The influence of abdominal sepsis on acute pancreatitis in rats: a study on mortality, permeability, arterial pressure, and intestinal blood flow.

Bacterial infection increases mortality and morbidity in acute pancreatitis. The aim of the present study was to analyze possible mechanisms by which bacterial infectious complications may worsen the course of the disease. Systemic arterial pressure, mucosal microcirculation, and intestinal, peritoneal, and pulmonary permeability of 125I-labeled human serum albumin were measured 3, 6, 12, 24, 48, and 72 h after sham operation, induction of pancreatitis (AP), abdominal sepsis (AS), or AP+AS. The mortality rate at 48 and 72 h was 33% in AS and 58 and 75%, respectively, in AP+AS, whereas there were no deaths in the AP or sham-operated groups. The systemic arterial pressure and intestinal blood flow decreased early in all study groups, with the lowest values for AP+AS. Bacterial infection aggravated the increase in intestinal, peritoneal, and pulmonary permeability to labeled albumin in pancreatitis. This was true for both intestinal endothelial permeability (blood to tissue) and mucosal barrier permeability (blood to lumen). The findings demonstrate the occurrence of circulatory failure and changes of the capillary barrier in multiple organs in acute pancreatitis. Moreover, the changes were aggravated by an intraabdominal septic challenge. The observations imply that bacterial infection may play a role in the development of multiple organ failure in acute pancreatitis, tentatively by aggravating alterations in tissue barrier function.

Release of platelet-activating factor in acute experimental pancreatitis.

This study demonstrates the formation of platelet-activating factor (PAF) in rats with acute experimental pancreatitis (AEP). The AEP was induced by infusing sodium taurodeoxycholate and trypsin into the bile-pancreatic duct. The PAF content was increased in blood samples and in pulmonary and pancreatic tissue as compared with control animals. Significant amounts of PAF were also found in peritoneal fluid. The PAF content did increase in blood samples and in pulmonary tissue after administration of endotoxin intravenously. The effects of intraperitoneal PAF administration were also studied and showed an increase of polymorphonuclear cells in blood samples. These findings suggest that acute pancreatitis might generate and release PAF. Whether PAF release is associated with the pathophysiology of complications in acute pancreatitis remains to be elucidated.

Epidermal growth factor induces cell proliferation in mouse pancreas and salivary glands.

Epidermal growth factor (EGF) is a mitogenic stimulus in many tissues and occurs in large amounts in the pancreas and salivary glands. Whether EGF is mitogenic in the pancreas is controversial, and the EGF effect has not been studied in the salivary glands. Therefore, the aim of the present study was to investigate the possible effects on the pancreas and parotid and submandibular glands at different time intervals after exogenous EGF administration. Human recombinant EGF was infused subcutaneously by osmotic minipumps in three groups of mice (for 1, 3, and 7 days, respectively) at a dosage of 10 micrograms/kg/h (1.6 mumol/kg/h). Tritiated thymidine was infused intraperitoneally by osmotic minipumps for the same time periods, but only for the last 3 days in the 7-day group. After 1 day the pancreas increased in weight and the increase persisted throughout the study. No effect was seen on the parotid or submandibular gland wet weight. A slight transient increase in pancreas protein content was observed, whereas amylase content was unaffected. The labeling index of serous and ductal cells in the parotid gland increased from the third day. After 7 days, all cell types studied in the pancreas and parotid and submandibular glands were in a hyperproliferative state. The results show that EGF evoked a strong proliferative response on all cell types studied in the pancreas and parotid and submandibular glands.

The ratio between anionic and cationic trypsin in rat pancreas varies with CCK stimulation.

