Cystic duct pressures after ligation with a novel absorbable device in an ex vivo caprine cholecystectomy model.

Laparoscopic cholecystectomy is the standard of care in human medicine for gall bladder disease. Although infrequently reported in veterinary literature, laparoscopic cholecystectomy is an option for uncomplicated gall bladder disease in canine patients. Due to the risk of cystic duct ligature slippage or clip dislodgement, we wanted to explore the use of a LigaTie; a novel absorbable medical device modeled after a cable tie. Our object was to describe the use of the LigaTie in a caprine cadaveric study of cholecystectomies as a model for canine patients and demonstrate the leak pressure of the cystic duct compared with cholecystectomies performed with 2 large endoscopic hemoclips. Samples of caprine gall bladder, liver, and cystic duct were collected. The cystic duct was ligated with either 2 large endoscopic hemoclips or a LigaTie. Maximum cystic duct pressure was recorded. Results showed that there was no statistically significant difference in the maximum cystic duct pressure achieved for cystic ducts ligated with 2 large endoscopic hemoclips or the LigaTie (P = 0.865). No leakage was observed from the cystic duct, hemoclip, or LigaTie site in either group. Supraphysiologic pressures were achieved in both groups and high pressure occlusion of the infusion pump determined the maximum intraluminal pressure achieved. Based on these results, the LigaTie may provide advantages in minimally invasive surgery, especially when considering ligation of a friable or thickened cystic duct during laparoscopic cholecystectomy. Future in vivo studies are warranted to determine minimally invasive maneuverability, tissue interaction, complications, and outcomes.

La cholécystectomie par laparoscopie est le standard de soin en médecine humaine pour les maladies de la vésicule biliaire. Bien que rapportée peu fréquemment dans la littérature vétérinaire, la cholécystectomie par laparoscopie est une option pour les maladies non-compliquées de la vésicule biliaire chez les patients canins. Due au risque de glissement de la ligature du canal cholédoque ou au déplacement de l'agrafe, nous avons voulu explorer l'utilisation de LigaTie; un nouveau dispositif médical résorbable modélisé d'après une attache de câble. Notre objectif était de décrire l'utilisation de LigaTie dans une étude sur des cadavres de chèvres de cholécystectomies comme modèle pour des patients canins et de démontrer la pression de fuite du canal cholédoque comparativement à des cholécystectomies réalisées avec deux larges agrafes hémostatiques endoscopiques. Des échantillons de vésicules biliaires, de foies et de canal cholédoques caprins ont été prélevés. Le canal cholédoque était ligaturé avec soit deux larges agrafes hémostatiques endoscopiques ou du LigaTie. La pression maximale dans le canal cholédoque fut enregistrée. Les résultats ont montré qu'il n'y avait pas de différence statistiquement significative dans la pression maximale atteinte dans le canal cholédoque par les deux méthodes de ligature (P = 0,865). Aucune fuite ne fut observée des sites de ligature du canal cholédoque que ce soit du groupe avec agrafes ou celui avec LigaTie. Des pressions supra-physiologiques ont été atteintes dans les deux groupes et l'occlusion de la pompe à infusion due à la haute pression a déterminé la pression intraluminale maximale atteinte. En fonction de ces résultats, le LigaTie est avantageux comme méthode chirurgicale minimalement invasive, surtout si l'on considère la ligature d'un canal cholédoque friable ou épaissi durant une cholécystectomie par laparoscopie. Des études in vivo ultérieures sont nécessaires afin de déterminer la manoeuvrabilité invasive minimale, l'interaction tissulaire, les complications et les résultats.(Traduit par Docteur Serge Messier).

Functional MR cholangiography of the cystic duct and sphincter of Oddi using gadoxetate disodium: is a 30-minute delay long enough?

