Prevalence and risk factors of extrapancreatic malignancies in a large cohort of patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

BACKGROUND: The objectives of this study are to estimate prevalence and incidence of extrapancreatic malignancies (EPMs) among intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, and to identify risk factors for their occurrence. PATIENTS AND METHODS: We conducted multicentric cohort study in Italy from January 2010 to January 2011 including 390 IPMN cases. EPMs were grouped as previous, synchronous (both prevalent) and metachronous (incident). We calculated the observed/expected (O/E) ratio of prevalent EPMs, and compared the distribution of demographic, medical history and lifestyle habits. RESULTS: Ninety-seven EPMs were diagnosed in 92 patients (23.6%), among them 78 (80.4%) were previous, 14 (14.4%) were synchronous and 5 (5.2%) were metachronous. O/E ratios for prevalent EPMs were significantly increased for colorectal carcinoma (2.26; CI 95% 1.17-3.96), renal cell carcinoma (6.00; CI 95% 2.74-11.39) and thyroid carcinoma (5.56; CI 95% 1.80-12.96). Increased age, heavy cigarette smoking, alcohol consumption and first-degree family history of gastric cancer are significant risk factors for EPMs, while first-degree family history of colorectal carcinoma was borderline. CONCLUSION: We report an increased prevalence of EPMs in Italian patients with IPMN, especially for colorectal carcinoma, renal cell and thyroid cancers. A systematic surveillance of IPMN cases for such cancer types would be advised.

Endoscopic ultrasound for differential diagnosis of duodenal lesions.

PURPOSE: Duodenal tumors are rare and require a different management from that of esophagogastric neoplasia. The present study retrospectively analyses the endoscopic ultrasound (EUS) features of duodenal tumors of both epithelial and subepithelial origin. MATERIALS AND METHODS: During a 12 year period, all duodenal tumors with histologic confirmation by surgery or biopsy were collected including endoscopic and endosonographic images. EUS images were analyzed for specific features (echogenicity, wall layer structure and relation, outer margins) to possibly distinguish epithelial (polyps and carcinoma versus lymphoma) and subepithelial (tumor type) tumors. RESULTS: 53/80 cases had histologic confirmation (mean age 53.1 ±â€Š11.4 years, m:f = 33:20), 31 were epithelial (13 adenomas, 12 carcinomas, 6 lymphomas) and 22 subepithelial (11 GISTs, 7 Brunneromas, 1 lipoma, 3 NETs). EUS did not recognize carcinomas in 2/13 adenomas. EUS features suggesting carcinoma were loss of wall layers and irregular margins. 5/6 lymphomas showed inhomogeneous thickening with layers partially recognizable. Tumor type of subepithelial lesions correlated with echogenicity: GIST tumors were mostly (62.5 %) hypocheoic with the 3 malignant cases being characterized by heterogeneous echopattern with irregular outer margins. Of the hyperechoic lesions, lipomas had a homogeneous whitish appearance, while NET and Brunneromas were less hyperechoic. In the latter, the endoscopic aspect was also helpful for differential diagnosis. Accuracy of combined endoscopic/EUS imaging for all duodenal lesions was 84.9 % (45/53). No procedural complications occurred among all patients that received EUS examinations. CONCLUSION: EUS contributes to the differential diagnosis of epithelial lesions known to be malignant; in subepithelial tumors, tissue confirmation is still required.

An Evaluation of European Countries' Health Systems through Distance Based Analysis.

