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PubMed1987

Pancreatic polypeptide response to a meal before and after cutting the extrinsic nerves of the upper gastrointestinal tract and the pancreas in the dog.

The role of the sympathetic and parasympathetic innervation in the release of pancreatic polypeptide (PP) basally and in response to a meal was studied after stepwise extrinsic denervation of the pancreas and the upper gastrointestinal tract in conscious dogs with gastric fistulae. One set of seven dogs was fed a meat meal (35 g/kg body weight) before and after truncal vagotomy and after truncal vagotomy plus celiac and superior mesenteric ganglionectomy, ie, extrinsic denervation of the pancreas and the upper gastrointestinal tract. In another set of six dogs, only ganglionectomy was performed. Experiments were repeated in the presence of atropine (50 micrograms/kg body weight, given as an intravenous bolus 60 min prior to the meal). Truncal vagotomy significantly (P less than 0.05) reduced the postprandial 120-min integrated plasma PP response (IPPPR) by 84% as compared to the prevagotomy response. Before truncal vagotomy, atropine significantly reduced the IPPPR by 57%. After truncal vagotomy, atropine completely abolished the residual PP response. Additional celiac and superior mesenteric ganglionectomy did not alter the IPPPR already reduced by truncal vagotomy. With the vagus nerves intact, ganglionectomy alone had no effect on the IPPPR whether or not atropine was given. These findings indicate that (1) the splanchnic nerves do not play a significant role in postprandial PP release and (2) that the vagus nerves are important mediators of the response to a meal. The effect of atropine on postprandial PP release after truncal vagotomy may be due to interruption of short enteropancreatic reflexes, suppression of the intrinsic cholinergic activity of the pancreas, or inhibition of hormonally induced PP release.

Animals↗

PubMed2004

Pathogenesis and treatment of neoplastic diseases of the papilla of Vater: Kausch-Whipple procedure with lymph node dissection in cancer of the papilla of Vater.

Cancer of the papilla or the ampulla of Vater appears, from a clinical point of view, to be an intraduodenal or ampullary cancer. An adenoma-dysplasia-carcinoma sequence has been established. In 20%-40% of the patients with an adenoma of the papilla, a cancerous lesion in the adenoma is additionally observed. Oncological resection using a Kausch-Whipple technique or a pylorus-preserving partial pancreatico-duodenectomy (PPPD) offers a 5-year survival probability of between 45% and 65%. The hospital mortality after oncological resection at experienced centers is below 5%. The most frequent treatment-related complication is pancreatic fistula, which occurs in around 20% of the patients. In about 10% of the patients with a pT1 cancer and in 25% to 67% with pT2 and pT3 cancer, lymph node involvement has been observed. Lymph nodes in front of and behind the head of the pancreas are the primary targets for cancer cell disseminations. In more than one-third of the patients, lymph nodes in the inter-aortocaval space and the lymph nodes around the superior mesenteric artery and the nodes in the pancreatic segment of the hepatoduodenal ligament are involved. Therefore, tissue dissection, including, selectively, the N2 lymph nodes, is an essential component of radical surgery for cancer of the papilla. A standard Kausch-Whipple resection or PPPD without a selective extended lymph node dissection, including the interaortocaval and superior mesenteric artery nodes, results in about 30% of the patients having an R2-resection, i.e., with cancer left behind. The long-term survival is determined by the tumor biological factors: (1) absence of lymph node involvement and (2) absence of infiltration into the pancreas. The surgeon's contribution to the cure of cancer of the papilla is to perform an R0-resection with low hospital mortality and low postoperative morbidity. Patients without lymph node involvement, and with absence of infiltration into the pancreas, no lymph vessel invasion, and tumor-negative margins have major benefits from oncological resection in regard to curability of the cancer.

Ampulla of Vater↗

PubMed1983

Effect of 1-phenylpentanol on release of secretin and exocrine pancreatic secretion in dogs and humans.

