International journal of pancreatology : official journal of the International Association of Pancreatology最新文献

This article reviews the literature and gives an overview on prevalence and possible explanations for pancreatic involvement in inflammatory bowel diseases (IBD). IBD patients have a markedly elevated risk for developing acute pancreatitis as well as pancreatic insufficiency. Multiple potential causes for pancreatitis in IBD patients exist. In the majority of cases acute pancreatitis appears to be related to drug side effects or local structural complications rather than a true extraintestinal manifestation of IBD. Nevertheless, some cases of acute pancreatitis remain unexplained. Prevalence of chronic pancreatitis in IBD patients also seems to be relatively high. However, etiology of pancreatic duct changes and/or the occurrence of exocrine insufficiency remain unclear. In most cases chronic pancreatitis is clinically unapparent, although in some patients it may be accompanied by clinically relevant exocrine insufficiency.

Background: We recently demonstrated that chronic physical exercise increases pancreatic protein content and basal amylase secretion. It is unknown whether chronic exercise causes hypertrophy or proliferation of pancreatic acinar cells.

Methods: Female F344 rats (age, 6 wk) were divided into control (n = 7) and exercise (n = 6) groups. Food consumption was matched between the 2 groups. Rats in the control group were kept sedentary. Rats in the exercise group were exercised for 60 min, 5 d/wk during the experiment. After 8 wk, the pancreas and hindlimb muscles were rapidly excised and weighed. Protein and DNA content and enzyme activity in pancreatic tissue were measured. Pancreatic tissues from control and exercised rats were also prepared for transmission electron microscopy.

Results: Inhibition of growth and hypertrophy of hindlimb muscles were exhibited by the exercise group. In the exercise group, pancreatic wet weight, protein content, and amylase and lipase activities, but not DNA content, were significantly higher than those in the control group. Electron micrographs clearly revealed that acinar cells were hypertrophied and zymogen granules were increased in number in exercised rats.

Conclusion: Chronic endurance exercise increases pancreatic weight, protein content and enzyme activity through hypertrophy of acinar cells.

Aim: To determine the early and late morbidity and mortality after surgical treatment of chronic pancreatitis.

Methods: We determined long-term outcome and early and late morbidity and mortality, respectively, in 484 consecutive patients undergoing surgery for chronic pancreatitis from 1976 through 1997. Sixty-five percent of the patients had small duct disease (main pancreatic duct <7 mm), whereas 35% had large duct disease. Indications for operation were pain (95%), suspicion of malignancy (28%), and complications involving adjacent organs (35%). Pseudocysts were present in 27% of patients. Hospital morbidity (8 vs 23%, p = 0.0002) and mortality (0 vs 1.9%, p = 0.12) were less after drainage procedures (n = 162) than after pancreatic resections (n = 286). Among resectional procedures, total pancreatectomy had the highest 30-d operative mortality (5%) and morbidity rates (47%), followed by pancreatoduodenectomy (3 and 32%, respectively). The best results with pain relief occurred after proximal pancreatic resection (89% after mean follow-up of 6.5 yr). The number of patients able to function normally after surgical treatment increased from 39 to 79% (p < 0.001). Long-term survival of our patients was lower than expected rates based on Minnesota life tables analysis (p < 0.0001) especially in alcoholics. Patients undergoing a ductal drainage procedure had the longest survival, whereas those after total pancreatectomy had the shortest survival (p = 0.06). Pancreatic insufficiency, peptic ulcer, and/or anastomotic ulcers caused significant morbidity after total pancreatectomy and pancreatoduodenectomy. A small percentage (3%) developed pancreatic cancer.

Conclusions: Operative treatment of chronic pancreatitis, when indicated, can be performed safely with good results in terms of pain relief and quality of life. Resectional procedures (especially total pancreatectomy) are associated with higher early and late morbidity, greater perioperative mortality, and lower survival rates compared with drainage procedures. Abstinence from alcohol is associated with longer survival rates, which, however, still remain lower than expected rates.

