J Gastrointest Surg DOI 10.1007/s11605-014-2530-4
ORIGINAL ARTICLE
Surgical and Endoscopic Management of Remnant Cystic Duct Lithiasis After Cholecystectomy—a Case Series Michael R. Phillips & Mark Joseph & Evan S. Dellon & Ian Grimm & Timothy M. Farrell & Christopher C. Rupp
Received: 18 December 2013 / Accepted: 21 April 2014 # 2014 The Society for Surgery of the Alimentary Tract
Abstract Introduction Postcholecystectomy syndrome (PCS) as a result of remnant cystic duct lithiasis (RCDL), or gallstones within the cystic duct after cholecystectomy, can cause persistent or recurrent symptoms after cholecystectomy. Study Design A retrospective descriptive analysis was performed for all patients with RDCL at a single institution between 2001 and 2012. Details of presentation, diagnosis, and surgical and endoscopic treatments, and outcomes were collected and analyzed. Results Twelve patients with RCDL were identified. The interval between cholecystectomy to RCDL discovery was 34.2 months (range 0.5–168 months). On a standard liver enzyme panel, 75 % of patients had derangements in ≥1 indices, with the most common single laboratory test abnormality occurring in gamma-glutamyl transferase (GGT) (80 %). Eight operative reports noted that the cystic duct was noticeably dilated at the time of cholecystectomy. Two patients developed a cystic duct leak (Strasberg type A bile duct injury) postoperatively, which was managed nonoperatively. Six cases of RCDL required surgery, and six were managed endoscopically. Conclusion RCDL is a potential cause of postcholecystectomy syndrome, but the true incidence is unknown. Laboratory analysis and imaging are helpful in establishing the diagnosis of RCDL. Endoscopic therapy has a role in the treatment of RCDL, but surgical excision of the remnant cystic duct lithiasis may be required. Keywords Remnant cystic duct lithiasis (RCDL) . Cholecystectomy . Postcholecystectomy syndrome Abbreviations RCDL Remnant cystic duct lithiasis GGT Gamma-glutamyl transferase PCS Postcholecystectomy syndrome AST Aspartate aminotransferase ALT Alanine aminotransferase M. R. Phillips (*) : M. Joseph : T. M. Farrell Department of Surgery, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27514, USA e-mail: [email protected] E. S. Dellon : I. Grimm Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27514, USA C. C. Rupp Department of Surgery, Prevea Health, 1715 Dousman Street, Green Bay, WI 54303, USA
Introduction Cholecystectomy is the most common abdominal operation performed by general surgeons, with an estimated 750,000 cases in the USA each year.1 Most cholecystectomies are performed due to the sequelae of cholelithiasis, with the vast majority of patients experiencing complete symptom relief after cholecystectomy. However, approximately 5 % of patients continue to have symptoms after cholecystectomy and are sometimes designated as – suffering from postcholecystectomy syndrome (PCS).2 6 It has been suggested that the majority of patients who develop PCS actually suffer from nonbiliary disorders, such as gastroesophageal reflux disease, peptic ulcer disease, nonulcer (functional) dyspepsia, or chronic pancreatitis.5 However, a small percentage of patients truly have symptoms attributable to the extrahepatic biliary tree, from etiologies such as biliary strictures, retained choledocholithiasis,
J Gastrointest Surg
sphincter of Oddi dysfunction, and remnant cystic duct lithiasis (RCDL). The etiology of true RCDL is presumed to be from calculi remaining from the initial cholecystectomy, rather than calculi developing de novo because of a subtotal cholecystectomy. Estimates suggest that at the time of cholecystectomy, nearly 15 % of patients have lithiasis present in the cystic duct, which has been shown to correlate preoperatively with choledocholithiasis, elevated liver enzymes, and pain in the months preceding cholecystectomy. Some series have reported that up to 30 % of patients suffering from PCS have RCDL as the , etiology of persistent symptoms.7 8 The true incidence of retained calculi in the cystic duct stump, however, has not been described. Most published series are small and aggregate heterogeneous disease processes, including patients with remnant gallbladders secondary to intentional or unintentional subtotal cholecystectomy along with patients truly having retained calculi in the cystic duct , stump.9 10 Estimating the actual incidence of remnant cystic duct lithiasis is difficult, if not impossible, because patients may obtain follow-up care from centers distinct from where the original procedure was performed. Given the difficulty in determining the burden of disease attributable to RCDL, we designed a study to evaluate our institutional experience with RCDL and herein describe the largest case series to date specific for the condition. Our primary goal was to define risk factors associated with RCDL. Secondarily, while the historical gold standard for the treatment of RCDL has been surgical excision of the cystic duct remnant, we describe our experience in diagnosing and treating these patients using a multidisciplinary approach.
Materials and Methods We conducted a retrospective study of all patients undergoing cholecystectomy or endoscopic retrograde cholangiopancreatography (ERCP) from August 2001 to May 2012 at the University of North Carolina (UNC) Hospitals. Electronic medical record and endoscopy databases were queried. Patients who underwent surgery for RCDL, or patients identified at ERCP as having RCDL, were selected for study inclusion in this case series. For each subject, we recorded demographic information, existing comorbidities, preoperative and postoperative symptoms, imaging results, operative and pathologic findings, postoperative complications, and mortality. Follow-up was conducted using postoperative clinic notes to monitor for recurrent symptoms. Statistical analysis was not performed given the small number of patients identified with the disease process. This study was approved by the Institutional Review Board of the UNC School of Medicine.
