Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It provides practical advice on how to achieve successful cannulation and sphincterotomy at minimum risk to the patient. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations 1 ESGE suggests that difficult biliary cannulation is defined by the presence of one or more of the following: more than 5 contacts with the papilla whilst attempting to cannulate; more than 5 minutes spent attempting to cannulate following visualization of the papilla; more than one unintended pancreatic duct cannulation or opacification (low quality evidence, weak recommendation). 2 ESGE recommends the guidewire-assisted technique for primary biliary cannulation, since it reduces the risk of post-ERCP pancreatitis (moderate quality evidence, strong recommendation). 3 ESGE recommends using pancreatic guidewire (PGW)-assisted biliary cannulation in patients where biliary cannulation is difficult and repeated unintentional access to the main pancreatic duct occurs (moderate quality evidence, strong recommendation). ESGE recommends attempting prophylactic pancreatic stenting in all patients with PGW-assisted attempts at biliary cannulation (moderate quality evidence, strong recommendation). 4 ESGE recommends needle-knife fistulotomy as the preferred technique for precutting (moderate quality evidence, strong recommendation). ESGE suggests that precutting should be used only by endoscopists who achieve selective biliary cannulation in more than 80 % of cases using standard cannulation techniques (low quality evidence, weak recommendation). When access to the pancreatic duct is easy to obtain, ESGE suggests placement of a pancreatic stent prior to precutting (moderate quality evidence, weak recommendation). 5 ESGE recommends that in patients with a small papilla that is difficult to cannulate, transpancreatic biliary sphincterotomy should be considered if unintentional insertion of a guidewire into the pancreatic duct occurs (moderate quality evidence, strong recommendation).In patients who have had transpancreatic sphincterotomy, ESGE suggests prophylactic pancreatic stenting (moderate quality evidence, strong recommendation). 6 ESGE recommends that mixed current is used for sphincterotomy rather than pure cut current alone, as there is a decreased risk of mild bleeding with the former (moderate quality evidence, strong recommendation). 7 ESGE suggests endoscopic papillary balloon dilation (EPBD) as an alternative to endoscopic sphincterotomy (EST) for extracting CBD stones < 8 mm in patients without anatomical or clinical contraindications, especially in the presence of coagulopathy or altered anatomy (moderate quality evidence, strong recommendation). 8 ESGE does not recommend routine biliary sphincterotomy for patients undergoing pancreatic sphincterotomy, and suggests that it is reserved for patients in whom there is evidence of coexisting bile duct obstruction or biliary sphincter of Oddi dysfunction (moderate quality evidence, weak recommendation). 9 In patients with periampullary diverticulum (PAD) and difficult cannulation, ESGE suggests that pancreatic duct stent placement followed by precut sphincterotomy or needle-knife fistulotomy are suitable options to achieve cannulation (low quality evidence, weak recommendation).ESGE suggests that EST is safe in patients with PAD. In cases where EST is technically difficult to complete as a result of a PAD, large stone removal can be facilitated by a small EST combined with EPBD or use of EPBD alone (low quality evidence, weak recommendation). 10 For cannulation of the minor papilla, ESGE suggests using wire-guided cannulation, with or without contrast, and sphincterotomy with a pull-type sphincterotome or a needle-knife over a plastic stent (low quality evidence, weak recommendation).When cannulation of the minor papilla is difficult, ESGE suggests secretin injection, which can be preceded by methylene blue spray in the duodenum (low quality evidence, weak recommendation). 11 In patients with choledocholithiasis who are scheduled for elective cholecystectomy, ESGE suggests intraoperative ERCP with laparoendoscopic rendezvous (moderate quality evidence, weak recommendation). ESGE suggests that when biliary cannulation is unsuccessful with a standard retrograde approach, anterograde guidewire insertion either by a percutaneous or endoscopic ultrasound (EUS)-guided approach can be used to achieve biliary access (low quality evidence, weak recommendation). 12 ESGE suggests that in patients with Billroth II gastrectomy ERCP should be performed in referral centers, with the side-viewing endoscope as a first option; forward-viewing endoscopes are the second choice in cases of failure (low quality evidence, weak recommendation). A straight standard ERCP catheter or an inverted sphincterotome, with or without the guidewire, is recommended by ESGE for biliopancreatic cannulation in patients who have undergone Billroth II gastrectomy (low quality evidence, strong recommendation). Endoscopic papillary ballon dilation (EPBD) is suggested as an alternative to sphincterotomy for stone extraction in the setting of patients with Billroth II gastrectomy (low quality evidence, weak recommendation).In patients with complex post-surgical anatomy ESGE suggests referral to a center where device-assisted enteroscopy techniques are available (very low quality evidence, weak recommendation).

