Daniel Reis Waisberg

Perfil do doador de pulmão disponibilizado no estado de São Paulo, Brasil, em 2006

OBJECTIVE: To analyze the rate at which lungs available for transplantation in the state of Sao Paulo in 2006 were utilized and to determine the lung donor profile in the same period. METHODS: A retrospective study of 497 clinical charts of lung tissue donors from January to December of 2006. RESULTS: According to the clinical charts, lungs were not offered for transplant in 149 cases (30%), which were therefore excluded from the study. Among the 348 lung donors eligible for inclusion in the study, the mean age was 37.4 ± 16.1 years, and 56.9% were males. The main causes of brain death among the donors were stroke (in 40.5%), skull-brain trauma (in 34.2%) and subarachnoid hemorrhage (in 10.9%). The great majority of these lung donors (90.5%) received vasoactive agents, and 13.5% presented cardiopulmonary arrest. The mean donor leukocyte count was 15,008 ± 6,467 cells/mm³, 67.8% of the donors received anti-bacterial agents, and 26.1% presented lung infection. Nearly 40% of the lung donors presented chest X-ray abnormalities. Only 4.9% of the lung donors were accepted, representing 28 lungs (allograft utilization rate of 4%). The causes for donor exclusion were gas exchange alterations (in 30.1%), infection (in 23.7%) and distance (in 10.9%). CONCLUSIONS: The lung utilization rate in the state of Sao Paulo is low when compared to mean rates worldwide. In addition, more than half of the donor pool was excluded due to altered gas exchange or pulmonary infection. The combination of better care of the potential donor and more flexible selection criteria could increase allograft utilization.

Abnormal expression of telomerase/apoptosis limits type II alveolar epithelial cell replication in the early remodeling of usual interstitial pneumonia/idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis is a distinctive, usually fatal, type of chronic fibrosing interstitial pneumonia of unknown cause that increases in prevalence with advanced age, characterized by failure of alveolar re-epithelization and progressive scar formation. Recently, limitation of the replicative capacity of tissues determined by telomerase/apoptosis balance has been implicated in pathogenesis of age-related diseases. In this study, we validated the importance of the expression of type 2 alveolar epithelial cells telomerase protein and studied the relationships between telomerase and apoptosis in early remodeling of usual interstitial pneumonia. We determined type 2 alveolar epithelial cells density, telomerase expression, and apoptosis in surgical lung biopsies from 24 patients with usual interstitial pneumonia, and in normal lung tissues from 18 subjects. We used immunohistochemistry, deoxynucleotidyl transferase method of end labeling, electron microscopy, and histomorphometry to evaluate the amount of type 2 alveolar epithelial cells staining for surfactant-A, telomerase, and in situ detection of apoptotic cells. Unaffected areas of usual interstitial pneumonia and normal lung tissue had similar densities of type 2 alveolar epithelial cells, but a significant minor subpopulation of type 2 alveolar epithelial cells was telomerase positive and a large population was telomerase negative. A significant inverse association was found between low type 2 alveolar epithelial cell telomerase expression and high apoptosis in unaffected areas of usual interstitial pneumonia. Although type 2 alveolar epithelial cell telomerase expression was higher than apoptosis in NLT group, no significant association was found between them. Electron microscopy confirmed epithelial apoptosis, alveolar collapse, and initial fibroplasia. We conclude that abnormal type 2 alveolar epithelial cells telomerase/apoptosis balance may reduce alveolar epithelial regenerative capacity, thus contributing to the early remodeling response in usual interstitial pneumonia.

