Où achat cialis sans ordonnance et acheter viagra en France.
Best Practice & Research Clinical Gastroenterology
Re´my F. Meier* MDGI-Unit, University Hospital Liestal, Kantonsspital Liestal, CH-4410 Liestal, Switzerland
Christoph Beglinger MDUniversity Hospital, Basel, Switzerland
The pancreas plays a major role in nutrient digestion. Therefore, in both acute and chronicpancreatitis, exocrine and endocrine pancreatic insufficiency can develop, impairing digestive andabsorptive processes. These changes can lead to malnutrition over time. In parallel to thesechanges, decreased caloric intake and increased metabolic activity are often present. Nutritionaldeficiencies negatively affect outcome if they are not treated.
Nutritional assessment and the clinical severity of the disease are important for planning anynutritional intervention.
In severe acute pancreatitis, enteral nutrition with a naso-jejunal feeding tube and a low moleculardiet displays clear advantages compared to parenteral nutrition. Infectious complications, lengthof hospital stay and the need for surgery are reduced. Furthermore, enteral nutrition is less costlythan parenteral nutrition. Parenteral nutrition is reserved for patients who do not tolerateenteral nutrition.
Abstinence from alcohol, dietary modifications and pancreatic enzyme supplementation issufficient in over 80% of patients with chronic pancreatitis. In addition, oral supplements arehelpful. Enteral nutrition can be necessary if weight loss continues. Parenteral nutrition is veryseldom used in patients with chronic pancreatitis.
Key words: Acute pancreatitis; Chronic pancreatitis; Enteral nutrition; Parenteral nutrition;Nutritional state assessment.
The two major inflammatory diseases of the pancreas are acute and chronicpancreatitis. In both circumstances nutrient digestion and absorption can be impaired,both short-term or indefinitely. Nutritional support is different in acute and chronicpancreatitis. Under normal conditions, the pancreas plays an important role in thedigestion and absorption of nutrients. An impaired pancreatic function has negativeconsequences for the patient. Nutritional deficiencies can occur in both acute andchronic pancreatitis. Malnutrition in acute pancreatitis can be caused by the acute
* Corresponding author. Tel.: C41 61 925 21 87; fax: C41 61 925 28 04.
1521-6918/$ - see front matter Q
2006 Elsevier Ltd. All rights reserved.
catabolic stress induced by the systemic inflammatory response, while in chronicpancreatitis malnutrition is due to pain and decreased nutrient digestion andabsorption. This overview focuses on the consequences of impaired pancreaticfunction and the importance of nutritional support to decrease morbidity and mortality.
Digestion and absorption of nutrients is a complex and well coordinated processinvolving multiple and interacting gastrointestinal secretory, absorptive, motor andcirculatory systems.Normal functioning of the pancreas is a prerequisite forundisturbed processing and mucosal uptake of nutrients.
The normal human pancreas secretes more than ten different enzymes together
with water, bicarbonate and other proteins. These enzymes are secreted in abundanceand hydrolyse macronutrients within the intestinal lumen, of which lipids, proteins andcarbohydrates are of particular importance. The regulation of human pancreaticsecretion is part of an overall, integrated, motor-secretory A meal is themost important physiological stimulus for pancreatic secretion. Pancreatic secretionalso occurs in the fasting (interdigestive) state in a coordinated regulated fashion. Thepostprandial pancreatic enzyme output reaches maximal rates following a mixed mealof 20 kcal/kg body weight. The duration of the response increases with greater caloricloads. The proportions of fat, carbohydrate and protein within a meal influence theduration and enzyme composition of the pancreatic response.
The tuned gastric emptying of small portions of pre-processed, liquid chyme into the
duodenum starts the pivotal period of intraluminal digestion. The duodenal entry ofnutrients is accompanied by bursts of pancreatic and biliary digestive secretions withwhich nutrients are instantly mixed. Exposed to a large mucosal area, digestion andsubsequent absorption of the nutrients occurs rapidly.
The generation of absorbable products as a result of intraduodenal digestive
processes is the major event for the regulation and integration of the postprandialgastrointestinal response. Multiple neuro-humoral mechanisms are involved incontrolling gastric emptying, secretory and metabolic responses.
A vagally-mediated cephalic phase contributes to the overall response, but the most
important mechanism inducing postprandial human pancreatic secretion is the presenceof nutrients within the duodenal lumen. Postprandial stimulation of pancreatic secretionby duodenal nutrients involves the activation of neural pathways (vagal-cholinergicreflexes) and the release of regulatory peptides (e.g. cholecystokinin (CCK)) andsecretin, with a tight interaction of neural- and humoral systems.
The regulation of human postprandial pancreatic secretion also involves inhibitory
mechanisms that probably serve to modulate and eventually terminate the response.
Somatostatin, pancreatic polypeptide (PP), peptide YY and glucagon-like peptide-1 areinvolved in this regulatory cir
In parallel with the induction of the postprandial pancreatic response, gastrointestinal
motility changes from basal interdigestive into postprandial activity. Induction,maintenance and duration of fed intestinal motility and pancreatic secretion are tightlycoupled and In the fasting state, characterised by the absence ofstimulatory nutrients within the lumen, the human pancreas is not quiescent but secretesin a characteristic pattern. Output of water, bicarbonate and enzymes occurs in parallelwith the phases of interdigestive cyclical motility (migrating motor complex, MMC).
† the well coordinated secretion and motility patterns are disturbed† nutritional status and the course of the disease are negatively influenced.
Epidemiology and aetiology of acute pancreatitis
The true incidence of acute pancreatitis is not known exactly and it varies in differentareas of the world. In the USA, Great Britain and Germany, 11–23 cases/100 000people have been reported.Biliary lithiasis and chronic alcoholism are the two mostimportant causes for acute pancreatitis (accounting for 80–90% of cases). After theexclusion of alcoholism and ductal obstruction, there are some less frequent aetiologiesthat should be considered (
In Germany, alcohol and biliary-induced acute pancreatitis have a similar frequency.
In the USA, Australia, South Africa and Italy, alcohol is the dominant factor whereas in
Table 1. Aetiology of acute pancreatitis.
Azathioprine, sulfonamide, didanosine, thiazide, furosemide, pentamidine, tetracycline, valproic acid,
Periarteriitis nodosaHypothermiaMalignant hypertension
Biliary stonesTraumaEndoscopic retrograde pancreatography (ERCP)Pancreatic malignancyPancreas divisum
Viral (e.g. Coxsackie virus)Ascaris lumbricoides
Great Britain biliary lithiasis is more often seen. Females appear to be more oftenaffected than males. In female patients, a higher prevalence secondary to biliary stonesis the most important aetiological factor, whereas in males the most frequent cause ofacute pancreatitis is excessive alcohol consumption. Acute pancreatitis occurs morefrequently in the population aged between 50 and 70 years. The highest mortality canbe seen after age 60. Acute alcoholic pancreatitis is more frequently seen in males andthe onset is earlier, between 30 and 45 years of age. Biliary-induced pancreatitis occursbetween 50 and 70 years of age, with a higher proportion being female. In areas wherealcohol consumption is increasing, the alcoholic aetiology of acute pancreatitis is alsoincreasing. Alcoholic pancreatitis develops in only 5% of alcoholics and after at least 10years of ethanol abuse.
The most common causes of acute pancreatitis are:
† alcohol abuse in men† biliary stone obstruction in women.
Diagnosis, classification and outcome of acute pancreatitis
Acute pancreatitis is an acute inflammatory process that may involve the peripancreatictissue or even remote organs.Acute pancreatitis presents with abdominal pain,tenderness and elevation of serum pancreatic enzyme concentrations. A rise inconcentration of serum amylase and lipase is typical. Acute pancreatitis can becharacterised as either a mild or severe disease, with local or systemic complications.