Preoperative biliary decompression preceding pancreaticoduodenectomy with plastic or self-expandable metallic stent.

BACKGROUND AND AIMS: The rainage (PBD) prior to pancreaticoduodenectomy (PD) is controversial. If PBD is required, large bore self-expandable metallic stents (SEMS) are thought to maintain better drainage and have fewer postoperative complications than plastic stents. The confirming evidence is scarce. The aim of the study was to compare outcomes of surgery in patients who underwent PBD with SEMS or plastic stents deployed at endoscopic retrograde cholangiopancreatography (ERCP). MATERIAL AND METHODS: This is a retrospective study of 366 patients having had PD during 2000-2009. Preceding endoscopic PBD was performed in 191 patients and nine had had percutaneous transhepatic drainage (PTD). At the time of operation, 163 patients had a plastic stent and 28 had SEMS. Due to stent exchanges, 176 plastic stents and 29 SEMS were placed in all. RESULTS AND CONCLUSIONS: The stent failure rate was 7.4% for plastic stents and 3.4% for SEMS (p = 0.697). A bilirubin level under 50 µmol/L was reached by 80% of the patients with plastic stents and by 61% of the patients with SEMS (p = 0.058). A postoperative infection complication and/or a pancreatic fistula was found in 26% while using plastic stents and in 25% using SEMS (p = 1.000). In unstented patients with biliary obstruction, the bile juice was sterile significantly more often than in endoscopically stented patients (100% vs 1%, p < 0.001). When the stented and unstented patients were compared regarding postoperative infection complications, there was no significant difference between the groups (p = 0.365). Plastic stents did not differ from SEMS regarding the stent failure rate, bilirubin level decrease, amount of bacteria in the bile juice, or postoperative complications when used for PBD. The significantly higher price of SEMS suggests their use in selected cases only.

Risk factors for complications of ERCP in primary sclerosing cholangitis.

BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiographic pancreatography (ERCP) is the most accurate technique for surveillance of patients with primary sclerosing cholangitis (PSC). Our aim was to evaluate risk factors for complications of ERCP in patients with PSC. PATIENTS AND METHODS: In 2007 - 2009 we performed 441 ERCPs in patients with PSC. The primary tools for ERCP were a guide wire and papillotomy knife to gain access into the biliary duct. If the primary cannulation failed, and the wire went only into the pancreatic duct, pancreatic sphincterotomy was performed. If necessary, a further oblique cut with a needle knife was done in order to expose the biliary duct. RESULTS: Primary cannulation was successful in 389 patients (88.2 %). Of these, 147 (37.8 %) had had biliary sphincterotomy performed previously. In the group with failed primary cannulation, access into the biliary duct was achieved after pancreatic sphincterotomy in 52 patients. In 11 of these, a further cut with a needle knife was performed. Post-ERCP pancreatitis (PEP) was diagnosed in 31 patients (7.0 %). Factors predicting PEP were female sex (odds ratio [OR] 2.6, P = 0.015) and a guide wire in the pancreatic duct (OR 8.2, P < 0.01). Previous biliary sphincterotomy was a protective factor (OR 0.28, P = 0.02). The risk of PEP increased with the number of times the wire accidentally passed into the pancreatic duct (P < 0.001). Cholangitis developed in 6 patients (1.4 %). CONCLUSIONS: In patients with PSC the incidence of ERCP complications remained relatively low. The complication risk increased with the complexity of cannulation. In a patient with PSC in whom follow-up ERCP is planned, biliary sphincterotomy should be considered, as it may protect against PEP.

Patient-controlled sedation for ERCP: a randomized double-blind comparison of alfentanil and remifentanil.

