Rapid Communication
Copyright ©2007 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2007; 13(43): 5745-5749
Published online Nov 21, 2007. doi: 10.3748/wjg.v13.i43.5745
Triple non-invasive diagnostic test for exclusion of common bile ducts stones before laparoscopic cholecystectomy
Bahram Pourseidi, Amir Khorram-Manesh
Bahram Pourseidi, Department of Surgery, Kerman University of Medical Science, Kerman, Iran
Amir Khorram-Manesh, Department of Surgery Kungälv and Sahlgrenska University Hospitals, Göteborg, Sweden
Author contributions: All authors contributed equally to the work.
Correspondence to: Amir Khorram-Manesh, MD, PhD, Department of General & Orthopedic Surgery, Kungälv Hospital, S-442 83 KUNGÄLV, Sweden. amir.khorram-manesh@surgery.gu.se
Telephone: +46-303-98008 Fax: +46-303-98326
Received: July 10, 2007
Revised: August 17, 2007
Accepted: October 12, 2007
Published online: November 21, 2007

Abstract

AIM: To evaluate the impact of a preoperative “triple non-invasive diagnostic test” for diagnosis and/or exclusion of common bile duct stones.

METHODS: All patients with symptomatic gallstone disease, operated on by laparoscopic cholecystectomy from March 2004 to March 2006 were studied retrospectively. Two hundred patients were included and reviewed by using a triple diagnostic test including: patient’s medical history, routine liver function tests and routine ultrasonography. All patients were followed up 2-24 mo after surgery to evaluate the impact of triple diagnostic test.

RESULTS: Twenty-five patients were identified to have common bile duct stones. Lack of history of stones, negative laboratory tests and normal ultrasonography alone was proven to exclude common bile duct stones in some patients. However, a combination of these three components (triple diagnostic), was proven to be the most statistically significant test to exclude common bile duct stones in patients with gallstone disease.

CONCLUSION: Using a combination of routinely used diagnostic components as triple diagnostic modality would increase the diagnostic accuracy of common bile duct stones preoperatively. This triple non-invasive test is recommended for excluding common bile duct stones and to identify patients in need for other investigations.

Key Words: Common bile duct stones, Laparoscopic cholecystectomy, Triple non-invasive diagnostic test



INTRODUCTION

Surgery is the treatment of choice in symptomatic gallstone disease and is also recommended in asymptomatic patients due to complications followed by stone release in common bile duct[1-5]. Coexisting common bile duct stones (CBDS) occur in 7%-20% of all patients undergoing cholecystectomy[2,3,6]. Although intraoperative cholangiography was routinely performed to diagnose CBDS during pre-laparoscopic era, its use in the laparoscopic era has been debated[7-10]. Consequently, other techniques for diagnosing CBDS have been introduced[6-8].

Preoperative liver function test (LFT) results might be diagnostic for CBDS, if abnormal. However, some patients might have normal LFT despite coexisting CBDS[5,7]. Ultrasonography is the major diagnostic modality to diagnose gallstones, but is less helpful for diagnosing CBDS[1-7]. Computed tomography is rarely useful for diagnosing gallstones[5,8]. Magnetic-resonance-cholangio-pancreatography (MRCP) has high specificity and sensitivity and accuracy similar to that of Endoscopic-Retrograde-Cholangio-Pancreatography (ERCP), but its accuracy decreases if gallstones are small (< 4 mm) or if they are located near Vater’s papilla[2,5,8,11]. In addition, MRCP is not widely available and unlike ERCP does not allow endoscopic extraction of stones[5,8,12]. ERCP is the most common technique used for both diagnostic and treatment of CBDS. It is however, expensive, invasive, technically demanding and associated with small but significant morbidity[6,7,13].

Clinical history of jaundice, pancreatitis or cholangitis, abnormal LFT results and or dilated common bile duct have been traditionally used to select possible candidates for ERCP preoperatively[5], but to the best of our knowledge, the accuracy of these parameters together in diagnosing and/or excluding CBDS has never been evaluated[5,6,8]. The aim of this retrospective study was to assess the accuracy of these variables alone and in combination for diagnosing/excluding CBDS in a consecutive group of patients with symptomatic gallstones disease operated on by laparoscopic cholecystectomy.

MATERIALS AND METHODS

From March 2004 to March 2006, all consecutive patients with ultrasound verified gallstones, in whom laparoscopic cholecystectomy was indicated, were studied retrospectively. The study was approved by the Afzali Hospital’s ethical committee.