According to the Atlanta criteriaapproximately 75% of patients have mild diseasewith a mortality rate of less than Mortality increases up to 20% if the diseaseprogresses to its severe necrotising form; in the most severe cases, mortality canexceed 30–40%.
Assessment of the severity and prediction of the progress of acute pancreatitis at the
time of admission can be difficult. Assessment at admission and during the course of thedisease is crucial for planing the optimal treatment. Several prognostic scoring systemsare available that include clinical aspects (e.g. Ranson score Glasgow score,Atlanta classification), laboratory and radiological criteria.The Atlanta classifi-cation of severity defines severe acute pancreatitis on the basis of standard clinicalmanifestations: a score of 3 or more in the Ranson criteria or a score of 8 or more inthe APACHE II criteria, as well as evidence of organ failure and intrapancreaticpathological findings (necrosis or interstitial Laboratory markersinclude the measurement of serum C-reactive protein (CRP) or urinary trypsinogenactivation peptide (TAP) concentration; both are useful in clinical practice. CRPconcentration has an independent prognostic value. A peak of more than 210 mg/l ondays 2 through 4, or more than 120 mg/l at the end of the first week has the samepredictive value as multiple-factor scoring systems.Urinary TAP level has been shownto predict the severity of acute pancreatitis 24 hour after onset. Urinary TAP level is
Table 2. Ranson criteria for severity assessment in acute pancreatitis.
During the first 48 hoursFall in haematocrit of
Table 3. CT grading of acute pancreatitis.
Focal, diffuse enlargement.
Contour IrregularityInhomogeneous attenuation
BCperipancreatic haziness/steady densities
B, CC ill-defined pancreatic fluid collection
B, CC2 ill-defined pancreatic fluid collections
suggested as a single marker for severity assessment, but it is not available as a routinetest.
The severity of acute pancreatitis can be graded using imaging on the basis of the
Balthazar score (which predicts severity from the computed tomography (CT)appearance, including the presence or absence of necrosis. An attack is defined as
† presents as mild or severe disease† has a mortality range of between !1–40% depending on severity† can be assessed for outcome using clinical, laboratory and imaging methods.
severe if more than 50% of the pancreatic gland does not show an enhancement of theparenchyma during the arterial phase of an intravenous contrast-enhanced CT scan.
The initial acute pancreatitis-inducing event has not yet been clarified in detail. The firststage in the initiation of acute pancreatitis is acinar cell injury with subsequent activationof trypsinogen to trypsin, which leads to autodigestion of the gland. Most patients havemild disease with minimal organ dysfunction and recover in a few days. In severe cases, asystemic inflammatory response syndrome (SIRS) develops, leading to pancreaticnecrosis and multiorgan failure. Inflammatory cytokines cause macrophages to migrateinto tissues that are distant from the pancreas, including the kidneys and lungs. Some ofthe cytokines (e.g. interleukin-1 and tumor necrosis factor (TNF) etc.) are involved inthe disease progression. Mast cells are very important in mediating both the local andsystemic effects. The local effects include alteration in microvascular and endothelialbarrier function. The systemic effects are mediated by the over-expression ofcytokines. The clinical presentation of the systemic effects are fever, tachycardia,tachypnoea, hypovolaemia, hypoxia, acute respiratory distress syndrome (ARDS),shock and ultimatively multiorgan failure.Furthermore, these mechanisms are
† nitrogen balance can become negative and may have an adverse effect on
† adequate nutritional support is of great importance.
involved in the hypermetabolic, hyperdynamic process that leads to catabolic stressassociated with nutritional deficiencies. This will have negative consequences, especiallyin patients already malnourished at the time of the initial attack.
Nutritional consequences during acute pancreatitis
Malnutrition is often seen in patients with acute pancreatitis prior to the first attack.Protein-calorie malnutrition arises or worsens due to the depletion of nutrients and to
† multiple mechanisms lead to autodigestion of the gland† the degree of the systemic inflammatory response syndrome predicts the
severity of the disease and the clinical outcome.
† to clarify whether a negative nitrogen balance has a direct influence on
† to stratified between the severity of pancreatitis and the degree of negative
the hypermetabolic state during the acute attack. Specific and non-specific metabolicchanges occur during acute pancreatitis. A variety of proinflammatory cytokinesincrease the basal metabolic rate. This results in increased energy consumptioIfpatients develop sepsis, 80% of them show a marked elevation in protein catabolism andan increased nutrient demandA negative nitrogen balance affects the clinicaloutcome. Sitzmann et reported a tenfold increase in the mortality rate when thenitrogen balance was negative, compared with those patients with a positive balance. Asyet, no study has been stratified according to disease severity and nitrogen balance.
Alteration of substrate metabolism during acute pancreatitis
Glucose metabolism in acute pancreatitis is determined by an increase in energydemand. Endogenous gluconeogenesis is increased as a consequence of the metabolicresponse. Glucose is an important source of energy and can partially counteract theintrinsic gluconeogenesis from protein degradation. This can compensate to a certaindegree the deleterious and unwanted effects of protein catabol
The maximum rate of glucose oxidation is approximately 4 mg/kg per minute. The
administration of glucose in excess of this can be harmful, because of lipogenesis andglucose recycling. Furthermore, hyperglycaemia and hypercapnia can occur. Hypergly-caemia is also associated with an increase in infections and metabolic complications.
Glucose levels can also be increased due to the frequently impaired insulin secretion.
There is little evidence that insulin supplementation is beneficial to these patients.
A negative nitrogen balance is often seen in severe acute pancreatitis. Protein loss shouldbe minimised in these patients, thus the increased protein turnover must be compensatedfor. Deficiency in certain amino acids may enhance pancreatic inflammation.
Hyperlipidaemia is often seen in acute pancreatitis. Increases in cholesterol and freefatty acid serum concentrations have been reported. The mechanism for these changesin lipid metabolism is not entirely clear. Alterations in lipid oxidation and lipid clearancemay both play a role. Serum lipid concentration returns to normal ranges if the patientrecovers. In some patients with pre-existing hyperlipidaemia, an increased risk of
† due to the catabolic state, the metabolism is altered for all three
† energy expenditure and protein catabolism are increased.
developing acute pancreatitis has been reported. Hyperglyceridaemia, ranging up to
† to elucidate the negative effect of amino acid deficiencies on pancreatic
† to define the mechanism of disturbed lipid metabolism in acute pancreatitis.
80–100 mmol/l has been seen in these paSeveral mechanisms have beensuggested as explanations for the harmful effects, but none of them has beenaccepted.
Are nutrients harmful in acute pancreatitis?
Intravenous glucose administration does not stimulate exocrine pancreaticsecretion.Enteral perfusion of glucose into the jejunum is only a weak stimulusfor exocrine pancreatic secretion.
Intravenous administration of protein hydrolysates either inhibits the exocrine
pancreatic secretory response, or has no effectHowever, amino acids canstimulate gastric acid secretion, which in turn may stimulate the pancreatic secretoryresponse. Jejunal perfusion of elemental diets containing defined amounts of protein oramino acids is well tolerated and does not significantly stimulate exocrine pancreaticsecretion. Regardless of whether an elemental diet is ingested orally or infused into theduodenum or the jejunum, the elemental diet results in lower stimulation than astandard diet infused at the same level.Elemental diets have been studied inpatients with acute pancreatitis and they were regarded as safe. However, clinicalexperience with the infusion of intact proteins into the jejunum has not been shown toinduce major negative effects on outcome.
