Abstract

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• Gallbladder Stones-Dissolve, Blast, or Extract? Laparoscopic Cholecystectomy versus âthe Restâ R. H. DOWLING Gastroenterology Unit, Guyâs Campus, UMDS of Guyâs & St Thomasâ Hospitals, London, England Dowling RH. Gallbladder stones-dissolve, blast, or extract? Laparoscopic cholecystectomy versus âthe restâ. Scand J Gastroenterol 1992;27 Suppl 192:67-76 This article reviews selected aspects of the non-surgical/minimally invasive treatments of gallbladder stones (GBS) and discusses briefly the residual role of these treatments in the era of laparoscopic cholecystectomy. In patients with specific, gallstone-related symptoms who wish to retain their âfunc- tioningâ gallbladders, there are at least six different management options. They range from rapid but invasive to slow but safe: i) the rotary lithotrite; ii) percutaneous cholecystolithotomy; iii) percutaneous transhepatic or iv) endoscopic retrograde cannulation of the gallbladder followed by instillation (manual or pump-assisted) of contact solvents; v) extracorporeal shock-wave lithotripsy + adjuvant bile acids and; vi) oral bile acids alone. The recommended investigation sequence is i) ultrasound (to diagnose the presence of the GBS), followed by ii) oral cholecystography (to assess cystic duct patency, gallbladder anatomy and GBS size, number, lucency, buoyancy, and contour), and iii) regional computed tom- ography scanning of the gallbladder (to predict stone composition and dissolvability and to plan routes of access to the gallbladder). The decision-making steps are i) choice of some form of active treatment versus no treatment (other than observation); ii) in those with specific symptoms and a patent cystic duct who opt for active treatment, to choose between removing versus retaining the gallbladder; and iii) in those who wish to retain their âfunctioningâ gallbladder, to offer and select the most appropriate of the alternative options. In conclusion, despite the excellence of laparoscopic cholecystectomy, there remains a place for the non-surgical/minimally invasive approaches in a carefully selected minority of symptomatic GBS patients. Although GBS may recur in approximately 50% of patients, the recurrent stones are often asymptomatic, can be detected âearlyâ by follow-up ultrasound, and are easily treated. Ultimately, the aim of gallstone research must be to prevent not only recurrent but also primary GBS formation, which would obviate the need for both medical and surgical treatment. Key words: Contact solvents; gallbladder stones; laparoscopic/conventional cholecystectomy ; lithotripsy; oral bile acids; percutaneous stone pulverisation/removal Professor R. H. Dowling, M. D . , F. R. C. P. , Gastroenterology Unit, 18th Floor, Guyâs Tower, Guyâs Hospital Campus, UMDS of Guyâs & St. Thomasâ Hospitals, London, U.K., SEI 9RT For various reasons (Table I), before 1987 many patients with symptomatic gallbladder stones (GBS) were reluctant to undergo cholecystectomy. As a result, several alternative management options evolved. These included i) oral bile acid treatment, first with chenodeoxycholic acid (CDCA) (1,2) and then with ursodeoxycholic acid (UDCA) (3,4) or the combination of the two bile acids (5,6); ii) extracorporeal shock-wave lithotripsy (ESWL) without (7) but more usually with (b10) adjuvant oral bile acids or occasionally direct âcontactâ solvents such as methyl-tert-butyl ether (MTBE) (1 1); iii) gallbladder cannulation, mostly by the percutaneous transhepatic route (1 1-13), although occasionally by the endoscopic retrograde (nasocholecystic (14,lS)) route, fol- lowed by the instillation/aspiration (manual or pump- assisted (16, 17)) of contact solvents for cholesterol (such as MTBE (11) or ethyl proprionate (18, 19)) or non-cholesterol (the calcium chelator ethylenediaminetetraacetic acid (EDTA) (20,21) and/or N-acetyl cysteine (22)) components of the gallstones; iv) percutaneous cannulation of the gall- bladder with dilatation of tract and insertion of wide-bore (24-30 French) Amplatz sheath followed by direct endo- scopic removal of the stones with or without prior contact lithotripsy (percutaneous cholecystolithotomy (PCCL) (23- 26)); and several experimental approaches such as v) per- cutaneous transhepatic (usually) insertion into the gallblad- der of rotor-driven impellers that pulverize the stones (the rotary lithotrite) (27,28) or vi) percutaneous stone removal followed by chemical or radiofrequency ablation of the gallbladder lumen (chemical cholecystectomy) (29). THE INFLUENCE OF LAPAROSCOPIC CHOLE- CYSTECTOMY In 1987, Philippe Mouret from Lyons pioneered the first laparoscopic cholecystectomy (30). His example was soon followed by other surgeons in France (31,32), the United States (33,34), Britain (35)), and elsewhere. Despite the complete lack of any random-allocation controlled trials, laparoscopic cholecystectomy has now taken the world by storm. In many countries it has become the surgical treat- Sc an d J G as tr oe nt er ol D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y U ni ve rs ity o f A de la id e on 1 2/ 18 /1 4 Fo r pe rs on al u se o nl y.
