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.

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.

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.

Endoscopic manometry of the sphincter of Oddi in sphincterotomized patients.

BACKGROUND/AIM: Endoscopic sphincterotomy (ES) of the sphincter of Oddi (SO) has been accepted as an effective method in extraction of common bile duct stones in postcholecystectomy patients. The purpose of this study was to examine the completeness of the performed ES and observe the post sphincterotomy pancreatic duct sphincter (PDS) activity using endoscopic manometry. MATERIALS AND METHODS: Activity of the sphincter of Oddi was examined in 15 sphincterotomized patients using endoscopic manometry one to 2.5 years after endoscopic sphincterotomy for choledocholithiasis. RESULTS: In eight patients absence of choledochoduodenal gradient, baseline pressure and the sphincter of Oddi phasic activity up to 2.5 years after endoscopic sphincterotomy indicated a complete sphincterotomy. In seven patients with incomplete endoscopic sphincterotomy, manometry exhibited either a lower choledochoduodenal gradient and baseline pressure without phasic activity of the sphincter of Oddi (three patients), a sphincter of Oddi activity without choledochoduodenal gradient (one patient), or a complete restitution of the sphincter of Oddi activity 1 to 2 years after endoscopic sphincterotomy (three patients). In five patients, with complete endoscopic sphincterotomy, measurements of pancreatic sphincter activity showed lower values of the pancreatic ductal pressure and baseline pressure, while the pancreatic sphincter phasic activity was equal to that found in the control group. CONCLUSIONS: Endoscopic manometry is method which enables us to test the completeness of endoscopic sphincterotomy and to follow the restitution of the phasic contractile function of the sphincter. Manometric findings reveal pancreatic sphincter in most patients as a separate sphincteric entity, the function of which is reduced but not eliminated by a complete endoscopic sphincterotomy.

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.

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.

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.

[Scanning electron microscopy analysis of peroperative injury at the junctions of the vasa vasorum and the collateral veins of venous autografts prepared for myocardial revascularization]. / Scann-elektronskomikroskopska analiza peroperativnih ostecenja utoka vasa vasorum i kolateralnih vena venoznog autotransplantata pripremljenog za revaskularizaciju miokarda.

The authors' objective was to determine the peroperative changes in affluences of collateral veins and vasa vasorum of venous autografts prepared for a coronary bypass by standard and proposed methods. The investigations were carried out on dogs. In control group, the veins were prepared by the standard method where the vein is presented by several minor incisions with "skin bridges" planted in between. In the second group, the veins were prepared by the method developed by the authors, where the vein is presented by a long incision, maintaining perfusion with its own blood throughout surgery. The scanning electron microscope analysis has shown that the standard method of vein preparation causes significant damage in collateral veins and vasa vasorum affluences which are actually part of an internal surface of future venous autograft prepared for myocardium revascularization. The proposed surgical method considerably reduces possible peroperative damage of the vasa vasorum and collateral vein affluence sites forming a portion of the internal surface of the venous autograft. Therefore, based on the obtained results, this method is recommended for clinical application.

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.

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.

[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.

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.

[Prolonged and postmature pregnancy terminated in non-hospital institutions]. / Produzena i prenesena trudnoca u uslovima vanbolnickih porodilista

Out of 4023 deliveries, the authors came across 291 prolonged ones, of which 39 were postmature deliveries. They followed the issue of these pregnancies in the conditions of non-hospital health care. The mortality rate of postmature deliveries was 10.2%. It is recommended that all prolonged and postmature pregnancies are referred to larger hospital-type maternity wards where more help can be offered to the pregnant woman and where the actual state of the fetoplacental unit can be properly followed. However, in cases when prolonged and postmature pregnancies are to be terminated in a non-hospital institution because of the women's refusal to go a larger maternity ward, it is proposed in present conditions to use as a diagnositc means also amnioscopy in addition to cytohormonal analysis.

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.

[Significance of cardiotocography and amnioscopy in establishing indications for cesarean section]. / Znacaj kardiotokografije i amnioskopije kod postavljanja indikacija za sectio caesarea

In the period of 2 years (1974-1975), out of 11,672 deliveries, 398 (3.41%) were induced by cesarean section. An important role in inducing labour surgically was played by cardiotocography and amnioscopy (in addition to other methods), i.e. in 84.22% (366 cases). At present it appears necessary to use cardiotocography and aminiscopy both in the last trimester and during the labour itself, so as to facilitate the estimation of the degree of a possible danger for the foetus.

Use of endoscopy to diagnose symptomatic duodenal duplication cyst in an adult.

The case of a female patient with a symptomatic duodenal duplication cyst diagnosed on endoscopy is reported. It is very important to discriminate between this rare anomaly and choledochocele as the treatment differs. Ultrasonography and ERCP are useful for the differential diagnosis. This rare anomaly is more often diagnosed in children. In adults duodenal duplication cysts may cause obstructive jaundice. The endoscopic finding of a cystic lesion in the medial wall of the second duodenal section at the papilla Vateri should be interpreted as a sign of the disease.