INTRODUCTION: The issue of evaluating the efficiency of health systems has been elaborated upon frequently. Since "health" is a multi-faceted concept, many variables of different measurement units must be included in its analysis; consequently, this presents a great obstacle for researchers to overcome. MATERIALS AND METHODS: A novel statistical approach for evaluating the efficiency of organizational units is here proposed, which can also be easily applied to the health sector. For these purposes, the health status of the 27 countries belonging to the European Union has been examined by employing a statistical Ivanovic-Jeremic Distance Based Analysis (DBA) on various health indicators. RESULTS: The subsequent outcome of the Distance Based Analysis has shown that Cyprus and Ireland have a most efficient health system sectors. Greece also has exceptional indicators of health service, yet health on the individual level is not comparable. LIMITATIONS: Since it synthesizes many variables into an efficiency score, a DBA can be easily applied to other regions/countries. However, the choice of input and output variables can be considered to be potential limitations since a different choice of variables may cause different efficiency scores for the countries selected. CONCLUSIONS: A DBA approach contributes significantly to the efficiency in the field of research measurement. This analysis can be additionally performed alongside DEA and SFA methods, as a new measure of efficiency.

The first transendoscopic plastic to self-expandable metal stent replacement in Serbia and Montenegro using a diagnostic duodenoscope.

Studies have shown that SEMS remain patient longer with fewer associated complications compared with conventional plastic strents. Zilver stent, a nitinol zig-zag mash SEMS has a special advantage, having a thin introducer diameter of 7 Fr with a fully deployed span of 10mm. For a 48-year-old woman presented with obstructive jaundice and a diagnosis of unresectable pancreatic carcinoma with consequent stenosis of common bile duct (CBD), infiltration of local blood vessels and life expectancy longer than six months, it was decided that an endoscopic palliative drainage procedure should be performed. The technique of transendoscopic plastic to metal stent exchange is described, using a diagnostic duodenoscope. The patient lived 7 months after implementation of Zilver stent and died anicteric due to progression of a primary disease. The transendoscopic plastic to metal stent exchange is feasible palliative method which requires a basic endoscopic equipment and experienced staff and therefore is applicable in developing countries as well.

[Acute upper gastrointestinal nonvariceal bleeding--how to determine low risk patients for rebleeding and mortality after endoscopic sclerotherapy?].

INTRODUCTION: Successful endoscopic sclerotherapy is effective in securing hemostasis for bleeding lesions and remains the first line and only needed therapy for most of the patients (pts), but bleeding reoccurs in 10% to 30% pts, and 4% to 14% of the pts die after acute nonvariceal upper gastrointestinal bleeding (UGIB). The need for hospitalization and its duration for all the bleeding pts is still a controversial question. AIM: To create the simple scoring system able to determine low risk pts for rebleeding and mortality by establishing the relative importance of risk factors for rebleeding and mortality after successful endoscopic sclerotherapy of acute nonvariceal UGIB. PATIENTS AND METHODS: Prospective study included 3 15 pts who where admitted to hospital because of acute nonvariceal UGIB. All of them underwent gastroscopy with successful sclerotherapy within 12 hours after the admission. We investigated the episode of rebleeding and death during the initial hospitalization, and analyzed the following parameters: age, gender, drug intake, shock, bleeding stigmata, location of bleeding lesion and comorbidity. RESULTS: Rebleeding occurred in 53 pts (16.8%) and was determined by shock, bleeding stigmata and comorbidity. Eleven pts (3.5%) died and shock, rebleeding and comorbidity were all independent, statistically significant predictors of pts' mortality. The numerical scores for determination of pts with different risk levels for rebleeding and mortality have been developed using the significant predictors of rebleeding and death. The score values for rebleeding ranged from 3 to 9 and pts with values < or = 4 had low risk of rebleeding. We identified 59 pts (18.7% of all) with score for rebleeding < or = 4. Score values for mortality risk ranged from 3 to 8 and the values < 5 revealed negligible risk of death. In our group we found 290 pts (92.1% of all) with low mortality score values. CONCLUSION: Following the successful initial endoscopic sclerotherapy, these scores can help to identify pts with low risk of rebleeding and negligible risk of death, so they can be treated as outpatients.

PCR detection of helicobacter pylori genome in colonic mucosa: normal and malignant.

