Reversal of stage 5 chronic kidney disease by aortic valve replacement in kidney transplant recipient: a case report.

BACKGROUND: Cardiorenal syndrome (CRS) is a group of pathophysiological disorders affecting heart and kidneys. CASE PRESENTATION: We present 44-year-old kidney transplant recipient with acute-on-chronic graft failure in the course of CRS due to acutely decompensated heart failure associated with severe aortic regurgitation successfully treated with aortic valve replacement. Because of graft failure progression and difficult to eradicate infections he was treated with dialysis and radical minimization of immunosuppression. After 74 days of renal replacement therapy the patient regained graft function after successful aortic valve replacement. The dialysis could be stopped and immunosuppressive therapy was reintroduced. Heart and renal function are stable and patient is doing well without dialysis for 3 years. CONCLUSIONS: The return of kidney graft function can occur even after a long period of dialysis therapy due to improved cardiovascular function. Therefore, distinguishing an acute-on-chronic CRS subtype is mandatory to enable specific patient approach.

Cell-free DNA levels in plasma of patients with non-small-cell lung cancer and inflammatory lung disease.

BACKGROUND: The analysis of plasma cell-free DNA (cfDNA) is expected to provide useful biomarkers for early diagnosis of non-small-cell lung cancer (NSCLC). However, it remains unclear whether the intense release of cfDNA into the bloodstream of NSCLC patients results from malignancy or chronic inflammatory response. Consequently, the current diagnostic utility of plasma cfDNA quantification has not been thoroughly validated in subjects with chronic respiratory inflammation. Here we assess the effect of chronic respiratory inflammation on plasma cfDNA levels and evaluate the potential clinical value of this phenomenon as an early lung cancer diagnostic tool. METHODS: We measured plasma cfDNA concentrations in 50 resectable NSCLC patients, 101 patients with chronic respiratory inflammation (chronic obstructive pulmonary disease, sarcoidosis, or asthma) and 40 healthy volunteers using real-time PCR. RESULTS: We found significantly higher plasma cfDNA levels in NSCLC patients than in subjects with chronic respiratory inflammation and healthy individuals (P<0.0001). There were no significant differences in plasma cfDNA levels between patients with chronic respiratory inflammation and healthy volunteers. The cutoff point of >2.8 ng ml(-1) provided 90% sensitivity and 80.5% specificity in discriminating NSCLC from healthy individuals (area under the curve (AUC)=0.90). The receiver-operating characteristics curve distinguishing NSCLC patients from subjects with chronic respiratory inflammation indicated 56% sensitivity and 91% specificity at the >5.25-ng ml(-1) cutoff (AUC=0.76). CONCLUSIONS: We demonstrated that elevated plasma cfDNA levels in NSCLC resulted primarily from tumour development rather than inflammatory response, raising the potential clinical implications for lung cancer screening and early diagnosis. Further research is necessary to better characterise and identify factors and processes regulating cfDNA levels in the blood under normal and pathological conditions.

Diagnostic accuracy of contrast-enhanced computed tomography and positron emission tomography with 18-FDG in identifying malignant solitary pulmonary nodules.

Contrast-enhanced computed tomography (CECT) and positron emission tomography with 18-FDG (FDG-PET/CT) are used to identify malignant solitary pulmonary nodules. The aim of the study was to evaluate the accuracy of CECT and FDG-PET/CT in diagnosing the etiology of solitary pulmonary nodule (SPN). Eighty patients with newly diagnosed SPN >8 mm were enrolled. The patients were scheduled for either or both, CECT and FDG-PET/CT. The nature of SPN (malignant or benign) was determined either by its pathological examination or radiological criteria. In 71 patients, the etiology of SPN was established and these patients were included in the final analysis. The median SPN diameter in these patients was 13 mm (range 8-30 mm). Twenty-two nodules (31%) were malignant, whereas 49 nodules were benign. FDG-PET/CT was performed in 40 patients, and CECT in 39 subjects. Diagnostic accuracy of CECT was 0.58 (95% confidence interval [CI] 0.41-0.74). The optimal cutoff level discriminating between malignant and benign SPN was an enhancement value of 19 Hounsfield units, for which the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CECT were 100%, 37%, 32%, and 100%, respectively. Diagnostic accuracy of FDG-PET/CT reached 0.9 (95% CI 0.76-0.9). The optimal cutoff level for FDG-PET/CT was maximal standardized uptake value (SUV max) 2.1. At this point, the sensitivity, specificity, PPV, and NPV were 77%, 92%, 83%, and 89%, respectively. The diagnostic accuracy of FDG-PET/CT is higher than that of CECT. The advantage of CECT is its high sensitivity and negative predictive value.

