Passiflora edulis peel intake and ulcerative colitis: approaches for prevention and treatment.

Inflammatory bowel disease is a chronic relapsing disease that affects millions of people worldwide; its pathogenesis is influenced by genetic, environmental, microbiological, and immunological factors. The aim of this study was to evaluate the effects of short- and long-term Passiflora edulis peel intake on the antioxidant status, microbiota, and short-chain fatty acids formation in rats with 2,4,6-trinitrobenzenesulphonic acid-induced colitis using two "in vivo" experiments: chronic (prevention) and acute (treatment). The colitis damage score was determined using macroscopic and microscopic analyses. In addition, the antioxidant activity in serum and other tissues (liver and colon) was evaluated. Bifidobacteria, lactobacilli, aerobic bacteria and enterobacteria, and the amount of short-chain fatty acids (acetic, butyric, and propionic acids) in cecum content were counted. Differences in the colon damage scores were observed; P. edulis peel intake improved serum antioxidant status. In the treatment protocol, decreased colon lipid peroxidation, a decreased number of aerobic bacteria and enterobacteria, and an improvement in acetic and butyric acid levels in the feces were observed. An improvement in the bifidobacteria and lactobacilli was observed in the prevention protocol. These results suggested that P. edulis peel can modulate microbiota and could be used as source of fiber and polyphenols in the prevention of oxidative stress through the improvement of serum and tissue antioxidant status.

Controversial predictors of biochemical recurrence after radical prostatectomy: a study from a Latin American (Brazilian) Institution

Purpose To analyze controversial clinicopathologic predictors of biochemical recurrence after surgery: age, race, tumor extent on surgical specimen, tumor extent on needle biopsy, Gleason score 3 + 4 vs 4 + 3, and amount of extent of extraprostatic extension and positive surgical margins. Materials and Methods The needle biopsies and the correspondent surgical specimens were analyzed from 400 patients. Time to recurrence was analyzed with the Kaplan-Meier curves and risk of shorter time to recurrence using Cox univariate and multivariate analysis. Results Except for age, race, maximum percentage of cancer per core, and number of cores with cancer, all other variables studied were significantly predictive of time to biochemical recurrence using the Kaplan-Meier curves. In univariate analysis, except for focal extraprostatic extension, age, race, focal positive surgical margins, and maximum extent and percentage of cancer per core, all other variables were significantly predictive of shorter time to recurrence. On multivariate analysis, diffuse positive surgical margins and preoperative PSA were independent predictors. Conclusions Young patients and non-whites were not significantly associated with time to biochemical recurrence. The time consuming tumor extent evaluation in surgical specimens seems not to add additional information to other well established predictive findings. The higher predictive value of Gleason score 4 + 3 = 7 vs 3 + 4 = 7 discloses the importance of grade 4 as the predominant pattern. Extent and not simply presence or absent of extraprostatic extension should be informed. Most tumor extent evaluations on needle biopsies are predictive of time to biochemical recurrence, however, maximum percentage of cancer in all cores was the strongest predictor. .

Rectal forceps biopsy procedure in cystic fibrosis: technical aspects and patients perspective for clinical trials feasibility.

