Lung Transplantation in Hungary From Cardiac Surgeons' Perspective.

Thoracic organ transplantation made a fresh start in Hungary with the first double lung transplant in December 2015. This major leap in Hungarian transplantation was preceded by almost 10 years of preparation, new infrastructure development, and structural changes not only at the organizational level but in human resources as well. In the following years, until recently, altogether 47 lung transplants were performed on 24 men and 23 women. The underlying pathologies were as follows: chronic obstructive pulmonary disease, 25; cystic fibrosis, 11; idiopathic pulmonary fibrosis, 7; as well as other diseases, including bronchiectasis, eosinophilic granuloma, lymphangioleiomyomatosis, and primary pulmonary hypertension in 4 cases. The youngest recipient was 13 and the oldest was 65 years old. Overall survival rates at 30 days and at 1 year were 96% and 82%, respectively. No patients were lost in the cystic fibrosis and other diseases group, whereas the 1-year survival rates of the chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis groups were 73% and 71%, respectively. The results show the robustness and viability of the program, although there is still opportunity for further improvement. In this short paper, we summarize the fields of possible further cooperation of thoracic and cardiac teams as well as future challenges facing the new Hungarian lung transplant program.

Antibody-Mediated Rejection in a Multiple Lung Transplant Patient: A Case Report.

Lung transplant is an effective way to treat many end-stage lung diseases. However, one of the main barriers of allograft organ transplant is still the immunologic rejection of transplanted tissue, which is a response of the HLA molecules. Rejection is a complex process involving both T-cell-mediated delayed-type hypersensitivity reactions and antibody-mediated hypersensitivity reactions to histocompatibility molecules on foreign grafts. We report the case of a 25-year-old female patient with cystic fibrosis who underwent 2 lung transplants because of her initial diagnosis and appearance of bronchiolitis obliterans syndrome after the first transplant. Only 13 months after the second transplant, despite the therapies applied, a new rejection occurred associated with high mean fluorescent intensity donor-specific antibody levels, which resulted later in the death of the patient. The present case draws attention to the importance of matching HLA molecules between donor and recipient in addition to immunosuppressive therapy.

The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas.

Thyroid transcription factor-1 (TTF-1) is a sensitive marker for pulmonary and thyroid adenocarcinomas. The aim of this work was to determine its usefulness in distinction between primary and metastatic lung adenocarcinomas. We have examined the expression of TTF-1 in 100 solitary pulmonary nodules. They included 50 stage I peripheral primary bronchial adenocarcinomas (30 men, 20 women, mean age: 60 years) and 50 metastatic pulmonary adenocarcinomas (21 men, 29 women, mean age: 57 years) of different origins, such as breast (13), colon (13), rectum (13), kidney (7), stomach (2), and thyroid gland (2). TTF-1 immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues. In primary bronchial adenocarcinomas we found immunopositivity in 46/50 cases, among them 30 cases showed strong nuclear immunostaining. In four primary adenocarcinoma cases the observed immunopositivity was localized to the cytoplasm. Out of the metastatic adenocarcinomas all but the 2 thyroid cancers were negative. Both thyroid tumors showed strong immunopositivity. Our results confirm that TTF-1 immunohistochemistry is a very sensitive and highly specific method in the differential diagnosis of primary and metastatic lung adenocarcinomas and should be used in the everyday clinical practice.

Antimicrobial activities of synthetic bismuth compounds against Clostridium difficile.

Clostridium difficile is a major nosocomial pathogen responsible for pseudomembranous colitis and many cases of antibiotic-associated diarrhea. Because of potential relapse of disease with current antimicrobial therapy protocols, there is a need for additional and/or alternative antimicrobial agents for the treatment of disease caused by C. difficile. We have synthesized a systematic series of 14 structurally simple bismuth compounds and assessed their biological activities against C. difficile and four other gastrointestinal species, including Helicobacter pylori. Here, we report on the activities of six compounds that exhibit antibacterial activities against C. difficile, and some of the compounds have MICs of less than 1 microgram/ml. Also tested, for comparison, were the activities of bismuth subcitrate and ranitidine bismuth citrate obtained from commercial sources. C. difficile and H. pylori were more sensitive both to the synthetic bismuth compounds and to the commercial products than were Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis, and the last three species were markedly resistant to the commercial bismuth salts. Testing with human foreskin fibroblast cells revealed that some of the synthetic compounds were more cytotoxic than others. Killing curves for C. difficile treated with the more active compounds revealed rapid death, and electron microscopy showed that the bismuth of these compounds was rapidly incorporated by C. difficile. Energy dispersive spectroscopy X-ray microanalysis of C. difficile cells containing electron-dense material confirmed the presence of internalized bismuth. Internalized bismuth was not observed in C. difficile treated with synthetic bismuth compounds that lacked antimicrobial activity, which suggests that the uptake of the metal is required for killing activity. The nature of the carrier would seem to determine whether bismuth is transported into susceptible bacteria like C. difficile.

P53 expression in stage I squamous cell lung cancer.

