F-18-fluorodeoxyglucose (FDG) positron-emission tomography of Echinococcus multilocularis liver lesions: prospective evaluation of its value for diagnosis and follow-up during benzimidazole therapy.

BACKGROUND: Long-term benzimidazole therapy benefits patients with non-resectable alveolar echinococcosis (AE). Methods to assess early therapeutic efficacy are lacking. Recently, AE liver lesions were reported to exhibit increased F-18-fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET). To assess the value of FDG-PET for diagnosis and follow-up of AE patients. PATIENTS/METHODS: Twenty-six consecutive patients with newly diagnosed AE were enrolled. Baseline evaluation included CT and FDG-PET. Thirteen patients (11 women; median age 50 years, range 40-76) were resected, the remaining 13 (8 women; median age 60 years, range 39-72) had non-resectable disease, were started on benzimidazoles, and CT and FDG-PET were repeated at 6, 12 and 24 months of therapy. Twelve consecutive patients with newly diagnosed cystic echinococcosis (CE) of the liver were also subjected to baseline FDG-PET. RESULTS: In 21/26 AE patients, baseline PET scans showed multifocally increased FDG uptake in the hepatic lesions' periphery, while liver lesions were FDG negative in 11/12 CE patients. Thus, sensitivity and specificity of FDG-PET for AE vs. CE were 81% and 92%, respectively. In 5 of 10 non-resectable patients with increased baseline FDG uptake, the intensity of uptake decreased (or disappeared) during benzimidazole therapy, in 3 by >or=2 grades within the initial 6 months. CONCLUSIONS: FDG-PET is a sensitive and specific adjunct in the diagnosis of suspected AE and can help in differentiating AE from CE. The rapid improvement of positive PET scans with benzimidazole therapy in some patients indicates that absent FDG uptake does not necessarily reflect parasite viability.

Waiting for a liver transplant: psychosocial well-being, spirituality, and need for counselling.

UNLABELLED: The number of patients in need of a liver transplant vastly exceeds the number of available organs; the demand worldwide for organs leads to increased waiting times and mortality of patients on the waiting list. The aim of our study was to assess the psychosocial well-being of transplant candidates and their need for psychosocial counselling. METHODS: Sixty-nine liver transplant candidates were asked about their psychosocial well-being, quality of life, spirituality, and need for counselling assessed by interview and questionnaire (HADS-D, FLZ, LOT, SOC, SF-36, SBI-15R) during the initial evaluation procedure for organ transplantation as well as 3 and 6 months after listing. RESULTS: Candidates for a liver transplant exhibited a significant limitation in the levels of their quality of life and psychological well-being, compared with the community normal samples. They showed significantly higher levels of anxiety, but lower levels of spirituality. Almost half of the candidates (47%) expressed a need for counselling during the evaluation procedure. Patients with advanced diseases reported a lower need. Age and the personality-related "Sense of Coherence" correlated negatively with need for counselling. On the waiting list, psychosocial parameters and functions remained largely stable; the need for counselling decreased significantly. CONCLUSIONS: There is a relevant need for psychosocial counselling during the process of liver transplant evaluation. Need for counselling is associated with personality and age, as well as with somatic parameters.

Intravenous iloprost bridging to orthotopic liver transplantation in portopulmonary hypertension.

Portopulmonary hypertension (PPHTN) is associated with poor prognosis and high perioperative mortality after orthotopic liver transplantation. This study documents the first case of a patient with PPHTN who was successfully bridged to orthotopic liver transplantation with i.v. iloprost, a stable prostacyclin analogue. The PPHTN had resolved completely 4 months after successful transplantation. In conclusion, portopulmonary hypertension is a relative contraindication to orthotopic liver transplantation, which should be attempted only if pulmonary haemodynamics improve with prostanoids. In this context, iloprost may be a valuable alternative to epoprostenol.

Mutations of the cystic fibrosis gene in patients with chronic pancreatitis.

OBJECTIVE: Several studies have reported an increased frequency of cystic fibrosis gene mutations in idiopathic but not in alcoholic chronic pancreatitis. The impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis has not been analyzed. The aim of our study was to determine the frequency of cystic fibrosis gene mutations in patients with chronic pancreatitis with long-term follow-up and to see whether patients with mutations have a clinically different natural course compared to those without mutations. METHODS: Eighty two patients with chronic pancreatitis and 11 patients with recurrent acute pancreatitis of our well defined pancreatitis cohort were screened for the 31 most common cystic fibrosis gene mutations. The impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis was assessed. RESULTS: A cystic fibrosis gene mutation was detected in five of 49 patients with alcoholic chronic pancreatitis (10.2%; 2.3 times the expected frequency) and in three of 14 patients with idiopathic-juvenile chronic pancreatitis (21.4%; 4.8 times the expected frequency). No mutations were found in the remaining patients with chronic pancreatitis of rare causes, hereditary pancreatitis, and recurrent acute pancreatitis. The frequency of pancreatic calcifications was significantly higher in patients with alcoholic chronic pancreatitis without mutations. This result was not confirmed in patients with idiopathic-juvenile chronic pancreatitis. The duration of pain and the frequency of exocrine and endocrine insufficiency was comparable in both subgroups irrespective of the mutation status. CONCLUSION: Our data indicate a significantly increased frequency of cystic fibrosis gene mutations both in patients with alcoholic and idiopathic-juvenile chronic pancreatitis. The natural course was similar in patients with mutations compared to those without mutations.

