Clinical significance of activin A and myostatin in patients with pancreatic adenocarcinoma and progressive weight loss.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by progressive weight loss and nutritional deterioration. Several cytokines, such as activin A and myostatin, ligands of the transforming growth factor-ß superfamily, have been shown to influence the pathogenesis of muscle wasting and tumor progression. The aim of our study was to assess the clinical significance of these cytokines in patients with different stages of PDAC. The study included 93 patients: 73 with newly diagnosed PDAC and 20 healthy volunteers as the control group. PDAC patients included 42 diagnosed with non-metastatic pancreatic cancer (stage I - III) and 31 patients with metastatic cancer (stage IV). The peripheral venous blood samples were collected from each patients at the time of cancer diagnosis and plasma concentrations of activin A and myostatin have been measured with an enzyme-linked immunoassay. Forty five patients (61.6%) presented weight loss > 5%, including 24 (57.1%) with stage I - II and 21 (67.7%) with metastatic PDAC (P > 0.05). Plasma levels of activing A were significantly higher in metastatic PDAC patients compared with stage I - III PDAC patients and control group (P < 0.01). The relationship between higher activin A levels and weight loss was also observed (P < 0.05). On the other hand, myostatin was not associated with weight loss in analysed group of patients. In conclusion, the current study demonstrates that high activin A plasma levels at the time of PDAC diagnosis is associated with unintentional weight loss and may be an useful biomarker for identifying patients with metastatic disease. However, further prospective studies are needed to fully explore the clinical significance of myostatin in pathogenesis of progressive weight loss in PDAC patients.

The assessment of serum concentration of adiponectin, leptin and serum carbohydrate antigen-19.9 in patients with pancreatic cancer and chronic pancreatitis.

UNLABELLED: Pancreatic cancer and chronic pancreatitis are still significant diagnostic and clinical problems. The clinical impact of preoperative serum carbohydrate antygen 19-9 (CA 19-9) levels have been disscussed. The aim of this study was a comparative analysis of the concentrations in serum of adipocytokines: adiponectin and leptin and CA 19-9 in patients with pancreatic cancer (PC), chronic pancreatitis (CP) and control group (CG). The study was performed in a group of 90 patients. Group 1 consisted of 30 patients with PC, group 2 consisted of 30 patients with CP. There was no coincidence of pancreatic cancer in CP group. Group 3 (CG) consisted of 30 persons and were recruited among patients operated for cholelithiasis. The serum samples were taken from patients and the concentration of adiponectin, leptin, CA 19-9 and CEA were evaluated. The revealed concentrations levels of the adiponectin were significantly higher in the PC serum samples compared to the CP and CG. There was no significant correlation between increased adiponectin concentration and body fat mass in the PC group. The concentration of leptin was significantly lower in CP serum samples compared to PC and CG. The concentration of leptin was similar in the PC and CG. The concentration of leptin was mainly dependent on body fat mass and fat distribution. Additionally, measurement of waist circumference and body composition was recorded using bioelectrical impedance analysis. CONCLUSIONS: significantly higher concentration levels of adiponectin in the PC group, independent of body fat mass, may play a potential role as a new tumor marker in PC and might be useful in the differential diagnosis between PC and CP, but this statement needs further investigation. To our knowledge, this was the first study evaluating not only body mass index but also the content and distribution of body fat in patients with PC and CP.

Concentrations and activities of metalloproteinases 2 and 9 and their inhibitors (TIMPS) in chronic pancreatitis and pancreatic adenocarcinoma.

UNLABELLED: Pancreatic cancer (PC) and chronic pancreatitis (CP) are still significant problems. The aim of this study was a comparative analysis of the activity and concentrations of matrix metalloproteinases 2 and 9 and the concentrations of their tissue inhibitors (TIMP 1 and 2) in the PC compared to CP tissue homogenates. The study was performed in a group of 63 patients with pancreatic cancer or chronic pancreatitis selected for resection procedures. Group 1 consisted of 31 patients with CP, group 2 consisted of 32 patients with PC. There was no coincidence of pancreatic cancer in CP group. The pancreatic tumor samples have been properly prepared in order to perform electrophoresis and immunoassay testing. The activity of MMPs and the concentrations of MMPs and TIMPs were evaluated. RESULTS: the revealed activities of gelatinases and concentrations levels of the gelatinases and their inhibitors were significantly higher in the PC tissue samples compared to CP. In both groups, higher concentrations of MMP9 compared to MMP2 and TIMP2 compared to TIMP1 were shown. High potential for tumor invasiveness demonstrated by the formation of lymph node metastases was characterized by the higher concentrations of MMP9 and TIMP2. However, in the case of infiltration of the nerve fibers, a decrease in the concentration of MMP2 was found. CONCLUSIONS: gelatinases and their inhibitors play important role in the pathogenesis of the CP as well as PC. The activity and concentration of gelatinases and the concentration of their inhibitors were all significantly higher in the PC group.

Vascular endothelial growth factor (VEGF) genotype and serum concentration in patients with pancreatic adenocarcinoma and chronic pancreatitis.