BACKGROUND: Measurements of CFTR function in rectal biopsies ex vivo have been used for diagnosis and prognosis of Cystic Fibrosis (CF) disease. Here, we aimed to evaluate this procedure regarding: i) viability of the rectal specimens obtained by biopsy forceps for ex vivo bioelectrical and biochemical laboratory analyses; and ii) overall assessment (comfort, invasiveness, pain, sedation requirement, etc.) of the rectal forceps biopsy procedure from the patients perspective to assess its feasibility as an outcome measure in clinical trials. METHODS: We compared three bowel preparation solutions (NaCl 0.9%, glycerol 12%, mannitol), and two biopsy forceps (standard and jumbo) in 580 rectal specimens from 132 individuals (CF and non-CF). Assessment of the overall rectal biopsy procedure (obtained by biopsy forceps) by patients was carried out by telephone surveys to 75 individuals who underwent the sigmoidoscopy procedure. RESULTS: Integrity and friability of the tissue specimens correlate with their transepithelial resistance (r = -0.438 and -0.305, respectively) and are influenced by the bowel preparation solution and biopsy forceps used, being NaCl and jumbo forceps the most compatible methods with the electrophysiological analysis. The great majority of the individuals (76%) did not report major discomfort due to the short procedure time (max 15 min) and considered it relatively painless (79%). Importantly, most (88%) accept repeating it at least for one more time and 53% for more than 4 times. CONCLUSIONS: Obtaining rectal biopsies with a flexible endoscope and jumbo forceps after bowel preparation with NaCl solution is a safe procedure that can be adopted for both adults and children of any age, yielding viable specimens for CFTR bioelectrical/biochemical analyses. The procedure is well tolerated by patients, demonstrating its feasibility as an outcome measure in clinical trials.

Controversial predictors of biochemical recurrence after radical prostatectomy: a study from a Latin American (Brazilian) institution.

PURPOSE: To analyze controversial clinicopathologic predictors of biochemical recurrence after surgery: age, race, tumor extent on surgical specimen, tumor extent on needle biopsy, Gleason score 3 + 4 vs 4 + 3, and amount of extent of extraprostatic extension and positive surgical margins. MATERIALS AND METHODS: The needle biopsies and the correspondent surgical specimens were analyzed from 400 patients. Time to recurrence was analyzed with the Kaplan-Meier curves and risk of shorter time to recurrence using Cox univariate and multivariate analysis. RESULTS: Except for age, race, maximum percentage of cancer per core, and number of cores with cancer, all other variables studied were significantly predictive of time to biochemical recurrence using the Kaplan-Meier curves. In univariate analysis, except for focal extraprostatic extension, age, race, focal positive surgical margins, and maximum extent and percentage of cancer per core, all other variables were significantly predictive of shorter time to recurrence. On multivariate analysis, diffuse positive surgical margins and preoperative PSA were independent predictors. CONCLUSIONS: Young patients and non-whites were not significantly associated with time to biochemical recurrence. The time consuming tumor extent evaluation in surgical specimens seems not to add additional information to other well established predictive findings. The higher predictive value of Gleason score 4 + 3 = 7 vs 3 + 4 = 7 discloses the importance of grade 4 as the predominant pattern. Extent and not simply presence or absent of extraprostatic extension should be informed. Most tumor extent evaluations on needle biopsies are predictive of time to biochemical recurrence, however, maximum percentage of cancer in all cores was the strongest predictor.

Prostate total tumor extent versus index tumor extent--which is predictive of biochemical recurrence following radical prostatectomy?

PURPOSE: It is controversial whether tumor extent in radical prostatectomies predicts biochemical recurrence following surgery. We compared the predictive value of total tumor extent vs dominant nodule (index tumor) extent. MATERIALS AND METHODS: A mean of 32 paraffin blocks was processed from prostate surgical specimens step sectioned at 3 to 5 mm intervals from 300 patients treated with radical retropubic prostatectomy. Each transverse section was subdivided into 2 anterolateral and 2 posterolateral quadrants. Tumor extent was evaluated by a semiquantitative point count method. Dominant nodule extent was recorded as the maximal number of positive points of the largest single focus of cancer in the quadrants. Time to biochemical recurrence was analyzed by Kaplan-Meier product limit analysis. Prediction of shorter time to biochemical recurrence was determined by univariate and multivariate Cox proportional hazards models. RESULTS: Except for age and race, total and index tumor extent was significantly associated with higher preoperative prostate specific antigen, clinical stage T2, pathological stage greater than T2, positive surgical margins and higher radical prostatectomy Gleason score. Total and index tumor extent was significantly associated with time to biochemical recurrence in Kaplan-Meier estimates. Total and index tumor extent significantly predicted shorter time to biochemical recurrence on univariate analysis but only index tumor extent was an independent predictor of time to biochemical recurrence on multivariate analysis. CONCLUSIONS: The study indicates that any tumor extent estimate in surgical specimens should be related to the dominant nodule (index tumor) and not to total tumor extent.

