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The Shock of the New

NEW treatments for gallbladder disease proliferateat a seemingly exponential rate, making it all the moreimportant to choose the most appropriate therapy forthe individual patient. Cholecystectomy had its

centenary recently, and shows no signs of beingentirely surpassed despite many potential rivals. Closeattention to antibiotic and antithrombotic

prophylaxis, and to surgical technique, and carefulexamination of the common bileduct for stones bycholangiography and choledochoscopy have madecholecystectomy a very safe and effective remedy forgallbladder stones. The usefulness of the operation forproducing relief of symptoms is less satisfactory. Twovery well-conducted studies have shown that about50% of patients who undergo a cholecystectomy areless than completely satisfied with the outcome.12Most gallbladder stones do not cause symptoms, as

lately confirmed by a Danish ultrasonography study.3This observation counsels caution in the selection of

patients for surgical or any other therapy, especiallysince the introduction of ultrasound scanning hasmade the diagnosis of gallbladder stones so easy.Recognition of the harmlessness of many gallstonesmay account for the dramatic fall in numbers of

cholecystectomies done in Sweden,4 and there is asuggestion of similar changes in Scotland, England,6 6and the USA. However, Rhodes and Lennard8

1. Ros E, Zambon D. Post-cholecystectomy symptoms: a prospective study of gallstonepatients before and two years after surgery. Gut 1987; 28: 1500-04.

2. Bates T, Mercer JC, Harrison M. Symptomatic gallstone disease: before and aftercholecystectomy. Gut 1984; 25: A579-80.

3 Jorgensen T. Prevalence of gallstones in a Danish population. Am J Epidemiol 1987;126: 912-21.

4 Norrby S, Fagerberg G, Sjodahl R. Decreasing incidence of gallstone disease in adefined Swedish population. Scand J Gastroenterol 1986; 21: 158-62

5. Bateson MC. Gallstone prevalence and cholecystectomy rate are independentlyvariable. Lancet 1984; ii: 521-25.

6 Philipp R, Barnard C, Pycock C, et al. Cholecystectomy rates. Lancet 1987; i: 170-71.7. Diehl AK. Trends in cholecystectomy rates in the United States. Lancet 1987, ii: 683.8. Rhodes M, Lennard TWJ. Satisfaction after cholecystectomy. Lancet 1988; i: 599.

clearly feel that their results are much more

satisfactory, and even expound the free use of

cholecystectomy for symptoms not caused bygallstones-this view is not widely accepted.When patients with cholelithiasis are unsuitable for

cholecystectomy, the gallbladder may be approachedby a percutaneous route to achieve drainage with orwithout retrieval of stones;9-12 this procedure requiressomething of a virtuoso performance and should notbe undertaken lightly. Stones in the common bileduct,although less frequent than gallbladder stones, aremuch more serious. Open choledochotomy carriesrisks which may sometimes be avoided by endoscopicretrograde cholangiography and papillotomy withdirect stone extraction.13 This last technique wasdeveloped in the 1970s and has proved so satisfactorythat it is widely regarded as the "gold standard"against which new methods are compared.Endoscopic retrograde cholangiography allows directcontact with stones, permitting physical shockwave14or laser lithotripsy,11.16 and also the placement ofnasobiliary tubes for infusion of solvents.

Other new treatments developed in the 1970sinclude oral dissolution therapy for radiolucent

gallbladder stones less than 15 mm in diameter; thistechnique is also a reserve therapy for commonbileduct stones. Standard treatment is now

ursodeoxycholic acid 750 mg/day or 10-12 mg/kg/day, although smaller doses (500 mg/day or 7

mg/kg/day) may be as good. Whilst this treatment isharmless, concern has been expressed about thedevelopment of gallstone calcification, which mightinterfere with dissolution, and the effect on the colonof altered bile acid patterns.17 Drawbacks includeunpredictability of response, the frequent need forprolonged treatment over years, and a recurrence rateof at least a third over several years’ follow-up. Acombination of about 7 mg/kg/day of both

ursodeoxycholic acid and chenodeoxycholic acid hasbeen suggested as a way of hastening response andavoiding stone calcification.18 Chenodeoxycholic acidalone is now used less because the larger dosesrequired to achieve good results in stone dissolution

9. Joachim-Burhenne H, Stoller JL. Minicholecystostomy and radiologic stone

extraction in high risk cholelithiasis patients. Am J Surg 1985; 149: 632-35.10. Kerlan RK, LaBerge JM, Ring EJ. Percutaneous cholecystolithotomy: preliminary

experience. Radiology 1985; 157: 653-56.11. Klimberg S, Hawkins I, Vogel SB. Percutaneous cholecystostomy for acute

cholecystitis in high risk patients. Am J Surg 1987; 153: 125-29.12. Kellett MJ, Wickham JEA, Russell RCG. Percutaneous cholecystolithotomy.

