Flumazenil in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double blind randomized placebo controlled study.

AIMS: The aim of this study was to evaluate the effects of flumazenil on hepatic encephalopathy in patients with liver cirrhosis. PATIENTS AND METHODS: . In the double blind randomized, placebo controlled study, 54 patients with hepatic encephalopathy grade III-IV were randomly assigned to receive either flumazenil 2 mg iv (group A) or placebo (group B); conventional treatment with branched-chain amino acid, saline, glucose, and lactulose was administered in both groups. A 24-hour observation period was established. Clinical improvement was defined as a 3 point decrease in the Glasgow coma score at any time within 24 hours. RESULTS: Clinical improvement was obtained in 22/28 patients in group A and in 14/26 in group B (p<0.05); improvement was observed within the first six hours in 21/22 patients in group A and only in 3/14 in group B. Mortality rate was not different between group A and B; however, all 6 non-responders in group A and only 5 out of 12 in group B died within 24 hours. Among patients with post-bleeding encephalopathy, 11 out of 17 in group A and only 2 out of 14 in group B improved (p<0.001). CONCLUSIONS: Flumazenil may exert a beneficial effect in a subset of patients with acute hepatic encephalopathy; encephalopathy associated with bleeding is more likely to respond to flumazenil; responders to the treatment usually improve within the first 6 hours while lack of response usually represents a bad prognostic sign.

Pseudocysts in acute nonalcoholic pancreatitis: incidence and natural history.

Epidemiological studies on pancreatic pseudocysts are retrospective analyses on alcoholic patients. The aims of this study were to investigate the incidence, natural history, and predictors of the appearance and disappearance of pancreatic fluid collections and pseudocysts after nonalcoholic acute pancreatitis. We carried out a prospective cohort study in a series of 926 patients with acute pancreatitis. Pancreatic fluid collections or pseudocysts were treated only after complications. We studied pancreatic fluid collections from 83 patients (8.9%): 48 of whom developed pseudocysts (5.1%). Both were less frequent after biliary pancreatitis (P < 0.0001). In the first 60 days of follow-up, patients with fluid collections or pseudocysts showed more complications than spontaneous disappearance; two of them died. After the 60th day, spontaneous disappearance was more frequent, and at one year the cumulative incidence of complications and spontaneous disappearance was 36% and 56%, respectively. A total of 33 patients with fluid collection needed interventional treatment (surgery or percutaneous or endoscopic drainage). Pseudocysts that were small (<5 cm) or developed in the tail had a higher incidence of spontaneous disappearance: 22/24 (91.7%) and 11/12 (91.7%), respectively. In conclusion, fluid collections and pseudocysts after non-alcoholic pancreatitis have a low incidence of complications and mortality with a high rate of spontaneous disappearance. We suggest treating them only after complications.

Helicobacter pylori infection, pattern of gastritis, and symptoms in erosive and nonerosive gastroesophageal reflux disease.

BACKGROUND: The aim of this study was to evaluate the prevalence of Helicobacter pylori infection and the characteristics of gastritis and symptoms of patients with erosive and nonerosive gastroesophageal reflux disease (GERD). METHODS: We studied 202 consecutive patients with a diagnosis of GERD (symptoms score and endoscopy): group A (n = 110), erosive GERD; group B (n = 92), nonerosive GERD; 200 patients with upper abdominal complaints without abnormalities at endoscopy (functional dyspepsia, group C); and 200 asymptomatic controls tested for H. pylori serum antibody (group D). Antral and body biopsy specimens were taken for histology and the rapid urease test in groups A, B, and C. RESULTS: The prevalence of H. pylori infection was higher in groups B and C (62% and 55%, respectively) than in A and D (36% and 40%) (P < 0.05). In positive patients H. pylori colonization and gastritis grade scores in the gastric body were higher in nonerosive than in erosive GERD and functional dyspepsia (P < 0.05). No differences in H. pylori colonization or gastritis grades were found in the antrum. Fifty-nine patients with nonerosive GERD (64%) and 42 with erosive GERD (38%) showed other dyspeptic symptoms associated with reflux symptoms (P < 0.05). CONCLUSIONS: H. pylori prevalence is higher in patients with nonerosive GERD than in normal subjects and in patients with erosive GERD and similar to that of patients with dyspepsia. Patients with nonerosive GERD often show dyspeptic symptoms and higher H. pylori colonization and inflammation grades in the proximal stomach. Our data support the hypothesis that in GERD H. pylori gastritis may, on the one hand, protect against the development of esophageal erosions and, on the other, contribute to the esophageal hypersensitivity to acid which is a feature of GERD.

Endoscopic sphincterotomy and recurrence of acute pancreatitis in gallstone patients considered unfit for surgery.

