Evaluation of gallbladder motility assessed by ultrasonography in dogs with hyperlipidemia.

BACKGROUND: The pathogenesis of gallbladder (GB) mucoceles in dogs is unknown. It has been proposed that hyperlipidemia could impair GB motility and contribute to GB mucocele formation. HYPOTHESIS/OBJECTIVES: The objective of this study was to compare GB motility in dogs with hyperlipidemia to control dogs using ultrasonography. We hypothesized that hyperlipidemic dogs will have decreased GB motility compared with controls. ANIMALS: Twenty-six hyperlipidemic and 28 healthy, age-matched control dogs were prospectively enrolled. METHODS: Cholesterol and triglyceride concentrations were measured in all dogs. Hyperlipidemia was defined as hypercholesterolemia (>332 mg/dL) and/or hypertriglyceridemia (>143 mg/dL) using a biochemical analyzer. Ultrasound was performed before feeding, and 60 and 120 minutes after ingestion of a high fat diet. Gallbladder volumes (GBV) and ejection fractions (EF) were calculated. RESULTS: Hyperlipidemic dogs had significantly larger GBVs (ml/kg) before feeding and 60 minutes after feeding of 1.2 (0.4-7.5; P = .008) and 0.6 (0.1-7.2; P = .04) compared with controls 0.6 (0.2-2.6) and 0.4 (0.1-1.9), respectively. Severely hyperlipidemic dogs had significantly larger GBV at baseline, 60 minutes, and 120 minutes of 1.7 (0.6-7.5; P = .03), 1.3 (0.4-7.2; P = .02), and 1.3 (0.2-8.2; P = .04), respectively compared with mildly hyperlipidemic dogs. EFs at 60 and 120 minutes between controls, hyperlipidemic, and severely hyperlipidemic were all 0.3 at 60 minutes and 0.5, 0.3, and 0.3 at 120 minutes, respectively which were not statistically different. CONCLUSIONS AND CLINICAL IMPORTANCE: Hyperlipidemia leads to GB distention in dogs which could lead to retention of bile and gallbladder disease.

A multicenter retrospective study assessing progression of biliary sludge in dogs using ultrasonography.

BACKGROUND: Biliary sludge (BS) frequently is identified on ultrasonographic examination and is described as incidental. It is hypothesized that biliary stasis and hypersecretion play a role in both BS and gallbladder mucocele (GBM) formation. Recent studies have documented similarities in composition of BS and GBM, and there are several examples of progression from BS to GBM in the veterinary literature. OBJECTIVES: To assess the relationship between the presence of BS and later development of GBM in dogs, over time periods >12 months. ANIMALS: A total of 154 dogs with BS and ultrasonographic follow-up >12 months. METHODS: Medical records were retrospectively collected from 9 UK-based referral centers for all available time points. A semiobjective scoring system was used to track volume of BS within the gall bladder (GB) over time. RESULTS: Twenty dogs developed GBM during the study period. Shetland Sheepdogs (odds ratio [OR], 40.99; 95% confidence interval [CI], 3.61-465.95; P = .003) and Border Terriers (OR, 11.66; 95% CI, 3.28-46.63; P < .001) were independent risk factors for the development of GBM. Non-gravity-dependent BS (NDBS) was noted to form before GBM development in 9/20 dogs, and breeds at-risk for GBM were more likely to have NDBS. Odds for the development of GBM increased with BS score. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with NDBS may be at risk for the development of GBM and a stratified BS scoring system could allow for semiobjective monitoring over time, particularly in at-risk breeds.

Usefulness of endoscopic ultrasound in patients with minilithiasis and/or biliary sludge as a cause of symptoms of probable biliary origin after cholecystectomy.