Results A total of 12 patients (5 men, 7 women) with RCDL were identified. The mean age at presentation for RCDL was 38.3 years (range 24–57 years), and average body mass index was 35.2 kg/m2. The mean interval from initial cholecystectomy to discovery of RCDL was 34.2 months (range 0.5–168 months). Final pathologic diagnoses at the initial cholecystectomy included chronic cholecystitis (seven), acute cholecystitis (four), and gangrenous cholecystitis (one). Only four of the patients had their initial surgery at our institution, and operative procedures performed included eight laparoscopic cholecystectomies (one with intraoperative cholangiogram) and two open cholecystectomies. The reasons for conversion to an open procedure or the omission of intraoperative cholangiogram at the time of initial surgery were not available. Each of the 12 patients had symptoms that persisted or recurred after their initial cholecystectomy, similar in quality to the pain experienced at their initial presentation. All patients reported right upper quadrant or epigastric pain. Four patients reported nausea/emesis. Three patients were discovered to have varying degrees of jaundice. Of note, 75 % of patients had derangements in ≥1 indices on a standard liver enzyme panel (total bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, and gamma-glutamyl transferase [GGT]). The most common laboratory abnormality occurred in GGT (abnormal in 80 % of those tested), followed by AST, ALT, and alkaline phosphatase (each abnormal in 58.3 %) (Table 1). Table 1 Liver enzyme panels for each patient with remnant cystic duct stump calculi at time of discovery Patient
TBili
AST
ALT
AlkPhos
GGT
1 2 3 4 5 6 7 8 9
0.3 4.1 1.4 0.7 1.3 1.5 3.0 0.1 1.3
25 96 67 103 92 156 925 17 31
22 316 209 128 370 269 819 23 49
10 415 160 150 70 181 185 73 125
20 527 316 157 N/A 311 889 N/A 190
10 11 12 Total abnormal (%)
0.7 0.7 0.6 50
32 144 31 58.3
44 115 30 58.3
130 102 127 58.3
159 401 15 80
Elevated values are listed in bold TBili total bilirubin (upper limit of normal 1.2 mg/dL), AST aspartate aminotransferase (upper limit of normal 55 U/L), ALT alanine aminotransferase (upper limit of normal 72 U/L), AlkPhos alkaline phosphatase (upper limit of normal 126 U/L), GGT gamma-glutamyl transferase (upper limit of normal 68 U/L), N/A not available
J Gastrointest Surg
Initial operations consisted of nine laparoscopic and three open cholecystectomies. No choledocholithiasis or cystic duct calculi were noted in any of the 12 initial cholecystectomies. Intraoperative cholangiography was performed in only one cholecystectomy (laparoscopic) without discovery of cystic duct lithiasis. While the actual diameter of the cystic duct was available in only three operative reports (5, >10, >10 mm), eight operative reports made specific notation that the cystic duct was noticeably dilated at the time of cholecystectomy. Only one operative report stated that the cystic duct was normal in caliber. Cystic duct ligation techniques were recorded. Five cystic ducts were ligated in what is considered “usual” laparoscopic means at our institution (application of standard titanium clip or Hem-o-lok® clip [Teleflex, Research Triangle Park, NC]). Of the remainder, four cystic ducts required a stapler transection, one required an Endoloop® (Ethicon Endo-Surgery, Cincinnati, OH), and two required hand-sewn closure techniques. Both the use of Endoloop® and suture ligation techniques were noted in the operative report to be necessary due to the enlarged diameter of the cystic duct. Two patients developed cystic duct stump leaks, also known as Strasberg type A bile duct injuries,11 after the initial surgery. Both injuries were successfully treated by percutaneous drainage. Radiologic imaging was utilized extensively in the evaluation of PCS in our series. Of all imaging modalities, magnetic resonance cholangiopancreatography (MRCP) was the most often utilized to obtain the diagnosis of RCDL (six). The remaining calculi were discovered by computerized tomography (CT) scan (two), ultrasonography (two), operative cholangiography (one), and ERCP (one) (Fig. 1). In most patients, there were multiple radiologic imaging modalities utilized in the evaluation process, with no discernible order
Fig. 1 Retained cystic duct calculi identified by endoscopic retrograde cholangiography (a) and MRCP (b). Arrow denotes filling defects identified in each imaging modality
identifiable. The relative utilization of the various common imaging modalities is presented in Table 2. Management of RCDL included several modalities. There was an equal distribution in the number of patients undergoing reoperation (six) compared to endoscopic treatment alone (six). Two of the six patients represented with the clinical constellation of symptoms and findings consistent with acute remnant cystic duct obstruction and inflammation that required urgent surgical intervention. These symptoms and findings included persistent right upper quadrant pain for >24 h, nausea and emesis, abnormal LFTs, leukocytosis, and cystic duct cholelithiasis with inflammatory changes on radiographic imaging. Due to the nature of clinical presentation, the patients were taken directly to surgery without attempted endoscopic intervention. Of the remaining four patients treated surgically, three had failed attempts to remove stones endoscopically, including one patient with Mirizzi syndrome and one patient with extravasation of contrast at initial ERCP. The final patient elected to proceed to surgery without attempted endoscopic stone retrieval. Of the patients undergoing repeat surgery, all were attempted laparoscopically but required conversion to an open procedure due to dense adhesions/chronic inflammation in the porta hepatis. Intraoperative cholangiography revealed the presence of concomitant choledocholithiasis in both patients, and a common bile duct exploration was employed for calculi removal at the time of reoperation. Six patients were managed by ERCP; three with sphincterotomy and balloon extraction; and one with sphincterotomy, lithotripsy, and basket retrieval. One patient required only balloon sweep of the common bile duct. In the remaining patient, the cystic duct stone could not be readily retrieved by ERCP and no further management was employed due to the patient’s preference.
