The Belgian national registry on chronic pancreatitis: A prospective multi-centre study covering more than 800 patients in one year.

BACKGROUND/OBJECTIVES: The epidemiology, natural history, complications, and therapeutic management of chronic pancreatitis (CP) are not well described at the national level. This multi-centre prospective observational study involving eight Belgian hospitals aimed to improve the understanding of these aspects of CP in Belgium. METHODS: All patients with a diagnosis of CP based on imaging were eligible for this study. Data were gathered regarding epidemiology, etiology, CP complications, and treatment modalities. RESULTS: A total of 809 patients were included between 1/9/2014 and 31/8/2015. Most patients (794) were adults ≥16-years old, 74% were male, the median age at symptom onset was 47 (38-57) years, the median disease duration was 7 (3-13) years, and the median Izbicki pain score (IPS) was 96 (0-195). The main etiological risk factors according to the TIGAR-O classification were alcohol and tobacco (67%). Current drinkers had lower body mass index (BMI) (21.4 kg/m2 vs 24.1 kg/m2), higher IPS (110 vs 56), and longer inability to work than non-drinkers. Current smokers had lower BMI (21.5 kg/m2 vs 25 kg/m2) and higher IPS (120 vs 30) than non-smokers. Endocrine insufficiency and/or clinical steatorrhea was recorded in 41% and 36% of patients, respectively. The highest IPS was reported in patients with ongoing endotherapy (166 vs 50 for patients who completed endoscopy). CONCLUSION: This multicentric study on CP patients showed that current alcohol drinking and smoking are associated with pain and malnutrition. Pain scores were higher in patients with ongoing endotherapy, independently of surgery.

An unusual case of rectal perforation after liver transplantation.

We present the case of a 50-year-old patient in whom an anastomotic biliary stricture after liver transplantation was treated endoscopically by sphincterotomy, dilatation and stenting using a plastic biliary stent. A distal migration of the stent caused a perforation of the rectum which was treated following stent extraction per anum -- conservatively with antibiotics and temporary bowel rest.

Hospital cost categories of one-stage versus two-stage management of common bile duct stones.

BACKGROUND: In the era of cost-conscious healthcare, hospitals are focusing on costs. Analysis of hospital costs per cost category may provide indications for potential cost-saving measures in the management of common bile duct stones (CBDS) with gallbladder in situ. METHODS: Between October 2005 and September 2006, 53 consecutive patients suffering from CBDS underwent either a one-stage procedure [laparoscopic common bile duct exploration (LCBDE) with stone clearance and cholecystectomy (LCCE)] or a two-stage procedure [endoscopic retrograde cholangiopancreatography with sphincterotomy and stone clearance (ERCP/ERS) followed by LCCE]. Costs were defined in different cost categories for each activity centre and were linked to the individual patient via the "bill of activities". Only patients (n = 38) with an uneventful post-procedural course and with available cost data were considered for cost analysis. Total length of hospital stay (LOS) was 2 (0-6) days after one-stage and 8 (3-18) days after two-stage procedure (p < 0.0001). RESULTS: Costs per patient were significantly (p < 0.0001) less after one-stage versus two-stage management, i.e. total hospital costs (euro2,636 versus euro4,608), hospitalisation costs (euro701 versus euro2,190), consumables/pharmacy (euro645 versus euro1,476) and para-medical personnel (euro1,035 versus euro1,860; p = 0.0002). Operation room (OR) costs were comparable for one-stage and two-stage management (euro1,278 versus euro1,232; p = 0.280). Total hospital costs during ERCP were euro2,648 (euro729-4,544), during LCCE without LCBDE were euro2,101 (euro1,033-4,269), and during LCCE with LCBDE were euro2,636 (euro1,176-4,235). CONCLUSION: In the management of patients with CBDS and gallbladder in situ a one-stage procedure is associated with significantly less costs as compared with a two-stage procedure. From the economical point of view these patients should preferably be treated via a one-stage procedure as long as safety and efficacy of this approach are provided.

Clinical models are inaccurate in predicting bile duct stones in situ for patients with gallbladder.