Background and aim: During the course of chronic pancreatitis, the gradual increase in the main pancreatic duct pressure is the main pathophysiological factor responsible for pain, but up to now, the intra ductal pressure has never been measured during and after endoscopic stenting and correlated with clinical results. Pressure measurements of this kind could thus provide objective information about the useful duration of stenting period.

Methods: Main pancreatic duct pressure was measured by performing endoscopic manometry on 13 chronic pancreatitis symptomatic patients (10 men, 3 women, mean age: 45.1+/-7.9 yr); clinical follow-up was carried out for a period of 29.0+/-16.1 mo. Before treatment, the main anatomical alteration present was a localized stenosis of the main pancreatic duct, i.e., one with a diameter of less than 2 mm (chronic pancreatitis alone), 10 cases; chronic pancreatitis associated with pancreas divisum, 3 cases). Stenosis was treated by endoscopic stenting: 7 F stent (7 cases) and 12 F stent (6 cases). The pressure was measured simultaneously in the duodenum (zero level) and within the main pancreatic duct, using an electronic device, The pancreatico-duodenal gradient was taken to be the difference between the pressure in the main pancreatic duct and the duodenum.

Results: The endoscopic stenting induced a nonsignificant decrease in the intraductal pressure (p = 0.16). Among the 9 patients with a normal pressure at the end of the stenting and a successful anatomical outcome, 6 were painless during the follow-up period whereas 3 presented with recurrent pancreatic-type pain. The remaining 4 patients were symptom-free during the entire follow-up period, although the main pancreatic duct pressure was high at the end of the stenting and the stenosis was not completely cured.

Conclusion: The intraductal pressure at the end of the stenting period was perfectly correlated with the anatomical result, whether or not it was successful, but was not an accurate predictor of a favorable clinical outcome in patients with a poor anatomical result.

Background: In an attempt to obtain evidence of the beneficial effects of TJ-10, we investigated the gene expression of PAP, an acute phase protein specific for pancreatitis in rat spontaneous chronic pancreatitis.

Methods: Four-wk-old male WBN/Kob rats were fed with MB-3 pellet diet containing herbal medicine. There were two administration groups for each drug: the prophylactic group administered from 4-12 wk, and the therapeutic group administered from 12-20 wk. Untreated control rats were fed with MB-3 alone. Histopathologic changes and PAP gene expressions were analyzed at 12 and 20 wk.

Results: In the prophylactic group, TJ-10-treated WBN/Kob rats showed no evidence of pancreatitis, and there was the amelioration of pancreatitis in the pancreata of the rats treated with other herbal medicines except TJ-24 at 12 wk. PAP mRNA was not expressed in the TJ-10-treated rats, and PAP gene expression was suppressed in rats treated with other drugs except TJ-107. In the therapeutic group, the amelioration of pancreatitis was seen only in TJ-10-treated rats, but PAP gene expression was significantly suppressed in the rats treated with all herbal medicines tested, compared with that in untreated control rats.

Conclusion: An herbal medicine Saiko-keishi-to (TJ-10) delayed the onset of chronic pancreatitis in the WBN/Kob rat, and suppressed the pancreatitis-associated protein (PAP) gene expression more significantly than other herbal medicines.

Background: The mechanism whereby methyl-2-oxopropylnitrosamine (MOP) is activated remains unknown. To begin investigating this mechanism, we followed MOP disappearance during its incubation with liver and pancreatic slices and homogenates from Syrian hamsters and rats.

Methods: After the incubations, disappearance of 100 microM MOP and appearance of a metabolite was followed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection.

