Gallstones: role of surgery

8

Gallstones: role of surgery RONALD

A. MALT

A hunter treed by his prey, Francis Glisson (1597-1677) probably had little idea that his excruciating abdominal pain was caused by a distended and obstructed gallbladder, in principle the same kind of agony caused when the liver capsule that commemorates his name is distended with parenchymal or neoplastic disease. At the time the only comment Glisson was known to have uttered was that the pain was so severe that ‘There is no relief except by death’. Centuries later Sir Walter Scott in vain rubbed searing hot salt on his chest for the same problem. Modern patients sometimes hang by their fingers from a door-top. All these unfortunates are likely to have been suffering from the same kind of physiological abnormality: namely, a stone impacted in the internal orifice of the cystic duct, confounding the effort of the smooth muscle of the gallbladder to expel it-like bladder spasms in a patient with blood or a bladder stone obstructing the urethra. Although many surgical residents and some of their superiors speak of a patient’s suffering from acute cholecystitis, when he or she really has only biliary colic, the difference is great (Diehl et al, 1990). Injection of a narcotic relieves biliary colic and aborts the attack. Biliary colic itself is never an emergency. Acute cholecystitis often requires drainage or removal of the gallbladder and can be lethal, even if it is less painful than biliary colic. CHOLECYSTECTOMY

Irrespective of what is wrong with the gallbladder, removal of the gallbladder solves most of the problems that concern it. Cholecystectomy eliminates infections of the gallbladder, gallstone formation and adenomyosis of the gallbladder (if adenomyosis really does cause symptoms). Cholecystectomy also prevents carcinoma of the gallbladder if removal is timely. Although remedy of biliary colic by cholecystectomy was known by the late nineteenth century, even now, when the cure is safe, certain and tolerable, some patients would rather submit themselves to almost anything else than to undergo an operation. That is the subject of the rest of this book. Safe biliary surgery was standard from the time of the Second World War II; yet, a pool of ill-trained cholecystectomists, proud of their machismo, still prevailed, relics of the early days of appendicectomy (the most common Baillikre’s Clinical GastroenterologyVol. 6, No. 4, November 1992 ISBN 0-7020-1625-X

743 Copyright 0 1992, by Baillitre All rights of reproduction in any form

Tindall reserved

744

R. A. MALT

abdominal operation of its day) when the motto for some surgeons was ‘two inches, two retractors, and two minutes’. Skeptics added ‘. . . and two months in the hospital’. When the Mayo brothers, Crile, Lahey and Cattell, came on the scene their counter-prescription was at all costs to achieve good exposure of the right-upper-quadrant structures, leaving a long scar. By the 1950s Cattell felt confident in saying that when he was called upon to correct the results of a biliary surgical mishap, if the initial operation had been done through a vertical incision it was too high, too medial and too short. If it had been done through an oblique exposure it was too high, too short and too oblique. Hence, the incision had not been placed where the gallbladder and its related structures were, and the former surgeon’s view of the structures within the triangle of Calot (Figure 1) had been inadequate. RIGHT

HEPATIC

ARTERY

Figure 1. Schema of the normal triangle of Calot. From Stremple (1986), with permission.

Indications for cholecystectomy Can there be any doubt that specialists tend to treat disease according to the therapeutic modalities available to them? Surgeons like knives, radiologists prefer catheters and stents, and endoscopists surround themselves with an amazing array of hot wires and prostheses. Trying to achieve consensus by assessing the opinions of both surgeons and non-surgeons with respect to the appropriateness of cholecystectomy for specific indications, consensus panels were convened by the London School of Hygiene and Tropical Medicine (Scott and Black, 1991). The panels first considered ten important indications for cholecystectomy, including both symptomatic and non-symptomatic indications. Tables 1 and 2 are examples of the panelists’ tasks. When surgeons were queried, they approved about twice as many indications for cholecystectomy (29% versus 13%) and designated only 27% of indications inappropriate, compared with the assessments of a panel composed of both surgeons and non-surgeons. Unfortunately, the outcome of the consensus panels was inconclusive because disagreement prevailed 30-50% of the time. But, since the attack rate of patients with gallstones was only 1% per year, there was wide latitude for opinion.

ROLE

745

OF SURGERY

Table

(A) (B) (C) (D) (E) (F) (G) (H) (I) (J)

1.

Medical indications for cholecystectomy.

Asymptomatic Vague symptoms such as flatulence, heartburn, etc Biliary colic, both a single attack and multiple attacks Acute cholecystitis: Suspected Confirmed, at least 2 months previously Asymptomatic porcelain gallbladder Silent onset of jaundice, in a patient in whom medical and therapeutic causes have been excluded Acute and acute recurrent pancreatitis, with and without a history of significant alcohol consumption Incidental cholecystectomy at the time of abdominal surgery for other reasons, excluding vascular surgery Long-term total parenteral nutrition Asymptomatic cholecystenteric fistula

Reproduced in modified form by permission of Gut and the British Table 2. Appropriate

Medical

indications for cholecystectomy-surgical

Association.

panel.

Indication

Investigative findings

Co-morbidity

Vague symptoms Single attack of biliary colic

Stone in CBD Stone(s) in GB or non-functioning Stone(s) in GB or non-functioning Stone(s) in GB or non-functioning Stone(s) in GB or

No + low No + low

Multiple attacks

of biliary colic

Confirmed acute cholecystitis Suspected acute cholecystitis Porcelain gallbladder Silent onset of jaundice Acute pancreatitis with and without appreciable alcohol intake Acute recurrent pancreatitis No significant alcohol intake Appreciable alcohol intake Incidental cholecystectomy + compatible symptoms

CBD or GB CBD or GB CBD or GB CBD

No + low No + low

Stone in CBD or dilated CBD Stone(s) in GB or CBD Stones in GB or CBD Stone in CBD

CBD, common bile duct; GB, gallbladder. Reproduced in modified form by permission of Gut and the Brifish

No + low No No + low No + low No, low + med No + low No

Medical

Association.

Aesthetics and function Even though the functional result is the touchstone of biliary surgery, the patient also wants a scar that looks good to him or her, not to mention when it is seen by others. Fortunately, aesthetics merge with function when the appropriate incision is chosen. The usual subcostal incision (Figure 2) is not the one of choice because it always cuts at least three nerves, sometimes making the right upper abdominal wall subject to paraesthesia and to the eventration of denervation. Moreover, the injudicious cholecystectomist may cut the abdominal wall so close to the rib margin that insufficient musculofascial tissue remains to allow its proper closure. Subcostal hernias

746

Figure 2. Subcostal nerve-dividing incisions-comparison of interneural incisions. Modified from Bluestone et al (1978), with permission.