The aim of the present prospective study was to investigate whether endoscopic sphincterotomy may be useful in preventing recurrence of acute pancreatitis in patients with gallstones and a high anesthesiological risk of cholecystectomy. Twenty-six elderly patients with severe cardiopulmonary, hepatic, and renal diseases were considered. Endoscopic sphincterotomy was successful in 19 cases (group A: mean age, 78.4 years; range, 71-87) and failed in 7 patients (group B: mean age, 79.8 years; range 73-85). In the follow-up period biliary pain without an increase in pancreatic serum enzymes occurred in six patients in group A and in all patients in group B (p = 0.002); recurrence of acute biliary pancreatitis with a need for hospitalization occurred in one patient in group A and in four patients in group B (p = 0.01). These results suggest that endoscopic sphincterotomy may be considered a very useful option in reducing the recurrence of acute biliary pancreatitis in elderly patients with gallstones and a high anesthesiological risk of cholecystectomy.

Nonsurgical treatment of acute necrotizing pancreatitis.

Our objective was to analyze conservative management in a large series of acute necrotizing pancreatitis (ANP) patients in a specialized center for pancreatic disease in the Internal Medicine and Emergency Department of a 1,500-bed hospital. One hundred ninety-nine patients with ANP were considered (mean age, 55.4 +/- 18.2 years; biliary etiology, 60.3%). Identification of necrotizing forms of acute pancreatitis was obtained by ultrasonography, computed tomography scan, and surgery (53 cases). Exclusion of infection of the necrosis was based on clinical findings and percutaneous aspiration with bacteriological sampling. Medical treatment was started in all cases; 37 patients required ICU treatment; 87 patients underwent early endoscopic cholangiopancreatography (ERCP), and endoscopic sphincterotomy was performed in 61 cases; and percutaneous guided aspiration of necrosis and fluid collections was performed in 78 cases and in 9 patients with acute pseudocysts. Fifty-three patients (26.6%) underwent surgery; all patients (n = 30) with infected necrosis were in this group. One hundred forty-six patients were unoperated (73.3%): clinical resolution of ANP and biochemical normalization was achieved in 132 cases (66.3%) at discharge. Ultrasonographic follow-up documented morphological resolution of necrosis and fluid collections in 84 cases (57.5%) at different periods from the onset of ANP (range, 2.2-63.5 weeks); 16 patients dropped out and seven patients are still being followed. Spontaneous regression of acute pseudocysts was observed in 59.2%; percutaneous/endoscopic aspiration was successful in 33.3%. Mortality was 9.5%, significantly lower than the mortality observed in operated patients (28.3%; p = 0.002). Conservative treatment of ANP with sterile necrosis may allow healing in most cases, independent of the extent of necrosis or its association with major complications.

Early prediction of aetiology and severity of acute pancreatitis by serum amylase and lipase assays.

OBJECTIVE: To evaluate whether simple pancreatic enzyme assays are useful in the early assessment of aetiology and prognosis of acute pancreatitis. DESIGN: A retrospective clinical study. SETTING: Department of Internal Medicine with a Pancreatic Disease Centre. PATIENTS: The study included 246 patients with acute pancreatitis admitted to our Unit within the first 24 hours from the onset of disease. Amylase and lipase serum levels and lipase/amylase ratio were evaluated. RESULTS: Serum amylase was higher in patients with necrotizing pancreatitis than oedematous and biliary pancreatitis than alcoholic (p < 0.009 and p < 0.05 respectively), but a high degree of overlap between values was found. No differences were noted in lipase serum levels. Lipase/amylase ratio was not different between patients with alcoholic and nonalcoholic pancreatitis. CONCLUSIONS: Evaluation of serum amylase and lipase is not useful for assessing aetiology and severity of acute pancreatitis, although amylase may be higher in severe and biliary forms.

[Predictive evaluation of acute necrotizing pancreatitis: results of a prospective study]. / Evaluation prédictive de la pancréatite aiguë nécrosante: résultats d'une étude prospective.