BACKGROUND AND STUDY AIMS: Self-administration of a propofol and opioid mixture by patients (patient-controlled sedation, PCS) could offer a practical alternative for individual sedation during endoscopic retrograde cholangiopancreatography (ERCP). However, what would be the most suitable sedative mixture for PCS is unknown. The aim of this study was to compare remifentanil and alfentanil in the PCS during ERCP. PATIENTS AND METHODS: Eighty-one patients undergoing elective ERCP received PCS with propofol and opioid in three different regimens. The concentrations of opioids in the sedative mixture were 0.02 mg/mL in the remifentanil group (R) and 0.04 mg/mL and 0.08 mg/mL in the alfentanil 1 (A1) and alfentanil 2 (A2) groups, respectively. The infusion pump was adjusted to deliver a 1 mL single dose with zero lockout time. We considered PCS as successful if no procedure interruption due to sedation-related complications occurred or if additional propofol was not needed. The consumption of propofol was registered, and sedation levels and vital signs were monitored. Endoscopist and patient satisfaction with sedation were assessed using structured questionnaires. RESULTS: The consumption (SD) of propofol was 177 (105)mg in group R, 197 (88) mg in group A1 and 162 (70)mg in group A2. PCS was successful in 74 /81 (91 %) of sedations, without differences between the groups in terms of propofol consumption, sedation success rate, sedation levels, vital signs, postprocedural pain, and endoscopist and patient satisfaction. Respiratory depression and nausea were observed more frequently with remifentanil than with alfentanil (P < 0.05). CONCLUSIONS: PCS is an acceptable method of sedation for ERCP. The combination of propofol and alfentanil should be recommended because a remifentanil - propofol mixture depresses spontaneous respiration more and produces nausea more frequently.

Surveillance and treatment of duodenal adenomatosis in familial adenomatous polyposis.

BACKGROUND AND STUDY AIMS: Patients with familial adenomatous polyposis (FAP) are at increased risk for duodenal cancer whereas colorectal cancer is largely prevented by prophylactic colectomy. We analyzed the results of endoscopic surveillance and different treatment modalities of duodenal adenomatosis in patients with FAP. PATIENTS AND METHODS: Data on endoscopies, histopathological examinations, and surgical therapies were collected from the medical histories of 129 patients with FAP. The cumulative incidences of duodenal adenomatosis and severe dysplasia and cancer were calculated using Kaplan-Meier analysis. RESULTS: By the age of 60 years, the cumulative incidence was 80% for any adenomatosis and 23% for severe dysplasia or cancer. Duodenal cancer was observed in six patients (4.7%). Fifteen endoscopic excisions in 14 patients, and 19 open duodenotomies in 17 patients were carried out. Later, pancreaticoduodenectomy was undertaken in six (35.3%) of these 17 patients. Altogether, 12 patients (9.3%) underwent pancreaticoduodenectomy. Except for one patient, the indication for surgery was based on follow-up endoscopies, and none of these patients died of duodenal cancer. No postoperative deaths occurred. Seven patients (58.3%) had major complications, four (33.3%) of which were surgical. CONCLUSIONS: The high incidence of severe dysplasia and cancer in duodenal polyps suggests that endoscopic surveillance is essential. Endoscopic polypectomies under sedation anesthesia have partly replaced open duodenotomies. High-risk patients with Spigelman IV adenomatosis or adenomas with persisting severe dysplasia should undergo surgery with pylorus-preserving pancreaticoduodenectomy before invasive cancer develops.

Endoscopic treatment of pancreatic pseudocysts.

BACKGROUND: This study aimed to assess the effectiveness of therapeutic endoscopy in the treatment of pancreatic pseudocysts, and to define factors limiting endoscopic therapy. METHODS: The results of therapeutic endoscopy were evaluated for 170 patients with pancreatic pseudocysts treated at the Department of Surgery, Helsinki University Central Hospital, during the 6-year period from 1998 to 2003. RESULTS: The therapeutic endoscopy success rate was 86.1%, with 23 (13.9%) patients requiring operative treatment because therapeutic endoscopy was unsuccessful or technically impossible. There was little morbidity and no procedure-related mortality. The majority of the 38 complications, which arose from 380 procedures, could be treated conservatively. CONCLUSIONS: Endoscopic methods are safe and effective for the treatment of pancreatic pseudocysts. The indications for surgery include inaccessible pancreatic duct, location, or content of the pseudocyst rendering the problem not amenable to endoscopic therapy, as well as complications of the endoscopic treatment.