BACKGROUND: The probability that a patient has common bile duct stones (CBDS) is a key factor in determining diagnostic and treatment strategies. This prospective cohort study evaluated the accuracy of clinical models in predicting CBDS for patients who will undergo cholecystectomy for lithiasis. METHODS: From October 2005 until September 2006, 335 consecutive patients with symptoms of gallstone disease underwent cholecystectomy. Statistical analysis was performed on prospective patient data obtained at the time of first presentation to the hospital. Demonstrable CBDS at the time of endoscopic retrograde cholangiopancreatography (ERCP) or intraoperative cholangiography (IOC) was considered the gold standard for the presence of CBDS. RESULTS: Common bile duct stones were demonstrated in 53 patients. For 35 patients, ERCP was performed, with successful stone clearance in 24 of 30 patients who had proven CBDS. In 29 patients, IOC showed CBDS, which were managed successfully via laparoscopic common bile duct exploration, with stone extraction at the time of cholecystectomy. Prospective validation of the existing model for CBDS resulted in a predictive accuracy rate of 73%. The new model showed a predictive accuracy rate of 79%. CONCLUSION: Clinical models are inaccurate in predicting CBDS in patients with cholelithiasis. Management strategies should be based on the local availability of therapeutic expertise.

Patients with large-duct primary sclerosing cholangitis and Crohn's disease have a better outcome than those with ulcerative colitis, or without IBD.

BACKGROUND: Approximately 20% of primary sclerosing cholangitis (PSC) patients with concomitant inflammatory bowel disease (IBD) have Crohn's disease (CD). AIM: To compare PSC/CD with other PSC patients. METHODS: Retrospective study of 240 PSC patients diagnosed between 1975 and 2012 (median follow-up 12 years). Activity of PSC at diagnosis was assessed by liver biopsy, Mayo risk and ERC scores. Survival without liver transplantation, number of transplantations and liver-related death were endpoints. RESULTS: Sixty-three per cent of patients had IBD: 105 UC, 32 CD and 14 IBD unclassified (IBDu). IBD was diagnosed before PSC in 50%. The yearly development of PSC after diagnosing IBD was similar in UC, CD or IBDu. Small-duct PSC was present in 28% of PSC/CD compared to 3% of PSC/UC. Small-duct PSC had a markedly better survival than large-duct PSC: no patient developed cholangiocarcinoma or liver-related death, but colorectal cancer occurred in three patients. In large-duct PSC, a more favourable outcome was evident in patients with CD. The liver disease was less progressive: one patient underwent liver transplantation compared to 28% and liver-related deaths were absent compared to 7% in the other PSC groups. CONCLUSIONS: The prevalence of PSC with concomitant Crohn's disease is relatively rare, but the outcome is more benign than PSC with UC or without IBD. Approximately one-fourth has small-duct PSC. In large-duct PSC/CD, liver disease is less aggressive and the outcome is much better. The outcome of PSC patients with UC resembled that of PSC without IBD.

Diagnosis and treatment of autoimmune hepatitis at age 65 and older.

AIM: To study features in older patients with autoimmune hepatitis, as this was considered mainly a disease of young females. METHODS: Analysis of 28 patients diagnosed at age > or =65 years compared with 84 younger patients. RESULTS: The incidence was similar at all age decades. The ratio M:F was 1:3 (> or =65 years) vs. 1:2 (<65 years). Presenting symptoms were not different when compared with younger patients and consisted of general malaise and fatigue (36%), jaundice +/- other symptoms (50%), or ascites (11%). Antinuclear antibodies (ANA) > or = 1/80 were positive in 93%, smooth muscle antibodies (SMA) > 1/40 in 50%, anti-liver kidney microsomes (anti-LKM) proved always negative. Histology showed acute necrotizing hepatitis in 19%, severe interphase hepatitis in 15%, chronic hepatitis with plasmo-lymphocytic infiltrate in 30%, cirrhosis in 29% (with active inflammation in one-third); biopsy was refused in 11%. The elderly responded very well to low doses of methylprednisolone (< or =8 mg) and azathioprine (1 mg/kg). This schedule obviates side-effects such as infections seen with higher dosages. CONCLUSION: Autoimmune hepatitis has to be also looked for in the elderly with acute and chronic hepatitis. The steroid therapy should be individualized but kept at a low dose.