INTRODUCTION: Endoscopic ultrasound (EUS) is a more sensitive technique than transabdominal ultrasound for the diagnosis of gallstones. This greater sensitivity, especially in the diagnosis of microlithiasis/biliary sludge, facilitates the indication of cholecystectomy in patients with symptoms of probable biliary origin but may result in over-indication of this surgery. OBJECTIVES: Evaluate the role of EUS in the diagnosis of minilithiasis/biliary sludge in patients with digestive symptoms of probable biliary origin by resolving the symptoms after cholecystectomy. Analyse factors related to the remission of symptoms following cholecystectomy. PATIENTS AND METHODS: Retrospective, longitudinal, single-centre study based on a prospective database of 1.121 patients undergoing EUS. Seventy-four patients were identified as meeting inclusion-exclusion criteria (diagnosed with minilithiasis/sludge by EUS after presenting digestive symptoms of probable biliary origin without a history of complicated cholelithiasis). A telephone questionnaire for symptoms was conducted with cholecystectomized patients. Factors related to a good response were analysed with logistic regression analysis. RESULTS: Of the 74 patients, 50 were cholecystectomized (67.5%), mean age 49 years (SEM 2.26) (41 women). Seventy percent of patients (35/50) presented remission of symptoms with median follow-up 353.5 days (95% CI, 270-632.2). The only variable associated with remission of symptoms was the presence of typical biliary colic with an OR of 7.8 (95% CI, 1.8-34; p=0.006). No complications associated with EUS were recorded. One patient (2%) suffered haemoperitoneum and 18% (9/50) suffered diarrhoea following cholecystectomy. CONCLUSIONS: EUS is a very useful technique for the indication of cholecystectomy in patients with minilithiasis/sludge and typical symptoms of biliary colic.

CEUS in the differential diagnosis between biliary sludge, benign lesions and malignant lesions.

PURPOSE: Conventional grayscale ultrasound (US) is accurate in the diagnosis of gallbladder disease (GD), but in some cases, it is not decisive. Contrast-enhanced ultrasound (CEUS) improves the diagnostic accuracy of US. The primary objective of this study is to assess the reliability of CEUS in the diagnosis of sludge; the secondary objective is to assess the ability of CEUS to diagnose cancer. METHODS: We retrospectively reviewed the US of 4137 patients positive for GD. In 43/4137 (1.04%), the use of could not discriminate between sludge and neoplasms. Then, we evaluated CEUS in only 39 of these patients, and in 4/43 (9%) cases it was not performable. After CEUS, the absence of enhancement was considered diagnostic for sludge, while contrast washout within 60 s diagnosed malignant lesions. RESULTS: Among the 39 patients, 16 had biliary sludge and 23 had lesions of the gallbladder wall; 9 of these were carcinomas and 14 were benign tumors. The absence of enhancement was present in 16/16 patients with sludge and in 0/23 patients with lesions of the gallbladder (sensitivity and specificity 100%). Washout was within 60 s in 9/9 gallbladder carcinomas and 2/14 benign lesions (sensitivity 100%; specificity 85%). CONCLUSIONS: US is confirmed to be accurate in the diagnosis of GD. In doubtful cases, CEUS is very accurate in biliary sludge diagnosis. An intralesional washout at 60 s is a pattern of malignancy that can orient towards a correct diagnosis, but it is limited by the presence of false positive results, especially for smaller lesions.

Retroperitoneal bile leak after laparoscopic cholecystectomy.

Bile duct injury (BDI) is a well-recognised complication of laparoscopic cholecystectomy (LC). Following a BDI, bile usually leaks into the peritoneal space and causes biliary peritonitis. This manifests as non-specific abdominal pain and fever occurring several days after the surgery. It can be managed by laparoscopic washout with or without bile duct repair. We present a rare case of retroperitoneal bile leak post-LC. The mechanism of injury here was likely partial avulsion from excessive traction of the cystic duct during intraoperative cholangiogram. Diagnosing retroperitoneal bile leak can be difficult because it is extremely rare and the presenting symptoms can be similar to an intraperitoneal bile leak. A high index of clinical suspicion is required. In cases of suspected bile leak, any mismatch between the exploratory laparoscopic findings and imaging findings should alert surgeons to consider the rare possibility of a retroperitoneal bile leak.

A newborn with combined pituitary hormone deficiency developing shock and sludge.