Histological features of the nasal mucosa in hematopoietic stem cell transplantation.

BACKGROUND: Immunosuppression is the leading cause of recurrent sinus infections after hematopoietic stem cell transplant (HSCT), with increased incidence of sinusitis in patients with chronic graft versus host disease (GVHD). Histological descriptions of the oral mucosa, lung ciliary epithelium, and intestinal mucosa related to HSCT have been described. However, few have described the nasal mucosa. We, therefore, sought to elucidate the histological and ultrastructural features of the nasal mucosa in patients after HSCT to better understand the pathophysiology of the immune response. METHODS: Uncinate processes from 24 HSCT patients and 12 immunocompetent patients were subjected to histological analyses via light and transmission electron microscopy (TEM). RESULTS: TEM revealed aberrant cilia structure, altered mitochondria quantity, microvilli, and cytoplasm vacuolization. All HSCT patients with rhinosinusitis had significant loss or absence of cilia (p = 0.018). Apoptotic bodies were increased and Goblet cells decreased in nasal epithelium from patients with chronic GVHD (p = 0.04). CONCLUSION: This tissue destruction likely enhances pathogen penetration resulting in recurrent infection.

Occurrence of fat embolism after liposuction surgery with or without lipografting: an experimental study.

BACKGROUND: Liposuction in plastic surgery consists of the removal of excess fatty tissue in healthy individuals. In recent decades, this procedure has become more common worldwide. Associated with liposuction, lipografting has also been used for improving body contours, and has become known as liposculpture. Liposuction sometimes causes complications, including fat embolism, as described in the medical literature. The present study aims at ascertaining whether there is intravascular mobilization of fat after mechanical liposuction surgery and/or fat graft when carried out using one of the most common specific procedures used for liposuction, the superwet technique. METHODS: A total of 30 Wistar rats were included in this study. Before the surgery, the animals were placed in the supine position and anesthetized with thiopental for 50 to 60 minutes, as it is generally performed in clinical practice. The animals were divided in the following 3 groups. Group A, consisting of 10 rats, served as controls, and were only anesthetized. Group B consisted of 10 rats, which underwent only liposuction. Group C also comprised 10 rats, which were liposuctioned and then lipografted in the dorsal region. Blood was collected just before and again, 48 hours after the procedure. After 48 hours, the animals were killed, and the lungs, kidneys, liver, and brain were histologically examined. RESULTS: All the collected samples were analyzed microscopically with 2 different stains, namely, hematoxylin and eosin, and Sudan black. Fat particles were found in the lungs of 3 animals in group B (those that underwent only liposuction) and in 6 animals of group C (liposuction and lipografting). No fat particles were found in any organ of the control group. CONCLUSIONS: With this experiment, the authors showed that there is a risk of systemic mobilization of fat after liposuction surgery and that this risk is even higher when fat grafts are also carried out.

Various morphometric measurements of cancer extent on needle prostatic biopsies: which is predictive of pathologic stage and biochemical recurrence following radical prostatectomy?