• 68 R. H . Dowling Table I. Reasons for declining surgery* ~ High risk for anaesthesia/surgery Friends/relatives with unsatisfactory cholecystectomy Fear of anaesthesia/surgery Cosmetic Adverse reactions to previous surgery Loss of income/care of children during hospitalisation and covalescence âNothing to loseâ philosophy about trial of medical treatment * Reasons given by a selected group of patients for declining conventional open abdominal cholecystectomy. Although some of these reasons also apply in the era of laparoscopic cholecystectomy, the cosmetic objection to a traditional surgical scar no longer applies. Furthermore, the time required in hospital and for subsequent convalescence is much shorter after laparoscopic than after con- ventional cholecystectomy. Therefore, the economic/social objec- tion to surgery is diminished. ment of choice for symptomatic patients with gallbladder stones. Initially, complications of âlap choleâ were relatively fre- quent, including uncontrollable haemorrhage and bile duct injury. Furthermore, in 520% of patients it was necessary to âconvertâ the laparoscopic, to the open abdominal, approach. This was particularly true in patients who had undergone previous upper abdominal surgery or in those who had an acutely inflamed gallbladder which was the seat of hyper- aemia, oedema, and inflammatory adhesions. However, like all new techniques, there is a âlearning curveâ, and with growing experience the complication rate of laparoscopic cholecystectomy decreased. Concerns that common duct stones would be missed have now largely been overcome, and, when indicated, intraoperative cholangiography can now be carried out at laparoscopy. The advantages of the laparoscopic over the traditional approach to cholecystectomy are reviewed elsewhere in these proceedings (36) and need not be restated here. Suffice it to say that with only four or five tiny incisions, post- operative pain is less, the duration of hospital stay is shorter, and cardiopulmonary complications are fewer, than with the conventional approach. As a result, the economic cost to the patient, the State, or private health insurance schemes is considerably less than that of open abdominal chole- cystectomy . Given this background, the question posed by the title is not so much whether we should dissolve, blast, or extract gallbladder stones as whether, in the era of laparoscopic cholecystectomy, these alternative approaches still have a place in their management? In the authorâs opinion, the answer is unequivocally âyesâ, but only in a selected minority of patients. The purpose of this article is not to review the seven non-surgical, or minimally invasive, management options in detail: this has been done by the author (37,38) and others (39) elsewhere. Instead, the aim is to highlight some recent developments in each of the alternative approaches and to recommend a decision-making sequence for the selection of gallstone patients who are likely to benefit from the options in which the gallbladder is retained. CLINICAL PRESENTATION The results of epidemiology studies suggest that in 6680% (or even 100% of men in one series (40)) of gallstone carriers the stones are silent or asymptomatic: only a minority present with specific, gallstone-related symptoms. In general and gastroenterologic practice, this means biliary pain or colic, arbitrarily defined (41) as a steady epigastric and/or right upper quadrant pain lasting more than 15-30min that is unrelated to bowel movements or passing flatus. An esti- mated 20-30% of patients referred with the diagnosis of biliary symptoms are judged, clinically, to have either a colonic motility disorder or non-specific âdyspepsiaâ unre- lated to their GBS. (Non-specific upper abdominal symp- toms occur with equal frequency in gallstone carriers and gallstone-free subjects (42,43)). An even smaller minority of gallstone patients present with âsurgicalâ complications, mainly due to cystic (acute cholecystitis with or without empyema formation or even the rare Mirizzi syndrome (44)) or common bile duct (cholestasis/jaundice, cholangitis or pancreatitis) obstruction. RADIOLOGICAL ASSESSMENT Ultrasound. When the clinical history suggests the possi- bility of GBS, their presence today is most commonly con- firmed by ultrasound. This is the most sensitive of the imaging techniques for detecting stones in the gallbladder, but not for stones in the bile duct, where the sensitivity of ultrasound is only 5 0 4 0 % . In patients who opt for or require cholecystectomy, it is seldom necessary to perform further imaging studies. However, in patients who wish to avoid surgery and/or be considered for one of the alternative approaches (see below), in addition to ultrasound we also routinely perform oral cholecystography (OCG) and localized computed tom- ography (CT) scanning of the gallbladder. Ultrasound tells us nothing about GBS composition. Moreover, although a âsignificantâ (either one-third or extent not defined) reduction of gallbladder volume in response to a cholecystokinetic stimulus, such as a fatty meal or an injection of cho- lecystokinin, predicts patency of the cystic duct with accept- able accuracy (45,46), such stimuli are seldom used in routine clinical ultrasonographic practice. Oral cholecystography. Opacification of the gallbladder during OCG confirms that the cystic duct is patent-a pre- requisite for oral bile acid treatment, almost invariably for ESWL + oral bile acids and, in the opinion of the author, also for treatment with contact solvents and PCCL. OCGs also provide valuable complementary information about gallbladder anatomy (the presence of lobes, septae, and Sc an d J G as tr oe nt er ol D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y U ni ve rs ity o f A de la id e on 1 2/ 18 /1 4 Fo r pe rs on al u se o nl y.
