Gallbladder ejection fraction declines with age in patients undergoing cholecystectomy for acalculous biliary symptoms but has low accuracy in the prediction of gallbladder pathology.

BACKGROUND/AIMS: Hepatobiliary Iminodiacetic Acid (HIDA) scan provides a technique to quantify gallbladder ejection fraction (EF) in patients suffering acalculous biliary colic (ACBC). We wished to evaluate the accuracy of EF in the prediction of gallbladder pathology in patients undergoing cholecystectomy. METHODS: Data were retrieved from a database of patients referred for HIDA scan for ACBC, including EF and the pathological outcome of those undergoing cholecystectomy, and compared to normal values obtained from a review of related studies. Significant associations were demonstrated by chi-square, Mann-Whitney test, and linear regression. The predictive accuracy of different cut-offs of EF was demonstrated by the ROC curve analysis. RESULTS: Of 83 patients referred for HIDA scan for ACBC, 41 underwent cholecystectomy. The median EF of this group (33%) was significantly lower than the composite normal median value from previous studies (56%). Thirty-two patients revealed evidence of gallbladder pathology. The EF declined with age (coefficient = -0.51, 95% CI = -0.99 to -0.33), but the median value did not differ between those with gallbladder pathology (34%) and those with normal gallbladders (29%). CONCLUSION/DISCUSSION: Although an EF cut-off of 35% had the greatest accuracy in the prediction of pathology of those tested (0.56), the poor negative predictive value (23.5%) was a major contributor to its low accuracy. Although patients with ACBC have reduced gallbladder EF compared to the normal population, its quantitative assessment is of limited value in the prediction of gallbladder pathology.

Traumatic bile leaks from blunt liver injury in children: a multidisciplinary and minimally invasive approach to management.

BACKGROUND: Selective non-operative management (NOM) of hemodynamically stable pediatric patients with blunt hepatic trauma is the standard of care. Traumatic bile leaks (TBL) are a potential complication following liver injury. The use of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis and treatment of TBL is described in adults, but limited in the pediatric literature. We report our experience with a multidisciplinary and minimally invasive approach to the management of TBL. METHODS: This was an IRB-approved 13-year retrospective review (January 1999-December 2012) of an institutional pediatric trauma registry; 294 patients (≤ 17 years old) sustained blunt hepatic injury. Those with TBL were identified. Patient demographics, mechanism of injury, management strategy and outcomes were reviewed. RESULTS: Eleven patients were identified with TBL. Hepatobiliary iminodiacetic scan (HIDA) was diagnostic. Combinations of peri-hepatic drain placement, ERCP with biliary stenting and/or sphincterotomy were performed with successful resolution of TBL in all cases. No child required surgical repair or reconstruction of the leak. Cholangitis developed in one child. There were no long-term complications. CONCLUSIONS: A multidisciplinary and minimally invasive approach employing peri-hepatic external drainage catheters and ERCP with sphincterotomy and stenting of the ampulla is a safe and effective management strategy for TBL in children.

Microlithiasis, endoscopic ultrasound, and children: not just little gallstones in little adults.

PURPOSE: Biliary microlithiasis is an uncommon but recognized cause of upper abdominal pain, cholecystitis, cholangitis, and pancreatitis in adults. Gallstones smaller than 3 mm may not be seen on transabdominal ultrasound and may only be seen on endoscopic ultrasound. This condition is poorly described in children. The aim of this study is to review the results of laparoscopic cholecystectomy to treat biliary microlithiasis in a pediatric case series. METHODS: We performed a retrospective case review of children with biliary microlithiasis who were treated with laparoscopic cholecystectomy. RESULTS: Three children were diagnosed with biliary microlithiasis. Two patients had recurrent right upper quadrant pain and nausea. A third patient had midepigastric pain and idiopathic pancreatitis. All 3 had a normal gallbladder on transabdominal ultrasound. Additional imaging with hepatobiliary scan, computed tomography, and magnetic resonance cholangiopancreatography revealed no biliary source for symptoms. Endoscopic ultrasound was performed on all 3 children, demonstrating microlithiasis of the gallbladder. Each child had a laparoscopic cholecystectomy with intraoperative cholangiogram. No abnormalities were seen on intraoperative cholangiogram. All 3 children had alleviation of pain and improvement of symptoms in postoperative follow-up. CONCLUSION: Children with biliary microlithiasis and associated clinical symptoms can be successfully treated with laparoscopic cholecystectomy. Endoscopic ultrasound should be considered in the evaluation of the child with clinical biliary symptoms and a negative transabdominal ultrasound result.