R.

A.

MALT

and transverse

are amongst the most difficult to fix for just such reasons; naturally they are also among the ones most likely to herniate or dehisce. The most desirable classical incision is one that can scarcely be perceived and that interferes minimally with neuromuscular function. The best in those respects is a transverse skin incision across the fascia of the right rectus abdominis muscle, followed by longitudinal splitting of the muscle within its sheath (Salembier, 1986). This incision should not be wider than the width of the rectus muscle itself. Less than 20% of the population is suitable for this incision, however, because it demands a lithe and muscled patient, usually a woman. Otherwise, the most aesthetic incision for a conventional cholecystectomy is an interneural incision (Figure 2) or one that is straight across from the end of the right ninth or tenth rib to whatever limit is necessary to perform the operation safely (Bluestone et al, 1978). This incision has the aesthetic function of placing a scar in a line of relaxed skin tension, thereby camouflaging it nearly completely. The scar also does not ripple as much as a vertical incision does when the patient bends in the postoperative period. Although obsolescent evidence suggests also that postoperative pulmonary function is better with a transverse incision as compared with a vertical or

ROLE

747

OF SURGERY

oblique incision, this issue is seldom of major importance, advanced state of anaesthetic management.

considering the

The ultimate incision Is there an ultimate incision? Yes, but the circumstances in which it can be used are so rare that few people have ever seen it: when a panniculectomy to remove lax abdominal skin after massive weight loss is performed, skin and fat cut from the pubis are rolled to the costal margins. A cholecystectomy can be carried out through the muscular layer alone, leaving the skin intact. Who would believe a patient if she sought medical attention and said that she had had her gallbladder removed, yet had no scar? Scarring is absent in the fetus, too, but so far even the boldest proponent of fetal surgery has yet to remove a gallbladder ex utero, let alone in utero. Subtotal cholecystectomy Despite admonitions to remove a diseased gallbladder completely so as to prevent recurrent calculous disease, wisdom dictates another course when the classic cholecystectomy would likely inflict major damage to bile ducts and blood vessels in the operative field (Cottier et al, 1991). Prime examples are: (1) acute cholecystitis in its ligneous phase cementing the ducts, veins and arteries of Calot’s triangle into an inseparable mess, and (2) Mirizzi’s syndrome, in which a stone within the ampulla of the gallbladder either compresses the common bile duct or erodes through its lateral wall. Cholecystectomy

in patients with cirrhosis

Likewise, subtotal cholecystectomy or cholecystostomy is often prudent in a cirrhotic patient (Aranha et al, 1982; Bloch et al, 1985). Torrential bleeding from the gallbladder bed often complicates removal of the gallbladder in a patient with portal hypertension and a coagulopathic syndrome. In these circumstances it is best to decapitate the gallbladder, to extract the stones within it, and to oversew the orifice of the cystic duct internally to prevent backflow of bile. The oversewn gallbladder remnant is then drained with a Malecot catheter or a mushroom catheter. Tube drainage of the gallbladder alone as a cholecystostomy is sometimes appropriate, provided that the gallbladder is solidly stitched to the internal abdominal wall so that no leak develops. Gallbladder sepsis contaminating ascites is a potential disaster. LAPAROSCOPIC

CHOLECYSTECTOMY

No operation in modern history has swept the field faster than laparoscopic cholecystectomy. From a short paper in 1988 by Mouret, a French gynaecologist in Lyons, to wholesale endorsement by the surgical community was a matter of months. Especially interesting to those of us who have been immersed in the endless bureaucracy of controlled trials before a drug or a

R. A.

MALT

device could be approved as being safe for Americans was the fusillade loosed by practitioners in favour of the procedure-and not a sign of bureaucratic disapproval nor of an effort to demand randomized trials. Had there been a demand for trials, it would have been impossible to fulfil because impassioned surgeons were often convinced from the start that reversion to the standards of a conventional cholecystectomy would be unethical. One hopes that an unbiased, dispassionate study of what happened can yet be adduced. A trial from British hospitals, where productivity is not directly tied to income, may provide the answer. Technique Laparoscopic cholecystectomy demands the introduction of carbon dioxide gas into the peritoneal cavity, as in any other form of laparoscopy. Patients with poor respiratory function may suffer hypercarbia, and every patient is potentially susceptible to the results of improper selection or improper surgery (Table 3). General anaesthesia is required if for no other reason than to eliminate the pain of chemical peritonitis that carbon dioxide causes. Table 3. Contraindications

to laparoscopic cholecystectomy.

Bile duct injury Cholangitis Coagulopathy Contraindication to general anaesthesia Pulmonary emphysema, severe Empyema Gangrene Morbid obesity Acute pancreatitis Peritonitis Portal hypertension Pregnancy, usually Retroperitoneal and subcutaneous emphysema, severe Modified from Cuschieri (1991).

Carbon dioxide is used, however, because of its rapid solubility in blood and other body fluids. Nitrous oxide and inert gases have been proposed as alternatives, but without sufficient evidence. Nitrous oxide is flammable in the presence of electrocautery and inert gases seem more likely than carbon dioxide to cause air embolism. The first technical problem is to perform insufflation without having the Veress automatically retracting needle enter a loop of bowel, a large blood vessel or the retroperitoneum. If inflation of the abdomen does not seem appropriate because a patient has too many adhesions from previous surgery or from inflammatory processes, an obturating Hasson cannula is tied under direct vision into a periumbilical site to provide access, somewhat like a procedure for peritoneal dialysis. Some surgeons, indeed, believe that for safety’s sake all peritoneal access should be gained by this means.