The effects of long-term hyperstimulation with cholecystokinin (CCK) on the pancreatic contents of anionic and cationic trypsin(ogen) and amylase were studied in the rat. Endogenous hyperCCKemia was evoked in rats by pancreaticobiliary diversion (PBD), and exogenous hyperCCKemia by continuous subcutaneous CCK infusion. In addition, the effect of continuous subcutaneous infusion of the CCK A receptor antagonist devazepide was studied. After 4 weeks blood samples were obtained for the determination of plasma CCK concentrations and the animals were sacrificed. The pancreatic glands were harvested, weighted, and extracted. The extracts were analyzed for anionic and cationic trypsin and amylase. Enzyme contents showed a large interindividual variation. The most consistent change in enzyme pattern was an increase in the ratio between anionic and cationic trypsin in animals with hyperCCKemia (PBD operated or CCK infused). Furthermore, this ratio decreased significantly in animals treated with devazepide. In conclusion, stimulation of the CCK receptor changed the ratio between anionic and cationic trypsin in the pancreatic gland, while it was reversed during blockade of the receptor.

Effects of pancreaticobiliary diversion and gastric fundectomy on azaserine-induced pancreatic carcinogenesis in the rat.

The effects of pancreaticobiliary diversion (PBD) and gastric fundectomy on the pancreas in azaserine-treated rats were studied over 14 months. Sham-operated azaserine-treated animals served as controls. A significant increase in pancreatic weight and total DNA and protein content was found in PBD-operated and fundectomized animals. DNA flow cytometry showed a significantly increased ratio of tetraploid to diploid cells in pancreatic tissue in both experimental groups. Mean values of all these variables were significantly higher after PBD than after fundectomy. Acidophilic atypical acinar cell foci of the pancreas were observed in all of the experimental and 75% of the control animals. The volume density of these foci was significantly higher in each experimental group than in the controls. The volume density, radioactive thymidine labeling index, and mitotic index of the foci were significantly higher after PBD than after fundectomy. Changes consistent with pancreatic adenoma were diagnosed in the PBD group only. It is concluded that not only PBD with endogenous hypercholecystokininemia, but also fundectomy with endogenous hypergastrinemia lasting about half of the life span in rats, induces pancreatic hypertrophy and enhances the development of precancerous pancreatic changes after azaserine treatment. In comparison with PBD, fundectomy caused less pronounced changes and no observable neoplasia.

Endogenous hypercholecystokininemia model in the hamster: trophic effect on the exocrine pancreas.

Using Syrian golden hamsters, we studied the effect of pancreaticobiliary diversion (PBD) on plasma cholecystokinin (CCK) and exocrine pancreatic tissue over 5, 10, and 24 days. As compared with sham-operated controls, PBD-operated animals had increased plasma CCK concentrations by 228, 318, and 207% at 5, 10, and 24 days, respectively. Correspondingly, pancreatic wet weight increased by 24, 61, and 87%; total pancreatic protein by 6, 57, and 73%; and total pancreatic DNA by 35, 52, and 98%, respectively. At 5 days, but not at 10 and 24 days, there was a significant increase in the pancreatic tissue DNA concentration (p less than 0.01) and [3]H-thymidine incorporation into DNA (p less than 0.02). Autoradiography showed increased [3]H-thymidine labeling index in acinar cells at 5 and 10 days after PBD (p less than 0.01 and p less than 0.005). Although not significant, ductal cell labeling index was also increased at 5 and 10 days. These findings provide evidence that, as in the rat, PBD in the hamster induces hypercholecystokininemia with ensuing pancreatic hyperplasia and hypertrophy. The hamster model may be useful for studies on the effect of endogenous CCK on pancreatic ductal cell carcinogenesis and diseases of the gallbladder, neither of which can be studied in the rat.

Effects of intraluminal trypsin and bile on the exocrine and endocrine pancreas after pancreaticobiliary diversion and biliodigestive shunt.