Liver transplantation using cavoportal transposition: an effective treatment in patients with complete splanchnic venous thrombosis.

Complete venous thrombosis of the splanchnic system remains a major challenge in liver transplantation surgery. Some of these patients have been treated successfully by multivisceral transplantation. Cavoportal transposition is another alternative to treat these patients. We reviewed our single-center experience with this technique. Five patients with operatively confirmed complete splanchnic thrombosis were transplanted with the cava portal transposition technique. All survived the procedure; 60% survived long term. This technique is a useful salvage procedure in moribund patients with diffuse portal thrombosis who would otherwise rapidly succumb.

Liver transplantation using livers from septuagenarian and octogenarian donors: an underused strategy to reduce mortality on the waiting list.

Shortage of liver grafts is the only limiting factor for application of liver transplantation and causes an increasing mortality on the waiting list. Very old donors (>70 to 80 years old) are rarely referred to transplant centers because of the assumption that these livers will not work properly. Alternatively, transplant teams may be reluctant to use these very old livers due to the risk of poor posttransplant outcome. We reviewed our experience with seven liver transplantations using very old donor livers. We found that the results in terms of graft function and patient survival are adequate. Interestingly, the majority of these donors originated from a single referring donor unit (of more than 20 units who belong to our donor network) that systematically refers all brain-dead donors to the transplant center, independent of the age of the potential donor. This implies that many of these donors are left undetected in other units. In conclusion, very old donors should be referred to transplant centers since results of transplantation with these grafts are favorable.

Budd-Chiari syndrome: reassessment of a step-wise treatment strategy.

BACKGROUND AND STUDY AIMS: The Budd-Chiari syndrome is a rare disorder characterized by hepatic venous outflow obstruction. A step-wise management was recently proposed. The aim of this study is to reassess our treatment approach and long-term outcome. PATIENTS AND METHODS: The data of 37 Budd-Chiari patients, seen in our unit, were critically analyzed and compared with the ENVIE (European Network For Vascular Disorders of the Liver) data. RESULTS: Most patients had multiple prothrombotic conditions (41%), of which an underlying myeloproliferative neoplasm was the most frequent (59%). The JAK2V617F mutation was associated with more complete occlusion of all hepatic veins (JAK2 mutation +: 70% vs JAK2 mutation -: 23% and a higher severity score. The step-wise treatment algorithm used in our unit, in function of the severity of the liver impairment and the number and the extension of hepatic veins occluded, resulted in the following treatments: only anticoagulation (n = 7.21%), recanalization procedure (n = 4.21%), portosystemic shunts (n = 9.26%) and liver transplantation (n = 14.44%). This resulted in a 10 year survival rate of 90%. Treatment of the underlying hemostatic disorder offered a low recurrence rate. None of the 21 patients with a myeloproliferative neoplasm died in relation to the hematologic disorder. CONCLUSIONS: An individualized treatment regimen consisting of anticoagulation and interventional radiology and/or transplantation when necessary and strict follow-up of the underlying hematologic disorder, provided an excellent long-term survival, which confirm the data of the ENVIE study.

Mutation detection in the alpha-1 antitrypsin gene (PI) using denaturing gradient gel electrophoresis.

A method for mutation detection in the alpha-1 antitrypsin gene (protease inhibitor 1; PI) has been developed using denaturing gradient gel electrophoresis of PCR amplified gene fragments. Using this experimental approach, all common phenotypes and mutations could be detected. Denaturing gradient gel electrophoresis (DGGE) was compared with standard isoelectric focusing (IEF) in 20 potential alpha1-antitrypsin deficient patients and their relatives. The genotype determined by DGGE was found to be more reliable in some cases than IEF, which is essential for a proper diagnosis of alpha-1 antitrypsin malfunctioning.

Energy supplementation in the last trimester of pregnancy in East Java, Indonesia: effect on breast-milk output.