PURPOSE: To determine if excreted contrast is consistently visualized in the gallbladder and duodenum after a 30-minute delay using gadoxetate disodium-enhanced MRI in patients without hepatobiliary disease. MATERIALS AND METHODS: Twenty-two patients without evidence of liver or biliary disease underwent gadoxetate disodium-enhanced magnetic resonance imaging (MRI) from February 17, 2009 through October 3, 2011. The mean age was 45 years (range 25-72). T1-weighted hepatobiliary phase images at 5, 10, 20, and 30 minutes after contrast injection were reviewed in consensus by two radiologists to determine the delay at which enhancement of the gallbladder and duodenum first occurred. RESULTS: Thirteen of 22 (59.1%) patients demonstrated duodenal filling by 20 minutes and 16/22 (72.7%) filled by 30 minutes. The mean time to duodenal enhancement was 19.9 minutes (range 11.4-30.2 min). Seventeen of 22 (77.3%) patients demonstrated gallbladder filling by 20 minutes and 21/22 (95.5%) filled by 30 minutes. The mean time to gallbladder enhancement was 16.5 minutes (range 4.4-30.2 min). CONCLUSION: A significant number of normal patients do not show duodenal filling by 30 minutes, while the majority fill the gallbladder by 30 minutes using functional MR cholangiography (fMRC) with gadoxetate disodium. These findings will guide fMRC protocol design for patients with suspected acute cholecystitis and sphincter of Oddi dysfunction.

Experimental investigation of the flow of bile in patient specific cystic duct models.

Three-dimensional scaled-up transparent models of three human cystic ducts were prepared on the basis of anatomical specimens. The measurement of pressure drop across the cystic duct models and visualization of the flow structures within these ducts were performed at conditions replicating the physiological state. The flow visualization study confirmed the laminar nature of the flow of bile inside the cystic duct and values of pressure drop coefficient (Cp) decreased as the Reynolds number (Re) increased. The three tested models showed comparable behavior for the curve of Reynolds number versus the pressure drop coefficient. The results show that the tested cystic ducts have both increased pressure drop and complicated flow structures when compared with straight conduits. High resistance in a cystic duct may indicate that the gallbladder has to exert large force in expelling bile to the cystic duct. For patients with diseased gallbladder, and even in healthy persons, gallbladder is known to stiffen with age and it may lose its compliance or flexibility. A high resistance cystic duct coupled with a stiffened gallbladder may result in prolonged stasis of bile in the gallbladder, which is assumed to encourage the formation of gallstones.

Closure of the cystic duct by ultrasonic energy: an electron-microscopic and biomechanical study in man.

BACKGROUND: Ultrasonic activated devices are currently used both for sealing of blood vessels and dissection of parenchymal organs. Recently, ultrasonic energy has been used to seal the cystic duct during successful clip-less cholecystectomy, but no study examined the mechanisms of tissue welding by ultrasonic energy or the biomechanical properties of the seal. This was the aim of our investigations. PATIENTS AND METHODS: Eight patients (7 women and 1 man, mean age 42+/-7 y) subjected to laparoscopic cholecystectomy had a cystic duct sealed and sectioned by Ultracision; after removal of the specimens, the distal end was processed for scanning electron microscopy and transmission electron microscopy, whereas the proximal end to the gallbladder was used for determination of the bursting pressure. RESULTS: The bursting pressure of the cystic duct sealed by ultrasonic energy was 168+/-47 mm Hg, well above the maximal pressure of the common bile duct. At scanning electron microscopy, the end of the cystic duct was closed by an amorphous, bundled, dense substance. The section proximal to the end showed destruction of the epithelial layer with dense amorphous bridges connecting the opposite sites of the wall. When the lumen was observed, it was filled with bile microaggregates. At transmission electron microscopy, 2 different findings were evident: (1) coagulative necrosis in the sectioned area and (2) a combination of coagulative necrosis and collagen denaturation in the more distal sections. The connective tissue was characterized by attenuation of collagen birefringence and swelling of fibers and bundles due to shrinkage of collagen. CONCLUSIONS: Ultrasonic energy can be applied to suitable tissues to obtain sealing of the walls with good biomechanical effects.

Distribution of the interstitial Cajal-like cells in the gallbladder and extrahepatic biliary duct of the guinea-pig.