A diagnostic dilemma of atypical gallbladder appearance on Tc-99m HIDA cholescintigraphy resolved with SPECT/CT.

Tc-99m HIDA cholescintigraphy is the diagnostic procedure of choice for acute cholecystitis. Acute cholecystitis is associated in vast majority of the cases with cystic duct obstruction. The demonstration of presence (cystic duct patency) or absence (cystic duct obstruction) of visualization of the gallbladder on cholescintigraphy is critical to the diagnosis of acute cholecystitis. The visualization of the gallbladder rules out acute cholecystitis in most of the cases. Although, in most cases, determination of visualization or nonvisualization of gallbladder is straight forward, occasionally it can be challenging. We describe a patient with suspected acute cholecystitis, in whom an unusual appearance of the gallbladder on hepatobiliary scintigraphy was clarified with SPECT/CT, an approach that is rarely used in Tc-99m HIDA cholescintigraphy.

Detection of a suspected bronchobiliary fistula by hepatobiliary scintigraphy.

Bronchobiliary fistula (BBF) represents a rare but severe complication in patients affected by liver metastases. Although a clinical suspicion can arise when specific clinical signs, in particular biliptysis, are present, conventional imaging modalities often fail to confirm the diagnosis. We present a case of a patient affected by colon cancer with liver metastases previously treated with partial right-sided hepatectomy and multiple thermo-ablative treatments combined with chemotherapy, who manifested a septic fever associated with productive cough and biliptysis. Diagnosis of BBF was confirmed only by hepatobiliary scintigraphy with (99m)Tc-heptoiminodiacetic acid.

Varying appearance of focal nodular hyperplasia in nuclear medicine imaging.

The focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor, which contains variable quantities of normal hepatic cellular elements: Kupffer cells, hepatocytes, bile ducts, and blood vessels. Two patients with suspicion of FNH were investigated by colloidal, blood pool, and hepatobiliary scintigraphy. Dynamic perfusion examination (with labeled RBCs), planar and SPECT studies were performed in all cases. Diagnosis was confirmed by histologic examination. We suggest the importance of combined imaging because of various appearance of the tumor. In our experience SPECT imaging after a planar study is a useful sequence, especially in small tumors in the exact location of activity.

Long-term changes in hepatobiliary physiology after Roux-en-Y hepaticojejunostomy.

Hepaticojejunostomy (HJ) is a common operation used to by-pass extrahepatic biliary obstructions and to establish biliary-enteric continuity after resections for benign and malignant diseases. Little is known about the effect of this procedure on hepatobiliary physiology. The aim of the present study was to investigate in a swine model the changes in biliary dynamics, bile composition, and hepatic histology induced by Roux-Y HJ. Twenty-four swine (57 (47 to 76) kg) underwent cholecystectomy, with HJ (Group I; n = 12) or without any biliodigestive anastomosis (Group II, n = 12), and were followed up for 6 or 12 mo by repeated weight scaling, blood, serum, and bile analysis, (99m)Technetium (Tc), diethyliminodiacetic acid (HIDA) dynamic biligraphy, and histological analysis. During follow-up, HJ was associated with less weight gain, colonization of the bile duct with aerobic bacteria Escherichia coli dominating (in 75% of the animals), a shortened hilum-intestine transit time but reduced liver clearance in dynamic biligraphy, and fibrous periportal changes in liver histology (in 50% of the animals). We conclude that during 1 y follow-up HJ with no anastomotic stricture formation is associated with improved extrahepatic bile drainage, but with ascending contamination of bile ducts with bacteria, which might be involved with the fibrous periportal changes in the liver resulting in diminished excretion of Tc-HIDA from the hepatocytes into the bile. The clinical significance of these changes, and the reduced weight gain observed is a topic of further investigations.