The influence of porcine pancreas digestion parameters and islet histomorphology on islet isolation outcome.

Transplantation of the pig islets of Langerhans is considered as the future treatment for patients suffering from type I diabetes mellitus. Despite the adaptation of modified Ricordi method and highly purified collagenase, the results of pancreas digestions are precarious. Selection of proper donor and optimal digestion procedure are fundamental. The aim of this study was to assess the impact of pancreas procuring parameters on pig islets yield. The pancreata were harvested from 69 market sows weighting over 150 kg. After intraductal injection of cold collagenase solution pancreata were transported in UW solution or under conditions of two layer method (TLM). In laboratory pancreata were digested at 37 degrees C according to Ricordi isolation method or stationary in the bottle. The particular parameters of isolation procedure were considered as substantial. Pig weight, volume of infused collagenase solution, TLM application and pancreas dividing before digestion positively affected islet yield. Additionally, the influence of pancreatic islet tissue histomorphology on isolation outcome was studied. Proper donor selection as well as adequate digestion parameters could improve pig islet recovery during islet isolation.

Neoadjuvant therapy affects tumor growth markers in early stage non-small-cell lung cancer.

INTRODUCTION: While adjuvant therapy of early-stage non-small-cell lung cancer (NSCLC) is widely accepted, literature data concerning neoadjuvant treatment provide contradictory results with both improved and unaffected survival rates. Also, data concerning potential effects of neo-adjuvant therapy on cellular level are scarce. OBJECTIVE: The aim of present study was to analyze the effect of chemotherapy followed by surgical resection on several key biological markers of tumor growth (TGF-beta, VEGF), apoptosis (sAPO-1/Fas/CD95) and invasiveness (TIMP-1) assessed in the sera of NSCLC early-stage patients (IB-IIIA). - MATERIAL AND METHODS: Measurements were performed by ELISA method in blood serum from 24 NSCLC patients (I-IIIA) collected prior therapy, one day before surgery and 3 days after. RESULTS: TGF-beta serum concentrations were significantly lower after both chemotherapy (P<0.05) and surgery (P<0.01) in comparison to the baseline. VEGF levels decreased following NEO therapy with subsequent significant up-regulation after surgery (P<0.001). Interestingly, post-surgery serum VEGF strongly correlated with TGF-beta concentration (r = 0.52, P = 0.014). No significant differences were observed for serum sAPO-1/CD95/FAS as well as TIMP-1 concentrations at any of three evaluated time-points. CONCLUSION: Neoadjuvant treatment of early-stage NSCLC affects mostly mechanisms responsible for tumor growth and vascularization. Its effect on cancer cells apoptotic activity needs further evaluation.

Evaluation of fluorescence-based methods for total vs. amplifiable DNA quantification in plasma of lung cancer patients.

In the last decade numerous reports demonstrated that free-circulating DNA in plasma/serum samples might be a promising biomarker in a number of pathologies, including cancer. Thus, choosing the reliable and efficient method of plasma DNA quantification would be an essential step prior to any clinical evaluation of cell-free DNA measurement in cancer patients. The aim of present study was to compare two highly-sensitive DNA quantification methods in regard to their applicability and effectiveness in monitoring the cell-free DNA level in the blood of patients with resectable non-small cell lung cancer. Plasma samples collected from 10 patients before any treatment, after neoadjuvant therapy and subsequent surgery, were used for DNA quantification by direct fluorescent PicoGreen staining and by real-time qPCR in SYBR Green and TaqMan probe approach using beta-actin gene as the amplifying target. The PicoGreen method demonstrated a high level of correlation with both the SYBR Green (r=0.87, P<0.0001) and TaqMan probe approach (r=0.94, P<0.0001). The total DNA content, determined by PicoGreen, proved to be several-fold higher than the amplifiable DNA amount measured by real-time qPCR. Consequently, intercalating fluorochromes, like PicoGreen, might serve as a rapid, accurate, and inexpensive alternative to real-time qPCR for routine dsDNA quantification and multicenter standardization.

p53 and HER2/neu expression in relation to chemotherapy response in patients with non-small cell lung cancer.