J Gastrointest Surg Table 2 Radiologic imaging modalities utilized in the evaluation of postcholecystectomy syndrome and their accuracy in identifying remnant cystic duct lithiasis (RCDL) Radiologic study
Patients undergoing imaging modality
Number of RCDL identified
Accuracy (%)
Ultrasonography CT scan MRI
9 7 9
5 5 8
55.6 71.4 88.9
Of the 12 patients treated with surgical or endoscopic intervention for RCDL at our institution, 9 were seen in follow-up clinic visits by the attending gastroenterologist or final operative surgeon. Two patients were lost to follow-up. One patient did not live local to our institution and after incomplete endoscopic treatment preferred no further endoscopic intervention or surgical referral. Of the nine patients with available follow-up clinic notes, seven experienced symptom resolution (77.8 %) with a mean follow-up of 11.8 months. Of the two patients with persistent symptoms, notes suggested that one patient may have had pain from fatty liver disease or a question of right upper quadrant incisional hernia and the other patient had ongoing work-up for persistent RCDL after initial endoscopic lithotripsy.
Discussion The burden of disease attributable to RCDL as a cause of postcholecystectomy syndrome has not been well-defined, and estimates vary in the literature. It is difficult to quantify the exact incidence at our institution, but RCDL is a rare cause of postcholecystectomy syndrome in our patient population. Rozsos et al. estimated that the cystic duct stump syndrome, or an excessively long cystic duct stump, is the cause of persistent or recurrent symptoms in 16 % of patients with PCS.12 There was no indication in this study regarding how many patients had RCDL versus an isolated cystic duct stump without calculi. In a recent study by Palanivelu et al., the incidence of remnant cystic duct stump calculi causing symptoms in patients undergoing standard laparoscopic cholecystectomy was estimated at 0.02 %.9 However, this estimation was based on the number of patients undergoing remnant resection at their institution and did not include patients undergoing successful endoscopic retrieval. In addition, it is unclear from this study how many patients had their initial operation at the same institution as the cystic duct stump excision, and thus, the denominator used may not be representative of the true extent of the disease burden. This exact situation is frequently encountered at our institution, and nearly half of the patients in the present series had their initial cholecystectomy at another facility. Thus, it is not possible for
us to accurately state the incidence of symptomatic RCDL on the basis of our single-institution study. In this series, symptoms associated with PCS in cases of RCDL, specifically right upper quadrant pain, appear to be associated with dilation of a hollow viscus, as there was a high rate of symptom resolution after both endoscopic and surgical interventions. Surgical pathology results and dense adhesions noted at the time of surgery suggest that the presence of RCDL leads to associated portal inflammation. However, the resolution of PCS in 77.8 % of patients in this series, regardless of method of treatment, suggests that ongoing symptoms are related to the presence of stones themselves within the hollow viscus. Proposed risk factors for recurrent symptoms due to RCDL include a cystic duct stump >1 cm in length, a low cystic duct insertion into the common bile duct, and use of nonabsorbable , , material for ligation of the cystic duct stump.9 13 14 The acceptable length of a cystic duct remnant in the laparoscopic era has been an area of discussion due to the fact that one technical aspect of a safe dissection within the hepatocystic triangle is to delineate the cystic duct at the cystic duct/gallbladder-infundibulum junction. In theory, this minimizes the chance for injury of the common bile duct. However, if the cystic duct is ligated in this location, there is often a long cystic duct remnant present. Previous studies have concluded that in more than 50 % of cholecystectomies, the length of the remnant cystic duct is ≥3 cm.15 With our current series, endoscopic and surgical reports did not describe the exact location of the stones in relation to the site of surgical transection or the origin of the cystic duct. One patient was noted to have a large stone within the distal cystic duct remnant causing Mirizzi syndrome at the time of representation. This makes it difficult to describe the exact relationship between cystic duct length and the occurrence of RCDL. In our opinion, given the potentially devastating consequences of common bile duct injury, a long cystic duct remnant confers less risk than aggressive dissection near the common bile duct. This assertion is strengthened by the fact that several of the patients in our study with RCDL were managed by endoscopic therapies alone. An interesting observation in our series was that the dictating surgeons noted a subjectively dilated cystic duct in 66.7 % of these cases, with two estimated to be >1 cm in diameter. This parallels the likelihood of surgeons utilizing special techniques for ligation of the cystic duct at the time of cholecystectomy, with 58.3 % choosing either a stapling device, ligation loop, or suturing method over titanium or Hem-o-lok clips, as is common at our institution. This detail may be an important indicator to the surgeon about the possibility of calculi within the cystic duct itself that should prompt further diagnostic modalities, such as use of intraoperative cholangiography. Notably, only one patient undergoing cholecystectomy in our study had a concomitant cholangiogram performed at the