OBJECTIVES: To find whether any particular method of measuring cancer extent on needle prostatic biopsies is superior to others in predicting pathological stage >T2 and biochemical recurrence following radical prostatectomy. MATERIALS AND METHODS: The study was based on 168 extended biopsies and the correspondent step-sectioned surgical specimens. Tumor extent was evaluated as: (1) number and percentage of cores with carcinoma; (2) total length and percentage of cancer in mm in all cores; and (3) the greatest length and percentage of cancer in a single core. RESULTS: All measurements significantly predicted stage >pT2 using logistic regression. With the exception of the greatest length and percentage of cancer in a single core, all other methods were also associated with a higher risk for biochemical recurrence (Cox method). Percentage of length of carcinoma in all cores was significantly and consistently stronger than other measures in all comparisons and combined to preoperative PSA and Gleason grade in multivariate analysis gained prediction for pathologic stage >T2 and was independent of risk of biochemical recurrence. CONCLUSIONS: Percentage of total length of carcinoma in mm in all cores of a needle biopsy had the strongest predictive positive value for stage >pT2 and risk for biochemical recurrence following radical prostatectomy. Combined with preoperative PSA and Gleason grade on biopsy may improve the predictive value for stage >pT2.

Histological features of the nasal mucosa in hematopoietic stem cell transplantation.

BACKGROUND: Immunosuppression is the leading cause of recurrent sinus infections after hematopoietic stem cell transplant (HSCT), with increased incidence of sinusitis in patients with chronic graft versus host disease (GVHD). Histological descriptions of the oral mucosa, lung ciliary epithelium, and intestinal mucosa related to HSCT have been described. However, few have described the nasal mucosa. We, therefore, sought to elucidate the histological and ultrastructural features of the nasal mucosa in patients after HSCT to better understand the pathophysiology of the immune response. METHODS: Uncinate processes from 24 HSCT patients and 12 immunocompetent patients were subjected to histological analyses via light and transmission electron microscopy (TEM). RESULTS: TEM revealed aberrant cilia structure, altered mitochondria quantity, microvilli, and cytoplasm vacuolization. All HSCT patients with rhinosinusitis had significant loss or absence of cilia (p = 0.018). Apoptotic bodies were increased and Goblet cells decreased in nasal epithelium from patients with chronic GVHD (p = 0.04). CONCLUSION: This tissue destruction likely enhances pathogen penetration resulting in recurrent infection.

Detection of epithelial apoptosis in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for patients with refractory ulcerative colitis (UC) and for familial adenomatous polyposis (FAP) with many rectal polyps. Pouchitis is one of the more frequent complications after IPAA in UC patients; however, it is rare in FAP. OBJECTIVE: Evaluate pro-apoptotic activity in endoscopically and histological normal mucosa of the ileal pouch in patients with UC and FAP. METHODS: Eighteen patients (nine with UC and nine with FAP) with J pouch after total rectocolectomy were studied. Biopsies were obtained from the mucosa of the pouch and from normal ileum. The specimens were snap-frozen and the expressions of Bax and Bcl-2 were determined by immunoblot of protein extracts and by immunohistochemistry analysis. FADD, Caspase-8, APAF-1 and Caspase-9 were evaluated by immunoprecipitation and immunoblot. RESULTS: Patients with UC had significantly higher protein levels of Bax and APAF-1, Caspase-9 than patients with FAP, but were similar to controls. The expressions of Bcl-2 and FADD, Caspase-8 were similar in the groups. Immunohistochemistry for Bax showed less intensity of immunoreactions in FAP than in UC and Controls. Bcl-2 immunostaining was similar among the groups. CONCLUSION: Patients with FAP present lower levels of pro-apoptotic proteins in all methods applied, even in the absence of clinical and endoscopic pouchitis and dysplasia in the histological analysis. These findings may explain a tendency of up-regulation of apoptosis in UC patients, resulting in higher rates of progression to pouchitis in these patients, which could correlate with mucosal atrophy that occurs in inflamed tissue. However, FAP patients had low pro-apoptotic activity in the mucosa, and it could explain the tendency to low cell turn over and presence of adenomas in this syndrome.

Evaluation of lateral lymph node metastases in advanced distal rectal cancer.