The aim of the study was to investigate a relation between p53 and HER2/neu expression in resected lung tumors and the response of those tumors to neoadjuvant chemotherapy. The study population included 67 consecutive patients with non-small cell lung cancer (NSCLC) in stage II or III who were operated on at the Institute of Tuberculosis, Warsaw, Poland, between 20 April 2001 and 10 March 2003. All patients received two cycles of chemotherapy consisting of cisplatin and vinorelbine prior to the operation. The response to therapy was assessed as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), on the basis of CT scans performed before and after neoadjuvant chemotherapy. p53 and HER2/neu protein expression were evaluated by immunohistochemistry (IHC) using antibodies against p53 (clone PAb 1801, Novocastra) and against HER2/neu (Dako) in paraffin-embedded specimens of tumors. A response to therapy (CR+PR) was observed in 27 patients, while 40 patients (SD+PD) were regarded as resistant to therapy. Resistance was observed significantly more often in tumors above 3 cm in diameter. p53 expression was found in 16 tumors (23.9%) and HER2/neu in 26 tumors (38.8%). We observed a nonsignificant tendency to chemoresistance in tumors with HER-2/neu overexpression and also in tumors with p53 overexpression. If we consider HER-2/neu and p53 together, chemoresistance was observed statistically significantly more often when one or both markers were positive (p<0.05). This significance was independent of tumor size.

Diagnostic utility of CYFRA 21-1 and CEA assays in pericardial fluid for the recognition of neoplastic pericarditis.

A positive cytology result in pericardial fluid is the gold standard for recognition of malignant pericardial effusion. Unfortunately, in 30-50% of patients with malignant pericardial effusion cytological examination of the pericardial fluid is negative. Tumor marker assessment in pericardial fluid may help to recognize malignant pericardial effusion. The aim of our study was to estimate the value of CYFRA 21-1 and CEA measurement in pericardial fluid for the recognition of malignant pericardial effusion. To our knowledge this is the first study on CYFRA 21-1 assessment in pericardial effusion. The examined group consisted of 50 patients with malignant pericardial effusion and 34 patients with non-malignant pericardial effusion. Median CEA concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 80 ng/mL (0-317) and 0.5 ng/mL (0-18.4), respectively (p<0.001). Median CYFRA 21-1 concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 260 ng/mL (5.3-10080) and 22.4 ng/mL (1.87-317.6), respectively (p<0.001). The optimal cutoff value for CYFRA 21-1 in pericardial effusion was 100 ng/mL. CYFRA 21-1 >100 ng/mL or CEA >5 ng/mL were found in 14/15 patients with malignant pericardial effusion and negative pericardial fluid cytology. We therefore strongly recommend the use of CYFRA 21-1 and/or CEA in addition to pericardial fluid cytology for the recognition of malignant pericardial effusion.

Diagnostic utility of CYFRA 21-1 and CEA assays in pericardial fluid for the recognition of neoplastic pericarditis.

A positive cytology result in pericardial fluid is the gold standard for recognition of malignant pericardial effusion. Unfortunately, in 30-50% of patients with malignant pericardial effusion cytological examination of the pericardial fluid is negative. Tumor marker assessment in pericardial fluid may help to recognize malignant pericardial effusion. The aim of our study was to estimate the value of CYFRA 21-1 and CEA measurement in pericardial fluid for the recognition of malignant pericardial effusion. To our knowledge this is the first study on CYFRA 21-1 assessment in pericardial effusion. The examined group consisted of 50 patients with malignant pericardial effusion and 34 patients with non-malignant pericardial effusion. Median CEA concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 80 ng/mL (0-317) and 0.5 ng/mL (0-18.4), respectively (p<0.001). Median CYFRA 21-1 concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 260 ng/mL (5.3-10080) and 22.4 ng/mL (1.87-317.6), respectively (p<0.001). The optimal cutoff value for CYFRA 21-1 in pericardial effusion was 100 ng/mL. CYFRA 21-1 >100 ng/mL or CEA >5 ng/mL were found in 14/15 patients with malignant pericardial effusion and negative pericardial fluid cytology. We therefore strongly recommend the use of CYFRA 21-1 and/or CEA in addition to pericardial fluid cytology for the recognition of malignant pericardial effusion. (Int J Biol Markers 2005; 20: 43-49).

Assessment of some porcine strains as donors of islets of Langerhans.