All information was collected based on a questionnaire including three different components. Patient’s data and medical history, age at operation, gender, history of jaundice (obstructive vs non-obstructive), cholangitis or pancreatitis (acute vs non-acute) were recorded. The results of ultrasonography, preoperative liver functions tests (LFT), serum-total bilirubin (S-Bil), alkaline phosphatase (S-ALP) and white blood cells counts (WBC) were obtained. The following cut-off values were considered abnormal: S-Bil ≥ 1.5 dL/L, S-ALP ≥ 400 Ul/L and WBC ≥ 10000/mm3. CBDS diagnosis was established by either demonstrating a stone in CBD or a wide CBD (diameter ≥ 10 mm). All patients were operated laparoscopically. No intraoperative cholangiography was performed. All included patients (n = 200) were followed up 2-24 mo postoperatively, by means of a questionnaire, completed by telephone interviews or clinical visit if needed.

Statistical analysis

The statistical analysis was performed using SPSS (version 11.0). The association between occurrence of CBDS and different variables was analyzed using Chi-square test. Sensitivity, specificity, positive and negative predictive values were calculated for all variables individually and in combination. Student t-test with separate variance estimates was performed to test the demographic differences. Fisher exact test and χ2-test were performed to compare between patients with a different number of suggested variables. P < 0.05 was considered statistically significant. Any patient with incomplete medical file or test results or any unclear information was excluded.

RESULTS

Two hundred patients, 43 men (21.5%) and 157 women (78.5%) were consecutively included in this study. The mean age of patients at the time of operation was 56.6 ± 18.2 and 51.6 ± 16.5 years for men and women, respectively. The average length of hospital stay was 30 (range 24-72) h for the whole group of patients, with no statistically significant difference between men and women.

Eighteen patients (9%) were found to have CBDS intraoperatively and additional 7 patients were found to have CBDS during the follow-up. The total number of patients with CBDS in this series was 25 patients (12.5%). The review of patient’s clinical history did not reveal any clinical evidence for CBDS (jaundice, cholangitis or pancreatitis) in the majority of patients (89.5%). In the remaining patients (10.5%), besides cholangitis, all other clinical variables were more common in men. In 16 out of 25 patients with CBDS (8 women and 8 men), obstructive jaundice was the most frequent variable in both genders (Table 1). The association between clinical evidence for CBDS and occurrence of CBDS was calculated (Table 2). Thirteen patients had one positive clinical variable and 8 patients had two positive clinical variables. Higher number of positive clinical variables was not statistically significant for diagnosing CBDS. CBDS was more common in men with clinical evidence of the disease. The difference between men and women in this aspect was statistically significant (Chi-square: 6.56, df: 2, P < 0.05) (Table 2).

Table 1 Frequency of clinical variables in 200 patients with gallstones n (%).
VariablesTotalWomenMen
Obstructive jaundice
Yes16 (8)8 (5.1)8 (18.6)
No183 (92)148 (94.9)35 (81.4)
Total199 (100)156 (100)43 (100)
History of jaundice
Yes5 (2.5)3 (1.9)2 (4.7)
No192 (97.5)151 (98.1)41 (95.3)
Total197 (100)154 (100)43 (100)
Cholangitis
Yes5 (2.5)5 (3.2)0
No192 (97.5)149 (96.8)43 (100)
Total197 (100)154 (100)43 (100)
Acute Pancreatitis
Yes1 (0.5)01 (2.3)
No196 (99.5)154 (100)42 (97.7)
Total197 (100)154 (100)43 (100)
History of Pancreatitis
Yes2(1)1 (0.6)1 (2.3)
No195(99)153 (99.4)42 (97.7)
Total197(100)154 (100)43 (100)
Table 2 Association between the number of positive clinical variables and CBDS n (%).
PatientsNegative history1 positive findings2 positive findingsTotal
Men6 (14)
Women145 (92.4)7 (4.5)5 (3.2)157 (100)
Total179 (89.5)13 (6.5)8 (4)200 (100)

The majority of patients in this cohort had a normal ultrasonography (n = 175, 87.3%). However, in 25 patients with CBDS (12 women and 13 men), 8 patients had a stone in common bile duct, 12 had obstruction in common bile duct, one had both a stone and obstruction of common bile duct, 3 had a widened common bile duct (> 10 mm), and finally one patient had widening of an intrahepatic bile branch. Positive ultrasonographic findings indicating CBDS were more common in men [13 out of 43 men (30%) and 12 out of 157 women (7%)] (Table 3). The difference in ultrasonographic diagnosis between men and women was statistically significant (Chi-square 20.23, df: 5 and P < 0.05).