The endoscopic management of pancreatic fistulas.

BACKGROUND: Interest in the use of therapeutic endoscopy for the treatment of pancreatic diseases has been on the increase for several years. Our aim was to assess the efficacy of endoscopic retrograde cholangiopancreaticography (ERCP) in the treatment of pancreatic fistulas. METHODS: We evaluated the results of therapeutic ERCP in 50 patients with pancreatic fistula treated at the Helsinki University Central Hospital from 1998 to 2003. RESULTS: The success rate of fistula closure after therapeutic ERCP was 82%. Five patients required operative treatment when ERCP was unsuccessful. There was little morbidity and no procedure-related mortality. Four patients died because severe illnesses made them unfit for any further procedures. CONCLUSION: ERCP is a safe and effective modality and should be considered as first-line therapy in the management of pancreatic fistula.

Effects of extrinsic denervation with or without ischemia-reperfusion injury on constitutional mucosal characteristics in porcine jejunoileum.

We investigated the effects of jejunoileal denervation with or without ischemia-reperfusion on mucosal characteristics and small intestinal structure. Growing pigs underwent sham laparotomy, jejunal transection, or extrinsic jejunoileal denervation with or without in situ ischemia-reperfusion. Small intestinal morphology, crypt cell proliferation, enterocyte ultrastructure, and disaccharidase activities were analyzed from jejunum and ileum after eight weeks. Immunohistological analysis of the ileum showed no staining of catecholaminergic neurons after extrinsic denervation. Neural isolation of the jejunoileum with or without ischemia-reperfusion injury reduced weight gain and villous enterocyte density in the ileum, abolished the proximodistal gradient of sucrase activity, and increased mucosal thickness, villus height, and villus surface area in the ileum. However, gross jejunoileal morphology, crypt cell proliferation, and enterocyte ultrastructure remained unchanged. In conclusion, jejunoileal denervation in growing pigs selectively modulates constitutional mucosal characteristics in the ileum, presumably due to altered enterocyte turnover, without a decrease in small intestinal absorptive surface area. These changes are independent of short ischemia and subsequent reperfusion.

Autotransplantation modulates ileal enteroendocrine cell expression in the pig.

BACKGROUND: Enteroendocrine cell-derived peptides modulate postresectional small bowel adaptation, which may be attenuated by transplantation. We investigated whether autotransplantation modulates the number and distribution of ileal enteroendocrine cells in pigs with proximal small bowel resection. MATERIALS AND METHODS: Fifteen pigs were assigned into either small intestinal transection or 75% proximal small intestinal resection with or without autotransplantation of the remaining ileum. After 14 weeks the number and subtype distribution of enteroendocrine cells, crypt cell proliferation, and mucosal histology were analyzed from the proximal and distal ends of the remaining ileum. RESULTS: When compared to resected controls, autotransplantation of the ileum decreased the absolute (P < 0.05 in proximal ileum) and proportional (P < 0.05 in distal ileum) crypt enteroendocrine cell number. In addition, autotransplantation reduced somatostatin and glicentin expressing cell counts and abolished the proximodistal gradient of the enteroendocrine cell number. When compared to transected controls, villus height, crypt depth, number of proliferating crypt cells, and crypt cell proliferation index increased after the proximal resection (P < 0.05 in all except in crypt depth and proliferation index of the distal ileum) but remained virtually unchanged after autotransplantation of the ileal remnant. CONCLUSIONS: Autotransplantation decreases the crypt enteroendocrine cell number and alters their proximodistal and subtype distribution in the remaining ileum in pigs with proximal small bowel resection. These alterations are associated with attenuated adaptive response of the autotransplanted ileum.

Does increased crypt cell proliferation impair cholesterol absorption after proximal gut resection?