Pancreaticobiliary diversion (PBD) and biliodigestive shunt (BDS) cause long-standing hypercholecystokininemia followed by pancreatic hyperplasia. These changes have been suggested to be due to the lack of intraluminal trypsin and bile, respectively, in the upper small intestine. The aim of these experiments was to study the effect of restoration of intraluminal trypsin and bile on plasma levels of cholecystokinin (CCK) and the changes found in exocrine and endocrine pancreas after PBD and BDS. Male Sprague-Dawley rats were used. PBD was done in 16 rats, eight of which had trypsin dissolved in 50 mM sodium bicarbonate (SB), and eight had SB only by gastric intubation twice daily. BDS was done in another 16 rats, eight of which had bile dissolved in SB, and eight had SB in a similar manner. Sham-operated rats had SB and served as controls. After 4 weeks, the rats were killed, and the concentrations of circulating CCK, gastrin, glucose, glucagon, and insulin were determined. The pancreas was removed, weighed, and analyzed for contents of water, protein, and DNA. In another study, PBD-operated rats got trypsin in varying dosages or trypsin and taurocholate in combination for 2 weeks before death. The concentrations of plasma CCK and glucagon were elevated after both PBD and BDS. PBD decreased the concentration of gastrin in plasma. PBD caused an increase of pancreatic weight and the contents of protein and DNA. Trypsin substitution to PBD-operated rats did not affect plasma CCK or glucagon levels, but the PBD-induced increases in weight and DNA content were counteracted by trypsin. Higher dosages of trypsin did not further influence the effects seen after PBD. Pancreatic weight and DNA content were increased after BDS. Bile administration completely abolished the increase in plasma CCK and glucagon, as well as the gain in pancreatic weight, and reduced the increase in pancreatic DNA. Substitution with bile to BDS-operated rats abolished the increase in the plasma levels of CCK and glucagon, as well as the trophic effects on the pancreas. Trypsin substitution to PBD-operated rats partly reversed the trophic effects on the pancreas but not the hormonal changes in plasma. Thus the trophic effects on the pancreas exerted by BDS seem to be dependent on the lack of bile in the upper small intestine, whereas the effects of PBD only partly are a consequence of the absence of intraluminal trypsin.

Effect of a platelet-activating factor antagonist on pancreatitis-associated gut barrier dysfunction in rats.

Platelet-activating factor (PAF) may play a critical and primary role in the pathogenesis of acute pancreatitis and pancreatitis-associated distant organ injury. The present study evaluated the effect of a PAF antagonist, lexipafant (an (S)-4-methyl-2[methyl-imidazo[4,5-c]pyridin-1-ylmethyl)-benzene sulphonyl]-amino]pentanoic acid ethyl ester, BB-882; British Biotech Ltd.), on the potential prevention of gut barrier dysfunction, by measuring gut origin sepsis, bidirectional permeability of the intestinal barrier, and pancreatic capillary endothelial barrier integrity, in acute pancreatitis induced by intraductal infusion of 5% sodium taurodeoxycholate. Pancreatic endothelial permeability significantly increased in animals with acute pancreatitis, whereas pretreatment with lexipafant had a preventive effect (p < 0.05 vs. pancreatitis with saline). Similarly, alterations noted in hematocrit and plasma levels of lipase and calcium were counteracted by the PAF antagonist. It also prevented the increase in albumin leakage from blood to the mucosal interstitium and from blood to the intestinal lumen in acute pancreatitis. Albumin passage from the gut lumen to blood in animals with pancreatitis pretreated with saline increased from 3 h and on, and lexipafant prevented alterations in mucosal epithelial permeability. Bacterial translocation was commonly seen in pancreatitis, whereas only a few positive cultures were observed in pancreatitis animals given lexipafant. Microthrombosis in intestinal villi seemed less frequent after lexipafant pretreatment. We conclude that (a) PAF may play a role in the pathogenesis of pancreatitis-associated intestinal dysfunction, (b) PAF may be involved in the development of distant organ dysfunction by triggering endothelial barrier dysfunction, and (c) PAF antagonists may provide potential agents for preventing pancreatitis-associated gut barrier dysfunction.