Pancreatic secretion is not stimulated by intravenous lipids.However, case
reports have been published in which acute pancreatitis developed after theintravenous infusion of fat emulsions.In all of these cases it was not clear whetherthe increase in serum triglycerides was a direct cause of the acute pancreatitis, orwhether it was caused by other factors (e.g. comorbidities and/or other drugtherapies). The stimulation of exocrine pancreatic secretion by enteral administration
In patients with acute pancreatitis needing nutritional support:
† the enteral jejunal route is the preferred method today† all macronutrients can be perfused to the jejunum† most trials have used low molecular weight enteral formulas (elemental diets).
To clarify what is the best enteral nutritional support:
† standard enteral formulas or immune-modulating formulas need to be
compared with low molecular weight formulas
† large and well controlled studies are needed.
of lipids depends on the anatomical site of administration. If lipids are given into theproximal jejunum, only a minimal stimulation of exocrine pancreatic secretion occurs.
Thus, there is no convincing evidence that would suggest that the use of glucose,
proteins and triglycerides or other fats is contraindicated in patients with acutepancreatitis, provided that those patients are monitored for hyperglycaemia andhypertriglyceridaemia.
NUTRITIONAL TREATMENT IN ACUTE PANCREATITIS
Until recently, enteral nutrition, given either orally or by enteral tubes, was believed tohave a negative impact on the progression of the disease due to stimulation of exocrinepancreatic secretion and the consequent worsening of the autodigestive processes.
Even so, nutritional deficits are frequent in severe acute pancreatitis and nutrition as apart of therapy was neglected for a long time.
Oral feeding can increase abdominal pain in patients with acute pancreatitis. To
overcome these problems, patients were either fasted or nutritional support wasprovided by the parenteral route. Parenteral nutrition (PN) was considered to be thestandard treatment with two main goals: (1) to meet the nutritional requirements and(2) to avoid stimulation of exocrine pancreatic secretion. A clear benefit of PN has,however, not been shown in various trials. Two studies in patients with mild tomoderate severe acute pancreatitis compared parenteral nutrition to no nutritionalsupportor to tube feeding.In the trial by Sax et alno difference in the mortalityrate could be demonstrated. Catheter-induced septicaemias, as well as hyperglycaemia,occurred significantly more often in the PN group. McClave et alcompared earlyenteral nutrition (EN) via a jejunal tube to PN in a randomised controlled prospectivestudy. Enteral nutrition was initiated within 48 hour after admission to the hospital. The
outcome in both groups revealed no statistical differences in infectious complications,length of intensive care unit (ICU) stay, length of hospital stay, or days to oral foodintake. A small advantage of PN was seen in the endpoint of reaching the caloric target.
This was achieved in 86% of patients having PN compared to 72% having EN. Allpatients in both groups survived. In the PN group, significantly higher glucoseconcentrations were found in the first 5 days and PN was four times more expensivethan EN. PN is, in general, associated with more cases of hyperglycaemia and othermetabolic disturbances. It has become clear that this complication was often theconsequence of overfeeding.Van Den Berghe et al 57 provided clinical evidence thatirrespective of the route of nutritional support, controlling hyperglycaemia with insulinreduced mortality in critically ill patients.
Compared to mild acute pancreatitis, the feeding support in severe acute pancreatitis is
different. A prospective, randomised trial compared naso-jejunal tube feeding using a semi-elemental diet with PNEnteral feeding was well tolerated without adverse effects on thecourse of the disease. Patients who received EN experienced fewer septic complicationsand fewer total complications than those receiving PN. Furthermore, the costs ofnutritional support were three times higher in patients receiving PN. Windsor et allaterconfirmed these data. PN was compared with EN in patients with mild to moderatepancreatitis (peripheral PN versus sip feeds) and severe pancreatitis (total PN versus tubefeeding). The SIRS was significantly attenuated in all enterally fed patients. Sepsis andmultiorgan failure as well the incidence of surgery were reduced. Two patients died in theparenteral group, whereas no death occurred in the enteral group. A major weakness ofthis study was the low number of patients with severe pancreatitis and the total amounts ofnutrient delivered, revealing marked differences between the enteral and the parenteralgroup. A further trial by Powell et alcould not demonstrate the same positive results.
They compared early tube feeding in patients with a severe acute pancreatitis to patientswithout artificial nutrition.
Abou-Assi et treated 156 patients with acute pancreatitis during the first
48 hour with only intravenous (iv) fluid and analgesics. Of the 156 patients, 87% hadmild, 10% had moderate and 3% had severe disease. Those patients who improvedwere orally fed. The non-responders were randomised to receive nutrients either bynaso-jejunal tube or by PN; 75% of the initially enrolled patients improved with theinitial regimen and were discharged within 4 days. In the randomised group, 54% of theEN group (nZ26) and 88% in the PN group (nZ27) had an inadequate energy intake.
However, the patients in the enteral group were fed for a significantly shorter periodand had significantly fewer metabolic and septic complications. Hyperglycaemiarequiring insulin therapy was significantly higher in the parenterally fed patients.
Mortality was not different between the two groups.
The meta-analysis of Marik and Zaloga compared PN versus EN in patients with
acute pancreatitis and concluded that EN should be the preferred route of nutritionalsupport in patients with acute pancreatitis, because it was associated with a significantlylower incidence of infections, a reduced rate of surgical interventions and a reducedlength of hospital stay. There were no significant differences in mortality and non-infectious complications.
Many studies in the last decade in patients with trauma, terminal injury and after
major gastrointestinal surgery have shown a reduction in septic complications withenteral feeding.Enteral nutrition helps to maintain mucosal functions and limits theabsorption of endotoxins and cytokines from the gut.Four prospective studieshave shown that jejunal delivery of nutrients is possible in most patients with acuteProximal migration of the feeding tube and a subsequent pancreatic
stimulation can aggravate acute pancreatitis, but this is a rare ocurrence.Theplacement of feeding tubes either by pushing blindly, with the aid of fluoroscopy or byendoscopy is feasible most of the time.
With the publication of Eatock et alit seems that naso-jejunal feeding in severe acute
pancreatitis may not be necessary all the time. They compared naso-gastric feeding withnaso-jejunal feeding in a randomised study. The results showed that naso-gastric feedingwas safe, with no differences in pain scores, analgesic requirements, serum CRPconcentrations, or clinical outcome. If there are no problems with gastric emptying, naso-gastric feeding can be tried.
Enteral nutrition has been possible in most patients with acute pancreatitis that have
been studied in controlled prospective trials. In a more general population, dealing withlarge patient groups or including all treated patients, this was not found to be the case.
Oleynikov et ahave reported that EN was not possible in most patients with severeacute pancreatitis with a mean APACHE II-score of 17.2 and a mean Ranson-score of 4.3 onadmission. This was probably due to severe retroperitoneal inflammatory changes.
Two studies using specific enteral formulations have been published recently. In a
small study, Halley et reported a beneficial effect of a glutamine-rich multifibre dietcompared to a standard fibre diet on the recovery of IgG and IgM-proteins, with ashorter disease duration. In a second study, the enteral administration of the probioticstrain Lactobacillus plantarum 299 and prebiotic oat fibre was examined in patients withsevere acute pancreatitis.Twenty-two patients received live bacteria and 23 patientsreceived the same formulation with heat-killed bacteria. In the live bacteria group, onlyone patient developed a septic pancreatic complication requiring surgery compared tothe control group where seven patients required surgery. Furthermore, the incidenceof infected necrosis and abscesses were significantly lower (4.5 versus 30.4%). Thesenew data are exciting, but the approach cannot be recommended outside clinical trialsat this time. Larger trials are needed to confirm these findings.