BACKGROUND: The effects of proximal small-bowel resection on absorption and synthesis of cholesterol are unclear. METHODS: To study cholesterol absorption and synthesis after proximal gut resections of variable length, plasma plant sterols, cholestanol, and cholesterol precursors were measured 1 and 2 months after 50% and 75% proximal small-bowel resection or transection. To examine the effect of increased crypt cell proliferation and brush border development on cholesterol absorption, the results were related to the mucosal morphology, crypt cell proliferation, and disaccharidase activities of the remaining small bowel. RESULTS: Campesterol levels in proportion to cholesterol decreased markedly more, and those of cholestanol markedly less, than would be expected simply due to the amount of proximal small intestine removed, whereas sitosterol proportions decreased in proportion to the length of gut resection. Campesterol proportions markedly (P = 0.06) increased between 1 and 2 months after 50% resection but remained unchanged after 75% resection. Crypt cell proliferation was only increased in the 75% resection group (P < 0.05). The longer the proximal gut resection, the lower was the mucosal enzyme activity. Both resection groups showed increased plasma cholesterol precursor proportions and crypt depth (P < 0.05), whereas villus height remained unchanged. After massive proximal resection campesterol and sitosterol proportions were inversely related to crypt cell proliferation (r = -0.86-0.83, P < 0.01). CONCLUSIONS: Increased crypt cell proliferation activated by massive proximal gut resection may act as a previously unrecognized factor in aggravating cholesterol malabsorption and retarding its recovery during the early postoperative period. These findings warrant further investigation.

Synchronous ileal autotransplantation impairs adaptation of remaining gut in pigs with proximal small bowel resection.

This study investigates the effects of ileal autotransplantation on morphology, crypt cell proliferation, and brush border disaccharidases of the remaining jejunoileum and colon in growing pigs with 75% proximal small bowel resection. Resection was performed on 30 pigs, of which 15 underwent an autotransplantation of the remaining ileum. The autotransplanted pigs showed reduced weight gain and remnant ileal length when compared to the resected controls. In the autotransplanted pigs, small bowel diameter and weight, mucosal weight and protein content, villus height and surface area, crypt depth, and the number of proliferating crypt cells were reduced similarly both in the intact jejunum and in the autotransplanted ileal remnant. Autotransplantation also decreased the number of proliferative crypt cells of the colon. Specific activities of maltase and sucrase tended to increase in the autotransplanted ileal remnant, whereas the total enzyme activities decreased. These results suggest that ileal autotransplantation disturbs postresectional adaptation of the remaining gut.

Bactericidal/permeability-increasing protein and group I and II phospholipase A2 during the induction phase of human acute pancreatitis.

Activated endogenous mediators of inflammation have important roles in the pathogenesis and complications of acute pancreatitis (AP). These mediators include bactericidal/ permeability-increasing protein (BPI) and phospholipase A2 (PLA2). The time course of their activation during human AP is not known. The aim of this study was to evaluate the kinetics of BPI, group I (pancreatic) and group II (synovial type) PLA2 during human AP with temporally defined onset, as being induced by endoscopic retrograde cholangiopancreatography (ERCP). Serum samples of 273 consecutive patients undergoing ERCP were collected before and at 3, 6, and 24 h after ERCP. Twenty-four (8.7%) patients developed ERCP-induced pancreatitis. Seven of them were graded to have a severe disease. Forty randomly selected patients undergoing ERCP without evidence of pancreatitis served as controls. The serum concentrations of BPI and groups I and II PLA2 were measured by specific immunoassays. The mean concentration of BPI increased from 14 to 26 microg/L at 24 h after ERCP in patients with AP. In the control group, BPI values remained unchanged, and the difference was statistically significant (p<0.001). The increase of BPI was seen in 22 of 28 patients with AP at 3 h after the onset of the disease. BPI values were higher in severe post-ERCP pancreatitis than in mild disease (p = 0.07; NS). The serum concentrations of group II PLA2 before ERCP were consistently higher in the control patients than in the patients with pancreatitis, 65.8 and 14.2 microg/L, respectively. High baseline values in the control group were associated with preexisting infectious diseases. Thereafter, the mean concentration decreased in the control group to 44 microg/L and increased in the pancreatitis group up to 27.5 microg/L. The difference was statistically significant (p = 0.007). Increased group II PLA2 values were seen in 10 of 17 patients with mild AP and in five of seven patients with severe disease. There were no significant differences in group I or II PLA2 values in patients with mild or severe AP. The serum concentration of group I PLA2 increased in the patients with post-ERCP pancreatitis from 5.4 to 37.5 microg/L at 24 h. The difference was statistically significant, (p< 0.001) as compared with controls. In conclusion, in acute pancreatitis, the increase of BPI in serum starts at 3 h after the onset of the disease, and the concentration seems to correlate with the severity of the disease. Increased group II PLA2 concentrations also were seen in patients with mild AP. The kinetics of group I PLA2 resembles that of other pancreatic enzymes.