• Gallbladder Stones 69 Phyrigian cap deformities), gallbladder contractile function in response to a fatty meal (a predictor of gallstone clearance after ESWL (47) and, also, one suspects, of complete gall- stone dissolution with oral bile acids, although this is less well documented). Nonetheless, 14-20% of stones that appear lucent by conventional radiology (plain roentgenogra- phy + OCG) are non-cholesterol in type (48,49), and radiolucent non-cholesterol stones are a relatively common cause of failed medical treatment (50). CT scanning. Approximately 50% of stones that appear radiolucent by traditional roentgenography are visibly dense on CT scanning and are unlikely to dissolve completely with contact solvents or oral bile acids (51). For this reason, in patients referred for non-surgical treatment we also routinely perform localized CT scanning of the gallbladder (5- 8 x 6 mm contiguous âcutsâ). Patients with CT-dense gall- stones (those with a maximum Hounsfield Unit score of >lo0 HU) are then excluded from treatment on the grounds that their stones are unlikely to dissolve completely. However, there is controversy about the most appropriate cut-off point in gallstone attenuation score: some believe that it should be >50 HU, some that it is 90-100 HU, and some that it should be as high as 140 HU. The benefits of CT screening CT scanning of the gallbladder, when combined with measurements of gallbladder bile and stone attenuation val- ues measured in Hounsfield Units, predicts GBS com- position with much greater sensitivity than does OCG. The maximum gallstone HU score predicts not only stone com- position but also its dissolvability with MTBE in vitro (51) and with oral bile acids in vivo (52,53) and, one suspects, with oral bile acids after ESWL and with MTBE in vivo, although these latter suspicions have not yet been confirmed by formal prospective trials. If percutaneous gallbladder puncture techniques are being considered (for the use of the rotary lithotrite, for PCCL, or for the insertion of cannulae into the gallbladder through which contact solvents may be instilled), CT helps to plan routes of access. It also provides valuable information about the thickness of the gallbladder wall-information that may also be obtained by ultrasound. NO TREATMENT CHOICE OF MANAGEMENT OPTIONS: THE DECISION-MAKING PROCESS The sequence of events In patients with known (by ultrasound) GBS we find it cost-effective to arrange both cholecystography and CT scanning of the GB in advance of the patientâs appointment. This approach is contrary to classical clinical teaching, since it means that the patient undergoes expensive radiologic investigations before a clinical history has been obtained and the patient has been examined. As a result, a few patients with atypical symptoms, in whom neither medical nor sur- gical treatment is advocated subsequently, are investigated unnecessarily. Despite this, the unconventional sequence proposed above minimizes recurrent hospital visits for roent- genographic investigations, and in most it speeds the decision-making process to the patientsâ advantage. Armed with the results of the radiologic assessment, one is now in a position to decide on which management options are most appropriate for the individual patient. Clinical trial protocols apart, the choice of treatment depends on the availability locally of equipment and exper- tise; on the patientâs preference, ideally based on an informed weighing-up of the advantages and disadvantages of each approach; and, increasingly, on economic con- siderations. STEP ONE (Fig. 1) The first decision is whether the patient needs no treatment (other than regular surveillance, if appropriate), or some form of active management. Asymptomatic patients and those with non-specific symp- toms such as fat intolerance, dyspepsia, and symptoms of the irritable bowel syndrome, require neither medical nor surgical treatment for their GBS (41,42). Possible excep- tions to this dogma include patients with diabetes mellitus (who may be at special risk (54), although this is debated (55,56)) , and those travelling to remote parts of the world, where medical/surgical help is not readily available. SOME FORM OF ACTIVE TREATMENT Fig. 1 . The first step in the decision-making process is to chose between no treatment, other than regular surveillance (the management option of choice for those with âsilentâ gallstones and those atypical and/ or non-specific symptoms) and some form of active medical or surgical therapy. Sc an d J G as tr oe nt er ol D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y U ni ve rs ity o f A de la id e on 1 2/ 18 /1 4 Fo r pe rs on al u se o nl y.