Lung transplantation for pulmonary alveolar microlithiasis: a case report

Pulmonary alveolar microlithiasis (PAM) is a rare idiopathic lung disease, characterized by the formation and accumulation of tiny, round corpuscles called “microliths” that consist primarily of calcium and phosphorus mixed with small amounts of magnesium and aluminum1. Most of the reported cases are of patients between 20 and 40 years of age. Autosomal recessive inheritance has been suggested to be a possible cause of the disease. Clinical features vary, and some patients may be asymptomatic for a long time until pulmonary function testing begins to demonstrate lung impairment along with progressive fibrosis and the development of a restrictive ventilatory defect culminating in cardiorespiratory decompensation.2 Currently, there is no medical therapy capable of definitively changing the progression of the disease. Lung transplantation is required once end-stage lung disease is established. To date, seven patients have received lung transplantation for this condition. We report a successful case of bilateral sequential lung transplantation in a patient with PAM.

Increased fibroblast telomerase expression precedes myofibroblast α-smooth muscle actin expression in idiopathic pulmonary fibrosis

OBJECTIVE: This study sought to identify the relationship between fibroblast telomerase expression, myofibroblasts, and telomerase-mediated regulatory signals in idiopathic pulmonary fibrosis. METHODS: Thirty-four surgical lung biopsies, which had been obtained from patients with idiopathic pulmonary fibrosis and histologically classified as usual interstitial pneumonia, were examined. Immunohistochemistry was used to evaluate fibroblast telomerase expression, myofibroblast α-smooth muscle actin expression and the tissue expression of interleukin-4, transforming growth factor-β, and basic fibroblast growth factor. The point-counting technique was used to quantify the expression of these markers in unaffected, collapsed, mural fibrosis, and honeycombing areas. The results were correlated to patient survival. RESULTS: Fibroblast telomerase expression and basic fibroblast growth factor tissue expression were higher in collapsed areas, whereas myofibroblast expression and interleukine-4 tissue expression were higher in areas of mural fibrosis. Transforming growth factor-β expression was higher in collapsed, mural fibrosis and honeycombing areas in comparison to unaffected areas. Positive correlations were found between basic fibroblast growth factor tissue expression and fibroblast telomerase expression and between interleukin-4 tissue expression and myofibroblast α-smooth muscle actin expression. Negative correlations were observed between interleukin-4 expression and basic fibroblast growth factor tissue expression in areas of mural fibrosis. Myofibroblast α-smooth muscle actin expression and interleukin-4 tissue expression in areas of mural fibrosis were negatively associated with patient survival. CONCLUSION: Fibroblast telomerase expression is higher in areas of early remodeling in lung tissues demonstrating typical interstitial pneumonia, whereas myofibroblast α-smooth muscle actin expression predominates in areas of late remodeling. These events seem to be regulated by basic fibroblast growth factor and interleukin-4 tissue expression, respectively.

Carcinoid of the minor duodenal papilla associated with pancreas divisum: case report and review of the literature

That carcinoid tumors of themajor duodenal papilla have been described more fre-quently than those of the minor papilla is probably becausethose of the major duodenal papilla often give rise to symp-toms (for example jaundice and pain) that demand inten-sive examination or surgery; while those of the minor pa-pilla are frequently asymptomatic.

CA72-4 antigen levels in serum and peritoneal washing in gastric cancer: correlation with morphological aspects of neoplasia

