692 Gut 1994; 35: 692-695 Percutaneous cholecystolithotomy: is gall stone recurrence inevitable? Gut: first published as 10.1136/gut.35.5.692 on 1 May 1994. Downloaded from

J J Donald, S Cheslyn-Curtis, A R Gillams, R C G Russell, W R Lees

Abstract are suitable for extracorporeal shockwave litho- Using radiological interventional techniques tripsy.3 Initial enthusiasm for these techniques the gall bladder can be cleared of stones with a has not been maintained as the treatment is high success rate. As with any treatment prolonged and the success rates are disappoint- option that leaves the gall bladder in situ there ingly low (38_50%).245 By comparison, the is an accompanying risk of stone recurrence, advantages of percutaneous cholecystolithotomy which is currently unknown for the radiological over the other non-operative techniques are that method. One hundred patients were studied it can be used in 78% of gall stone patients prospectively to determine the recurrence rate (irrespective of stone size, number or composi- of stones and clinical outcome after successful tion),6 a patent cystic duct is not required, the percutaneous cholecystolithotomy. Follow up gall bladder can be cleared as a single stage included both clinical assessment and ultra- procedure, and the method has a high success sound examination at 3, 6, and 12 months and rate of90% and over.61'2 then annual intervals thereafter. The overall There have been several studies investigating stone recurrence rate was 31% at a mean follow stone recurrence rates after complete clearance up of 26 months (range, 3-50 months). By with oral dissolution therapy and extracorporeal actuarial life table analysis, the cumulative pro- shockwave lithotripsy, but to date, no data are portion of gall stone recurrence was 7, 19, 28, available for after the percutaneous radiologic- 35, and 44% at 6, 12, 24, 36, and 48 months ally guided technique of stone removal. The aim respectively. Of the 31 patients with recurrent of this study was to determine the stone recur- stones; 17 remain asymptomatic, seven have rence rate and clinical outcome after successful experienced biliary colic, two abdominal pain, percutaneous cholecystolithotomy. three non-specific upper gastrointestinal symptoms, and two jaundice secondary to http://gut.bmj.com/ common duct stones. Thirteen of the stone Patients and methods free patients have remained symptomatic; six with abdominal pain and seven with non- PATIENTS specific upper gastrointestinal symptoms. Between January 1988 and December 1990, 113 Eight patients have subsequently had a patients had a percutaneous cholecystolithotomy cholecystectomy. No significant difference for the treatment of symptomatic gall stones. was found between the sex ofthe patient or the Details of the selection criteria and technique on October 1, 2021 by guest. Protected copyright. number of stones before treatment and the have been previously described.6 Successful stone recurrence rates. The cumulative stone stone clearance was confirmed at the time of the recurrence rate was significantly less in the 56 procedure by endoscopic inspection of the gall patients who received adjuvant chemolitholy- bladder and by a negative cholecystogram 10 sis (p<005). These data show that stone days later, before catheter removal. In 100 of 113 recurrence after successful percutaneous patients in whom the technique was considered cholecystolithotomy occurs in the minority, successful a prospective follow up study has been and is usually asymptomatic. It is concluded performed. that the technique remains justified in the management of selected patients with gall stones. ADJUVANT THERAPY (Gut 1994; 35: 692-695) Adjuvant therapy was not given to the first 44 successfully treated patients. It was introduced after the finding that some tiny fragments, Departments of Although cholecystectomy is the most effective adherent to or embedded in the gall bladder Radiology longterm treatment for gall bladder stones,' not mucosa, were difficult to remove completely and J J Donald A R Gillams all patients, such as the elderly and high risk, are that some gall bladders showed cholesterolosis. W R Lees suitable even for the modern less invasive Therefore, in the subsequent 56 patients methods of minicholecystectomy and laparo- adjuvant therapy with chenodeoxycholic acid and Surgery, The Middlesex Hospital, scopic cholecystectomy. A small group of 7 mg/kg/day and ursodeoxycholic acid 5 mg/kg/ London patients continue to require alternative, non or day was given for an arbitrary period of three S Cheslyn-Curtis minimally invasive methods, including oral dis- months after the procedure. R C G Russell solution therapy, extracorporeal shockwave Correspondence to: Dr JJ Donald, Department of lithotripsy or percutaneous cholecystolithotomy Radiology, The Middlesex for the management oftheir gall stones. As few as FOLLOW UP METHODS Hospital, Mortimer Street, London WIN 8AA. 10% of patients are suitable for oral dissolution Patients were reviewed at 3, 6, and 12 months Accepted for publication therapy2 and using the selection criteria laid after percutaneous cholecystolithotomy, and 9 August 1993 down in the Munich study only 15% of patients then at yearly intervals. Follow up consisted of Percutaneous cholecystolithotomy: isgallstone recurrence inevitable? 693

an ultrasound examination and a clinical assess- test to identify any significant difference between ment. the stone free and recurrent stone groups. The log rank test was used to determine if there was any significant difference in the cumulative stone