A male neonate was born at 41 weeks of gestation with a birth weight of 3320 g. Artificial respiratory management was required due to respiratory disturbance 1 h after birth, and subsequently catecholamine-refractory low cardiac output-induced shock occurred. Severe combined pituitary hormone deficiency (CPHD) was considered based on the presence of his respiratory disturbance, hypoglycemia and micropenis. After hydrocortisone (HDC) administration, circulatory dynamics rapidly improved. Brain magnetic resonance imaging (MRI) showed aplasia of the anterior pituitary gland and ectopic posterior gland. γ-Glutamyltranspeptidase (γ-GTP) increased from day 10 after birth and direct bilirubin increased from day 18. On ultrasonography, sludge filling the common bile duct and gall bladder was observed. After initiating treatment with both ursodeoxycholic acid and recombinant human growth hormone (rhGH), cholestasis improved and the sludge disappeared at 3 months after birth. In newborns with CPHD, severe central adrenal insufficiency might induce cardiogenic shock after birth. Early diagnosis and intervention are necessary.

Primary tuberculosis of cystic duct lymph node.

Tuberculosis (TC) is very common and significant cause of morbidity and mortality worldwide. Isolated cystic duct lymph node TC cases without involvement of gallbladder are exceedingly rare. It is difficult to diagnose preoperatively because of lack of characteristic signs and symptoms of TC. We report a man aged 45 years who presented with right upper abdominal pain since 1week. It was associated with nausea and postprandial fullness. There was no evidence of jaundice and lymphadenopathy. Abdominal examination showed moderate right upper quadrant tenderness with positive Murphy's sign and splenomegaly but no signs of peritonism. Abdomen ultrasound revealed sludge in gallbladder, dilated pancreatic duct, coarse exotexture of liver, splenomegaly and no lymphadenopathy. He underwent laparoscopic cholecystectomy; histological report showed chronic caseating granulomatous lymphadenitis with Langhans type of giant cells in lymph node near cystic duct with chronic cholecystitis of gallbladder. Standard antituberculosis therapy was given for 12 months.

Tumefactive Gallbladder Sludge at US: Prevalence and Clinical Importance.

Purpose To evaluate the prevalence of tumefactive sludge of the gallbladder detected at ultrasonography (US) and to assess whether any clinical and imaging differences exist between benign and malignant tumefactive sludge. Materials and Methods The institutional review board approved this retrospective study. The requirement for informed consent was waived. The study included a cohort (n = 6898) of patients with gallbladder sludge drawn from all adults (n = 115 178) who underwent abdominal US between March 2001 and March 2015. Tumefactive sludge was identified according to the following US findings: (a) nonmovable mass-like lesion and (b) absence of posterior acoustic shadowing at B-mode US and vascularity at color Doppler US. Follow-up examinations were arranged to ascertain whether the results showed true sludge or gallbladder cancer. Risk factors for malignant tumefactive sludge based on clinical and US characteristics were identified with multivariate logistic regression analysis. Results The prevalence of gallbladder and tumefactive sludge at abdominal US during the observation period was 6.0% (6898 of 115 178) and 0.1% (135 of 115 178), respectively. Twenty-eight (20.7%) patients were lost to follow-up. Of the 107 with tumefactive sludge, 15 (14%) were confirmed to have malignant tumefactive sludge. The risk factors for malignant tumefactive sludge were old age (odds ratio [OR], 1.06; P = .035), female sex (OR, 5.48; P = .014), and absence of hyperechoic spots within the sludge (OR, 6.78; P = .008). Conclusion Although the prevalence of tumefactive sludge at US was rare, a considerable proportion of patients had a malignancy. Careful follow-up is essential, especially for older patients, women, and those with an absence of hyperechoic spots at US. © RSNA, 2016 Online supplemental material is available for this article.

Novel laparoscopic narrow band imaging for real-time detection of bile leak during hepatectomy: proof of the concept in a porcine model.