Duodenogastric reflux after choledochoduodenostomy: evaluation by technetium-99m scintigraphy.

BACKGROUND/AIMS: Persistence of dyspeptic symptoms after choledochoduodenostomy (CDD) is common. There is evidence that at least some of these symptoms may be attributed to duodenogastric reflux (DGR). The aim of the study was to quantify DGR after CDD. METHODOLOGY: A total of 6 patients who had undergone cholecystectomy with a standard side-to-end CDD for choledocholithiasis or Lemmel syndrome were studied by symptom evaluation, biliary scintigraphy and endoscopy at least 6 months after surgery. Duodenogastric reflux was quantified using continuous intravenous infusion of 99mTc-HIDA. RESULTS: The incidence of DGR after CDD was 67% compared to healthy control. In the majority of the patients the DGR was mild to moderate, but not with the clinical symptoms. CONCLUSIONS: 99mTc-HIDA scanning of the hepatobiliary system is a reasonable and reliable method for the quantitative evaluation of DGR. CDD is associated with a high incidence of DGR, but its occurrence does not produce significant clinical symptoms.

[Congenital bronchobiliary fistula detected by cholescintigraphy]. / Fistula broncobiliar congénita detectada por colescintigrafía.

A case of a six-year-old female patient diagnosed with congenital bronchobiliary fistula is presented. Only 20 cases have been reported in the literature of this disease in this institution. The patient showed signs and symptoms of a respiratory illness from birth that complicated progressively. She was submitted to multiple imaging studies like chest X rays, CT, ultrasound and Tc-99m HIDA cholescintigraphy. This procedure confirmed the presence of a bronchobiliary fistula that was corrected by surgery, with subsequent improvement of clinical symptoms.

In vivo imaging of hepatobiliary transport function mediated by multidrug resistance associated protein and P-glycoprotein.

Multidrug resistance associated proteins (MRPs) and P-glycoprotein (P-gp) are involved in hepatobiliary transport of various compounds. Our aim was (1) to define transporter specificity of the cholescintigraphic agents 99mTc-HIDA and 99mTc-MIBI, which are used clinically for myocardial perfusion measurements; and (2) to deduce MRP and P-gp functions in vivo from hepatic 99mTc kinetics. Accumulation of radioactivity was measured in the human tumor cell lines GLC4, GLC4/ADR150x (MRP1-overexpressing/P-gp-negative) and GLC4/P-gp (P-gp-overexpressing). Bile secretion was quantified in untreated and in glutathione-depleted control and MRP2-deficient (GY/TR-) rats. Hepatobiliary transport was measured using a gamma camera in both types of rats. 99mTc-HIDA accumulated 5.8-fold less in GLC4/ADR150x calls than in GLC4 or GLC4/P-gp cells. In GLC4/ADR150x, the cellular 99mTc-HIDA content was increased 3.4-fold by the MRP1,2 inhibitor MK571 (50 microM), while MK571 had no measurable effect in GLC4 and GLC4/P-gp cells. 99mTc-MIBI accumulated less in GLC4/P-gp and GLC4/ADR150x cells than in GLC4 cells. Bile secretion of 99mTc-HIDA was impaired in GY/TR- compared to control rats and not affected by glutathione depletion in GY/TR- rats. Hepatic secretion of 99mTc-HIDA was slower in GY/TR- (t1/2 40 min) than in control rats (t1/2 7 min). Bile secretion of 99mTc-MIBI was similar in both rat strains and impaired by glutathione depletion in control rats only, indicating compensatory activity of additional transporter(s) in GY/TR- rats. 99mTc-HIDA is transported only by MRP1,2 only, while 99mTc-MIBI is transported by P-gp and MRP1,2. The results indicate that hepatic P-gp and MRP1,2 function can be assessed in vivo by sequential use of both radiopharmaceuticals.

Bronchobiliary fistula as a complication of liver metastases: diagnosis by HIDA scan.

