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.

Persistent elevation of serum CA 19-9 with no evidence of malignant disease.

BACKGROUND: Serum CA 19-9 is the mainstay marker for the diagnosis of biliopancreatic malignancies, though a persistent elevation can also be observed in various benign diseases. AIMS: In this study, a marked increase of serum CA 19-9 was seen in 10 patients who had no evidence of malignant disease. The possible causes of this finding are discussed. PATIENTS: Nine women and one man were studied, whose admitting diagnoses were as follows: pulmonary fibrosis in two, diabetes in two, non-ulcer dyspepsia in two, obesity in one, acute diarrhoea in one, colon diverticula in one and gastric ulcer in one. METHODS: Routine blood tests, tumour marker determinations, imaging studies and endoscopy were carried out at admission. RESULTS: Serum CA 19-9 levels ranged from 112 to 1338 IU/ml (mean 517 IU/ml). Abdominal ultrasonography, CT-scan, upper gastrointestinal X-ray series and gastrointestinal endoscopies were negative for malignancy. During the follow-up period (range 2-7 years) serum CA 19-9 values were persistently elevated in all patients. CONCLUSIONS: Our study shows that persistent and significant elevation of serum CA 19-9 can be found in non-malignant and non-cholestatic disease.

Capsule endoscopy for the detection of bleeding Meckel's diverticulum. A case report.

The case of a 59-year-old man with a history of recurrent severe gastrointestinal bleeding due to Meckel's diverticulum is described. The diagnosis was achieved by means of capsule endoscopy. The histological examination revealed the presence of Meckel's diverticulum with ectopic gastric mucosa. The use of capsule endoscopy for the detection of Meckel's diverticulum is discussed.

Efficacy and safety of Nd:YAG laser for the treatment of bleeding from radiation proctocolitis.

BACKGROUND: Bleeding due to radiation proctocolitis is a frequent and severe complication of radiotherapy in cancers of the pelvis. AIM: The aim of this study was to evaluate the efficacy and safety of endoscopic treatment with Nd:YAG laser in this condition. PATIENTS AND METHODS: A series of 9 patients with radiation-induced damage in the rectum and sigma were treated with endoscopic Nd:YAG laser until significant bleeding stopped and endoscopic features of proctocolitis improved. They received a median of 3 laser treatments (range 1-10) over a maximum time period of 11 months. RESULTS: In 4 cases, bleeding ceased and, in 4, it was reduced to occasional spotting. In the remaining patient, laser therapy led to only a transient improvement, but did not modify the requirement of blood transfusion. In the 5 patients also suffering from urgency, incontinence and/or rectal mucoid discharge, the laser therapy course also relieved these symptoms. No significant treatment-related complications were observed. CONCLUSIONS: Endoscopic Nd: YAG laser is a useful and safe treatment for patients with bleeding due to radiation proctocolitis.

Impaired fecal elastase excretion in uremic pancreopathy.

To evaluate pancreatic exocrine function in uremia, 25 patients undergoing regular hemodialysis without clinical evidence of pancreatic disease and 25 healthy control subjects were studied by fecal elastase 1 and chymotrypsin. Abdominal ultrasonography and measurement of serum lipase, calcium, phosphate, and parathormone were also carried out. Fecal elastase was significantly lower (P < 0.001) in patients than in controls. Abnormally low values were found in 12/25 patients of whom six had values <100 microg/g. Fecal chymotrypsin was significantly lower (P < 0.05) in patients than in controls, with lower than normal values found in 10/25 patients. Fecal elastase was not related to the serum calcium, phosphate, or parathormone levels or to the period of dialysis. In patients serum lipase was normal or slightly elevated (<300 units/liter), and there was no evidence of pancreatic disease at ultrasound examination. The results lend further support to the existence of pancreatic function impairment in a significant number of patients with renal failure despite the absence of clinical and morphological evidence of pancreatic disease.

Severe gastrointestinal bleeding in a uremic patient treated with estrogen-progesterone therapy.