BACKGROUND AND AIMS: The aim of this study was to detect Helicobacter pylori (H. pylori) in colorectal cancer tissue specimens and relate the possible role of this microorganism in the etiology of colorectal cancer. PATIENTS AND METHODS: From February 2002 to April 2003 83 CRC patients (55 male, 28 female) and 40 control patients (19 male, 21 female) entered the prospective study. The biopsy samples of CRC tissue and normal mucosa were obtained during open surgery on CRC patients. In the control patients biopsy samples were taken during colonoscopy. Pathology confirmed adenocarcinoma in all the CRC patients. The existence of genetic material of H. pylori was determined by detection of the ureA gene by nested PCR. K-ras PCR was also performed on all patients. RESULTS: H. pylori PCR was positive in 1 case (1.2%) of CRC in the tumour tissue and in all 5 samples (6.0%) of the normal colonic mucosa in the cancer patients. The control patients were PCR positive to H. pylori in 13 samples (32.5%). According to Chi-square test, there is no statistical correlation between H. pylori infection and CRC (x2 = 2.9395; p > 0.05) but there is a significant prevalence of H. pylori infection in controls compared to CRC (x2 = 15.5625; p < 0.01). The K-ras PCR showed gene mutations in 19 tumour tissues of CRC (31.6%) and in 2 cases (3.4%) of normal colonic mucosa of CRC patients . In controls K-ras PCR showed one gene mutation (3.0%). There is a significant statistical correlation between K-ras mutation and CRC (x2 = 16.0694; p < 0.01). CONCLUSION: Our established PCR for H. pylori is feasible for CRC tissue as well. However, H. pylori is not considered to play an important role in the pathogenesis of CRC. The identification of K-ras mutations in routine PCR analysis correlates with the presence of CRC.

Review article: uncomplicated diverticular disease of the colon.

Diverticular disease of the colon is the fifth most important gastrointestinal disease in terms of direct and indirect health care costs in western countries. Uncomplicated diverticular disease is defined as the presence of diverticula in the absence of complications such as perforation, fistula, obstruction and/or bleeding. The distribution of diverticula along the colon varies worldwide being almost always left-sided and directly related to age in western countries and right-sided where diet is rich in fibre. The pathophysiology of diverticular disease is complex and relates to abnormal colonic motility, changes in the colonic wall, chronic mucosal low-grade inflammation, imbalance in colonic microflora and visceral hypersensitivity. Moreover, there can be genetic factors involved in the development of colonic diverticula. The use of non-absorbable antibiotics is the mainstay of therapy in patients with mild to moderate symptoms, and the effect of fibre-supplementation alone does not appear to be significantly different from placebo, although no definite data are available. More recently, alternative treatments have been reported. Mesalazine acts as a local mucosal immunomodulator and has been shown to improve symptoms and prevent recurrence of diverticulitis. In addition, probiotics have also been shown to be beneficial by re-establishing a normal gut microflora. In this study, the current literature on uncomplicated diverticular disease of the colon is reviewed.

Multiple stenting of refractory pancreatic duct strictures in severe chronic pancreatitis: long-term results.

BACKGROUND AND STUDY AIMS: Dominant pancreatic duct strictures located in the head of the pancreas in patients with severe chronic pancreatitis are often managed by endoscopic placement of a single plastic stent. Patients with refractory strictures after prolonged stenting require repeated stent replacement or surgical pancreaticojejunostomy. Placement of multiple plastic stents has proved effective in managing postoperative biliary strictures. The aim of this study was to investigate the feasibility, efficacy, and long-term results of multiple stenting of refractory pancreatic strictures in severe chronic pancreatitis. PATIENTS AND METHODS: 19 patients with severe chronic pancreatitis (16 men, three women; mean age 45 years) and with a single pancreatic stent through a refractory dominant stricture in the pancreatic head underwent the following protocol: (i) removal of the single pancreatic stent; (ii) balloon dilation of the stricture; (iii) insertion of the maximum number of stents allowed by the stricture tightness and the pancreatic duct diameter; and (iv) removal of stents after 6 to 12 months. RESULTS: The median number of stents placed through the major or minor papilla was 3, with diameters ranging from 8.5 to 11.5 Fr and length from 4 to 7 cm. Only one patient (5.5 %) had persistent stricture after multiple stenting. During a mean follow-up of 38 months after removal, 84 % of patients were asymptomatic, and 10.5 % had symptomatic stricture recurrence. No major complications were recorded. CONCLUSION: Endoscopic multiple stenting of dominant pancreatic duct strictures in chronic pancreatitis is a feasible and safe technique. Multiple pancreatic stenting is promising in obtaining persistent stricture dilation on long-term follow-up in the setting of severe chronic pancreatitis.