Biliodigestive shunt evokes hyperCCKemia and trophic effects in the rat pancreas, but not in the liver or gastrointestinal tract.

The influence of bile on the release of cholecystokinin (CCK) and, thereby, on the regulation of exocrine pancreatic function and growth is unsettled. The aim of this study was to elucidate the effect of long-term diversion of bile from the upper small intestine of CCK release and on the pancreas, liver, and gastrointestinal tract. A surgical biliodigestive shunt was performed in rats, diverting the bile flow directly to the middle of the small intestine. The animals were killed after 4 or 12 weeks. Plasma CCK and trophic effects on the pancreas, liver, and gastrointestinal tract were determined, as were the trypsin and chymotrypsin contents in the intestine. The CCK concentration in plasma increased 10-fold at both time points studied. The pancreas doubled its weight from 4 weeks onward. Also, pancreatic protein, DNA, and amylase contents were increased throughout the study. The liver and gastrointestinal tract were unaffected. Intraluminal bile plays a role in the feedback regulation of CCK release and is involved in this way in the control of pancreatic growth but has no similar effects on the liver or gastrointestinal tract.

Routine preoperative infusion cholangiography versus intraoperative cholangiography at elective cholecystectomy: a prospective study in 995 patients.

BACKGROUND: There has been a resurgence of interest in recent years in preoperative infusion cholangiography (PIC). The role of routine PIC compared to routine intraoperative cholangiography (IOC) has not been clearly defined. STUDY DESIGN: In our department between 1985 and 1991, 1,042 of 1,576 consecutive patients with biliary calculous disease had elective cholecystectomy: 694 patients were prospectively scheduled for PIC, and 348 patients were randomly allocated to IOC. The patients in the PIC and IOC groups were similar with regard to age, history of biliopancreatic complications, and laboratory findings. The cost of PIC in Sweden is nearly five times greater than the cost of IOC. RESULTS: Satisfactory opacification of the biliary system was obtained in 90.1 and 96.8 percent of patients who underwent PIC and IOC, respectively. Preoperative infusion cholangiography required support by IOC in 19.5 percent of patients. There were no statistically significant differences between the PIC and IOC groups with regard to the incidence (7 percent in both groups) of or positive predictive value (68 and 80 percent, respectively) for bile duct stones, rate of retained stones (6 and 20 percent, respectively), intraoperative (5.6 and 6.3 percent, respectively) or postoperative (13.3 and 15.9 percent, respectively) morbidity, or incidence of bile duct anomalies (0.9 and 0.3 percent, respectively). Median operative time was longer in patients with (95 minutes) compared to those without (75 minutes) IOC (p < 0.001). More postoperative complications occurred after bile duct exploration (26 of 75 patients) compared to cholecystectomy alone (114 of 917 patients, p < 0.001). The 30-day mortality was zero. Minor bile duct injuries occurred in two patients (0.2 percent) at cholecystectomy, (one with and one without bile duct exploration). In no patient was the cholangiographic finding of a biliary anomaly crucial for the safe execution of cholecystectomy. CONCLUSIONS: In our study, PIC and IOC were comparable, but routine use of either method did not promote the safety of cholecystectomy and thus their routine use is not warranted. The shorter operative time and preoperative identification of common bile duct (CBD) stones provided by PIC might favor this examination when applied selectively in patients with increased risk of having CBD stones. However, this potential advantage is offset by the need for PIC to be supported by IOC in approximately 20 percent of patients. Also, the cost of PIC is greater than the cost of IOC.

Computed tomography and laparoscopy in the assessment of the patient with pancreatic cancer.