Nerve terminals containing neuropeptides decrease in number after massive proximal small bowel resection in the piglet.

The aim of this study was to evaluate possible changes in the neuropeptide innervation pattern of the remaining porcine ileum following 75% proximal resection of the small intestine. Three-month-old piglets were operated on and two months postoperatively full-thickness specimens of the proximal part of the distal ileum wall were taken. Age-matched 3- and 5-month-old unoperated piglets were used as controls. The number and intensity of VIP-, galanin-, enkephalin-, substance P-, and somatostatin-containing nerve fibers were estimated in sections processed for immunofluorescence microscopy and subjected to quantitative scoring. The VIP-, galanin-, and enkephalin-immunoreactive fibers of the circular muscle layer and villi were also quantitated by computer-assisted morphometry. The number and intensity of VIP-immunoreactive fibers in the mucosa and circular muscle layer markedly decreased after resection as compared to 3-month-old and 5-month-old controls (P < 0.05). The galanin immunoreactivity index decreased significantly after resection in the circular muscle layer as compared to both control groups (P < 0.05). The increase in the number of enkephalin-immunoreactive nerve fibers that normally occurred from 3 to 5 months of age was inhibited by the resection. We were not able to see any differences in somatostatin or substance P immunoreactivity between the groups. The results suggest that massive resection induces significant changes in the neuropeptide-containing innervation of the remaining small intestine. These findings are compatible with altered motor activity and mucosa function in the remain intestine.

Absorption, excretion, and distribution of plant sterols after proximal gut resection and autotransplantation of porcine ileum.

Contribution of different gut segments to plant sterol absorption, adaptation of plant sterol absorption after partial small bowel resection, and effects of gut transplantation (necessitates extrinsic autonomic denervation and lymphatic disruption) on plant sterol biodynamics are unclear. We studied the consequences of massive proximal small bowel resection and autotransplantation of the remaining ileum on the adaptive absorption and biodynamics of plant sterols. Dietary, fecal, biliary, hepatic and plasma plant sterols, fecal elimination and absorption of cholesterol, small bowel morphology, and intestinal transit were determined before (n = 5) and at 4, 8, and 14 wk after resection of the proximal 75% of the jejunoileum (n = 15) and autotransplantation of the remaining ileum (n = 15) or transection (n = 5). Proximal gut resection significantly reduced cholesterol absorption efficiency; percentage absorption and biliary secretion of plant sterols; plasma, biliary and hepatic campesterol-to-cholesterol proportions; and sitosterol proportions in plasma and bile. Autotransplantation of the remaining ileum further significantly decreased cholesterol absorption efficiency; percentage absorption and biliary secretion of campesterol; campesterol proportions in plasma, bile and liver; and plasma proportions of sitosterol while increasing fecal excretion of neutral and acidic steroids. Plasma proportions of the two plant sterols, but absorption of just campesterol, were gradually improved with increasing cholesterol absorption and villus height after proximal gut resection; the same result was observed to a lesser degree after ileal autotransplantation. In addition, significant positive correlations were found between percentage cholesterol and campesterol absorption and the plasma plant sterol proportions in both proximal resection groups, between campesterol absorption and ileal villus height in the resection group, and between campesterol absorption and intestinal transit time in the autotransplantation group. In conclusion, plasma campesterol and sitosterol closely reflect absorption of cholesterol and plant sterols from intact and autotransplanted ileum during adaptation to proximal gut resection. A loss of proximal gut absorptive surface impairs cholesterol and campesterol absorption more than sitosterol absorption, the latter being apparently less dependent on available jejunal villus surface area.

