Károly Szentpáli

The role of the glucocorticoid-dependent mechanism in the progression of sodium taurocholate-induced acute pancreatitis in the rat.

The effects of glucocorticoids on acute pancreatitis (AP) have remained contradictory. The aim of this study was to investigate the time courses of the effects of the exogenous glucocorticoid agonists dexamethasone (DEX) and hydrocortisone (HYD) and a glucocorticoid antagonist (RU-38486) and to characterize the local and systemic responses in AP in rats. The glucocorticoid antagonist and agonists were administered just before AP induction. Serum amylase activity determinations, IL-6 bioassays, pancreatic weight/body weight ratio measurements, and survival analysis were performed. Liver and lung injuries were assessed via neutrophil leukocyte infiltration in myeloperoxidase (MPO) assays, tissue adenosine triphosphate (ATP) level determinations, and histology. In the glucocorticoid agonist groups, the survival rate increased, while the serum amylase level, the IL-6 activity, and the pancreatic weight/body weight ratio decreased significantly as compared with the control and RU-treated groups. AP resulted in significant decreases in tissue ATP levels in both the liver and the lung. In the DEX- or HYD-treated groups, the liver ATP levels were significantly elevated, while both the liver and the lung MPO levels were attenuated as compared with the AP and RU-treated groups. These results suggest that glucocorticoids may play important roles in mitigating the progression of the inflammatory reaction during the early phases of AP.

Importance of Sentinel Lymph Node Biopsy in Surgical Therapy of in situ Breast Cancer

The aim of this retrospective study was to determine the rate of sentinel lymph node (SLN) positivity in patients with a final diagnosis of ductal in situ cancer (DCIS) of the breast. Between October 2002 and January 2007, 57 patients with DCIS underwent wide excision after radio-guided lesion localization; 53 of them (53/57, 93%) had participated in simultaneous SLN mapping. SLNs were analysed by 250-micron step-sectioning with haematoxylin and eosin staining and immunohistochemical evaluation. The histologic investigation verified pure breast DCIS in 44 cases (44/57, 77.2%), DCIS with microinvasion in eight cases (8/57, 14%) and lobular in situ breast cancer in five cases (5/57, 8.8%). SLNs were identified in 49 cases (49/53, 92.5%) and removed in 48 cases (48/53, 90.6%), i.e. an average of 1.6 SLNs per patient. In four patients (4/53, 7.6%), the SLN biopsy was unsuccessful because of the failure of the radiocolloid substance to migrate. In these cases, axillary sampling was performed. In one case (1/53, 1.9%), only a parasternal SLN was detected; this was not removed. Histologic analysis of the SLNs and the axillary lymph nodes with haematoxylin and eosin or cytokeratin immunohistochemistry did not prove the presence of metastases. The international data and our present results suggest that routine SLN biopsy is not to be recommended in pure DCIS cases. If the final histology verifies an invasive or microinvasive tumour, or if mastectomy is to be performed, SLN mapping is suggested.

Microcirculatory changes in the canine oesophageal mucosa during experimental reflux oesophagitis: Comparison of the effects of acid and bile

Background: The response of the oesophageal microcirculation to luminal damaging agents may play an important role in reflux‐induced mucosal injury. We characterized the microcirculatory consequences of exposure to bile with or without hydrochloric acid, and determined the changes in the constitutive nitric oxide synthase and inducible nitric oxide synthase activities in a canine model of acute reflux oesophagitis. Methods: Group 1 served as a saline‐treated control, while groups 2–4 were exposed for 3 h to bile alone, to hydrochloric acid, or to bile + hydrochloric acid, respectively. The mucosal microcirculation was observed continuously by means of intravital videomicroscopy with an orthogonal polarization spectral imaging technique. Myeloperoxidase, constitutive and inducible nitric oxide synthase activities were measured via tissue biopsies, while the degree of mucosal damage was evaluated histologically. Results: Bile evoked deep tissue damage and leucocyte accumulation in the mucosa and muscle layer. The capillary red blood cell velocity and the relative vessel area increased significantly (P < 0.05). The constitutive NO synthase activity was decreased, and the inducible NO synthase activity was increased significantly. In the hydrochloric acid‐treated group the functional capillary density decreased, the mucosal damage was less severe, the constitutive NO synthase activity did not change, whereas the inducible NO synthase activity was increased significantly. The constitutive NO synthase activity did not change after the bile + hydrochloric acid treatment either. Conclusion: Reflux components induce characteristic microcirculatory alterations. The structural damage and leucocyte invasion are accompanied by bile‐induced constitutive NO synthase inhibition when hydrochloric acid production is suppressed.

Endoscopic intubation with conventional plastic stents: a safe and cost-effective palliation for inoperable esophageal cancer.

