Kazimierz Rembiasz

Dual, time-dependent deleterious and protective effect of anandamide on the course of cerulein-induced acute pancreatitis. Role of sensory nerves

Some recent studies indicate that cannabis may induce acute pancreatitis in humans and administration of anandamide increases the severity of acute pancreatitis; whereas another study exhibits some therapeutic effects in acute pancreatitis. Aim of the present study was to discover what is the reason for these opposite confusing results and to determine the role of sensory nerves in this effect. Acute pancreatitis was induced in rats by cerulein. Anandamide, an endogenous cannabinoid, was administered i.p. (1.5 micromol/kg) before or 2 h after cerulein administration. Stimulation of sensory nerves was performed by capsaicin (0.5 mg/kg s.c.). In rats treated with combination of anandamide plus capsaicin, capsaicin was given 10 min after each dose of anandamide. After the last injection of cerulein or 4 h later, the study was terminated. In our study we observed that stimulation of sensory nerves by capsaicin, before administration of cerulein, reduced the severity of acute pancreatitis. Anandamide, administered alone before cerulein, increased pancreatic damage in acute pancreatitis. Anandamide administered in combination with capsaicin, before cerulein, abolished the capsaicin-induced protective effect on the pancreas. Opposite effects were observed when capsaicin and anandamide were administered after injection of cerulein. Capsaicin increased the severity of acute pancreatitis, whereas anandamide reduced pancreatic damage and reversed the deleterious effect of capsaicin. We conclude that the effect of anandamide on the severity of acute pancreatitis depends on the phase of this disease. Administration of anandamide, before induction of pancreatitis, aggravates pancreatic damage; whereas anandamide administered after induction of pancreatitis, reduces the severity of acute pancreatitis. Sensory nerves are involved in the mechanism of this biphasic effect of anandamide.

Gene expression of ornithine decarboxylase, cyclooxygenase-2, and gastrin in atrophic gastric mucosa infected with Helicobacter pylori before and after eradication therapy

H. pylori (Hp) -induced atrophic gastritis is a well-known risk factor for the development of gastric cancer. Whether Hp eradication can prevent or retard the progress of atrophy and metaplasia has been the topic of numerous studies but the subject remains controversial. Recently, the increased expression of ornithine decarboxylase (ODC), gastrin and cyclooxygenase (COX)-2 has been shown to be increased in premalignant lesions in gastric mucosa and to play an essential role in the malignant transformation. The aim of the study is to assess the effect of eradication therapy on atrophic gastritis and analyze the gene expression for ODC, COX-2 and gastrin in gastric mucosa after succesful eradication in patients with atrophic gastritis. Twenty patients with chronic atrophic gastritis including both corpus and antrum of the stomach were included in this study. Four antral mucosal biopsy specimens were obtained from antrum and four from corpus. The histopathologic evaluation of gastritis was based on Sydney classification of gastritis. All patients were Hp positive based on the [13C] urea breath test (UBT) and the presence of anti-Hp IgG and anti-CagA-antibodies detected by ELISA. The patients were then eradicated with triple therapy consiting of omeprazol (2 × 20 mg), amoxycillin (2 × 1 g) and clarithromycin (2 × 500 mg) for seven days and vitamin C 1 g/day for three months. In gastric mucosal samples obtained from the antrum and corpus before and after eradication, the mRNA expression for ODC, COX-2, and gastrin was assessed by reverse-transcription polymerase chain reaction (RT-PCR). In all patients the gastric secretory analysis was performed by measuring gastric acid output and serum gastrin levels. After triple therapy the successful eradication assessed by UBT was observed in 95% of patients. In 45% of patients the infection with CagA-positive Hp strain was observed. Three months after eradication a significant reduction in the gastric activity (neutrophilic infiltrate) and severity (mononuclear infiltrate) of gastritis was observed. The atrophy score improved in both antrum and corpus after eradication. The expression of COX-2 and ODC was significantly up-regulated in the gastric mucosa of patients with atrophic gastritis and significantly reduced after eradication therapy. In all successfully eradicated patients with atrophic gastritis a significant increase in gastric acid secretion and decrease in serum gastrin were observed. We conclude that: (1) Hp eradication leads to the decrease in ODC and COX-2 gene expression in the gastric mucosa, and this may be relevant for the prevention of the Hp-associated gastric carcinogenesis. (2) gastric atrophy ameliorates upon successful Hp eradication therapy.