BACKGROUND: In most patients with pancreatic cancer, the tumor is unresectable. Nonoperative methods for palliation of jaundice, duodenal obstruction, and pain currently are being developed. Preoperative assessment of resectability of the tumor is becoming more and more important to avoid unnecessary operations. The aim of this study was to compare computed tomography (CT) and laparoscopy with special reference to the additive role of the latter technique in predicting unresectability of pancreatic cancers. STUDY DESIGN: Sixty patients with exocrine pancreatic cancer were assessed prospectively with both CT and laparoscopy. On the basis of metastatic spread or signs of vascular involvement, the radiologist and the laparoscopist independently reported the tumors as probably unresectable or resectable. RESULTS: The predictive value for unresectability was 100% for both CT and laparoscopy. Sensitivity in predicting unresectability was 69% for both techniques, and the corresponding figure for specificity was 100%. When CT and laparoscopy were evaluated together, an improvement in sensitivity to 87% was observed (p < 0.05). Separately, CT and laparoscopy correctly predicted resectability in only 30% and 38% of the patients, respectively. The presence of liver metastases was overlooked by CT in 13 of 32 patients (40%). Every fourth patient who was found to have unresectable tumor at CT was falsely classified as resectable by the laparoscopist, leading to unnecessary laparotomies. On the other hand, 9 of 24 patients (38%) with resectable disease at CT were deemed unresectable at the subsequent laparoscopy. CONCLUSIONS: Laparoscopy and CT independently and reliably predicted unresectability of pancreatic cancer, but the methods were inaccurate in forecasting resectability. The results suggest that CT examination should be done in patients who are candidates for attempted curative surgical procedures, whereas laparoscopy should be restricted to Those Judged resectable at CT.

Percutaneous transhepatic portography in bile duct carcinoma. Correlation with percutaneous transhepatic cholangiography and angiography.

In 16 patients with carcinoma of the extrahepatic bile ducts, percutaneous transhepatic portography (PTP) and cholangiography (PTC) were performed. Fourteen of these patients also had angiography, which failed to show the tumor in 7 cases. Findings indicating non-extirpability of the tumor were demonstrated by angiography in 3 patients. At PTP non-extirpability was confirmed in these cases. PTP further indicated non-extirpability in one patient and gave hints of infiltration of the liver by the tumor in 5 patients because of intra or extrahepatic invasion of the portal vein.

[Percutaneous transhepatic intubation of bile ducts for combined internal and external drainage in extrahepatic cholestasis (author's transl)]. / Perkutane transhepatische Intubation der Gallengänge zur kombinierten inneren und äusseren Drainage bei extrahepatischer Cholestase.

In 37 patients with extrahepatic cholestasis of different origin, percutaneous transhepatic intubation of the bile ducts was performed for combined internal and external drainage. In 5 cases with stones in the extrahepatic bile ducts and in 12 cases with periampullary tumors, the bile ducts were drained preoperatively. In 3 of these patients, temporary drainage was performed because of postoperative complications. Thirteen patients with non-resectable tumors received a permanent drainage as palliation. In 4 patients temporary drainage was performed during radiation/cytostatic therapy. One patient with an iatrogenic bile duct lesion and one patient with an inflammatory tumor in the liver hilum had a drainage catheter placed because a bile duct resection with creation of a biliodigestive anastomosis was not possible. In one patient with a non-resectable periampullary carcinoma the drainage catheter was replaced by a teflon bile duct endoprosthesis inserted by the percutaneous transhepatic approach. The complications of non-operative percutaneous transhepatic bile drainage are discussed.

Surgical management of pure pancreatic fistulas.

This paper reports on 13 patients with pure pancreatic fistulas defined as persistent lesions originating directly from the gland tissue and not from a pancreatico-intestinal or pancreatico-gastric anastomosis. Six fistulas were external and seven internal. All external fistulas were postoperative whereas all the internal ones were due to chronic pancreatitis. Conservative treatment of 2 to 36 months duration was unsuccessful, so that all patients underwent surgery. To establish a proper surgical strategy, preoperative mapping of the fistula by endoscopic retrograde cholangiopancreaticography (ERCP), fistulography and/or computerized tomography proved of value. In eleven patients, pancreatic fistula flow was surgically redirected into the gastrointestinal tract, while the remaining two were submitted to a pancreatic left resection. There were no hospital deaths and the complication rate was low. During the follow-up time of 6 to 96 months no recurrent fistulas were seen.