INTRODUCTION: Bile leakage is a serious complication occurring in up to 10 % of hepatic resections. Intraoperative detection of bile leakage is challenging, and concomitant blood oozing can mask the presence of bile. Intraductal dye injection [methylene blue or indocyanine green (ICG)] is a validated technique to detect bile leakage. However, this method is time-consuming, particularly in the laparoscopic setting. A novel narrow band imaging (NBI) modality (SPECTRA-A; Karl Storz, Tuttlingen, Germany) allows easy discrimination of the presence of bile, which appears in clear orange, by image processing. The aim of this experimental study was to evaluate SPECTRA-A ability to detect bile leakage. METHODS: Twelve laparoscopic partial hepatectomies were performed in seven pigs. The common bile duct was clipped distally and dissected, and a catheter was inserted and secured with a suture or a clip. Liver dissection was achieved with an ultrasonic cutting device. Dissection surfaces were checked by frequently switching on the SPECTRA filter to identify the presence of bile leakage. Intraductal ICG injection through the catheter was performed to confirm SPECTRA findings. RESULTS: Three active bile leakages were obtained out of 12 hepatectomies and successfully detected intraoperatively by the SPECTRA. There was complete concordance between NBI and ICG fluorescence detection. No active leaks were found in the remaining cases with both techniques. The leaking area identified was sutured, and SPECTRA was used to assess the success of the repair. CONCLUSIONS: The SPECTRA laparoscopic image processing system allows for rapid detection of bile leaks following hepatectomy without any contrast injection.

Transport mechanisms of hepatic uptake and bile excretion in clinical hepatobiliary scintigraphy with 99mTc-N-pyridoxyl-5-methyltryptophan.

INTRODUCTION: In clinical hepatobiliary scintigraphy, (99m)Tc-N-pyridoxyl-5-methyltryptophan ((99m)Tc-PMT) is an effective radiotracer among the (99m)Tc-pyridoxylaminates. However, the mechanisms of human hepatic uptake and bile excretion transport of (99m)Tc-PMT have not been determined. We thus investigated the transport mechanisms of human hepatic uptake and bile excretion in hepatobiliary scintigraphy with (99m)Tc-PMT. METHODS: Four solute carrier (SLC) transporters involved in hepatic uptake were evaluated using human embryonic kidney (HEK) and HeLa cells with high expression of SLC transporters (organic anion transporting polypeptide (OATP)1B1, OATP1B3, OATP2B1, organic anion transporters (OAT)2 and organic cation transporters (OCT)1) after 5 min of (99m)Tc-PMT incubation. Metabolic analysis of (99m)Tc-PMT was performed using pooled human liver S9. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters for bile excretion were examined using hepatic ABC transporter vesicles human expressing multiple drug resistance 1 (MDR1), multidrug resistance-associated protein 2 (MRP2), breast cancer resistance protein or bile salt export pump. (99m)Tc-PMT was incubated for 1, 3 and 5 min with ATP or adenosine monophosphate and these vesicles. SPECT scans were performed in normal and Eisai hyperbilirubinemic (EHBR) model rats, deficient in Mrp2 transporters, without and with verapamil (rat Mdr1 and human MDR1 inhibitor) after intravenous injection of (99m)Tc-PMT. RESULTS: Uptake of (99m)Tc-PMT in HEK293/OATP1B1 and HeLa/OATP1B3 was significantly higher than that in HEK293- and HeLa-mock cells. (99m)Tc-PMT was not metabolized in the human liver S9. In vesicles with high expression of ABC transporters, uptake of MDR1 or MRP2 was significantly higher at all incubation times. Bile excretion of (99m)Tc-PMT was also identified by comparison between normal and EHBR rats with and without verapamil on in-vivo imaging. CONCLUSIONS: Human hepatic uptake of (99m)Tc-PMT was transferred by OATP1B1 and OATP1B3, and excretion into bile canaliculi via MDR1 and MRP2. (99m)Tc-PMT hepatobiliary scintigraphy may be a useful ligand as a noninvasive method of visualizing and quantifying hepatobiliary transporter functionality, which could predict drug pharmacokinetics.

Decreased gallbladder emptying in dogs with biliary sludge or gallbladder mucocele.

