Laparoscopic nephroureterectomy in children: a prospective study on Ligasure versus Clip/Ligation.

PURPOSE: The present study was performed to compare dissection of the renal hilar vessels in laparoscopic transabdominal nephrectomy in children using the Endo-Ligasure vessel sealing system versus clip/ligation. PATIENTS AND METHODS: In a prospective and comparative study carried out from February 2003 to April 2004, 10 consecutive patients (group 1) underwent laparoscopic transabdominal nephroureterectomy using clips or intracorporeally performed ligations, respectively. From April 2004 to April 2005, 10 consecutive patients (group 2) underwent the same procedure using the Endo-Ligasure vessel sealing system. Indications for surgery were confirmed non-functioning kidneys secondary to benign unilateral renal disease and no prior surgery. The age and underlying disease distribution and the affected side were not significantly different between the two groups. RESULTS: The operating time was significantly lower in the Endo-Ligasure group (group 1: median 167 vs. group 2: 108 min, p < 0.05). Bleeding of the renal artery occurred due to dislocation of a suture ligation, which was treated laparoscopically with an intracorporeal suture ligation. Blood loss was negligible in all patients. All procedures were completed laparoscopically and recovery was uneventful. CONCLUSIONS: Endo-Ligasure is a beneficial tool in laparoscopic transabdominal nephrectomy. It is safe, effective, and reduces operating times compared to clip application and intracorporeal suturing.

Laparoscopic resection of congenital choledochal cyst, choledochojejunostomy, and extraabdominal Roux-en-Y anastomosis.

BACKGROUND: The feasibility of laparoscopic resection of choledochal cyst and hepaticojejunostomy in children is still unclear. This report presents the author's experience with a first series of patients. METHODS: Data from 11 consecutive children (median age 17.5 months, SD 22, range 2 to 70) with choledochal cyst scheduled for laparoscopy were collected prospectively. There were nine type I and 2 type V cysts according to Todani's classification. All except one patient had intermittent jaundice or recurrent pancreatitis. The laparoscopic technique included excision of the cyst. A Roux-en-Y anastomosis was constructed after exteriorization of the small bowel via the infraumbilical trocar incision. After repositioning of the bowel an end-to-side hepaticojejunostomy was carried out laparoscopically. RESULTS: The procedures were carried out in nine children without intraoperative events and a median duration of 289 min (SD 62). In two patients, the operation was converted after 60 and 90 min due to a lack of overview at the dorsal margin with problems in separation of the portal vein. Oral food intake was started within 2 days and tolerated well in all except one patient, in whom biliar fluid from the drain led to laparoscopic reevaluation on day 1. A small leak was resutured and the patient was discharged on day 5. In one patient, recurrent cholangitis and a dilated Roux-en-Y loop led to correction of some kinking of the loop via laparotomy after 3 months. All other patients are well with bile-stained stools after a mean follow-up of 13 months. CONCLUSIONS: Laparoscopic resection of congenital choledochal cyst and choledochojejunostomy in children is feasible. We feel that there is a considerable learning curve with the technique. Future studies will have to prove the feasibility of laparoscopic Roux-en-Y bowel anastomosis without the need for bowel exteriorization.

Identification and biochemical characterization of the human brain galanin receptor.

Human galanin (hGal) is an important neuro-modulator present in the brain, gastrointestinal system and the hypothalamo-pituitary axis. A specific receptor for hGal has been identified in various areas in human brain. A single class of high affinity binding sites was found on plasma membranes of the amygdala (Kd 0.23 nM, Bmax 44 fmol/mg), the hypothalamus (Kd 0.20 nM, Bmax 25 fmol/mg) and the cortex cerebri (Kd 0.11 nM, Bmax 8.2 fmol/mg). Other brain areas, i.e. cerebellum, thalamus or pons, expressed binding sites of identical high affinity in lower quantities (Bmax < 3 fmol/mg). Specific binding of 125I-labelled hGal was found to be reversible, time- and temperature-dependent and inhibited by Ca2+, Na+ and K+ ions at a concentration of 5 mM. Non-hydrolysable guanosine nucleotides potently reduced specific binding of 125-I-labelled hGal by more than 80%. Synthetic hGal analogues substituted in the N-terminal region exhibited strongly reduced binding affinity for the hGal receptor. Using 3-[(3-cholamidopropyl) dimethylammonio]-2-hydroxy-1-propanesulphonate, hGal receptors were successfully solubilized from human cortical membranes, exhibiting no significant loss of binding affinity. Affinity cross-linking to 125I-labelled hGal revealed a labelled band of approximately 60 kDa sensitive to unlabelled Gal. This putative hGal receptor is glycosylated since its molecular size was reduced after treatment with endoglycosidase F. Receptors bound to 125I-labelled hGal could be specifically adsorbed to wheat germ agglutinin and ricinus communis agglutinin, suggesting that receptor glycosylation involves N-acetyl glucosamine and galactose respectively.