BACKGROUND/AIMS: The importance of lateral node dissection has not yet been fully investigated in advanced rectal cancer. To evaluate tumor cells in perirectal and lateral lymph nodes dissection from rectal adenocarcinomas considered free of disease by the hematoxylin-eosin test. METHODOLOGY: Fifteen patients submitted to neoadjuvant therapy and surgery for rectal adenocarcinoma with lateral node dissection were studied, retrospectively. The paraffin blocs of the nodes were analyzed with a immunohistochemical study and multiples cross section of the nodes. RESULTS: A total of 331 lymph nodes from these 15 patients were assessed, distributed as 258 perirectal nodes, 73 non perirectal, and 27 lateral nodes. The average was 22.1 lymph nodes per patient. Three patients out of 15 (20%) with histological negative lateral lymph node had occult metastasis detected by pancytokeratins AE1 and AE3. One of these cases didn't present tumor in the surgical specimen of the rectum. A case of positive lateral node identified by hematoxylin-eosin was also identified by immunohistochemical study. CONCLUSIONS: Although we had a small number of patients in the present study, lateral node dissection is important in selected cases of advanced cancer. Pancytokeratins AE1 and AE3 had a potential to improve study for detection of occult node metastasis, being helpful in rectal cancer prognosis.

Analysis of the histologic features in the differential diagnosis of intrahepatic neonatal cholestasis.

AIM: To compare the histologic features of the liver in intrahepatic neonatal cholestasis (IHNC) with infectious, genetic-endocrine-metabolic, and idiopathic etiologies. METHODS: Liver biopsies from 86 infants with IHNC were evaluated. The inclusion criteria consisted of jaundice beginning at 3 mo of age and a hepatic biopsy during the 1st year of life. The following histologic features were evaluated: cholestasis, eosinophilia, giant cells, erythropoiesis, siderosis, portal fibrosis, and the presence of a septum. RESULTS: Based on the diagnosis, patients were classified into three groups: group 1 (infectious; n=18), group 2 (genetic-endocrine-metabolic; n=18), and group 3 (idiopathic; n=50). There were no significant differences with respect to the following variables: cholestasis, eosinophilia, giant cells, siderosis, portal fibrosis, and presence of a septum. A significant difference was observed with respect to erythropoiesis, which was more severe in group 1 (Fisher's exact test, P=0.016). CONCLUSION: A significant difference was observed in IHNC of infectious etiology, in which erythropoiesis was more severe than that in genetic-endocrine-metabolic and idiopathic etiologies, whereas there were no significant differences among cholestasis, eosinophilia, giant cells, siderosis, portal fibrosis, and the presence of a septum.

Ablation of primary afferent neurons by neonatal capsaicin treatment reduces the susceptibility of the portal hypertensive gastric mucosa to ethanol-induced injury in cirrhotic rats.

Primary sensory afferent neurons modulate the hyperdynamic circulation in cirrhotic rats with portal hypertension. The stomach of cirrhotic rats is prone to damage induced by ethanol, a phenomenon associated with reduced gastric hyperemic response to acid-back diffusion. The aim of this study was to examine the impact of ablation of capsaicin-sensitive neurons and the tachykinin NK(1) receptor antagonist A5330 on the susceptibility of the portal hypertensive gastric mucosa to ethanol-induced injury and its effects on gastric cyclooxygenase (COX) and nitric oxide synthase (NOS) mRNA expression. Capsaicin was administered to neonatal, male, Wistar rats and the animals were allowed to grow. Cirrhosis was then induced by bile duct ligation in adult rats while controls had sham operation. Ethanol-induced gastric damage was assessed using ex vivo gastric chamber experiments. Gastric blood flow was measured as well as COX/NOS mRNA expression. Topical application of ethanol produced significant gastric damage in cirrhotic rats compared to controls, which was reversed in capsaicin- and A5330-treated animals. Mean arterial and portal pressure was normalized in capsaicin-treated cirrhotic rats. Capsaicin and A5330 administration restored gastric blood flow responses to topical application of ethanol followed by acid in cirrhotic rats. Differential COX and NOS mRNA expression was noted in bile duct ligated rats relative to controls. Capsaicin treatment significantly modified gastric eNOS/iNOS/COX-2 mRNA expression in cirrhotic rats. Capsaicin-sensitive neurons modulate the susceptibility of the portal hypertensive gastric mucosa to injury induced by ethanol via tachykinin NK(1) receptors and signalling of prostaglandin and NO production/release.