Gastrointestinal bleeding is a frequent complication in hemodialysis patients; angiodysplasia is a potential cause, with a higher incidence in uremic patients. We describe a case of severe anemia (Hemoglobin up to 3.5 g/dl) secondary to diffuse angiodysplastic lesions in a hemodialysis patient with mixed connective tissue disease. The case is characterised both by the severity of the clinical picture (extension and entity of angiodysplastic lesions, frequency of bleeding episodes) and by the patient's religious faith which made her reject blood transfusions. We underline the efficacy of estrogen-progesterone therapy in view of the modest results obtained with other therapeutic strategies on bleeding.

Fecal elastase 1 determination in chronic pancreatitis.

This study assessed the diagnostic accuracy of fecal elastase 1 in chronic pancreatitis. Fifty-three healthy subjects, 44 patients with chronic pancreatitis (22 severe, 13 moderate, and 9 mild), and 43 patients with nonpancreatic digestive disease were studied. Elastase 1 concentration was determined on a small sample of feces using a commercially available kit. Fecal chymotrypsin was also measured. With a cutoff level of 190 microg/g, all healthy controls except one (98.1%), and the majority of patients with nonpancreatic digestive diseases (40 of 43; 93.0%) had elastase values above this limit. Among the 44 patients with chronic pancreatitis, 34 (77.3%) had pathological values: all 22 (100%) with severe disease, 10 of 13 (76.9%) with moderate disease and 2 of 9 (22.2%) with mild disease. Chymotrypsin values were pathological in 25 of 44 (56.8%) patients with chronic pancreatitis: 17 of 22 (77.2%) with severe pancreatitis, 7 of 13 (53.8%) with moderate pancreatitis, and 1 of 9 (11.1%) with mild disease. The specificity was 95.8% for elastase 1 and 85.4% for chymotrypsin. The difference both in sensitivity and specificity of the two enzymes was statistically significant (P < 0.05). Fecal elastase 1 has a high sensitivity, superior to that of fecal chymotrypsin, in the diagnosis of chronic pancreatitis. For its simplicity and rapidity, it could represent the tubeless test of choice in chronic pancreatitis.

Macroamylase detection in serum using selective precipitation: a rapid and reliable assay.

BACKGROUND AND AIM: Available assays for measurement of pancreatic isoamylase in serum based on specific immunoinhibition of salivary fraction are unable to detect macroamylase. We combined a polyethylene glycol test which identifies macroamylase by selective precipitation with an automated assay for total amylase and pancreatic isoamylase measurement. METHODS: We analysed 24 sera proven positive for macroamylase using gel filtration chromatography and 80 negative sera. Precipitation of macroamylase with polyethylene glycol, colourimetric measurement of total amylase activity and immunoinhibition for the determination of pancreatic isoamylase were carried out. RESULTS: Macroamylasaemic sera showed precipitation of at least 71% of the amylase activity, while sera with normal-sized amylase exhibited a maximum of 61%. In all the macroamylasaemic sera but two, the immunoinhibition test showed a rise in pancreatic isoamylase, which was found to be the prevalent fraction in 16. In 21 out of 24 sera with macroamylase and 67 out of 80 with normal-sized amylase, the precipitated amylase activity was also measured after immunoinhibition of non pancreatic activity. In macroamylasaemic sera, the percentage of precipitated pancreatic isoamylase activity ranged from 75% to 98%, while in samples with normal-sized amylase it was less than 71%. CONCLUSIONS: Polyethylene glycol precipitation can easily be combined with automated assays for the determination of pancreatic isoamylase and should be carried out whenever dealing with hyperamylasaemia of unclear origin.

Serum CA 242: the search for a valid marker of pancreatic cancer.