Evidence for non-neurotensin receptor-mediated effects of xenin (1-25)--focus on intestinal microcirculation.

Xenin (1-25) has been detected in various locations in mammalians. It has structural similarities with neurotensin and its intestinal effects are claimed to be mediated by neurotensin receptors. It has been shown to influence gastrointestinal motility. The effects of xenin (1-25) on intestinal microvascular perfusion after ischemia/reperfusion have not been investigated yet. Therefore, the superior mesenteric artery was clamped for 40 min in Wistar rats (n=8). Ten minutes prior to reperfusion, intravenous infusion of xenin (1-25) (5 nmol/kg/h) was started. By means of intravital microscopy, microvascular perfusion in the mucosal layer was assessed. Animals (n=8) with and without clamping of the superior mesenteric artery and infusion of the carrier solution served as controls. After ischemia/reperfusion, xenin (1-25) increased the density of perfused microvessels and the capillary red blood cell velocity compared to ischemic controls. Capillary red blood cell velocity was elevated (p<0.05). Xenin (1-25) improved the heterogeneous distribution of mucosal blood flow during reperfusion demonstrated by an increase of both the perfusion index and the percentage of perfused microvessels. We conclude that the effects of xenin (1-25) on intestinal microcirculation are significantly different from those previously described for neurotensin. A more complex effector mechanism must be postulated that may involve other regulatory peptides and receptors.

Role of neurotensin in the regulation of exocrine pancreatic secretion in dogs.

A potential physiological function of the regulatory gastrointestinal peptide neurotensin (NT) is the stimulation of exocrine pancreatic secretion. We investigated therefore whether immunoneutralization of the postprandially circulating peptide, intravenous application of either atropine or the highly specific CCK receptor antagonist, L-364,718, could influence neurotensin-mediated pancreatic secretion in dogs. The use of CCK receptor antagonist (0.1 mg kg-1 intraduodenally) inhibited postprandial and NT-mediated exocrine pancreatic secretion. The integrated postprandial protein secretion fell from 31 +/- 1.6 to 23 +/- 2.1 g 180 min-1 while the corresponding values in response to i.v.-NT (postprandial neurotensin concentration course was imitated by the infusion of 50 pmol kg h-1 NT) fell from 22 +/- 1.9 to 7.5 +/- 0.8 g 180 min-1. Immunoneutralization of postprandial NT led to a simultaneous significant reduction in postprandial pancreatic secretion (integrated protein release 31 +/- 1.6 and 15.5 +/- 1.4 g 180 min-1 respectively). The i.v. application of atropine lowered NT-mediated pancreatic secretion (e.g., protein output) from 22 +/- 1.9 to 7.1 +/- 7.1 +/- 0.9 g 180 min-1. We conclude that NT plays an important role in the endocrine regulation of exocrine pancreatic secretion. This influence could be mediated by a CCK-dependent cholinergic mechanism.

On the effect of xenin and xenin fragments on exocrine pancreas secretion in vivo.

A stimulatory effect on exocrine pancreas secretion could be demonstrated with high concentrations of the 25-amino-acid peptide xenin in non-anesthetized dogs. This peptide has been isolated from gastric mucosa and it is part of a structural coat protein. It has close structural similarities to neurotensin. The longer C-terminal fragments xenin-(13--25) and xenin-(18--25) are essential for the stimulation of exocrine pancreas secretion in vivo. The smaller peptide fragments xenin-(21--25) and xenin-(22--25) failed to stimulate the pancreas as well as the N-terminal peptide fragment xenin-(1--23). The stimulatory effects of xenin may be mediated via neural neurotensin pathways, because neurotensin receptor blockade abolished the stimulatory effect on pancreatic secretion. Cholinergic pathways are not involved, because atropine had no inhibiting effect.