Mass isolation of viable porcine islets is a difficult task because of their fragility, and because of donor variability with respect to strain, age, sex, feeding, and methods of slaughtering. Not all strains are equally suitable for islet separation. The aim of this study was to evaluate porcine pancreata as an alternative source of islets for clinical transplantation. Pancreata were digested from pig strains available in Poland: 248 market weight slaughterhouse pigs and 42 pigs, belonging to the Polish Large White (WBP, 14 sows and 3 males), Polish White Pendant-Ears (PBZ; 16 sows), Pietrain (8 sows), and Yorkshire (1 sow) races. Prepurification data of recoverable islets/g and islet equivalents/g were considered as representative for the number of recoverable islets. Acceptable results namely, islet and/or islet-equivalent (IE) number of at least 1000/g, were obtained from only 56 of 248 slaughterhouse pigs, namely 2073 +/- 137.4 SE (median 1767/g) islets with values of IE of 2994 +/- 303 SE (median 1874/g). Our data support Krickhahn et al suggesting that only pancreata with an average islet size exceeding 199 microm should be digested and that only from 1 of 3 to 5 porcine pancreata is an adequate amount of islets generated.

Management of purulent pericarditis.

A 50 year old man was admitted to ICU due to purulent pericarditis, purulent inflammation of the soft tissue of the neck, purulent mediastinitis and pneumonia. Subxyphoid periocardiotomy followed by the insertion of a drain into the pericardial space was performed. Four other drains were also inserted to drain purulent fluid from the neck (two drains) and mediastinum (two drains). During the surgical procedure, 700 ml of purulent pericardial fluid from the pericardial sac and 200 ml of purulent fluid from the mediastinum were drained. Antibiotic therapy was started upon admission to the hospital. Streptococcus species, Acinetobacter baumani and Enterococcus casseliflavus were cultured. Antibiotic therapy was adjusted to the results of the antibiogram. Despite revised antibiotic therapy, daily drainage from the pericardium--during several days after surgery--was around 200 ml. Due to the huge purulent pericardial drainage streptokinase, delivered directly into pericardial space, was given. The clinical effect of intrapericardial streptokinase administration was excellent. After 17 days drainage of purulent pericardial fluid was not observed. No clinical signs and symptoms of constrictive pericarditis developed. Repeated echocardiography examinations showed no signs of constrictive pericarditis and no pericardial fluid. The patient was discharged in good general condition.

[Primary lung hemangiopericytoma--a rare neoplasm with a long course of recurrence over many years]. / Pierwotny hemangiopericytoma pluca--rzadki nowotwór o nawracajacym, wieloletnim przebiegu.

Hemangiopericytoma (HPC) is a rare neoplasm arising from pericytes that occur mostly around smaller vessels. Up to now only about 100 cases have been reported to arise primarily in the lung. The behavior of pulmonary hemangiopericytomas is difficult to predict and all tumors should be considered potentially malignant, even though the criteria for malignancy are not well developed. The diagnosis of HPC is known to confound even experienced pathologist. Pericytes lack readily identifiable morphologic features, therefore hemangiopericytomas are often confused with other soft tissue tumors that may have hemangiopericytoma--like pattern. We report a rare case of primary HPC of the lung with an asymptomatic, long course of the disease. The diagnosis of hamartoma was established after the first operation. Subsequently, seven years later, a chest radiograph revealed new lesions. Histological examination, including immunohistochemistry lead to the final diagnosis of hemangiopericytoma. The small number of cases of primary pulmonary hemangiopericytoma makes it difficult to define the correct histopathological diagnosis especially without modern methods.

Surgical treatment of stage III non-small cell lung cancer.

The resectability of NSCLC is determined by its stage. The surgical treatment in stage I and II NSCLC remains a golden standard. Stage IIIA NSCLC constitutes a non-homogenous group, and many patients are potentially non-resectable. The patients in stage IIIA NSCLC also constitute a non-homogenous group. The patients in stage T3N1 usually undergo surgical resection, but many patients with N2 disease are disqualified from surgical treatment due to the negative prognostic factors. The negative prognostic factors comprise: (1) metastases to upper paratracheal (no 2), anterior paratracheal (no 3), and subcarinal (no 7) lymph nodes; (2) metastases to multiple mediastinal lymph nodes; (3) occurrence of the so called 'bulky disease'; (4) capsular lymph node invasion. The occurrence of one of these negative prognostic factors disqualifies the patient with N2 disease from radical surgical treatment. In more advanced cases, i.e. stage IIIB, and stage IV NSCLC, patients are rarely operated. It regards the patients in stage T4 N1, and in M1 disease with a single metastasis (mainly to CNS) accompanied by the stage I, or II, of the primary focus. In these cases N2 disease always constitutes the contraindication to the surgical treatment. Multidisciplinary approach in the treatment of NSCLC is supposed to improve the results of the treatment of NSCLC.