OBJECTIVES: The aim of this study has been to evaluate the prognostic efficiency of some indexes based on biochemical and clinical criteria and computed tomography (CT) findings in the early phase of necrotizing acute pancreatitis. METHODS: Prospective evaluation of 53 patients selected in two groups: a) 21 cases with severe prognosis (11 deaths and 10 patients with a complicated clinical outcome of more than 3 months) and b) 32 cases with lighter prognosis (clinical recovery within 3 months and no deaths). The prognostic indexes we considered were: CT-scan score, simplified prognostic criteria, modified Glasgow criteria, Hong-Kong criteria and C-reactive Protein serum value. RESULTS: The best values of sensitivity were obtained by C-reactive protein (100%) and CT findings (90.4%), the best values of specificity by Hong-Kong criteria (87.5%) and of efficiency by CT (85.1%). As concerns sensitivity, the statistical comparison (McNemar test) showed a significantly lower Hong-Kong level versus all the other indexes and a significantly greater level C-reactive protein versus simplified prognostic criteria and modified Glasgow score. The comparison of the specificity results showed a significantly greater level of CT, Hong-Kong and simplified prognostic criteria versus C-reactive protein and versus modified Glasgow score. Associating CT-score with Hong-Kong improved the value of specificity (90.3%) and efficiency (90.3%). CONCLUSIONS: Contrast enhancement CT-scan score showed the most valuable prognostic efficiency early during a severe form of necrotizing acute pancreatitis: the association with a simple biochemical index like Hong-Kong criteria (based on blood urea and glucose) yields an even greater accuracy in prognostic evaluation.

Fusion and duplication variants of pancreatic duct system. Clinical and pancreatographic evaluation.

The aim of this study was to assess the incidence of fusion and duplication variants of the pancreatic duct system and their clinical significance. A total of 650 endoscopic retrograde cholangiopancreatography were reviewed; 485 cases with satisfactory imaging of the pancreatic ducts were included in the study. Anatomic variants were observed in 48 patients (9.9%), fusion variants were 54.1% of the cases (22 pancreas divisum and 4 functional divisum), and duplication variants were 45.8% (13 bifurcations of the main pancreatic duct, 4 loop, 2N-shape, 3 ring). Clinical indications to endoscopic cholangiopancreatography were idiopathic acute pancreatitis (33.3%), suspected chronic pancreatitis (18.7%), unexplained abdominal pain (14.5%), suspected pancreatic mass (10.4%), chronic hyperamylasemia (6.2%), and acute biliary pancreatitis (16.6%). Except for acute biliary pancreatitis (significantly more frequent in duplication variants), no statistical difference was observed between the groups with anatomical variants concerning clinical features.

Early prognostic assessment of acute pancreatitis with sterile necrosis. A perspective clinical study.

In an attempt to early assess the prognosis of acute pancreatitis with sterile necrosis, we have perspectively studied 40 patients with necrotizing acute pancreatitis and sterile necrosis in the first 48 hours of disease. As prognostic parameters, we have considered the computed tomography score according to Balthazar, simplified prognostic criteria according to Agarwal, Glasgow criteria and C reactive protein. Patients were divided in A group, 5 patients who died, and B group, 35 patients who survived. Computed tomography score, simplified prognostic criteria and Glasgow criteria were significantly higher in A group than B (9.5 +/- 1 vs 6.3 +/- 1.9, 3.6 +/- 0.5 vs 1.2 +/- 1.2 and 5.4 +/- 1.7 vs 2.7 +/- 1.9 respectively); conversely, C reactive protein serum levels did not show significantly difference in the two groups. We conclude that the extension of pancreatic and extrapancreatic necrosis, as measured by computed tomography, as well as the failure of extrapancreatic organs and the development of systemic and metabolic complications, as assessed by simplified prognostic score and Glasgow criteria, are the most important determinant of prognosis in necrotizing acute pancreatitis with sterile necrosis.

[Serum pancreatic enzymes in patients with chronic renal failure on hemodialysis and in transplant patients]. / Enzimi pancreatici sierici in pazienti con insufficienza renale cronica in trattamento emodialitico ed in pazienti trapiantati.

OBJECTIVE: The aim of this study was to evaluate which of serum pancreatic enzymes was less influenced by chronic renal failure (CRF). MATERIALS AND METHODS: 40 patients with CRF undergoing hemodialysis (A group) and 24 renal transplant patients (B group) were considered. None of these patients showed clinical and instrumental findings of exocrine pancreas disease. Total amylase (T Amy), pancreatic isoamylase (P Amy), lipase (L) and Elastase-1 (E-1) were measured (in A group immediately before hemodialysis). RESULTS: In A group T Amy and P Amy showed a significant correlation with serum creatinine level. In A group T Amy serum levels were increased in 65% of cases, P Amy in 72.5%, L in 47.5%, E-1 in 10%; in B group T Amy serum levels were increased in 41.6%, P Amy in 20.1%, L in 8.3% and E-1 in 4.1%. Statistical comparison showed a significantly lower percentages in B group considering P Amy (p < 0.001) and L (p = 0.003). CONCLUSIONS: Our data suggest that E-1 is the only pancreatic enzyme whose specificity is not limited by CRF and thereby may be of value in the diagnosis of the exocrine pancreatic disease in patients with CRF on hemodialysis.

Soluble interleukin-2 receptor: a new marker in pancreatic adenocarcinoma?