1-Phenyl-1-hydroxy-N-pentane is a synthetic derivative of an ingredient of Curcuma longa that is used as a condiment and dye. The effects of 1-phenyl-1- hydroxy-N-pentane on release of secretin, gastrin, and pancreatic secretion of bicarbonate and protein were studied in both dogs and humans. In fasting dogs with gastric fistulas and modified Herrera's pancreatic fistulas, intraduodenal administration of 1-phenyl-1-hydroxy-N-pentane (pH 6.7) in three different doses (25, 50, and 100 mg/kg) resulted in significant increases in both plasma secretin concentration and bicarbonate output. The increases in the two variables were dose related. The bicarbonate output and plasma secretin concentration produced by the doses of 1-phenyl-1-hydroxy-N-pentane correlated well. No significant change occurred in either protein output or plasma gastrin concentration. The effect of intragastric 1-phenyl-1-hydroxy-N-pentane on release of secretin and pancreatic secretion was also studied in the digestive state. While gastric pH was maintained at 5.5 by intragastric titration with 1 N NaOH after intragastric administration of 5% liver extract solution, intragastric administration of 1-phenyl-1-hydroxy-N-pentane (100 mg/kg) resulted in significant increases in both plasma secretin concentrations and pancreatic bicarbonate output. In the same experiment, the plasma gastrin concentration did not change significantly, whereas gastric acid secretion decreased significantly after the 1-phenyl-1-hydroxy-N-pentane administration. In 6 human volunteers, both plasma secretin concentration and pancreatic bicarbonate output significantly increased when 2% 1-phenyl-1-hydroxy-N-pentane solution, 30 ml/30 min, was infused in the upper jejunum. Again, no increase in the protein output was apparent. These studies indicate that endogenous secretin is released by an agent other than acid and suggest strongly that the increased pancreatic bicarbonate secretion is attributed to the increased plasma concentration of secretin. 1-Phenyl-1-hydroxy-N-pentane may be a useful agent for release of secretin in subjects with achlorhydria, severe hyposecretory state, or total gastrectomy.

Adult↗

PubMed2001

Randomized structured triglycerides increase lymphatic absorption of tocopherol and retinol compared with the equivalent physical mixture in a rat model of fat malabsorption.

Previously we demonstrated that the digestion, absorption and lymphatic transport of lipid and key essential fatty acids (EFA) from randomly interesterified fish oil/medium-chain structured triglycerides (STG) were significantly higher than an equivalent physical mixture (PM) in a normal lymph fistula rat model and in a rat model of lipid malabsorption caused by ischemia/reperfusion (I/R) injury. The goals of this study were to further explore the potential absorptive benefits of STG by comparing the intestinal absorption and lymphatic transport of tocopherol and retinol when delivered gastrically with either STG or PM under normal conditions and after I/R injury to the small bowel. Food-deprived male Sprague-Dawley rats were randomly assigned to two treatments (sham controls or I/R). Under halothane anesthesia, the superior mesenteric artery (SMA) was occluded for 20 min and then reperfused in I/R rats. The SMA was isolated but not occluded in control rats. In both groups, the mesenteric lymph duct was cannulated and a gastric tube was inserted. Each treatment group received 1 mL of the fish oil/MCT STG or PM (7 rats/group) along with (14)C-alpha-tocopherol and (3)H-retinol through the gastric tube followed by an infusion of PBS at 3 mL/h for 8 h. Lymph was collected hourly for 8 h. Under steady-state conditions, the amount of (14)C-alpha-tocopherol and (3)H-retinol transported into lymph was significantly higher in the STG-fed rats compared with those fed PM in both control and I/R groups. In addition, control and I/R rats given STG had earlier steady-state outputs of (14)C-alpha-tocopherol and (3)H-retinol and maintained approximately 30% higher outputs in lymph throughout the 8-h lymph collection period compared with rats given the PM. We conclude that STG provides the opportunity to potentiate improved absorption of fat-soluble vitamins under normal and malabsorptive states.

Animals↗

PubMed2002

Prenatal ultrasonographic detection of gastrointestinal obstruction: results from 18 European congenital anomaly registries.

OBJECTIVES: We evaluated the prenatal detection of gastrointestinal obstruction (GIO, including atresia, stenosis, absence or fistula) by routine ultrasonographic examination in an unselected population all over Europe. METHODS: Data from 18 congenital malformation registries in 11 European countries were analysed. These multisource registries used the same methodology. All fetuses/neonates with GIO confirmed within 1 week after birth who had prenatal sonography and were born during the study period (1 July 1996 to 31 December 1998) were included. RESULTS: There were 670 793 births in the area covered and 349 fetuses/neonates had GIO. The prenatal detection rate of GIO was 34%; of these 40% were detected < or = 24 weeks of gestation (WG). A total of 31% (60/192) of the isolated GIO were detected prenatally, as were 38% (59/157) of the associated GIO (p=0.26). The detection rate was 25% for esophageal obstruction (31/122), 52% for duodenal obstruction (33/64), 40% for small intestine obstruction (27/68) and 29% for large intestine obstruction (28/95) (p=0.002). The detection rate was higher in countries with a policy of routine obstetric ultrasound. Fifteen percent of pregnancies were terminated (51/349). Eleven of these had chromosomal anomalies, 31 multiple malformations, eight non-chromosomal recognized syndromes, and one isolated GIO. The participating registries reflect the various national policies for termination of pregnancy (TOP), but TOPs after 24 WG (11/51) do not appear to be performed more frequently in countries with a liberal TOP policy. CONCLUSION: This European study shows that the detection rate of GIO depends on the screening policy and on the sonographic detectability of GIO subgroups.