• 70 R. H. Dowling RETAIN GALLBLADDER INVASIVE/QUICK vs NON-INVASIVEISLOW A OPEN vs LAPAROSCOPIC CHOLECYSTECTOMY Fig. 2. The second step is to decide, with the patient, whether the gallbladder, and the stones it contains, should be removed by open or laparoscopic cholecystectomy or, in patients whose cystic duct remains patent, whether the gallbladder should be retained, and a number of management options offered ranging from quick but invasive, to slow but non-invasive (see Fig. 3 ) . STEP TWO (Fig. 2) In symptomatic GBS patients with a blocked cystic duct who want and/or need cholecystectomy, the decision is between laparoscopic and open abdominal removal of the gallblad- der. However, in those with a patent cystic duct who wish to retain their âfunctioningâ gallbladder, the decision lies between rapid but invasive versus slow but non-invasive approaches. THE VALIDITY OF RETAINING A FUNCTIONING GALLBLADDER The results of epidemiologic studies from Italy show that when GBS are diagnosed by ultrasound and the carriers are studied further by oral cholecystography, approximately 30% have a non-visualizing gallbladder (57). They are pre- sumed, therefore, to have a blocked cystic duct. (This may not be a valid assumption, since there are many reasons, other than a blocked cystic duct, for non-opacification of the gallbladder during OCG.) As noted above, most of these gallstone carriers have silent or asymptomatic stones and only a few will develop symptoms (biliary colic). In those who do and whose cystic duct remains patent, many feel strongly that, if possible, they should retain their âfunc- tioningâ gallbladder. The questions raised Are we right to encourage this belief? Around this central issue revolves the whole future of non-surgical treatments for GBS. And related to this issue, one may pose the following questions: i) What are the normal functions of the gallbladder? ii) How well do patients fare without it? iii) If the gallbladder is retained, what is the natural history of âchronic cholecystitisâ? (Histologic examination of gallblad- ders removed from patients with cholelithiasis almost invariably shows some degree of chronic cholecystitis.) iv) What are the risks of recurrent gallbladder stones, and what is their natural history? v) If the gallbladder is retained, what is the risk of gallbladder cancer in the presence of, or after clearance of, the GBS? and vi) What is the evidence that cholecystectomy predisposes to colon cancer? The answers A detailed discussion of these rhetorical questions is beyond the scope of the present review, but in the opinion of the author the situation is as follows. The normal functions of the gallbladder. The principal functions of the gallbladder are to store and concentrate bile and to co-ordinate its delivery to the duodenum to coincide with the arrival there of food. The gallbladder secretes hydrogen ion, and its mucosa synthesizes and secretes mucus glycoprotein and immunoglobulins. These functions are important in the pathogenesis of calcium carbonate-con- taining and/or cholesterol-rich gallstones, and in âauto- protectionâ against infection/inflammation. However, they probably do not confer any advantage to the body as a whole. The role of gallbladder bile in gastrointestinal homeo- statis, in gut hormone secretion, and in immune surveillance is uncertain. The clinical consequences of cholecystectomy. Although cholecystectomy (or blockage of the cystic duct) leads to relatively subtle changes in bile acid and bile lipid compo- sition, the functional reserve of the gut is such that in the large majority of patients there are no clinical consequences of excluding the gallbladder. In patients who have undergone gastric surgery, however, the combination of vagotomy and cholecystectomy is often associated with bile acid-mediated diarrhoea, which, occasionally, may be severe (58). The natural history of chronic cholecystitis in the retained gallbladder. The natural history of histologically defined chronic cholecystitis is unknown, mainly because the gallbladder is largely an inaccessible organ and the ways of judging its absorptive and contractile functions clinically are comparatively crude. The chances of developing recurrent gallbladder stones. The risk of developing recurrent GBS is now well docu- mented after oral bile acid treatment (59-62) and is mod- erately well documented after ESWL and MTBE (11,63). With these latter two approaches, however, the duration of follow-up after gallstone clearance is still relatively short. When oral bile acid treatment is withdrawn after complete GBS dissolution, gallstones recur at a rate of 10-15% per annum, reaching a cumulative actuarial (life-table analysis) plateau of between 40% and 70% (mean around 50%) after 5-10 years (64). After lithotripsy and adjuvant oral bile acid treatment, initial results suggest that the recurrence plateau is only 20% after 2 years (63). The lower recurrence rate after ESWL is probably due to the fact that a high proportion of patients selected for lithotripsy have solitary stones and the fact that the recurrence rate in patients who originally had single stones is approximately one-third of that in patients who, before treatment, had multiple stones (61,63,65). In most series the natural history of recurrent Sc an d J G as tr oe nt er ol D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y U ni ve rs ity o f A de la id e on 1 2/ 18 /1 4 Fo r pe rs on al u se o nl y.