749

ROLE OF SURGERY

Once the peritoneal cavity is distended to a maximal pressure of 15 mmHg, either a straight (00) lo-mm diameter telescope or a 30” telescope+ither one with a video camera at its distal end providing x 4 magnification-is introduced into the peritoneal cavity through the periumbilical site. Before 1992 has passed, the present video screen for monitoring the operation will probably have been replaced by a better one, and in 1993 or 1994 by high-definition screens capable of displaying true colour with great resolution, If there are not too many adhesions or too much inflammation from previous intra-abdominal disease, two long forceps with corrugated grasping surfaces are introduced through right subcostal ports into the abdominal cavity. The function of one is to push the fundus of the gallbladder up and over the dome of the liver, the second to retract the ampullary region of the gallbladder and to permit traction on that region later in the procedure to disclose structures in the triangle of Calot (Figure 1). A loop normally used for snaring colonic polyps is a good retractor of the ampulla of the gallbladder when the ampullary wall is compliant. Subsequently, the operator’s instruments are introduced through a left paraxiphoid port (Figure 3). Taking Cushieri’s advice (Cuschieri, 1991; Cuschieri et al, 1991), I prefer to pass the operator’s cannula to the left of the midline through the lower part of the falciform ligament to avoid battling the right-flank cannulas. In general, the surgeon bluntly pulls connective tissue, fat and scar tissue from whatever is obscuring the important anatomy. The goal is obviously to remove the gallbladder with no leakage of bile or loss of blood, while not injuring any of the important surrounding structures. Interstitial blood clots are the more important problem because they obscure the field and are impossible to remove-analogous to infiltration of blood into the structures of the spermatic cord during herniorrhaphy. As experience is gained, even scar and inflammation are not necessarily contraindications (Cooperman, 1990; Reddick et al, 1991). Indeed, obesity may be an indication for laparoscopic cholecystectomy (Unger et al, 1991).

4-s 01

Figure 3. Ports for endoscopic laparotomy Cuschieri.

instruments for cholecystectomy according to

R.

A.

MALT

Instruments A simple electrocoagulating probe is generally the only other instrument required, except for a cannula to admit water for cleaning the operative site and for aspirating free blood and bile. Lasers are pretty toys and lucrative enticements for naive patients, but they have no manifest advantages over a simple electrocoagulation paddle, except for the paucity of obscuring smoke when a laser is used, as compared with the volume of smoke emitted after an electrocoagulation probe has been used to dissect a gallbladder from its bed. Major injuries have occurred because of the laser beam inadvertently severing an important structure within its range. Coumarin-green, dyetuned lasers are safer than others because their beam is not absorbed by haemoglobin; none the less, they are less well suited to dissection because they are not efficient. Clipping the cystic duct twice or ligating it with a Roeder slip knot of chromic catgut (Nathanson et al, 1991a; 1991b), once close to the ampulla of the gallbladder and twice near the common bile duct, completes the difficult part of the operation. About 7040% of the time the cystic artery passes beneath the common bile duct or the common hepatic duct before ramifying on the gallbladder, often sending arterial branches around the cystic duct. The cystic artery is normally controlled by placing two clips near the source of the cystic artery from the hepatic artery and one clip at the distal reach of the cystic artery as it enters the gallbladder wall. A bifid cystic artery is common, and electrocoagulation works about as well in controlling the cystic artery as clips do. After its enucleation by an electrocautery or a laser, the gallbladder is removed from either the umbilical port or the epigastric port through which the surgeon has been operating. If the stones within the gallbladder are too large to permit the sac to be drawn through either large port easily, an ultrasonic lithotriptor is introduced to pulverize the contents. Open fascia beneath either or both of the large ports is stitched closed with 2-O Vicryl stitches; the other sites are closed with strips of tape on the skin alone. Results Initially the merits of laparoscopic cholecystectomy were debated as matters of aesthetics and time compared with those of conventional cholecystectomy : whether four incisions for the laparoscopic ports (or for an occasional fifth port) add up to more or lessvisible injury than is inflicted by the incisions from conventional cholecystectomy. However, discomfort from laparoscopic cholecystectomy proved so evanescent that the new procedure carried the day. Although short incisions probably hurt less than long ones, the role of the Hawthorne effect cannot be denied. The Hawthorne effect (i.e. the positive effects of any intervention) has to be operative in surgery just as it was in the industrial plants that first demonstrated increased productivity either when the intensity of ambient lighting was increased or when it was diminished. Whether in conventional cholecystectomy or in laparoscopic cholecystectomy, however, patients who are primed to believe that they will be

751

ROLE OF SURGERY

discharged 1 or 2 days after conventional cholecystectomy fare almost as well in terms of their comfort and length of stay as patients do undergoing laparoscopic cholecystectomy. Among 500 consecutive patients who had either elective cholecystectomy or an urgent, difficult cholecystectomy, 25% were discharged in 24 h and 50% in 48 h (Saltzstein et al, 1991). Thus, most patients may leave the hospital within 48 h. I believe that laparoscopic inflation of the abdominal cavity alone distends muscles and prevents much postoperative abdominal discomfort. Even though the hospital stay of patients after laparoscopic cholecystectomy is shorter than after conventional cholecystectomy, proper demographic comparisons need to be made for the statistics to have much meaning. The momentary paradigm for the results of laparoscopic cholecystectomy is the report of the Southern Surgeons Group (1991). Uncontrolled and unstructured, its heuristic value is to show that: (1) surgeons are capable of adapting rapidly to new procedures requiring vastly different sensorimotor skills than ones they are used to; (2) the rate of associated bile duct injury (0.5-0.7%) is not prohibitive; (3) the incidence of local infections (1.1%) is acceptable; and (4) the incidence of conversion from contemplated laparoscopic cholecystectomy to conventional cholecystectomy is only 4.7%.

LAPAROSCOPIC CHOLECYSTECTECTOMY SUSPECT

BILE LEAK

BILIARY

SCAN

NEGATIVE

POSITIVE

t EXCLUDEOTHER CAUSES (BOWEL PERF., UTI 1

LOCALIZED

FLUID

NEGATIVEOBSERVE

t CT SCAN

NEGATIVE

ASCITES

POSITIVESTENT

Figure 4. Algorithm for investigating and treating bile duct injuries. CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; THC, percutaneous transhepatic cholangiography; UTI, urinary tract infection. From Peters et al (1991), with permission.

752

R. A.

MALT

None the less, because of many possibilities for bias, the report should be considered a demonstration project rather than an epidemiological study. In addition, the incidence of major injuries to the bile ducts as a result of laparoscopic surgery at the hands of surgeons less skilled than those in the Southern Surgeons Club will probably never be known (Moosa et al, 1990; Garden, 1991; Voyles et al, 1991). The array of major ductal injuries in New England is impressive in both degree and severity. Figure 4 shows an algorithm for the evaluation of possible complications resulting from bile duct injuries (Peters et al, 1991). Expense: hidden and apparent Aside from its benefits to patients and the advantage to hospital administrators in having many short-stay profitable ‘encounters’, laparoscopic cholecystectomy is a goose that seems certain to lay a golden egg for the manufacturers of instruments for laparoscopic surgery, especially as many laparoscopic instruments are one-use, disposable products (Figures 5 and 6; Table 4). -

$ Market Size (U.S.)