It has been suggested that interstitial Cajal-like cells (ICLC) may be involved in the spontaneous rhythmic electrical activities of the extrahepatic bile duct system. The present study investigated the distribution and characteristics of ICLC, which are immunopositive for CD117/ Kit receptor tyrosine kinase, using immunohistochemistry employing a monoclonal antibody raised against CD117/Kit on whole-mount preparations. The Kit-positive ICLC were examined using confocal laser scanning microscopy or fluorescence microscopy. ICLC, immunoreactive for Kit, were pleiomorphic and/or spindle-shaped cells with a few bipolar processes and distributed in the smooth muscle layers of the gallbladder and bile duct system. They were scattered in the hepatic duct, cystic duct and gallbladder as well as in the upper part of the common bile duct. The ICLC gradually increased in number and formed a completed cellular network in the lower part of the common bile duct and ampulla. The numbers of ICLC in the ampulla were similar to that of the duodenum and significantly much greater in number than in the gallbladder and bile ducts. The density of the ICLC in the common bile duct was significantly higher than that of other bile ducts. Our results suggested that the ICLC might contribute to the regulation of the spontaneous rhythmic contraction and development of motility disorders of the bile duct system.

Cystic duct and Heister's "valves".

The anatomy and physiology of the cystic duct have been relatively neglected by anatomists and the function of the spiral mucosal folds or "valves" of Heister, first described in 1732, remains obscure. The gross and microscopic anatomy of the cystic duct is reviewed together with results from laboratory investigations into the function of the cystic duct and its spirally arranged folds. The duct and spiral folds contain muscle fibers responsive to pharmacologic, hormonal, and neural stimuli. There is, however, no convincing evidence of a discrete muscular sphincter within the duct. Although the cystic duct is unlikely to play a major role in gallbladder filling and emptying, it appears to function as more than a passive conduit. Coordinated, graded muscular activity in the cystic duct in response to hormonal and neural stimuli may facilitate gallbladder emptying. The principal function of the internal spiral folds that are found in man and other animals may be to preserve patency of this narrow, tortuous tube rather than to regulate bile flow.

Influence of indomethacin on effects of endothelin-1 on guinea pig isolated rings of common bile duct and sphincter of Oddi.

The effects of endothelin-1 on motility of guinea pig extra-hepatic biliary tract portions were studied. Endothelin-1 (< or =100 nM) failed to contract rings of hepatic, cystic, proximal or distal common bile ducts, or choledochal or papillary halves of sphincter of Oddi. At 100 nM, endothelin-1 or sarafotoxin S6c (selective endothelin ET(B) receptor agonist) inhibited contractions of choledochal (but not papillary) sphincter of Oddi to carbachol (1 microM) by 63+/-5 and 45+/-9%, respectively. In distal common bile duct, indomethacin (5.6 microM) unmasked potent contractile effects of endothelin-1 [EC(50) 7.8 (5.5-11.1) nM; E(MAX) 80+/-6% of response to 80 mM KCl] and enhanced the contractile potency of carbachol (585-fold at EC(50) level), but not cholecystokinin C-terminal octapeptide. Inhibition of cholinergic responsiveness of the choledochal sphincter of Oddi by endothelin-1 was reduced by BQ-123 (1 microM; endothelin ET(A) receptor antagonist; cyclo[DTrp-DAsp-Pro-DVal-Leu]) and abolished by either BQ-123 plus BQ-788 (1 microM; endothelin ET(B) receptor antagonist; N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D-1-methoxycarboyl-D-norleucine) or indomethacin. Thus, eicosanoids of the cyclo-oxygenase pathway (i.e. prostanoids) suppress endothelin-1-induced contractions of distal common bile duct and mediate endothelin ET(A) and ET(B) receptor-dependent inhibition of cholinergic responsiveness of the choledochal portion of the sphincter of Oddi.

Effectiveness of the ultrasonic coagulating shears, LigaSure vessel sealer, and surgical clip application in biliary surgery: a comparative analysis.