Adult↗

PubMed1984

100 patient-years of ambulatory home total parenteral nutrition.

More than 100 patient-years' experience has been acquired in the treatment of 133 patients with ambulatory home total parenteral nutrition (TPN) between May 1974 and December 1983. Indications for chronic or permanent home TPN include short bowel syndrome, malabsorption, scleroderma, and vasoactive intestinal polypeptide syndrome. Indications for acute or temporary home TPN include Crohn's disease, malignancies, gastrointestinal fistulas, ulcerative colitis, anorexia nervosa, and numerous other disorders. Eighty-two patients in the acute group were treated primarily with percutaneously placed standard subclavian catheters and 51 patients in the chronic group have been treated thus far with implanted silicone rubber, Dacron-cuffed catheters for a cumulative total of 38,939 patient days. Of the 125 implanted catheters, 115 were placed in the superior vena cava and ten in the inferior vena cava for an average duration of 250 catheter-days, the longest single catheter remaining in situ for more than 8 1/2 years. Catheter-related sepsis occurred 33 times with the implanted catheters, or once every 2.6 catheter-years. One hundred and fourteen temporary catheters were placed percutaneously in the superior vena cava via a subclavian vein for an average duration of 68 days, the longest single catheter remaining in situ for 213 days. Catheter-related sepsis occurred seven times, equivalent to one episode per 3 catheter-years. Total catheter-related complications were quite infrequent and were directly related to duration of catheterization. They included venous thrombosis (12), clotted catheter (11), catheter failure or rupture (8), catheter compression (5) and inadvertent catheter removal (4). Twenty-six catheters were repaired or spliced in situ when the external segment was accidentally damaged or deteriorated secondary to long-term material fatigue. One remarkable patient has been maintained exclusively by TPN originally as an inpatient and subsequently as an outpatient for the entire 13 years of his life.

Adolescent↗

PubMed2004

Increased fibronectin expression in developing embryos is associated with abnormal notochord in the Adriamycin rat model.

BACKGROUND: The VACTERL association is a spectrum of clinical conditions, including esophageal atresia (EA) and tracheoesophageal fistula (TEF), which affects approximately 1 in 5,000 live human births. The administration of intraperitoneal Adriamycin to pregnant rats reliably induces anomalies, such as EA and TEF, in their offspring, in what is known as the Adriamycin rat model (ARM). In affected embryos the presence of gross notochord abnormalities is commonly found, with typical features being ectopic ventral branches and adherence of the notochord to the foregut. Fibronectin (FN) is an extracellular matrix (ECM) glycoprotein present on most cell surfaces, in extracellular fluids and in plasma. FN is involved in various functions, including cell adhesion, cell motility and wound healing. Previous studies in rats have shown that a single dose of Adriamycin can produce an appreciable rise in FN levels in various organs such as kidney and heart. We hypothesised that Adriamycin administration could promote upregulation of FN expression contributing to increased gut-notochord adherence and the development of abnormal ventral notochordal branching in the ARM. This study was designed to investigate FN expression in ARM embryos. METHODS: Adriamycin (1.75 mg/kg) was administered intraperitoneally to pregnant rats on days 7,8 and 9 of gestation (E7, E8 and E9 respectively). Control animals were given saline. Embryos recovered on E10-E14 were fixed, embedded in paraffin and sectioned. Immunohistochemistry using an anti-FN rabbit polyclonal antibody was performed. RESULTS: FN expression in both Adriamycin and control embryos on E10, E11 and E12 was comparable. However, the levels of FN expression in Adriamycin embryos on E13 and E14 were significantly greater in embryos with abnormal notochords than in equivalent control embryos. CONCLUSION: Adriamycin-induced increased expression of FN, in the ARM, may contribute to abnormal notochord development leading to the VACTERL association.

Abnormalities, Drug-Induced↗

PubMed2006

A lightweight polypropylene mesh (TiMesh) for laparoscopic intraperitoneal repair of abdominal wall hernias: comparison of biocompatibility with the DualMesh in an experimental study using the porcine model.

