Sclerotherapy of the gallbladder in pigs. Development of a balloon catheter for a single-step procedure

Gallbladder sclerotherapy after permanent cystic duct occlusion, to prevent gallstone recurrence in nonsurgical gallstone therapy, is at least a two-stage procedure. A balloon catheter was developed to perform gallbladder sclerotherapy with only temporary occlusion of the cystic duct, and the efficacy and safety of this method was subsequently investigated. Twenty pigs underwent cholecystostomy for positioning of a 7-Fr triple-lumen balloon catheter with proximal side holes. Sclerotherapy with 96% ethanol and 3% sodium tetradecyl sulfate for 20 minutes was performed. The animals were killed 24 hours, two, six, and 12 weeks after the procedure. The balloon catheter functioned well and seems suitable for procedures in which a temporary occlusion of the cystic duct is required. Although gallbladders after six and 12 weeks were shrunken and fibrotic, a single treatment of gallbladder sclerotherapy with subsequent catheter removal and no permanent cystic duct occlusion, as performed in this experiment, did not produce complete gallbladder ablation. In this study, sclerotherapy proved safe in the short term, but long-term effects remain to be assessed.     

Percutaneous chemical gallbladder sclerosis after laser-induced cystic duct obliteration: results in an experimental model.

OBJECTIVE. Chemical gallbladder sclerosis has been attempted as a way to defunctionalize the gallbladder in patients who have undergone nonsurgical removal of gallstones and who are unable to undergo surgical/laparoscopic cholecystectomy. The purpose of this investigation was threefold: to study an animal model for chemical sclerosis of the gallbladder with 95% ethanol and 3% sodium tetradecyl sulfate, to attempt chemical sclerosis immediately after percutaneous cystic duct obliteration by laser thermocoagulation, and to assess histopathologic changes in the gallbladder after sclerosis. MATERIALS AND METHODS. Percutaneous cholecystostomy and laser thermocoagulation of the cystic duct was performed in 13 pigs. Eight pigs underwent immediate gallbladder sclerosis with 95% ethanol and 3% sodium tetradecyl sulfate while two pigs received 95% ethanol only. The remaining three pigs served as controls. The cholecystostomy catheter was removed immediately after the procedure. All animals were sacrificed 6 weeks after laser thermocoagulation. Multiple sections through the gallbladder, which included the adjacent liver, the cystic duct, and the common bile duct, were obtained for histologic examination. RESULTS. At autopsy, the gallbladder in all 10 animals who underwent gallbladder sclerosis was reduced in size compared with controls. In all treated animals, the gallbladder mucosa was denuded; however, in nine of 10 cases reepithelialization had occurred. Complete sclerosis without reepithelialization was achieved in one pig who received both ethanol and sodium tetradecyl sulfate. In the two animals who received ethanol only, the depth of wall necrosis around the gallbladder lumen was less than in those pigs who received both ethanol and sodium tetradecyl sulfate. No pigs showed signs of hepatic necrosis or injury to the common bile duct. CONCLUSION. Cystic duct laser thermocoagulation allows immediate gallbladder sclerotherapy without injury to the common bile duct. Sclerosis with ethanol and sodium tetradecyl sulfate results in denudation of the gallbladder mucosa. However, a single therapeutic session with immediate removal of the cholecystostomy catheter was inadequate for gallbladder ablation in this model because of reepithelialization.     

A new method for thermocholecystectomy. Initial experience and comparison with other techniques.