Advancements in laparoscopic surgery are often dictated by the limitations of technical instrumentation. Energy sources other than electrosurgery have become popular with the promise of quick and effective vascular control. With their success surgeons have begun using these on structures other than blood vessels with little or no data establishing their efficacy or safety. This study evaluates alternative energy sources in sealing ductal structures for possible use in liver or gallbladder surgery. After elective cholecystectomy cystic ducts (n = 45) were resealed ex vivo with surgical clips (n = 14), ultrasonic coagulating shears (n = 16), or electrothermal bipolar vessel sealer (n = 15), and bursting pressures were measured. Nineteen additional human cystic ducts were randomized to seal by ultrasonic coagulating shears (n = 9) or electrothermal bipolar vessel sealer (n = 10) and fixed in 10 per cent buffered formalin for histologic evaluation of thermal spread (mm). After this nine adult pigs were randomized to laparoscopic ligation and transection of the common bile duct using surgical clips (n = 3), ultrasonic coagulating shears (n = 3), or electrothermal bipolar vessel sealer (n = 3). The animals underwent necropsy for assessment of seal integrity on the sixth postoperative day. In the ex vivo study the mean cystic duct bursting pressure was 621 mm Hg with surgical clips and 482 mm Hg with the electrothermal bipolar vessel sealer (P = 0.39). The mean cystic duct bursting pressure after ultrasonic coagulating shears was 278 mm Hg, which was statistically less than surgical clips (P = 0.007) and electrothermal bipolar vessel sealer (P = 0.02). The mean thermal spread was 3.5 mm for ultrasonic coagulating shears and 13.4 mm for electrothermal bipolar vessel sealer (P = 0.0002). All animals undergoing ligation and transection of the common bile duct with ultrasonic coagulating shears and electrothermal bipolar vessel sealer developed bile peritonitis by postoperative day 6 as a result of seal leak. All animals undergoing surgical clip ligation and transection of the common bile duct maintained seal integrity. The mean common bile duct pressure above the surgical clip was 12 mm Hg (range 10-14). In conclusion the acute ex vivo study demonstrated a significant difference in the cystic duct bursting pressure between surgical clips and ultrasonic coagulating shears and between electrothermal bipolar vessel sealer and ultrasonic coagulating shears. The ultrasonic coagulating shears and electrothermal bipolar vessel sealer failed to maintain seal integrity in the in vivo animal study. Given the failure of the ultrasonic coagulating shears and electrothermal bipolar vessel sealer in the animal model these energy sources should not be used for transection of the cystic duct or major hepatic ducts during hepatobiliary surgery.

Biliary patency imaging after endoscopic retrograde sphincterotomy with gallbladder in situ. Clinical impact of nonvisualization.

We prospectively performed nuclear biliary patency imaging (HIDA scanning) in 62 patients who had undergone endoscopic retrograde sphincterotomy for management of pancreaticobiliary disease with their gallbladders in situ. Elective cholecystectomy was not recommended because of advanced age, comorbidity, or absence of gallstones. All patients had patent cystic ducts at endoscopic retrograde cholangiopancreatography balloon cholangiography. Eighteen (29.1%) of 62 patients had nonvisualizing HIDA scans, and in 44 (70.9%) of 62 visualization was normal or delayed. Six cholecystectomies were required for colic (n = 1), acute cholecystitis (n = 4), and acute cholecystocholedochal fistula with cholangitis (n = 1). Among the patients with cholelithiasis and nonvisualization (n = 13), five (38.5%) required surgery, whereas only one (4.8%) of 21 patients with cholelithiasis and visualization required surgery. Nonvisualizing HIDA scans are frequent (30%) after endoscopic retrograde sphincterotomy and have no clinical relevance in patients without cholelithiasis but predict the need for cholecystectomy within 16 months in 38.5% of patients with cholelithiasis.

Biomechanical study of the bile duct system outside the liver.

Diseases of the bile duct system in the digestive system after surgery are common. In order to clarify the cause of these diseases, research on the diseases from a biomechanical perspective is increasing; however, the same cannot be said of biochemical research. In this paper, by using a new, well-devised testing apparatus, specimens extracted from the bile duct system of canine body are tested. The test data are analyzed using the finite deformation theory, and mechanical properties of the bile duct system outside the liver are investigated. The conclusions show that the viscoelasticity of the bile duct system is very small. In its normal physiological condition, the bile duct wall has an almost uniform distribution of circumferential and longitudinal stress. However, when the diseases of the bile duct system cause high pressure at the bile duct, the circumferential stress and longitudinal stress at the bile inside wall suddenly increase and are much larger than those stresses at the outside wall. The elastic modulus gradually becomes small from the common bile duct and the common hepatic duct to hepatic duct, and the value of elastic modulus for the cystic duct is almost equal to that of the hepatic duct.

Changes in gallbladder volume do not affect cystic duct resistance.