Trypsinogen gene mutations in patients with chronic or recurrent acute pancreatitis.

Three-point mutations (R117H, N211, A16V) within the cationic trypsinogen gene have been identified in patients with hereditary pancreatitis (HP). A genetic background has also been discussed for idiopathic juvenile chronic pancreatitis (IJCP), which closely mimicks the clinical pattern of HP, and alcoholic chronic pancreatitis because only a small number of heavy drinkers develop pancreatitis. This prompted us to screen 104 patients in our well-defined pancreatitis cohort for the currently known cationic trypsinogen gene mutations. The R117H mutation was detected in seven patients (six patients of two clinically classified HP families, one patient with clinically classified IJCP) and the A16V mutation in one IJCP patient. No cationic trypsinogen gene mutations were found in the remaining 96 patients with chronic and recurrent acute pancreatitis of various etiologies. Our results demonstrate the need for genetic testing to exclude HP, particularly in the presence of an atypical or unknown family history. In addition, cationic trypsinogen gene mutations are no predisposing factor in patients with chronic and recurrent acute pancreatitis of different etiologies.

The natural history of pain in alcoholic chronic pancreatitis.

BACKGROUND & AIMS: The pain pattern of chronic pancreatitis (CP) and its surgical implications are discussed. The aim of this study was to (1) define typical pain patterns, (2) correlate pain patterns with the presumptive causes of the pain, and (3) compare the natural history of patients treated conservatively or surgically with respect to pain relief, pancreatic dysfunction, and clinical outcome. METHODS: A cohort in this prospective long-term study included 207 patients with alcoholic CP (91 without and 116 with surgery for pain relief). A clinically based staging system was applied to characterize pain in the evolution from onset to end-stage CP. RESULTS: Average duration of CP was 17 years. In early-stage CP, episodes of recurrent (acute) pancreatitis predominated. Chronic pain was typically associated with local complications (mainly pseudocysts, 84 of 155; 54%), relieved definitely by a single (drainage) procedure in approximately two thirds of patients. Additional surgery was required for late pain recurrence in 39 patients (34%), primarily symptomatic cholestasis (18 of 39; 46%). All patients achieved complete pain relief in advanced CP. CONCLUSIONS: In our experience, relief of chronic pain regularly follows selective surgery tailored to the presumptive pain cause or occurs spontaneously in uncomplicated advanced CP.

Alcoholic nonprogressive chronic pancreatitis: prospective long-term study of a large cohort with alcoholic acute pancreatitis (1976-1992).

140 patients with alcoholic acute (recurrent) pancreatitis were enrolled in a prospective long-term study over the last 16 years. Regular control studies regarding progression to advanced chronic pancreatitis were performed. Based on long-term outcome the patients were classified into two groups: group A (n = 109; 77.8%) with progression to advanced chronic pancreatitis (84% with calcification, 95% with exocrine insufficiency) and group B (n = 31; 22.2%) without progression (no calcification, no exocrine insufficiency). The two groups were comparable in age, sex, and mean duration of disease from onset (13.1 +/- 5.2 vs. 13.8 +/- 4.9 years). Surgery for pseudocysts was performed in 47% of group A and in 29% of group B. In group B, no pancreatic duct dilatation occurred (in 86% > 8 years from onset). However, 4 of 7 patients with adequate histology showed unequivocal chronic pancreatitis. Surprisingly, all patients of group B except two got spontaneous lasting pain relief irrespective of alcohol intake or normal pancreatic function. Our findings indicate that a subgroup of alcoholic acute pancreatitis does not progress to advanced chronic pancreatitis. This subgroup may be identical with "small duct" chronic pancreatitis. The factors responsible for progression (group A) or nonprogression (group B) remain to be elucidated.

Progression of alcoholic acute to chronic pancreatitis.

Alcoholic chronic pancreatitis usually progresses from acute attacks to chronic pancreatitis within one to 19 years. The factors responsible for the appreciable variability in progression are unclear. In this study the relation between progression and the incidence and severity of acute episodes in a large cohort of patients with alcoholic chronic pancreatitis was analysed. All patients with at least one documented episode of acute pancreatitis have been studied prospectively over the past 30 years according to our protocol. Patients were classified according to their long term course into (a) calcific (n = 185), (b) non-calcific (n = 30), and (c) non-progressive (n = 39) chronic pancreatitis groups. The yearly incidence of acute attacks of pancreatitis was significantly higher in groups (a) and (b) than in group (c). Furthermore, the progression rate to advanced chronic pancreatitis (groups (a) and (b)) correlated with the incidence of severe pancreatitis (associated with pseudocysts in more than 55%). Pseudocysts were located primarily in the cephalic pancreas in groups (a) and (b) (58-71%) and in the pancreatic tail in group (c) (61%). In conclusion, these data suggest that the progression of acute to chronic pancreatitis is closely related to the incidence and severity of acute attacks. This finding and the primary location of pseudocysts in the cephalic pancreas (groups (a) plus (b)) are compatible with the 'necrosis-fibrosis' pathogenetic hypothesis.