P53 expression was studied using immunohistochemistry in patients (n=94) with pathologic stage I squamous cell lung cancer treated surgically between 1991-1992. The overall p53 positivity ratio was 48/94. 83 of the cases proved to be suitable for follow-up analysis carried out in November, 1995. 46/83 were p53 positive, and 25/46 patients were alive at the time of analysis. The patients who died (21/46) had a mean survival time of 17.5 months. In p53 negative cases (37/83), however, 29/37 patients were still alive at the time of follow-up, and 8/37 had died with a mean survival time of 23.1 months. A significant correlation could be found between p53 immunopositivity and reduced survival time (p=0.0125). Interestingly, out of 83 cases analyzed histologic evidence of tuberculous scar tissue was present in 9 tumors with a p53 positivity ratio of only 1/9. When flow cytometry was used to examine tumor samples from all subgroups mentioned above (n=32), no correlation was found between the p53 immunopositivity or the prognosis and the DNA content of tumor tissues. Our results suggest that in the early stage of squamous cell lung cancer the p53 positivity may be an indicator of a more aggressive tumor behavior and a shortened survival time.

Chemical structure of bismuth compounds determines their gastric ulcer healing efficacy and anti-Helicobacter pylori activity.

The recognition of the role of Helicobacter pylori in the pathogenesis of peptic ulcer disease has led to renewed interest in bismuth pharmacology since bismuth compounds have both anti-Helicobacter pylori and ulcer healing properties. The precise chemical structure of current bismuth compounds is not known. This has hindered the development of new and potentially more efficacious formulations. We have created two new compounds, 2-chloro-1,3-dithia-2-bismolane (CDTB) and 1,2-[bis(1,3-dithia-2-bismolane)thio]ethane (BTBT), with known structure. In a rat model of gastric ulceration, BTBT was comparable to, and CDTB was significantly less effective than colloidal bismuth subcitrate in healing cryoprobe-induced ulcers. However, both BTBT and CDTB inhibited H. pylori growth in vitro at concentrations <1/10 that of colloidal bismuth subcitrate. The effects on ulcer healing are not mediated by suppression of acid secretion, pepsin inhibition, or prostaglandin production. Since all treated animals received the same amount of elemental bismuth, it appears that the efficacy of bismuth compounds varies with compound structure and is not simply dependent on the delivery of bismuth ion. Because the structure of the novel compounds is known, our understanding of the relationship of bismuth compound structure and to biologic activity will increase. In the future it may be possible to design other novel bismuth compounds with more potent anti-H. pylori and ulcer healing effects.

[Surgical management of pulmonary aspergilloma]. / A tüdöaspergilloma sebészi kezelése.

Between 1983 and 1996., 79 patients'--operated on for pulmonary aspergilloma--clinical data has been analysed. The patients were comprised of 67 males and 12 females, with a mean age of 49 years (range, 24 to 69). Previous lung disorders were observed in about half of the cases (most frequently tuberculosis), while in the other half aspergilloma was developed on the basis of (sub)-acute infections. The most common symptom was haemoptysis (in 45% of cases). Aspergilloma was diagnosed preoperatively (especially by typical chest x-ray) in 62 patients. In the other cases tb, lung cancer, pyosclerosis were suspected. 67 patients underwent pulmonary resection (50 lobectomies, 12 wedge resections, 5 pneumonectomies), 12 cavities were opened by cavernostomy. The postoperative mortality rate was 10.1%. The most frequent complications were bleeding, prolonged air leak, pleural rest space, empyema, bronchial fistula and wound infection, which were occurred in cases with bigger cavities near chest wall. In most cases with pulmonary aspergilloma surgery remains the only effective treatment. Operation has a lower risk in asymptomatic patients, without chest wall involvement. In several cases cavernostomy might be applied successfully.

Transhiatal closure of right-sided esophageal rupture after a left pneumonectomy.

Right-sided spontaneous esophageal rupture developed 2 days after left pneumonectomy and vomiting. To avoid contamination of the pneumonectomized left thoracic cavity as well as a contralateral thoracotomy, we used a transhiatal approach for primary repair of the rupture, combined with right-sided pleural and mediastinal drainage, gastrostomy, and feeding jejunostomy. The 7-day barium meal control showed healing of the rupture.

Surgery for pulmonary aspergillosis.

OBJECTIVE: Surgery of pulmonary aspergillosis followed by higher incidence of post-operative complications. This was the purpose to evaluate our material. METHODS: Between January 1983 and December 1995, the operation was carried out on a total of 84 patients for pulmonary aspergillosis. The patients were comprised of 71 males and 13 females, with a mean age of 49 years (range, 24-71). Previous lung disorders were observed in about half of the cases (most frequently tuberculosis), while in the other half aspergillosis was developed on the basis of (sub)-acute infections. Haemoptysis was present in 48% of patients. The diagnosis was suspected in 47 cases by chest X-ray. Aspergilloma was diagnosed in 50 patients pre-operatively (excluding 12 typical aspergillomas for cavernostomies), with the other pre-operative diagnoses being tuberculosis, lung cancer, pyoscelrosis, etc. RESULTS: In 71 cases pulmonary resection was carried out (52 lobectomies, 13 wedge resections and six pulmonectomies). A total of 12 cavities were opened by cavernostomy and one lung biopsy was performed for disseminated lung disease. The post-operative mortality rate was 9.5%. The most common complications were bleeding, empyema, bronchial fistula and wound infection. In 23 patients with developed prolonged air leak and/or residual air space, complications were observed more frequently in patients with greater cavitation near the chest wall. CONCLUSIONS: In most cases of pulmonary aspergilloma surgical intervention remains the only effective therapy. The operation has a lower risk factor in asymptomatic patients and in patients without pleural or chest wall involvement. In some cases, cavernostomy may be the only remaining surgical choice.