To our knowledge, the relationship between gallbladder volume and cystic duct function has not been studied. We hypothesized that changes in gallbladder volume would influence cystic duct resistance. The effect of gallbladder volume changes on cystic duct resistance to both prograde (emptying) and retrograde (filling) steady-state flow was tested in 12 dogs under basal cholecystokinin-stimulated conditions utilizing a multiport catheter with a highly compliant balloon placed within the gallbladder fundus. Gallbladder volume was regulated by varying balloon volume from empty to just beyond physiologic distention. Cystic duct resistance was not affected by balloon volume under basal or stimulated conditions or by the direction of perfusate flow. This study demonstrated no relationship between gallbladder volume and cystic duct resistance and did not demonstrate a cystic duct sphincter mechanism at physiologic gallbladder volumes.

Functional gradients in muscle cells isolated from gallbladder, cystic duct, and common bile duct.

The existence of a gradient inherent to muscle cells of the biliary tract was examined in muscle cells isolated separately from the fundus of the gallbladder, cystic duct, and common bile duct of the dog. Muscle cells, measured in suspension or as single perfused cells, exhibited a proximal-to-distal gradient expressed by the magnitude of response and the sensitivity to hormonal cholecystokinin octapeptide and neural (acetylcholine and methionine-enkephalin) contractile agonists. Measurements in suspensions showed that cells from the fundus 1) were 7-40 times more sensitive to contractile agonists than cells from the cystic duct and 13-200 times more sensitive than cells from the common bile duct and 2) generated greater maximal contraction. The latter was expressed by the ratio of maximal responses (fundus: cystic duct cells, 1.90 +/- 0.12, P less than 0.001; fundus: common bile duct cells, 1.50 +/- 0.07 P less than 0.001), which was independent of sensitivity to agonists. Similar results were obtained in measurements on single cells with respect to relative sensitivity and to ratio of maximal responses (fundus: cystic duct cells, 1.80 +/- 0.08, P less than 0.001; fundus: common bile duct cells, 1.49 +/- 0.06, P less than 0.001). The ratio of responses to low concentrations of agonists was even higher (three- to fourfold), reflecting both the greater sensitivity and the greater contraction of muscle cells of the fundus. We conclude that a proximal-to-distal biliary gradient exists that is an inherent property of muscle cells from various regions of the biliary tract; the gradient would act to facilitate gallbladder emptying in response to hormonal and neural stimulation.

The etiology of "white bile" in the biliary tree.

"White bile" is the colorless fluid occasionally found in occluded biliary systems. The absence of pigments in this "bile" was not satisfactorily explained. The objectives of this study were to assess its etiology. In dogs, "white bile" developed whenever both the common bile duct and the cystic duct were ligated. In comparison, dark green ("black") bile occurred when only the common bile duct was ligated leaving the gallbladder in communication with the obstructed ducts. The pressure in extrahepatic ducts containing "white bile" was significantly higher than in those filled with "black bile." Flow in the extrahepatic ducts was assessed by the aid of radioiodinated human serum albumin (RIHSA). When "black bile" was present, the direction of flow was from the extrahepatic ducts into the gallbladder. Whenever "white bile" developed, a reverse flow from the extrahepatic ducts into the liver was observed. Thus, the role of the gallbladder appears to be decompression of the biliary system allowing bile flow from the liver even in obstruction. In the absence of the gallbladder water absorption activity, the colorless secretion of the bile ducts seems to "back wash" into the liver and replace the bile present in the ducts at the time of occlusion.

Cholecystokinin constricts the canine cystic duct.

The effects of cholecystokinin and cholecystokinin-octapeptide on the canine cystic duct have been studied. The resistance to flow through the duct in vivo, assessed by measuring the flow rate of saline that was perfused through the duct at constant pressure, was increased by cholecystokinin in a dose-dependent manner. Cholecystokinin also produced the well-recognized, dose-dependent elevations of gallbladder intraluminal pressure. Comparison of dose-response curves prepared in each animal indicated that the sensitivity of the cystic duct was significantly lower than that of the gallbladder. Isolated strips of cystic duct and gallbladder in vitro were contracted by cholecystokinin or cholecystokinin-octapeptide; again, cystic duct muscle displayed a lower sensitivity than gallbladder to the contractile effects of these agents. It is not known whether cholecystokinin can affect cystic duct resistance under physiologic conditions.