Influence of gastrointestinal hormones on the course of acute experimental pancreatitis.

The influence of exogenous administration and endogenous release of certain g.i. hormones on the course of acute experimental pancreatitis was studied. Administration of 2 g of a pellet diet every eight hours decreased survival, as did repeated s.c. administration of the cholecystokinin-analogue caerulein. Also oral administration of a trypsin inhibitor--releasing intestinal factors or hormones stimulating pancreatic enzyme synthesis and secretion--decreased survival. On the other hand repeated s.c. administration of secretin or an anticholinergic drug (Pro-Banthine), or oral administration of 0.1 N HCl every eight hours did not influence survival. At blind macroscopic evaluation, caerulein was found to cause signs of more severe disease. All pancreatic rats had increased S-amylase levels, but there was no difference between any of the groups. In peritoneal fluid, however, caerulein caused an increase in the amylase activity. The results suggest that elevated S-levels of g.i. hormones, which primarily stimulate pancreatic enzyme synthesis and secretion, are harmful in acute experimental pancreatitis.

Endoscopic sphincterotomy for bile duct calculi-factors influencing the success rate.

BACKGROUND/AIMS: Endoscopic sphincterotomy is an established treatment of retained or recurrent common bile duct calculi after cholecystectomy and in the majority of patients with an intact gallbladder. In order to identify patients ultimately requiring additional endoscopic procedures or surgery, factors predictive of decreased endoscopic bile duct clearance were sought. MATERIAL AND METHODS: Between 1981 and 1992 endoscopic sphincterotomy was performed in 393 consecutive patients with either intact gallbladders (n = 246), recurrent (n = 92) or retained (n = 55) calculi. RESULTS: There was a 9.4% overall early complication rate for the procedure and a 30-day mortality rate of 0.5% (two patients, non-procedure related). Complete removal of all bile duct calculi failed in 35/393 patients (8.9%). In patients with intact gallbladder the clearance rate at first attempt was higher (p = 0.002; Chi-square test) in the presence of solitary as compared to multiple stones. The same was found in patients with recurrent stones as well (p < 0.001). In non-cholecystectomized patients with single or multiple stones smaller than 10 mm, the clearance rate was higher at first (p = 0.02) as well as at final (p < 0.002) attempt as compared to patients with larger stones. Single small ( < 10 mm) compared to single large stones in patients with intact gallbladder had a higher clearance rate at final (p = 0.002) but not at first (p = 0.18) attempt. Patients with intact gallbladder and pancreatitis had higher clearance rate at first attempt compared to patients with jaundice (p = 0.001) or patients without concomitant pancreatobiliary disease (p = 0.002). Clearance rate was the same in patients with and without endoscopic sphincterotomy complications, except for patients with basket impaction, in whom the clearance rate was decreased (p = 0.02). CONCLUSIONS: Thus, in patients with intact gallbladder surgery should be considered after failed complete bile duct clearance at first attempt.

Recurrence of exocrine pancreatic cancer--local or hepatic?

The results of radical surgery for pancreatic cancer depend, like all other cancer surgery, on the technique used, and the biology of the disease. We have analysed the site and time of recurrence after pancreatectomy for exocrine pancreatic cancer in 74 patients who died more than six months postoperatively. All patients had recurrent disease, 64 patients had local recurrence in the pancreatic bed and 68 had liver metastases. Local recurrence without liver metastases was found in six patients, and ten had liver metastases, but no local recurrence. Both the time from operation to clinically evident recurrence and the postoperative survival time were significantly longer for patients with local recurrence only. Although not statistically significant, there was a tendency (5 out of 8) for smaller, well-differentiated tumors without spread outside the pancreas to be associated with local recurrences without liver metastases. We conclude that, in retrospect, the surgical procedures used were inappropriate and inadequate. To cure these patients, a more radical operation and/or effective adjuvant treatment is needed.