Not all patients with acute pancreatitis need specific nutritional support. There is no
evidence that nutritional support (enteral or parenteral) has a beneficial effect onclinical outcome in patients with mild acute pancreatitis. In mild acute pancreatitis, theclinical course is usually uncomplicated and patients can consume an oral diet low in fatwithin 3–7 days. The disease does not have a major impact on nutritional status, or onenergy and substrate metabolism. It is not clear whether this is true in cases with pre-existing malnutrition. It is crucial for patients with signs of malnutrition that theirrequirements are met by providing artificial nutrition.
The European Society of Parenteral and Enteral Nutrition (ESPEN) Guidelines
recommend three steps for the nutritional support of patients with mild acutepancreatitis, if they can consume an oral diet within 5–7 days (
† In the first 2–5 days fasting, analgesics, iv fluid and electrolyte replacement is the
† If pain is controlled and enzymes are regredient, a diet rich in carbohydrates and
moderate in protein and fat can be started.
† Normally these patients can be discharged to home after 4–7 days with a normal diet.
In acute severe pancreatitis, early EN by a jejunal tube is recommended as the first step.
If side-effects occur, or the caloric goal cannot be reached, EN should be combined withPN. There is substantial experimental evidence to support the notion that enteral feedingin severe acute pancreatitis can down-regulate the systemic inflammatory response andpromote beneficial effects on gastrointestinal functions. EN may prevent the colonisation
NPO, IV fluids, electrolytes, analgesics
Assessment of severity of acute pancreatitis
continuous small amountsof an enteral diet
Figure 1. Nutritional support in acute pancreatitis.
of the intestine by pathogenic bacteria and reduce bacterial translocation in the intestinalwall, with a reduction in superinfection of the pancreatic necrosis. For this reason, a lowvolume of enteral solution continuously perfused to the jejunum (10–30 ml/hour) shouldbe started and, if necessary, given in parallel with PN. Nutrient delivery (enteral orparenteral) should be determined by the patient’s tolerance. This approach allows thenutritional goals to be reached in the most efficient way.
In patients with severe acute pancreatitis who have complications or who need
surgery, the ESPEN Guidelines recommend the following (
† Begin early with a continuous enteral feeding by a jejunal tube as soon as the clinical
† An elemental diet is used most often, but standard enteral or immune-enhancing
† At present, due to the lack of controlled trials, no recommendation for a specific
† If EN is insufficient, PN should be added.
† The administration of fat in PN can be regarded as safe.
† Hyperglycaemia (!10 mmol/l) and hyperglyceridaemia (!12 mmol/l) should be
For future studies, there are several unanswered questions that need clarification:
† Is gastric feeding safe? If so, when and in which patients?† Which is the best formula for enteral nutrition (EN) in severe
† What is the role of pre- and probiotics in patients with acute pancreatitis?† Could immune-enhancing formulas be more beneficial?
Oral refeeding can be started if the patient is stable, gastric outlet obstruction has
resolved, pain has ceased and amylase and lipase values are decreasing.Oral refeeding witha diet that is rich in carbohydrates and moderate in proteins and in fat is recommended, butno clinical trials are available to support this strategy. If the diet is well tolerated, oralnutrition can be increased continuously. Specific products do not have to be used.
The nutrient requirements depend on the severity of the disease. Patients with
severe acute pancreatitis are hypermetabolic. If the disease is complicated by sepsis ormultiorgan failure, the resting energy expenditure is significantly increased.Inpatients with severe acute pancreatitis, it is recommended that over- or underfeedingshould be avoided. For EN or PN, 25–35 kcal/kg body weight/day are recommended. Inseverely ill patients, indirect calorimetry can be helpful for assessing the resting energyexpenditure properly. It is important to avoid hyperglycaemia. Blood glucoseconcentration should not exceed 10 mmol/l. Insulin treatment is then recommended.
The dose should not be higher than 4–6 units/hour, because the impaired glucoseoxidation rate cannot be normalised by insulin administration or by increasing glucoseadministration. Normally 3–6 g/kg body weight/day of carbohydrates are sufficient.
The optimal goal for supplying protein is to administer between 1.2 and 1.5 g/kg
body weight/day. A higher protein intake should only be given to patients with a severenegative nitrogen balance. A lower protein intake is sometimes necessary in patientswith severe renal or hepatic failure.
Fat can be given safely up to 2 g/kg body weight/day, but triglyceride levels must be
monitored carefully. The level should not exceed 12 mmol/l. Ideally fat serum levelsshould be kept within normal ranges.
Nutrient recommendations are easier to obtain with PN than with EN. Enteral
solutions contain fixed amount of the different nutrients. The enteral intake of thedifferent nutrients can only be regulated by changing the application time. Today a 24-hour continuous jejunal feeding regimen is most commonly used.
Epidemiology and aetiology of chronic pancreatitis
There have been only a few population-based studies on the frequency of chronicpancreatitis. The estimated incidence varies between 5 and 10/100 000 per year.Chronic pancreatitis is more frequent in males than in females. In Western countries,the most common cause of chronic pancreatitis, in up to 80% of patients, is intake ofalcohol.The frequency of chronic pancreatitis is, however, considerably lower thanthe frequency of heavy alcohol drinking. It is not known why only a few heavy drinkersdevelop chronic pancreatitis. Compared to alcohol-induced liver cirrhosis, chronicpancreatitis is significantly less frequent. An additional important co-factor may besmoking. The mean age of patients with chronic pancreatitis is about 45 years.Apartfrom alcohol-induced chronic pancreatitis, pancreatic duct obstruction, pancreasdivisum, hereditary pancreatitis and tropical pancreatitis are other aetiologies, butclearly less common in Western countries. In 10–20% no apparent underlying disease(idiopathic chronic pancreatitis) can be identified (
Diagnosis, classification and outcome of chronic pancreatitis
Chronic pancreatitis is an inflammatory disorder that causes irreversible anatomicalchanges and damage, including infiltration of inflammatory cells, fibrosis andcalcification of the pancreas. The diagnosis of chronic pancreatitis is based on ductalchanges observed using imaging procedures such as abdominal ultrasound, endoscopicultrasound, endoscopic retrograde pancreatography (ERCP), magnetic resonancepancreatography or CT scans.Furthermore, functional evaluation of the pancreas can
Table 4. Aetiology of chronic pancreatitis.
Alcohol (60–70%)ObstructionHereditaryTropicalIdiopathic (15–35%)
confirm pancreatic insufficiency. Several non-invasive tests are available such as thepancreolauryltest, as well as several breath tests using 13C-labelled substrates. Inaddition, pancreatic enzyme concentration (elastase) can be measured in faeces. Finally,exocrine pancreatic function can also be indirectly assessed by means of faecal fatquantification. This test reflects fat digestion and, therefore, indirectly the capacity ofpancreatic lipase activity. The non-invasive pancreatic function tests are simple androutinely applicable in a clinical setting.
Data on the natural history of chronic pancreatitis are rare and conflicting. In the
early stage of chronic pancreatitis, episodes of recurrent acute pancreatitispredominate. Severe persistent pain is typically associated with local complications.
Maldigestion is a late complication of chronic pancreatitis and depends on theunderlying disease. The medium latency between onset of first symptoms and signs ofmaldigestion is about 8–9 years in alcoholic chronic pancreatitis and more than 15 yearsin idiopathic non-alcoholic pancreatitis.
