICU due to dyspnoea and atrial fibrillation, where respiratory insufficiency developed and required respiratory therapy. Surgery was performed in this high anaesthetic risk patient, since removal of the tumour was the only chance for surviving. The patient left the hospital healthy after successful surgery and cumbersome postoperative period. He returned to his original job and no recurrence was detected one year after surgery.

[Mediastinal parathyroid adenoma: a surgically treated case]. / Mediastinalis mellékpajzsmirigy-adenoma operált esete.

Sixteen percent of primary hyperparathyroidism is caused by ectopic parathyroid glands. These cases present diagnostic and therapeutic challenges. In this article we present the case of a patient underwent surgery for a mediastinal parathyroid adenoma causing symptomatic hypercalcaemia.

[A unique reconstructive technique in a young patient after manubrial recestion in grade II chondrosarcoma]. / Egyedi mutéti megoldás fiatal férfi betegen manubriumresectio után Grade II chondrosarcomában.

OBJECTIVE: Approximately 30% of malignant, primary bone tumors are chondrosarcomas, which occur on the anterior chest wall most frequently. Patients who are treated with adequate surgical intervention recover well, 10 years survival rate is 97%. Besides the aesthetic outcome, preservation of breathing and loading are crucial. METHODS: Authors present a case of a 44-year-old male patient who worked as a sport masseur operated on Grade II chondrosarcoma of the manubrium. Concerning the age of the patient, an immediate reconstruction was carried out. The involved part of the sternum was resected with wide margins. The reconstruction was performed with Dual Mesh covered by a pedicled left sided pectoral major muscle. As a unique technique, authors used the tendons of the semitendinous and gracilis muscles to fix both claviculas together to give the proper stability and function for the shoulder girdle. RESULT: After an uneventful postoperative period the patient had a fast recovery. CONCLUSION: There are no data in the literature for such a method of fixation of the anterior chest wall. The method is suggested by the authors.

[Surgical treatment of acute descending necrotising mediastinitis]. / Az acut descendáló necrotizáló mediastinitis sebészi kezelése.

INTRODUCTION: Acute descending necrotizing mediastinitis (DNM) is a severe septic inflammation of the mediastinum with necrosis, which progrediates rapidly and leads to death without adequate surgical treatment in 80% of cases. PATIENTS AND METHOD: 17 patients were treated with acute DNM between 1999 and 2012 at the Thoracic Surgical Department of Koranyi National Institute and Semmelweis University of Hungary. The infection source was primarily in the head-neck region with dental infections in eight cases, retro/parapharyngeal abscess in four patients, primary collar phlegmone and abscess in one case and two retrotonsillar abscesses. Further, in one case there was a previous operation (mediastinoscopy) in the history and in another case there was "difficult intubation process" (not recognized trachea-laesion) mentioned during abdominal operation. Primary exploration was performed from the neck in nine cases, thoracotomies plus collar incisions were carried out in four cases, athoracotomy only was done in one and orofacial exploration in further three patients. Disease progression could be evaluated by computer tomography which had to be followed by immediate surgery. RESULTS: Four patients needed two operations, five patients underwent exploration three times, while three patients needed 4 interventions four times. More than one anatomical region was explored in 70% of the cases. Based on our experience prognosis is affected by the time elapsed between detection and surgical intervention, age of the patient and comorbidites such as diabetes mellitus. We lost nine patients (53%), eight patients recovered and symptom free (47%). CONCLUSIONS: Successful treatment is based on early diagnosis, urgent elimination of the primary source, adequate exploration of the cervico-facial region, debridement, collar and upper mediastinal drainage. If the inflammation spreads below the azygos vein or the aortic arch, a right thoracotomy should be performed with wide mediastinal exploration, debridement, and thoracic suction-lavage drainage. Treatment should be completed with broad spectrum and targeted antibiotics as well as organ support. Mortality and morbidity can be reduced with prompt and aggressive therapy.

[Pseudomyxoma of the pleura and of the peritoneum -- case report of a rare disease]. / Pseudomyxoma peritonei et pleurae -- egy ritka betegségrol kezelt esetünk kapcsán.