RATIONALE AND OBJECTIVES. The authors tested the feasibility of thermocholecystectomy for gallbladder ablation in an animal model. METHODS. Thermal treatment of the cystic duct followed by heating of the saline-filled gallbladder using a separately designed heater/expander was performed in 13 pigs (group I). In four animals, heating of the gallbladder alone was performed (group II). Two animals served as controls (group III). All animals were killed 12 weeks after treatment. RESULTS. There was cystic duct occlusion in 10 (77%) of 13 of group I animals. In 6 (60%) of 10 of these animals with cystic duct occlusion, there was complete ablation of the gallbladder mucosa and complete obliteration of the gallbladder lumen. In group II animals, all cystic ducts were intact with an unchanged gallbladder volume in all four animals (100%), and normal gallbladder mucosa were intact in three (75%) of four animals. The gallbladders and cystic ducts in group III animals were normal. CONCLUSIONS. This study demonstrates many technical difficulties with thermal cholecystectomy. However, under ideal conditions, permanent gallbladder ablation is feasible in our animal model using a specially designed heating system.     

Ablation of the cystic duct and gallbladder: clinical observations

The cystic duct and gallbladder were ablated in eight patients with acute gallbladder disease who had been treated with minicholecystostomy instead of cholecystectomy because of multiple risk factors. First, endoluminal transcatheter radio-frequency electrocoagulation of the cystic duct was performed under fluoroscopic control, which resulted in complete occlusion in all eight patients. Next, the mucosa of the isolated gallbladder was sclerosed with 95% ethanol and 3% sodium tetradecyl sulfate in one to four sessions; no analgesics were required. The gallbladder volumes of all patients, estimated by means of ultrasound, were 1.5-22 cm3 (average, less than 10 cm3) after a mean follow-up period of 5 months. One patient died of a cerebrovascular accident 15 months after sclerotherapy. In all surviving patients, the gallbladder fistulas are dry and obliterated. These early clinical data indicate that electrocoagulation permits reliable, safe obliteration of the human cystic duct. The authors believe that sclerotherapy of the isolated gallbladder is feasible without toxic effects but that their treatment needs adjustment to achieve complete ablation of the gallbladder mucosa in a shorter period and in all patients.     

Cystic duct occlusion and transcatheter sclerosis of the gallbladder in the rabbit

We have identified a reliable sclerosant of the gallbladder in rabbits. After ligating the cystic ducts with a silk ligature in 24 rabbits and aspirating the bile from the gallbladder, we instilled a mixture of 95% ethanol and either 2 M% trifluoroacetic acid (TFA) or 5 M% TFA into the gallbladder. The animals were killed after 6 or 8 weeks. Ethanol with TFA resulted in replacement of gallbladder lumen with fibrous tissue in 22 rabbits. The two sclerosants were equally reliable and produced quantitatively similar fibrosis in the rabbits. The tendency for normal biliary mucosa to repopulate a sclerosed gallbladder can be obviated by complete occlusion of the cystic duct. The parameters for successful transcatheter sclerosis of the gallbladder have now been defined in an animal model.     

介入性胆囊切除术的实验研究

本文采用输精管粘堵剂闭塞胆囊管,以两种不同浓度的酒精和消痔灵注射液行32只家兔胆囊切除,结果显示仅1例因技术原因胆囊再通,病理检查表明:2周后 A、B 两组动物胆囊粘膜均表现为充血,水肿;4周后,A 组胆囊粘膜完全破坏,而 B 组尚有部分残留;8周后 A 组8只动物有7只胆囊完全被纤维组织代替而 B 组仅2例,同时肝肾未见受损。我们认为:本实验所行胆囊切除是可行、安全的,其中高浓度组效果更为理想。     

Long-term occlusion of the porcine cystic duct by means of endoluminal radio-frequency electrocoagulation

Recurrent cholelithiasis must be expected after gallstone removal without cholecystectomy. Chemical gallbladder ablation may offer prevention but requires preliminary cystic duct occlusion. Radio-frequency (RF) electrocoagulation of the cystic duct was performed in 15 pigs to induce occlusion by a controlled thermal epithelial injury. A flexible coagulation catheter was placed into the cystic duct lumen under fluoroscopic control by means of either subhepatic cholecystostomy or direct, percutaneous transhepatic gallbladder puncture. Complete cystic duct occlusion was proved in 14 animals. Follow-up ranged from 1 to 17 weeks (mean, 11 weeks). Histologically, the RF technique induced an intense chronic inflammatory and fibroblastic reaction, which eventually obliterated the coagulated cystic duct segments. There was no epithelial regeneration or recanalization of the fibrotic cystic duct segments. The adjacent structures, particularly the cystic artery, were intact in all specimens.     

