How to cite this article: Sánchez-Fernández P, Martínez-Ordaz JL, Sánchez-Reyes K, Ferat-Osorio E. Usefulness of hepatobiliary scintigraphy in the follow-up of patients with biliary reconstruction. Rev Med Inst Mex Seguro Soc. 2015;53(5):538-45.
Received: April15th 2014
Accepted March 4th 2015
Patricio Sánchez-Fernández,a José Luis Martínez-Ordaz,a Karina Sánchez-Reyes,a Eduardo Ferat-Osorioa
aServicio de Cirugía Gastro-Intestinal, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Distrito Federal, México
Communication with: Patricio Sánchez-Fernández
Telephone: (55) 5574 8724
Background: The relevance of biliary tract injury patients is not only related to diagnosis and treatment but also to follow-up for the possibility of late complications and medical and legal aspects. Hepatobiliary scintigraphy has played a principal roll in diagnosis of many hepatobiliary diseases.
Methods: we carried out a descriptive and retrospective study. Included were all patients with biliary tract injuries who underwent biliary reconstruction and liver biopsy. Clinical, laboratory exams and hepatobiliary scintigraphy follow-up was done.
Results: from January 2001 to december 2009 one hundred patients, sixty-five women and thirty-five men were registered. According to Strasberg´s classification we had 13 % type E1, 17 % type E2, 38 % type E3 and 32 % type E4. All of them underwent biliary tract reconstruction, eighty-four Hepp-Couinaud type and sixteen conventional jejunum-hepatic anastomosis (Roux-Y). Liver biopsy demonstrated twelve patients with inflammation, forty-nine with cholestasis, nineteen with ductular proliferation and nineteen with fibrosis. When we compare pathologic results of liver biopsy with pre and postoperatively hepatobiliary scintigraphy we found significance in those patients with cholestasis and ductular proliferation in hepatobiliary scintigraphy elimination step, but none in those with inflamation and fibrosis.
Conclusions: hepatobiliary scintigraphy is an adequate study to the follow-up of patients who underwent hepatobiliary reconstruction been more significative in patients with cholestasis and ductular proliferation.
Keywords: Gallbladder, Cholecystectomy, Common bile duct, Radionuclide imaging
The most common surgical antecedent that can lead to injury of the bile duct is cholecystectomy, which is probably the elective abdominal surgery most frequently performed and with the highest degree of safety. Operative mortality rate from this procedure is estimated to be less than 0.5% in patients younger than 65 years, since in patients over this age with medical history and emergency surgery the rate can increase. When carrying out the exploration of the bile duct mortality rates rise, especially when jaundice and/or cholangitis is present.1 Laparoscopic cholecystectomy has evolved to become the treatment of choice for patients when symptomatic cholecystolithiasis occurs. When compared with the traditional method, the incidence of biliary complications is greater in laparoscopy; also injuries related to laparoscopic cholecystectomy are much more complex and serious than those related to the traditional way.2 The incidence of injury in laparoscopic bile duct surgery is estimated at 1 in 200 to 400 patients,3 and this is due to the fact that there are more lesions of the bile duct in laparoscopy, anatomically speaking, as compared to traditional surgery; as such a high incidence of concomitant hepatic arterial injury can be anticipated.4-6
The relevance of a case of biliary tract injury involves not only a timely diagnosis and treatment but also long-term monitoring for the possibility of later complications and medical and legal aspects.7,8
Nuclear medicine has played an important role in the diagnosis of hepatosplenic disease via image, although many of radiopharmaceuticals, methodologies and guidelines have changed over time. The cholescintigraphy and the HIDA scan exemplify the continued importance of physiological and functional imaging techniques in the diagnosis of multiple hepatobiliary diseases such as acute cholecystitis, biliary obstruction and bile leakage, at a time in which the diagnostic anatomical imaging techniques offer increasingly high quality images and are in continuous and rapid evolution.9 The objective was to demonstrate the importance of the use of the HIDA scan in monitoring patients who have undergone reconstruction of the bile duct due to injury thereof.
Observational, retrospective, transversal and analytical study. Records of patients that were admitted to the Gastrointestinal Surgery Service with bile duct injuries and that underwent biliodigestive reconstruction were reviewed. The factors analyzed were: gender, age, initial diagnosis, type of initial surgery (open or laparoscopic), time between injury and initial repair (performed in the referral hospital or our hospital), type of injury according Strasberg classification,2 type of repair surgery outside the hospital, clinical data upon admission to the service, duration of symptoms, laboratory tests (blood count, blood chemistry, liver function tests), imaging studies, type of reconstruction in the hospital, complications, liver biopsy results, postoperative laboratory study (the same as in the preoperative) and nuclear medicine.