Transdiaphragmatic cyst-jejunostomy with Roux-en-Y loop for an exclusively mediastinal pancreatic pseudocyst.

In a patient presenting with a roentgenographic retrocardiac density, left pleural effusion and distal oesophageal displacement, echocardiography confirmed presence of a pseudocyst in the posterior mediastinum. Pancreatic origin was suspected. Left thoracolaparotomy revealed the large (900 ml), exclusively mediastinal pseudocyst, surrounding the aorta and adherent to the diaphragm, with high amylase content. Decompression was achieved with a retrocolic and gastric Roux-en-Y loop by transdiaphragmatic cystojejunostomy.

[Early diagnostic pitfalls in esophageal perforation and spontaneous rupture of the esophagus]. / A korai diagnózis útvesztöi nyelöcsö-perforációkban és spontán nyelöcsörupturákban.

In this retrospective study (1981-1993) of 31 cases of esophageal perforations and ruptures circumstances the delay or misdiagnosis with undoubtable influence on the survival have been discussed. The over-all mortality was 16.1% but in cases of early (24 h) perforations or ruptures (12) no patients were lost. The unfavourable consequence of the superficial case history, underestimated pain, incomplete roentgenographic study, diagnostic confusion inadequate surgical exploration and misinterpreted postoperative complications of the formal esophageal surgery are analyzed. The authors emphasized the methods to decrease the number of the false-negative contrast esophagograms as well as the value of the intraoperative endoluminal diluted methylin-blue injection to detect esophageal leak. The early diagnosis is the first prerequisite for a favourable outcome in this life-threatening emergency.

[Surgical treatment of pulmonary metastases from colorectal tumors]. / A colorectalis daganatok tüdömetasztázisainak sebészi kezelése.

Authors analysed 25 colorectal cancer lung metastases. Among them were 13 male 12 female. Ages ranged from 45 to 70 years. The lung nodules were discovered without any symptoms in 19 cases. The disease was localized on the right in 16 patients, in 7 on the left side and 2 others were bilateral. There were 19 solitary and 6 multiple nodules. In two-third of the cases developed metastases within 3 years of colorectal interventions. In 23 cases was performed partial lung resection (wedge or lobectomy) except one pneumonectomy. In one of the patients lung biopsy was just carried out. A case presentation is detailed where the right upper lobe metastasis was resected by videothoracoscopic method. They observed no postoperative mortality. The cumulative five year survival rate is 28% (for solitary lesions 31.6%, for multiple nodules 17%).

Is cardiac test availability a significant factor in weekend delays in discharge for chest pain patients?

The authors assessed whether the lack of weekend cardiac test availability significantly contributed to weekend delays in hospital discharge for "low-risk" chest pain patients. Mean lengths of stay were compared for late-week versus early-week admissions. Patients with late-week admissions had a 19% greater length of stay than did patients admitted earlier in the week (2.36 +/- 1.87 vs 1.91 +/- 1.21 days, p = 0.10, with p = 0.015 after adjusting for severity of illness). Cardiac diagnostic tests were ordered for only 4% of study patients. Therefore, the "weekend effect" existed in an environment where cardiac diagnostic tests were infrequently ordered.

Reducing lengths of stay for patients hospitalized with chest pain using medical practice guidelines and opinion leaders.

There are few available data on the effectiveness and safety of medical practice guidelines when used for patient care in the coronary and intermediate care units. The aim of this study was to examine the effect of educating physicians about practice guidelines to promote shorter lengths of stay for "low-risk" patients hospitalized with chest pain. Such guidelines were disseminated to physicians working in a health maintenance organization (HMO) by educational conferences, written memoranda, endorsement by opinion leaders, concurrent written feedback, and nursing-to-physician cues. A total of 208 patients were enrolled in the study. Following implementation of the practice guidelines, hospital lengths of stay were reduced from 2.51 +/- 2.1 to 1.96 +/- 1.3 days (22% reduction, p = 0.03) and intermediate care unit lengths of stay from 33.9 +/- 19 to 28.2 +/- 14 hours (17% reduction, p = 0.02) for patients with low-risk chest pain. The reduction in length of stay for patients with low-risk chest pain exceeded reductions in stay for patients hospitalized with cardiac conditions for which no guidelines were introduced. None of the patients treated according to guideline recommendations had unexpected "life-threatening" adverse events in the 2-week period after hospital discharge (95%, confidence interval 0%, 3%). This study supports the effectiveness and possible safety of practice guidelines to reduce lengths of stay for patients with low-risk chest pain.