Br Med J 1988; 296: 453-55.13. Davidson BR, Neoptolemos J, Carr-Locke DL. Endoscopic sphincterotomy for CBD

calculi in patients with gallbladder in situ considered unfit for surgery. Gut 1988;29: 114-20.

14. Liguory CL, Bonnel D, Canard JM, Cornud F, Dumont JL. Intracorporealelectrohydraulic shockwave lithotripsy of common bile duct stones: preliminaryresults in 7 cases. Endoscopy 1987; 19: 237-40.

15. Lux G, Ell Ch, Hochberger J, Muller D, Demling L. The first successful endoscopicretrograde laser lithotripsy of common bile duct stones in man using a pulsedneodymium-YAG laser. Endoscopy 1986; 18: 144-45.

16. Nishioka NS, Levins PC, Murray SC, Parrish JA, Anderson RR. Fragmentation ofbiliary calculi with tunable dye lasers. Gastroenterology 1987; 93: 250-55.

17. Owen RW, Dodo M, Thompson MH, Hill MJ. Fecal steroid loss in healthy subjectsduring short-term treatment with ursodeoxycholic acid. J Steroid Biochem 1987;26: 503-07.

18. Fromm H. Gallstone dissolution therapy: current status and future prospects.Gastroenterology 1986, 91: 1560-67.

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lead to diarrhoea. (However, it seems to command auniquely useful place in the management of the rarenervous disease, cerebrotendinous xanthomatosis

[CTX].19) Ursodeoxycholic acid alone has been usedfor control of biliary and other dyspepticsymptoms2O,21 and, more importantly, for

symptomatic and biochemical control of cholestaticliver diseases such as primary biliary cirrhosis22 andchronic active hepatitis.23

Local dissolution therapy for radiolucent

gallstones, when direct access can be gained by biliarydrains or nasobiliary catheters, has long excitedinterest.24 Patient Japanese workers achieved excellentresults over several weeks with the cholesterol solventd-limonene.25 Continuous infusions of mono-

octanoin produced reasonable dissolution rates over afew days.26 Ideas have now moved into a different gearwith the advent of methyl-tertiary-butyl ether

(MTBE), the most powerful cholesterol solvent yetintroduced. This compound is an explosiveanaesthetic agent which has to be used with great care,but it shows considerable promise in the hands ofsome27,28 if not a1129 workers. A great attraction is its

potential for complete dissolution of stones in hours,which leads to another approach that is worth

considering-direct percutaneous gallbladderpuncture with repeated instillation and aspiration ofMTBE. 27 This procedure has been carried out inmore than sixty patients at the Mayo Clinic with goodresults, but it is very labour-intensive; introduction ofautomatic pumps may make the technique morewidely applicable. Selection of radiolucentcholesterol-rich stones is important for all thesedissolution methods, and results may be improved bycomputerised tomography to detect subradiographiccalcification, and magnetic resonance imaging forestimation of stone density and chemical analysis inthe patient.The story does not stop here-not only can one cut

out, pull out, or dissolve many stones, one can nowsmash them to gravel or powder. Modern gallstonelithotripsy is very much the child of the 1980s,

19 Berginer VM, Salen G, Shefers S. Long-term treatment of CTX with CDCA. N EnglJ Med 1984; 311: 1649-52

20 Stefaniwsky AB, Tint GS, Speck J, Shefers S, Salen G. Ursodeoxycholic acid in thetreatment of bile reflux gastritis Gastroenterology 1985; 89: 1000-04.

21. Aggio L, Mastropaolo G, Mario F, Cannizaro F, Naccarato R UDCA in thetreatment of non-organic dyspepsia Min Diet Gastroenterol 1986; 32: 303-06.

22. Poupon R, Chretien Y, Poupon RE, Ballet F, Calmus Y, Darnis D. Is ursodeoxycholicacid an effective treatment for primary biliary cirrhosis? Lancet 1987; i: 834-36

23. Leuschner U, Leuschner M, Sieratzki J, Kurtz W, Hubner K. Gallstone dissolutionwith ursodeoxycholic acid in patients with chronic active hepatitis and two yearsfollow up Dig Dis Sci 1985, 30: 642-49.

24 Neoptolemos JP, Hofmann AF, Moossa AR Chemical treatment of stones in thebiliary tree. Br J Surg 1986; 73: 515-24.

25. Igimi H, Hisatsugu T, Nishimura M The use of d-limonene preparation as adissolving agent of gallstones Dig Dis Sci 1976; 21: 926-39.