BACKGROUND: Despite numerous experimental studies, conducted most often with the open small-animal model, the ideal structure for a mesh with maximum biocompatibility in the intraabdominal region has yet to be found. To date, few experimental models have been concerned with the laparoscopic intraabdominal implantation of meshes. Numerous experimental and clinical studies appear to have identified expanded polytetrafluoroethylene (ePTFE), in the form of DualMesh, as the gold standard. Since publications have reported fistula formation and marked adhesions to be associated with the use of polypropylene meshes, only few studies have investigated meshes made of this material. It is known, however, that a reduction in the amount of material and an increase in pore size results in better mesh biocompatibility. METHODS: Six pigs each underwent laparoscopic intraabdominal placement of either a TiMesh or a DualMesh, both of which were prepared for implantation in standardized fashion. After 87 +/- 2 days, the pigs were killed, and postmortem laparoscopy was performed, followed by the removal of the tissue embedding the mesh for assessment of adhesions and shrinkage, and for histologic workup. The specimens were processed both histologically and immunohistochemically. RESULTS: In all but one case, the greater omentum adhered, usually over discrete areas, to the mesh. In every case the omentum was separable from the mesh surface only by sharp dissection. With the titanium-coated polypropylene meshes, the average total adhesion area was only 0.085, as compared with 0.25 for the GoreTex meshes (p = 0.055). The GoreTex meshes showed an average shrinkage to almost half of the original surface area (median, 0.435). The average shrinkage of the TiMesh, was to 0.18 of the original area (p = 0.006), which thus was significantly smaller. Determination of the partial volume of the inflammatory cells showed significantly lower median figures for the TiMesh (p = 0.009). Measurements of the proliferation marker Ki67 showed significantly higher values for ePTFE than for TiMesh (p = 0.011). The apoptosis index was significantly higher for the ePTFE membranes (p = 0.002). CONCLUSIONS: Titanium-coated polypropylene mesh (TiMesh) is clearly superior to the DualMesh in terms of biocompatibility, and is thus suitable for the laparoscopic intraperitoneal repair of abdominal wall and incisional hernias.

Abdominal Wall↗

PubMed2003

Long-term outcome of percutaneous transhepatic cholangioscopic lithotomy for hepatolithiasis.

OBJECTIVES: Percutaneous transhepatic cholangioscopic lithotomy (PTCSL) for the treatment of hepatolithiasis is particularly suited for those patients who are poor surgical risks or who refuse surgery and those with previous biliary surgery or stones distributed in multiple segments. However, hepatolithiasis is characterized by high rates of treatment failure and recurrence. We examined the long-term results of 245 patients with hepatolithiasis treated by PTCSL. METHODS: This was a retrospective study of 245 patients who underwent PTCSL for hepatolithiasis; the patients were followed for 1-22 yr to evaluate the immediate and long-term results. Sonography was used to search for stone recurrence every year or whenever the patients presented symptoms suggestive of cholangitis. Cholangiography and/or CT were performed to verify recurrence. RESULTS: PTCSL achieved complete clearance of hepatolithiasis in 209 patients (85.3%); the rate of incomplete clearance was higher in patients with intrahepatic duct stricture (29/118, 24.6% vs 7/127, 5.5%; p = 0.002). The rate of major complications was 1.6% (4/245) and included liver laceration (n = 2), intra-abdominal abscess (n = 1), and disruption of the percutaneous transhepatic biliary drainage fistula (n = 1). The overall recurrence rate of hepatolithiasis and/or cholangitis was 63.2%. The absolute rate of stone recurrence was not significantly related to the presence of intrahepatic duct stricture (51/89, 56.2% vs 53/120, 44.4%; p = 0.08), although the median time to recurrence was less in those with stricture (11 vs 18 yr; p = 0.007). In the patients without intrahepatic duct stricture, the rate of complete stone clearance was not related to the presence of dilation (34/38, 89.5% vs 86/89, 96.6%; p = 0.196), but the recurrence rate was higher in those with dilation (20/34, 58.8% vs 33/86, 38.4%; p = 0.042). Among the 209 patients with a successful initial PTCSL, the incidence of recurrent cholangitis or cholangiocarcinoma was significantly higher in those with incompletely removed recurrent hepatolithiasis than in those without coexisting hepatolithiasis (44.3%, 27/61 vs 16.2%, 24/148; p < 0.001 and 6.6%, 4/61 vs 0.7%, 1/148; p = 0.026). CONCLUSIONS: PTCSL is a relatively safe and effective procedure for treating hepatolithiasis. Long-term follow-up is required because the overall recurrence rate of hepatolithiasis and/or cholangitis is high. The rate of complete stone clearance and the median time to stone recurrence are less in the presence of stricture, but the absolute rate of stone recurrence is not significantly related to stricture. In the absence of stricture, the rate of stone recurrence is higher in patients with dilated intrahepatic duct. Complete stone clearance is necessary, because the incidence of recurrent cholangitis or cholangiocarcinoma is higher in patients with incomplete clearance of recurrent hepatolithiasis.

Adolescent↗