Table 3 The results of ultrasound investigations in 200 patients with gallstones (per gender) n (%).
PatientsMenWomenTotal
CBDS5 (11.9)3 (1.9)8 (4.1)
CBD obstruction6 (14.3)6 (3.9)12 (6.1)
CBDS and obstruction1 (2.4)0 (0)1 (0.5)
CBD diameter > 10 mm1 (2.4)2 (1.3)3 (1.5)
Dilated intrahepatic0 (0)1 (0.6)1 (0.5)
bile duct branches
Normal30 (69)145 (92.3)175 (87.3)
Total43 (100)157 (100)200 (100)

The abnormal S-Bil and S-ALP results in men and women with CBDS are shown in Table 4. The majority of patients had normal laboratory results (> 85%). In 13 men (30.2%) serum bilirubin concentration was higher than 1.5 dL/L [compared to 11 women (7%)] and in 14 men (32.6%) the concentration of alkaline phosphatase was higher than 400 Ul/L [compared to 16 women (10%)]. All patients with S-Bil ≥ 1.5 dL/L had CBDS. These changes were more common in men and the difference between men and women was statistically significant (Chi-square 17.24, df: 1 and P < 0.05).

Table 4 Results of liver tests in patients with gallstones (per gender) n (%).
GenderS-bilirubin ≥ 1.5 dL/L
Alkaline phosphatase ≥ 400 UL/L
YesNoTotalYesNoTotal
Men13 (30.2)30 (69.8)43 (100)14 (32.6)29 (67.4)43 (100)
Women11 (7)146 (93)157 (100)16 (10.2)141 (89.8)157 (100)
Total24 (12)176 (88)200 (100)30 (15)170 (85)200 (100)

The sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of each variable of medical history, LFT results and ultrasonography alone or in different combination for diagnosis/exclusion of CBDS was evaluated statistically (Table 5). As a single diagnostic test, ultrasonography had higher sensitivity (64%), specificity (97.1%), negative and positive predictive values (95% and 76.2%, respectively) than medical history, S-Bil and S-ALP. As a triple diagnostic modality, a combination of medical history, ultrasonographic findings and LFT results was proven to be the best diagnostic modality to exclude CBDS. White blood cells count had no impact in diagnosis of CBDS.

Table 5 Diagnostic value of each of the triple tests, alone and in combination n (%).
VariablesSensitivitySpecificityNPVPPV
1. Medical history4492.590.538.1
2. Ultrasound6497.19576.2
3. Alkaline phosphatase ≥ 400 Ul/L32959026.7
4. Serum bilirubin ≥ 1.5 dL/L30.376.289.225
2 + 3 + 48082.996.740
2 + 3 or 2 + 43297.190.961.5
2 + 1+ 3 or 48481.797.339.6
DISCUSSION

Although the majority of patients with gallstone disease have an uncomplicated surgical course, a few may become complicated due to occurrence of CBDS[1-3]. Due to fewer intraoperative cholangiographies during laparoscopic cholecystectomies[6,7], ERCP has been recommended for pre- or postoperative extraction of CBDS. It is however, an invasive investigation with high risk for complications and should be reserved for selected cases[12,14,15]. MRCP is not available in all institutions and its accuracy depends on the size and position of CBDS[4,11,12]. There is thus a need for easy-performing, non-invasive, and reliable test modalities to diagnose or exclude CBDS, by which selected patients can benefit from ERCP, MRCP or other expensive investigations[13-15]. Earlier studies on some clinical, laboratory or radiological variables have been performed[16,17]. There is however, as far as we know, no study performed evaluating a combination of these investigating modalities. The majority of patients with gallstones are routinely evaluated by their clinical history, ultrasonography and LFT (S-Bil and S-ALP)[3,5]. The main object of this study was to evaluate the efficacy of these non-invasive investigation methods for exclusion of CBDS diagnosis.