Bronchobiliary fistulas are rare, may result from infection with Echinococcus or Amebiasis, trauma, or hepatic malignancy, and present with biliptysis, the expectoration of bile. The authors present a 49-year-old woman who presented with frank biliptysis as a result of previously treated metastatic colon cancer to the liver. A hepatobiliary scan is the noninvasive diagnostic imaging test of choice for demonstration of such fistulas, and was useful in confirming the diagnosis in our patient.

Small bowel transit and gastric emptying after biliodigestive anastomosis using the uncut jejunal loop.

BACKGROUND: The Roux-en-Y loop is an effective procedure for biliodigestive drainage. However, up to 15% of patients suffer from postoperative cholangitis or blind loop syndrome. A new technique to prevent motility abnormalities has been developed. METHODS: Male Lewis rats were used to compare gastric emptying and transit in the small bowel after either a standard Roux-en-Y anastomosis or a new biliodigestive anastomosis technique which involves creating an "uncut" jejunal loop with luminal occlusion. Unoperated rats served as controls. (99)Technetium HIDA and (111)Indium-tagged amberlite were respectively used to investigate small bowel transit and gastric emptying. RESULTS: Histopathology showed distinctive abnormalities only in the liver of conventional Roux-en-Y animals. No recanalization of the obliterated gut lumen occurred in uncut Roux animals. Distribution of (99)Tc-HIDA and (111)In showed were similar in both groups. Gastric emptying is slowed in both groups. CONCLUSIONS: The uncut proximal jejunum loop is a good alternative to the conventional Roux-en-Y loop and showed preserved small bowel motility and adequate jejunal transit. Gastric emptying is slowed in both groups.

[Conservative treatment of traumatic rupture of the biliary ducts: a case report]. / Traitement conservateur des ruptures traumatiques des voies biliaires: à propos d'un cas.

The diagnosis of a biliary duct transection after blunt trauma is difficult in children. Surgery is often performed late and therefore complicated. We present a case of mini-invasive approach for biliary duct transection in a 12-year-old child and review the literature. Transhepatic cholangiography is at the moment the most used technique to make the diagnosis but necessitates general anaesthesia. Stent placement is possible by the way. Endoscopic retrograde cholangiogram (ERCP) has been proposed even in children. Stent placement may be easier by this technique. For the diagnosis, Technetium 99m dimethylminodiacetic acid (HIDA) scanning seems interesting in terms of both sensitivity and specificity. Another promising diagnostic technique is MRI with 3D reconstruction.

[Hepatobiliogastroscintigraphy in assessment of the hepatobiliary system in primary cancer of the liver]. / Gepatobiligastrostsintigrafiia v otsenke sostoianiia gepatobiliarnoi sistemy pri pervichnom rake pecheni.

Primary cancer of the liver is characterized not only by laboratory evidence for cytolytic (87.5% cases), cholestatic (100% cases) syndromes, high levels of oncomarkers (CA-19-9, 50%; CEA, 68.75%; alpha FP, 43.75%) and activation of hemostasis system but, as shown at hepatobiligastroscintigraphy with 99m-Tc-brommeside, by at least 2-fold decline in absorptive and excretory function of hepatic polygonal cells (in 75% cases), at least a 5-fold decline in secretory function of the gallbladder (in 100% cases), cholestasis (in 100% cases) manifesting as a 3.8-fold reduction, on the average, of the ratio of secretory function of the gallbladder to that of the intrahepatic bile ducts, dilation of the latter (in 50% cases), Oddi's sphincter hypotonicity (in 50% cases). None of the patients showed duodenogastric reflux.

Is bile flow reduced in patients with hypothyroidism?

