Dilemmas of lung transplantation in Poland

Przeszczepienie płuc to sposób leczenia zarezerwowany dla krańcowych stadiów schorzeń układu oddechowego, niepoddających się innym konwencjonalnym rodzajom terapii. Najczęstszymi wskazaniami do wykonania przeszczepienia są: uogólniona rozedma, idiopatyczne włóknienie płuc i zwyrodnienie wielotorbielowate. Rocznie na świecie wykonuje się około 1600 przeszczepień pojedynczego płuca i obu płuc. W Polsce, mimo relatywnie dobrego rozwoju transplantacji innych narządów (w tym serca), liczba przeszczepień płuc jest znikoma, chociaż szacowane zapotrzebowanie wynosi minimum 50 transplantacji rocznie. W niniejszym artykule krótko omówiono historię, wskazania i przeciwwskazania do operacji oraz najczęstsze, wczesne i późne powikłania. Podjęto próbę przeanalizowania przyczyn małej liczby chorych przedstawianych torakochirurgom jako potencjalni biorcy płuc oraz zaproponowano pakiet rozwiązań interdyscyplinarnych mających na celu poprawę istniejącego stanu rzeczy.Lung transplantations remain the treatment option offered for patients suffering from end-stage pulmonary diseases who do not respond to conventional therapy. The most frequent indications include homogenous emphysema, idiopathic pulmonary fibrosis and cystic fibrosis. There are approximately 1600 single lung and double lung transplantations performed worldwide per year. In opposition, the number of lung transplantations in Poland is dramatically low, despite well established programs of other organs allotransplantations (including heart). The estimated required number of lung transplantations in Poland exceeds 50 cases per year. The article describes briefly history, indications, contraindications, early and late postoperative complications. Author tries to analyze the reasons for low number of potential recipients referred to thoracic surgeons and proposes some solutions based on multidisciplinary approach and cooperation intended to improve the existing state-of-the-art

Proteomic patterns analysis with multivariate calculations as a promising tool for prompt differentiation of early stage lung tissue with cancer and unchanged tissue material

<p>Abstract</p> <p>Background</p> <p>Lung cancer diagnosis in tissue material with commonly used histological techniques is sometimes inconvenient and in a number of cases leads to ambiguous conclusions. Frequently advanced immunostaining techniques have to be employed, yet they are both time consuming and limited. In this study a proteomic approach is presented which may help provide unambiguous pathologic diagnosis of tissue material.</p> <p>Methods</p> <p>Lung tissue material found to be pathologically changed was prepared to isolate proteome with fast and non selective procedure. Isolated peptides and proteins in ranging from 3.5 to 20 kDa were analysed directly using high resolution mass spectrometer (MALDI-TOF/TOF) with sinapic acid as a matrix. Recorded complex spectra of a single run were then analyzed with multivariate statistical analysis algorithms (principle component analysis, classification methods). In the applied protocol we focused on obtaining the spectra richest in protein signals constituting a pattern of change within the sample containing detailed information about its protein composition. Advanced statistical methods were to indicate differences between examined groups.</p> <p>Results</p> <p>Obtained results indicate changes in proteome profiles of changed tissues in comparison to physiologically unchanged material (control group) which were reflected in the result of principle component analysis (PCA). Points representing spectra of control group were located in different areas of multidimensional space and were less diffused in comparison to cancer tissues. Three different classification algorithms showed recognition capability of 100% regarding classification of examined material into an appropriate group.</p> <p>Conclusion</p> <p>The application of the presented protocol and method enabled finding pathological changes in tissue material regardless of localization and size of abnormalities in the sample volume. Proteomic profile as a complex, rich in signals spectrum of proteins can be expressed as a single point in multidimensional space and than analysed using advanced statistical methods. This approach seems to provide more precise information about a pathology and may be considered in futer evaluation of biomarkers for clinical applications in different pathology. Multiparameter statistical methods may be helpful in elucidation of newly expressed sensitive biomarkers defined as many factors "in one point".</p

1,25-Dihydroxycholecalciferol with low-calcium diet reduces acute rejection in rat lung allotransplantation