Determination of plasma cholecystokinin (CCK) concentrations by bioassay and radioimmunoassay in man. A critical evaluation.

The present investigation was designed to perform a direct comparison of a rat pancreatic acini bioassay system and a specific CCK radioimmunoassay (antiserum G-160) for the measurement of fasting and meal-stimulated plasma CCK in the presence and absence of the CCK receptor antagonist loxiglumide. The G-160 CCK antiserum is directed against the C-terminal O-sulfated tyrosine residue of the CCK molecule which is essential for full bioactivity of CCK peptides. For plasma extraction prior to bioassay measurement, hydrophobic reverse-phase chromatography on octadecylsilane cartridges was employed and resulted in simultaneous adsorption and elution of both CCK peptides and loxiglumide with recoveries of 87.5 +/- 9% and 75.0 +/- 5.9%, respectively. In the absence of loxiglumide, fasting and meal-stimulated values for CCK-like bioactivity and CCK-immunoreactivity (IR-CCK) were nearly identical (basal values: 1-2 pmol/l; meal-stimulated plateau levels: 4-6 pmol/l). After intravenous infusion of loxiglumide (30 mg/kg/h for 10 min, 10 mg/kg/h thereafter), resulting in plasma steady state levels of 200-300 mumol/l, meal-stimulated CCK-like bioactivity was undetectable, whereas IR-CCK levels were augmented 6.5-fold. In the bioassay system, standard samples containing 50 mumol/l loxiglumide produced complete inhibition of acinar lipase release in response to 50 pmol/l synthetic CCK-8. We conclude, that postprandial circulating non-CCK-like factors do not contribute significantly to the direct receptor-mediated stimulation of exocrine pancreatic secretion. The good agreement of CCK-like bioactivity and IR-CCK levels in the absence of loxiglumide confirms the sensitive and specific recognition of bioactive CCK peptides by the G-160 antiserum and suggests that this antibody exerts binding characteristics probably similar to a pancreatic acinar receptor.

Feedback regulation of exocrine pancreatic secretion in dogs.

Important basic physiological mechanisms of exocrine pancreas secretion were delineated in a canine model. However, dogs have been considered unsuitable for the study of the controversial feedback regulation of exocrine pancreas secretion. The present study reveals a marked modification of pancreas secretion following the intraduodenal instillation of lipase: The postprandial lipase secretion decreases from 2,421 U x 180 min-1 to 1,490 U x 180 min-1, but simultaneously determined cholecystokinin (CCK) concentrations in plasma do not increase under these circumstances. The intraduodenal application of a protease inhibitor (800 mg camostate) significantly stimulates the secretion of the exocrine pancreas in the fasting dog: After 15 min the protein release increased to 133 +/- 30 mg. Intravenous atropine blocks this increase. The plasma concentrations of CCK are not significantly influenced. These results in our canine model show that the secretory activity of the exocrine pancreas depends on the intraduodenal enzyme content. CCK is irrelevant in this context.

Exocrine pancreatic function in dogs with denervated pancreas.

There is strong evidence that the vagus nerve plays an important role in exocrine pancreatic secretion. In the present study we examined the effect of total extrinsic denervation of the pancreas on exocrine pancreatic secretion to different stimuli in dogs. In the experiments we used the model of the orthotopic autotransplanted dog pancreas as described by Debas et al. Denervation of the gland did not significantly alter water and bicarbonate response to secretin. The dose-response curve of caerulein showed the denervated pancreas as sensitive as the intact gland. However, autotransplantation of the pancreas caused a significant decrease (p less than 0.05) in protein secretion during intraintestinal L-tryptophan in increasing doses. Furthermore, bicarbonate and protein secretion after food intake was significantly decreased in the denervated pancreas (protein: peak levels 380 mg/15 min and 135 mg/15 min; bicarbonate: 3.2 mEq/15 min and 1.4 mEq/15 min) (p less than 0.02). From our data we conclude that the denervated pancreas is as sensitive as the intact pancreas to stimulation by exogenous secretin and caerulein, whereas denervation of the pancreas causes an important influence in the intestinal phase of pancreatic secretion.

Plasma concentrations of neurotensin and CCK in patients with chronic pancreatitis with and without enzyme substitution.