Vascular endothelial growth factor (VEGF) is necessary for microvasculature development and important for growth and spread of pancreatic tumors. Functional polymorphism of VEGF gene at position C-460T and G+405C may influence VEGF serum level. VEGF gene polymorphisms at position C-460T and G+405C were evaluated in 85 patients with pancreatic adenocarcinoma (PA), 72 - with chronic pancreatitis (CP) and 50 healthy volunteers. VEGF genotypes were studied in DNA isolated from blood samples and serum VEGF concentrations were measured. We found an increased frequency of the homozygous +405C/C VEGF genotype in patients with PA (55.3%) compared with CP (25%) and control group (16%; p<0.01). In contrast, the distribution of genotype and allele frequencies of the -460C/T polymorphism in the PA patients did not differ from those in CP and control groups. Serum levels of VEGF were significantly higher in PA patients (mean level: 441 ± 37.2 pg/ml) compared with CP patients (217 ± 13.6 pg/ml; p<0.001) and control group (137 ± 7.7 pg/ml; p<0.001). No relationship between VEGF serum levels and VEGF gene polymorphisms have been found. Our findings suggest that +405C/C VEGF genotype may contribute to pancreatic carcinogenesis. VEGF serum levels, although elevated in PA patients, are not associated with analysed VEGF polymorphisms.

Surgical management of pancreaticopleural fistulas.

BACKGROUND: Pancreaticopleural fistula is defined as a communication between the pancreatic duct and the pleural cavity. Initially, it is treated conservatively and endoscopically. Surgery is performed within a small group of patients in whom other therapeutic approaches failed. PATIENTS AND METHODS: In this retrospective study, nine patients with pancreaticopleural fistulas were treated. In 8 of nine patients, conservative treatment was used experimentally. Patients were considered as having a pancreaticopleural fistula before operation if a fistulous tract was seen on radiologic examination or if a large exudative pleural effusion was present with an amylase level > 5.000 U/L and total pleural fluid protein content > 3 g/L. All patients were evaluated for computed tomography (CT), ultrasonography (USG) examination and endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: The mean age of patients was 47 (35-51) years. Pancreatic effusion was present in the left pleural cavity in 6 cases, in the right cavity in 2 and on both sides in 1 case. The causes of fistula formation were as follows : chronic pancreatitis due to alcohol abuse--seven patients, rupture of the pancreas and main pancreatic duct due to trauma--one patient and pancreatolithiasis--1 patient. Endoscopic stenting of the main pancreatic duct was unsuccessful in all patients except one. Five patients underwent distal (n = 4) or corporocaudal pancreatectomy (n = 1) with splenectomy, two underwent pancreatic duct anastomosis with an intestinal loop (the Partington-Rochelle procedure) and one underwent pancreaticoduodenectomy. Postoperative complications were observed in two patients. There were no cases of hospital mortality. The mean time of hospitalization was 16 days. Seven patients reported for the follow-up examination in the postoperative period of 10 to 67 months. No recurrence of pleural effusion was noted in any case. CONCLUSION: Surgical treatment is effective and safe for the management of a pancreaticopleural fistula when conservative and endoscopic therapy has failed.

Management of necrotizing pancreatitis: flexible approach depending on intra-operative assessment of necrosis.

INTRODUCTION: The surgical management of necrotizing pancreatitis (NP) has changed over the years. MATERIAL AND METHODS: Among 144 patients, 12.5% (n = 18) were treated conservatively and 87.5% (n = 126) underwent surgery. The choice of operative method depended on the intra-operative assessment of consistency and on the extent of necrosis. A group of 126 patients underwent necrosectomy, followed by laparostomy with open packing in 80% (n = 101) cases, drainage in 14% (n = 18) and continuous closed lavage in 6% (n = 7). RESULTS: Postoperative complications occurred in 42.8% (n = 54) of the patients who underwent the surgery. Hospital mortality rate over all patients was 18% and 20.6% (n = 26) in the group of patients who underwent the surgery. Mean hospital stay was 61 +/- 36 days. Patients managed conservatively (n = 18) were discharged without surgical intervention. In this group no complications or deaths were observed. CONCLUSION: Using the three different surgical techniques in the management of NP, depending on intra-operative assessment of necrosis, showed promising results. A flexible approach targeted at a single patient and tailored to the clinical course and intra-operative situation should be considered in the treatment of NP.

Necrosectomy with an ultrasonic dissector in the treatment of necrotizing pancreatitis.

BACKGROUND: The surgical techniques for the treatment of necrotizing pancreatitis (NP) are varied and the ideal method is still debated. METHODS: Necrosectomy with an ultrasound dissector was performed. After the necrotic tissue was removed the bed was filled with a gentamicin-containing sponge. In the upper part of the abdominal wound a laparostomy was formed. The laparostomic cavity was packed with Mikulicz pads with physiological saline. Packs were changed every 24-48 h. RESULTS: There were 43 patients in the study with a mean age of 54 years (range 33-77). Reasons for surgical treatment were sterile necrosis- 53.5% (n = 23), infected necrosis- 39.5% (n = 17), abscess- 7% (n = 3). The mean number of packing changes under sedation was 5 (range 1-19). Postoperative complications occurred in 25.6% of patients (n = 11). There were five deaths (11.6%) after surgery. CONCLUSION: Necrosectomy with an ultrasonic dissector and gentamicin-containing sponge inserted into the post-necrotic bed are effective and well tolerated in the open packing treatment of NP.