Access to expensive equipment and costly self-expanding metal endoprostheses is limited in some regions where unresectable esophageal cancer is not infrequent. The aim of this study was to review the long-term results of palliation of malignant esophageal obstruction using low-priced conventional plastic stents. One hundred sixty-nine patients with dysphagia due to inoperable esophageal cancer underwent esophageal intubation under endoscopic control alone, without general anesthesia, by the pulsion method. Stents mounted on their delivery device were inserted over an endoscopically placed guide wire. Improvement in swallowing was seen in all patients. Dysphagia scores have improved from 3.64 ± 0.21 to 1.08 ± 0.17. Major early procedure-related morbidity was high at 0.6% with one intramural perforation (no transmural perforation at all). Minimal mucosal bleeding was seen with 72 cases (42.6%). Procedure-related mortality was 0%. Late procedure-related complications requiring further endoscopic procedures occurred in 8.2% (tube occlusion: 5.3%, tube dislocation: 2.9%). Our 7-day mortality was 0% and 5 patients died within 30 days, usually from the disease itself. Those surviving the procedure (more than 7 days) had a mean survival of 209 days. Esophageal plastic stents can be accurately and safely placed under direct endoscopic control with lower costs. Therefore, endoscopic intubation remains a useful palliative treatment for patients with unresectable carcinoma of the esophagus.

Bile-induced adenosine triphosphate depletion and mucosal damage during reflux esophagitis

Background: This study was designed to investigate the role of bile in a large animal model of acute esophageal reflux disease. Methods: An agar electrode was used to measure the transmucosal potential difference of the esophagus in anaesthetized dogs. The vascular permeability index and the epithelial permeability index of the mucosa were evaluated by means of the Evans blue and the sodium-fluorescein clearance method, respectively. The tissue adenosine triphosphate (ATP) level and the myeloperoxidase activity were determined from tissue biopsies, while the degree of mucosal damage was evaluated histologically on a grade 0-100 scale. Group 1 (n = 8) served as saline-treated control; groups 2 (n = 8), 3 (n = 5) and 4 (n = 5) were exposed for 4 h to canine bile alone, to hydrochloric acid + bile, or to hydrochloric acid alone, respectively. Results: In Groups 2, 3 and 4 the degree of mucosal damage was significantly increased, and a 4-fold elevation in myeloperoxidase activity was observed. The transmucosal potential difference was decreased significantly below the control level, while the vascular and epithelial permeability indices were significantly increased compared with the control values. Bile, but not hydrochloric acid, evoked a significant (40%) decrease in the ATP level of the esophageal tissue. Conclusions: We propose that mucosal dysfunction, structural damage and leukocyte invasion during hydrochloric acid-induced esophageal injury are exacerbated by bile-induced changes in tissue ATP concentrations during experimental esophageal reflux disease.BACKGROUND This study was designed to investigate the role of bile in a large animal model of acute esophageal reflux disease. METHODS An agar electrode was used to measure the transmucosal potential difference of the esophagus in anaesthetized dogs. The vascular permeability index and the epithelial permeability index of the mucosa were evaluated by means of the Evans blue and the sodium-fluorescein clearance method, respectively. The tissue adenosine triphosphate (ATP) level and the myeloperoxidase activity were determined from tissue biopsies, while the degree of mucosal damage was evaluated histologically on a grade 0-100 scale. Group 1 (n = 8) served as saline-treated control; groups 2 (n = 8), 3 (n = 5) and 4 (n = 5) were exposed for 4 h to canine bile alone, to hydrochloric acid + bile, or to hydrochloric acid alone, respectively. RESULTS In Groups 2, 3 and 4 the degree of mucosal damage was significantly increased, and a 4-fold elevation in myeloperoxidase activity was observed. The transmucosal potential difference was decreased significantly below the control level, while the vascular and epithelial permeability indices were significantly increased compared with the control values. Bile, but not hydrochloric acid, evoked a significant (40%) decrease in the ATP level of the esophageal tissue. CONCLUSIONS We propose that mucosal dysfunction, structural damage and leukocyte invasion during hydrochloric acid-induced esophageal injury are exacerbated by bile-induced changes in tissue ATP concentrations during experimental esophageal reflux disease.

Esophageal cancer complicated with azygos continuation of the inferior vena cava

Neoadjuvant (preoperative) therapy and combined modality therapy have become focuses of interest in the effort to prolong survival and to reduce recurrence rates in patients with esophageal cancer. Staging of the tumor is a critical step in establishing which therapeutic option is appropriate. Once surgical management is advocated, adequate medical imaging is crucial in determining individual anatomical variations. In this communication we report a case of a patient with azygos continuation who underwent chemoradiotherapy with successful downstaging of tumor status from T3-4 to T0 and a nodal status from N1 to N0 as evaluated by medical imaging and who then proceeded to curative surgical resection. This case highlights the potential ability of radiological techniques to confirm both anatomical variations and responses to neoadjuvant therapy.