Breast-milk output was measured in women who during the last trimester of pregnancy consumed a high- or low-energy supplement (53 and 55 women, respectively). Infant and mother pairs were enrolled at 2 or 6 wk postpartum. Test weighings were done four times at 8-wk intervals. Mean breast-milk output ranged from 682 to 744 g/d in the age period of 2 wk to 7 mo. There was no difference in milk output between the two experimental groups. In all cohorts, breast-feeding frequency influenced milk output positively. Only at age 18-22 wk did the mothers' prepregnancy or 4-wk postpartum body mass index play an additional role. The results confirm that breast-milk output of mildly undernourished women is comparable with that of well-nourished women. Short-term energy supplementation during pregnancy did not increase breast-milk output, probably because the sample studied was not at nutritional risk.

Endoscopic biliary endoprosthesis in elderly patients with large bile duct stones: long-term follow-up.

OBJECTIVE: To assess the long-term evolution of elderly patients with large or impacted bile duct stones, treated by an endoscopic biliary endoprosthesis. DESIGN: Case series. SETTING: Tertiary care center. PATIENTS: Twenty-three patients with a mean (+/- SD) age of 86 +/- 5 years (range, 77-97 years). On admission, 96% were highly symptomatic. These patients represent 8.4% of a group of 273 elderly patients (greater than or equal to 70 years old) with choledocholithiasis treated by endoscopic sphincterotomy between November 1984 and May 1989. INTERVENTION: Endoscopic insertion of a biliary endoprosthesis. RESULTS: Eight-seven percent (20/23) remained completely free of biliary symptoms and died of unrelated illness (48%) after a mean follow-up of 23 months or are still alive (39%) with a mean follow-up of 52 months. In four cases, this asymptomatic evolution now extends for more than 5 years. CONCLUSION: Insertion of a biliary endoprosthesis offers an effective method for long-term treatment of non-extractable biliary stones in elderly patients.

Percutaneous transhepatic cholangioscopy for diagnosis and therapy of biliary diseases in older patients.

OBJECTIVE: To describe the use of percutaneous cholangioscopy in older patients with complex diagnostic and therapeutic bile duct disorders. DESIGN: Case series. SETTING: Tertiary care center. PATIENTS: Fourteen patients with a mean age of 74 (SD +/- 9) years (range, 60-91 years) underwent percutaneous cholangioscopy. Eleven of these patients presented with endoscopically irretrievable bile duct stones. These 11 patients represent 4.1% of a group of 342 patients (age > or = 60 years) with a mean age of 76 (SD +/- 9) years who were treated endoscopically because of common bile duct stones between January 1993 and January 1996. Three patients presented with obstructive jaundice resulting from a bile duct stricture. In these three patients, brushing cytology of the strictures had proved to be negative. INTERVENTION: After creation and dilatation of a percutaneous transhepatic tract, cholangioscopy was carried out with a flexible cholangioscope. All procedures were performed under mild sedation and analgesia. Stone disintegration was obtained by electrohydraulic lithotripsy, applied through the working channel of the cholangioscope. RESULTS: Complete stone disintegration and removal was obtained after one to three cholangioscopic sessions in all 11 patients with stones. A histological diagnosis of malignancy was obtained in the three patients with biliary strictures. CONCLUSIONS: Percutaneous cholangioscopy is a well tolerated and promising technique in our diagnostic and therapeutic strategy in older patients with complex biliary disorders not responsive to peroral endoscopic diagnosis or treatment.

Percutaneous transhepatic cholecystostomy for acute complicated calculous cholecystitis in elderly patients.