Biliary sludge in dogs is dismissed commonly as an incidental finding. On the other hand, gallbladder mucocele is reported increasingly in dogs and can lead to biliary obstruction or gallbladder rupture. Cholestasis is suspected to play a role in development of sludge and mucoceles, though there are no data in dogs to support this. We investigated gallbladder emptying, a key factor in biliary flow, in dogs with mobile sludge, immobile sludge, or gallbladder mucocele and in healthy controls. Gallbladder ejection fraction estimated by ultrasonography was used as the index of gallbladder emptying. The ejection fraction at 60 min after eating was significantly decreased in all three abnormal groups. Moreover, all dogs with sludge or a mucocele had gallbladder distension. These changes were the greatest in the mucocele group. Thus, biliary stasis occurs not only in dogs with gallbladder mucocele but also in dogs with biliary sludge. Cholestasis may play a role in the pathogenesis or progression of these diseases in dogs.

Lack of significant liver enzyme elevation and gallstones and/or sludge on ultrasound on day 1 of acute pancreatitis is associated with recurrence after cholecystectomy: a population-based study.

BACKGROUND: In a population-based study, we examined recurrence rates of acute pancreatitis (AP) after cholecystectomy performed to prevent recurrences of AP. METHODS: We abstracted data from medical records of all Olmsted county residents who underwent cholecystectomy at Mayo Clinic for the management of presumed gallstone or idiopathic AP between 1990 and 2005 (n = 239). Based on (i) significantly elevated liver enzymes (≥threefold increase of alanine aminotransferase or aspartate aminotransferase) on day 1 and (ii) the presence of gallstones/sludge in the gall bladder, we categorized patients into 4 groups: A (i + ii), B (i but not ii), C (ii but not i), and D (neither i nor ii). Recurrence rates of AP after cholecystectomy were determined in all groups. RESULTS: The median follow-up after cholecystectomy was 99 months (range, 8-220). AP recurred in 13 of 142 patients (9%) in group A, 1 of 17 patients (6%) in group B, 13 of 57 patients (23%) in group C, and 14 of 23 patients (61%) in group D (P < .0001 D vs. all other groups and P = .001 C vs. groups A and B). No difference was seen in recurrence rates in groups A vs. B (P = 1.0). Recurrences were more frequent in patients with normal liver enzymes (A + B vs. C + D; P = .000003) and in patients without sonographic evidence of gallstones/sludge (A + C vs. B + D; P = .0008). CONCLUSION: When AP is associated with significantly elevated liver enzymes on day 1, recurrence rates after cholecystectomy are low (9%). However, postcholecystectomy recurrence rates of AP are high in those without such laboratory abnormalities (34%), especially in those without gall bladder stones/sludge (61%) on abdominal ultrasonography. Our results raise doubts about the efficacy of cholecystectomy to prevent recurrent AP in patients with the absence of either a significant elevation of liver tests on day 1 of AP or gallstones and/or sludge in the gall bladder on initial ultrasound examination.

The role of intraductal US in the management of idiopathic recurrent pancreatitis without a definite cause on ERCP.

BACKGROUND: The cause of pancreatitis is unknown in as many as 30% of cases of recurrent acute pancreatitis, even after ERCP. OBJECTIVE: To investigate the role of intraductal US (IDUS) for managing idiopathic recurrent pancreatitis (IRP). DESIGN: Prospective study. SETTING: Tertiary referral hospital. PATIENTS: Thirty-one patients with suspicious IRP with negative findings on ERCP. INTERVENTIONS: IDUS during ERCP. MAIN OUTCOME MEASUREMENTS: IDUS findings showing any possible cause of pancreatitis. RESULTS: IDUS revealed small bile duct stones (≤3 mm) in 5 patients (16.1%) and sludge in 3 patients (9.7%). The detection rate for a bile duct stone and sludge was significantly higher in patients with a dilated CBD than a nondilated CBD on ERCP (71.4 vs 12.5%; P < .05). Recurrent pancreatitis did not develop in 7 of 8 patients with biliary stones or sludge after an endoscopic sphincterotomy (EST). Two patients (6.5%) demonstrated a small polypoid lesion on the distal end of the pancreatic duct. One patient underwent surgery for intra-ampullary cancer, and another one underwent EST without another attack of pancreatitis. Three patients (9.7%) showed evidence of chronic pancreatitis with small pancreatic stones and/or calcifications on IDUS. LIMITATIONS: Small number of patients. IDUS results were not compared with those of conventional EUS. There was no reference standard for chronic pancreatitis as diagnosed by IDUS. CONCLUSIONS: IDUS identified a possible cause of idiopathic recurrent pancreatitis in 42% of patients with negative findings on ERCP. The IDUS-guided approach combined with ERCP and EST may be useful for decreasing recurring attacks of pancreatitis.