Many efforts have been made to find valuable serum tumour markers which help the diagnosis of pancreatic cancer. In the present study we investigated the diagnostic value of CA 242 in comparison with two other routinely used tumour markers (CA 19-9 and CA 50). Two-hundred and seventy six subjects were enrolled in this study: 46 patients with pancreatic cancer preoperatively, 53 with chronic pancreatitis, 28 with acute pancreatitis, 49 with other malignancies, 50 with miscellaneous non-neoplastic digestive diseases, and 50 healthy subjects. CA 242 was determined in serum by means of a two-step fluoroimmunometric assay. Sensitivities of CA 242, CA 19-9 and CA 50 for pancreatic cancer when all patients were considered were 41.3%, 54.3% and 47.8%, respectively (95% specificity level). No significant improvement was achieved by combination of CA 242 with CA 19-9 and/or CA 50. Cholestasis affected serum levels of CA 242 in patients without pancreatic cancer, but not in those with this tumour. The metastatic stage of pancreatic cancer appeared to influence the levels of CA 242. In conclusion, CA 242 serum assay does not seem to improve diagnostic accuracy for pancreatic cancer compared to CA 19-9 and CA 50.

13C labelled cholesteryl octanoate breath test for assessing pancreatic exocrine insufficiency.

BACKGROUND: A non-invasive test for assessment of fat digestion has been developed based on the intraluminal hydrolysis of cholesteryl-[1-13C]octanoate by pancreatic esterase. AIMS: To determine the diagnostic performance of this breath test in the assessment of exocrine pancreatic function. METHODS: The test was performed in 20 healthy controls, 22 patients with chronic pancreatic disease (CPD), four with biliopancreatic diversion (BPD), and 32 with non-pancreatic digestive diseases (NPD); results were compared with those of other tubeless tests (faecal chymotrypsin and fluorescein dilaurate test). RESULTS: Hourly recoveries of 13CO2 were significantly lower in CPD when compared with healthy controls or NPD. In patients with CPD with mild to moderate insufficiency, the curve of 13CO2 recovery was similar to that of healthy controls, while in those with severe insufficiency it was flat. In three patients with CPD with severe steatorrhoea, a repeat test after pancreatic enzyme supplementation showed a significant rise in 13CO2 recovery. The four BPD patients had low and delayed 13CO2 recovery. Only eight of the 32 patients with NPD had abnormal breath test results. There was a significant correlation between the results of the breath test and those of faecal chymotrypsin, the fluorescein dilaurate test, and faecal fat measurements. For the diagnosis of pancreatic disease using the three hour cumulative 13CO2 recovery test, the sensitivity was 68.2% and specificity 75.0%; values were similar to those of the other two tubeless pancreatic function tests. In seven healthy controls, nine patients with CPD, and nine with NPD a second breath test was performed using Na-[1-13C]octanoate and a pancreatic function index was calculated as the ratio of 13C recovery obtained in the two tests: at three hours this index was abnormal in eight patients with CPD and in three with NPD. CONCLUSION: The cholesteryl-1[1-13C]octanoate breath test can be useful for the diagnosis of fat malabsorption and exocrine pancreatic insufficiency.

Determination of fecal fat concentration by near infrared spectrometry for the screening of pancreatic steatorrhea.

CONCLUSIONS: Near infrared reflectance analysis (NIRA) is a useful test for diagnosing fat malabsorption. Three-day stool collection and determination of fecal fat output are recommended. The measurement of fat concentration on spot samples may be of some use only in screening malabsorption of pancreatic origin; moreover, it does not discriminate between steatorrhea resulting from pancreatic insufficiency and that caused by gastrointestinal disorders. BACKGROUND: NIRA has been proposed as an accurate method for the determination of fecal fat excretion. The aim of this study was to ascertain whether utilization of this technique to measure fat concentration in spot samples of feces is useful in screening for malabsorption. METHODS: Twenty-five patients with chronic pancreatic disease and 95 with other digestive disorders were studied. In all patients, fecal fat assay with NIRA was performed on three different samples from each daily stool collection for 3 d. In 14 patients with pancreatic disease and 21 with gastrointestinal disorders, a colorimetric assay for fecal fat was performed for comparison. RESULTS: When mean 3-d or daily fat fecal output were considered, a strict linear relationship was found between NIRA and the colorimetric method (r = 0.97 and 0.94, respectively). Using fat concentration, the two tests correlated less well (r= 0.74). Fat concentration was significantly higher in pancreatic than in nonpancreatic steatorrhea, even though values overlapped widely, and thus discrimination was not possible. The diagnostic efficiency of fat concentration for pancreatic and nonpancreatic steatorrhea was 72 and 61%, respectively.