$ Millions

1990

1991

1992

~ 1993

~ 1994

II 1995

1996

Figure 5. Laparoscopic surgery--estimated market size (USA) for total (0) and disposable (m) laparoscopic cholecystectomy apparatus from 1990 to 1996. Data courtesy of E. James Hutchens, Microsurge.

Perhaps land-fills will become as choked with the debris from laparoscopic cholecystectomy as they are now with disposable nappies. Contrariwise, the laparoscope manufacturers must be apprehensive that a revolution such as the one they precipitated at the expense of manufacturers of biliary lithotripsy machines could be at hand for them.

753

ROLE OF SURGERY

Projected

Procedures

79904996

m # Procedures

(U.S.) ,127,432

1

1990

1991

1992

1993

1995

1994

1996

Figure 6. Laparoscopic surgery-projected laparoscopic procedures (USA) from 1990 to 1996. Data courtesy of E. James Hutchens, Microsurge.

Table 4. Market-size projections for laparoscopic procedures in the USA, 1991 and 1996. 1991

1996

250000 12000 30000 5000 12000 4000 8000

595000

321000

1414000

3000

152000

Other gynaecology Tubal ligation Other laparoscopic procedures Total

243000 265000

323000 500000

508000

823000

Total procedures

832000

2449000

General surgery Cholecystectomy Appendicectomy Hernia repair Abdominal adhesiolysis Bowel resection Vagotomy Liver biopsy Total Urology/diagnostic

procedures

150000 360000 75000 230000 19000 45000

Percentage of total procedures 90 30 56 16 18 70 42

Courtesy of E. James Hutchens, Microsurge.

Cholangiography

in laparoscopic cholecystectomy

Cholangiography as a part of laparoscopic cholecystectomy is normally a straightforward task. Radiographic contrast medium is injected through one of the right lateral ports to allow passage of a small, rigid cannula with an angulated tip into a nick made in the side of the cystic duct. Afterwards clips close the nick. The value of cholangiography is as much to display the

754

R. A. MALT

anatomy and to help prevent an injury to the bile duct as it is to assess the presence or absence of gallstones in the common bile duct. The safety of endoscopic papillotomy and stone extraction has engendered almost a cavalier attitude to the presence of common duct stones. Alternatively, perhaps the fashion will revert to using intravenously injected cholangiographic contrast media to examine the contents of the common bile duct (Joyce et al, 1991). Contrast media now being developed do not seem to have so many complications associated with them as the older preparations did. Ultrasonography, of course, is not particularly sensitive in identifying the presence of gallstones in the common bile duct. Laparoscopic cholecystectomy has made the ‘mini-lap’ passe. It always was a difficult way to glean information more readily found by other means.

CHOLECYSTOLITHOTOMY From time to time someone launches a crusade to spare the gallbladder. Why, after all, remove a gallbladder if stones are at fault? The obvious reasons are that: (1) the gallbladder that contains stones is abnormal in and of itself and contributes to the formation of gallstones; and (2) the apparently simple operation of cholecystolithotomy may be nearly as complex as is cholecystectomy in any of its guises. Thus, despite persuasive arguments for retaining the gallbladder to prevent loss of its reservoir function and putative effects on gastro-oesophageal reflux and other symptoms (Walsh and Russell, 1992), from a practical aspect it is as well lost. Except as an emergency procedure to avoid having to dissect a dangerously inflamed gallbladder, cholecystostomy suits the stubborn or the terminal patient, but has little else to recommend it, since the stones invariably return. However, if an ex tempore drainage procedure, asfor acalculouscholecystitis, has to be conducted in the radiology department or at the patient’s bedside for any of a variety of reasons, this is it (Werbel et al, 1989). The big problem in deciding how to treat cholelithiasis and its complications is that decisions about what is feasible and appropriate are often made by specialists who do not normally treat patients with gallstones except with a single therapeutic modality at their command, e.g. endoscopic papillotomy. As a consequence they cannot weigh the relative merits of a standard surgical procedure as opposed to those-or that-under their normal control. The tendency among some physicians also is to assume that a patient is too ill for an operation to be carried out successfully, whereas the truth is that the patient is too ill not to have a cholecystectomy, which can normally be performed without difficulty by any experienced surgeon.

RECURRENCE

OF GALLSTONES

Among 63 patients recently treated by percutaneous cholecystostomy British Columbia, the 48 who were available for recall a mean 18 f 12

in (SE)

ROLE

755

OF SURGERY

months later had a recurrence rate of 27% (Gibney et al, 1989). This datum is considerably lower than the one resulting from studies in Sweden in 1954 and 1955, however, when 53 patients were operated on with the intent of removing stones and preserving gallbladder function and whatever else is contributed by the presence of a gallbladder. The recurrence rate was 83% within 15 years (Norrby and Schdnebeck, 1970). With passage of time, other groups are likely to confirm this unenviable statistic. After extracorporeal shockwave lithotripsy in the late 1980s however, the predicted recurrence rate was only about 45% in 5 years. The remarkable thing was that even if the stones recurred after shockwave lithotripsy, they were largely asymptomatic. Indeed, a single treatment with extracorporeal lithotripsy seems to free a patient permanently from gallbladder colic. GALLBLADDER