Percutaneous obliteration of the cystic duct with a holmium:yttrium-aluminum-garnet laser: results of in vitro and animal experiments.

OBJECTIVE. The purpose of this study was to investigate the feasibility of using a holmium:yttrium-aluminum-garnet laser to permanently occlude the cystic duct in order to isolate the gallbladder from the biliary-enteric circulation and prevent gallstone formation. MATERIALS AND METHODS. To determine the optimal laser parameters (power and pulsing rate) for cystic duct thermocoagulation, 20 freshly excised porcine gallbladders with intact cystic ducts underwent low-energy (0.075-0.085 J/pulse) or high-energy (0.20-0.25 J/pulse) thermocoagulation. Histopathologic examination was done to determine the extent of cystic duct injury. After in vitro experiments, percutaneous transcholecystic laser thermocoagulation of the cystic duct was performed on 23 anesthetized domestic pigs (four controls). Cholangiograms immediately after laser thermocoagulation were obtained to assess cystic duct occlusion. Animals were sacrificed for histopathologic correlation immediately after laser thermocoagulation (n = 4), 72 hr later (n = 4), and 6 weeks later (n = 15). RESULTS. In the in vitro studies, all 10 cystic ducts in the high-energy group were occluded, while only four in the low-energy group were occluded. At histology, all cases in both groups showed circumferential injury to the cystic duct wall without injury to the cystic artery or vein. In the in vitro experiments, the cystic duct was successfully cannulated in 21 (91%) of 23 animals. Cholangiography after thermocoagulation showed occlusion of the cystic duct in 16 (84%) of 19 cases. Immediately after laser thermocoagulation, the cystic duct mucosa was circumferentially destroyed, whereas after 72 hr necrosis of the cystic duct wall and periductal tissues had occurred. By 6 weeks, all pigs had complete cystic duct fibrosis without injury to the common bile duct. CONCLUSION. Holmium:yttrium-aluminum-garnet laser thermocoagulation of the cystic duct can be performed easily, results in immediate cystic duct occlusion, and leads to permanent fibrous ductal obliteration by 6 weeks.     

Sclerotherapy for ablation of the gallbladder after gallstone lithotripsy with a mechanical lithotriptor. An experimental study in pigs on the effect of absolute ethanol on edematous gallbladder wall.

Chemical ablation of the gallbladder with absolute ethanol following mechanical lithotripsy with the RotoLith lithotriptor was attempted in 10 pigs after open cholecystostomy. Two gallbladders removed immediately after the sclerotherapy demonstrated extensive ulcerations of the mucosa with preserved glands and sinuses under the ulcerations. In 8 gallbladders removed 8 weeks after sclerotherapy a gallbladder remnant with hydrops and/or mucus and more or less intact epithelium was seen in all the pigs. In order to prevent regeneration of epithelium from gallbladder sinuses and glands, more effective sclerosing agents must be found.     

Transcatheter sclerosis of the gallbladder in rabbits. A preliminary study

Catheter sclerosis of 56 rabbit gallbladders was attempted at laparotomy. The proximal cystic duct was occluded with a hemoclip and transcatheter administration of six different sclerosing agents and a saline control was performed. Eight animals were used for each agent, three being sacrificed after two weeks and the remainder after six weeks. Hot contrast and sotradecol were comparable with saline in their lack of effect on gallbladder mucosa. Alcohol alone, tetracycline, methylcyanoacrylate and alcohol plus trifluoroacetic acid were successful at two weeks in denuding the gallbladder epithelium and promoting fibrosis of the gallbladder wall. After six weeks, evidence of mucosal regeneration was present with all agents, and the epithelium appeared to have grown back from the occluded cystic duct. Late regeneration has not been previously reported and its significance when considering the application of the technique to the human gallbladder is discussed.     