Clinical onset of the Crohn's disease after eradication therapy of Helicobacter pylori infection. Does Helicobacter pylori infection interact with natural history of inflammatory bowel diseases?

BACKGROUND: There are conflicting reports concerning the prevalence of Helicobacter pylori infection in patients with inflammatory bowel diseases: some studies connected Sulphasalazine therapy and lower incidence of Helicobacter pylori infection, but others showed lower prevalence of Helicobacter pylori infection in inflammatory bowel diseases despite the choice of therapy. CASE REPORT: A 28-year-old male patient presented in January 1996 with the symptoms of ulcer like dyspepsia. There was no significant abnormality on physical examination, laboratory testing and abdominal ultrasound. Histology examination of the biopsy specimen taken during the upper endoscopy revealed Helicobacter pylori associated active gastritis only in the corporal part of the stomach. After two weeks eradication therapy (Omeprazole, Amoxicillin) he was well. Three months later, at the control endoscopy, granulomatous gastritis of the corporal localization was detected, without Helicobacter pylori present. Antral mucosa appeared normal, both, on endoscopy and histology examination. In July 1996 he started with cramping abdominal pain, mild periodical fever and episodes of watery diarrhea. In laboratory results we found nonspecific signs of inflammation. We repeated upper endoscopy, colonoscopy and enteroclysis--with evidence of segmental stenotic lesions of the upper part of ileum and jejunum. Again, we confirmed granulomatous gastritis and small granuloma in the proximal jejunum. After starting the 5-ASA therapy in combination with Metronidazol, patient was better clinical condition, and laboratory results were normal. We suggested mesalamine maintenance therapy 1 gr. every day, and three years later he is well, in clinical remission of Crohn's disease. CONCLUSION: The clinical course of the Crohn's disease maybe "sui generis" connected with Helicobacter pylori infection- but the exact mechanisms remain to be discovered.

[Topographic and structural characteristics of the minor duodenal papilla]. / Topografske i strukturne karakteristike papillae duodeni minor.

The study of minor duodenal papilla topography and structure was carried out on 36 fresh autopsy specimens of human duodenopancreas. We performed precise measurements of its distance to the major duodenal papilla and to the superior duodenal flexure. There was no correlation between the position of the minor papilla and the incidence of duodenal ulcer disease. Microdissection and histological staining of the minor papilla did not reveal an anatomically defined sphincter around the terminal portion of the accessory pancreatic duct. All the specimens of the minor papilla contained within acini of pancreatic tissue. A terminal dilation of the accessory pancreatic duct was found in 22% of the cases.

Computerized planimetry of normal and abnormal postmortem pancreatograms.

The aim of this study was to evaluate postmortem pancreatograms by means of computerized planimetry of the ductal drainage area. This method was applied to a total of 136 pancreatograms from autopsy specimens of the human duodenopancreas, with and without pathological changes. The mean value of the total ductal drainage surface area was 5,054 mm2 for normal specimens and 3,938 mm2 in cases with chronic pancreatitis; this difference was statistically highly significant. The analyses also included measuring the accessory duct drainage area (if an accessory duct was present), and the percentage of its share in the total gland area. This share was significantly larger in cases with chronic pancreatitis (24.4%) in comparison to the normal specimens (16.8%). In conclusion, computerized planimetry of pancreatograms supplies valuable data not only on the pathogenesis of chronic inflammation of the gland, but also on some of the possible predisposing factors for this condition.

Serum insulin-like growth factor (IGF)-II is more closely associated with liver dysfunction than is IGF-I in patients with cirrhosis.