The peptide hormones neurotensin (NT) and cholecystokinin (CCK) are commonly attributed with a physiological role in the stimulation of exocrine pancreatic secretion. However, on the other hand, little is known about the effect of diminished exocrine pancreatic function and of the resulting maldigestion on postprandial plasma levels of these two gastrointestinal peptides. We investigated, therefore, the effect of enzyme substitution therapy on the magnitude and time course of plasma concentrations of both hormones in patients suffering from severe chronic pancreatitis. Pancreatic insufficiency led to elevated NT-concentrations, in response to a standard meal, which could be reduced by enzyme replacement therapy. Prior to enzyme therapy, the mean integrated postprandial release of NT amounted to 2800 +/- 250 pg/ml after 60 min in patients with severe chronic pancreatitis. This amount was significantly reduced to 1250 +/- 150 pg/ml after 60 min after enzyme therapy, compared to 810 +/- 90 pg/ml after 60 min in healthy volunteers after the standard meal. The integrated postprandial CCK level in patients investigated was significantly lower (35 +/- 4.8 pmol/L after 60 min) without any substitution therapy, compared to the integrated peptide amount in healthy volunteers (145 +/- 13.5 pmol/L after 60 min). Enzyme therapy in patients suffering from chronic pancreatitis led to an increased postprandial CCK-level (80 +/- 9.6 pmol/L after 60 min). Elevated CCK-plasma concentrations have not been demonstrated in these patients with pancreatic insufficiency. We therefore suggest that CCK might not play a major role in feedback regulation in patients with chronic pancreatitis. However, in light of elevated NT plasma concentrations in patients with chronic pancreatitis, NT-mediated influence on the pancreas deserves further study.

Effect of total extrinsic denervation and atropine on HCl-stimulated pancreatic exocrine secretion and CCK release in conscious dogs.

In 10 dogs with pancreatic fistulas, we studied the effect of extrinsic pancreatic innervation and atropine on protein and bicarbonate secretion and cholecystokinin (CCK) release after intraduodenal perfusion with HCl. Before and after extrinsic denervation of the pancreas, the dogs were given 0.05 M HCl in increasing doses (1.5-48 mmol/h). Tests were repeated with atropine. Increasing doses of HCl resulted in a dose-dependent release of protein and bicarbonate output in both the intact and the denervated pancreas. However, pancreatic denervation significantly decreased pancreatic secretion in response to low loads but not to high loads of HCl. HCl-stimulated CCK release was not altered by pancreatic denervation. In the intact pancreas, atropine significantly reduced bicarbonate and protein response to low loads but not to high doses of HCl. In the denervated gland, atropine had no further inhibitory effect on exocrine pancreatic secretion. Furthermore, atropine showed no influence on HCl-stimulated CCK release under either condition.

On the role of gastrin-releasing peptide in meal-stimulated exocrine pancreatic secretion.

The contribution of gastrin-releasing peptide (GRP) in the physiologic pancreatic response to a meal is unknown. We therefore investigated whether immunoneutralization of GRP could influence the exocrine pancreatic response to a meal as well as plasma concentrations of the peptide hormones neurotensin (NT) and cholecystokinin (CCK). Modified Herrera fistulas were implanted in five mongrel dogs. After a standard meal, we analyzed plasma NT, CCK, and GRP, and protein and enzyme (amylase, lipase, trypsin) content of exocrine pancreatic juice. An unspecific rabbit immunoglobulin solution was administered intravenously as a control. This experiment was repeated with a specific anti-GRP-immunoglobulin. The i.v. administration of the anti-GRP-antibody significantly inhibited meal-stimulated pancreatic secretion. Integrated protein output decreased from 58.4 to 36.8 g/180 min (p < 0.05), as did amylase (2,102 to 1,145 KU/180 min; p < 0.05), lipase (2,258 to 1,172 KU/180 min; p < 0.05), and trypsin (5,321 to 4,990 U/180 min). Postprandially released NT decreased from 8,271 to 5,825 pmol/180 min (p < 0.05). In contrast, integrated amounts of CCK remained relatively stable with 473 to 611 pmol/180 min. The neuropeptide GRP is one of the biologically important regulatory factors influencing meal-stimulated pancreatic secretion, as well as the postprandial plasma level of the peptide hormone NT in the dog. These mentioned effects of postprandially released GRP seem not to be mediated by CCK in an endocrine manner.