• Gallbladder Stones 71 stones is benign, as indeed it is with primary stones, but there are too few data to say whether it is the same as, or different from, that of the primary stone disease. The risk of gallbladder cancer in GBS disease. In developed societies the cumulative risk of developing gallbladder cancer (approximately 0.01% over 20 years (66)) is less than the operative mortality of open abdominal cholecystectomy (approximately 0.5% (67)) and probably also less than that of laparoscopic cholecystectomy (approximately 0.1 %, although the number of published reports makes this diffi- cult to assess (R. McCloy. Personnel communication)). In Chile, however, where the prevalence of GBS is particu- larly high (68), the probability of developing gallbladder cancer, at around 2-3%, is such that many gastroenterolo- gists there recommend prophylactic cholecystectomy even if the stones are silent. The influence of stone removal plus retention of the gallbladder on cholecystic cancer rates is unknown. The risk of colon cancer after cholecystectomy. Despite the large number of publications that have addressed this problem, the evidence that cholecystectomy induces colon cancer is controversial. Nonetheless, the consensus of these various reports, and the results of meta-analyses, suggest that the chances of developing colon cancer, particularly on the right side, are increased slightly after removing the gallbladder (69). STEP THREE In symptomatic patients with GBS in a functioning gallblad- der who have decided against cholecystectomy, there are at least six different management options. These are summa- rized schematically, on a scale of invasive/rapid to non- invasive/slow, in Fig. 3. As stated earlier, the purpose of this article is not to review these non-surgical/minimally invasive approaches in detail. Rather, the aim is to highlight a few recent developments in each area and, in this age of laparoscopic cholecystectomy, to discuss the residual indi- cations, if any, for the different alternative approaches. The rotary lithotrite This device was developed by the Baxter Company in Irvine, California. It is introduced into the gallbladder by the percutaneous transheptic route. The shaft of the instrument measures 7.4-10.3 French. Once in place, a cage of prongs, which resembles the ribs of a miniature umbrella blown inside-out, is opened within the gallbladder lumen to a diameter of approximately 25 mm, to splint the gallbladder wall and protect it from the rotating paddles of a high-speed impeller and from flying fragments of the disrupted stones. The paddles are driven by a rotor at up to 30,000 rpm. This creates a vortex into which the gallstones are sucked and pulverized, often in 30 min or less, in much the same manner that solid food particles are reduced to tiny fragments in a domestic blender or food processor. Haemobilia, from trauma to the gallbladder mucosa (prob- ably as a result of high-velocity gallstone particles), is invariable but allegedly settles spontaneously, and the gallbladder mucosa is thought to âre-epithelializeâ within 1-3 days. In theory, the rotary lithotrite may be used to pulverize stones of any composition, and in principle, it does not require adjuvant dissolution therapy. The resultant stone debris is either washed out of the gallbladder at the time of cannulation or is left to pass down the cystic duct and out in the stools. Although the lithotrite has been used successfully to treat GBS in small series of patients from the USA (27), Britain (70), and elsewhere, its future remains uncertain. Indeed, with the advent of laparoscopic cholecystectomy, the manu- facturers seem to have become disenchanted with the tech- nique, and the instrument is no longer being developed for the market. Besides, the stainless steel Rotolith kit is not intended for reuse, and its high cost (approx. GBP 800) means that it is unlikely ever to become widely accepted as a realistic alternative to laparoscopic removal of GBS. Percutaneous cholecystolithotomy This was an adaptation of the percutaneous nephro- INVASIVE NON-INVASIVE Fig. 3. In symptomatic gallstone patients who have a patent cystic duct and who wish to retain their âfunctioningâ gallbladders, the management options range from new rapid invasive and experimental approaches, such as the use of the rotary lithotrite, through percutaneous cholecystolithotomy (PCCL), percutaneous transhepatic gallbladder cannulation (FTGBC), or endoscopic retrograde gallbladder cannulation (ERGBC) for instillation of contact solvents such as methyl-tea-butyl ether (MTBE), and extracorporeal shock-wave lithotripsy (ESWL) plus adjuvant oral bile acids (OBA), to the slow non- invasive established option of oral bile acids alone. Sc an d J G as tr oe nt er ol D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y U ni ve rs ity o f A de la id e on 1 2/ 18 /1 4 Fo r pe rs on al u se o nl y.