Esophageal ATP synthase and keratinocyte growth factor gene expression changes after acid and bile-induced mucosal damage

Abstract.Objective and design: Intramural gene expression changes may be critically involved in tissue damage, defense and repair after esophageal regurgitation. The aims were to characterize the consequences of short-term exposure to luminal bile, acid, or bile mixed with acid on the β-ATPase, keratinocyte growth factor 1 (KGF-1) and KGF receptor (KGF-R) expressions within the mucosa and the muscle layer in a large animal model.Materials and subjects: Esophageal segments of anesthetized dogs were exposed to saline (n = 3), diluted canine bile (n = 6), hydrochloric acid (n = 5) or bile + hydrochloric acid (n = 5), and tissue biopsies were taken at the end of the 180-min observation period. Semiquantitative reverse transcriptase polymerase chain reactions were carried out and the degree of histological damage was evaluated on the 0–16-grade Geisinger scoring scale.Results: Acid exposure was followed by a significant decrease in the level of β-ATPase expression in the mucosa, and parallel increases in KGF-1 and KGF-R expression. Corresponding changes in the muscle layer were not significant. Bile alone evoked more severe tissue damage, with significantly decreased β-ATPase levels in both the mucosa and the muscle, whereas the KGF-1 expression did not change significantly. The bile + acid treatment induced an intermediate state, with significant β-ATPase transcription level decreases in both layers, while the mucosal KGF-1 expression was lower than that following acid treatment alone.Conclusions: The acid-induced transcriptional level downregulation of mucosal β-ATPase gene expression in the smooth muscle layer was exacerbated by bile, but the concomitant KGF and KGF-R gene expression changes may indicate the start of a consecutive repair process.

Efficacy and drawbacks of neoadjuvant chemoradiotherapy in squamous cell carcinoma of the thoracic esophagus.

BACKGROUND/AIMS Neoadjuvant chemoradiotherapy (CRT) is widely applied in locally advanced esophageal tumors to improve resectability and local tumor control. In this study, we retrospectively analyzed the perioperative course of patients who underwent esophagectomy or esophagectomy following CRT. METHODOLOGY Forty one patients were admitted with non-advanced disease (T1-2, N0), and primary resection was performed. Additional 21 patients received neoadjuvant CRT because of locally advanced, T2-4, N0-1 disease. To investigate predictive factors for responsiveness to CRT, we determined the p53, p21 and Ki67 oncogene expressions in the biopsy samples from the CRT patients. RESULTS Following primary esophagectomy and esophagogastrostomy, the postoperative course was in most cases uneventful. Anastomotic leaks developed in 3 of the 41 cases (7.3%), and postoperative death in 1 case (2.4%). In response to CRT, significant down-staging was observed in 11 of the 21 patients (58%); in these cases esophagectomy was performed. However, in this group the rates of anastomotic leak (2 patients) and postoperative death (2 patients) were higher than in the first group (18% each). CONCLUSIONS Preoperative CRT is a good option for patients with locally advanced tumors, when primary R0 resection is hopeless. However, the rate and risk of postoperative complications are higher than after primary resection of non-advanced tumors.

Medical and Surgical Evaluation of Barrett’s Esophagus and Barrett’s Cancer

Objective: This study reviews the development of Barrett’s esophagus in patients with gastroesophageal reflux disease. Here we evaluate the progression of the disorder into esophageal adenocarcinoma in patients with Barrett’s esophagus under treatment, and the effectiveness of current medical or surgical therapy regarding mucosal regression or progression. Methods: A MEDLINE search was performed to analyze data published in English between 1980 and 2002. Results: Despite successful surgery, Barrett’s esophagus developed in 5.8–18.9% of patients with gastroesophageal reflux disease. The rate was higher in patients receiving medical therapy (11.1–33.8%). In long-term follow-up studies the mucosal changes (length of Barrett’s mucosa, histological malformations) were reported to progress in 13.8–40.7% of patients after medical therapy and in 3.4–15.3% after surgical intervention. The risk of developing esophageal carcinoma on grounds of Barrett’s esophagus was 1.3–4.6 and 0–8.1% in patients receiving medical and surgical treatment, respectively. In the published studies, the rate of complete regression of Barrett’s esophagus following surgery varied between 0 and 26.4%. Discussion: Long-term follow-up studies confirm the histological progression in Barrett’s esophagus. Therefore, the current medical or surgical therapies do not prevent malignant transformation of the columnar epithelial lining of the esophagus. However, their combination may delay progression and cancer formation.