Ablation of the cystic duct and the gallbladder. Experimental basis and initial clinical observations

Bipolar radiofrequency electrocoagulation of the cystic duct by catheter can be performed safely and reproducibly using fluoroscopic control and induces endoluminal scar formation. The scar within the cystic duct forms a reliable barrier between the gallbladder and the biliary system and avoids recanalization of the cystic duct at a later date. Sclerotherapy of the isolated gallbladder with 95% ethanol and 3% STS can be performed without toxic or otherwise adverse effects and is suitable to ablate the porcine gallbladder. Initial clinical trials with this new technique on a small number of patients are promising and have demonstrated that the protocol can be applied safely to humans. The electrocoagulation technique by catheter appears suitable to ablate the human cystic duct. Follow-up evaluation of our first patients is under way and must determine whether our regimen is appropriate to ablate the human gallbladder on a long-term basis. Further development of this new approach may eventually enable definitive nonoperative treatment of cholecystolithiasis in selected patients.     

Thermal ablation of the gallbladder

Gallbladder ablation by means of injection of hot contrast medium was attempted in 13 dogs. Room temperature contrast medium was injected into the gallbladders of two additional dogs (controls). After midline laparotomy was performed to expose the gallbladder, temperature probes were placed in the liver adjacent to the gallbladder, and on the surface and in the lumen of the gallbladder. A 7-F catheter with multiple side holes was placed into the gallbladder. The cystic duct was clamped during the procedure. After injection of boiling contrast medium, the mean temperature in the gallbladder lumen was 80 degrees C; in the adjacent liver, 43.5 degrees C; and on the gallbladder surface, 45.8 degrees C. After the procedure, the cystic duct was unclamped, temperature probes and catheter were removed, and the laparotomy was closed in standard fashion. In the hot contrast medium group, one dog each was sacrificed at 2, 4, 8, and 12 weeks, and at 6 months. Six animals were sacrificed at 1 year. The gallbladder was completely ablated in 11 of 13 animals in the hot contrast medium group. One dog was sacrificed at 8 days because of bile leakage, and another was sacrificed at 17 days because of gallbladder rupture. The two control animals were sacrificed at 12 and 13 weeks, and their gallbladders were normal at that time.     

Cystic Duct Embolization with Chemical Gallbladder Ablation for the Treatment of Acute Calculous Cholecystitis in High-Risk Patients: A Prospective Single-Center Study

PurposeTo demonstrate the feasibility of cystic duct embolization and chemical gallbladder ablation as an alternative to cholecystectomy in high-risk patients with calculous cholecystitis who were not candidates for surgery.Materials and MethodsThis prospective study included 10 patients with acute cholecystitis (7 males and 3 females) aged 70–91 years (average age, 81.6 years) between 2013 and 2019. A cholecystostomy catheter was inserted during the acute phase, followed by cystic duct coil embolization performed via the existing drainage tube tract. Once asymptomatic, 3% aethoxysklerol was injected into the gallbladder, and the drain was removed upon sonographic confirmation that the gallbladder remained contracted. Each phase of the procedure was performed with an interval of 2–3 weeks. Clinical, cholangiographic, and sonographic data were collected before and after drain removal at 1-month follow-up.ResultsCystic duct embolization was technically successful in all patients, with no immediate post-procedure complications. Gallbladder ablation performed in 10 patients was technically successful in all of them (median follow-up, 11 months). One patient required repeat ablation at 14 months, and the prolonged biliary excretions of 1 other patient ceased only at 8 months.ConclusionsCystic duct embolization with gallbladder ablation is a feasible procedure for patients in whom cholecystectomy is contraindicated.     