J Gastrointest Surg Fig. 2 Current institutional algorithm used for the management of postcholecystectomy syndrome and remnant cystic duct lithiasis
time of initial operation. Despite numerous well-designed studies evaluating the value of intraoperative cholangiography, there is still a lively discussion regarding the utility of routine versus selective cholangiography. It seems reasonable to suggest that if a selective approach is used for the identification of choledocholithiasis, then a dilated cystic duct may be a potential indication to proceed with cholangiography. However, the utility and predictive value of this strategy would need further investigation. Radiologic imaging guidelines for the evaluation of patients with suspected PCS do not exist. Previous studies evaluating the diagnostic accuracy of various radiologic imaging modalities have found ultrasonography and MRCP to be 60 and 92 % accurate, respectively.9 Our results are similar, showing the accuracy of ultrasonography and MRCP at 55.6 and 88.9 %, respectively. While these findings support the use of MRCP as the imaging modality of choice in the evaluation of suspected PCS, however, the additional cost of MRCP as well as the availability and local expertise regarding the interpretation of MCRP images must be considered. Anecdotally, our initial strategy for use of radiologic imaging began with the least expensive and most readily available option, ultrasonography. If this was unrevealing, then computerized tomography and magnetic resonance imaging were employed for further investigation. Although the accuracy of ultrasonography is lower than MRCP, it may be a more reasonable option in the initial evaluation, when other diagnoses are being entertained. Our current institutional algorithm omits the use of ultrasonography in postcholecystectomy patients with abnormal liver function tests (Fig. 2). The delay of nearly 4 years in our study between cholecystectomy and diagnosis of RCDL
speaks to the potential difficulty of this diagnosis and the need of a high index of suspicion in patients with persistent symptoms.
Conclusion ,
Management of RCDL has traditionally been surgical.8 16 With the advent of advanced minimally invasive techniques, successful laparoscopic management of this condition has , been reported,9 17 and our institution’s current algorithm reflects these changes (Fig. 2). In our experience, the six patients who required operative intervention were ultimately treated through an open approach after conversion from laparoscopy. In all patients, the reason for conversion was dense chronic inflammatory tissue in the porta hepatis and inability to safely visualize the vasculo-biliary anatomy. Our institutional bias in these situations is for early conversion to open techniques to minimize the potential risk for vasculo-biliary injury, although we acknowledge that this is institution-dependent. Of note, six of the patients in our series were managed by endoscopic techniques with successful calculi extraction from the cystic duct remnant. This approach has previously been described, but the actual utilization and availability of endoscopic techniques are not clearly defined.18 To our knowledge, this high rate of successful endoscopic management of remnant cystic duct calculi has not been described before. In our experience, endoscopy is a reasonable initial treatment option as it provides diagnostic and in some cases therapeutic alternatives. The endoscopic approach would be favored as initial therapy in patients presenting without recurrent inflammation of the
J Gastrointest Surg
remnant cystic duct. The only contraindications to endoscopic intervention would be those associated with the endoscopic procedure itself (inability to cannulate the sphincter of Oddi, coagulopathy, etc.). The early involvement of a biliary endoscopist in the evaluation and treatment of PCS is crucial to the successful management of RCDL and may obviate the need for repeat surgery altogether. In conclusion, RCDL can be a cause of postcholecystectomy syndrome and the diagnosis should be entertained in a patient with persistent or recurrent symptoms after cholecystectomy. The ultimate diagnosis of RCDL is difficult and requires a multidisciplinary approach, for successful management. In many circumstances, surgery can be avoided by endoscopic cystic duct stone retrieval methods.
Conflict of Interest All authors declare that they have no conflicts of interest. This paper has not been published previously. Funding Institutional support was provided by the Department of Surgery at the University of North Carolina at Chapel Hill. There are no relevant financial disclosures.
References 1. Russo MW, Wei JT, Thiny MT, Gangarosa LM, et al. Digestive and liver diseases statistics, 2004. Gastroenterology 2004;126:1448-53. 2. Zhou PH, Liu FL, Yao LQ, Qin XY. Endoscopic diagnosis and treatment of post-cholecystectomy syndrome. Hepatobiliary Pancreat Dis Int 2003;2:117-20. 3. Mergener K, Clavien PA, Branch MS, Baillie J. A stone in a grossly dilated cystic duct stump: a rare cause of postcholecystectomy pain. Am J Gastroenterol 1999;94:229-31.