OBJECTIVES The effect of 1,25-dihydroxycholecalciferol (calcitriol, vitamin D3) with a low-calcium diet on the acute lung allograft rejection in a rat unilateral left lung transplantation model was evaluated. METHODS Three transplantation groups were studied (n=5, male Brown-Norway to Fischer F344, 235±15g body weight): calcitriol and low-calcium diet, low-calcium diet and normal diet. Calcitriol (4μg/kg/day) was injected intraperitoneally for 5 days, starting from the day of transplantation. In addition, two non-transplantation groups were compared: (n=3, Brown-Norway) to measure the level of cytokines, and Fischer F344 receiving calcitriol and a low-calcium diet to measure the serum calcium level. The recipients of transplantation were killed on Day 5 post-transplant. The contralateral right main bronchus and the pulmonary artery were occluded for 5min and blood was drawn for the blood gas analysis, and the grafts were assessed for histology (International Society for Heart and Lung Transplantation 1996/rank scale). Lung levels of interleukin (IL)-2, IL-6, IL-12 and tumour necrosis factor-α (TNF-α) were assessed within the calcitriol and low-calcium diet, low-calcium diet and Brown-Norway groups. The serum calcium level was assessed in the Fischer F344 group. An analysis of variance with Tukey's post hoc test was used to compare the arterial blood oxygen pressure and the lung cytokine expression between groups. A non-parametric Kruskal-Wallis test followed by the Siegel and Castellan post hoc test was used to assess the differences between the groups according to the lung graft rejection grading. Student's paired t-test was used to compare the serum calcium level. RESULTS The arterial PaO2 was significantly higher in the calcitriol and the low-calcium diet groups when compared with low-calcium diet or normal diet groups (356±72mmHg; P<0.05 vs other groups). The arterial and bronchial rejection observed in calcitriol and low-calcium diet group was significantly milder than in the low-calcium diet or normal diet groups (A1-2, B1-2; P<0.05 vs other groups). IL-2 and IL-6 levels were significantly higher in low-calcium diet vs calcitriol and low-calcium diet and Brown-Norway groups. IL-12 and TNF-α did not differ among the groups. There was no significant difference in serum calcium level before and after the treatment in the Fischer F344 group. CONCLUSIONS Calcitriol with a low-calcium diet treatment improves lung function, reduces lung allograft acute rejection, decreases IL-2 and IL-6 allograft expression and does not change the serum calcium level significantl

Strong additive effect of 1,25-dihydroxycholecalciferol and cyclosporine A but not tacrolimus in rat lung allotransplantation

Objectives: 1,25-Dihydroxycholecalciferol (calcitriol, vitamin D3) has immunosuppressive properties. This study evaluates the effect of calcitriol in combination with either cyclosporine A or tacrolimus on acute lung allograft rejection in a rat model of unilateral left lung allotransplantation. Methods: Unilateral left lung transplantation was performed in male rats (Brown-Norway to Fischer F344, 200-250 g body weight). For immunosuppression, the following subtherapeutic doses were used: calcitriol 0.5 μg/kg/day, cyclosporine A 2.5 mg/kg/day i.p., and tacrolimus 40 μg/kg i.m. Five groups (n=5) were analyzed: cyclosporine A; cyclosporine A and calcitriol; calcitriol; tacrolimus and calcitriol; and tacrolimus. The injections were performed for 5 days starting from the day of transplantation. Recipients were sacrificed on day 5 post-transplant. The contralateral right main bronchus and pulmonary artery were occluded for 5 min and blood was drawn for blood gas analysis. The grafts were excised, fixed in formaline and embedded in paraffin. Histological evaluation was done in blinded fashion (ISHLT 1999/rank scale). The mean and standard error of the mean (PaO2) or the median and range (rejection grading) are given. ANOVA followed by planned comparison for the PaO2 and Kruskal-Wallis ANOVA for rejection grading were applied, p<0.05 considered significant. Results: Arterial PaO2 on day 5 was very low in animals treated with subtherapeutic dosages of either cyclosporine A (48±10 mmHg), calcitriol (51±3) or tacrolimus (86±22). Combined treatment with cyclosporine A and calcitriol revealed a significant improvement (248±78; p<0.05 vs. other groups), whereas the combination of tacrolimus with calcitriol did not reveal any benefit (65±9). Rejection grading with these subtherapeutic doses did not show any significant difference between groups. Conclusions: Our data indicate that cyclosporine A, but not tacrolimus, has a strong additive effect with calcitriol on acute rat lung allograft rejectio

Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation

Objective: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. Methods: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4×20ms impulses at 200V/cm) 24h prior to the transplantation. Group A (n=5) received CsA (2.5mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5μg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. Results: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233±123mmHg, vs 44±8mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II–IIIA). hIL-10 serum levels on day 5 were 14±7pg/ml in group B vs. 0 in group A. Conclusions: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantation

Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation

Objective: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. Methods: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4×20ms impulses at 200V/cm) 24h prior to the transplantation. Group A (n=5) received CsA (2.5mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5μg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. Results: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233±123mmHg, vs 44±8mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II-IIIA). hIL-10 serum levels on day 5 were 14±7pg/ml in group B vs. 0 in group A. Conclusions: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantatio

Przydatność badań scyntygraficznych w diagnostyce autoprzeszczepów śledzionowych do płuc - opis przypadku

Thoracic splenosis of the left lung and upper abdominal area was described. Left minithoracotomy was performed due to unclear results from a fine needle biopsy and following the suggestion to obtain a tissue sample. Clinical findings were similar to neoplasmatic disease; intraoperative extension of the disease was larger than CT view and correlated with postoperative assessment with 99mTc sulphur colloid. This confirmed the usefulness of scintigraphic assessment in preoperative diagnosis in order to avoid thoracotomy in such cases.W pracy przedstawiono rzadki przypadek pourazowych autoprzeszczepów tkanki śledzionowej przebiegających pod postacią obwodowego cienia płuca lewego, którego obraz sugerował charakter nowotworowy. Wynik biopsji cienkoigłowej był niejednoznaczny i wymagał potwierdzenia otwartą biopsją płuca. Obraz śródoperacyjny wykazał większe rozprzestrzenienie zmian niż w tomografii komputerowej i korelował z wynikiem wykonanej w okresie późniejszym scyntygrafii z użyciem koloidu siarczkowego znakowanego 99mTc, potwierdzając jej przydatność, zwłaszcza w diagnostyce przedoperacyjnej

Program of early detection of pulmonary neoplasms by the computed tomography - preliminary Szczecin experience