OBJECTIVE: To assess the immediate and long-term outcomes of elderly patients with acute complicated cholecystitis treated by percutaneous cholecystostomy. To assess the results of bile cultures obtained in this group of patients. DESIGN: Case series. SETTING: Tertiary care center. PATIENTS: Thirty-two patients, with a mean (+/- S.D.) age of 78 +/- 8 years (range, 58-92 years), and who presented with acute cholecystitis complicated by empyema formation. Sixty-six percent had associated disorders, which rendered them at high risk for surgical intervention. INTERVENTION: Percutaneous transhepatic catheter drainage of the gallbladder, with a mean drainage time of 20 days (range 0-84 days). In addition, endoscopic sphincterotomy with removal of common bile duct stones was performed in six patients and percutaneous aspiration of an associated liver abscess in four cases. RESULTS: Percutaneous cholecystostomy was followed by rapid regression of clinical symptoms and of radiologic abnormalities in all patients. Sixteen cases (50%) underwent elective cholecystectomy 1-12 weeks after cholecystostomy. One of them died of aspiration pneumonia, whereas 15 had no post-operative problems and were discharged 9 days (mean) after surgery. Forty-four percent (14/32) were considered inoperable: they remained completely free of biliary symptoms and died of unrelated illness (22%) after a mean follow-up of 6 months (range, 1-22 months) or are still alive (22%) with a mean follow-up of 15 months (range, 5-36 months). Bile cultures were positive in 75% of the patients. Escherichia coli, other aerobic Gram-negative micro-organisms, and anaerobic bacterial species accounted for 35% (16/46), 28% (13/46), and 20% (9/46) of the isolated bacteria, respectively. All aerobic Gram-negative species tested in vitro were susceptible to gentamicin and to temocillin. CONCLUSIONS: Percutaneous transhepatic cholecystostomy is a safe and effective procedure in the treatment of elderly high-risk patients with acute cholecystitis complicated by empyema formation. It can be followed by elective cholecystectomy, if possible, or by expectant conservative management in patients who are inoperable because of systemic disease.

A pancreatic mucinous cystadenoma in a man with mesenchymal stroma, expressing oestrogen and progesterone receptors.

A 43-year-old man presented with abdominal discomfort caused by relapsing pancreatitis. Radiological examination revealed a multilocular cystic mass in the tail of the pancreas, which was resected. Gross examination showed a multilocular cystic lesion measuring 2.5 cm in diameter and containing clear fluid. Microscopically, a mucinous cystadenoma with mesenchymal stroma was diagnosed. The lesion showed two different components: a cyst lined by a columnar, mucin-secreting epithelium and a moderate cellular stroma composed of spindle cells. The stromal element appeared similar to primitive mesenchyme. Immunohistochemical staining confirmed this origin through vimentin expression and showed moderate to strong nuclear staining with oestrogen and progesterone receptor antibodies. Cystadenomas are rare tumours of the pancreas, but mesenchymal stroma is uncommon in such tumours; it is more frequently described in the liver and the bile ducts, and primarily in women.

Is early enteral nutrition in acute pancreatitis dangerous? About 20 patients fed by an endoscopically placed nasogastrojejunal tube.

Bowel rest during treatment of acute pancreatitis deprives the gut of nutrients and affects its structure and function. Enteral feeding is usually performed late in the course of acute pancreatitis and therefore cannot prevent intestinal barrier dysfunction and possible bacterial translocation. To assess the effect of early enteral nutrition we performed a prospective study on 21 patients (11 males/10 females) presenting with severe acute pancreatitis (13 biliary, 6 alcoholic, and 2 miscellaneous). Severity was established by a mean Ranson score of 3.57. All but one patient could be fed through a double-lumen nasogastrojejunal tube within 60 h after admission. No significant complication of the technique was observed. We conclude that early jejunal feeding can be used safely in severe acute pancreatitis. Further comparative studies are necessary to demonstrate any superiority to total parenteral nutrition.

Hepatocellular carcinoma in Belgium: clinical and virological characteristics of 154 consecutive cirrhotic and non-cirrhotic patients.