ULTRASOUND EXAMINATION recurrence rates between the patients who did Gut: first published as 10.1136/gut.35.5.692 on 1 May 1994. Downloaded from Ultrasound examinations were performed with and those who did not receive adjuvant treat- 3-5 and 5 mHz transducers on either an Acuson ment. 128 or an ATL Ultramark 4 DBF. Patients were fasted for a minimum of six hours and examined before and 30 minutes after a fatty meal (com- Results mercial chocolate bar, Mars bar). Details of the gall bladder contents (none, sludge or LENGTH OF FOLLOW UP stones) and appearances of the gall bladder wall Follow up ranged from 3-50 months (mean, 26 (normal, focal abnormalities or thickening) were months). During this period, seven patients have recorded. A functional assessment of the gall died, four from ischaemic heart disease, one bladder was made by measuring gall bladder from carcinomatosis (primary unknown), and volumes before and after a fatty meal. Volume two from pancreatic carcinoma. None of the (V) was calculated using the previously des- deaths were procedure related. In the two cases cribed ellipsoid method where V=0 52x of carcinoma of the pancreas all the imaging has heightxwidthx length.'3 Percentage gall bladder been reviewed and the diagnosis was not evident contraction was calculated by dividing the either before the percutaneous cholecystolitho- change in volume before and after a fatty meal by tomy or for a 12 month period after treatment. the fasting volumex 100%. Gall bladder empty- Five patients were lost to follow up and two ing was considered satisfactory if a reduction in patients refused further follow up, both ofwhom volume of 30% or more occurred on functional remain asymptomatic. assessment, and poor or non-functional below this level. ULTRASOUND FINDINGS

CLINICAL ASSESSMENT Gall stone recurrence Symptoms were classified as follows: none, non- Overall the stone recurrence rate was 31%. By specific upper gastrointestinal tract complaints actuarial life table analysis, the cumulative pro- (dyspepsia, flatulence), abdominal pain, biliary portion of gall stone recurrence was 4, 7, 19, 28, colic, and jaundice. Details ofany additional gall 35, and 44% at 3, 6, 12, 24, 36, and 48 months

stone related procedures including endoscopic respectively (Figure) with a plateau after 42 http://gut.bmj.com/ retrograde cholangiography and cholecystec- months. In three cases of recurrent stones tomy were recorded. (identified on two separate ultrasound examina- tions over a six month period), further follow up showed them to clear spontaneously. Sludge was POSSIBLE PREDISPOSING FACTORS seen within the gall bladder in nine patients, Patients' sex and number of stones before treat- three of whom have developed stones on further

ment were recorded. Use of oral chemolitholysis follow up. on October 1, 2021 by guest. Protected copyright. in the last 56 patients of the series was noted. Gall bladder wall ANALYSIS AND STATISTICAL METHODS Focal hyperechoic areas within the fundal wall of Actuarial life table analysis was used to calculate the gall bladder were identified in five patients. the cumulative proportion of stone recurrence. This was presumed to represent local scarring/ This analytical method compensates for variable fibrosis after the fundal puncture. In five patients follow up periods and takes into account patients during follow up the gall bladder progressively who have been lost to follow up. Patients' sex reduced in volume, became thick walled (greater Percentage cumulative and number of stones before percutaneous than 3 mm), and non-functional. probability ofgall stone cholecystolithotomy were analysed using the x2 recurrence afterpercutaneous cnoletL 1- cystolathotomy.Z:L . Gall bladderfunction 50 - Gall bladder function was satisfactory (30% reduction in volume or greater gall bladder 440 - / contraction) after percutaneous cholecystolitho- .0 tomy in 84/96 patients (mean reduction in I - a)0.' I30 volume, 52%). In 12 patients (of whom, three presented with an acute empyema and three with a non-functional the bladder Cu 220 / gall bladder) gall either became or remained non-functioning (less E 30% volume In 14 cases the 1 10 _ reduction). gall /thanbladder was non-functional before percutaneous 0 6 1 1 2 3 3 4 48 cholecystolithotomy because of impacted stones D 6 12 18 24 30 36 42 48 54 within Hartmann's pouch. Gall bladder function Mths was successfully restored in 11 of these patients 100 95 86 74 65 59 37 11 2 1 and also in six of 10 patients who presented No of patients with an acute empyema. Presence of a fundal 694 Donald, Cheslyn-Curtis, Gillams, Russell, Lees