The monitoring of each patient was performed as follows: 1) a clinical outpatient review a week after discharge; 2) further consultation one month after surgery; 3) with laboratory results three months after surgery; 4) with laboratory results and a control HIDA scan six months after surgery; 5) subsequently, every six months with results from laboratory studies or the patient coming in as required if there is any clinical abnormality; 6) according to the result of the HIDA scan (normal or abnormal) and clinical history of each patient, the study is conducted every six or twelve months.
In the HIDA scan following were analyzed: the radiopharmaceutical uptake, the purification (elimination) of the image, the time taken (considered normal until exceeding 60 minutes) and postoperative control as well as the permeability of the anastomosis. The radiopharmaceutical used was IDA labeled with Tecnecio-99m.
Hematoxylin-eosin and Masson trichrome were used for liver biopsies obtained during reconstructive surgery; the result was classified as inflammation, cholestasis, ductopenia and/or fibrosis.10
The Student’s t test was used with the package SPSS 15.0 for Windows for statistical analysis of the differences between continuous preoperative values and postoperative values . The differences in values were considered statistically significant when p <0.05.
In a period from January 2001 to December 2009 patients who entered the Gastrointestinal Surgery Service on an urgent or scheduled basis were registered when diagnosed with secondary bile injury from a cholecystectomy procedure and/or intervention of the bile duct by a benign disease. One hundred patients, thirty-five men (35%) and 65 women (65%) with a mean age of 38.8 years (18-68 years), most of whom (98%) had been referred from second-level hospitals and two from our hospital (2%). Surgical procedures initially performed were laparoscopic cholecystectomy (CCT) for 73 (73%); open CCT for 27 (27%) and for 3 bile duct exploration. The postoperative diagnosis was chronic cholecystitis due to gallstones in 91 patients (91%), hydrocholecystis in five (5%) and cholecystis with empyema in four (4%). The time of evolution from when the injury occurred (when initial surgery was performed) until it was repaired (whether in our hospital or another) was 95.53 days on average (1-540).
Twenty-six patients (26%) underwent reoperation in their referral hospital; three of them (3%) had their bile duct drained with a feeding tube or T catheter. Twenty-three patients (23%) underwent surgery consisting of: hepatic-jejunal anastomosis in Roux-en-Y in nine patients (9%); hepatic-jejunal anastomosis in Omega Braun in five patients (5%), duct-to-duct anastomosis five patients (5%) and four patients duct-jejunal anastomosis (4%). A patient undergoing duct-to-duct anastomosis was reoperated on to re-do the procedure, and another patient undergoing duct-to-duct anastomosis was reoperated on and underwent duct-jejunal anastomosis.
The types of injury to the bile duct according to Strasberg rankings were: type E1, 13 patients (13%); Type E2, 17 patients (17%); Type E3, 38 patients (38%), and Type E4, 32 patients (32%). Clinical data obtained upon admission to our services were: jaundice (97%), acholia (96%), dark urine (96%), abdominal pain (84%), fever (76%), abdominal distension (55%), tachycardia (26%), vomiting (6%), edema (5%), oliguria (4%), dyspnea (3%) and acute abdomen (3%). Twenty-one patients had bile leakage via drainage (21%). The time of development of symptoms was on average 82.5 days (1-360).
Upon admission, sixty-eight patients (68%) had anemia (hemoglobin <12.5 g), all with elevated leukocyte count. In Table I the comparative results of liver function tests before (hospital admission) and after surgery (six months) are shown.
|Table I Liver function tests before and after reconstructive surgery|
|Test||Before||After||Significance (CI 95 %)|
|BIL. Direc.||4.034||2.021||p < 0.001 (1.54 - 2.47)|
|BIL. Indirec.||1.426||0.7080||p < 0.001 (0.577 - 0.822)|
|TGO||69.69||46.636||p < 0.001 (16.30 - 29.99)|
|TGP||69.71||46.474||p < 0.001 (16.94 - 29.62)|
|FA||751.42||374.85||p < 0.001 (293.84 - 459.33)|
|GGT||697.85||339.32||p < 0.001 (277.91 - 444.14)|
Upon admission, all patients underwent chest radiography with abnormality found in 8 of them (8%) characterized by pleural effusion and/or pneumonia; and a simple abdominal radiography, twenty-one (21%) with liquid filling the cavity and/or ileus.