The biological relevance of N-terminal neurotensin fragments in the regulation of exocrine pancreas secretion.

Stimulation of the exocrine pancreas is one of the biological effects attributed to the tridecapeptide neurotensin (NT). Only the C-terminal 8-13 fragment with its extremely short plasma half-life in the peripheral circulation was considered to be necessary for biological activity. The N-terminal fragments that are detectable in peripheral blood in much greater concentrations were considered to be of no importance. In order to elucidate the biological relevance of these N-terminal fragments, five dogs were infused with neurotensin at a rate (50 pmol/kg/h) that had been determined to give physiological plasma concentrations. Pancreatic secretions were collected from previously implanted modified Herrera pouches. The effects of the N-terminal fragments NT 1-8 and NT 1-11 on the exocrine pancreas secretion were tested in the same way. It was possible for the first time to demonstrate a biological effect of the N-terminal fragments found in the postprandial circulation in vivo. The plasma concentrations determined by radioimmunoassay remained within the physiological range (less than 40 pg/ml). These N-terminal neurotensin fragments may therefore participate in the hormonal regulation of the exocrine pancreas secretion.

Partial hepatectomy affects pancreatic size and function in rats.

The effect of partial hepatectomy (62 +/- 2% of liver mass) or sham laparotomy on the pancreas was studied in rats. Pancreatic contents of DNA, protein, and digestive enzymes were measured 14 days postoperatively. Pancreatic acini were prepared to study exocrine pancreatic function after hormonal stimulation. Islet hormone release was investigated in the isolated perfused pancreas. Liver regeneration reached 93 +/- 1% within 14 days. Water contents in liver and pancreas remained unaltered. Simultaneously, the pancreatic weight increased significantly. Pancreatic enzymes showed a parallel elevation, whereas DNA remained unaffected. Amylase secretion from pancreatic acini was unaltered. Stimulated insulin and somatostatin release from the perfused pancreas were both increased. Plasma cholecystokinin levels were elevated, whereas neurotensin was decreased. Insulin and gastrin remained unchanged. In conclusion, after partial hepatectomy, enhanced cholecystokinin and decreased neurotensin blood levels are suggested to contribute to a hypertrophic effect on the exocrine pancreas and an adaptive regulation of the endocrine gland.

Pancreatic trophism following colectomy in rats: the potential role of gastrointestinal hormones.

It has been shown that the large bowel contains substances with a potential to inhibit exocrine pancreatic function. Following large bowel removal in rats, there is an increase of pancreatic weight, digestive enzyme concentration, and secretion capacity in vitro. To evaluate the role of various GI hormones in the exocrine pancreatic adaptation following colectomy, we measured plasma cholecystokinin (CCK), neurotensin, glucagon, and insulin after meal stimulation. The test meal was applied via a transabdominal gastric tube in eight colectomized Wistar rats after a median of 18 days following surgery. Ten rats with a gastric tube without previous bowel surgery served as controls. After large bowel removal, there was impaired glucose tolerance and attenuated plasma insulin secretion. Baseline plasma glucagon levels were increased after colon removal, whereas the total postprandial glucagon release was decreased. Baseline and postprandial neurotensin values were comparable in both the experimental and control animals. Baseline and postprandial CCK plasma levels were intensely increased in the colectomized rats. It is assumed that the baseline and postprandial CCK pattern in rats after subtotal colectomy is responsible for exocrine pancreatic adaptation.

Postcholecystectomy syndrome with special regard to children--a review.

The incidence of abdominal symptoms after cholecystectomy in adults is high. Up to one third of the patients consult a doctor because of abdominal complaints within 1 year after the operation. In addition, a higher incidence of colon carcinoma after cholecystectomy has been reported in female patients. This article reviews the known facts on the "postcholecystectomy syndrome". However, little is known about postcholecystectomy symptoms in children. Reports on cholecystectomy in children deal rather with feasibility than long-term outcome. Therapeutic concepts for children with symptomatic gallstone disease should consider the differences in the etiology of gallstone formation between children and adults. Therefore, we recommend a specific concept, including laparoscopic cholecystotomy, for children with temporary disorders causing gallstones, and laparoscopic cholecystectomy for all other patients. The impact of these procedures on postcholecystectomy symptoms in children and the impact of cholecystectomy during childhood on the incidence of right-sided colonic carcinoma remains to be determined.