Effects of cyclooxygenase-2 inhibition on serum and tumor gastrins and expression of apoptosis-related proteins in colorectal cancer

The objective of the present study was to determine the influence of cyclooxygenase-2 (COX-2) inhibition by Celecoxib (CLX) in humans with distal colorectal adenocarcinoma (CRC) on serum and tumor levels of progastrin and gastrin and serum levels of proinflammatory cytokines (IL-8, TNF-α). In addition, the effects of this CLX treatment on tumor and adjacent mucosa expression of gastrin, its receptors (CCK2), and COX-1 and COX-2, as well as protein expression of the active form of nuclear factor κ B (NFκ B) and the apoptotic-related proteins Bcl-2 and survivin, have been examined. Ten distal CRC patients were examined twice, once before and then after 14-day treatment with CLX (200 mg bid). Large biopsy samples were taken from the tumor and intact mucosa 10 cm above the tumor. For comparison, 20 age- and sex-matched healthy controls were enrolled and treated with CLX as CRC patients. Serum levels of IL-8 and TNF-α were measured by enzyme-linked immunosorbent assay, and serum levels of amidated gastrins and progastrin, by specific radioimmunoassay. The gene or protein expressions of progastrin, gastrin, CCK2, COX-1, COX-2, Bcl-2, and survivin as well as NFκ B were determined by RT-PCR or Western blot in biopsy samples of tumor and intact mucosa of CRC patients. Serum IL-8 and TNF-α values were severalfold higher in CRC patients than in controls. The increase in serum proinflammatory cytokines was accompanied by increased expression of the active form of NFκ B. Serum progastrin levels were also found to be significantly higher in CRC than in controls. Treatment of CRC with CLX resulted in a significant decrease in serum levels of progastrin and this was accompanied by an increment in tumor expression of COX-2 with a concomitant reduction in gastrin, Bcl-2, survivin, and NFκ B expression. We conclude that (1) distal CRC patients show significantly higher serum progastrin levels than matched healthy controls, confirming that this hormone may be implicated in rectal carcinogenesis; (2) CRC patients exhibit significantly higher serum levels of IL-8 and TNF-α than healthy controls, probably reflecting more widespread inflammatory reaction in the colonic mucosa in CRC; (3) gastrin, COX-2, Bcl-2, survivin, and NFκ B were overexpressed in CRC tumor compared to intact mucosa, but treatment with CLX significantly reduced serum levels of progastrin and IL-8 and TNF-α, which could mediate the up-regulation of COX-2 in CRC; and (4) CLX also enhanced expression of COX-2, while inhibiting the expression of gastrin, Bcl-2, survivin, and NFκ B, suggesting that COX-2 inhibition might be useful in chemoprevention against CRC, possibly due to suppression of the antiapoptotic proteins and reduction in progastrin-induced and NFκ B-promoted tumor growth.

Cystic adrenal lesions - analysis of indications and results of treatment.

UNLABELLED Cysts are a rare pathology of adrenal glands. As the development of new diagnostic techniques takes place, the occurrence of adrenal cystic lesions has been rapidly increasing. The majority of them are solid adrenal lesions, but localized fluid collections are also more frequently diagnosed. In case of solid adrenal lesions, there are straight indications for surgery, but on the other hand there are no clear guidelines and recommendations in case of adrenal cysts. The aim of the study was to analyze surgical methods and evaluate treatment effects in patients who were qualified for laparoscopic adrenalectomy due to adrenal cystic lesions. METARIAL AND METHODS: Identical criteria were used to qualify patients with solid and cystic lesions of the adrenal gland for surgery. Out of the whole number of 345 patients who underwent laparoscopic surgery for adrenal tumors, 28 had adrenal cysts. 16 of them (57%) were women and 12 (43%) men. The average age of the studied group was 46.4 years (25-62 years). The average cyst diameter in CT was 5.32 cm (1.1-10 cm). Most of the lesions were hormonally inactive (22 patients), but in 6 cases increased level of adrenal hormones was observed. RESULTS Pathological analysis revealed 4 (14%) pheochromocytomas and 2 (7%) dermoid cysts. In case of 22 (79%) patients, the postoperative material was profiled by pathologists as insignificant according to potential neoplasmatic transformation risk: 5 (17.5%) - endothelial vascular cysts, 3 (11%) endothelial lymphatic cysts, 7 (25.5%) pseudocysts, 3 (11%) simple cysts, 2 (7%) bronchogenic cysts, 1 (3.5%) - cortical adenoma and 1 (3.5%) cyst was of myelolipoma type. CONCLUSIONS Based on the performed research and previous experience in treating patients with adrenal lesions we can conclude that application of the same evaluating algorithm for both cystic and solid lesions is valid.