SEPSIS

Even though the majority of septic gallbladder disease is simple and is remediable by simple antibiotics and drainage of the bile duct or gallbladder, or both, complex cases abound, even at the smallest hospitals. Because of nasobiliary tubes, endoscopic papillotomy and percutaneous transhepatic cholangiographically guided insertion of tubes to drain pus and blood from the gallbladder and bile ducts into the intestinal tract, together with potent and specific antibiotics, the once feared complication of septic cholecystitis and cholangitis is ordinarily just another hurdle to be cleared. The major problem is recognizing when a patient must have timely and adept percutaneous drainage of the gallbladder or cholecystectomy with drainage of its area of local sepsis. Oedema in the gallbladder bed facilitates removal of a gallbladder filled with pus. The major problem is preventing bleeding from the plethoric, friable gallbladder bed. None the less, simple tamponade of the bed with a large gauze pad faced with a rubber dam (or other non-adherent surface) to prevent the pad from sticking to the blood clot and pulling it away, is the only treatment normally required. If that method is unavailing, the gauze pad might have to be laid over a sheet of thrombin-soaked microcrystalline collagen. In extremis, when the gallbladder bed bleeds excessively, and the right liver that is not too turgid, it can be folded upon itself in the plane of the gallbladder bed and kept bent for tamponade of bleeding by judicious insertion of a few heavy chromic catgut sutures. Sometimes these sutures have to be tied over Teflon bolsters to keep them from cutting through the liver tissue. Emphysema of the gallbladder (emphysematous cholecystitis) is a special variety of cholecystitis, in which the contents of the gallbladder are aerobic gas-forming organisms, such as Clostridium perfringens (Ruby et al, 1983). Gas that forms within the gallbladder forces its way into the hepatic ducts and biliary radicals to make an unforgettable radiological image (Figure 7) and a fine surgical specimen. Appropriate antibiotics against the microbial species presumed to be at fault are started, and changed as the culture data require.

756

R. A. MALT

Figure

ACALCULOUS

7. Emphysema of the gallbladder.

CHOLECYSTITIS

Bile has been called malevolent when it refluxes into the stomach and causes so-called bile gastritis. That is not the only source of difficulty, however. The coalescence of poorly emulsified bile into sludge within the gallbladder can precipitate acute cholecystitis even in the absence of gallstones or bacteria, Loss of normal patterns of emulsification and of expulsion of gallbladder contents in the bedridden patient who spurns food or in the gallbladder of a patient maintained on total parenteral nutrition, unable to eat, is another common source of biliary sludge. Whether the disease in a particular patient is termed calculous or acalculous, and whether it is caused by total parenteral nutrition itself or by failure to eat, is often a matter of how the person responsible for administering care views the subject (Messing et al, 1983; Roslyn et al, 1983). As a side event, we have come to know that bile itself is probably not malevolent; rather, it is the activated pepsin, trypsin and, perhaps, lysolecithins associated with bile in the course of gastrointestinal mixing that may be at fault-either that or multifocal areas of

ROLE

757

OF SURGERY

small-vessel arterial ischaemia that bear analogy to low-flow states in the splanchnic circulation (Warren, 1992). The important clinical point is that acalculous cholecystitis in a weak, depleted and confused patient often manifests itself only by the presence of unexplained fever, often slight. Despite minimal signs and symptoms, the disease may be lethal. Forty per cent of 40 patients with acalculous cholecystitis at the Massachusetts General Hospital in one time interval, who had an operation more than 48 h after the onset of symptoms, had a perforated gallbladder, compared with perforation in only 8% when the delay was shorter (Johnson, 1987). The fact that the death rate for patients with acalculous cholecystitis is high is more a reflection of the disease that gave them an atonic gallbladder than of any problem with the gallbladder itself or with the drainage procedure. The emergency treatment of early acute acalculous cholecystitis is direct drainage of the gallbladder by a percutaneously introduced, ultrasonically guided drainage catheter under appropriate antibiotic coverage, or by surgery (Lee et al, 1991). Cholecystectomy is appropriate only when percutaneously guided gallbladder drainage is not available, when the gallbladder is gangrenous, or when there is reason to inspect or to treat other organs in the vicinity. Although complications of the drainage procedure are few, they include duodenal puncture and liver injury. Because cholecystokinin octapeptide (CCK-OP) is a harmless and inexpensive cholecystogogue ($17 per unit), routine administration of CCK-OP to patients at risk and to protect the lumen of the gallbladder from harm by toxic products in sludge or by some component of biliary excretion may be appropriate. A randomized trial in progress should produce relevant data. DIABETES

AND GALLBLADDER

DISEASE

In 1962 an article from the Massachusetts General Hospital strengthened a long-held, poorly established concept that diabetes confers a major surgical risk upon the patient who also has gallbladder disease, chiefly because of perforation (Mundth, 1962). The risk allegedly was so strong that prophylactic cholecystectomy was recommended in some quarters. The manuscript is now, however, chiefly of interest to epidemiologists in teaching elementary classes the biases of such studies. SICKLE

CELL

DISEASE

Because many patients with pigment gallstones are of mediterranean or Middle Eastern extraction, gallstones and sickle cell disease often co-exist. Forty per cent of patients with sickle cell disease may expect to have gallstones detectable by ultrasonography by the age of 18 years. In addition there are secondary manifestations of sickle cell disease. These tend to be primarily or secondarily thrombotic phenomena, such as osteomyelitis, avascular necrosis of the femoral head, splenic infarction and abscess

758

R. A. MALT

formation, priapism, retinopathy, renal disease and leg ulcers (Ware et al, 1988). Victims of the haemoglobinopathy are also at risk of a peculiar and severe form of pulmonary disease. Because of their heredity or their medical history, patients who might be in danger of these complications must be treated by assessment of their HbS genotype and their liability to sickling. In anticipation of surgery in general and of gallstone disease in particular, replacement of HbS blood with HbA blood is the essence of treatment (Banerjee et al, 1991). Supplements of plasma or electrolyte solutions to decrease the viscosity of the blood are also required. The ideal haematocrit is <45%; an HbS level of 30% is acceptable. POST-CHOLECYSTECTOMY

SYMPTOMS

Despite the enthusiasm and bias for surgery displayed in the preceding pages, the sad fact is that all patients are not cured of episodic biliary colic, or what seems to be colic, by removal of their gallbladder (Bar-Meir et al, 1984; Houghton et al, 1984; Lasson, 1987; Jorgensen et al, 1991). Furthermore, dyspepsia and other digestive abnormalities of obscure origin develop in 47% of patients (Tables 5 and 6). This datum is not a firm one, however, Table 5. Causes of post-cholecystectomy syndrome. Common duct stone Retained gallbladder Stricture of bile duct Long common duct remnant Stenosis of papilla of Vater Modified from Moody (1986). Table 6. Mimics of post-cholecystectomy syndrome.