[Pancreatic function and quality of life after resection of the head of the pancreas in chronic pancreatitis. A prospective, randomized comparative study after duodenum preserving resection of the head of the pancreas versus Whipple's operation]. / Pankreasfunktion und Lebensqualität nach Pankreaskopfresektion bei der chronischen Pankreatitis. Eine prospektive, randomisierte Vergleichsstudie nach duodenumerhaltender Pankreaskopfresektion versus Whipple'scher Operation.

Given an indication for surgery in patients with chronic pancreatitis, such as distal common bile duct obstruction, duodenal stenosis, or dilated pancreatic duct with stones and congestion, the surgeon must decide the type of operation to perform. A duodenopancreatectomy, the Whipple procedure, is widely considered to be the gold standard. It is highly effective in relieving pain and eliminating the structural abnormalities noted above. Duodenum-preserving resection of the head of the pancreas (DPRHP) seems to be an attractive alternative to pancreaticoduodenectomy (PD) in the treatment of chronic pancreatitis. In a clinical prospective randomized trial the efficiency of both operative methods was investigated. Between 7/1987 and 12/1993 43 patients were randomly assigned to undergo either a Whipple procedure (n = 21) or DPRHP (n = 22). Data on postoperative course, mortality, and postoperative morbidity were compiled. As concerns long-term results, postoperative hormonal status (insulin, neurotensin, cholecystokinin, gastrin) was checked, basal and stimulated with a standardized meal, using standard hormonal assay kits. All patients with PD survived, whereas one with DPRHP died from peritonitis. Patients with DPRHP had a significant more rapid convalescence (16.5 vs. 21.7 days). The range for postoperative follow-up is from 36 months to 5.5 years. In the DPRHP group 18 patients are in good condition. Two had diabetes and one developed carcinoma. In the PD group one died from hepatic coma, 14 are in good condition and 6 developed diabetes. All gained body weight with an average of 6.4 vs. 4.9 kg, DPRHP vs. PD. A difference between DPRHP and PD was obvious for the postoperative hormonal status. Results are satisfactory in both groups. For patients with DPRHP however, we see a quicker convalescence and a significant benefit as concerns postoperative hormonal status.

Thoracic wall reconstruction for primary malignancies in children: short- and long-term results.

AIM: Primary thoracic wall malignancy is a rare and diverse entity in children. Surgical treatment commonly involves major chest wall resection causing large defects requiring complex reconstruction. In adults, the use of alloplastic and/or xenogenic materials and muscle flap repair is well established. However, literature provides only little information on procedures in children. We report our experience in 8 consecutive children who underwent chest wall resection and reconstruction with regard to surgical treatment and outcome. PATIENTS AND METHODS: Retrospective study of all children with primary malignant chest wall tumors requiring rib resection and reconstruction with prosthetic material performed in our institution between November 2002 and April 2010. Endpoints were postoperative complications and long-term results, focusing on scoliosis defined radiologically by the Cobb angle. RESULTS: 8 children (7 male, 1 female) with a median age of 10.6 (4.1-18.9) years underwent resection of thoracic wall tumors. A mean number of 3 (1-5) ribs were resected. Stability was obtained using rigid prosthetic material (STRATOS™ titanium bar) in 2 patients and/or non-rigid prosthetic material (Goretex® patch in 6 patients, Vicryl® patch in 3 patients, Tutopatch® in 1 patient). A muscular flap was added in 5 patients. Postoperative complications included superficial wound infection (n = 2) and dislocation of a titanium bar necessitating removal in 1 patient. No infections of the prosthetic material were observed. No perioperative mortality occurred. At a mean follow-up of 37.5 (4-97) months, 6 patients were alive. 2 patients died due to early tumor recurrence. Mild scoliosis (Cobb angle 10-20°) was detected in 2 of the surviving patients (33%). CONCLUSION: Surgical reconstruction after resection of malignant thoracic wall tumors using non-rigid prosthetic material is safe and effective in pediatric patients, whereas rigid prosthetic material might dislocate. Scoliosis represents a long-term complication after chest wall reconstruction and should be monitored during routine follow-up.