• 12 R. H . Dowling lithotomy technique and was based on experience gained by interventional radiologists in emergency drainage of acutely inflamed gallbladders. It was pioneered in Japan by Akiyama et al. (71), in the US by Kerlan et al. (23), and in Britain by Kellett et al. (24) and Chiverton et al. (25). In brief, the procedure is usually carried out with the patient under general anaesthesia. The gallbladder is punc- tured percutaneously, usually by the sub-hepatic route, under ultrasound and/or fluoroscopic control. A guidewire is then inserted into the gallbladder and remains in situ throughout. Next, a track is dilated serially until it is wide enough to admit a 2 4 3 0 Fr Amplatz sheath through which an endoscope (usually a nephrosocope with an offset eyepiece) is passed, and the stones are extracted, with or without prior on-table lithotripsy, under direct vision. The patients usually stay in hospital for 2-3 days (range, 1-5), but to minimize the chances of a bile leak, a self-retaining catheter (usually of the Foley type) is left in the gallbladder for 1CL14 days. A catheter cholecystogram is then performed. Provided that the âtubogramâ shows no residual calculi at this time, the Foley catheter is then removed. This usually necessitates a further overnight stay in hospital to exclude a bile leak. Since the stones are removed rather than dissolved, they can be of any composition. The technique is particularly useful, therefore, in symptomatic patients with radiopaque, non-dissolvable stones with attenuation scores of >lo0 HU who have a patent cystic duct and who wish to retain their functioning gallbladders. PCCL calls for a team effort, including an anaesthetist, an interventional radiologist, and an endoscopist/urologist . Under favourable circumstances the tract can be dilated in 20-30min and, depending on their size and number, the stones removed in about the same time. Although the Foley catheter âsafety valveâ is not a major inconvenience, the further overnight admission to hospital after its removal means that the total inpatient time and cost compare unfavourably with that required for laparoscopic chole- cystectomy. The advantages of PCCL over laparoscopic chole- cystectomy are that the patient only has one small abdominal scar (as opposed to the four, or occasionally five, stab wounds required for lap chole) and that a working gallblad- der is retained. However, these advantages are marginal and, although we continue to offer PCCL in our unit, it is suitable for only a selected minority of patients. Outside a few specialized centres, therefore, lap chole has displaced PCCL from the list of management options. direct, one-stage puncture and dilatation of the gallbladder with a relatively large trocar. Alternatively, the fundus of the gallbladder can be immobilized using a hollow, two- layered concentric suction tube that is passed through a mini-laparotomy incision (72). Finally, the fundus of the gallbladder can be secured during laparoscopy and the stones removed by the laparoscopic route, whilst retaining the gallbladder. Cannulation of the gallbladder for instillation of contact sol- vents The technique of percutaneous transhepatic cannulation of the gallbladder was developed at the Mayo Clinic by Thistle et al. (11) and was extended by Hellstern et al. in Germany (12). It is usually performed with the patient under local anaesthesia. However, despite intravenous sedation and analgesia, some patients experience considerable pain during the placement of this pig-tail catheter, particularly as the thick guidewire is coiled within the gallbladder. In the opinion of the author the procedure is at the limits of acceptability as a technique suitable for local anaesthesia. In patients with cholesterol-rich dissolvable stones, MTBE or the more recently introduced ethyl proprionate (18,19) dissolves GBS rapidly. The time required to achieve gall- stone dissolution varies from patient to patient but averages 6-12 h. However, it is a tiring procedure for patients and medical attendants alike, and sometimes the solvent instillation/aspiration âsessionsâ have to be spread over 2 or even 3 days, with corresponding inpatient hospital charges. Furthermore, it is an invasive technique that has not enjoyed widespread popularity, even with the help of automated delivery pumps, which make the procedure more rapid, less labour-intensive, and less costly, than manual instillation/ aspiration. In my unit (73) and in publications by Thistle et al. (11) and Hellstern et al. (12), incomplete gallstone dissolution was relatively common. In the Mayo Clinic report ( l l ) , for example, no fewer than 51 of 75 patients were left with some residual gallstone debris requiring adjuvant oral bile acid treatment. This incomplete dissolution seems to occur more often with contact solvent treatment than with oral bile acids, although there is no a priori reason why this should be so. Fortunately, the undissolved residues seldom cause symp- toms (73), and the residual particles often disappear com- pletely with the oral therapy. Nevertheless, the need for weeks or months of adjuvant oral bile acids partly defeats the aim of rapid, complete gallstone dissolution by âprimary intentionâ. Variations on PCCL technique, including âcholecystopexyâ, whereby the fundus of the gallbladder is anchored to the anterior abdominal wall (C. K. McSherry. Personal communication). This permits An alternative approach is endoscopic retrograde cath- There are several minor variations on the PCCL eterisation, not only of the common bile duct through the spinchter of Oddi, but also of the gallbladder (ERGBC) through the cystic duct (14,15). In skilled hands, ERGBC is possible in up to 7540% of patients, but even with the Sc an d J G as tr oe nt er ol D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y U ni ve rs ity o f A de la id e on 1 2/ 18 /1 4 Fo r pe rs on al u se o nl y.