Irritable bowel Peptic ulcer disease Reflux oesophagitis Non-biliary pancreatitis Hepatic disease Coronary artery disease Painful or painless neuromas Modified from Moody (1986).

since the adequacy of control groups is often uncertain. Recently 274 consecutive patients were loosely followed by means of a questionnaire survey and by recurrent observation. Results were analysed by multivariant discriminant analysis. Risk factors for postoperative dissatisfaction with surgery were: (1) preoperative flatulence; and (2) the history of a long duration of putative biliary symptoms, including pain (as assessed on a linear

ROLE

759

OF SURGERY

analogue scale). Somewhat to the surprise of older clinicians, gallstones impacted in a long cystic duct stump or gallstones thought to be periodically shed into the common bile duct were not incriminated. Although these studies were conducted on a presumably reasonably homogeneous group of patients in the UK and were conducted with as much accuracy and precision as is likely to be possible, the outcome was less than definitive. But that is their nature. Perhaps psychometrics would add firmness to conclusions. Bile duct manometrics do seem to be abnormal in 14% of patients after cholecystectomy. The carry-home message is that there is postoperative disgruntlement in the hustings, and one had better be prepared to anticipate it. Perhaps in one respect the issue is merely that loss of their gallbladder allows patients who have had a cholecystectomy to eat what they please, but even a 4.6% gain of weight in men and a 3.3% gain in women 6 months after cholecystectomy is grudgingly laid at the surgeon’s door (Houghton et al, 1984; Bates et al, 1991). WANDERING

GALLSTONES

As if biliary colic and septic cholecystitis were not punishment enough, sufferers from gallstone disease, especially those in the geriatric age group, are liable to harbour large gallstones. By pressure necrosis, large gallstones can erode through the gallbladder into adjacent bowel, causing a cholecystoenteric fistula. Potential complications of this situation are cholangitis, gastrointestinal haemorrhage and migration of calculi into the lumen of the small intestine or duodenum into the small bowel or, less commonly, into the colon. Bile salts are lost from the enterohepatic circulation. In both the small bowel and the colon certain tight areas exist: one region near the ligament of Treitz, one at the distal end of the descending colon, and one just proximal to the ileocaecal valve. Three quarters of large gallstones passing through the intestinal tract are held up at the terminal ileum (Clavien et al, 1990). A liberated stone is likely to be stopped at one of these areas, producing so-called gallstone ileus, i.e. small bowel obstruction from obturation of the stone in the gut. The discovery by imaging studies of air in the biliary radicals as a result of their communication with the intestinal tract, plus signs of small bowel obstruction makes the diagnosis. Figure 8 illustrates a computed tomographic image of a gallstone with a central translucent nidus and dense peripheral calcification trapped in the small bowel. Since the stone is apparently smooth, this is likely to be a solitary calculus. If it were a faceted stone, the implication would be that other stones pressing against it must have been present within the gallbladder and that they are capable of dropping into the gut to cause recurrent gallstone ileus anytimeunless they are so small that they are passed unknowingly and uneventfully in the stool. Sackmann and his colleagues (1991) caused exactly that situation to happen therapeutically by fragmenting an obturating gallstone with shockwaves from an electrohydraulic lithotripter at maximal voltage.

760

R. A. MALT

Figure 8. Computed tomographic scan of gallstone with calcified rim (arrowed), impacted in small bowel, and central clear nidus; not faceted.

The question then arises as to whether or not the site of the enteric fistula should simply be left as it is because the (usually) elderly patient is too frail for a contemporaneous major operation. Although a period of delay or of no surgery at all has traditionally been urged, the present state of technological and physiological expertise is such that a poor outcome is uncommon. Prompt attention to evacuation of the contents of the cholecystenteric fistula is good prophylaxis against recurrent gallstone ileus in any event. To the contrary, if a patient is too frail for a concurrent operation, but subsequently has a normal cholecystocholangiogram (i.e. no stones in the gallbladder and common duct) and no subsequent pain, the gallbladder shrinks to a fibrotic nubbin and the fistula normally closes spontaneously. CARCINOMA

OF THE GALLBLADDER

Insidious and nearly always incurable, this is the worst complication of gallstones-but fortunately is also the most rare. The surgeon usually begins to think about carcinoma only when confronted by having to work exceptionally hard to remove a gallbladder from its liver bed. Although gallbladder cancer is uncommon in the USA, metabolic abnormalities amongst some Mexicans and the Pima Indians of the American south-west cause them to form gallstones at an early age; gallstones, in turn, are probably responsible for irritative phenomena within the gallbladder, predisposing to hyperplasia and cancer. The incidence of gallbladder cancer in Indians is six times that in non-Indians. In Mexico, gallbladder cancer is the second most common gastrointestinal malignancy, excepting only gastric cancer. Although one could invoke putative clinical carcinogens from transformed bile salts as an explanation for this concurrence of diseases,

ROLE OF SURGERY

761

Occam’s razor would indict only hyperplasia and dysplasia of the gallbladder wall. Data showing that elderly patients have a lO-17% incidence of gallbladder cancer are probably skewed by ascertainment bias. Bias is probably also responsible for the statistic that gallstones of 2.0-2.9 cm in diameter are associated with an odds ratio of cancer of 2.4 and stones > 3.0 cm in diameter with a 10.1 odds ratio. Indeed, apparently authoritative government statistics about gallbladder cancer may be wrong, because until recently gallbladder cancer, cancer of the extrahepatic bile ducts and cancer of the ampulla of Vater were lumped into a single diagnostic category. Practically the only gallbladder cancers ever cured are those discovered incidentally during an apparently routine cholecystectomy. Provided that the cancer does not penetrate the muscular layer of the gallbladder wall, cure is likely. Once the gallbladder wall is transgressed by cancer, hope is forlorn. Microscopic examination of every gallbladder removed from an elderly patient while in the operating room to see whether a cancer exists is counsel of perfection and of poor economics.

Figure 9. Venous drainage of gallbladder direct to the liver bed and associated lymphatics. Modified from Fahim et al (1962).

762

R. A.

MALT

In an attempt to counter fate, aggressive surgeons plea for regional hepatectomy to eliminate neoplastic cells in the area surrounding the cancerous gallbladder. Although this attitude transiently buoys the patient and her family (oestrogens being a carcinogen or a promoter of gallbladder cancer), it accomplishes nothing therapeutic because the venous drainage of the gallbladder is direct into the liver, and its nodal drainage along the portal triad and behind the duodenum is beyond resection (Figure 9).