26. Palmer KR, Hofmann AF. Intraductal mono-octanoin for the direct dissolution of bileduct stones, experience in 343 patients Gut 1986; 27: 196-202

27 Allen MJ, Borody TJ, Buguosi TF, May GR, Larusso NF, Thistle JL. Rapiddemolition of gallstones with methyl-tertiary-butyl ether N Engl J Med 1985, 312:217-20

28. Murray WR, Laferca G, Fullarton GM. Choledocholithiasis—in vivo stone

dissolution using MTBE. Gut 1988, 29: 143-44.29 Padova C, Padova F, Montorsi W, Tritapepe R MTBE fails to dissolve retained

radiolucent CBD stones Gastroenterology 1986; 91: 1296-300

although the technique of physically crushing stoneswas known before. Internal lithotripsy may be carriedout by electrohydraulic shockwaves or crystal-tiplaser. (One oriental paper30 even described the use ofthe explosive lead azide in a kind of quarryingtechnique.) Of much more practical relevance is thedevelopment of external focused shockwave

lithotripsy with electrohydraulic, ultrasonographic, orpiezoelectric methods. 31-37 Radiolucent stones in

functioning gallbladders or in common bileducts arelocated by diagnostic ultrasonography and thenshattered by waves focused upon them. The mostextensive reported experience with extracorporealshockwave lithotripsy (ESWL) is from Munich,where over 300 patients have been treated.32 The olderequipment involved a general anaesthetic andimmersion of the patient in a water bath, but painlesslithotripsy can be achieved with more modem ESWLmachines and by ceramic piezoelectric techniques. 38,39Almost all radiolucent gallbladder calculi can besmashed and adjuvant treatment with

ursodeoxycholic acid and chenodeoxycholic acid isgiven for clearance of the fragments. After eighteenmonths, more than 90% of stones up to 30 mm indiameter are completely cleared. Not surprisingly,better results are obtained with smaller stones.What are the drawbacks of lithotripsy? The

machines are expensive and only about a quarter ofselected patients referred for treatment are suitable,giving an overall figure for suitability in gallstonedisease of approximately 10%. Up to a third ofpatients have biliary colic while passing stone

fragments. Skin petechiae may be expected in 14%and haematuria in 3%. When the treatment fails,alternative procedures are needed. The risk ofrecurrence of gallbladder stones would be the same asfor other techniques of management of gallstones thatdo not involve removal of the gallbladder, althoughrepeat lithotripsy or full-dose continuous bile acidtherapy may avoid this difficulty. The treatment hasseveral glossy advantages. It is quick-treatmentsessions typically last about three-quarters of anhour-and it does not require admission to hospital. Italso avoids the abdominal scar that many patients see

30. Kuwahara M-A, Kambe K, Kurosu S, et al. Clinical application of extracorporealshock wave lithotripsy using micro explosions J Urol 1987; 137: 837-40.

31. Harrison J, Morris DL, Haynes J, Hitchcock A, Womack C, Wherry DCElectrohydraulic lithotripsy of gallstones—in vitro and animal studies. Gut 1987,28: 267-71.

32. Paumgartner G, Stiehl A, Gerok W. Trends in bile acid research In:Proceedings of XInternational Bile Acid Meeting, June, 1988 Lancaster: Kluwer (in press).

33 Ell C, Kerzel W, Heyder N, Becker V, Hermanek P, Domschke W. Piezoelectriclithotripsy of gallstones. Lancet 1987; ii: 1149-50.

34. Sackmann M, Delius M, Sauerbruch T, et al. Shockwave lithotripsy of gallbladderstones. N Engl J Med 1988; 318: 393-97.

35 Hood KA, Keightley A, Dowling RH, Dick JA, Mallinson CN. Piezo-ceramiclithotripsy of gallbladder stones: initial expenence in 38 patients. Lancet 1988, i:

1322-24.

36. Gacetta DJ, Cohen MJ, Crummy HB, Joseph DB, Kuglitsh M, Mack E. Ultrasoniclithotripsy of gallstones after cholecystectomy AJR 1984; 143: 1088-89

37. Bateson MC. Bile acids in health and disease J R Soc Med 1988; 81: 301-0238. Sackmann M, Weber W, Delius M, et al. Extracorporeal shock-wave lithotripsy of

gallstones without general anaestheuc: first clinical experience. Ann Intern Med1987; 107: 347-48.

39 Philp T, Kellet MJ, Whitfield HN, Wickham JEA. Painless lithotripsy: experiencewith 100 patients Lancet 1988; i: 41-43

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as the only and unappealing evidence of the surgeon’sefforts.How are health service administrators going to be

persuaded that such treatment for a minority ofgallstone patients is practical economics? The abilitiesof British doctors to assess the usefulness of expensivemedical techniques have been criticised because of toolittle evaluation, advice, research, and consultation.40For gallstone lithotripsy these arguments are partlyanswered by the encouraging experiences in differentcentres in Germany and the USA where the

procedure is widely used. There is at least one mobilelithotriptor going the rounds of patients in the UnitedStates, rather like the old fairground dentist.