The aim of this investigation was to determine the total concentrations of the insulin-like growth factors (IGF-I and IGF-II) in the blood serum of patients with liver cirrhosis and to evaluate their association with the condition. Cirrhosis was alcohol induced (n=27), of viral origin (n=17) or due to combined or other causes (n=21) and was moderate or severe in similar numbers of cases (Child A: n=21; Child B: n=21; Child C: n=23). While serum levels of both peptides were lower in patients than in age-matched healthy subjects (n=81), there was considerable overlap into the lower normal range for IGF-I. Moreover, no correlation between disease severity (Child score) and serum IGF-I was observed. Since a total of 78% of the results for IGF-II were outside the normal range (95% confidence interval) and serum concentrations were correlated with Child score (P=0.007), it is suggested that serum IGF-II concentrations may reflect compromised hepatic function more closely than IGF-I.

Role of autologous fibrin tissue adhesive in abdominal surgery.

Fibrin tissue adhesive (FTA) is an agent developed for achieving better hemostasis and adhesion of living tissue. FTA appears to have no tissue toxicity, promotes a firm seal in seconds to minutes, is reabsorbed in days to weeks following application, and appears to promote local tissue growth and repair. It can be used in various surgical procedures. It has been used preoperatively, perioperatively and postoperatively in abdominal surgical procedures. There were no side effects. Improvement of surgical hemostasis was obvious in all patients. Anastomotic leakages were closed in a shorter time without surgical intervention. Sero-lymphatic drainage after surgical procedures that include extensive lymph node dissections was less. Use of FTA in treatment of fistula in ano was successful. The data would indicate that use of FTA may be a good alternative in solving various conditions in every day clinical practice, although a bigger randomized series, and longer follow up is needed.

Endoscopic biliary manometry in cholecystectomized patients with and without choledocholithiasis.

BACKGROUND/AIMS: Direct study of the function of the sphincter of Oddi became possible recently with the advent of endoscopic manometry. A dysfunction of the bilio-pancreatic sphincter apparatus has been implicated in some bilio-pancreatic disorders. The purpose of this study was to examine the relation between dysfunction of the sphincter of Oddi and the formation of common bile duct stones. METHODOLOGY: Endoscopic biliary manometry was performed on 45 cholecystectomized patients. Endoscopic retrograde cholangiography showed choledocholithiasis in 26 patients while 19 patients were free of common bile duct stones. Nine healthy subjects served as controls. RESULTS: Manometric investigation showed a significant increase in the percentage of retrograde phasic contractions of the sphincter of Oddi (SO) in patients with choledocholithiasis compared to the control group (p < 0.05). Also, a significantly higher frequency of SO phasic contractions was found in the group of patients with choledocholithiasis when compared to the cholecystectomized group without common bile duct stones (p < 0.05), but there was no difference when compared with the control group. Markedly increased SO basal pressure was found in 5 patients with choledocholithiasis as well as in one cholecystectomized patient without choledocholithiasis (greater than x + 3SD). However, the SO basal pressure, phasic SO pressure, amplitude and duration of the phasic contractions as well as the choledochal pressure did not differ significantly between the groups. CONCLUSIONS: This study demonstrates manometric abnormalities in the SO of patients with choledocholithiasis which suggests that SO dysfunction and pathophysiological mechanisms are related to the formation of common bile duct stones.

[Leiomyoma of the esophagus. Case report]. / Leomiom jednjaka. Prikaz bolesnika.

Of all oesophageal tumours benign tumours account for less than 10%, of which 4% are leiomyomas. These tumours are most frequently asymptomatic, mostly localized in the lower oesophageal third. The most frequent symptoms, if any, are the following: dysphagia, unspecific retrostemal pain, heartburn, and occasionally, weight loss. Tumour enucleation is a therapy of choice in patients with oesophageal leiomyoma. In case of successful surgical removal, the prognosis is good and complains are practically eliminated. A male patient, aged 53, with paroxysmal tachycardia, in whom transhiatal enucleation was carried out in order to remove a large oesophageal leiomyoma after which cardiac complains were eliminated, is reported.