INTRODUCTION: Pseudomyxoma Peritonei (PMP) is a rare condition, which arises from the abdominal cavity and it may also involve the pleural cavity occasionally. Concomitant involvement of both cavities is rare. The disease is characterized by production of mucinous ascites, and a low-grade carcinoma deriving mostly from the appendix. Pleural seeding may be due to diaphragmatic perforation during surgical intervention, tumour progression, or persistent congenital malformation between the abdominal and pleural cavities. CASE REPORT: A 44 year-old female patient was treated with pleuropulmonary involvement of pseudomyxoma. Since both the lungs and pleura were involved, radical resection could not have been carried out, and cytoreduction with intraoperative chemotherapy was applied only. DISCUSSION: Pleural progression of pseudomyxoma is uncommon and carries a poor prognosis. Management is similar to abdominal PMP, which involves aggressive cytoreduction and local and/or systemic chemotherapy, if possible. CONCLUSION: PMP is a very uncommon disease with poor prognosis. Extra-abdominal manifestation is rare, too. However, early recognition of the condition may enhance treatment options.

[Isolated bronchial resection for tumor]. / Tumor miatt végzett izolált hörgoresectio.

Tumors that are confined to specific areas of the airway (e.g. left main stem bronchus or the bronchus intermedius) can be removed with resections of the bronchus only and preservation of the parenchyma. During the period of January 2004 to February 2009 five patients underwent isolated bronchial resection for lung tumor with curative intent. In this study we analyzed the data of five men with a median age of 47.6 years (range 29­68 years). In four cases resection of the intermediate bronchus was performed, and in one case left main bronchus was removed. Intraoperative frozen section revealed negative bronchial resection margins in all cases. Four patients had carcinoid tumors, while one was diagnosed with chemodectoma. Minor postoperative complications were observed in two patients only. Isolated bronchial resection for lung tumor is associated with low morbidity and mortality. Lung sparing procedures are preferable in the above cases but sufficient experience and conditions are mandatory to achieve adequate results.

[Primary suppurative costochondritis--one of our successfully treated cases]. / Primer suppurativ costochondritisrol--egy sikeresen kezelt esetünk kapcsán.

Secondary chest wall infections after previous surgical procedures are well known but the primary form of this is a relatively rare entity. We present a case of a 34-year-old man who suffered from primary suppurative costochondritis diagnosed by ultrasound and chest CT scan. The patient underwent a wide necrosectomy with a muscle flap reconstruction.

Sporadic desmoid tumors of the chest: long-term follow-up of 28 multimodally treated patients.

INTRODUCTION: Desmoids of the chest are extremely rare borderline tumors. Radical surgical resection is considered to be the primary treatment. Achieving negative margins is often a challenge. Cases with positive surgical margins are associated with high risk of local recurrence. METHODS: A retrospective multicenter review was undertaken of 28 patients who underwent surgery for sporadically appearing desmoids of the chest between 1988 and 2008. Clinico-pathological data were investigated in detail. Authors have statistically analyzed the relationships between gender, age, tumor size, radicality of the first surgery, impact of the pharmacologic treatment, estrogen receptor positivity, and the development of local recurrences after a median follow-up period of 104 months. RESULTS: Primary surgery was radical in 14 patients (50%). Mean pathologic diameter was 72.14mm. Wide surgical excision was performed in 27 primary cases, out of which 10 cases (37%) were full- and 17 cases (63%) partial-thickness chest wall resections. Synthetic mesh stabilization was used in nine cases and soft tissue coverage in six patients. Morbidity rate was 25%. Recurrences were found in 63% of the cases, with a mean time of 30.5 months to first recurrences. Our investigation confirmed that microscopically free surgical margin of the first tumor resection significantly affected local tumor control. CONCLUSIONS: Because the radicality of the first surgical resection is of essential importance for long-time local control of chest desmoids, accurate preoperative diagnostics and well-planned aggressive surgical resection of the primary tumor is recommended. Due to the low incidence of desmoids, multicentric randomized investigations would be mandatory to establish evidence-based protocol for desmoid tumors.

[Surgical challenges of chest wall and intra-thoracic desmoid tumors]. / Mellkasfali és intrathoracalis desmoid tumorok sebészi kezelésének kihívásai.

Chest wall desmoids are rare, borderline tumors. Radical surgical excision is considered to be the primary treatment. Tendency of desmoids to infiltrate the chest wall, the shoulder girdle, lung parenchyma, brachial plexus and vital components of the mediastinum provides a difficult surgical challenge in the efforts of achieving microscopically negative margins. Implantation of synthetic meshes and reconstructive plastic surgical techniques might be necessary to perform in order to preserve stability of the thorax, and to achieve optimal functional and aesthetic results. Multidisciplinary surgeries may result in a high rate of morbidity even in specialized centers. Within the framework of a retrospective multicenter review, authors assessed surgical techniques implemented in the case of patients who underwent surgical management for sporadically appearing chest-wall and intra-thoracic desmoids, and reviewed the relevant literature.

