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.

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.

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 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.

Diagnostic and prognostic value of antibody-dependent cellular cytotoxicity and lectin-induced cellular cytotoxicity tests for renal graft rejection.

Peripheral blood lymphocytes from both normal subjects and kidney allograft recipients, before and on the 4th to 5th days after transplantation, were examined for antibody-dependent cellular cytotoxicity (ADCC) and lectin-induced cellular cytotoxicity (LICC). The graft recipients were treated with standard immunosuppression, which included azathioprine and prednisolone. 51Cr-labeled L1210 cells were used as targets for these two tests. ADCC and LICC activity were evaluated in the presence of rabbit anti-L1210 anti-serum and phytohemagglutinin (PHA), respectively. Comparison of the results obtained from healthy subjects with those of patients before grafting showed a significantly higher LICC activity in the latter group. The ADCC activity did not differ between the groups of healthy females and those awaiting transplantation but it was significantly decreased in the group of males awaiting transplantation as compared to healthy males. Four to 5 days after transplantation, the activity of ADCC and LICC remained unchanged in spite of the immunosuppressive treatment in 37 and 61% of the patients studied, respectively. In most of the patients, high ADCC and/or LIcC activity was followed by an accelerated acute rejection episode. A correlation between the ADCC and LICC activities, measured 4 to 5 days after transplantation, and the time of the first rejection episode was found. We conclude that double screening with ADCC and LICC tests in the 1st week after transplantation is valuable.

Palliative intubation of the tracheobronchial tree.

Sixteen patients with far-advanced neoplastic lesions in the trachea and main-stem bronchi were studied. Ten of them were admitted to the ward in extremely poor general condition with marked cyanosis and dyspnea at rest. Palliative intubation was undertaken with two types of tubes: a Neville tracheal prosthesis and a Tracheoflex tracheostomy tube. Both types of tubes had to be specially prepared, as they had originally been designed for other purposes. The tubes were placed in the stenotic sections of the trachea and, depending on anatomical relations, within the right or left main bronchus as well. Intubation of the bronchus in the case of changes involving only the trachea was necessary to properly position and fasten the tube in the bronchial tree and to prevent displacement of the prosthesis inside the trachea. In two patients the esophagus was intubated as well. An improvement in the general condition of all patients was observed. Intubation resulted in reexpansion of a completely collapsed lung in two patients. The longest time of intubation was 9 months. The method is simple, and every physician experienced in endoscopy can use it. The results obtained encourage its further and wider application.

Leiomyoma of the lung.

A case of asymptomatic pulmonary leiomyoma diagnosed by routine chest radiography and treated by lobectomy is reported. There is no particular clinical pattern that distinguishes this lesion, and diagnostic maneuvers to identify its nature are generally unrewarding except for biopsy. Resection is the recommended treatment.

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.

A 2.5-year follow-up of local immunotherapy of advanced stomach and intestinal adenocarcinoma with Propionibacterium granulosum.

Intratumoral injections of 10 mg cells walls from Propionibacterium granulosum strain KP-45 (PG) were applied in 14 patients with advanced, metastatic stomach (five cases) and colorectal (nine cases) adenocarcinoma. Each patient had his own "twin" control. All patients received no other anticancer treatment, except analgetics and/or palliative surgery. Treatment with PG resulted in partial regression of tumors accompanied by improvement of the clinical state of these patients as well as the reappearance of normal values in blood count biochemical parameters. In each pair of twin cases, survival of the PG-treated patient was longer than the untreated control. The mean survival of PG-treated patients was 23.5 months (4 of 14 patients being still alive after 2.5 years follow-up), while all control patients died with a mean survival period of 6.4 months. The difference between these two patient groups of about 17 months is significant (p greater than 0.01).

Evaluation of a porcine internal mammary artery (No-React II) as a small-diameter conduit.

BACKGROUND: The patency of biologic small-diameter vascular grafts in the aortocoronary position is still unsatisfactory. Most of the studies suggest that xenografts are to be avoided as an aortocoronary bypass. METHODS: The porcine internal mammary artery treated by the No-React II procedure was developed for use as an alternative coronary artery bypass conduit. The attempt of this study was to evaluate the patency and histologic changes of the porcine internal mammary artery in animals. Five calves underwent coronary artery bypass grafting with a porcine internal mammary artery graft to the right coronary artery. After euthanasia of the animals 103 days later, the samples of these grafts were studied morphologically for patency, structural changes, calcifications, and inflammatory and immunologic response. RESULTS: One animal died during the procedure as result of acute thrombosis of the porcine internal mammary artery graft. In the other 4 animals all grafts became occluded. In the histologic sections of the grafts we noted multiple calcifications and a host-graft immunologic reaction (severe chronic rejection). CONCLUSIONS: The present study demonstrates a very poor experience with the porcine internal mammary artery (No-React II) conduit. We do not recommend this prosthesis for clinical use in humans.