[The application of sinusoidal modulated currents for the treatment of biliary sludge in an outpatient clinic].

The objective of the present study was to evaluate therapeutic effects of sinusoidal modulated currents (SMC) applied for the treatment of patients at different stages of biliary sludge (BS) under conditions of an outpatient clinic. Biliary sludge is currently considered to be a precursor of cholelithiasis known to be a leading pathology of the digestive system responsible for the high surgery rate. It was shown that the introduction of the technique based on sinusoidal modulated currents into the clinical practice of an outpatient clinic increases the efficacy of management of the patients presenting with stage 1 and 2 biliary sludge and showing neither well-apparent clinical symptoms nor signs of metabolic disorders that imply the necessity of more thorough examination and combined application of sinusoidal modulated currents and mediacmental therapy.

Western blotting in the diagnosis of duodenal-biliary and pancreaticobiliary refluxes in biliary diseases.

BACKGROUND: Currently adopted diagnostic methods for duodenal-biliary and pancreaticobiliary refluxes carry many flaws, so the incidence of the two refluxes demands further larger sample size studies. This study aimed to evaluate Western blotting for the diagnosis of refluxes in biliary diseases. METHODS: An oral radionuclide 99mTc-DTPA test (radionuclide, RN) was conducted for the observation of duodenal-biliary reflux prior to measuring bile radioactivity and Western blotting for detecting bile enterokinase (EK). Pancreaticobiliary reflux was assessed by biochemical and Western blotting tests for biliary amylase activity and trypsin-1, respectively. In accordance with bile sample origin, our samples were classified into ductal bile and gall bile groups; based on each individual biliary disease, we further classified the ductal bile group into five sub-groups, and the gall bile group into four sub-groups. Western blotting was conducted to assess the two refluxes in biliary diseases. RESULTS: Consistencies were noted between EK and RN tests when diagnosing duodenal-biliary reflux (P<0.001). The amylase and trypsin-1 tests also showed consistency in diagnosing pancreaticobiliary reflux (P<0.001). Amylase and lipase levels within gall and ductal bile were strongly correlated (P<0.05). In the common bile duct pigment stone group, the EK and trypsin-1 positive rates were found to be insignificant (P>0.05); in the common bile duct cyst group, the EK positive rate was significantly lower than the trypsin-1 positive rate (P<0.05). CONCLUSIONS: Western blotting can accurately reflect duodenal-biliary and pancreaticobiliary refluxes. EK has greater sensitivity than RN for duodenal-biliary reflux. The majority of biliary amylase and lipase comes from the pancreas in all biliary diseases; pancreaticobiliary reflux is the predominant source in the common bile duct cyst group and duodenal-biliary reflux is responsible for the ductal pigment stone group.

Prognostic implications of bile lakes after surgery for biliary atresia.

PURPOSE: The aim of the study was to establish the natural history of bile lakes (BLs) in patients with postportoenterostomy biliary atresia (BA) and assess their prognostic implications, in particular, if they are a risk factor for cholangitis. METHODS: One hundred twenty-one postsurgical BA patients were divided into 2 groups as follows: period 1, or preliver transplantation era group (n = 56), and period 2, or liver transplantation era group (n = 65). Presence of BL and outcome were examined in relation to the incidence of cholangitis. RESULTS: In period 1, there were more multiple BLs (MBLs) in nonsurvivors than survivors. Non-BL survivors had significantly lower mean total number of episodes of cholangitis than MBL survivors (P < .01). In period 2, 58 survived (native liver in 35; transplanted liver in 23). Bile lakes were present in 9/58 (16%) survivors (single in five, multiple BLs in four), and 1/7 (14%) nonsurvivors had MBLs. Mean total number of episodes of cholangitis in the 4 MBL survivors and the 49 non-BL survivors were not significantly different. CONCLUSION: Our results suggest that presence of BL is a risk factor for cholangitis in the long-term but not in the short-term.