[Sarcoid reaction in patients with lung neoplasm--personal experiments]. / Odczyn sarkoidalny u chorych na raka pluca--doswiadczenia wlasne.

In two cases histological examination of the lymph nodes excised during mediastinoscopy showed non-caseous epithelioid granulomas. In one patient with hilar lymphadenopathy sarcoidosis was misdiagnosed. One-year later progression of lesions in lungs was found and adenocarcinoma was diagnosed. In second patient with tumour in chest x-ray examination after misdiagnosed sarcoidosis thoracotomy was done and histological examination of samples from tumour showed nonsmall cell lung cancer. In both carcinomatous cases sarcoid reaction was recognised.

[Pulmonary amyloidosis--own experience]. / Amyloidoza ukladu oddechowego--doswiadczenia wlasne.

Three cases of amyloidosis were described. In all diagnosis was confirmed by histological examination. There was amyloidosis limited to the lungs in 2 cases and in 1 generalised. In 1 patient lobectomia was performed. Next 2 pts were treated with prednisone and cytostatic drugs (melphalane and cyclophosphamide).

Tetracationic porphyrins inhibit angiogenesis induced by human tumor cells in vivo.

BACKGROUND: Cationic porphyrin TMPyP4, but not its isomer TMPyP2, inhibits telomerase in tumor cells in vitro and induces chromosome destabilization in vivo. MATERIALS AND METHODS: To examine the effects of these porphyrins on tumor-induced angiogenesis, 25-200 micrograms TMPyP4 or TMPyP2 were injected daily for 3 days in mice with intradermally implanted primary human tumor cells. Alternatively, tumor cells were exposed for 90 minutes to 2.5-20 microM porphyrins prior to implantation in mice. RESULTS: Either subcutaneous injections (> or = 50 micrograms/mouse) or preincubation with > or = 5 microM porphyrins significantly inhibited angiogenesis. CONCLUSION: Antiangiogenic activity is apparently unrelated to the ability of the porphyrins to inhibit telomerase.

Experimental study of the effects of different stapling devices in healing of the mechanically sutured bronchial stump.

OBJECTIVE: The invention of the mechanical suture of the bronchial stump resulted in the significant decrease of the incidence of bronchial fistulas. Bronchial fistula constitutes the most dangerous complication of the pulmonary resection. In connection with some negative opinions in world literature regarding the safety of applying some types of mechanical suture, the multi-factor analysis of efficacy of bronchial stump closure following the total pneumonectomy by two different types of stapling devices was performed. METHODS: The experimental study was performed on 22 sheep. Each sheep underwent left pneumonectomy. In group I the bronchus was closed by the hinged-jaw stapling device (TA-Premium, Auto-Suture). In group II the bronchus was closed by the stapling device of parallel pattern (RLV 30 Ethicon). The macroscopic parameters (i.e. linear structure of staples, degree of staples closure, the symmetry of staples closure in the medial and lateral part of bronchial stump) as well as microscopic parameters (i.e. degree of inflammatory reaction, degree disorder in collagen fibers system, degree of disorders in cartilaginous system, degree of vascular proliferation and nervous regeneration) were evaluated. RESULTS: In three cases of group I the serious abnormalities in staples closure in the medial part of the bronchial stump were revealed. Abnormalities were found also in microscopic evaluation of the specimens. In the whole group the inflammatory reaction predominated in the medial part of bronchial stump near the hinge of the cartridge (P value <0.05). The disorder in the collagen fibers system as well as in the stratified structure of muscular fibers and cartilaginous system was proved. On the other hand, in group II all staples were properly closed in adequate linear structure, without any symmetry in both medial and lateral end of the bronchial stump. The microscopic findings were only the subtle inflammatory process and a slight disarrangement in muscular, collagen and cartilaginous systems. CONCLUSION: The listed abnormalities of mechanical, hinged-jaw suture of bronchial stump seem to be due to the inaccurate placement of staples, their incomplete closure, and excessive damage to the sutured tissues. We conclude that the application of the hinged-jaw mechanical suture of the bronchial stump might result in higher incidence of bronchial fistula after pneumonectomy.