Differential diagnosis of gallbladder distention by angiography (author's transl)

The angiography alterations of 42 cases with gallbladder distention in inflammatory or malignant disease are compared with 44 those of gallbaldder distension in distal occlusion of the common bile duct. Branches of the cystic artery were more frequent and wider in patients with gallbladder disease than those with distal common duct occlusion. In the first group, there is more often accumulation of contrast medium in the gallbladder wall, and the opacified wall is wider than in common duct obstruction. Tumor vessels are observed in 50% of malignant gallbladder disease, significant difference in the diameter of the cystic artery trunc could not be found.     

Percutaneous Transcholecystic Biliary Interventions Using Gallbladder Anchors: Feasibility Study in the Swine

The purpose of this study was to report our initial experience with a swine model for biliary interventions by using a percutaneous transcholecystic access after suture anchor of the gallbladder. Telepaque tablets were given to five pigs to opacify the gallbladder. Under fluoroscopy, the opacified gallbladder was punctured percutaneously and three suture anchors were used to fix the anterior wall of the gallbladder to the abdominal wall. Two weeks later, the gallbladder was punctured and access into the distal common bile was obtained through the cystic duct. Balloon expandable stents were deployed into the distal common bile duct. Follow-up cholangiograms were obtained at 1 and 2 weeks. Necropsy was performed after 2 weeks to evaluate the relationship between the gallbladder and abdominal wall. Suture anchor placement was successful in all five pigs. One pig with a deep and highly positioned gallbladder developed fever, anorexia, and vomiting secondary to excessive stretch of the gallbladder. Placement of the guidewire through the extremely tortuous and small cystic ducts proved to be the most challenging step of the procedure. Metallic stents were successfully deployed in all four pigs in which it was attempted. Four animals tolerated the procedures without changes in their clinical conditions and no symptoms. Successful follow-up cholangiograms were performed at 1 and 2 weeks post-stent deployment without complications. All stents remained patent during the follow-up period. Necropsy demonstrated close attachment and adherence of the gallbladders to the antero-lateral abdominal wall in all four animals. Suture anchoring of the gallbladder is feasible in most pigs with superficially located gallbladders. This technique allows a safe and repeat access into the biliary system using a transcholecystic approach.     

Efficacy and Safety of Balloon-Occluded Retrograde Transvenous Obliteration with Sodium Tetradecyl Sulfate Liquid Sclerotherapy

Objective

To evaluate the efficacy and safety of balloon-occluded retrograde transvenous obliteration (BRTO) with sodium tetradecyl sulfate (STS) liquid sclerotherapy of gastric varices.

Materials and Methods

Between February 2012 and August 2014, STS liquid sclerotherapy was performed in 17 consecutive patients (male:female = 8:9; mean age 58.6 years, range 44–86 years) with gastric varices. Retrograde venography was performed after occlusion of the gastrorenal shunt using a balloon catheter and embolization of collateral draining veins using coils or gelfoam pledgets, to evaluate the anatomy of the gastric varices. We prepared 2% liquid STS by mixing 3% STS and contrast media in a ratio of 2:1. A 2% STS solution was injected into the gastric varices until minimal filling of the afferent portal vein branch was observed (mean 19.9 mL, range 6–33 mL). Patients were followed up using computed tomography (CT) or endoscopy.

Results

Technical success was achieved in 16 of 17 patients (94.1%). The procedure failed in one patient because the shunt could not be occluded due to the large diameter of gastrorenal shunt. Complete obliteration of gastric varices was observed in 15 of 16 patients (93.8%) with follow-up CT or endoscopy. There was no rebleeding after the procedure. There was no procedure-related mortality.

Conclusion

BRTO using STS liquid can be a safe and useful treatment option in patients with gastric varices.     