An abdominal ultrasound was also performed, and bile duct dilatation was found in 85 patients (85%), with an average of 15.13 mm (9-25 mm), intra-abdominal collections in 15 patients (15%), and altered liver parenchymal echogenicity diagnosed as local or diffuse liver disease in 24 patients (24%). In ten patients (10%) an abdominal computed tomography was performed and abdominal collections were found. Twenty-seven patients (27%) underwent percutaneous cholangiography with drainage of the bile duct, and three (3%) T Catheter cholangiotography (which they had upon admission) that confirmed the injury to the bile duct. Sixty-eight patients (68%) underwent endoscopic-retrograde cholangiopancreatography-(ERCP) where the injury to the bile duct was confirmed and in some cases (20%) drained via biliary stent or tube drained while they underwent surgery.
Forty-five patients (45%) had magnetic resonance cholangiography performed identifying the location and degree of injury to the bile duct.
In ninety-nine patients (99%) the HIDA scan was performed preoperatively, and in a hundred, postoperatively; in the case of one patient it was not possible to perform a preoperative study due to the lack of radiopharmaceuticals at the time of admission. It only took place in the postoperative control (Table II) (Figure 1 and 2).
|Table II Preoperative and postoperative HIDA scan results|
|Total||99||100||p < 0.002|
|Total||99||100||p < 0.001|
|* The average preoperative elimination time was 87.9 minutes (61-180) and for 13% removal was null. The average postoperative elimination time in normal cases was 41.7 minutes (10-60), and 67.3 minutes (65 - 80) in patients with abnormality.|
Figure 1 HIDA scan study of a preoperative patient with bile duct injury post-cholecystectomy. The radiopharmaceutical step is null from baseline to 52 minutes.
Figure 2 Study of a postoperative patient’s control HIDA scan (reconstruction of the bile duct). Sequential images are presented for the first fifteen minutes where it is noted that as of the seventh minute the radiopharmaceutical is identifiable in the loop of jejunum of anastomosis. Liver biopsy showed injury as inflammation.
All patients underwent reconstructive surgery of the bile duct; eighty-four (84%) with the Hepp-Couinaud (HC) technique, and 16 patients (16%) with the conventional technique of hepatic-jejunal Roux-Y anastomosis (HYA). Also, all patients underwent liver biopsy during surgery. The types of alteration seen in the biopsy were classified as inflammation, cholestasis, ductopenia and/or fibrosis. Twelve patients (12%) had inflammation; forty-nine (49%) cholestasis; nineteen (19%) ductopenia, and nineteen (19%) fibrosis. The result of one liver biopsy sample was not included (for the patient who was not given the HIDA scan either).
Table III lists the results of the pre- and postoperative HIDA scans with histopathologic findings.
|Table III Relationship between results of histopathological findings and HIDA scan findings|
|Postoperative uptake||12||0||p = 0.47|
|Postoperative elimination||12||0||p = 0.21|
|Postoperative uptake||43||6||p = 0.079|
|Postoperative elimination||42||7||p = 0.001|
|Postoperative uptake||13||6||p = 0.10|
|Postoperative elimination||11||8||p = 0.002|
|Postoperative uptake||5||14||p = 1.00|
|Postoperative elimination||5||14||p = 0.046|
By comparing the time of the bile duct injury’s development with the findings of the HIDA scans (uptake and elimination) it could be seen that at 20 days after injury 51% of patients had abnormal results. The higher the healing time, the higher the percentage of patients with abnormalities. In connection with the elimination, as of the tenth day of the injury’s healing, 86% had abnormal results and as of day 20, 91%.
There were postoperative complications in 35 patients: nineteen patients with surgical site infection (19%), 5 patients with surgical site bleeding (5%), three patients with urinary tract infections (3%), three with pneumonia (3%) and the following complications with one in each case: colon perforation, spontaneous pneumothorax, intra-abdominal collection, acute renal failure and deep vein thrombosis.
The IDA radiopharmaceuticals labeled with Tc-99m (technetium) were originally synthesized for use in cardiac imaging techniques due to the similarities between IDA molecules and lidocaine. The high liver uptake of a precursor compound of IDA (IDA dimethyl) prompted the use of the acronym HIDA to refer to hepatobiliary IDA.
Analogues of Tc-99m IDA follow the same mechanisms of uptake, transport and excretion as bilirubin. After intravenous injection, the Tc-99m IDA binds tightly to plasma proteins, which reduces renal elimination. The radio-marker is introduced to the hepatocyte interior via an anion clearance mechanism, mediated by a high-capacity transporter. Through the hepatocellular uptake, it reaches the bile canaliculi through a system of active membrane transport. Analogs of Tc-99m IDA are stable in vivo and, unlike bilirubin, are eliminated in their original form without becoming radiochemical conjugates or suffering significant metabolism. By employing the same pathways as bilirubin, said analogues of Tc-99m IDA are subjected to competitive inhibition mechanisms in hyperbilirubinemia cases.