Results: Disappearance rates were 1.2 nmol/mg protein/h for hamster liver slices; zero for hamster pancreatic slices, ducts and acini; zero for rat liver and pancreatic slices; and 11.8, 12.8, 1.3, and 2.3 nmol MOP/mg/h for hamster liver homogenate and cytosol, and hamster pancreas homogenate and microsomes, respectively. The principal MOP metabolite was identified as methyl-2-hydroxypropylnitrosamine (MHP) by its HPLC behavior and its 1H-NMR and mass spectra. MHP yields were generally similar to MOP consumption, but were zero for hamster pancreatic homogenate despite its ability to metabolize MOP.

Conclusion: MOP is a pancreatic carcinogen in hamsters but not in rats. In metabolic studies, hamster liver slices and homogenate (especially the cytosol) produced MHP from MOP. This is probably an inactivation reaction. Hamster pancreas homogenate (especially the microsome fraction), but not rat pancreas homogenate, metabolized MOP without forming MHP, indicating another route of metabolism, perhaps activation to give the proximal carcinogen.

Background: Bacterial translocation from the gut to mesenteric lymph nodes and other extraintestinal sites is an important source of infection in acute pancreatitis. Impaired host immunity is known to promote bacterial translocation. Interleukin-6 (IL-6) is a multifunctional cytokine that regulates the immune response, acute phase reaction, and hematopoiesis.

Methods: Twenty-four mongrel dogs (18-29 kg) were studied in four equal groups. In Groups I and II, acute pancreatitis was induced by direct pressure injection of 4% taurocholate and trypsin into the pancreatic duct at laparotomy. Groups III and IV had only laparotomy. Group I and III dogs were given IL-6 (50 microg/kg/d, sq) daily starting 24 h after operation and Group II and IV dogs received an equal volume of saline administered at similar time. All animals had blood drawn for culture, complete blood count (CBC), platelets, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and amylase on d 0, 1, 4, and 7. On d 7, mesenteric lymph nodes (MLN), spleen, liver, pancreas, and cecum were harvested for pathology study and for cultures of aerobic and anaerobic bacteria. Quantitative cecal cultures of aerobic and anaerobic bacteria were obtained.

Results: All Group I and Group II dogs had severe pancreatitis. The increase of plasma CRP in Group I was sustained throughout treatment (1.3+/-0.3 on d 0 vs 3.1+/-0.3*, 3.0+/-0.3*, and 2.9+/-0.3* on d 1,4, and 7, respectively). Plasma CRP was increased in Group II on d 1 and d 4 (1.3+/-0.3 mg/dL on d 0 vs 3.6+/-0.3* mg/dL on d 1, and 3.1+/-0.3* on d 4, *p < 0.05). There were no differences in white blood cell (WBC) count, differential, platelets, and ESR between Groups I and II. Bacterial translocation to MLN was lower in Group I (1/6) than in Group II (6/6) (p < 0.05). All 6 dogs in Group II had bacterial spread to distant sites compared to 2 of 6 dogs in Group I (p = 0.066). Both MLN and other distant organ cultures were negative in Group III and only 1 of 6 MLN cultures was positive in Group IV.

Conclusions: IL-6 treatment decreases bacterial translocation to MLN and may be beneficial in reducing septic complications in acute pancreatitis.

This review addresses the history of the ras oncogene, the techniques used to detect molecular alterations in the ras oncogene, and the application of polymerase chain reaction (PCR)-based methods to determine point mutations in clinical samples of patients with pancreatic diseases, namely pancreatic carcinoma and chronic pancreatitis. The frequency of ras mutations in pancreatic carcinoma is high, ranging from 70 to almost 100%. The frequence of ras mutations in chronic pancreatitis, either in pancreatic tissue or pancreatic secretions, vary between 0 and 100%. This wide range in part may be owing to differences in sampling, DNA extraction, or PCR method. The meaning of a k-ras mutation is under debate. Taking into account the positivity of ductal hyperplasias in normal pancreas and ras mutations in normal appearing duct cells, this molecular finding may not mean anything. In contrast, ras mutations are associated with smoking, one acknowledged risk factor for pancreatic carcinoma. The need for large prospective cohort studies is emphasized.