Gleason score as predictor of clinicopathologic findings and biochemical (PSA) progression following radical prostatectomy.

OBJECTIVE: There is evidence showing that Gleason grading of prostatic adenocarcinoma is one of the most powerful predictors of biological behavior and one of the most influential factors used to determine treatment for prostate cancer. The aim of the current study was to compare the Gleason score for needle biopsy to the Gleason score for the correspondent surgical specimen, find any possible difference in the biochemical (PSA) progression following surgery in upgraded cases, correlate Gleason score in the specimens to several clinicopathologic variables, and compare outcomes between patients with low-grade vs. high-grade Gleason and Gleason scores 3+4 vs. 4+3. MATERIALS AND METHODS: The study population consisted of 200 consecutive patients submitted to radical prostatectomy. Biochemical progression was defined as PSA > or = 0.2 ng/mL. Time to PSA progression was studied using the Kaplan-Meier product-limit analysis. RESULTS: In 47.1% of the cases, there was an exact correlation and 40.6% of cases were underestimated in the biopsies. Half of the tumors graded Gleason 6 at biopsy were Gleason score 7 at surgery. These upgraded tumors had outcomes similar to tumors with Gleason score 7 in both biopsy and surgery. There was a positive correlation of high-grade Gleason score in the surgical specimens to higher preoperative PSA, more extensive tumors, positive margins and more advanced pathologic staging. Tumors with a Gleason score > or = 7 have lower PSA progression-free survival vs. Gleason scores < 7. In this series, there was no significant difference when comparing Gleason scores of 3+4 vs. 4+3. CONCLUSIONS: The findings support the importance of Gleason grading for nomograms, which are used by clinicians to counsel individual patients and help them make important decisions regarding their disease.

Gleason score as predictor of clinicopathologic findings and biochemical (PSA) progression following radical prostatectomy

OBJECTIVE: There is evidence showing that Gleason grading of prostatic adenocarcinoma is one of the most powerful predictors of biological behavior and one of the most influential factors used to determine treatment for prostate cancer. The aim of the current study was to compare the Gleason score for needle biopsy to the Gleason score for the correspondent surgical specimen, find any possible difference in the biochemical (PSA) progression following surgery in upgraded cases, correlate Gleason score in the specimens to several clinicopathologic variables, and compare outcomes between patients with low-grade vs. high-grade Gleason and Gleason scores 3+4 vs. 4+3. MATERIALS AND METHODS: The study population consisted of 200 consecutive patients submitted to radical prostatectomy. Biochemical progression was defined as PSA > 0.2 ng/mL. Time to PSA progression was studied using the Kaplan-Meier product-limit analysis. RESULTS: In 47.1 percent of the cases, there was an exact correlation and 40.6 percent of cases were underestimated in the biopsies. Half of the tumors graded Gleason 6 at biopsy were Gleason score 7 at surgery. These upgraded tumors had outcomes similar to tumors with Gleason score 7 in both biopsy and surgery. There was a positive correlation of high-grade Gleason score in the surgical specimens to higher preoperative PSA, more extensive tumors, positive margins and more advanced pathologic staging. Tumors with a Gleason score > 7 have lower PSA progression-free survival vs. Gleason scores < 7. In this series, there was no significant difference when comparing Gleason scores of 3+4 vs. 4+3. CONCLUSIONS: The findings support the importance of Gleason grading for nomograms, which are used by clinicians to counsel individual patients and help them make important decisions regarding their disease.