Neuroendocrine pancreatic carcinoma causing sinistral portal hypertension.

BACKGROUND: Non-functioning neuroendocrine pancreatic tumors are usually connected with non-specific syndromes. CASE REPORT: This case history presents the diagnosis and treatment of a non-functioning neuroendocrine pancreatic tumor causing sinistral portal hypertension and gastrointestinal bleeding in a 36-year-old man. RESULTS: A peripheral resection of the pancreas with splenectomy was performed. Intraoperative examination of the specimen revealed a malignant neoplasm, probably neuroendocrinal carcinoma. CONCLUSIONS: Peripheral resection of the pancreas with splenectomy treats not only the symptoms of segmental portal hypertension caused by pathology of this organ, but also allows the etiology of the disease to be determined.

[Manometric examinations in esophageal peristalsis disorders]. / Manometryczne badania w zaburzeniach motoryki przelyku i wpustu.

Many centers besides radiography and endoscopy, perform manometric measurements in the diagnostics of diseases concerning esophagus and cardia. They which allow to determine esophageal body peristalsis, LES length with spatial distribution of pressures (Vector Volume). The aim of our study was the estimation of usefulness the esophageal and cardial computed manometry in disorders concerning motor activity of the upper part of gastrointestinal tract. In our hospital between March 1997 and March 1998 we examined 12 patients with cardial achalasia, 9 patients with hiatal hernia, 2 ones with features of gastroesophageal reflux without hernia and 1 patient with diffuse esophageal spasm. All patients were examined preoperatively, on the 7th postoperative day and postoperatively--after a month. Computer recording of pressures was made. In postoperative examination we revealed favourable improvement in gastroesophageal passage with marked decrease of LES pressures in patients after dilation. However in patients after Nissen's operation LES pressures exceeded upper normal range on the 7th day postoperatively, but they came back to normal range within a month after operation.

[The modified laparostomy with the use of ultrasound dissector and garamycin sponge in the treatment of complicated acute pancreatitis]. / Zmodyfikowana laparostomia z zastosowaniem dyssektora ultradzwiekowego i gabki garamycynowej w leczeniu powiklan ostrego zapalenia trzustki.

In the report a new modified technique of complicated pancreatitis treatment by laparostomy was showed. In included the use of ultrasound dissector for removing necrotic tissues and locating of garamycin sponge which should protect against secondary infection. Between January and May 1998 12 patients were treated using this method. In 8 cases (66%) we obtained rapid improvement of patients' general condition. One patient died and in 6 cases postoperative complications occurred. The use of ultrasound dissector shortens time of necrotic demarcation in pancreas and peripancreatic tissues. Garamycin sponge is effective protection from late infections concerning laparostomic wound. Modified laparostomy decreases about 50% number of secondary re-laparostomies, period of hospitalization and cost of complications treatment in acute pancreatitis in comparison with conventional method.

[Surgical intraduodenal drainage of bile duct: an introductory report]. / Operacyjny dodwunastniczy drenaz drogi zólciowej--doniesienie wstepne.

UNLABELLED: Reconstructing operations, performed on extrahepatic bile ducts, usually need protection of anastomosis by means of drainage. Classic Kehr's drainage is loaded with the risk of complications. Since 1993 the authors have been applying the alter way of drainage: an intraduodenal drainage by endoprothesis Y (DEY). Endoscopical removal of the drain was performed in 3-4 months after the operation. This way of drainage was used between III 1993--V 1997 in 23 patients. We did not observed any complications or pancreas reactions. Clinical control of patients was made after operation with ECW. In 4 cases the results of treatment were unsuccessful. In other 16 patients results of performed operations were favourable. CONCLUSION: Proposed way of protection of bile duct's reconstruction's site using DEY decreases the number of complications connected with classic Kehr's drainage.

[Changes in activity of antioxidant enzymes in the early period after classical and laparoscopic cholecystectomy]. / Zmiany aktywnosci enzymów antyoksydacyjnych we wczesnym okresie po cholecystektomii klasycznej i laparoskopowej.

In our study we examined the influence of surgical treatment of gallstones on erythrocyte antioxidant system. The investigated group consisted of thirty three (33) women patients 15 were operated laparoscopically and 18-by means of open cholecystectomy. Using proper criteria of classification to the study we obtained 2 similar groups of patients. We compared changes in activity of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and level of lipid peroxides (MDA) in early period after operation. The study revealed that laparoscopic cholecystectomy causes minor changes in activity of antioxidant enzymes and level of MDA than open cholecystectomy. Laparoscopic method causes less "oxidative stress" in human erythrocytes which suggests its minor traumatic effect than the open method.