BACKGROUND Determining levels of tumor markers in peritoneal washing enables likelihood of peritoneal recurrence to be ascertained in patients with high marker levels, thereby allowing provision of more accurate adjuvant treatment and postoperative follow up. AIM To analyze the relationship between levels of tumor marker CA72-4 in serum and peritoneal washing, and morphological aspects of gastric carcinoma. METHOD This study analyzed 32 consecutively-operated patients with gastric carcinoma, who underwent subtotal, total or palliative gastrectomy. The variables studied were CA72-4 levels in serum and peritoneal washing, lesion site, stage, degree of cell differentiation, operation performed, and number of extirpated and involvement lymph nodes. Of the 32 patient sample, 21 (65.6%) were male and 11 (34.4%) female. Mean age was 62.6 +/- 14.2 years (29 to 91 years). Following anesthetic induction, peripherical venous blood was collected through percutaneous punction of an upper limb vein. After the procedure, 50 mL of physiologic solution at 37 degrees C was introduced into the cul-de-sac. A 10 mL volume of this liquid was aspirated from the cavity and the peritoneal washing tested for CA72-4 levels. Normal values for CA72-4 levels in serum were considered < or =7 U/mL and high levels as >7 U/mL, whilst for the peritoneal washing normal levels were < or =0.61 U/mL, and abnormal >0.61 U/mL. RESULTS Mean pre-operative serum levels for CA72-4 were 6.55 U/mL +/- 15.30 (0.3 to 75.30 U/mL) whilst the mean level of CA72-4 in peritoneal washing was 8.50 U/mL +/- 26.72 (0.3 to 142.00 U/mL); correlation between these levels was significant. Lymph nodes involvement by the gastric carcinoma correlated significantly with higher CA72-4 levels in both serum and peritoneal wash. There was no statistically significant correlation between serum level of CA72-4 and invasion into serosa by the gastric carcinoma. There was however, significant correlation between peritoneal washing levels of CA72-4 and involvement of serosa by gastric carcinoma. There was also a significant correlation between more advanced stages of gastric carcinoma and higher levels of CA72-4 in the peritoneal washing, although serum levels of CA72-4 and more advanced stage of gastric neoplasia showed no significant correlation. Degrees of cellular differentiation in the gastric carcinoma did not differ significantly with CA72-4 levels in serum or peritoneal washing. CONCLUSION High levels of CA72-4 in peritoneal washing correlated significantly with lymph node metastasis and serosa involvement by the neoplasia, and also with more advanced stage of gastric carcinoma. The levels of CA72-4 in the blood correlated significantly with lymph node involvement by the gastric carcinoma, but not with serosa invasion or more advanced stage of neoplasia.

NM23 protein expression in colorectal carcinoma using TMA (tissue microarray): association with metastases and survival

CONTEXT NM23, a metastasis suppressor gene, may be associated with prognosis in patients with colorectal carcinoma. OBJECTIVE To analyze NM23 expression and its association with the presence of lymph node and liver metastases and survival in patients operated on for colorectal carcinoma. METHODS One hundred thirty patients operated on for colorectal carcinoma were investigated. Tissue microarray blocks containing neoplastic tissue and tumor-adjacent non-neoplastic mucosa were obtained and analyzed by immunohistochemical staining using a monoclonal anti-NM23 antibody. Immunohistochemical expression was assessed using a semiquantitative scoring method, counting the percentage of stained cells. The results were compared regarding morphological and histological characteristics of the colorectal carcinoma, presence of lymph node and liver metastases, tumor staging, and patient survival. Statistical analysis was performed using the Mann-Whitney test, the Kruskal-Wallis test and Fishers exact test. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. RESULTS NM23 expression was higher in colorectal carcinoma tissue than in adjacent non-neoplastic mucosa (P<0.0001). NM23 protein expression did not correlate with degree of cell differentiation (P = 0.57), vascular invasion (P = 0.85), lymphatic invasion (P = 0.41), perineural infiltration (P = 0.46), staging (P = 0.19), lymph node metastases (P = 0.08), or liver metastases (P = 0.59). Disease-free survival showed significant association (P = 0.01) with the intensity of NM23 protein immunohistochemical expression in colorectal carcinoma tissue, whereas overall survival showed no association with NM23 protein expression (P = 0.13). CONCLUSIONS NM23 protein expression was higher in neoplastic colorectal carcinoma tissue than in adjacent non-neoplastic mucosa, showing no correlation with morphological aspects, presence of lymph node or liver metastases, colorectal carcinoma staging, or overall survival. Disease-free survival was higher in patients with increased NM23 expression.