In the development of chronic pancreatitis the pancreatic glands undergomorphological changes. These include oedema, acute inflammation and necrosis,superimposed on a background of chronic changes that include fibrosis, calcification,inflammation and the loss of exocrine tissue. The pancreatic ducts can be dilated andcan contain intraductal protein plaques, which can be calcified.Pancreatic stonescan be seen in chronic alcoholic, tropical, hereditary and idiopathic pancreatitis.Adifferent pathophysiological feature is seen in tropical pancreatitis. This non-alcoholic,fibrocalcific type of chronic pancreatitis develops at a young age and is associated withsevere early diabetes. A major risk factor for tropical pancreatitis is believed to bemalnutrition in childhood.
During the evolution of chronic pancreatitis, enzyme secretion is gradually
decreased, resulting in maldigestion with steatorrhea and azotorrhea when morethan 90% of the pancreatic tissue is destroyed. In the late course of chronic pancreatitis,diabetes will develop due to the loss of insulin producing beta-cells in the pancreas. Theacinar cells are usually affected before the islet cells.
Nutritional consequences during chronic pancreatitis
A late symptom of chronic pancreatitis is malnutrition. The severity of malnutrition iscorrelated with complications and outcome, but specific studies investigating this issueare not available. The two major factors causing malnutrition are depletion of nutrientsand increased metabolic activity. Persistent alcohol intake, pain after a meal andmaldigestion are the main causes of weight loss. Resting energy expenditure isincreased by up to 30–50% in patients with chronic pancreatitis.Weight loss isstrongly associated with maldigestion of fat. Clinical steatorrhea is seen when over 90%of the pancreatic exocrine secretory function is Steatorrhea is more severe anddevelops earlier than maldigestion of protein and carbohydrates. A deficiency invitamins A, D, E and K occurs in parallel with the severity of steatorrhea. Specificdeficiencies in calcium, magnesium, zinc, thiamine and folic acids have also beenreported.
Alteration of substrate metabolism during chronic pancreatitis
In exocrine pancreatic insufficiency, carbohydrate digestion is maintained for a longtime by salivary amylase and brush-border oligosaccharidases. The loss of endocrinefunction leads to glucose intolerance. Glucose intolerance occurs in 40–90% of all caseswith severe chronic pancreatitis. In 20–30% of all patients an insulin-dependant diabetesdevelops associated with impaired glucagon release.
Protein digestion is initiated by intragastric proteolytic activity, it is continued byintestinal brush-border peptidases and is maintained even in the absence of luminalpancreatic proteolytic activity.Azotorrhea is a very late symptom in chronicpancreatitis.
Luminal lipid digestion within the small intestine depends on the combined action ofpancreatic lipase and cofactors such as colipase and bile acids. There are notriglyceride-digestion enzyme systems within the intestinal brush-border membrane.
Lipid digestion is decreased by insufficient lipase secretion and reduced luminal bile acidconcentration. In chronic exocrine pancreatic insufficiency, bicarbonate secretion isalso diminished. Postprandial intraduodenal pH may fall below 4. It is known that lipaseis more sensitive to acid destruction than are other enzymes. Luminal lipasedegradation occurs more rapidly than that of other enzymes due to its greaterinstability when proteolysis occurs. The small residual quantities of lipase secreted intothe duodenum may be further inactivated by low intraluminal pH. All these actions leadto a decrease in fat digestion and overt steatorrhea. Gastric lipase potentiallycompensates for the lack of pancreatic lipase.
Nutritional treatment in chronic pancreatitis
Chronic maldigestion of macronutrients is the major cause of progressive nutritionaland metabolic impairment in patients with chronic pancreatitis. Nutritionalinterventions depend on the degree of maldigestion and the nutritional status.
It is necessary to assess the nutritional status in patients with chronic pancreatitis.
Nutritional assessment is easy to perform. Weight loss over time, body mass index,anthropometry and some laboratory values are useful parameters. Furthermore,several nutritional screening scores, e.g. subjective global assessment (SGA), ESPEN-nutritional risk score (ESPEN-NRS) and the minimal nutritional assessment (MNA), areavailable for detecting those patients with nutritional deficiencies who are at risk ofdeveloping complications.
The main goals for nutritional interventions are to decrease maldigestion and
malabsorption in order to prevent malnutrition.
The treatment of exocrine deficiency begins with dietary recommendations and
pancreatic enzyme supplementation.About 80% of patients can be managed byanalgesics, dietary recommendations and pancreatic enzyme supplements, while
10–15% need oral nutritional supplements, 5% need enteral tube feeding and around1% require PN.
Adequate nutritional therapy and effective pain treatment have a positive impact on
the nutritional status. Often, calorie intake increases after an attenuation ofpostprandial pain.
Dietary recommendations begin with total abstinence from alcohol. In addition, an
adequate number of calories should be taken because of increased resting energyexpenditure. Frequent meals (4–5 times a day) should be given. The diet should be richin carbohydrates and proteins. The carbohydrate intake should be limited when anovert diabetes mellitus is present. A protein diet of 1.0–1.5 g/kg body weight/day isgenerally sufficient and well tolerated. Fat must also be given to reach the necessarycaloric goal. Usually, if 30–40% of the calories are given as fat this is well tolerated,especially when the foods are rich in vegetable fats. If weight gain is insufficient and/orsteatorrhea persists, medium chain triglycerides (MCT) can be tried to increase fatabsorption.MCT are absorbed directly across the small bowel into the portal vein,even in the absence of lipase, colipase and bile salts. The drawbacks of MCTs are theirlow energy density and unpalatable taste. Sometimes MCTs also casue cramps, nauseaand diarrhoea. Fat soluble vitamins (A, D, E and K), vitamin B12 and othermicronutrients should be supplemented if serum levels indicate deficienciIngeneral, a low fibre diet is recommended, because fibre may absorb enzymes and delaythe absorption of nutrients.
An adequate quantity of exogenous pancreatic enzymes is necessary to correct
protein and lipid maldigestion.Steatorrhea is usually more difficult to correct thanazotorrhea. Therefore, a suitable amount of lipase per meal is necessary to provideadequate lipolysis. There is no defined dose for these enzyme supplements and patientswill need to take 2–6 pills with each meal. Weight control, symptomatic relief ofsteatorrhoea, or a decrease in 72-hour faecal fat excretion are practical endpoints forthis therapy. It is important to give the enzymes before the meal to ensure adequatemixing. If the enzyme treatment response is not satisfactory, the addition of an acidinhibitor (proton pump inhibitor) can be tried. Decreasing the duodenal acid load canprevent the inactivation of lipase in the small bowel. Several enzyme supplements areavailable that differ in enzyme content as well as in the galenical formulation. There is noevidence that encapsulated formulations are superior to standard enzyme supplements.
In 10–15% of patients oral supplements can help to attenuate weight loss and delay
† more than 80% can be treated with normal food supplemented by pancreatic
† 10–15% of all patients require enzyme supplements† adequate nutritional therapy as well pain treatment may have a positive effect
† caloric intake increases if postprandial pain is controlled.
† In chronic pancreatitis it is necessary to study the impact of malnutrition on
EN is generally indicated when patients do not have a sufficient calorie intake. The
cause for inadequate calorie consumption can be anatomical (pyloro-duodenal-stenosis), inflammatory with acute complications (new attack of acute pancreatitis ordevelopment of fistulas) or prior to a surgical intervention. It is recommended that thecalories are given via naso-jejunal tube. For long-term therapy a percutanousendoscopic gastrostomy (PEG) with a jejunal tube is probably more convenient. Ithas been shown that continuous overnight delivery of the nutrients is suitable. Thereare no studies available that show an improvement in the nutritional status by enteralfeeding. A semi-elemental diet can be recommended. The use of a polymeric diet can betried, but there are no clinical data available that show a beneficial effect.