Porcelain gallbladder One has to be perplexed about the lack of agreement concerning the propriety of removing a porcelain gallbladder (one with a more-or-less calcified wall) just because some authorities say that such a gallbladder is associated with a 20-60% risk of gallbladder cancer. Neither I nor any of my colleagues at the Massachusetts General Hospital has seen a porcelain gallbladder with cancer in it, nor have we discovered such an association while studying the records of patients with carcinomatous gallbladders over the past two decades. We must therefore defer to those who are impressed by such an association and who have estimated the resultant risk of gallbladder cancer as being 0.3-2.0% of all elderly patients. The relationship between gallbladder cancer and chronic ulcerative colitis in 12 patients appears to make a stronger case for causality.

INFECTIONS

IN GALLBLADDER

SURGERY

In a prospective, uncontrolled study of wound infection in 347 patients having gallbladder surgery over a period of almost 3 years (1982-1984) at The University of Connecticut School of Medicine, 64% of patients received a prophylactic cephalosporin (Garibaldi et al, 1986). None the less, 13 of 347 (3.7%) patients had wound infections: a 1.9% rate for cholecystectomy alone and an 18.4% rate for patients undergoing cholangiography or exploration of the common bile duct, or both. As in other studies, jaundice was a risk factor for the presence of severe infection, and patients with bactibilia had a six-fold incidence of postoperative infection as compared with the results of bile cultures from patients whose bile was sterile. Obviously the presence of jaundice itself introduced bias and confounding. Therefore, assessments of relative risk are weak. The practice of culturing the gallbladder at the time of surgery may be an expensive irrelevancy, inasmuch as the species and number of bacteria isolated from bile during surgery, the number of bacteria in the wound at its closing and in septic wounds later, and the species of bacteria isolated from the gallbladder were not the same bacteria identified as being responsible for postoperative sepsis (Garibaldi et al, 1986).

763

ROLE OF SURGERY

COLIC

WITHOUT

GALLSTONES

For more than 20 years a syndrome of recurrent right-upper-quadrant pain, ostensibly exactly like that of biliary colic but not associated with gallstones, has been described (Valberg et al, 1971). Even so, American surgeons who believed in this entity were reluctant to act on their instincts to remove the gallbladder of sufferers because tissue committees auditing the propriety of gallbladder surgery were also unable to identify a disease of the gallbladder. The operator was subject to censure for unnecessary removal of a ‘normal’ gallbladder (Yap et al, 1991). Now, evidence is good that gallbladder colic or its mimic occurs in some patients, especially women, and especially in the absence of calculous disease (Valberg et al, 1971). The cause of this putative syndrome probably relates to the presence of abnormal motility patterns and chronic acalculous inflammation in both the gallbladder itself and in the region of the papilla of Vater. In quantitative measurements of the gallbladder ejection fraction*, 40% ejection was defined as the normal level (Yap et al, 1991). Subjects who had an abnormally low level were randomized either to cholecystectomy or observation alone. In patients randomized to cholecystectomy, 12 of 13 gallbladders showed chronic cholecystitis or other abnormalities when examined histologically. Those randomized to observation lost their symptoms gradually over 3 years. * Gallbladder ejection fraction (%) = change in gallbladder activity X 100.

activity/base-line

gallbladder

REFERENCES Aranha GV, Sontag SJ & Greenlee HB (1982) Cholecystectomy in cirrhotic patients: a formidable operation. American Journal of Surgery 143: S-60. Banerjee AK, Layton DM, Rennie JA & Bellingham AJ (1991) Safe surgery in sickle cell disease. British Journal of Surgery 78: 516-517. Bar-Meir S, Halpern Z, Bardan E & Gilat T (1984) Frequency of papillary dysfunction among cholecystectomized patients. Hepatology 4: 328-330. Bates T, Ebbs SR, Harrison M & Hern RPA (1991) Influence of cholecystectomy on symptoms. British Journal of Surgery 78: 964-967. Bloch RS, Allaben RD &Walt AJ (1985) Cholecystectomy in patients with cirrhosis. A surgical challenge. Archives of Surgery 120: 669-672. Bluestone L, Freed JS & Szuchmacher PH (1978) The interneural incision for biliary tract operations. Surgery, Gynecology and Obstetrics 147: 21-24. Clavien PA, Richon J, Burgan S & Rohner A (1990) Gallstone ileus. British Journal of Surgery 77: 737-742. Cooperman AM (1990) Laparoscopic cholecystectomy for severe acute, embedded, and gangrenous cholecystitis. Journal of Laparoendoscopic Surgery 1: 37-40. Cottier DJ, McKay C & Anderson JR (1991) Subtotal cholecystectomy. British Journal of Surgery 78: 13261328. Cuschieri A (1991) Minimal access surgery and the future of interventional laparoscopy. American

Journal

of Surgery

161: 404-407.

Cuschieri A, Dubois F, Mouiel J et al (1991) The European experience with laparoscopic cholecystectomy. American Journal of Surgery 161: 385-387.

R. A.

MALT

Diehl AK, Sugarek NJ & Todd KH (1990) Clinical evaluation for gallstone disease: usefulness of symptoms and signs in diagnosis. American Journal of Medicine 89: 2933. Fahim RB, McDonald JR, Richards JC & Ferris DO (1962) Carcinoma of the gallbladder: a study of its mode of spread. Annals of Surgery 156: 114124. Garden OJ (1991) Iatrogenic injury to the bile duct. British Journal of Surgery 78: 1412-1413. Garibaldi RA, Maglio S, Lyons R et al (1986) Postcholecystectomy wound infection. The impact of prophylactic antibiotics on the epidemiology of infections. Annals of Surgery 204: 650-6.54. Gibney RG, Chow K, So CB et al (1989) Gallstone recurrence after cholecystolithotomy. American

Journal

of Roentgenology

153: 287-289.

Houghton PWJ, Donaldson LA, Jenkinson LR & Crumplin MKH (1984) Weight gain after cholecystectomy. British Medical Journal 289: 13.50. Johnson LB (1987) The importance of early diagnosis of acute acalculus cholecystitis. Surgery, Gynecology

and Obstetrics

164: 197-203.

Jorgensen T, Teglbjerg JS, Wille-Jorgensen P & Bille TE, Thorvaldsen P (1991) Persisting pain after cholecystectomy. A prospective investigation. Scandinavian Journal of Gastroenterology 26: 124-128. Joyce WP, Keane R, Burke GJ et al (1991) Identification of bile duct stones in patients undergoing laparoscopic cholecystectomy. British Journal of Surgery 78: 1174-1176. Lasson 8, (1987) The postcholecystectomy syndrome: diagnostic and therapeutic strategy. Scandinavian

Journal

of Gastroenterology

22: 897-902.