• Gallbladder Stones 73 use of steerable-tip catheters, the limiting factor is often the calibre and plasticity of the cystic duct and the tortuosity of its spiral valve of Heister. Once the nasocholecystic catheter is in place, cholesterol-rich GBS may be dissolved with contact solvents as described above for the percutaneogs route. However, repositioning of endoscopically placed nasocholecystic catheters can be difficult when the presence of multiple stones, sited in unusual loci, calls for this ma- nouevre. In summary, percutaneous transhepatic cannulation of the gallbladder to facilitate contact solvent GBS dissolution is a rapid but invasive technique suitable for any number of cholesterol-rich dissolvable stones in symptomatic patients with a âfunctioningâ GB. The presence of a catheter within the gallbladder facilitates easy imaging to assess dissolution progress. However, MTBE may induce oedema of the gallbladder mucosa and spasm of the gallbladder wall, which makes catheter cholecystograms difficult to interpret. Fur- thermore, with the catheter in situ, ultrasound imaging is difficult, and reliance on catheter cholecystograms has resulted in âfalse-negativeâ conclusions about complete dis- solution of stones when, in reality, undissolved particles remain. MTBE has an unpleasant smell and sedative-anaesthetic properties and carries a small risk of spark explosion. Apart from the changes in the gallbladder mucosa, it can cause other transient side-effects such as duodenitis, haemolysis, and even renal damage. Ethyl proprionate seems to lack many of these disadvantages, but to date experience with it is limited. In the opinion of the author there is still a place for contact solvent dissolution of gallstones but probably only in a few specialized centres where there is a large experience with this invasive technique. Extracorporeal shock-wave lithotripsy plus oral bile acids ESWL enjoyed a frenetic burst of popularity in the late 1980s, but for the most part the enthusiasm for it was short- lived, and in 1992 ESWL is regarded by most as âyesterdayâs treatmentâ. The basic principles of the three main types of ESWL machine (spark-gap, piezo-electric/ceramic, and electro- magnetic), the indications for treatment, the selection and exclusion criteria, the need for adjuvant oral bile acid treat- ment, the efficacy of targeting, fragmentation and clearance, the short- and long-term side-effects, the cost/benefit con- siderations, and the risk of gallstone recurrence have all been discussed many times previously and need not be restated here. The best results are obtained in patients with solitary, radiolucent (by conventional roentgenography) and CT- lucent stones measuring less than 20 mm in diameter, in a âfunctioningâ gallbladder. They represent a highly selected subset of less than 20% of symptomatic gallstone patients and less than 5% of all gallstone carriers. Nonetheless, the author believes that there is still a small, but useful, role for ESWL in patients who fulfill these selection criteria and opt for lithotripsy. Again, the treatment should probably be confined to a few specialized centres. Even then, given the high capital cost of the equipment and its depreciation and maintenance costs, it does not make economic sense to have an ESWL machine dedicated solely to the treatment of gallstones. Rather, it is best used in conjunction with urol- ogists who treat renal stone disease by lithotripsy. In our experience approximately 90-95% of the lithotripsy machine time is devoted to treatment of renal stones and only 5 1 0 % to gallstones. However, ESWL is of undoubted benefit for occasional gallstone patients, and provided that the machine is capable of âearning its keepâ by treating renal stones, we continue to use it for well-selected patients with GBS. The adverse effects of obesity on GBS targeting, fragmen- tation, and clearance Although a detailed review of the advantages and dis- advantages of ESWL is not appropriate here, one new observation, based on an analysis of long-term results, does merit attention: the influence of obesity and body weight Most reports suggest that gallstones can be targeted in 95- 100% of patients. However, using a piezo-ceramic litho- triptor (Wolf), which initially had one (âPiezolith 2200â) and now has two (âPiezolith 2300/2500â) integral ultrasound probes for gallstone localisation, we found that it was not always possible to target GBS. This was particularly true in the obese and in those with small contracted gallbladders or those with high, intrahepatic gallbladders masked by the costal margin. Thus, our overall efficacy in targeting GBS was just under 80%, although in those with solitary stones, it was close to 90%. In retrospect, we found that the mean body weight in patients in whom targeting was successful (71 kg) was significantly (p < 0.005) different from that in those in whom it was not (88 kg). When we began using ESWL in mid-1977, there were no data on the influence of post-lithotripsy fragment size on subsequent GBS clearance rates. At that time, therefore, we arbitrarily described fragmentation as âsuccessfulâ if the post-ESWL gallstone particles measured
