Cholecystitis Without Gallstones

Some degree of cholecystitis is inevitably found in gallbladders that contain calculi. Yet both acute and chronic inflammation, of the gallbladder can arise in the absence of stones. Acute acalculous choleycstitis is a dangerous disease that is sometimes encountered among seriously ill patients who are kept alive in a surgical intensive therapy unit. Chronic acalculous cholecystitis is a rather shadowy entity, but it certainly accounts for some patients with "typical" biliary pain in whom investigations are repeatedly negative for gallstones. Identification of such patients is difficult but worthwhile, because cholecystectomy is as likely to be curative as it is in calculous disease. Occasionallly there is a clear-cut cause for acalculous inflammation of the gallbladder, such as a specific bacteraemia or mechanical obstruction of the cystic duct. This review will consider the acute and chronic types of acalculous cholecystitis plus these secondary forms of the disease, terminating with a brief discussion of cholecystitis without gallstones in paediatric practice.


INTRODUCTION
Some degree of cholecystitis is inevitably found in gallbladders that contain calculi. Yet both acute and chronic inflammation, of the gallbladder can arise in the absence of stones. Acute acalculous choleycstitis is a dangerous disease that is sometimes encountered among seriously ill patients who are kept alive in a surgical intensive therapy unit. Chronic acalculous cholecystitis is a rather shadowy entity, but it certainly accounts for some patients with "typical" biliary pain in whom investigations are repeatedly negative for gallstones. Identification of such patients is difficult but worthwhile, because cholecystectomy is as likely to be curative as it is in calculous disease. Occasionallly there is a clear-cut cause for acalculous inflammation of the gallbladder, such as a specific bacteraemia or mechanical obstruction of the cystic duct. This review will consider the acute and chronic types of acalculous cholecystitis plus these secondary forms of the disease, terminating with a brief discussion of cholecystitis without gallstones in paediatric practice.

ACUTE ACALCULOUS CHOLEYCYSTITIS
Epidemiology Approximately 10 per cent of all cases of acute cholecystitis develop in the absence of gallstones 1, precise figures ranging from [6][7][8][9][10][11][12][13][14][15][16][17] per cent in different series2-5. Acute acalculous cholecystitis (AAC) particularly affects patients who have undergone recent trauma or major surgical operations: in 3 large series bet.we.e.n 12-49 per cent Z of cases of AAC belonged to one or other of these two categories Amongst the remainder, underlying conditions of possible aetiological significance include cardiovascular disease, liver disease, systemic infections, diabetes mellitus, lupus erythematosus and polyarteritis nodosa2'7. In Lygidakis' experience of 80 patients, three 7 other causative factors loomed large in AAC. Papillitis was present in 25 per cent of patients, as demonstrated by histological examination and manometry, 6 per cent had had previous truncal vagotomy (presumably causing biliary stasis) and in 18 per cent the cystic duct was described as long and tortuous (difficult criteria to define) and thus a potential cause of outflow obstruction from the gallbladder. According to Glenn2, however, up to half the cases of AAC are idiopathic, i.e. they develop spontaneously in the absence of concomitant disease.
Increasingly AAC is recognised as a disease of surgical patients in hospital.
Among postoperative patients or those with recent trauma, between 33 and 100 per cent of attacks of acute cholecystitis are acalculous [8][9][10][11][12][13][14][15][16] compared to 10 per cent of attacks complicating medical illnesses or developing overall 12. The actual prevalence of post-traumatic or postoperative AAC depends upon the clinical setting. It affects in 25,000 patients if all surgical procedures are considered or 0.1-1.6 per cent of those requiring intensive care following major operations in general or cardiac surgery [17][18][19]. AAC developed in 0.3% of patients undergoing elective repair of an aortic aneurysm comoared to 13.6% of patients requiring emergency operation for ruptured aneurysm2. Among war casualties AAC occurs in 0.5 per cent of cases9, while in victims of major burn injuries the proportion rises to 3.5 per cent21.
Gallstones and thus calculous cholecystitis are commoner in women, but there is a slight male preponderance (up to 1.5:1) for AAC overall2'6. The male/female,ratio rises to 7:1 for postoperative cases and reaches 20:1 for post-traumatic patients"'. By contrast, the sex ratios for acute calculous cholecystitis approach unity in those with recent operations or trauma22. This discrepancy could indicate that acute calculous cholecystitis in these settings is coincidental and unrelated to the recent injury13.
Alternatively, factors that promote the development of AAC also provoke acute cholecystitis in gallbladders with pre-existing stones, the calculi being incidental23. Patients with post-traumatic AAC tend to be younger than patients with postoperative AAC22, probably because trauma victims tend to be young men13.
AAC can occur from a few davs to several months after the operation or injury but usually within 2-4 weeks 16". Postoperative AAC is especially likely after gastrointestinal surgery 16, in those with surgical complications24 and in those with parenteral nutrition3.
There is evidence that AAC is becoming more frequent in recent years. In 1982 Glenn and Becker reported an increase over a 30-year period in both the number of cases ofAAC as well as the proportion ofacalculous cases amongst patients with acute cholecystitis23. Petersen and Sheldon also founl an increase in the frequency of AAC over a 6-year period in their institution; this increase paralleled the growing use of parenteral nutrition. Likewise Gutman reported an increase in the fre, quency of acalculous cholecystitis, both acute and chronic, over a fifteen-year period"J.