4. Goenka MK, Kochhar R, Nagi B, Bhasin DK, et al. Endoscopic retrograde cholangiopancreatography in postcholecystectomy syndrome. J Assoc Physicians India 1996;44:119-22. 5. Rogy MA, Fugger R, Herbst F, Schulz F. Reoperation after cholecystectomy. The role of the cystic duct stump. HPB Surg 1991;4:12934; discussion 34-5. 6. Stefanini P, Carboni M, Patrassi N, Loriga P, et al. Factors influencing the long term results of cholecystectomy. Surg Gynecol Obstet 1974;139:734-8. 7. Gui GP, Cheruvu CV, West N, Sivaniah K, et al. Is cholecystectomy effective treatment for symptomatic gallstones? Clinical outcome after long-term follow-up. Ann R Coll Surg Engl 1998;80:25-32. 8. Walsh RM, Ponsky JL, Dumot J. Retained gallbladder/cystic duct remnant calculi as a cause of postcholecystectomy pain. Surg Endosc 2002;16:981-4. 9. Palanivelu C, Rangarajan M, Jategaonkar PA, Madankumar MV, et al. Laparoscopic management of remnant cystic duct calculi: a retrospective study. Ann R Coll Surg Engl 2009;91:25-9. 10. Pernice LM, Andreoli F. Laparoscopic treatment of stone recurrence in a gallbladder remnant: report of an additional case and literature review. J Gastrointest Surg 2009;13:2084-91. 11. Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of biliary injury during laparoscopic cholecystectomy. J Am Coll Surg 1995;180:101-25. 12. Rozsos I, Magyarodi Z, Orban P. [Cystic duct syndrome and minimally invasive surgery]. Orv Hetil 1997;138:2397-401. 13. Sitenko VM, Nechai AI, Stukalov VV, Kalashnikov SA. [Large stump of the cystic duct]. Vestn Khir Im I I Grek 1976;116:56-9. 14. Freud M, Djaldetti M, De Vries A, Leffkowitz M. Postcholecystectomy syndrome: a survey of 114 patients after biliary tract surgery. Gastroenterologia 1960;93:288-93. 15. Sezeur A, Akel K. Cystic duct remnant calculi after cholecystectomy. J Visc Surg 2011;148:e287-90. 16. Glenn F, McSherry CK. Secondary abdominal operations for symptoms following biliary tract surgery. Surg Gynecol Obstet 1965;121:979-88. 17. Chowbey PK, Bandyopadhyay SK, Sharma A, Khullar R, et al. Laparoscopic reintervention for residual gallstone disease. Surg Laparosc Endosc Percutan Tech 2003;13:31-5. 18. Benninger J, Rabenstein T, Farnbacher M, Keppler J, et al. Extracorporeal shockwave lithotripsy of gallstones in cystic duct remnants and Mirizzi syndrome. Gastrointest Endosc 2004;60:454-9.
ORIGINAL ARTICLE
Surgical and Endoscopic Management of Remnant Cystic Duct Lithiasis After Cholecystectomy—a Case Series Michael R. Phillips & Mark Joseph & Evan S. Dellon & Ian Grimm & Timothy M. Farrell & Christopher C. Rupp
Received: 18 December 2013 / Accepted: 21 April 2014 # 2014 The Society for Surgery of the Alimentary Tract
Abstract Introduction Postcholecystectomy syndrome (PCS) as a result of remnant cystic duct lithiasis (RCDL), or gallstones within the cystic duct after cholecystectomy, can cause persistent or recurrent symptoms after cholecystectomy. Study Design A retrospective descriptive analysis was performed for all patients with RDCL at a single institution between 2001 and 2012. Details of presentation, diagnosis, and surgical and endoscopic treatments, and outcomes were collected and analyzed. Results Twelve patients with RCDL were identified. The interval between cholecystectomy to RCDL discovery was 34.2 months (range 0.5–168 months). On a standard liver enzyme panel, 75 % of patients had derangements in ≥1 indices, with the most common single laboratory test abnormality occurring in gamma-glutamyl transferase (GGT) (80 %). Eight operative reports noted that the cystic duct was noticeably dilated at the time of cholecystectomy. Two patients developed a cystic duct leak (Strasberg type A bile duct injury) postoperatively, which was managed nonoperatively. Six cases of RCDL required surgery, and six were managed endoscopically. Conclusion RCDL is a potential cause of postcholecystectomy syndrome, but the true incidence is unknown. Laboratory analysis and imaging are helpful in establishing the diagnosis of RCDL. Endoscopic therapy has a role in the treatment of RCDL, but surgical excision of the remnant cystic duct lithiasis may be required. Keywords Remnant cystic duct lithiasis (RCDL) . Cholecystectomy . Postcholecystectomy syndrome Abbreviations RCDL Remnant cystic duct lithiasis GGT Gamma-glutamyl transferase PCS Postcholecystectomy syndrome AST Aspartate aminotransferase ALT Alanine aminotransferase M. R. Phillips (*) : M. Joseph : T. M. Farrell Department of Surgery, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27514, USA e-mail: [email protected] E. S. Dellon : I. Grimm Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27514, USA C. C. Rupp Department of Surgery, Prevea Health, 1715 Dousman Street, Green Bay, WI 54303, USA
Introduction Cholecystectomy is the most common abdominal operation performed by general surgeons, with an estimated 750,000 cases in the USA each year.1 Most cholecystectomies are performed due to the sequelae of cholelithiasis, with the vast majority of patients experiencing complete symptom relief after cholecystectomy. However, approximately 5 % of patients continue to have symptoms after cholecystectomy and are sometimes designated as – suffering from postcholecystectomy syndrome (PCS).2 6 It has been suggested that the majority of patients who develop PCS actually suffer from nonbiliary disorders, such as gastroesophageal reflux disease, peptic ulcer disease, nonulcer (functional) dyspepsia, or chronic pancreatitis.5 However, a small percentage of patients truly have symptoms attributable to the extrahepatic biliary tree, from etiologies such as biliary strictures, retained choledocholithiasis,
J Gastrointest Surg
sphincter of Oddi dysfunction, and remnant cystic duct lithiasis (RCDL). The etiology of true RCDL is presumed to be from calculi remaining from the initial cholecystectomy, rather than calculi developing de novo because of a subtotal cholecystectomy. Estimates suggest that at the time of cholecystectomy, nearly 15 % of patients have lithiasis present in the cystic duct, which has been shown to correlate preoperatively with choledocholithiasis, elevated liver enzymes, and pain in the months preceding cholecystectomy. Some series have reported that up to 30 % of patients suffering from PCS have RCDL as the , etiology of persistent symptoms.7 8 The true incidence of retained calculi in the cystic duct stump, however, has not been described. Most published series are small and aggregate heterogeneous disease processes, including patients with remnant gallbladders secondary to intentional or unintentional subtotal cholecystectomy along with patients truly having retained calculi in the cystic duct , stump.9 10 Estimating the actual incidence of remnant cystic duct lithiasis is difficult, if not impossible, because patients may obtain follow-up care from centers distinct from where the original procedure was performed. Given the difficulty in determining the burden of disease attributable to RCDL, we designed a study to evaluate our institutional experience with RCDL and herein describe the largest case series to date specific for the condition. Our primary goal was to define risk factors associated with RCDL. Secondarily, while the historical gold standard for the treatment of RCDL has been surgical excision of the cystic duct remnant, we describe our experience in diagnosing and treating these patients using a multidisciplinary approach.