Wstęp: Rak płuca (RP) stanowi jeden z najpoważniejszych problemów epidemiologicznych i klinicznych w Polsce i na świecie. Wyniki leczenia RP są niezadowalające. Jedną z przyczyn wysokiej umieralności z powodu RP jest niski odsetek pacjentów identyfikowanych we wczesnym stadium choroby. Obecnie na świecie prowadzi się kilka programów przesiewowych RP opartych na tomografii komputerowej (TK). W Polsce dotychczas nie przeprowadzono tego typu badań. Materiał i metody: Badaniami przesiewowymi objęto mieszkańców Szczecina znajdujących się w grupie podwyższonego ryzyka zachorowania na raka płuca: wiek 55-65 lat, obie płcie, osoby palące tytoń lub mające w wywiadzie przynajmniej 20 paczkolat palenia. Program zaplanowano na minimum 3 kolejne lata i rozpoczęto 1 maja 2008 roku. Do 31 grudnia 2008 roku przebadano 3647 osób. Algorytm dalszego postępowania z pacjentami w zależności od rodzaju wykrytych zmian oparto na protokole International Early Lung Cancer Action Program (IELCAP) oraz na programie NELSON. Wyniki: Wykryto 25 nowotworów złośliwych, w tym 21 niedrobnokomórkowych RP (17 kobiet, 4 mężczyzn), z tego 70% w stadium I. W porównywalnej grupie wiekowej diagnozowanej na podstawie objawów odsetek RP w stadium IA wynosił jedynie 16,8%. Pięćdziesięciu siedmiu chorych operowano, wykonując radykalne wycięcie płata lub płuca z limfadenektomią śródpiersia w 16 przypadkach. U 3 osób przeprowadzono resekcję brzeżną, u 2 kolejnych segmentektomię. Śmiertelność okołooperacyjna wyniosła 0%. Usunięto również 3 przerzuty do płuc oraz pobrano wycinki międzybłoniaka złośliwego. W 32 przypadkach usunięto zmiany łagodne (gruźliczaki, odpryskowiaki, zmiany zapalne, grzybicze, sarkoidalne i inne) o różnym znaczeniu klinicznym. U 996 osób stwierdzono ogółem 1365 zmian w obrębie klatki piersiowej, które były diagnozowane zgodnie z przyjętym algorytmem. Wnioski: Program wczesnego wykrywania nowotworów płuc zainicjowany w Szczecinie pozwolił istotnie zwiększyć liczbę pacjentów zidentyfikowanych we wczesnym stadium choroby, a następnie leczonych radykalnie. Wykryto znaczną liczbę zmian o zróżnicowanym znaczeniu klinicznym, podlegających dalszej ocenie.Introduction: Lung cancer (LC) remains one of the most serious epidemiological and clinical challenges both in the world and Poland. Results of LC therapy are far from satisfaction. One of the reasons of high LC mortality is its late detection. Currently, few centers in the world conduct LC screening programs based on low-dose spiral computed tomography (CT) of the chest. There have been no such programs in Poland up to date. Material and methods: The program of LC early detection based on CT for citizens of Szczecin aged 55-65, who smoked at least 20 pack/years, was introduced on May 1st 2008 and was planned for 3 years. There were 3647 subjects examined till December 31st 2008. Algorithm of further action for detected lesions was based on the IELCAP and NELSON trial protocols. Results: There were 25 malignancies detected, including 21 LC (17 females and 4 males) up to date (70% were in stage I TNM). In contrast - there was only 16.8% stage IA LC detected in the comparable group diagnosed on the symptoms basis. Fifty seven patients were treated surgically, of whom 16 underwent lobectomy or pneumonectomy coupled with radical mediastinal lymphadenectomy. There were 3 wedge resections and 2 segmentectomies performed, too. Perioperative mortality was 0%. There were 32 benign lesions of different clinical importance resected as well (tuberculoma, hamartoma, inflammatory, mycotic and sarcoidal lesions). In our group 1365 lesions were detected in 996 persons &#8212; they are followed up in accordance with the IELCAP algorithm. Conclusions: Early LC detection program initiated in Szczecin resulted in significant increase of stage IA TNM detected patients subsequently treated radically. There was also a large number of small non malignant lesions detected

Diagnostic and therapeutic difficulties in mediastinal fibromatosis. Case report

Włókniakowatość (fibromatosis) śródpiersia to bardzo rzadki mezenchymalny guz wywodzący się z tkanki włóknistej. W pracy przedstawiono przypadek 26-letniego mężczyzny z guzem śródpiersia wywołującym niewydolność oddechową oraz dysfagię. Objawy te spowodowane były uciskiem przełyku oraz naciekaniem i zamknięciem oskrzela głównego lewego przez masę guzowatą śródpiersia. Etiologia guza została ostatecznie ustalona na podstawie badania histopatologicznego wycinków pobranych podczas torakotomii próbnej dopiero po 3 latach i przeprowadzeniu wielu badań diagnostycznych. Autorzy opisują trudności w diagnostyce guzów śródpiersia, szczególnie tych rzadko występujących.Mediastinal fibromatosis is a very rare mesenchymal tumor originated from fibrous tissue. A case of 26-year old men with mediastinal tumor causes respiratory insufficiency and dysphagia is described. This sympthoms occured due to esophageal impression and infiltration with occlusion of main left bronchus by mediastinal tumor. Ethiology of the tumor was established based on histopathology assesment of the tissue samples taken during explorative thoracotomy after 3 years and many other diagnostic procedures undertaken. The authors describe difficulties in diagnosis of mediastinal tumors, especially those rare observed