Ghrelin and gastrin in advanced gastric cancer before and after gastrectomy

AIM To investigate plasma ghrelin, gastrin and growth hormone secretagogue receptor (GHS-R) expression in advanced gastric cancer (GC) before and after resection. METHODS Seventy subjects in whom endoscopy of the upper gastrointestinal tract was performed in the Department of General Surgery at Cracow University during the past decade: (1) 25 patients with GC associated with Helicobacter pylori (H. pylori) infection; (2) 10 patients with GC 4-5 years after (total or subtotal) gastrectomy; (3) 25 healthy H. pylori-negative controls, matched by age and BMI to the above two groups; and (4) 10 GC patients 4-5 years after total gastrectomy. Ghrelin and gastrin plasma concentrations were measured by specific radioimmunoassay under fasting conditions and postprandially at 60 and 90 min after ingestion of a mixed meal. GHS-R expression was examined in biopsy samples from intact healthy mucosa and GC tissue using semi-quantitative reverse transcription-polymerase chain reaction. RESULTS In healthy controls, fasting plasma ghrelin levels were significantly elevated and declined markedly at 60 and 90 min after a mixed meal. The concomitant enhanced ghrelin, GHS-R and gastrin expression in GC tissue over that recorded in intact mucosa, and the marked rise in plasma gastrin in these subjects under fasting conditions indicate the role of these hormonal factors in GC formation. Fasting plasma levels and postprandial response of ghrelin and gastrin appear to be inversely correlated in healthy subjects. Feeding in the controls resulted in a significant fall in plasma ghrelin with a subsequent rise in plasma gastrin, but in H. pylori-positive GC patients submitted to total or distal gastrectomy, feeding failed to affect significantly the fall in plasma ghrelin that was recorded in these patients before surgery. Fasting ghrelin concentrations were significantly lower in patients 4-5 years after total gastrectomy compared to those in healthy controls and to these in GC patients before surgery. CONCLUSION Elevated plasma gastrin and suppression of fasting ghrelin in patients with GC suggest the existence of a close relationship between these two hormones in gastric carcinogenesis.

Laparosocopic Appendectomy, Cost-Effectiveness of Three Different Techniques Used to Close the Appendix Stump.

UNLABELLED It is generally agreed that laparoscopic appendectomy is a valuable operative method. The aim of the study was to evaluate cost-effectiveness of three different techniques used to close the appendix stump. MATERIAL AND METHODS We conducted a retrospective study that compared three groups of patients who were operated on laparoscopically for acute appendicitis in 2013 at our institution. We used an endoscopic clip to close the appendix stump in the first group (n=20), endoscopic stapler was applied in the second group (n=20), and in the third group of patients the appendix base was closed with a laparoscopic suture (n=20). These groups were matched by age, sex and BMI. RESULTS The average operative cost was the highest in the second group. Cost of the laparoscopic appendectomy with the application of the endoscopic clip was significantly lower (first group) and comparable to the third group. Observed differences in total hospitalization costs were associated only with the chosen appendix stump closure technique. CONCLUSIONS Clip closure of the appendix base is an easy and cost-effective procedure. The laparoscopic suture technique is the cheapest but technically demanding. According to our experience endoscopic stapler may be useful in some cases, although it is the most expensive method.

Enhanced recovery (ERAS) protocol in patients undergoing laparoscopic total gastrectomy

Introduction Laparoscopic technique combined with the ERAS (Enhanced Recovery after Surgery) protocol enables a shorter hospital stay and a lower complication rate. Although it has been widely used in many patients undergoing elective abdominal surgery, especially in patients with colorectal cancer, there are only a few papers describing laparoscopic total gastrectomy and the enhanced recovery protocol in patients with gastric cancer. Minimally invasive gastrectomy is still an uncommon procedure, mostly because of its difficulty. Aim To present the preliminary results of treatment of patients with gastric neoplasms who underwent laparoscopic gastrectomy D2 with perioperative care according to ERAS principles. Material and methods Eleven patients (5 male and 6 female, age 52–77 years) underwent laparoscopic D2 gastrectomy with intracorporeal esophagojejunal anastomosis. In all patients the ERAS protocol was implemented. We analyzed operation time, complications and hospital stay. Additionally we focused on operative technique as well as the perioperative care protocol. Results The mean duration of the procedure was 245 min. There was 1 conversion due to unclear tumor infiltration. Mean hospital stay was 4.6 days. One postoperative complication (central venous catheter sepsis) was reported. Histological analysis confirmed the tentative diagnosis (R0 resection) in 10/11 patients. There were no readmissions. Conclusions Laparoscopic gastrectomy is a valuable alternative to the classical approach and combined with the ERAS protocol can result in reduced hospital stay. However, due to the small group of patients it is difficult to adequately assess the incidence of early and late complications of the laparoscopic procedures; therefore further research is needed.

Multifocal atrophic gastritis: pathogenesis and therapeutic implications.