Quality control study of H2 breath testing for the diagnosis of carbohydrate malabsorption in Italy. The "Tenue Club" Group.

BACKGROUND AND AIMS: H2 breath testing is increasingly used in Italy. The aim of this multicenter study was to assess the accuracy of this technique in the diagnosis of carbohydrate malabsorption. METHODS: An anonymous questionnaire was used to collect information about H2 breath testing methods and to design the quality control study. Fifteen out of 23 laboratories responded to the questionnaire and 12/23 completed the entire study. RESULTS: The survey revealed that a large variety of H2 testing methods are employed in Italy, but none have been previously tested for accuracy. This prospective study showed that these tests fail to identify > 20% of patients with malabsorption. In contrast, a new method based on single H2 breath measurement at 6 hours after lactulose ingestion and a cutoff value of greater than 5 ppm, had a sensitivity of 92% +/- 4% and a specificity of 94% +/- 0.5%. Increasing the cut-off to 10 ppm resulted in a sensitivity of 88% +/- 9% and a specificity of 100%. This improved accuracy was obtained with a much simpler testing procedure in which only one breath sample is analyzed, in contrast to the baseline and multiple subsequent samples that are analyzed using the currently employed techniques. CONCLUSIONS: A great improvement in the accuracy of the H2 breath test, as well as a considerable saving in terms of time and costs, may be possible through the use of a new, simplified H2 breath test followed by careful H2 analysis.

Diagnostic value of the amino acid consumption test in pancreatic diseases.

The amino acid consumption test (AACT) has been proposed as a simple tubeless test of pancreatic function, but studies of its diagnostic accuracy have produced conflicting results. Eighty-three consecutive patients with clinical suspicion of pancreatic disease underwent pancreatic stimulation for 1 h with an intravenous infusion of cerulein (50 ng/kg/h); the total plasma amino acid concentration was measured at -15, 0, 30, 45, and 60 min of infusion. The maximal percentage decrease in plasma amino acid concentration during cerulein infusion was taken as an index of pancreatic function. In addition, patients had pancreatic function assessed with the pancreolauryl test (PLT). Of the 83 patients studied, 24 were found to have chronic pancreatitis and four pancreatic cancer; the remaining 55 had various nonpancreatic digestive disorders. Pancreatic function, as assessed by the PLT, was impaired in 22 of the 28 patients with pancreatic diseases, and it was normal in all but four patients with nonpancreatic disorders. Cerulein infusion caused a decrease in total plasma amino acid concentration that was generally more pronounced in patients with nonpancreatic diseases (maximal percentage decrease: median, 14%; range, 4-28%) than in those with pancreatic diseases (maximal percentage decrease: median, 9%; range, 0-21%) (p < 0.001). Using a cutoff of a 14% amino acid decrease, the sensitivity of the AACT was 89% and the specificity 53% (diagnostic accuracy, 65%); with a cutoff of 12%, the sensitivity was 75% and the specificity 69% (diagnostic accuracy, 71%). The sensitivity of the PLT was 79% and the specificity 93% (diagnostic accuracy, 88%). The results indicate that the sensitivity of the AACT is relatively high, but they show that the specificity is low, making the test unsuitable for clinical use, at least in its present form.

Alterations of exocrine pancreas in end-stage renal disease. Do they reflect a clinically relevant uremic pancreopathy?