Enteral nutritional support can be very useful before pancreatic surgery. Data from
patients undergoing general abdominal surgery have provided evidence that apreoperative enteral or oral nutritional support with an immune-enhancing dietimproved outcome (1) by reducing postoperative infection complications and (2) by areduction in the length of hospital stayFurthermore, early enteral nutrition with afine-needle catheter-jejunostomy or a naso-jejunal tube after major abdominal surgerycan be beneficial.
PN is seldom used in patients with chronic pancreatitis. PN should be instituted
when gastric emptying is blocked, when the patient needs gastric decompression, whena tube can not be introduced into the jejunum, or when a complicated fistula is present.
There are no reported series of patients with chronic pancreatic insufficiency who havebeen treated with intravenous nutrition for a long period. PN is mainly performed overthe short term, e.g. in apparent severe malnutrition prior to pancreatic surgery ifenteral feeding is not possible.
† 5% of patients need tube feeding† in less than 1% parenteral nutrition (PN) is necessary.
† is gastric or jejunal feeding necessary?† which type of nutrients (semi-elemental or polymeric diets) are most
† what is the benefit of using medium chain triglycerides (MCTs).
Severe acute and chronic pancreatitis interferes with nutrient digestion and absorption.
Inadequate food supply and increased demands lead to nutritional deficiencies andweight loss.
In both diseases, it is crucial to assess the nutritional status, because the severity of a
pre-existing or developing malnutrition affects outcome. Several easy methods for anutritional assessment are available.
Severe acute pancreatitis is associated with autodigestion of the pancreatic gland,
protein catabolism, metabolic instability and increased nutritional requirements. In thelast decade, nutritional support in acute pancreatitis has changed. It has been shownthat in mild and severe acute pancreatitis, parenteral nutrition was not beneficial. Inaddition, it was shown that PN increased complications due to overfeeding anduncontrolled hyperglycaemia. Several studies have demonstrated that enteral nutritionvia a naso-enteral tube is possible and beneficial in patients with severe pancreatitispatients. EN is safer and less expensive than PN. Although EN can sometimes not reachthe estimated caloric and protein needs, the clinical results clearly show a superiority ofEN over PN. Specific nutritional support is only necessary in severe acute pancreatitiswith local and systemic complications. In mild acute pancreatitis enteral and parenteralnutritional support has shown no beneficial effect. These patients can be fed orally veryearly and can be discharged in less than a week. PN should be reserved for patients withsevere pancreatitis not tolerating EN, those that have an exacerbation of their diseasewith enteral feeding and before pancreatic surgery if the patient has severe signs ofmalnutrition.
Abstinence from alcohol, dietary modification and pancreatic enzyme supplements
are the corner stones of nutritional management in patients with chronic pancreatitis.
There are no good trials available to document a beneficial effect of EN or PN inpatients with chronic pancreatitis and severe maldigestion and malnutrition. EN can beuseful, when dietary recommendations fail or before, and after, pancreatic surgery.
Jejunal applications of low molecular diets are well tolerated. The recommendations onEN and PN are still empirical, because prospective trials in patients with chronicpancreatitis using enteral or parenteral feeding protocols are lacking.
1. Alpers DH. Digestion and absorption of carbohydrates and protein. In Johnson LR et al (eds.) Physiology of
the Gastrointestinal Tract, 2nd edn. New York: Raven Press, 1987, pp. 1469–1487.
2. Borgstro¨m B. Luminal digestion of fat. In Go VLW et al (eds.) The Pancreas, 2nd edn. New York: Raven
3. DiMagno EP & Layer P. Human exocrine pancreatic enzyme secretion. In Go VLW et al (eds.) The
Pancreas: Biology, Pathobiology, and Diseases, 2nd edn. New York: Raven Press, 1993, pp. 275–300.
4. Brunner H, Northfield TC, Hofmann AF et al. Gastric emptying and secretion of bile acids, cholesterol,
and pancreatic enzymes during digestion. Duodenal perfusion studies in healthy subjects. Mayo Clin Proc1974; 49: 851–860.
* 5. Layer P, von der Ohe MR, Holst JJ et al. Altered postprandial motility in chronic pancreatitis: role of
malabsorption. Gastroenterology 1997; 112: 1624–1634.
6. Greenberg GR, McCloy RF, Adrian TE et al. Inhibition of pancreas and gallbladder by pancreatic
polypeptide. Lancet 1978; 2: 1280–1282.
7. Hildebrand P, Ensinck JW, Gyr K et al. Evidence for hormonal inhibition of exocrine pancreatic function
by somatostatin 28 in humans. Gastroenterology 1992; 103: 240–247.
8. Malagelada JR, Go VL & Summerskill WH. Different gastric, pancreatic, and biliary responses to solid–
liquid or homogenized meals. Dig Dis Sci 1979; 24: 101–110.
9. Vantrappen GR, Peeters TL & Janssens J. The secretory component of the interdigestive migrating motor
complex in man. Scand J Gastroenterol 1979; 14: 663–667.
10. DiMagno EP, Hendricks JC, Go VL & Dozois RR. Relationships among canine fasting pancreatic and biliary
secretions, pancreatic duct pressure, and duodenal phase III motor activity—Boldyreff revisited. Dig DisSci 1979; 24: 689–693.
11. Cavallini G, Riela A, Brocco G et al. Epidemiology of acute pancreatitis. In Beger HG & Bu¨chler M (eds.)
Acute Pancreatitis, 1st edn. Berlin: Springer, 1987, pp. 25–31.
12. Seidner DL & Fish JA. Nutritional management of patients with feeding-induced pain: acute pancreatitis.
Semin Gastrointest Dis 1998; 9: 200–209.
13. Bradley EL. Members of the Atlanta international symposium. A clinically based classification system for
acute pancreatitis. Summary of the international symposium on acute pancreatitis, Atlanta, GA,September 11 through 13, 1992. Arch Surg 1993; 128: 586–590.
14. Winslet M, Hall C, London NJ & Neoptolemos JP. Relation of diagnostic serum amylase levels to aetiology
and severity of acute pancreatitis. Gut 1992; 33: 982–986.
15. Bradley EL. Indications for surgery in necrotizing pancreatitis: a millennium review. J Pancreas 2000; 1: 1–3.
16. Ashley SW, Perez A, Pierce EA et al. Necrotizing pancreatitis: contemporary analysis of 99 consecutive
cases. Ann Surg 2001; 234: 572–580.
17. Slavin J, Ghaneh P, Sutton R et al. Management of necrotizing pancreatitis. World J Gastroenterol 2001; 7:
18. Flint R, Windsor J & Bonham M. Trends in the management of severe acute pancreatitis: interventions and
outcome. ANZ J Surg 2004; 74: 335–342.
19. Blamey SL, Imrie CW, O’Neill J et al. Prognostic factors in acute pancreatitis. Gut 1984; 25: 1340–1346.
20. Knaus WA, Draper EA, Wagner DP & Zimmerman JE. APACHE II: a severity of disease classification
system. Crit Care Med 1985; 13: 818–829.
21. Ranson JH, Rifkind KM, Roses DF et al. Prognostic signs and the role of operative management in acute
pancreatitis. Surg Gynecol Obstet 1974; 139: 69–81.
22. Wilson C, Heads A, Shenkin A & Imrie CW. C-reactive protein, antiproteases and complement factors as
objective markers of severity in acute pancreatitis. Br J Surg 1989; 76: 177–181.