'scar' did not significantly change gall bladder patients with cholesterol stones, whereas percu- function. taneous cholecystolithotomy can be used in 78% of patients with gall stones, irrespective of size, number, and composition.6 Percutaneous

CLINICAL OUTCOME cholecystolithotomy also has the advantage of a Gut: first published as 10.1136/gut.35.5.692 on 1 May 1994. Downloaded from Of the 31 patients with recurrent stones: 17 high stone clearance success rate (90% and over), remain asymptomatic, seven have experienced which can be achieved as a single stage pro- biliary colic, two abdominal pain, and three non- cedure.'2 specific upper gastrointestinal symptoms (flatu- If gall stones recur, our experience would lence and dyspepsia). Two patients developed suggest that most patients will remain asympto- jaundice secondary to common duct calculi, matic. Whether recurrent stones will act like de which required endoscopic sphincterotomy and novo stones is unknown. Studies of the natural stone removal. Thirteen ofthe stone free patients history of silent gall stones show that most of have remained symptomatic: six with abdominal these patients will remain asymptomatic with a pain and seven with non-specific upper gastro- reported incidence of biliary colic of only 18% at intestinal symptoms. 15 years.'920 Therefore, it seems reasonable with Eight patients have subsequently had a laparo- current evidence to manage recurrent stones scopic cholecystectomy, seven for recurrent, expectantly, with only symptomatic patients symptomatic stones and in one patient for per- needing active treatment. During the follow up sistent abdominal pain after an acute empyema. period only 8% ofpatients have had a subsequent Adhesions between the fundus of the gall blad- laparoscopic cholecystectomy. It was successful der and the peritoneum were present in all cases. in all cases and not precluded by adhesions In two patients the laparoscopic procedure was formed secondary to the previous percutaneous technically difficult requiring careful time con- approach, although it was made technicaly more suming dissection of the adhesions. One of these difficult in two ofthe cases (one ofwhom initially patients developed a postoperative fluid collec- presented with an empyema). Biliary colic was a tion within the gall bladder fossa, which quickly reliable positive predictor of recurrent stones resolved after drainage under ultrasound and did not occur in any of the stone free guidance. No cases required conversion to an patients. Stone recurrences may have been the open cholecystectomy. result of incomplete clearance of the gall bladder despite the more thorough endoscopic approach, because of tiny fragments adherent to or embed- RELIABILITY OF BILIARY PAIN AS A PREDICTOR OF ded in the mucosa, which in turn could act as a GALL STONE RECURRENCE nidus for stone formation. This hypothesis is Biliary colic occurred in a total of seven patients, supported by the finding in this series of a http://gut.bmj.com/ all ofwhom had recurrent stones. significantly reduced stone recurrence rate in the 56 patients who were given adjuvant oral dissolu- tion therapy in comparison with the other 44 POSSIBLE PREDISPOSING FACTORS patients. No significant difference was found between the Persistence or recurrence of symptoms after sex of the patient or the number of stones before cholecystectomy is a well recognised pheno- treatment and the stone recurrence rates. Eleven mena, occurring in up to 50% of patients.2122 on October 1, 2021 by guest. Protected copyright. of 56 patients who received three months After a successful percutaneous cholecystolitho- adjuvant therapy developed recurrent stones in tomy within the stone free group, most comparison with 20 of 44 patients who did not patients became asymptomatic and to date, only receive any adjuvant therapy. Statistical analysis 13 patients (19%) have developed or remained of the cumulative stone recurrence rates in these symptomatic with either abdominal pain or non- patients found this difference to be significant specific upper gastrointestinal symptoms. (p<005). Although the gall bladder is considered to be dispensable, its preservation may result in a reduction of postcholecystectomy symptoms. A Discussion further consideration is the evidence of an Percutaneous cholecystolithotomy, like all treat- increased risk of colonic carcinoma in women ment options that leave the gall bladder in situ who have had cholecystectomy.2" are disadvantaged by the inherent risk of stone It remains unclear why some subjects reform recurrence. Contrary with the intuitive assump- stones and others do not. If risk factors could be tion by some investigators, gall stone recurrence identified it would allow us to determine the does not seem inevitable. In this series, after a patients who require close follow up and those successful percutaneous cholecystolithotomy who might benefit from prophylactic dissolution stones recurred in 31% ofpatients with a cumula- therapy. Potential predisposing factors for tive probability of 44% at four years. These recurrence that have been identified include; results are comparable with those reported for exogenous oestrogens,24 the number of stones oral dissolution therapy and extracorporeal before treatment, with significantly higher shockwave lithotripsy.I'll Interestingly, we recurrence rates in patients who initially had found that the risk of stone recurrence seems to multiple stones than in those with solitary decrease and plateau after the first few years. stones2425 and sudden weight loss in obese Similar findings have been seen after oral dis- patients.26 Hood et al noted a significantly lower solution therapy.I'46 Using current selection incidence of postdissolution recurrence in criteria, the non-invasive methods have limited patients on therapeutic doses of non-steroidal applications, being suitable for only 10-30% of anti-inflammatory drugs for rheumatic com- Percutaneous cholecystolithotomy: isgall stone recurrence inevitable? 695