An increase in soluble Interleukin-2 receptor has been observed in several lymphoproliferative diseases and in certain solid neoplasms. Little is known, however, of the serum levels of this marker in pancreatic cancer. We studied the behaviour of the soluble Interleukin-2 receptor in 32 patients with pancreatic cancer versus 17 patients with alcoholic chronic pancreatitis and 24 healthy controls. The results obtained showed a significant statistical difference (Student's "t"-test and Mann Whitney U test) between pancreatic cancer on one hand and chronic pancreatitis plus healthy controls on the other (p < 0.0001).

Pancreatico-choledochal junction and pancreatic duct system morphology in acute biliary pancreatitis. A prospective study with early ERCP.

Sixty-two patients with acute biliary pancreatitis (ABP) were prospectively studied by early ERCP in order to evaluate the morphology of the pancreatico-choledochal junction and the pancreatic duct system (PDS) and compared with 62 control patients. Abnormalities of the ampulla of Vater were observed in 66.1% (33.5% in controls; p = 0.001). A common channel for the common bile duct and the main pancreatic duct (MPD) were found in 70.9% of ABP cases; the length of common channel was < or = 5 mm in 79.5% and > 5 mm in 20.4%; the angle between CBD and MPD was < or = 30 degrees in 88.6% and > 30 degrees in 11.4% (no difference compared to the control group). A patent Santorini's duct were found in 37% of ABP cases vs 38.7% in controls (NS); there was no significant difference in patency of the duct of Santorini between edematous and necrotizing cases of ABP. Morphological changes of the PDS were found in all patients with necrotizing (22 cases) and in 15 out of 40 patients with edematous ABP (p < 0.0001).

[The role of clinical, biochemical and echographic data in identifying the biliary pathogenesis of acute pancreatitis]. / Ruolo dei dati clinici, biochimici ed ecografici nella identificazione della patogenesi biliare della pancreatite acuta.

The role of clinical (biliary pain and/or jaundice), laboratory (discriminant function (DF) calculated using AST, ALT, AlkPh and GGT serum values) and ultrasonographic (US)(dilation and/or stone of common bile duct (CBD)) findings in identification of the biliary etiology of acute pancreatitis (AP) was studied in 60 patients. AP biliary etiology was defined by ERCP executed in the early phase of the disease (lithiasis and/or stenosis of CBD; endoscopic features of forced papilla in patients with gallstone). US showed the best values of sensitivity (84.6%) and diagnostic efficacy (76.7%); DF showed the best results of specificity (62.5%) and of test positive predictive value (92.8%). The statistical evaluation (McNemar test) showed a significant increase of sensitivity for US vs clinical findings and of specificity for DS vs clinical findings (p less than 0.05). The sensitivity, specificity, accuracy, test negative and positive predictive value were improved to 96.1, 87.5, 96.6, 77.1 and 92% by the combination of US and DF. Therefore the association of US and DF can provide the best non invasive method in rapidly detecting CBD pathology as an etiological factor in AP and then the enough accurate indication to early operative ERCP.

Early endoscopic cholangiopancreatography and sphincterotomy in acute biliary pancreatitis: report of 50 cases.

Endoscopic retrograde cholangiopancreatography (ERCP) was successfully performed in 49/50 consecutive patients with acute pancreatitis and suspected biliary aetiology in the early phases of the disease (24-72 hours from admission). ERCP showed common bile duct lithiasis and/or stenosis (25 cholecystectomized patients) in 41/49 cases (83.7%). In 38 patients endoscopic sphincterotomy (ES) was performed: stone removal was possible in lithiasic patients (36 cases, 13 previously cholecystectomized); 3 further patients showed a main pancreatic duct stenosis (2 of these underwent pancreatic ES). The patients treated with ES showed a quick improvement in symptomatology and clinical outcome; no adverse effect of ERCP was found; no mortality was registered. Comparison with a previous series of 130 cases of acute biliary pancreatitis (ABP) showed a reduction in mortality, complications and length of hospitalization. These findings suggest that, from a diagnostic and therapeutic point of view, early ERCP is safe and useful in ABP.

[The clinical, histological and ultrastructural findings in a case of acute steatosis of pregnancy with a severe cholestatic syndrome]. / Rilievi clinici, istologici e ultrastrutturali in un caso di steatosi acuta gravidica con grave sindrome colestatica.

A case of acute steatosis in pregnancy featuring unusually severe cholestasis is discussed with details of the successful outcome for mother and foetus. The correspondence between clinical picture, histological and ultrasound findings is reported together with a detailed review of the latest reports in the literature and what they reveal about the true incidence of the disease, the variability of the clinical picture, whether and when it is better for both mother and child to interrupt.