Materials and Methods We conducted a retrospective study of all patients undergoing cholecystectomy or endoscopic retrograde cholangiopancreatography (ERCP) from August 2001 to May 2012 at the University of North Carolina (UNC) Hospitals. Electronic medical record and endoscopy databases were queried. Patients who underwent surgery for RCDL, or patients identified at ERCP as having RCDL, were selected for study inclusion in this case series. For each subject, we recorded demographic information, existing comorbidities, preoperative and postoperative symptoms, imaging results, operative and pathologic findings, postoperative complications, and mortality. Follow-up was conducted using postoperative clinic notes to monitor for recurrent symptoms. Statistical analysis was not performed given the small number of patients identified with the disease process. This study was approved by the Institutional Review Board of the UNC School of Medicine.
Results A total of 12 patients (5 men, 7 women) with RCDL were identified. The mean age at presentation for RCDL was 38.3 years (range 24–57 years), and average body mass index was 35.2 kg/m2. The mean interval from initial cholecystectomy to discovery of RCDL was 34.2 months (range 0.5–168 months). Final pathologic diagnoses at the initial cholecystectomy included chronic cholecystitis (seven), acute cholecystitis (four), and gangrenous cholecystitis (one). Only four of the patients had their initial surgery at our institution, and operative procedures performed included eight laparoscopic cholecystectomies (one with intraoperative cholangiogram) and two open cholecystectomies. The reasons for conversion to an open procedure or the omission of intraoperative cholangiogram at the time of initial surgery were not available. Each of the 12 patients had symptoms that persisted or recurred after their initial cholecystectomy, similar in quality to the pain experienced at their initial presentation. All patients reported right upper quadrant or epigastric pain. Four patients reported nausea/emesis. Three patients were discovered to have varying degrees of jaundice. Of note, 75 % of patients had derangements in ≥1 indices on a standard liver enzyme panel (total bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, and gamma-glutamyl transferase [GGT]). The most common laboratory abnormality occurred in GGT (abnormal in 80 % of those tested), followed by AST, ALT, and alkaline phosphatase (each abnormal in 58.3 %) (Table 1). Table 1 Liver enzyme panels for each patient with remnant cystic duct stump calculi at time of discovery Patient
TBili
AST
ALT
AlkPhos
GGT
1 2 3 4 5 6 7 8 9
0.3 4.1 1.4 0.7 1.3 1.5 3.0 0.1 1.3
25 96 67 103 92 156 925 17 31
22 316 209 128 370 269 819 23 49
10 415 160 150 70 181 185 73 125
20 527 316 157 N/A 311 889 N/A 190
10 11 12 Total abnormal (%)
0.7 0.7 0.6 50
32 144 31 58.3
44 115 30 58.3
130 102 127 58.3
159 401 15 80
Elevated values are listed in bold TBili total bilirubin (upper limit of normal 1.2 mg/dL), AST aspartate aminotransferase (upper limit of normal 55 U/L), ALT alanine aminotransferase (upper limit of normal 72 U/L), AlkPhos alkaline phosphatase (upper limit of normal 126 U/L), GGT gamma-glutamyl transferase (upper limit of normal 68 U/L), N/A not available
J Gastrointest Surg
Initial operations consisted of nine laparoscopic and three open cholecystectomies. No choledocholithiasis or cystic duct calculi were noted in any of the 12 initial cholecystectomies. Intraoperative cholangiography was performed in only one cholecystectomy (laparoscopic) without discovery of cystic duct lithiasis. While the actual diameter of the cystic duct was available in only three operative reports (5, >10, >10 mm), eight operative reports made specific notation that the cystic duct was noticeably dilated at the time of cholecystectomy. Only one operative report stated that the cystic duct was normal in caliber. Cystic duct ligation techniques were recorded. Five cystic ducts were ligated in what is considered “usual” laparoscopic means at our institution (application of standard titanium clip or Hem-o-lok® clip [Teleflex, Research Triangle Park, NC]). Of the remainder, four cystic ducts required a stapler transection, one required an Endoloop® (Ethicon Endo-Surgery, Cincinnati, OH), and two required hand-sewn closure techniques. Both the use of Endoloop® and suture ligation techniques were noted in the operative report to be necessary due to the enlarged diameter of the cystic duct. Two patients developed cystic duct stump leaks, also known as Strasberg type A bile duct injuries,11 after the initial surgery. Both injuries were successfully treated by percutaneous drainage. Radiologic imaging was utilized extensively in the evaluation of PCS in our series. Of all imaging modalities, magnetic resonance cholangiopancreatography (MRCP) was the most often utilized to obtain the diagnosis of RCDL (six). The remaining calculi were discovered by computerized tomography (CT) scan (two), ultrasonography (two), operative cholangiography (one), and ERCP (one) (Fig. 1). In most patients, there were multiple radiologic imaging modalities utilized in the evaluation process, with no discernible order
Fig. 1 Retained cystic duct calculi identified by endoscopic retrograde cholangiography (a) and MRCP (b). Arrow denotes filling defects identified in each imaging modality