Lymphokine-supressing cells in patients after kidney transplantation.

Streptococcal antigens elicit Leukocyte Migration Inhibitory Factor (LMIF) production by sensitive human lymphocytes in vitro leading to an inhibition of leukocyte migration in agarose plates. When mononuclear cells isolated from peripheral blood of healthy donors are added to the assay system, no significant alteration of LMIF generation occurs. Likewise, cells from patients with kidney allografts obtained during an uneventful postoperative course did not influence lymphokine synthesis. Conversely, cells isolated from patients undergoing acute graft rejection abolished SKSD-induced LMIF production by normal lymphocytes. These results support our earlier report of the existence of lymphokine-suppressing cells in man and suggest that they may play yet poorly defined role in certain immunopathologic situations.

Niridazole as an adjunct to "conventional" immunosuppression in kidney allograft transplantation. Long-term follow up.

To assess the value of niridazole as adjuvant immunosuppressant to conventional steroid and azathioprine therapy, a prospective randomized clinical study in 26 cadaver kidney recipients had been performed. No beneficial effect was observed on the kidney graft survival with the addition of niridazole. Neither was there any additional immunosuppressive action demonstrated in the serum of the patients in this group. On the basis of our limited clinical experience niridazole can not be recommended as an adjunct agent for kidney graft recipients.

Study of antibody dependent cellular cytotoxicity (ADCC). II. ADCC activity in renal graft recipients and acute accelerated graft rejection.

ADCC activity in 27 cadaver renal allograft recipients was studied. All the patients were given standard immunosuppressive treatment. Significant positive correlation between high ADCC activity during first 5 days after grafting and accelerated rjection crisis was found. The high positive ADCC test may signalize the possibility of acute accelerated rejection of renal allograft.

Study of antibody dependent cellular cytotoxicity (ADCC). III. Preliminary findings concerning the influence of immunosuppressive drugs.

The present studies were undertaken to characterize cytotoxic activity of lymphocyte-(ADCC) in the course of primary glomerulonephritis and to evaluate the influence of some of the immunosuppressive drugs on lymphocytes of examined patients. 18 patients were studied; 12 of them were treated by combined therapy with prednisone, azathioprine and chlorambucil. Results were analyzed on the basis of healthy individuals ADCC activity. In the 11 treated patients significant decrease of ADCC activity was observed while non-treated group exhibited as high activity as healthy individuals. Which of given drugs is responsible for the decreased ADCC activity, remains questionable and is currently under the study.

The comparison of antibody-dependent (ADCC) and lectin-induced (LICC) cytotoxic activities of human blood lymphocytes in healthy and diseased subjects.

Antibody-dependent and PHA-induced cytotoxicity of peripheral blood lymphocytes in healthy human subjects and in patients with primary glomerulopathies (non-treated and on immunosuppressive treatment) as well as hemodialyzed and transplanted patients were investigated. Heavy disorders of ADCC and LICC activity in the groups of uremic patients and in patients on immunosuppressive therapy were found. Higher sensitivity to immunosuppressive treatment demonstrated that the lymphocytes exerted an antibody-dependent rather than a PHA-induced cytotoxicity. Results presented suggested the participation of two different lymphocyte subpopulations with ADCC and LICC activity in the regulatory and pathological processes.

The effect of uremia and dialysis on cell-mediated immunity.

Delayed-type hypersensitivity to PPD, two types T rosettes as well as lymphokine production were studied in patients with end-stage renal failure maintained on hemodialysis. A significant impairment of skin reactivity and the lowering of the number of T cells were found, while no definite changes of lymphokine production were detected. No conclusive data are obtained as to the role of hemodialysis in reversing of immunologic deficits noted in uremia.

Lymphocyte dependent antibody (LDA) test in renal transplanted patients.

Using LDA test the presence of antibodies in patients prior to and post renal transplantation was studied. The relationship between the results of LDA test and graft rejection episodes, the treatment with large doses of prednisolone and CDC test performed simultaneously were analized. No correlation between results of LDA test prior to transplantation or its response to prednisolone treatment and acute rejection crises was found. The value of LDA test in predicting rejection episodes was not confirmed. LDA test detects antibodies 10 times more frequently than CDC test. The presence of cytotoxic antibodies CDC was not always connected with the presence of LDA and vice versa.