Lee MJ, Saini S, Brink JA et al (1991) Treatment of critically ill patients with sepsis of unknown cause: value of percutaneous cholecystostomy. American Journal of Roentgenology 156: 1163-1166. Messing B, Bories C, Kunstlinger F & Bernier JJ (1983) Does total parenteral nutrition induce gallbladder sludge formation and lithiasis? Gastroenterology 84: 1012-1019. Moody FG (1987) Postcholecystectomy syndromes. Surgery Annual 19: 205-220. Moosa AR, Mayer AD & Stabile B (1990) Iatrogenic injury to the bile duct: who, how, where? Archives

of Surgery

125: 1028-1031.

Mundth ED (1962) Cholecystitis and diabetes mellitus. New England Journal of Medicine 267: 642-646. Nathanson LK, Easter DW & Cuschieri A (1991a) Ligation of the structures of the cystic pedicle during laparoscopic cholecystectomy. American Journal of Surgery 161: 350354. Nathanson LK, Shimi S & Cuschieri A (1991b) Laparoscopic cholecystectomy: the Dundee technique. British Journal of Surgery 78: 155-159. Norrby S & Schdnebeck J (1970) Long-term results with cholecystolithotomy. Acta Chirurgica Scandinavica 136: 711-713. Nussbaum R & Fromm H (1992) Laparoscopic cholecystectomy: a new procedure in need of further study (Comments on:). Gastroenterology 102: 362-364. Olsen DO (1991) Laparoscopic cholecystectomy. American Journal of Surgery 161: 339-344. Patti MG, Leichter RF & Pellegrini CA (1991) Biliary surgery: stones and strictures. Current Opinion

in Gastroenterology

7: 794-799.

Perissat J, Collet D, Belliard R, Dost C & Bikandou G (1990) Cholecystectomies par laparoscopie. La technique optratoire. Les resultats des 100 premieres observations. Journal

de Chirurgie

(Paris)

127: 347-355.

Perissat J, Collet D & Belliard R (1991) Laparoscopic surgery for gallbladder stones. Annals Medicine

of

23: 233-236.

Peters JH, Gibbons GD, Innes JT et al (1991) Complications of laparoscopic cholecystectomy. Surgery

110: 769-778.

Phillips E, Daykhovsky L, Carroll B, Gershman A & Grundfest WS (1990) Laparoscopic cholecystectomy: instrumentation and technique. Journal of Laparoendoscopic Surgery 1: 3-15. Ponsky JL (1991) Complications of laparoscopic cholecystectomy. American Journal of Surgery 161: 393-395. Reddick EJ, Olsen D, Spaw A et al (1991) Safe performance of difficult laparoscopic cholecystectomies. American Journal of Surgery 161: 377-381. Roslyn JJ, Pitt HA, Mann LL, Ament ME & DenBesten L (1983) Gallbladder disease in patients on long-term parenteral nutrition. Gastroenterology 84: 148-154.

ROLE

OF SURGERY

765

Ruby ST, Gladstone A, Treat M & Weber CJ (1983) Emphysematous cholecystitis. A case report. Journal of the American Medical Association 249: 248-249. Sackier JM, Berci G, Phillips E et al (1991) The role of cholangiography in laparoscopic cholecystectomy. Archives of Surgery 126: 1021-1026. Sackmann M, Ho11 J, Haerlin Met al (1991) Gallstone ileus successfully treated by shock-wave lithotripsy. Digestive Diseases and Sciences 36: 1794-1795. Salembier Y (1986) Cholecystectomie par une courte incision transverse. Presse Medicale 15: 210-211. Saltzstein EC, Mercer LC, Peacock JB & Dougherty SH (1991) Twenty-four hour hospitalization after cholecystectomy. Surgery, Gynecology and Obstetrics 173: 367-370. Scott EA & Black NO (1991) Appropriateness of cholecystectomy in the United Kingdom-a consensus panel approach. Gut 32: 1066-1070. Southern Surgeons Club(1991) A prospective analysis of 1518 laparoscopic cholecystectomies. New E&and Journal of Medicine 324: 1073-1078. Stremple JF-(1986) The need for careful operative dissection in Moosman’s area during cholecystectomy. Surgery, Gynecology and Obstetrics 163: 169173. Thomas MG, Grace PA, Benjamin IS & Williamson RCN (1991) Carcinoma of the gallbladder, acute cholecystitis and cholecystostomy. European Journal of Gastroenterology and Hepatology

3: 277-279.

Unger SW, Scott JS, Unger HM & Edelman DS (1991) Laparoscopic approach to gallstones in the morbidly obese patient. Surgical Endoscopy 5: 116117. Valberg LS, Jabbari M, Kerr JW et al (1971) Biliary pain in young women in the absence of gallstones. Gastroenterology 60: 1020-1026. Voyles CR, Petro AB, Meena AL, Haick AJ & Koury AM (1991) A practical approach to laparoscopic cholecystectomy. American Journal of Surgery 161: 365-370. Walsh TN & Russell RCG (1992) Cholecystectomy and gallbladder conservation. British Journal

of Surgery

79: 45.

Ware R, Filston HC, Schultz WH & Kinney TR (1988) Elective cholecystectomy in children with sickle hemoglobinopathies. Successful outcome using a preoperative transfusion regimen. Annals of Surgery 208: 17-22. Warren BL (1992) Small vessel occlusion in acute acalculous cholecystitis. Surgery 111: 163-168. Welch JP & Malt RA (1972) Outcome of cholecystostomy. Surgery, Gynecology and Obstetrics 135: 717-721. Werbel GB, Nahrwold DL, Joehl RJ, Vogelzang RL & Rege RV (1989) Percutaneous cholecystostomy in the diagnosis and treatment of acute cholecystitis in the high-risk patient. Archives of Surgery 124: 782-786. Wittgen CM, Andrus CH, Fitzgerald SD et al (1991) Analysis of the hemodynamic and ventilatory effects of laparoscopic cholecystectomy. Archives of Surgery 126: 997-1001. Wolfe BM, Gardiner BN, Leary BF & Frey CF (1991) Endoscopic cholecystectomy. An analysis of complications. Archives of Surgery 126: 1192-1198. Yap L, Wycherley AG, Morphett AD & Toouli J (1991) Acalculous biliary pain: cholecystectomy alleviates symptoms in patients with abnormal cholescintigraphy. Gastroenterology 101: 786-793.