One advantage of scintigraphy (technectium-99 HIDA scan) is it is adequate for the diagnosis of biliary leak, the permeability of the anastomosis or recurrent obstruction; it is also useful in identifying the type of reconstruction made (e.g. bile-jejunal anastomosis, hepatic-jejunal anastomosis) in the case of prior reconstructive surgery.
The gamagraphic detection of hourly intestinal excretion, regardless of whether or not ductal dilation exists, indicates the functional permeability of the anastomosis. When the production of intestinal excretion takes more than 1 hour, a partial obstruction should be suspected. However, the retention of activity in the bile ducts is more of a sure sign. The persistence or increased retention of activity in the bile ducts after 1-2 hours have passed are quite specific signs of obstruction. This is when you can view the stasis of activity, minimal intestinal excretion and accumulation in the region of the biliary enteric anastomosis. These signs may depend on factors such as the patient’s position, preexisting liver disease, acute inflammatory disease (cholangitis) related to gallbladder or biliary (bile duct injury and/or reconstruction) surgery, and hepatocellular damage related to the time of the evolution of obstruction.9,11-14
It is expected that the laboratory tests, specifically those for liver function, will improve after the obstructive process is resolved, as significant difference before and after was observed in our patients; yet even with the process resolved, testing levels did not reach normality according to standard measurement ranges. Fialkowsky et al. established in a review of 73 patients who had undergone reconstruction of the bile duct followed up by liver function tests, that elevation of alkaline phosphatase, total bilirubin, SGOT and SGPT is common even after 5 years of reconstruction and that the first two tests may diminish over time.15
When comparing the results of HIDA scan before and after reconstructive surgery, with respect to (both normal and abnormal) uptake and elimination, significant difference existed. Improvement is expected once the obstruction is resolved. Regarding the thirteen patients (13%) with no preoperative elimination, it is evident that the severity of the histopathological damage on liver biopsy obtained operatively is proportionally correlated with a longer history of obstruction, so that the patients with severe damage (fibrosis) had a minimum of 15 days for their time of evolution (Figures 3 and 4).
Figure 3 Relationship between histopathological liver damage and the days of evolution in 13 patients with no elimination in the HIDA scan study.
Figure 4 Study of technectium-99 HIDA scan control for a patient in a postoperative state after bile duct reconstruction. It is observed that as of minute twenty the jejunal loop from anastomosis is identifiable. In subsequent sequences radiopharmaceuticals are still observed in the liver parenchyma. The liver biopsy report was ductopenia.
Hepatocellular injury is an invariable feature of cholestasis, because it causes liver dysfunction, promotes fibrogenesis, and can contribute to hepatic failure.16 Biliary obstruction caused by stenosis starts complex histopathological liver changes that result in progressive liver fibrosis and secondary biliary cirrhosis.10
Liver fibrosis is usually considered an irreversible process, even if the causes that generate it can be resolved.17
Of the patients enrolled in this study, the average time of development of biliary obstruction was 95 days and the presence of symptoms of 82 days, which represents a significant adverse factor. As was mentioned in the results, with regard to the imaging of the technectium-99 HIDA scan, as of day 20 more than 50% of patients had abnormal uptake, i.e.: the longer the history, the higher the percentage of abnormal uptake. With regard to the elimination, in over 80% of cases abnormality was present as of day 10, and as of day 20 in more than 90%, which makes it clear that there is impaired liver function from the first 10 days of evolution due to the obstruction of the bile duct.
Relating the histopathological findings to the HIDA scan in pre and postoperative studies, we found that they were statistically significant for removal in patients with cholestasis and ductopenia, but not in those with inflammation and fibrosis. In patients with severe damage from histopathology the HIDA scan study is less useful; those with fibrosis will have altered uptake and elimination in preoperative and postoperative studies due to the already established damage, which is not reversible. Despite the lack of statistical significance for patients with inflammation, after the reconstruction uptake and elimination improved for most of them. The same happened with HIDA scan uptake in patients with cholestasis and ductopenia.
Previously altered drainage of bile should improve in patients who undergo surgical resolution of bile duct obstruction. However, biliary drainage is related to the obstruction’s time of development with hepatocellular damage as a result. For these patients, the HIDA scan turns out to be a suitable follow-up study to assess hepatic uptake and elimination of the radiopharmaceutical used, which correlates with normal liver function, since these radiopharmaceuticals use the same path as bilirubin. Its best use is in patients with histopathological results for cholestasis and ductopenia. Patients with severe liver damage, i.e., fibrosis, will have a permanently altered uptake and elimination. The longer the history of obstruction, the greater the functional and histopathological effects will be.
Conflict of interest statement: The authors have completed and submitted the form translated into Spanish for the declaration of potential conflicts of interest of the International Committee of Medical Journal Editors, and none were reported in relation to this article.