Increased plasma, biliary, and hepatic cholesterol precursors in pigs with ileal autotransplantation-induced malabsorption of cholesterol and bile acids.

BACKGROUND: Small-bowel transplantation impairs intestinal absorptive function for unknown reasons. METHODS: The proportions of plasma, biliary, and hepatic cholesterol precursors to cholesterol were determined by gas-liquid chromatography after resection of the proximal 75% of the porcine jejunoileum (n = 15) and autotransplantation of the remaining ileum (n = 15) and were related to in vivo absorption and fecal excretion of cholesterol. RESULTS: Ileal autotransplantation significantly decreased serum (18%; P < 0.05) and liver (7.6%; P < 0.05) cholesterol content, the esterification percentage of serum cholesterol (5.1%; P < 0.0001), and the total amount of cholesterol absorbed (48%; P < 0.05) and increased fecal excretion of bile acids (108%; P < 0.0001), net cholesterol elimination (53%; P < 0.001), and the proportions of plasma (207%; P < 0.0001), biliary (183%; P < 0.0001), and hepatic (114%; P < 0.0001) cholesterol precursors. The increases were most striking for the side-chain-saturated demethylated sterols, cholesterol and lathosterol, and monomethyl sterols, whose bile/liver and plasma/liver ratios were increased in the autotransplantation group. Plasma, biliary, and hepatic precursor proportions were positively related to each other and similarly correlated with fecal bile acids and the net elimination of cholesterol in feces. CONCLUSIONS: These findings suggest that ileal autotransplantation in pigs with proximal gut resection increased the levels of cholesterol precursor sterols in plasma, bile, and liver mainly due to a bile-acid-malabsorption-induced increase in hepatic synthesis of cholesterol. Enhanced secretion of cholesterol precursors from the liver into the plasma and bile may have contributed to their increased values during the increased rate of cholesterogenesis.

Intestinal adaptation after massive proximal small-bowel resection in the pig.

BACKGROUND: Small-intestinal adaptation to resection has been extensively studied in rats. The present study investigates morphology, crypt cell proliferation, and disaccharidase activities of the remaining small intestine and colon after 75% proximal resection of porcine small intestine. METHODS: Specimens were obtained from the proximal jejunum, middle and distal ileum, and proximal colon preoperatively (n = 5) and 14 weeks after small-bowel transection (n = 5) or resection (n = 5). Proliferation was analyzed immunohistochemically with the Ki-67 antigen MIB-1. Disaccharidase activities were determined in accordance with the method of Dahlqvist. RESULTS: In addition to macroscopic enlargement, resection markedly increased the villi and crypts of the remaining small bowel. Crypt cell proliferation decreased with advancing age after transection but remained at the preoperative level after resection. Specific, but not total, activities of maltase and sucrase in the mid-ileum decreased after resection. CONCLUSION: Small-intestinal adaptation in the pig involves macroscopic enlargement and a prompt increase in villus size, which is associated with high crypt cell proliferation.

How to diagnose chronic rejection. A study in porcine intestinal allografts.

Porcine small bowel allografts were followed for 18 weeks during immunosuppression with cyclosporine-A (CyA), azatioprine and prednisone. The mucosal alterations noted at the 12th week were epithelial vacuolation and loss of Goblet cells. Moderate infiltration of inflammatory cells, mainly lymphocytes, was found in the lamina propria. In addition, a few grafts exhibited oedema and fibrosis. Vessels already showed endothelial swelling and intimal proliferation at the 12th week. In the submucosa, the infiltration of inflammatory cells was not present till the 18th week. Further changes in the mucosa at the 18th week were the blunting of villi, cuboidal epithelium, crypt abscesses and epithelial atrophy. The histological alterations of mucosa and lamina propria existing in the full thickness biopsies were mostly also detectable in mucosal biopsies, provided that multiple biopsies were taken. Thus these parameters analyzed from mucosal biopsy material are suitable for the diagnosis and monitoring of chronic small bowel rejection. In autopsy, the most prominent features were in the mesenterial arteries: intimal proliferation, vasculitis, proliferation of media and endothelial alterations. The activity of the mucosal disaccharidases maltase and sucrase remained near the initial level till the 12th week and had decreased markedly by the 18th week.