Fortunately, there is even better support from anothersource: lithotripsy in urolithiasis is now recognised asa first-line treatment and modern equipment can alsobe used to satisfy the much lesser requirement forlithotripsy in cholelithiasis. In the UK, it would be asplendidly effective long-term economy to provideadditional dual-purpose lithotriptors in each of theEnglish health service regions together with Glasgow,South Wales, and Belfast to serve the whole of theBritish Isles. Since lithotripsy is now displacing manyurolithotomy and at least some gallstone operations, aclear economic gain can be demonstrated for theoutlay. The time must surely come when each healthregion should plan for a local lithotripsy service; if onewaits for private enterprise to fill the gap facilities arelikely to be patchy and ultimately more expensive.And the future? Perhaps percutaneous gallbladderpuncture and MTBE infusion with automatic pumpswill join endoscopic retrograde cholangio-pancreatography and papillotomy and become part ofthe armamentarium of the district general hospitalinterventional radiologist.

HIV TESTING IN THE WORKPLACE

As the AIDS epidemic grows, occupational physiciansface mounting pressure to test routinely for human

immunodeficiency virus (HIV) infection in the workplace.In February the Society of Occupational Medicine and thenewly formed Association of National Health Service

Occupational Physicians convened a meeting at the RoyalCollege of Physicians, London, to debate which

occupational groups, if any, should be screened.Benefits must be weighed against costs. The costs of HIV

screening lie in the anxieties produced by a positive test at atime when there is no proven treatment for symptomlessinfection; in the personal and financial implications forindividuals who are tested, and especially for those found tobe infected (eg, difficulties in obtaining life assurance andmortgages); and in the expense of the test itself, implying asit does the need for preliminary counselling and properly

40 Council for Science and Society. Expensive medical techniques London. Calvert’sPress, 1982.

informed consent. The last consideration assumes added

importance if testing is to be repeated frequently.A possible benefit from occupational screening could be

the protection of the public. Various mechanisms have beenproposed whereby HIV infection in an occupational groupmight present a hazard to the general populace. There isconcern that an infected doctor carrying out invasive

procedures could transmit the virus to his patients; at leastone airline has introduced routine HIV testing for its pilotson the grounds that dementia is sometimes a presentingfeature of AIDS, and might cause accidents; and it has beensuggested that food handlers with AIDS may be more likelyto carry and excrete enteric pathogens. However, all theserisks are theoretical. Moreover, the last two are open toalternative methods of control. Since impaired mentalfunction in pilots is much more likely to arise from otherdisorders (eg, alcoholism) than from AIDS, for the

prevention of accidents it may be better to rely on regularpsychometric and job performance testing, and on

monitoring by co-pilots-an approach that is in line with arecommendation of the World Health Organisation. 1

Similarly, transmission of enteric infection by food handlerscan be controlled by the standard techniques withoutknowledge of HIV status.A second reason for HIV testing might be to protect

employees. Whilst it has been argued that travellers tothird-world countries should be screened because of the

dangers of live vaccines and exotic infections in

immunocompromised individuals, the gains from such apolicy are uncertain, particularly when the prevalence ofHIV infection in a workforce is low. A bigger problem is theneed to protect health-care and laboratory research workersfrom the small but well-documented risk of becominginfected by HIV through their work.12 Repeated screeningof these occupational groups would allow more accurateepidemiological assessment of the hazard accompanyingspecific procedures and activities, and perhaps lead to betterpreventive measures. But without information on

behavioural risk factors the value of such data would belimited.

Employers might also seek benefits from HIV screening.Some companies--eg, in the service industries-may ask fora screening programme because they perceive a commercialadvantage in a "clean"image. If doctors accede to such

requests, they will only reinforce underlying prejudicesabout the nature and transmission of the disease. A strongercase for HIV testing can be made when a new employee isrecruited for prolonged and expensive training; in thesecircumstances it is common practice to screen for healthproblems which might jeopardise the employer’sinvestment. HIV testing is not normally a requirement forentry to company pension or insurance schemes, and even ifit were it would not be a reason for automatic screening ofnew employees since membership of such schemes is nowvoluntary.Judgments on the balance between benefits and costs

depend on personal values, especially when the benefits areenjoyed by one party and the costs suffered by another. Themeeting did not achieve consensus, but most participantssaw no case at present for routine HIV testing of any groupof workers or prospective employees.

1 Department of Health and Social Security AIDS: HIV-infected health care workers.Report of the recommendations of the expert advisory group on AIDS LondonHM Stationery Office, 1988.

2 Weiss SH, Goedert JJ, Gartner S, et al. Risk of human immunodeficiency virus

HIS-1, infection among laboratory workers Science 1988, 239: 68-71