plaints. 7 In this series, neither the sex of the 4 Fache JS, Rawat B, Burhenne HJ. Extracorporeal cholecysto- lithotripsy without oral chemolitholysis. Radiology 1990; patient or the number of stones before treatment 177: 719-21. showed any significant difference in stone recur- 5 Zeman RK, Davros WJ, Goldberg JA, Fanney D, Forer LE, Garra BS, et al. Gallstone lithotripsy: results when number rence rates. Data on non-steroidal anti-inflam- of stones is excluded as a-criterion for treatment. AjR 1991;

matory therapy are not available for the patients 157: 747-52. Gut: first published as 10.1136/gut.35.5.692 on 1 May 1994. Downloaded from 6 Cheslyn-Curtis S, Gillams AR, Russell RCG, Donald JJ, Lake in this study. SP, Ainley CA, et al. Selection, management, and early Both oral dissolution therapy and extra- outcome of 113 patients with symptomatic gall stones treated by percutaneous cholecystolithotomy. Gut 1992; 33: corporeal shockwave lithotripsy require a patent 1253-9. duct and are ofno value in the treatment of 7 Chiverton SG, Inglis JA, Hudd C, Kellett MJ, Russell RCG, cystic Wickham JEA. Percutaneous cholecystolithotomy: the first an acute empyema (when extracorporeal shock- 60 patients. BMJ 1990; 300: 1310-2. wave lithotripsy is contraindicated). As was the 8 Cope C, Burke DA, Meranze SG. Percutaneous extraction of gallstones in 20 patients. Radiology 1990; 176: 19-24. case in 10% of the patients, the technique can be 9 Hruby W, Stackl W, Urban M, Armbruster C, Marberger M. used to clear the gall bladder of stones after the Percutaneous endoscopic cholecystolithotripsy. Radiology 1989; 173: 477-9. radiological drainage and clinical relief of an 10 Kellett MJ, Wickham JEA, Russell RCG. Percutaneous acute empyema. It is safe and can be performed cholecystolithotomy. BMJ 1988; 2%: 453-7. 11 Kerlan RK, La Berge JM, Ring EJ. Percutaneous cholecysto- in multiple stages under local anaesthetic. In this lithotomy: preliminary experience. Radiology 1985; 157: series, before percutaneous cholecystolithotomy 653-6. 12 Picus D, Marx MV, Hicks ME, Lang EV, Edmundowicz SA. therapy, the gall bladder was non-functional in Percutaneous cholecystolithotomy: preliminary experience 14 of a stone impacted in and technical considerations. Radiology 1989; 173: 487-91. patients because 13 Dodds WJ, Groh WJ, Darweesh RMA, Lawson TL, Kishk Hartmann's pouch. In our experience, this does SMA, Kern MK. Sonographic measurement of gallbladder not preclude a successful procedure with the volume. AJR 1985; 145: 1009-10. 14 Dowling RH, Gleeson DC, Hood KA, Ruppin DC, British- recovery ofcystic duct patency and restoration of Belgian Gallstone Study Group. Gallstone recurrence and as occurred 11 these post dissolution management. In: Paumgartner G, Stiehl A, function, in of patients. Gerok W, eds. Bile acids and the liver. Lancaster: MTP Cholelithiasis is a common problem in the Press, 1987: 355-67. in up to 40% of patients 15 Lanzini A, Jazrawi RP, Kupfer RM, Maudgal DP, Joseph elderly, occurring AEA, Northfield TC. Gallstone recurrence after medical greater than 70 years of age.28 After the sixth dissolution. An overestimated threat? J7 Hepatol 1986; 3: there is a increase in death and 241-6. decade steady 16 O'Donnell LDJ, Heaton KW. Recurrence and re-recurrence morbidity rates for elective cholecystectomy29 of gall stones after medical dissolution: longterm follow up. situation death rates may Gut 1988; 29: 655-8. and in the emergency 17 Sackmann M, Ippisch E, Sauerbruch T, Holl J, Brendel W, be as high as 19%.3° In this series, 24% of the Paumgartner G. Early gallstone recurrence rate after suc- over there were no cessful shock-wave therapy. Gastroenterology 1990; 98: patients were the age of 70, 392-6. procedure related deaths and none of these 18 Darzi A, McCollum P, Leahy A, Tanner WA, Keane FBV. have required a cholecystectomy. If Gallstone recurrence after successful shock wave lithotripsy. patients BrJ Surg 1990; 77: A703. recurrent stones do develop in elderly patients 19 Gracie WA, Ransohoff DF. The natural history of silent