• 74 R. H . Dowling peak, and the succeeding small negative peak, in the pressure/time response of the shock-wave generate a cavitation/implosion effect within the stone (76,77). We also know that liver and adipose tissue âbluntâ or attenuate the pressure-time profile of the shock-wave, presumably with corresponding loss of fragmentation efficacy. Finally, the actuarial rates of complete GBS clearance after ESWL and adjuvant oral bile acids were again influ- enced adversely by obesity. Of the patients who achieved âadequateâ fragmentation ( 100 HU) attenuation scores has already been discussed. By ensuring that only those with potentially dissolvable stones are considered for treatment, up to 80% of those given the combination of CDCA plus UDCA achieved confirmed, complete gallstone dissolution (by life-table analysis) at 18 months (53). However, because of the development of a blocked cystic duct, which is often asymptomatic, or of surgical âcomplicationsâ during treatment, one will never reach a figure of 100% efficacy for oral bile acid treatment in achieving the goal of a symptom-free, stone-free patient. CONCLUSIONS In patients who wish to avoid cholecystectomy the ânon- surgicalâ treatments offer alternative management options. These âmedicalâ approaches work moderately well but are expensive, require long-term surveillance, often with a cumulative radiation hazard as a result of repeated chole- cystography, and there is a recurrence rate of approximately 50% at 5 years. There are three major components in the pathogenesis of primary, and therefore of recurrent, GBS-the so-called triple defect (81): i) supersaturated bile, ii) nucleation defects with an imbalance between pro- and anti-nucleating factors, and iii) stasis due to gallbladder motor dysfunction and/or excess mucus glycoprotein synthesis and secretion by the gallbladder, which results in crystal trapping in the surface gel. When gallstones have been dissolved or cleared, recur- rence of supersaturated bile is almost invariable (82) within 1-4 weeks (83). The gallbladder motor defect, which charac- terizes untreated GBS disease, also persists in most, if not all, patients (84), and yet up to 50% of individuals with gallstone disease may never develop recurrent stones. By exclusion, therefore, we can speculate that the factor that is most likely to predict recurrence versus non-recurrence must be the nucleation defect related, perhaps, to changes in mucus glycoprotein synthesis and secretion. The challenge for the 199Os, therefore, is to identify and manipulate these factors with the aim not only of preventing recurrent but also of inhibiting primary gallbladder stone formation. As in many fields of medicine, our ultimate goal in gallstone research must be to prevent rather than to treat gallbladder stones, either medically or surgically. ACKNOWLEDGEMENTS This review is based on work by many past and present colleagues, to whom the author is grateful; they include Drs. Bell, Ellul, Gleeson, Hood, Hussaini, Iser, Keightley, Kennedy, Maton, Meredith, Mok, Murphy, Pereira, Reuben, Walters, and Williams. He is also grateful to Mrs. Ann Hollington for her help with the preparation of this manuscript. REFERENCES 1. Danzinger RG, Hofmann AF, Thistle JL, Schoenfield LJ. Dis- solution of gallstones by chenodeoxycholic acid. N Engl J Med 2. Bell GD, Whitney B, Dowling RH. Gallstone dissolution in man using chenodeoxycholic acid. Lancet 1972;2:12134. 3. Makino I, Shinozaki K, Yoshino K, Nakagawa S . Dissolution of cholesterol gallstones by ursodeoxycholic acid. Jpn J Gas- troenterol 197572: 6!W-702. 4. Maton PN, Murphy GM, Dowling RH. Ursodeoxycholic acid treatment of gallstones. Dose response study and possible mech- anism of action. Lancet 1977;2: 1297-1301. 5. Podda M, Zuin M, Dioguardi ML, Festarazzi S , Dioguardi N. A combination of chenodeoxycholic acid and ursodeoxycholic acid is more effective than either alone in reducing biliary cholesterol saturation. Hepatology 1982;2:3349. 6. Stiehl A, Raedsch R, Czygan P, Gotz R, Manner CH, Walker S. Effects of biliary bile acid composition on biliary cholesterol saturation in gallstone patients treated with chenodeoxycholic acid and/or ursodeoxycholic acid. Gastroenterology 1980;79: 1192-8. 7. Fache JS, Rawat B, Burhenne HJ. Extracorporeal chole- cystolithotripsy without oral chemolitholysis. Radiology 1990; 177:71%21. 1972;286:1-8. Sc an d J G as tr oe nt er ol D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y U ni ve rs ity o f A de la id e on 1 2/ 18 /1 4 Fo r pe rs on al u se o nl y.
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