Increased intragallbladder pressure response to cholecystokinin-octapeptide following vagotomy and pyloroplasty.

One of the late effects of truncal vagotomy is gallbladder dilatation. However, the early physiologic mechanisms responsible for this phenomenon have not been clearly elucidated. Therefore, the hypothesis that truncal vagotomy alters the gallbladder's or cystic duct's response to hormonal stimulation was tested. Adult male prairie dogs underwent either truncal vagotomy and pyloroplasty or sham laparotomy. All animals were then fed a trace-cholesterol (nonlithogenic) diet for 3 months. In acute terminal experiments the gallbladder was aspirated and cannulated with a pressure-monitored perfusion catheter. The common bile duct was cannulated with a drainage catheter. Aspirated gallbladder volume and cystic duct closing pressure were the same in vagotomized and sham animals. Unstimulated intragallbladder pressure and cystic duct outflow resistance were also the same in both groups. However, during an intravenous infusion (10 ng/kg/min) of cholecystokinin-octapeptide (CCK-OP), the maximal intragallbladder pressure increase was greater (P less than 0.01) in vagotomized animals (3.50 +/- 0.41 mm Hg) than in sham animals (1.63 +/- 0.36 mm Hg). Intragallbladder pressure remained significantly higher (P less than 0.05) in vagotomized animals throughout the 30-min infusion of CCK-OP. Despite increased intragallbladder pressure, gallbladder emptying was unaffected by vagotomy. It is concluded that altered gallbladder or cystic duct hormonal response is an early effect of vagotomy that may result in gallbladder dilatation.

Stimulatory and inhibitory histamine receptors in canine cystic duct.

1 The effects of histamine receptor stimulation were assessed on the resistance of the canine cystic duct in vivo and on the contractility of circular muscle preparations of canine cystic duct in vitro. 2 In anaesthetized dogs, the H1-receptor agonist, 2-pyridylethylamine (0.05 to 15 mumol, i.a.), elicited dose-dependent increases in cystic duct resistance, whereas the H2-receptor agonist, 4-methylhistamine (0.05 to 15 mumol, i.a.) decreased cystic duct resistance. These responses were antagonized by the H1-receptor antagonist, diphenhydramine, and the H2-receptor antagonist, cimetidine, respectively. 3 Histamine (0.1 to 3000 nmol, i.a.) also increased cystic duct resistance in vivo. In the presence of diphenhydramine, the stimulatory effect of histamine was antagonized and slight decreases in cystic duct resistance became apparent. Cimetidine or prazosin also antagonized the stimulatory effects of histamine. 4 Histamine (1 to 100 microM) or 2-pyridylethylamine (1 to 100 microM) contracted, whereas 4-methylhistamine (1 to 100 microM) relaxed, circular muscle preparations of cystic duct. These excitatory and inhibitory responses were antagonized by diphenhydramine and cimetidine, respectively. 5 These results indicate that the canine cystic duct possesses excitatory H1- and inhibitory H2-receptors. The predominant effect of histamine is an H1-receptor-mediated increase in cystic duct resistance. Histamine, which may be released in association with cholecystitis, may exert significant effects on the regulation of bile flow in and out of the gallbladder and may contribute to gallbladder stasis during biliary disease.

Resistance and sphincter-like properties of the cystic duct.

The canine cystic duct, like that in man, has an extremely thin layer of muscle deep to the mucosal layer, surrounded by a dense layer of collagen fibers. The resistance to flow through the duct was studied in 16 anesthetized dogs by perfusing the duct with saline solution at constant pressure and recording the flow rate of the solution. The flow rate varied with respiratory movements, but there were also nonrespiratory variations which might be due to spontaneous sphincter-like contractions. Significant reductions in flow through the duct followed systemic intravenous or local intra-arterial injections of morphine or pharmacologic concentrations of adrenaline or cholecystokinin. It was concluded that an extremely small amount of muscle in the wall of the duct was capable of sphincter-like activity. The resistances to flow were the same in either direction through the duct, an indication that the prominent mucosal folds, valves of Heister, did not function as unidirectional valves. In view of the high resistance to flow through the duct and the possibility that sphincter-like activity may also occur under physiologic conditions, the function of the duct requires more attention than it has received in the past.