Objective This study, carried out on 51 patients with multifocal atrophic gastritis (MAG) and 92 age and sex-matched dyspeptic controls, was designed to examine both exocrine (gastric acid) and endocrine (gastrin) gastric secretion before and after therapeutic intervention including Helicobacter pylori eradication and vitamin C treatment. Methods Fasting and gastrin-releasing peptide-induced gastric acid secretion, serum levels of gastrin and proinflammatory (IL-1&bgr;, IL-8, TNF-&agr;) as well as gastric mucosal gene expression of ornithine decarboxylase (ODC), cyclooxygenase 2 (COX-2) and growth factors (epidermal growth factor and transforming growth factor alpha) were determined before and after the eradication of Helicobacter pylori and therapy with large doses (1 g/d) of vitamin C for 3 months. Results The H. pylori eradication, assessed by 13C-urea breath test, and vitamin C therapy failed to reverse the histological atrophy of the gastric mucosa but improved significantly the functional status of the atrophied mucosa, especially its exocrine and endocrine secretory activities, attenuated the expression of premalignant markers such as ODC and COX-2, raised the production of growth factors and diminished the release of proinflammatory cytokines. Conclusions These results indicate that MAG may be considered as an environmental disease of the gastric mucosa, whose functional status can be improved by the eradication of H. pylori combined with antioxidant therapy with large doses of vitamin C.

Percutaneous ultrasound-guided drainage of the biliary tree in palliative treatment of mechanical jaundice: 17 years of experience.

Introduction Advanced malignant tumours involving the head of the pancreas, gallbladder or extrahepatic bile ducts usually lead to the development of cholestasis. In such cases improvement of the quality of life of patients can be achieved with the decompression of jaundice. Endoscopic implantation of self-expanding or (seldom) rigid plastic stents into the biliary tree constitutes the most common technique allowing for restoration of bile duct patency. In some patients however the use of such a procedure is technically impossible. In this particular group percutaneous drainage of the biliary tree can constitute the only method of management. Aim Presentation of our experience with the use of percutaneous ultrasound-guided drainage of the biliary tree in patients with mechanical jaundice resulting from malignant tumours. Material and methods There were 852 patients with mechanical jaundice resulting from malignant neoplasms treated in the 2nd Chair of Surgery of Jagiellonian University Medical College from January 1994 to December 2010. In 199 of them jaundice was decompressed by means of open – radical or palliative – surgical operations. In 539 patients endoscopic treatment was implemented while in 114 of them percutaneous ultrasound-guided drainage was performed. Results In 5 patients percutaneous drainage was introduced to prepare them for radical surgical treatment, while in the remaining 109 it constituted the definitive way of management. The average hospitalization time for women was 6.5 days (range: 1-22 days) and proved to be twice as short as in men – 12.2 days (range: 1-38 days). The duration of percutaneous drainage prior to surgical treatment averaged 7.2 days (range: 6-10 days). Mean volume of the bile drained during the first day was 370 ml (range: 10-1300 ml), increased to 450 ml (range: 100-1150 ml) during the second day and reached 780 ml (range: 80-1600 ml) during the third day. Mean bilirubin level before the drainage was 320-23 µmol/l (range: 658-130.7 µmol/l) and decreased by half before discharge or before the operation, reaching on average 181.87 µmol/l (range: 14.5-343 µmol/l). Conclusions Complications of the percutaneous ultrasound-guided technique were found sporadically and resulted from leakage of the bile into the peritoneum.

Laparoscopic Transperitoneal Lateral Adrenalectomy for Large Adrenal Tumors.

Background: Laparoscopic adrenalectomy is the gold standard for treatment of benign adrenal lesions. Tumor size is a factor that might influence decision-making concerning the use of laparoscopic approach. The aim of this study was to analyze the results of adrenalectomy for tumors ≥6 cm in diameter. Methods: Two groups of patients were analyzed: first group comprised 441 patients with tumors <6 cm in diameter and second group consisted of 89 patients with tumors ≥6 cm. Both groups were compared with regard to the duration of surgery, intraoperative blood loss, conversion and complications rate. Results: Median duration of surgery in groups 1 and 2 amounted to 86.6 and 111.9 min (p < 0.0001), respectively. Median intraoperative blood loss in groups 1 and 2 was 56.5 and 172.8 ml (p < 0.0001), respectively. There was a linear relationship between tumor size and the duration of surgery, and between tumor size and intraoperative blood loss (p < 0.0001). There were 2 (0.5%) and 6 (6.7%) conversions in groups 1 and 2, respectively. There were 41 (9.3%) and 14 (15.7%) complications in groups 1 and 2 (p = 0.0692), respectively. Conclusions: Laparoscopic adrenalectomy of tumors ≥6 cm is more difficult, but it can be regarded safe and beneficial for patients.