identifiable. The relative utilization of the various common imaging modalities is presented in Table 2. Management of RCDL included several modalities. There was an equal distribution in the number of patients undergoing reoperation (six) compared to endoscopic treatment alone (six). Two of the six patients represented with the clinical constellation of symptoms and findings consistent with acute remnant cystic duct obstruction and inflammation that required urgent surgical intervention. These symptoms and findings included persistent right upper quadrant pain for >24 h, nausea and emesis, abnormal LFTs, leukocytosis, and cystic duct cholelithiasis with inflammatory changes on radiographic imaging. Due to the nature of clinical presentation, the patients were taken directly to surgery without attempted endoscopic intervention. Of the remaining four patients treated surgically, three had failed attempts to remove stones endoscopically, including one patient with Mirizzi syndrome and one patient with extravasation of contrast at initial ERCP. The final patient elected to proceed to surgery without attempted endoscopic stone retrieval. Of the patients undergoing repeat surgery, all were attempted laparoscopically but required conversion to an open procedure due to dense adhesions/chronic inflammation in the porta hepatis. Intraoperative cholangiography revealed the presence of concomitant choledocholithiasis in both patients, and a common bile duct exploration was employed for calculi removal at the time of reoperation. Six patients were managed by ERCP; three with sphincterotomy and balloon extraction; and one with sphincterotomy, lithotripsy, and basket retrieval. One patient required only balloon sweep of the common bile duct. In the remaining patient, the cystic duct stone could not be readily retrieved by ERCP and no further management was employed due to the patient’s preference.
J Gastrointest Surg Table 2 Radiologic imaging modalities utilized in the evaluation of postcholecystectomy syndrome and their accuracy in identifying remnant cystic duct lithiasis (RCDL) Radiologic study
Patients undergoing imaging modality
Number of RCDL identified
Accuracy (%)
Ultrasonography CT scan MRI
9 7 9
5 5 8
55.6 71.4 88.9
Of the 12 patients treated with surgical or endoscopic intervention for RCDL at our institution, 9 were seen in follow-up clinic visits by the attending gastroenterologist or final operative surgeon. Two patients were lost to follow-up. One patient did not live local to our institution and after incomplete endoscopic treatment preferred no further endoscopic intervention or surgical referral. Of the nine patients with available follow-up clinic notes, seven experienced symptom resolution (77.8 %) with a mean follow-up of 11.8 months. Of the two patients with persistent symptoms, notes suggested that one patient may have had pain from fatty liver disease or a question of right upper quadrant incisional hernia and the other patient had ongoing work-up for persistent RCDL after initial endoscopic lithotripsy.
Discussion The burden of disease attributable to RCDL as a cause of postcholecystectomy syndrome has not been well-defined, and estimates vary in the literature. It is difficult to quantify the exact incidence at our institution, but RCDL is a rare cause of postcholecystectomy syndrome in our patient population. Rozsos et al. estimated that the cystic duct stump syndrome, or an excessively long cystic duct stump, is the cause of persistent or recurrent symptoms in 16 % of patients with PCS.12 There was no indication in this study regarding how many patients had RCDL versus an isolated cystic duct stump without calculi. In a recent study by Palanivelu et al., the incidence of remnant cystic duct stump calculi causing symptoms in patients undergoing standard laparoscopic cholecystectomy was estimated at 0.02 %.9 However, this estimation was based on the number of patients undergoing remnant resection at their institution and did not include patients undergoing successful endoscopic retrieval. In addition, it is unclear from this study how many patients had their initial operation at the same institution as the cystic duct stump excision, and thus, the denominator used may not be representative of the true extent of the disease burden. This exact situation is frequently encountered at our institution, and nearly half of the patients in the present series had their initial cholecystectomy at another facility. Thus, it is not possible for
us to accurately state the incidence of symptomatic RCDL on the basis of our single-institution study. In this series, symptoms associated with PCS in cases of RCDL, specifically right upper quadrant pain, appear to be associated with dilation of a hollow viscus, as there was a high rate of symptom resolution after both endoscopic and surgical interventions. Surgical pathology results and dense adhesions noted at the time of surgery suggest that the presence of RCDL leads to associated portal inflammation. However, the resolution of PCS in 77.8 % of patients in this series, regardless of method of treatment, suggests that ongoing symptoms are related to the presence of stones themselves within the hollow viscus. Proposed risk factors for recurrent symptoms due to RCDL include a cystic duct stump >1 cm in length, a low cystic duct insertion into the common bile duct, and use of nonabsorbable , , material for ligation of the cystic duct stump.9 13 14 The acceptable length of a cystic duct remnant in the laparoscopic era has been an area of discussion due to the fact that one technical aspect of a safe dissection within the hepatocystic triangle is to delineate the cystic duct at the cystic duct/gallbladder-infundibulum junction. In theory, this minimizes the chance for injury of the common bile duct. However, if the cystic duct is ligated in this location, there is often a long cystic duct remnant present. Previous studies have concluded that in more than 50 % of cholecystectomies, the length of the remnant cystic duct is ≥3 cm.15 With our current series, endoscopic and surgical reports did not describe the exact location of the stones in relation to the site of surgical transection or the origin of the cystic duct. One patient was noted to have a large stone within the distal cystic duct remnant causing Mirizzi syndrome at the time of representation. This makes it difficult to describe the exact relationship