[Repair for anterior chest wall deformity by Nuss procedure performed in young adults and older adolescents]. / Elülso mellkasfali deformitás Nuss szerinti rekonstrukciója fiatal felnotteken és idosebb kamaszokon.

Results of 86 minimally invasive anterior chest wall reconstructions for pectus excavatum by the method of Nuss are evaluated retrospectively. Complications, possible ways of avoiding those and technical details of the operation are discussed. Nuss method is also evaluated in terms of suitability patients' age. Minimally invasive anterior chest wall reconstructions were performed in 86 patients in the last seven years. The average age was 21.4 years. There were no severe intra-operative complications. Four dislocations of the metal bar (12 and 53 days after chest reconstruction) were observed and treated by Nuss-technique. One metal bar had to be removed on the 13th postoperative day for local septic complication, and another one for significant sterile dislocation 14 months after the operation. One patient asked for removal of the metal bar because of pain. In one case bleeding from a small side-branch of the internal mammary artery was stopped by VATS technique, a small superficial lung injury was treated by thoracic drainage. Over 90 percent of patients were satisfied with the cosmetic results. Operating time and length of hospital stay gradually decreased throughout the years. Nuss technique can be performed safely in young adults for pectus excavatum with excellent long-term results. Less pain and shorter operating time of minimally invasive repair are the advantages of the procedure. Age above 30 years and previous open chest correction increases the risk for operation.

[Lung harvesting in Hungary--results of the first two years]. / Donortüdok kiemelése Magyarországon--az elso két év eredményei.

OBJECTIVE: Hungarian patients undergo lung transplantation within bilateral cooperation in Vienna, Austria since 1995. Lung harvesting was introduced in 2002 in Hungary. Before 2002 Hungarian patients get 16 donor lungs from abroad, and 4 patients died while being on the waiting list for transplantation. METHODS: Between 15/1/2002 and 31/12/2003 Hungarotransplant offered 164 potential lung donors to the Korányi National Institute for Pulmonology. Donor selection was performed according to international guidelines. All operations were performed as part of multiorgan harvesting. Immediately before cross clamping the aorta 500 microg epoprostenol (Flolan) was administered intravenously for opening the pulmonary vascular bed. The lung was perfused through the main pulmonary trunk with a single flush of 6 litre 4 degrees C extra cellular type low potassium dextran solution (Perfadex). During the perfusion both thoraces were cooled topical by 0.9% saline ice slush. After back table separation the donor lungs was packed and transported with topical cooling. RESULTS: The offer was refused in 27 cases due to donor history, in 31 cases due to allograft pathology. In 57 cases the harvesting was not performed due to logistic reasons. Forty three donor lungs have been transplanted, 6 harvested lungs underwent only histopathology. From 43 harvested lungs 41 bilateral and 3 single lung transplant procedures were performed. The mean cold ischaemic time (=CIT) was 3 75 +/- 50 minutes (range: 230-560 min). Forty two donor lungs showed excellent primary graft function. One allograft underwent down-sizing lobectomy, where the histology of the specimen showed multiple microembolization, and signs of fibrosis, bronchiolitis and anthracosis. In this case the cold ischaemic time was 385 min. The patient needed an extracorporeal membrane oxygenation (ECMO) support immediately postoperatively, and died on the 4th postoperative day. After induction of lung harvesting in Hungary the average waiting time of Hungarian citizens dropped within one year from 14 +/- 8 weeks (range: 2-36 weeks) to 2.6 +/- 1.3 weeks (range: 1-4 weeks). In 2002 3 Hungarian patients died while being on the waiting list, their waiting time was 1, 1, and 7 days. In 2003 the waiting list mortality for Hungarian patients was 0%. CONCLUSIONS: After the introduction of lung harvesting both the waiting time and the waiting list mortality for Hungarian patients decreased. The potential yearly lung donor pool of Hungary is in the range of 5/1 million people.

[Prevention and treatment of bronchopleural fistula using pedicled muscle flaps]. / Bronchopleuralis fisztulák megelozése es kezelése nyeles izomlebeny plasztikával.

Authors used pedicled muscle flaps for prevention and treatment of bronchopleural fistulas in 55 patients. Thirty five flaps were used for prevention and 21 for treatment of bronchial stump leak. After using 19 pectoral, 18 latissimus, 10 diaphragm, 3 intercostals, 2 serratus and 4 double muscle flaps, only two flap necrosis occurred due to insufficient flap perfusion. Latissimus and diaphragm flaps were used mainly for the purpose of prevention and the pectoral flaps for the treatment of bronchopleural fistula. The authors reveal the advantages, disadvantages and indications of using different muscle flaps for different purposes. Using this technique is an essential practice in everyday thoracic surgery.