Obesity Is a Risk Factor for Significant Carotid Atherosclerosis in Patients Aged 39 to 55 Years

We compared the prevalence of risk factors between young and old individuals with significant carotid atherosclerosis. We retrospectively reviewed the records of patients aged 39 to 55 years (group I) and aged ≥60 years (group II) with significant atherosclerotic stenosis at the carotid bifurcation. Group I patients had significantly higher values for the following factors: weight, height, body mass index, diastolic pressure, prevalence of current smoking, total and low-density lipoprotein cholesterol and significant lower values for systolic pressure, creatinine, and prevalence of coronary artery disease. Group I patients were more symptomatic and showed higher rates of carotid occlusion and near occlusion. Atherosclerosis of the carotid bifurcation was more aggressive in the younger group, with a higher rate of occlusion and near occlusion. Obesity and smoking were significant risk factors for young patients in this sample.

Colonic carcinoid tumors: a clinicopathologic study of 23 patients from a single institution

CONTEXT Colonic carcinoids, excluding those arising in the appendix, have proved to be extremely rare. Due to their rarity, the characteristics and behavior of this unusual malignancy remain unclear. OBJECTIVE To review the clinicopathologic features of patients operated on carcinoid tumors of the colon. METHODS Twenty-three patients (12 males and 11 females) were operated on colonic carcinoids. The mean age of the patients was 63.0 +/- 12.9 years (42 to 85 years). The clinical and histopathological data of patients who were pathologically diagnosed as having carcinoid tumors and submitted to surgical treatment over a 30-year period (1977-2007) were gathered. Actuarial patient survival was estimated using the Kaplan-Meier method, with carcinoid-specific death as the outcome. RESULTS The mean time elapsed between onset of symptoms and surgical treatment was 8.3 months (1.5 to 20 months). The most frequent symptoms or signs encountered were abdominal pain followed by anorexia or weight loss, diarrhea, abdominal tenderness, palpable abdominal mass, and rectal bleeding. No carcinoid syndrome was noted. The lesion was located in the cecum in 16 (69.6%) patients, in the sigmoid in 3 patients (13.0%), in the ascending colon in 3 patients (13.0%), and in the transverse colon in one patient (4.3%). Twenty-one (91.3%) patients were operated on curative intent. Spreading of the disease to the liver and peritoneum was found in two (8.7%) patients who submitted to intestinal bypass. The mean size of the largest mass was 3.7 +/- 1.2 cm (1.5 to 6.2 cm). There were multiple (two or more) lesions in three cases (13.0%). In the resected cases, the lymph nodes were compromised in 10 patients (47.6%) and disease-free in 11 (52.4%). Venous invasion and neural infiltration were both present in five (23.8%) patients. The tumors had penetrated the muscularis propria in all resected cases. Four (17.4%) patients had a second non-carcinoid primary tumor. Three (13.0%) patients died due to postoperative complications and five (21.7%) patients died from metachronous metastases or local recurrence. Fifteen patients (65.2%) remain alive without evidence of active disease. The mean follow-up period was 12 years (1.2 to 18 years), whereas the mean global survival was 50.7 +/- 34.2 months and the crude survival rate at 5 years was 62.7%. CONCLUSIONS Carcinoid tumors of the colon are frequently right-sided and may be clinically occult until an advanced stage is reached. Based on the relatively poor survival rates reported, it is recommended that, in addition to standard surgical resection, vigorous surveillance for metastatic disease must be performed, particularly during the first 2 years after surgery. In addition, these patients require evaluation of the entire gastrointestinal tract for evidence of coexisting malignancy, along with an extended period of follow-up, because tumor recurrences after 5 years are not uncommon.

Bilateral Lung Transplantation in Asymmetric Thorax : Case Reports

Suppurative lung diseases, such as cystic fibrosis and bronchiectasis, when diffuse and associated with important functional loss, can be treated with bilateral lung transplantation with good results. These diseases are frequently associated with previous lung resections presenting an asymmetric thorax, thus making lung extraction difficult and generating disproportion between the graft and the pleural cavity. To treat this condition, pneumonectomy and single lung transplantation is a feasible option; however, there are associated comorbidities and an invariable need for extracorporeal circulation. Described herein are 2 patients with an asymmetric thorax, treated with bilateral transplantation and lung volume reduction with lobectomy.