Chronic liver abnormalities in sickle cell disease: a clinicopathological study in 70 living patients.

BACKGROUND AND AIM: The present study aimed to evaluate the incidence and etiology of chronic liver abnormalities in 70 living patients with sickle cell disease from the Hematology and Hemotherapy Center of the State University of Campinas. METHODS: Clinical and laboratory investigations, including liver function tests, serological tests for viral hepatitis and abdominal ultrasound, were performed in all patients. Additionally, liver biopsies were taken from 20 patients. RESULTS: Sixty-seven (96%) patients had some liver abnormality; these included abnormal liver function tests, viral hepatitis, liver ultrasonographic changes or cholelithiasis. The sickling process was the only explanation for the abnormal liver function tests or liver ultrasonographic changes in 24% of these patients. One or more defined reasons, including viral hepatitis, cholelithiasis, clinical hemosiderosis, alcoholism or diabetes, justified the liver abnormalities in 76% of the patients. Nineteen of the 20 liver biopsies presented some degree of vascular lesion; other histological findings were associated with hemosiderosis, viral hepatitis or cholestasis. CONCLUSIONS: In patients with sickle cell disease, chronic liver abnormalities are frequent and seem to be a multifactorial phenomenon, depending on overlapping factors such as cholelithiasis, viral damage, iron overload and also the primary disease itself.

Changes in intestinal motility and in the myenteric plexus in a rat model of intestinal ischemia-reperfusion.

BACKGROUND/PURPOSE: Early histologic changes induced by intestinal ischemia-reperfusion injury (IIRI) have been extensively studied using animal models. However, information regarding late effects on intestinal motility is lacking. The aim of this study was to investigate the late effects of IIRI on myenteric plexus histology and intestinal motility. MATERIALS AND METHODS: Thirty-two postweaning male rats weighing between 58 and 103 g were divided randomly into 4 groups: Control (unoperated), Sham (celiotomy), 30-minute ischemia (celiotomy and superior mesenteric artery ischemia for 30 minutes), and 45-minute ischemia (celiotomy and superior mesenteric artery ischemia for 45 minutes). Postoperative intestinal motility was assessed by weighing total fecal output for 24 hours on the 3rd, 7th, 14th, and 21st day after surgery. Segments of duodenum, jejunum, and ileum were examined at light microscopy for changes in the myenteric plexus. RESULTS: Three weeks after IIRI, the ganglion cells from the myenteric plexus appeared in light microscopy, spongy or foamy, containing many vacuoles in their cytoplasm. The neuronal nucleus became irregular, with degenerative signs. These alterations did not occur among animals from the control or sham groups. Although the animals of the 45-minute ischemia group showed a significant drop in fecal output in the 21st postoperative day, this appeared to have no effect on weight gain. CONCLUSIONS: The results suggest that intestinal ischemia-reperfusion causes late neuronal damage. These changes resulted in alterations of intestinal motility, which, within the conditions of the present study, had no repercussion on general weight gain.

Extent of prostatic atrophy in needle biopsies and serum PSA levels: is there an association?

OBJECTIVES: Prostatic atrophy is one of the most frequent benign mimics of prostate adenocarcinoma. Regardless of the cause, we hypothesized that damaged epithelial cells in the atrophic acini could be a source of the elevation of serum prostate-specific antigen (PSA). The aim of this study was to find any possible association between the extent of prostatic atrophy in needle biopsies and serum PSA level. METHODS: The study was based on 131 needle prostatic biopsies corresponding to 107 patients. The only diagnosis in all biopsies was focal prostatic atrophy without the presence of cancer, high-grade prostatic intraepithelial neoplasia, or areas suspicious for cancer. The extent of atrophy was measured in two ways: the linear extent in millimeters and the percentage of linear extent showing atrophy for each biopsy. Spearman's coefficient of rank correlation was used to evaluate the association of atrophy extent with total and free serum PSA levels. RESULTS: A positive and statistically significant correlation was found between the linear atrophy extent and the total serum PSA level (r = 0.25, P = <0.01) and free PSA level (r = 0.23, P = 0.01). A positive and statistically significant correlation was found between the percentage of the linear extent showing atrophy and the total serum PSA level (r = 0.23, P = 0.01) and free PSA level (r = 0.20, P = 0.02). CONCLUSIONS: A positive and significant association was found between the extent of atrophy and the total or free serum PSA elevation. The findings suggest that damaged epithelial cells in atrophic acini, regardless of cause, could be a source of serum PSA elevation.