23. Neoptolemos JP, Kemppainen EA, Mayer JM et al. Early prediction of severity in acute pancreatitis by
urinary trypsinogen activation peptide: a multicentre study. Lancet 2000; 355: 1955–1960.
24. Balthazar EJ, Robinson DL, Megibow AJ & Ranson JH. Acute pancreatitis: value of CT in establishing
prognosis. Radiology 1990; 174: 331–336.
25. Norman J. The role of cytokines in the pathogenesis of acute pancreatitis. Am J Surg 1998; 175: 76–83.
26. Robin AP, Campbell R, Palani CK et al. Total parenteral nutrition during acute pancreatitis: clinical
experience with 156 patients. World J Surg 1990; 14: 572–579.
27. Shaw JH & Wolfe RR. Glucose, fatty acid, and urea kinetics in patients with severe pancreatitis. The
response to substrate infusion and total parenteral nutrition. Ann Surg 1986; 204: 665–672.
* 28. Dickerson RN, Vehe KL, Mullen JL & Feurer ID. Resting energy expenditure in patients with pancreatitis.
29. Sitzmann JV, Steinborn PA, Zinner MJ & Cameron JL. Total parenteral nutrition and alternate energy
substrates in treatment of severe acute pancreatitis. Surg Gynecol Obstet 1989; 168: 311–317.
* 30. Klein S, Kinney J, Jeejeebhoy K et al. Nutrition support in clinical practice: review of published data and
recommendations for future research directions. National Institutes of Health, American Society forParenteral and Enteral Nutrition, and American Society for Clinical Nutrition. J Parenter Enteral Nutr 1997;21: 133–156.
31. Silberman H, Dixon NP & Eisenberg D. The safety and efficacy of a lipid-based system of parenteral
nutrition in acute pancreatitis. Am J Gastroenterol 1982; 77: 494–497.
32. Greenberger NJ. Pancreatitis and hyperlipemia. N Engl J Med 1973; 289: 586–587.
33. Cameron JL, Capuzzi DM, Zuidema GD & Margolis S. Acute pancreatitis with hyperlipemia. Evidence for a
persistent defect in lipid metabolism. Am J Med 1974; 56: 482–487.
34. Farmer RG, Winkelman EI, Brown HB & Lewis LA. Hyperlipoproteinemia and pancreatitis. Am J Med
35. Niederau C, Sonnenberg A & Erckenbrecht J. Effects of intravenous infusion of amino acids, fat, or glucose
on unstimulated pancreatic secretion in healthy humans. Dig Dis Sci 1985; 30: 445–455.
36. Klein E, Shnebaum S, Ben-Ari G & Dreiling DA. Effects of total parenteral nutrition on exocrine pancreatic
secretion. Am J Gastroenterol 1983; 78: 31–33.
37. Lam WF, Masclee AA, de Boer SY et al. Effect of acute hyperglycemia on basal and cholecystokinin
stimulated exocrine pancreatic secretion in humans. Life Sci 1997; 60: 2183–2190.
38. Variyam EP, Fuller RK, Brown FM & Quallich LG. Effect of parenteral amino acids on human pancreatic
exocrine secretion. Dig Dis Sci 1985; 30: 541–546.
39. Stabile BE & Debas HT. Intravenous versus intraduodenal amino acids, fats, and glucose as stimulants of
pancreatic secretion. Surg Forum 1981; 32: 224–226.
40. McArdle AH, Echave W, Brown RA & Thompson AG. Effect of elemental diet on pancreatic secretion. Am
41. Guan D, Ohta H & Green GM. Rat pancreatic secretory response to intraduodenal infusion of elemental
vs polymeric defined-formula diet. J Parenter Enteral Nutr 1994; 18: 335–339.
42. Cassim MM & Allardyce DB. Pancreatic secretion in response to jejunal feeding of elemental diet. Ann Surg
43. Grant JP, Davey-McCrae J & Snyder PJ. Effect of enteral nutrition on human pancreatic secretions.
J Parenter Enteral Nutr 1987; 11: 302–304.
44. Vison N, Hecketsweiler P, Butel J & Bernier JJ. Effect of continuous jejunal perfusion of elemental and
complex nutritional solutions on pancreatic enzyme secretion in human subjects. Gut 1978; 19: 194–198.
45. Ragins H, Levenson SM, Signer R et al. Intrajejunal administration of an elemental diet at neutral pH avoids
pancreatic stimulation. Studies in dog and man. Am J Surg 1973; 126: 606–614.
46. Burns GP & Stein TA. Pancreatic enzyme secretion during intravenous fat infusion. J Parenter Enteral Nutr
47. Fried GM, Ogden WD, Rhea A et al. Pancreatic protein secretion and gastrointestinal hormone release in
response to parenteral amino acids and lipid in dogs. Surgery 1982; 92: 902–905.
48. Konturek SJ, Tasler J, Cieszkowski M et al. Intravenous amino acids and fat stimulate pancreatic secretion.
Am J Physiol 1979; 236: E678–E684.
49. Stabile BE, Borzatta M, Stubbs RS & Debas HT. Intravenous mixed amino acids and fats do not stimulate
exocrine pancreatic secretion. Am J Physiol 1984; 246: G274–G280.
50. Edelmann K & Valenzuela JE. Effect of intravenous lipid on human pancreatic secretion. Gastroenterology
51. Buckspan R, Woltering E & Waterhouse G. Pancreatitis induced by intravenous infusion of a fat emulsion
in an alcoholic patient. South Med J 1984; 77: 251–252.
52. Lashner BA, Kirsner JB & Hanauer SB. Acute pancreatitis associated with high-concentration lipid
emulsion during total parenteral nutrition therapy for Crohn’s disease. Gastroenterology 1986; 90: 1039–1041.
53. Noseworthy J, Colodny AH & Eraklis AJ. Pancreatitis and intravenous fat: an association in patients with
inflammatory bowel disease. J Pediatr Surg 1983; 18: 269–272.
* 54. Sax HC, Warner BW, Talamini MA et al. Early total parenteral nutrition in acute pancreatitis: lack of
beneficial effects. Am J Surg 1987; 153: 117–124.
* 55. McClave SA, Greene LM, Snider HL et al. Comparison of the safety of early enteral vs parenteral nutrition
in mild acute pancreatitis. J Parenter Enteral Nutr 1997; 21: 14–20.
56. Nordenstrom J & Thorne A. Benefits and complications of parenteral nutritional support. Eur J Clin Nutr
* 57. Van den Berghe G, Wouters P, Weekers F et al. Intensive insulin therapy in the critically ill patients. N Engl
* 58. Kalfarentzos F, Kehagias J, Mead N et al. Enteral nutrition is superior to parenteral nutrition in severe
acute pancreatitis: results of a randomized prospective trial. Br J Surg 1997; 84: 1665–1669.
59. Windsor AC, Kanwar S, Li AG et al. Compared with parenteral nutrition, enteral feeding attenuates
the acute phase response and improves disease severity in acute pancreatitis. Gut 1998; 42: 431–435.
60. Powell JJ, Murchison JT, Fearon KC et al. Randomized controlled trial of the effect of early enteral
nutrition on markers of the inflammatory response in predicted severe acute pancreatitis. Br J Surg 2000;87: 1375–1381.
* 61. Abou-Assi S, Craig K & O’Keefe SJ. Hypocaloric jejunal feeding is better than total parenteral nutrition
in acute pancreatitis: results of a randomized comparative study. Am J Gastroenterol 2002; 97: 2255–2262.
* 62. Marik PE & Zaloga GP. Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute
pancreatitis. Br Med J 2004; 328: 1407.