The importance of careful review of patient’s history has been reported in many earlier studies. A focused positive patient’s history may be an early indication of CBDS[3,6,16-18]. Hyperbilirubinemia preoperatively, had a high diagnostic significant in our study and is also reported by others[7,19]. Ultrasonographic investigation is a reliable diagnostic modality with high availability and lower cost. However, the result of the investigation depends highly on investigators experience[3,14,20]. In our study, ultrasonography was performed by one radiologist and our results are comparable with earlier reports[3,6]. As also earlier reported by others, our study indicates that in patients who lacked clinical, radiological and laboratory signs of CBDS, there is no need for performing ERCP[6,14,21-25]. It also indicates that by using patient’s complete medical history (with special focus on the most common clinical complication of gallstone diseases such as pancreatitis), customary laboratory tests such as S-Bil and S-ALP and ultrasonography one may exclude CBDS diagnosis with high accuracy[26-29].

We used different variables as predictors i.e., these variables were used to predict or explain the value(s) of one or more dependent variables (also referred to as dependent or outcome variables statistically). The positive predictive value (PPV), or precision rate, is defined as the proportion of patients with positive test results who are correctly diagnosed. Hence the PPV is used to indicate the probability that, in case of a positive test, the patient really has the specified disease. However there may be more than one cause for a disease and any single potential cause may not always result in the overt disease seen in a patient. In our study only ultrasonographic investigation has highest PPV followed by a combination of ultrasound investigation and LFT results. Since we were interested in evaluating the impact and usefulness of the negative ultrasonography or LFT results and the lack of clinical evidence (negative history of pancreatitis, cholecystitis and cholangitis) of CBDS, in our study, we used the negative predictive value (NPV), which is the proportion of patients with negative test results who are correctly diagnosed. Higher NPV means then higher sensitivity for excluding CBDS as shown in our study; combining several tests in our study increased the negative predictive value and sensitivity of CBDS exclusion with almost equal specificity[16-18,30].

We concluded that patients with normal ultrasono-graphy, LFT results and no clinical evidence of CBDS “negative triple test” (NPV of 97.3%) may undergo laparoscopic surgery without any need for preoperative MRCP or ERCP. The availability and non-invasiveness of this triple diagnostic test are additional benefits, which makes it more interesting.

COMMENTS
Background

Coexisting common bile duct stones (CBDS) may complicate the course of gallstone disease. During open surgical removal of gallstones (open cholecystectomy), cholangiography is performed to exclude, or if needed, to remove CBDS. With laparoscopic cholecystectomy becoming the first surgical choice for treatment of gallstones, preoperative cholangiography has not been performed routinely and the procedure itself has been debated. Consequently, other techniques have been used to exclude CBDS. These techniques, however, are either invasive, with consequent risk for complications, or only diagnostic; some of them not available at all hospitals. There is thus a need to establish a simple, non-invasive and cheap diagnostic method, available at all units, to identify patients with CBDS for further evaluation with invasive and more expensive techniques.

Research frontiers

The research front in this area is focused on developing different imaging techniques. The most promising technique is Magnetic-Resonance-Cholangio-Pancreatography (MRCP). It has high specificity and sensitivity and accuracy similar to that of ERCP (Endoscopic-Retrograde-Cholangio-Pancreatography), but its accuracy decreases if gallstones are small (< 4 mm) or if they are located near Vater’s papilla. In addition MRCP is not widely available and unlike ERCP does not allow endoscopic extraction of stones. ERCP is the most common technique used for both diagnostic and treatment of CBDS. It is however, expensive, invasive, technically demanding and associated with small but significant morbidity.

Innovations and breakthroughs

By using already existed parameters; liver functions test, ultrasonography together with complete review of patient’s medical history (triple diagnostic), we offer a simple, cheap and, for all clinicians, available triple technique, to diagnose or exclude CBDS without any extra cost or diagnostic delay.

Applications

The majority of patients without CBDS will be identified by this triple diagnostic technique, leaving the remaining few, to be investigated by MRCP or ERCP. The availability and non-invasiveness of this test are additional benefits, which makes it more interesting.

Terminology

Cholangiography: X-ray examination of the bile ducts following administration of a radiopaque contrast medium. Magnetic-Resonance-Cholangio-Pancreatography: is a medical imaging technique which uses magnetic resonance imaging to visualise the biliary and pancreatic ducts in a non-invasive manner. Endoscopic-Retrograde-Cholangio-Pancreatography: refers to the use of an endoscope; a thin, flexible tube with a tiny video camera and light on the end to diagnose and treat various problems of the GI tract (stomach, intestine, liver, pancreas, and gallbladder).