The value of ultrasound in staging the severity of acute pancreatitis.

The authors asses the accuracy and role of early ultrasound examination in staging the severity of acute pancreatitis. A total of 110 consecutive patients with acute pancreatitis were included into the study. The ultrasound findings were categorized into six categories and compared with a modification of multiple prognostic criteria, computerized tomography, operative findings (when available) and clinical outcome. The probability of a positive ultrasound finding in a patient with clinically severe acute pancreatitis was 89.6% (sensitivity). In comparison to computerized tomography the sensitivity of ultrasound in discovering CT diagnosed moderate and severe forms of acute pancreatitis was 86.6%. The sensitivity of ultrasound in discovering moderate and severe forms of acute pancreatitis as defined at laparotomy was 77.8%. The specificity of ultrasound was low (44.0%) in comparison with modified prognostic criteria, but high in comparison with computerized tomography (87.5%) and staging at laparotomy (85.7%). There was a good correlation between US defined moderate and severe forms of acute pancreatitis and clinical outcome (average number of hospital days and case fatality). The authors conclude that early ultrasound examination in acute pancreatitis is indicated and can help stage the severity of the disease and affect decision making.

The significance of aductal zones on pancreatograms: an anatomo-clinical assessment.

The authors analyzed 177 endoscopic retrograde pancreatograms (ERPs) with normal findings. The complete visualization of the side branches was achieved in 128 patients (72.3%), and aductal zones in the isthmus and mid-body of the pancreas were noted in 49 (27.3%) of these patients. The existence and incidence of the aductal zones were evaluated and verified in 141 anatomical duodenopancreas specimens. Thirty-two corrosion casts and 109 postmortem pancreatograms were analyzed. The postmortem specimens had a 36.2% incidence of aductal zones in the same location, with no statistically significant difference compared with the clinical pancreatograms. The visualization of the side branches was 100% on the postmortem pancreatograms, indicating that the clinical ERCP incidence of aductal zones is realistic.

Endoscopic manometry of the sphincter of Oddi and pancreatic duct in patients with chronic pancreatitis.

CONCLUSION: Endoscopic manometry in patients with chronic pancreatitis has demonstrated some manometric abnormalities in the sphincter of Oddi, but these abnormalities have no significant role in the pathogenesis of chronic pancreatitis. BACKGROUND: The study was undertaken to determine whether the sphincter of Oddi dysfunction plays a significant role in the pathogenesis of chronic pancreatitis. METHODS: Manometric investigation was performed in 32 patients with chronic pancreatitis. Twenty-three of them had alcohol-induced chronic pancreatitis, seven had biliary pancreatitis, and two patients had annular pancreas with chronic pancreatitis. Fifteen of them had dilated main pancreatic duct. Twenty-one cholecystectomized patients with no abnormality of the pancreas and biliary system served as controls. RESULTS: This study showed no significant difference in the mean pressures in the pancreatic duct, sphincter of Oddi (basal and phasic), and frequency of the sphincter of Oddi phasic contractions when comparing patients and controls. Sphincter of Oddi basal pressure (26-44 mmHg) was markedly increased in seven patients, whereas three patients (two of them had increased sphincter of Oddi basal pressure) had increased pancreatic duct pressure (20-24 mmHg). Increased numbers of retrograde contractions were found in seven patients.

Unusual variants of the tributaries of the main pancreatic duct revealed by postmortem and endoscopic pancreatography.

Analysis of 97 human postmortem pancreatograms and 103 endoscopic pancreatograms revealed a total of 3 cases (1.5%) with isolated variants in the branches of the main pancreatic duct. In the first one, tortuous branches were present in the upper head-body region. The second case involved joint tributaries bridging over an unstenosed segment of the main pancreatic duct. In the third case, we found three branches from the uncinate process running down to the main duct. In all of these cases no pathological substrate was found, and they should be considered as anatomical variants observed during interpretation of a radiogram.