63. Trice S, Melnik G & Page CP. Complications and costs of early postoperative parenteral versus enteral
nutrition in trauma patients. Nutr Clin Pract 1997; 12: 114–119.
64. Heyland DK, Novak F, Drover JW et al. Should immunonutrition become routine in critically ill patients?
A systematic review of the evidence. J Am Med Assoc 2001; 286: 944–953.
65. Buchman AL, Moukarzel AA, Bhuta S et al. Parenteral nutrition is associated with intestinal morphologic
and functional changes in humans. J Parenter Enteral Nutr 1995; 19: 453–460.
66. Lange JF, van Gool J & Tytgat GN. The protective effect of a reduction in intestinal flora on mortality of
acute haemorrhagic pancreatitis in the rat. Hepatogastroenterology 1987; 34: 28–30.
67. Hallay J, Kovacs G, Szatmari K et al. Early jejunal nutrition and changes in the immunological parameters of
patients with acute pancreatitis. Hepatogastroenterology 2001; 48: 1488–1492.
68. Cravo M, Camilo ME, Marques A & Pinto Correia J. Early tube feeding in acute pancreatitis: a prospective
69. Kudsk KA, Campbell SM, O’Brien T & Fuller R. Postoperative jejunal feedings following complicated
pancreatitis. Nutr Clin Pract 1990; 5: 14–17.
70. Nakad A, Piessevaux H, Marot JC et al. Is early enteral nutrition in acute pancreatitis dangerous? About 20
patients fed by an endoscopically placed nasogastrojejunal tube. Pancreas 1998; 17: 187–193.
71. Scolapio JS, Malhi-Chowla N & Ukleja A. Nutrition supplementation in patients with acute and chronic
pancreatitis. Gastroenterol Clin North Am 1999; 28: 695–707.
72. Eatock FC, Brombacher GD, Steven A et al. Nasogastric feeding in severe acute pancreatitis may be
practical and safe. Int J Pancreatol 2000; 28: 23–29.
73. Oleynikov D, Cook C, Sellers B et al. Decreased mortality from necrotizing pancreatitis. Am J Surg 1998;
* 74. Olah K, Belagyi T, Issekutz A et al. Randomized clinical trial of specific lactobacillus and fibre supplement
to early enteral nutrition in patients with acute pancreatitis. Br J Surg 2002; 89: 1103–1107.
75. Meier R, Beglinger C, Layer P et al. ESPEN Consensus Group. ESPEN guidelines on nutrition in
acute pancreatitis. European society of parenteral and enteral nutrition. Clin Nutr 2002; 21: 173–183.
76. Levy P, Heresbach D, Pariente EA et al. Frequency and risk factors of recurrent pain during refeeding in
patients with acute pancreatitis: a multivariate multicentre prospective study of 116 patients. Gut 1997;40: 262–266.
77. Bouffard YH, Delafosse BX, Annat GJ et al. Energy expenditure during severe acute pancreatitis. J Parenter
78. Lowenfels AB & Maisonneuve P. Epidemiology of chronic pancreatitis and the risk of cancer. In
Bu¨chler MW, Friess H, Uhl W & Malfertheiner P (eds.) Chronic Pancreatitis. Novel Concepts in Biology andTherapy. Oxford: Blackwell Publishing, 2002, pp. 29–36.
* 79. Steer ML, Waxman I & Freedman S. Chronic pancreatitis. N Engl J Med 1995; 332: 1482–1490.
80. Lowenfels AB, Maisonneuve P, Cavallini G et al. Pancreatitis and the risk of pancreatic cancer.
International Pancreatitis Study Group. N Engl J Med 1993; 328: 1433–1437.
81. Mitchell RM, Byrne MF & Baillie J. Pancreatitis. Lancet 2003; 361: 1447–1455.
82. Dominguez-Munoz JE. Noninvasive pancreatic function tests. In Bu¨chler MW, Friess H, Uhl W &
Malfertheiner P (eds.) Chronic Pancreatitis. Novel Concepts in Biology and Therapy. Oxford: BlackwellPublishing, 2002, pp. 225–232.
83. Layer P & Keller J. How to make use of pancreatic function tests and do we need them? In Bu¨chler MW,
Friess H, Uhl W & Malfertheiner P (eds.) Chronic Pancreatitis. Novel Concepts in Biology and Therapy. Oxford:Blackwell Publishing, 2002, pp. 233–242.
84. Layer P, Yamamoto H, Kalthoff L et al. The different courses of early- and late-onset idiopathic and
alcoholic chronic pancreatitis. Gastroenterology 1994; 107: 1481–1487.
85. Singer MV, Gyr K & Sarles H. Revised classification of pancreatitis. Report of the second international
symposium on the classification of pancreatitis in Marseille, France, March 28–30, 1984. Gastroenterology1985; 89: 683–685.
86. Sarner M & Cotton PB. Classification of pancreatitis. Gut 1984; 25: 756–759.
87. Forsmark CE. Chronic pancreatitis. In Feldman M, Friedman LS & Sleisenger MH et al (eds.) Sleisenger and
Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management, 7th edn. Philadelphia,PA: Saunders, 2002, pp. 913–941.
88. Mohan V, Premalatha G & Pitchumoni CS. Tropical chronic pancreatitis: an update. J Clin Gastroenterol
89. Hebuterne X, Hastier P, Peroux JL et al. Resting energy expenditure in patients with alcoholic chronic
pancreatitis. Dig Dis Sci 1996; 41: 533–539.
90. Latifi R, McIntosh JK & Dudrick SJ. Nutritional management of acute and chronic pancreatitis. Surg Clin
91. DiMagno EP, Malagelada JR & Go VL. Relationship between alcoholism and pancreatic insufficiency. Ann N
92. Detsky AS, Smalley PS & Chang J. The rational clinical examination. Is this patient malnourished? J Am Med
93. Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative TPN in surgical
patients. N Engl J Med 1991; 325: 525–532.
94. Guigoz Y, Vellas B & Garry P. Assessing the nutritional status of the elderly: the mini nutritional
assessment as part of the geriatric evaluation. Nutr Rev 1996; 54: S59–S65.
* 95. Kondrup J, Rasmussen HH, Hamberg O et al. Nutritional risk screening (NRS 2002): a new method based
on an analysis of controlled clinical trials. Clin Nutr 2003; 22: 321–336.
96. DiMagno EP. Medical treatment of pancreatic insufficiency. Mayo Clin Proc 1979; 54: 435–442.
97. Havala T, Shronts E & Cerra F. Nutritional support in acute pancreatitis. Gastroenterol Clin North Am 1989;
98. DiMagno EP, Malagelada JR, Go VL & Moertel CG. Fate of orally ingested enzymes in pancreatic
insufficiency. Comparison of two dosage schedules. N Engl J Med 1977; 296: 1318–1322.
PosterJet 7.5 SP2 and the Canon iPF-series Particularities when using PosterJet 7.5 SP2 with the new Canon imagePROGRAF printers of the iPF-series The Canon imagePROGRAF iPF9000 can print While creating a PosterJet media profile for the Canon borderless only up to 42-inch width. PosterJet 7.5 SP2 imagePROGRAF iPF5000 Proof or the iPF9000 Proof, currently allows creating a print j
Developments in the Law of Economic Loss and Liability under Design & Build Situations ORGANISED BY Society of Construction Law (Singapore) 15th – 17th October 2006, Grand Copthorne Waterfront Hotel, Singapore by COLIN Y.C. ONG 1 General Introduction to the Law of Economic Loss The current position depicting the law of economic loss even among Commonwealth coun