Peer review

Through retrospective study, the authors concluded that using a combination of routinely used diagnostic components as triple diagnostic modality would increase the diagnostic accuracy of common bile duct stones. The result is reasonable and persuasive.

Footnotes

S- Editor Zhu LH L- Editor Negro F E- Editor Wang HF

References
1.  Sakorafas GH, Milingos D, Peros G. Asymptomatic cholelithiasis: is cholecystectomy really needed? A critical reappraisal 15 years after the introduction of laparoscopic cholecystectomy. Dig Dis Sci. 2007;52:1313-1325.  [PubMed]  [DOI]
2.  Freitas ML, Bell RL, Duffy AJ. Choledocholithiasis: evolving standards for diagnosis and management. World J Gastroenterol. 2006;12:3162-3167.  [PubMed]  [DOI]
3.  Martin DJ, Vernon DR, Toouli J. Surgical versus endoscopic treatment of bile duct stones. Cochrane Database Syst Rev. 2006;CD003327.  [PubMed]  [DOI]
4.  Slanetz PJ, Boland GW, Mueller PR. Imaging and interventional radiology in laparoscopic injuries to the gallbladder and biliary system. Radiology. 1996;201:595-603.  [PubMed]  [DOI]
5.  Portincasa P, Moschetta A, Petruzzelli M, Palasciano G, Di Ciaula A, Pezzolla A. Gallstone disease: Symptoms and diagnosis of gallbladder stones. Best Pract Res Clin Gastroenterol. 2006;20:1017-1029.  [PubMed]  [DOI]
6.  Lakatos L, Mester G, Reti G, Nagy A, Lakatos PL. Selection criteria for preoperative endoscopic retrograde cholangiopancreatography before laparoscopic cholecystectomy and endoscopic treatment of bile duct stones: results of a retrospective, single center study between 1996-2002. World J Gastroenterol. 2004;10:3495-3499.  [PubMed]  [DOI]
7.  Livingston EH, Miller JA, Coan B, Rege RV. Indications for selective intraoperative cholangiography. J Gastrointest Surg. 2005;9:1371-1377.  [PubMed]  [DOI]
8.  Majeed AW, Ross B, Johnson AG, Reed MW. Common duct diameter as an independent predictor of choledocholithiasis: is it useful? Clin Radiol. 1999;54:170-172.  [PubMed]  [DOI]
9.  Machi J, Oishi AJ, Tajiri T, Murayama KM, Furumoto NL, Oishi RH. Routine laparoscopic ultrasound can significantly reduce the need for selective intraoperative cholangiography during cholecystectomy. Surg Endosc. 2007;21:270-274.  [PubMed]  [DOI]
10.  Ledniczky G, Fiore N, Bognár G, Ondrejka P, Grosfeld JL. Evaluation of perioperative cholangiography in one thousand laparoscopic cholecystectomies. Chirurgia (Bucur). 2006;101:267-272.  [PubMed]  [DOI]
11.  Guarise A, Baltieri S, Mainardi P, Faccioli N. Diagnostic accuracy of MRCP in choledocholithiasis. Radiol Med. 2005;109:239-251.  [PubMed]  [DOI]
12.  Chang L, Lo S, Stabile BE, Lewis RJ, Toosie K, de Virgilio C. Preoperative versus postoperative endoscopic retrograde cholangiopancreatography in mild to moderate gallstone pancreatitis: a prospective randomized trial. Ann Surg. 2000;231:82-87.  [PubMed]  [DOI]
13.  Wai CT, Seto KY, Sutedja DS. Clinics in diagnostic imaging (115). Extraluminal biliary tree obstruction due to compression by pancreatic head tumour. Singapore Med J. 2007;48:361-366; quiz 367.  [PubMed]  [DOI]
14.  Ney MV, Maluf-Filho F, Sakai P, Zilberstein B, Gama-Rodrigues J, Rosa H. Echo-endoscopy versus endoscopic retrograde cholangiography for the diagnosis of choledocholithiasis: the influence of the size of the stone and diameter of the common bile duct. Arq Gastroenterol. 2005;42:239-243.  [PubMed]  [DOI]