OBJECTIVE: This study analyses the characteristics of patients with hepatocellular carcinoma (HCC) in a low endemic area with special emphasis on the differences between cirrhotic and non-cirrhotic patients. DESIGN AND SETTING: The files of 154 consecutive patients with HCC observed in a single tertiary care hospital have been investigated to determine epidemiological parameters and diagnostic procedures. RESULTS: Compared to non-cirrhotic cases, cirrhotic patients with HCC are older and have a more pronounced male predominance. Their disease is more advanced, they usually present with multi-focal tumours, rarely located in the left liver lobe. Antibodies to hepatitis C (anti-HCV) are present in 55%, 52% ever had contact with hepatitis B (HBV) and 31% were hepatitis B surface antigen (HBsAg)-positive. Six non-cirrhotic cases were anti-HCV-positive. alpha-Fetoprotein (AFP) elevation > 50 and > 400 microg/l was more frequently observed in cirrhotic patients with HCC (P = 0.016). A striking association was found between enhanced AFP levels and the presence of anti-HCV (P = 0.0006), while no such relation existed for AFP and HBV markers. The sensitivity of a 'routine' ultrasound examination is disappointing for the early detection of HCC in cirrhotic patients. CONCLUSIONS: In our hospital, in a low endemic area for HCC, we have a surprisingly high proportion of non-cirrhotic patients with HCC (40%). In cirrhosis, usually the consequence of alcohol abuse or hepatitis B or C, small tumours can be missed by ultrasonography if not specifically looked for. AFP levels are particularly elevated in hepatitis C-induced HCC.

Traditional infant feeding practices: right or wrong?

Infant feeding practices, breastmilk and food intake and post-natal growth in Madura, East Java, Indonesia and Machakos, Kenya are described. Breastfeeding is commonly practised. Additional foods are introduced the first week post-partum in Madura and at age 2-3 months in Machakos. Growth started to falter at 2-3 months in Madura but was acceptable during the first 6 months in Machakos. It was felt that apart from breastfeeding and morbidity, other factors pertaining to mother's perceptions about what infants should eat and her possibility to make suitable weaning foods, should be considered to understand the background of growth faltering.

Nutritional transition during infancy in East Java, Indonesia: 1. A longitudinal study of feeding pattern, breast milk intake and the consumption of additional foods.

Infant feeding pattern was studied longitudinally from birth to 52 weeks among all infants born in the period September 1982-December 1984 in three villages in Madura, East Java (n = 687). Genuine demand breast-feeding was practised but it is the custom to force-feed infants from as early as the third day after birth until about 16 weeks. In a sub-sample the intake of breast milk and additional foods were measured, longitudinally in 76 infants and cross-sectionally in 77 infants. Breast milk intake ranged from 745 g per 24 h in the first month to 640 g per 24 h in the 12th month. Force-feeding did not have a negative influence on breast milk intake. The main constraint in infant feeding is the low intake of additional foods, which remained at 180 kcal and 3 g protein per day from the age of 16 weeks onwards.

Nutritional transition during infancy in East Java, Indonesia: 2. A longitudinal study of growth in relation to the intake of breast milk and additional foods.

Weight and length of infants, born in two villages in Madura, East Java were measured longitudinally from birth to 12 months (n = 391). In a sub-sample (n = 76) the intake of breast milk and additional foods during 48 h were also measured. The shape of the weight curve of Madurese infants is comparable to that of healthy, exclusively breast-fed infants in the UK and US during the first 6 months of life, in spite of the custom to force-feed from as early as the first week. The use of a more 'appropriate' growth curve of exclusively breast-fed, healthy infants instead of the NCHS reference failed to define more accurately the age at which growth faltering starts. It is recommended to use weight increments as an indicator of the onset of growth faltering. Breast milk intake correlated significantly with attained weight. However, it explains only a small percentage of the variation in weight, viz. 12-24 per cent. There was no correlation between energy or protein intake from breast milk and additional foods and weight gain.

PIP: Weight and length of infants, born in 2 villages in Madura, East Java, were measured longitudinally from birth-12 months (n=391). In a subsample (n=76), the intake of breastmilk and additional foods during a 48 period were also measured. The shape of the weight curve of Madurese infants is comparable to that of healthy, exclusively breastfed infants in the United Kingdom and the US during the 1st 6 months of life, in spite of the custom of force feeding from as early as the 1st week of life. The use of a more appropriate growth curve of exclusively breastfed, healthy infants instead of the NCHS reference failed to define more accurately the age at which growth faltering starts. It is recommended that weight increments be used as an indicator of the onset of growth faltering. Breastmilk intake correlated significantly with attained weight. However, it explains only a small % of the variation in weight, approximately 12-24%. There was no correlation between energy or protein intake from breastmilk and additional foods and weight gain.