between cystic duct length and the occurrence of RCDL. In our opinion, given the potentially devastating consequences of common bile duct injury, a long cystic duct remnant confers less risk than aggressive dissection near the common bile duct. This assertion is strengthened by the fact that several of the patients in our study with RCDL were managed by endoscopic therapies alone. An interesting observation in our series was that the dictating surgeons noted a subjectively dilated cystic duct in 66.7 % of these cases, with two estimated to be >1 cm in diameter. This parallels the likelihood of surgeons utilizing special techniques for ligation of the cystic duct at the time of cholecystectomy, with 58.3 % choosing either a stapling device, ligation loop, or suturing method over titanium or Hem-o-lok clips, as is common at our institution. This detail may be an important indicator to the surgeon about the possibility of calculi within the cystic duct itself that should prompt further diagnostic modalities, such as use of intraoperative cholangiography. Notably, only one patient undergoing cholecystectomy in our study had a concomitant cholangiogram performed at the
J Gastrointest Surg Fig. 2 Current institutional algorithm used for the management of postcholecystectomy syndrome and remnant cystic duct lithiasis
time of initial operation. Despite numerous well-designed studies evaluating the value of intraoperative cholangiography, there is still a lively discussion regarding the utility of routine versus selective cholangiography. It seems reasonable to suggest that if a selective approach is used for the identification of choledocholithiasis, then a dilated cystic duct may be a potential indication to proceed with cholangiography. However, the utility and predictive value of this strategy would need further investigation. Radiologic imaging guidelines for the evaluation of patients with suspected PCS do not exist. Previous studies evaluating the diagnostic accuracy of various radiologic imaging modalities have found ultrasonography and MRCP to be 60 and 92 % accurate, respectively.9 Our results are similar, showing the accuracy of ultrasonography and MRCP at 55.6 and 88.9 %, respectively. While these findings support the use of MRCP as the imaging modality of choice in the evaluation of suspected PCS, however, the additional cost of MRCP as well as the availability and local expertise regarding the interpretation of MCRP images must be considered. Anecdotally, our initial strategy for use of radiologic imaging began with the least expensive and most readily available option, ultrasonography. If this was unrevealing, then computerized tomography and magnetic resonance imaging were employed for further investigation. Although the accuracy of ultrasonography is lower than MRCP, it may be a more reasonable option in the initial evaluation, when other diagnoses are being entertained. Our current institutional algorithm omits the use of ultrasonography in postcholecystectomy patients with abnormal liver function tests (Fig. 2). The delay of nearly 4 years in our study between cholecystectomy and diagnosis of RCDL
speaks to the potential difficulty of this diagnosis and the need of a high index of suspicion in patients with persistent symptoms.
Conclusion ,
Management of RCDL has traditionally been surgical.8 16 With the advent of advanced minimally invasive techniques, successful laparoscopic management of this condition has , been reported,9 17 and our institution’s current algorithm reflects these changes (Fig. 2). In our experience, the six patients who required operative intervention were ultimately treated through an open approach after conversion from laparoscopy. In all patients, the reason for conversion was dense chronic inflammatory tissue in the porta hepatis and inability to safely visualize the vasculo-biliary anatomy. Our institutional bias in these situations is for early conversion to open techniques to minimize the potential risk for vasculo-biliary injury, although we acknowledge that this is institution-dependent. Of note, six of the patients in our series were managed by endoscopic techniques with successful calculi extraction from the cystic duct remnant. This approach has previously been described, but the actual utilization and availability of endoscopic techniques are not clearly defined.18 To our knowledge, this high rate of successful endoscopic management of remnant cystic duct calculi has not been described before. In our experience, endoscopy is a reasonable initial treatment option as it provides diagnostic and in some cases therapeutic alternatives. The endoscopic approach would be favored as initial therapy in patients presenting without recurrent inflammation of the
J Gastrointest Surg
remnant cystic duct. The only contraindications to endoscopic intervention would be those associated with the endoscopic procedure itself (inability to cannulate the sphincter of Oddi, coagulopathy, etc.). The early involvement of a biliary endoscopist in the evaluation and treatment of PCS is crucial to the successful management of RCDL and may obviate the need for repeat surgery altogether. In conclusion, RCDL can be a cause of postcholecystectomy syndrome and the diagnosis should be entertained in a patient with persistent or recurrent symptoms after cholecystectomy. The ultimate diagnosis of RCDL is difficult and requires a multidisciplinary approach, for successful management. In many circumstances, surgery can be avoided by endoscopic cystic duct stone retrieval methods.
Conflict of Interest All authors declare that they have no conflicts of interest. This paper has not been published previously. Funding Institutional support was provided by the Department of Surgery at the University of North Carolina at Chapel Hill. There are no relevant financial disclosures.
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