Serum pancreatic enzyme behavior, exocrine function, and morphology of the pancreas were studied in 28 patients with end-stage renal disease undergoing regular hemodialysis, in order to better delineate and assess the clinical relevance of the pancreatic alterations that occur in these patients. Twenty-eight healthy subjects served as controls. Initial studies included serum amylase, isoamylase, and lipase assays; fecal chymotrypsin measurement; and abdominal ultrasonography. The amylase, lipase, and chymotrypsin determinations, as well as ultrasound examination, were repeated four years later. None of the patients had clinical evidence of pancreatic disease at entry into the study, but one had had previous attacks of pancreatitis and another developed mild acute pancreatitis one month after entry. Initial mean serum enzyme levels were significantly higher in patients than in controls (amylase, pancreatic isoamylase, and lipase, P < 0.001; salivary isoamylase P < 0.05). Serum amylase was raised in 16/28 patients; pancreatic isoamylase in 15/28, and lipase in 7/28; these elevations were generally mild. Mean fecal chymotrypsin was significantly lower (P < 0.001) in patients than in controls: abnormally low values were found in 9/28 patients. Amylase, lipase and chymotrypsin measurements repeated after four years showed no significant difference with respect to the first study. Ultrasonographic changes were rare and mild: one patient had a small cyst in the pancreas head, another, an increase in echogenicity of the gland not related to age; these findings were unchanged at repeat examination. The results demonstrate that the frequent elevations of serum pancreatic enzymes and the rare sonographic changes found in patients undergoing hemodialysis do not generally reflect a relevant pancreopathy. However, the finding of significantly decreased fecal chymotrypsin may indicate the presence of pancreatic dysfunction in end-stage renal disease.

Clinical evaluation of a new rapid assay for serum lipase determination.

We evaluated a new continuous colorimetric method for serum lipase determination based on the use of a 1,2-diglyceride as substrate and a specific 2-monoglyceride lipase. This test was compared with a turbidimetric assay and also with serum alpha-amylase and pancreatic isoamylase determinations. We studied 32 patients with acute pancreatitis, 27 with chronic pancreatitis in acute painful relapse, 19 with pancreatic cancer, 44 with other digestive diseases, 53 with end-stage renal disease, and 102 healthy controls. The results of the new test were closely correlated with those of the turbidimetric method (r = 0.96). Sensitivity of the new method was elevated (100%): it was the same as that of the turbidimetric method, but slightly higher than that of alpha-amylase and pancreatic isoamylase determinations (93.7 and 96.9%, respectively). Specificity was 95.5%, i.e. higher than that observed using the other tests (86.4, 84.1 and 88.6% for lipase turbidimetric assay, amylase, and pancreatic isoamylase determinations, respectively). The results demonstrate that this new lipase assay is a sensitive, specific test for the diagnosis of acute pancreatitis.

Evaluation of the effect of rifaximin in colon diverticular disease by means of lactulose hydrogen breath test.

To understand better the mechanism by which rifaximin produces symptomatic relief in diverticular disease of the colon, the effect of this antibiotic on orocaecal transit time and on the production of hydrogen by intestinal microflora after ingestion of lactulose was studied in 33 patients with this disease and in 11 healthy subjects. An hydrogen breath test was carried out to measure pulmonary hydrogen excreted during the 3 hours after ingestion of 10 g lactulose. In patients, the hydrogen breath test with lactulose was repeated after treatment with 400 mg rifaximin twice daily for 10 days. In patients under basal conditions and controls, orocaecal transit time did not differ significantly, but hydrogen production was significantly higher in the former (p < 0.02). In patients, transit time and hydrogen excretion in response to lactulose administration did not differ significantly before and after treatment with rifaximin, and these two parameters were inversely correlated both before (r = 0.49, p < 0.01) and after rifaximin (r = 0.58, p < 0.001). Fifteen of the 33 patients showed accelerated transit time after treatment with the antibiotic, 10 showed no variation, and 8 showed prolonged transit. In 19 patients a reduction in hydrogen production was noted after rifaximin, while in 14 an increase was demonstrated. Twenty-one of the 33 patients reported an improvement in their symptoms with rifaximin; of these, only 10 showed accelerated transit time and 9 a reduction in hydrogen production after rifaximin.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of pancreatic ascites with somatostatin.

Pancreatic ascites is a rare complication of chronic pancreatitis, whose treatment continues to represent a difficult clinical problem. In this report we describe a case of a patient with chronic pancreatitis and pancreatic ascites who was successfully treated with somatostatin given by continuous intravenous infusion of 1.5 micrograms/kg/h for 2 weeks.