they will probably not live long enough to have gallstone. The innocent gallstone is not a myth. N Engl http://gut.bmj.com/ J Med 1982; 307: 798-800. problems, as a mean delay ofeight years between 20 Gibney EJ. Asymptomatic gallstones. BrJSurg 1990; 77: 368- stone formation and the development of symp- 72. 21 Bates T, Mercer JC, Harrison M. Symptomatic gall stone toms has been calculated using carbon dating disease before and after cholecystectomy. Gut 1984; 25: We recommend the A579-80. techniques.3" currently 22 Ros E, Zambon D. Postcholecystectomy symptoms. A pros- minimally invasive percutaneous cholecysto- pective study ofgallstone patients before and two years after in the elderly and in those surgery. Gut 1987; 28: 1500-4. lithotomy procedure 23 Linos DA, Berad CM. O'Fallon WM, Dockerty MB, Beart patients with coexisting medical conditions for RW, Kurland LT. Cholecystectomy and carcinoma of the on October 1, 2021 by guest. Protected copyright. whom management carries high risks. colon. Lancet 1981; ii: 379-81. operative 24 Scholz DG, McCullough JE, Peterson BT, Thistle JL. Gall- In conclusion, gall stone recurrence is not stone recurrence following complete dissolution with bile a acid therapy or methyl tert-butyl ether. Hepatology 1988; 8: inevitable after successful percutaneous A1372. cholecystolithotomy. It occurs in a few patients, 25 Villanova N, Bazzoli F, Taroni F, Frabboni R, Mazzella G, is and does not preclude a Gesti D, et al. Gallstone recurrence after successful oral bile usually asymptomatic, acid treatment. Gastroenterology 1989; 97: 726-31. subsequent laparoscopic cholecystectomy (ifand 26 Broomfield PH, Chopra R, Sheinbaum RC, Bonorris GG, when It offers a valuable therapeutic Silverman A, Schoenfield LJ, et al. Effects of ursode- required). oxycholic acid and aspirin on the formation oflithogenic bile alternative to conventional surgery in the small and gallstones during loss of weight. N Engl J Med 1988; ever of risk and elderly 319:1567-72. but increasing group high 27 Hood K, Gleeson D, Ruppin DC, Dowling RH. Prevention of patients and has inherent advantages over the gallstone recurrence by non-steroidal anti-inflammatory other non-invasive methods. drugs. Lancet 1988; ii: 1223-4. 28 Glenn F, Dillon LD. Developing trends in acute cholecystitis and choledocholithiasis. Surg Gynecol Obstet 1980; 151t: 528- 1 McSherry CK. Cholecystectomy: the gold standard. Am J 32. Surg 1989; 158: 174-8. 29 Greenburg AG, Salk RP, Farris JM, Peskin GW. Operative 2 Maton PN, Iser JH, Reuben A, Saxton HM, Murphy GM, mortality in general surgery. AmJ7 Surg 1982; 144: 22-8. Dowling RH. Outcome of chenodeoxycholic acid (CDCA) 30 Houghton PWJ, Jenkinson LR, Donaldson LA. Cholecystec- treatment in 125 patients with radiolucent gallstones. tomy in the elderly: a prospective study. BrJ Surg 1985; 72: Medicine 1982; 61: 85-96. 220-2. 3 Brink JA, Simeone JF, Mueller PR, Richter JM, Prien EL, 31 Mok HY, Druffel ER, Rampone WM. Chronology of chole- Ferrucci JT. Physical characteristics of gallstones removed lithiasis. Dating gallstones from atmospheric radiocarbon at cholecystectomy: implications for extracorporeal shock- produced by nuclear bomb explosions. N EnglJ7 Med 1986; wave lithotripsy. AJR 1988; 151: 927-31. 314: 1075-7.