BACKGROUND: Disturbances in the sphincter of Oddi (SO) function may prevent normal bile flow and thus enhance the probability of common bile duct stone (CBDS) formation. We have previously shown increased prevalence of diagnosed hypothyroidism in CBDS patients, thyroxine (T(4)) -induced inhibition of the SO contractility both in animal and in human experiments ex vivo, and reduced bile flow to duodenum in hypothyroid rats. The aim of the present study was to investigate human biliary dynamics in relation to altered thyroid gland function. METHODS: Eight female patients, 1 with diagnosed untreated hypothyroidism and 7 with total thyroidectomy performed due to thyroid cancer, were studied in hypothyroid stage and again after thyroxine replacement therapy in euthyroid stage, with quantitative (99m)Tc HIDA cholescintigraphy (QC), biliary ultrasonography, and serum determinations. Each patient served as her own control in the 2 stages of the study. RESULTS: In QC, maximal uptake of (99m)Tc HIDA was not changed in hypothyroidism compared to euthyroidism. The first appearance of radioactivity to large bile ducts at the hepatic hilum remained unchanged in the 2 stages of the study. Hepatic clearance of (99m)Tc HIDA was decreased at 45 minutes (28% [11-38] vs 50% [33-54]; P =.028; median and range) and at 60 minutes (55% [28-80] vs 69% [61-79]; P =.028; median and range) and hilum-duodenal transit time increased by 31% compared to euthyroid stage. In US no changes were seen in gall bladder or bile ducts in the 2 stages of the study. Serum hypercholesterolemia was observed in the hypothyroid stage. CONCLUSIONS: We conclude that hypothyroidism may result in delayed emptying of the biliary tract, as studied with QC. In addition to the changes in bile composition and excretion rate suggested before to take place in hypothyroidism, according to the present study changes in biliary emptying also may be included in the probable causes for the increased prevalence of CBDS in hypothyroidism. This may be due to the absence of the prorelaxing effect of thyroxine on SO, which we have shown before to exist ex vivo.

Gallbladder function before and after fundoplication.

No study has reported an association between gastroesophageal reflux disease (GERD) or its therapies and gallbladder function. We compared pre- and postoperative gallbladder function in patients undergoing fundoplication to determine the following: (1) whether patients with chronic GERD have preexisting gallbladder motor dysfunction; (2) whether medical or surgical therapy alters gallbladder function; and (3) whether division of the hepatic branch of the anterior vagus nerve is detrimental to gallbladder motility. Nineteen patients with documented GERD consented to a preoperative cholecystokinin-stimulated technetium hepatobiliary (CCK-HIDA) scan to quantify the gallbladder ejection fraction (GBEF). All patients underwent laparoscopic Nissen fundoplication. One month after fundoplication, 12 patients completed a repeat CCK-HIDA scan for determination of GBEF, with comparison to the preoperative GBEF. Among patients with preoperative GERD, 11 (58%) of 19 met the scintigraphic criteria for gallbladder dysfunction (GBEF <35%), which is a ratio comparable to that in patients undergoing a CCK-HIDA scan for presumed biliary dyskinesia during the same time period (31 [60%] of 53; P = NS, chi-square test) and exceeds the rate of abnormal GBEF reported in healthy volunteers (3%). Six of seven patients with a low preoperative GBEF who underwent repeat evaluation postoperatively had normalization of the GBEF (P < 0.05, paired t-test). In the 12 patients who underwent postoperative CCK-HIDA scanning, there was no association between preservation or division of the hepatic branch of the anterior vagus nerve and postoperative gallbladder dysfunction (P = NS, chi-square test). Unexpectedly, 58% of patients with GERD demonstrated gallbladder motor dysfunction prior to fundoplication, with improvement to normal occurring in most of those studied postoperatively. These data support controlled trials to determine the effect of chronic GERD and antisecretory therapy on gallbladder and global gastrointestinal smooth muscle function. Preservation of the hepatic branch of the anterior vagus nerve during fundoplication offered no clear benefit with regard to early postoperative gallbladder function.

Patency of anastomoses after bilio-intestinal bypass: radioisotope demonstration.