15.  Nathanson LK, O'Rourke NA, Martin IJ, Fielding GA, Cowen AE, Roberts RK, Kendall BJ, Kerlin P, Devereux BM. Postoperative ERCP versus laparoscopic choledochotomy for clearance of selected bile duct calculi: a randomized trial. Ann Surg. 2005;242:188-192.  [PubMed]  [DOI]
16.  Koo KP, Traverso LW. Do preoperative indicators predict the presence of common bile duct stones during laparoscopic cholecystectomy? Am J Surg. 1996;171:495-499.  [PubMed]  [DOI]
17.  Alponat A, Kum CK, Rajnakova A, Koh BC, Goh PM. Predictive factors for synchronous common bile duct stones in patients with cholelithiasis. Surg Endosc. 1997;11:928-932.  [PubMed]  [DOI]
18.  Bose SM, Mazumdar A, Prakash VS, Kocher R, Katariya S, Pathak CM. Evaluation of the predictors of choledocholithiasis: comparative analysis of clinical, biochemical, radiological, radionuclear, and intraoperative parameters. Surg Today. 2001;31:117-122.  [PubMed]  [DOI]
19.  Hayat JO, Loew CJ, Asrress KN, McIntyre AS, Gorard DA. Contrasting liver function test patterns in obstructive jaundice due to biliary strictures [corrected] and stones. QJM. 2005;98:35-40.  [PubMed]  [DOI]
20.  Pilleul F. Asymptomatic or paucisymptomatic CBD dilatation on US after cholecystectomy: management. J Radiol. 2006;87:494-499.  [PubMed]  [DOI]
21.  Testoni PA. Preventing post-ERCP pancreatitis: where are we? JOP. 2003;4:22-32.  [PubMed]  [DOI]
22.  Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ, Moore JP, Fennerty MB, Ryan ME, Shaw MJ. Complications of endoscopic biliary sphincterotomy. N Engl J Med. 1996;335:909-918.  [PubMed]  [DOI]
23.  Freeman ML, DiSario JA, Nelson DB, Fennerty MB, Lee JG, Bjorkman DJ, Overby CS, Aas J, Ryan ME, Bochna GS. Risk factors for post-ERCP pancreatitis: a prospective, multicenter study. Gastrointest Endosc. 2001;54:425-434.  [PubMed]  [DOI]
24.  Varadarajulu S, Eloubeidi MA, Wilcox CM, Hawes RH, Cotton PB. Do all patients with abnormal intraoperative cholangiogram merit endoscopic retrograde cholangiopancreatography? Surg Endosc. 2006;20:801-805.  [PubMed]  [DOI]
25.  Katz D, Nikfarjam M, Sfakiotaki A, Christophi C. Selective endoscopic cholangiography for the detection of common bile duct stones in patients with cholelithiasis. Endoscopy. 2004;36:1045-1049.  [PubMed]  [DOI]
26.  Rösch T, Meining A, Frühmorgen S, Zillinger C, Schusdziarra V, Hellerhoff K, Classen M, Helmberger H. A prospective comparison of the diagnostic accuracy of ERCP, MRCP, CT, and EUS in biliary strictures. Gastrointest Endosc. 2002;55:870-876.  [PubMed]  [DOI]
27.  Chang L, Lo SK, Stabile BE, Lewis RJ, de Virgilio C. Gallstone pancreatitis: a prospective study on the incidence of cholangitis and clinical predictors of retained common bile duct stones. Am J Gastroenterol. 1998;93:527-531.  [PubMed]  [DOI]
28.  Neoptolemos JP, London N, Bailey I, Shaw D, Carr-Locke DL, Fossard DP, Moossa AR. The role of clinical and biochemical criteria and endoscopic retrograde cholangiopancreatography in the urgent diagnosis of common bile duct stones in acute pancreatitis. Surgery. 1986;100:732-742.  [PubMed]  [DOI]
29.  Leitman IM, Fisher ML, McKinley MJ, Rothman R, Ward RJ, Reiner DS, Tortolani AJ. The evaluation and management of known or suspected stones of the common bile duct in the era of minimal access surgery. Surg Gynecol Obstet. 1993;176:527-533.  [PubMed]  [DOI]
30.  Hariri J, Øster A. The negative predictive value of p16INK4a to assess the outcome of cervical intraepithelial neoplasia 1 in the uterine cervix. Int J Gynecol Pathol. 2007;26:223-228.  [PubMed]  [DOI]