Factors predictive of early complications of endoscopic treatment of bile duct calculi.

BACKGROUND/AIMS: Factors associated with an increased early complication rate of the endoscopic sphincterotomy procedure have been identified. Precut or needle knife papillotomy has been shown to improve the success rate of endoscopic retrograde cholangiography and endoscopic sphincterotomy, but has often been reported to be hazardous. In order to identify patients with bile duct stones at risk for a complicated course in connection with endoscopic clearance of the calculi, factors predictive of early complications were sought. METHODOLOGY: 417 consecutive patients with bile duct calculi at endoscopic retrograde cholangiography were considered for endoscopic treatment in our department from 1981 to 1992. Endoscopic sphincterotomy was performed in 246 patients with intact gallbladders and in 147 with prior cholecystectomy, 55 of whom had retained calculi. RESULTS: There was a 9.4% overall and 7.1% major early complication rate of the EST procedure and a 30-day mortality of 0.5% (2 patients, non-procedure related). In 22% (6/27) of the patients with major complications, surgery was required or preferred to additional endoscopic measures. Complete stone removal failed in 35/393 patients (8.9%). The immediate and early complication rate of standard sphincterotomy was not found to be increased in patients with prior or present biliopancreatic complications, failed bile duct clearance at first attempt, or juxtapapillary diverticula. It was the same after standard sphincterotomy as after precut papillotomy followed by immediate or delayed sphincterotomy. No increased morbidity was found after failed therapy as compared to failed diagnostic precut papillotomy. There was neither a greater need for, nor an increased complication rate following, precut papillotomy in patients with, as compared to those without, juxtapapillary diverticula. Endoscopic experience did not influence the complication rate. There were no significant differences regarding outcome or risk factors associated morbidity between patients with and without intact gallbladder. CONCLUSIONS: These findings confirm that endoscopic treatment is safe and that precut papillotomy can be performed without increased morbidity. Furthermore, none of the commonly identified factors associated with increased morbidity were found to be risk factors in this study.

[Combination therapy in oncology (multimodal treatment) in pancreatic tumors]. / Kombinationstherapie in der Onkologie (multimodale Behandlung) bei Pankreastumoren.

The majority of patients with pancreatic cancer have systemic disease already at diagnosis, and nearly all patients will develop recurrence following radical resection. Thus, surgical treatment alone is insufficient. The paper focuses on adjuvant multimodal treatment and reviews the current status of pre- and postoperative chemoradiation, intraoperative radiotherapy (IORT), adjuvant chemotherapy, and regional infusion therapy. Studies in this area are hampered by often being non-randomized and with too few patients included. Overall there presently is no adjuvant multimodal treatment which can be suggested for routine use. However, two ongoing prospective randomized studies (ESPAC-1 and an EORTC study) will have enough statistical power to give reliable information on the topic. It is hoped that these and other studies will form the basis for further proper clinical trials on multimodal treatment in pancreatic cancer with the aim at long last to improve the extremely poor survival in these patients.

Is there still an indication for pancreatic duct drainage in chronic pancreatitis?

Pain in chronic pancreatitis is supposed to be multifactorial in origin. Pancreatic duct/tissue hypertension is today proved in patients with chronic pancreatitis and pain. Duct drainage reportedly normalizes pancreatic duct/tissue pressure and reduces pain in 70% of the patients. Also, duct drainage by endoscopy may relieve pain. Surgical duct decompression is parenchyma-preserving and even suggested to prevent further progress of exocrine insufficiency. Recent experience indicates that such operations are pain-relieving not only in patients with dilated ducts but also in those with small duct disease.