BACKGROUND: Bilio-intestinal bypass (BIB) is effective for the treatment of refractory obesity. BIB permits bile flow into the non-functional jejunum, whereas food transit occurs via the remaining intestine. We used the radioisotope method of 99mTc-Hida cholescintigraphy (HC) in the follow-up of patients. METHODS: 21 patients were studied 3 months to 3 years after BIB with HC. After 3 hours acquisition, images were reviewed by two independent observers. Regions of interest (ROIs) were drawn on images: liver parenchyma, cholecysto-jejunal anastomosis (CC), choledochus (COL). Radioactivity taken up by liver was compared with radioactivity of CC and COL. % radioactivity passing through CC (%CC) and through COL (%COL) were determined. The final parameter, -COL, indicates the radioactive bile which does not pass through the choledochus. RESULTS: Anastomoses were found patent a few months to 3 years after operation. -COL showed linear correlation with the decrease in cholesterolemia and in body weight in the 1st year after BIB. CONCLUSIONS: HC shows passage of radioactive bile through anastomoses and provides semiquantitative evaluation of bile flux diversion. Bile flux towards the gallbladder and non-functional jejunal limb far exceeds flux directed towards the duodenum via the choledochus.

Dynamic 99Tcm-HIDA SPET: non-invasive measuring of intrahepatic bile flow. Description of the method and a study in primary sclerosing cholangitis.

In this study dynamic 99Tcm-HIDA single photon emission tomography (SPET) was performed in patients with primary sclerosing cholangitis and normal test subjects. The method offers the possibility of functional analysis of individual liver segments. After injection of 120 MBq of 99Tcm-HIDA, 12 consecutive SPET examinations were performed at 6-min intervals. The segmental borders of liver segments as seen on computed tomography or magnetic resonance examinations were superimposed on the scintigraphic images allowing placement of regions of interest (ROIs) in specific liver segments. Sampling from the same ROIs in consecutive SPET images enabled creation of time-activity curves for individual liver segments. A range of normal values was created by quantitative analysis of normal volunteer studies. Results of the studies in patients correlated well with cholangiographic extent of disease, liver function tests and histological stage. The technique may have particular value in diseases that affect the liver in a nonhomogenous or segmental fashion. Giving an indication of bile clearance from individual liver segments, it can quantify the functional importance of radiologically detected strictures. Percutaneous liver biopsy can be directed to the worst affected parts of the liver, making biopsy more representative. Sequential studies may allow monitoring of disease progression, aiding in selection and timing of therapeutic procedures.

Directing portal flow is essential for graft survival in auxiliary partial heterotopic liver transplantation in the dog.

BACKGROUND/PURPOSE: Auxiliary liver transplantation is an attractive alternative for orthotopic liver transplantation in patients with certain inborn errors of metabolism of the liver in which complete resection of the liver is unnecessary or even contraindicated. Because in these diseases portal hypertension is mostly absent, finding a balance in portal blood distribution between native liver and graft is complicated. The objective of this study was to investigate requirements for long-term (180 days) graft survival in auxiliary partial heterotopic liver transplantation (APHLT) in a dog model. METHODS: A metabolic defect was corrected in 26 dalmation dogs with a 60% beagle heterotopic auxiliary liver graft. Four groups of different portal inflow were studied. In the ligation group the portal vein to the host liver was ligated. In the split-flow group graft and host liver received separate portal inflow. In the banding group the distribution of the portal flow was regulated with an adjustable strapband and in the free-flow group the portal blood was allowed to flow randomly to host or graft liver. RESULTS: Metabolic correction increased in all groups after transplantation from 0.19 +/- 0.02 to 0.70 +/- 0.05 (P< .0001) but remained significantly better in the ligation and split-flow groups (graft survival, 135 +/- 27 and 144 +/- 31 days). In the banding group metabolic correction decreased significantly after 70 days, and although the grafts kept some function for 155 +/- 14 days, in 4 of 6 dogs portal thrombosis was found. In the free-flow group, competition for the portal blood led to reduced correction within 12 days and total loss of function in 96 +/- 14 days. Graft function also was assessed with technetium (Tc) 99m dimethyl-iminodiacetic acid uptake. A good linear association between HIDA uptake and metabolic correction was observed (r = 0.74; P < .0005). Grafts that contributed more than 15% to the total uptake of HIDA showed biochemical correction. This indicates a critical graft mass of about 15% to 20% of the hepatocyte volume to correct this metabolic defect. CONCLUSION: Auxiliary partial heterotopic liver transplantation can be a valuable alternative treatment for inborn errors of hepatic metabolism if the native liver and the graft receive separate portal blood inflow.