Prostatic atrophy: immunohistochemical study of hypoxia induced factors.

BACKGROUND: There is evidence that chronic local ischemia may be one possible etiology of prostatic atrophy (PA). Our aim was to study the expression of hypoxia induced factors in areas of PA. DESIGN: The immunohistochemical expression of hypoxia-inducible factor-1 alpha (HIF-1) and vascular endothelial growth factor (VEGF) was studied in atrophic acini of 33 needle prostatic biopsies. Prostatic atrophy was the only diagnosis in these biopsies. For HIF-1alpha, a total of 27,158, 10,060 and 9920 nuclei were counted in atrophic acini, acini with squamous metaplasia, and acini without squamous metaplasia surrounding acute infarct, respectively. For VEGF, a total of 24,966, 9849 and 9918 nuclei were counted for the same acini. A total of 1326 nuclei were counted in acini of the needle biopsy used as negative control. The Student's test for independent samples with significance level at 5% (p<0.05) was used to compare the mean ratio (MR) of positive nuclei over total nuclei for HIF-1 and VEGF. RESULTS: For HIF-1, 108 (MR=0.004), 6877 (MR=0.68), and 6566 (MR=0.66) nuclei were positive in atrophic acini, acini with squamous metaplasia, and acini without squamous metaplasia surrounding acute infarct, respectively. There was a highly significant difference (p<0.001) between atrophic acini and acini surrounding acute infarct. For VEGF, 139 (MR=0.05), 5926 (MR=0.60), and 4948 (MR=0.50) nuclei were positive in the same acini. The difference was highly significant (p<0.001). All 1326 nuclei counted in the needle biopsy with essentially normal findings were negative for HIF-1 and VEGF. CONCLUSIONS: This study showed that prostatic atrophic acini are not on acute ischemia. However, local chronic ischemia cannot be ruled out. Experimental data showed that on chronic ischemia, the signal triggering HIF-1alpha accumulation may disappear despite continuous hypoxia suggesting that compensatory mechanisms triggered during prolonged hypoxia may be able to restore normal tissue oxygen levels.

Prostatic atrophy: evidence for a possible role of local ischemia in its pathogenesis.

Prostatic atrophy may be histologically and at ultrasound similar to adenocarcinoma causing diagnostic confusion, its frequency increases with age but the etiopathogenesis is unknown. Based on a systematic study in autopsies previously done by one of us, ischemia due to local intense arteriosclerosis seems to be a potential factor for its pathogenesis. Absent blood flow in areas of prostatic atrophy might be a further evidence for a possible role of ischemia. From a total of 298 patients biopsied and studied by gray-scale and color Doppler transrectal ultrasound in the period 1998 to 2001, 33 patients had suspicious lesions (37 hypoechoic nodules and 3 heterogeneous lesions) showing prostatic atrophy as the only diagnosis on all these biopsied lesions. Adenocarcinoma, high-grade intraepithelial neoplasia or other atypical lesions were absent in all patients. On color Doppler the suspicious areas showed absent flow in 24/40 (60%), present flow in 12/40 (30%), and increased flow in 4/40 (10%) of the lesions. Absent flow in the majority of the lesions studied may be a further evidence for a possible role of local ischemia in the etiopathogenesis of prostatic atrophy.