Sonographically guided ethanol sclerotherapy for benign thyroid cysts: results in 22 patients

OBJECTIVE: We evaluate the efficacy and safety of sonographically guided ethanol sclerotherapy for benign thyroid cysts. SUBJECTS AND METHODS: We examined 22 patients with benign thyroid cysts (13 complex cysts and nine pure cysts) confirmed by fine-needle aspiration biopsy. Sonographically guided aspiration of the cystic fluid was followed by instillation of absolute ethanol (99.9%) into the cystic cavity: the injected volume of ethanol was 40-100% of the volume of fluid aspirated. The procedure was performed every 1 or 3 months for one or two sessions (mean, 1.2 sessions). Follow-up sonography was performed 1-10 months after the final session, and we observed patients after ethanol sclerotherapy for complications. RESULTS: The initial volume of the cysts ranged from 3.5 to 42 ml. In 21 patients, the volume of the cyst decreased or the cyst was obliterated. The volume of the cyst was reduced by 50-99% in 13 patients and by 1-49% in six patients, and the cyst was obliterated in two patients. In one patient, the volume of the cyst increased. The volume of ethanol instilled was significantly correlated with the volume reduction rate of the cyst. There was a difference in the volume reduction rate between patients in whom 10 ml or more of initial volume was used and those in whom less than 10 ml of initial volume was used; that is, the volume reduction rate of the group with the initial cyst volume of more than 10 ml was higher than that of the other group. Important long-standing and severe complications were not observed. CONCLUSION: Sonographically guided ethanol sclerotherapy is a safe and effective tool for the therapy of benign thyroid cysts.     

直接胆管造影时胆囊不显影的意义探讨

本文回顾性分析连续130例(ERCP 78例、PTC 52例)肝内外胆管显影好、技术上满意、未作胆囊切除而胆囊或胆囊管不显影的直接胆管造影片及手术结果。按使胆囊不显影病变的部位将所有病例分成3组:(1)胆囊和/或胆囊管病变(83例,63.8％):(2)胆总管中下段病变(37例,28.5％);(3)肝总管远端或胆总管近端病变(9例,6.9％)。分析胆囊和/或胆囊管不显影的原因及发病机制。 本研究证明:直接胆管造影中,(1)如果肝内外胆管显影好且无梗阻性病变,胆囊和/或胆囊管不显影可下“病理胆囊”的诊断;(2)如果肝内外胆管显影好,胆总管或肝总管远端有梗阻性病变,胆囊和/或胆囊管不显影不一定提示胆囊或胆囊管病变。     

胆囊颈管结石致胆总管扩张的研究

目的：以前瞻性方式研究对比胆囊颈管结石（ｎ＝３０）与胆囊体部结石（ｎ＝５０）对胆总管直径的影响。材料和方法：对比两组胆总管超声内径和术中实测外径。结果：胆囊颈管结石组胆总管超声内径和术中实测外径（６９ｍｍ，１１５ｍｍ）大于胆囊体结石组（４７ｍｍ，８２ｍｍ）。结论：胆囊颈管结石是胆总管轻度扩张的原因之一。     

Significance of the nonopacified gallbladder in endoscopic retrograde cholangiography.

Failure to visualize the cystic duct and gallbladder during endoscopic retrograde cholangiography, while obtaining satisfactory opacification of the rest of the biliary system, is a radiographic sign of undetermined meaning. The diagnostic implication of this finding was analyzed in 63 patients with pathologically proven diagnoses. One patient was normal at surgery. Three groups of abnormal patients had: (1) obstructing lesions of the distal common bile duct (35 patients); (2) primary lesions of the cystic duct or gallbladder (19 patients); or (3) obstructing lesions about the common hepatic/cystic duct junction (8 patients). The results indicate that obstructing lesions of the distal common bile duct may cause stasis of bile within the biliary system, increased biliary pressure, and sludge formation that prevent the flow of contrast material through the cystic duct and into the gallbladder, which can cause nonopacification. If the extrahepatic biliary system is of normal caliber without evidence of an obstructing process, nonfilling of the cystic duct and gallbladder is highly predictive of pathology.