Aetiology
Relevant aetiological factors in AAC are summarised in Table 1 Table 4) non-specific Mechanical obstruction (see Table 4) Others activation of factor XII-dependent pathway increase in prostaglandin E levels in gallbladder mucosa Several other factors contribute to bile stasis in surgical patients. Fever and dehydration will increase bile viscosity. Opiate drugs have a spasmoenic effect on the sphincter of Oddi and will thus further promote biliary stasis32-34. Assisted ventilation with oositive end-expiratory pressure will also reduce bile flow into the duodenum35"and may therefore help to cause AAC. Parenteral nutrition has recently been found to be a risk factor for the development of both calculous and 3 1936 acalculous cholecystitis Absence of oral intake and thus impaired Cholecystokinin (CCK) secretion is probably the dominant factor leading to bile stasis in this situation. Glenn and Wantz had previously described a temporal relationship between resumption of feeding, when the gallbladder presumably tries to evacuate its r 38 contents, and the onset of AAC37. Although Levin eported similar findings sub-sequent authors have been unable to confirm this relationship 11 '12'16'39. Patients in an intensive therapy unit often receive both ventilation, parenteral nutrition and regular opiates and are thus good candidates for AAC. Gallbladder stasis in postoperative or otherwise acutely ill patients can theoretically be prevented or treated by resumption of food intake or by administration of a cholecystagogue. In the dog model, daily infusions of cholecystokinin octpeptide prevented the gallbladder stasis resulting from total parenteral nutrition v. In a group of patients who had undergone oesophagectomy, enteral feeding via an enterostomy as early as the fifth postoperative day prevented or reduced biliary stasis and development of debris in the gallbladder4.
In some series of AAC many patients had received large-volume blood tranfu-sions9'34. It was suggested that the increased bile pigment load secondary to transfusion may injure the gallbladder. A similar effect may occur in the resorption of sequestered blood from fracture sites and haematomas in trauma patients. However, Long found no differences in the amount of blood transfused in patients with AAC compared to control subjectsl9.
Once biliary stasis and functional obstruction have developed, either progressive distension of the gallbladder or forceful contraction could start a vicious cycle whereby venous and lymphatic channels in the wall are compressed. Even the arterial supply might be compromised by mural oedema. Ischaemia would increase the susceptibility of the gallbladder to noxious agents such as toxins, enzymes, chemical agents and bacteria. Ischaemia could be a major risk factor for AAC in elderly patients with arteriosclerosis and in critically ill patients with episodes of hypotension, especially if vasoactive drugs are administered. Sympathetic overactivity during shock may further constrict gallbladder blood vessels. Sympathectomy protects against experimental acute cholecystitis in dogs42, while hypotensive shock can 43 cause focal necrosis of the gallbladder wall As in acute calculous cholecystitis44, infection is probably not a direct cause of AAC but rather a secondary phenomenon 4'45. Certainly, a proportion of bile cultures in every series turns out to be sterile. However, the presence of open wounds is said to predispose to AAC 19. In two other series, 8 of 9 patients with AAC had had bacteraemia in the preceeding week, 39 and 6 of 9 patients with positive bile cultures had previous wound infections with the same organism9. Therefore infection could have a primary role in the causation of AAC in some cases.
Becker suggested the involvement of Factor Xll-dependent pathways in the pathogenesis of AAC46. These pathways may be activated by the transfusion of blood products or by gram-negative bacterial toxins. He demonstrated intense injury to blood vessels in the muscularis and serosa ofdog gallbladders by the systemic injection of Factor XII activators. Other abdominal viscera were affected to a lesser degree or not at all.
Concentrations of prostaglandin E but not prostaglandin F in the gallbladder were noted to be higher in AAC when compared to controls or patients with calculous disease47'48. These levels correlated with the severity of histological inflammation, so prostaglandins could mediate the inflammatory response49.

Clinical Features
The symptoms and signs of AAC are essentially the same as those of acute calculous cholecystitis, except perhaps that constitutional upset tends to be greater6'16 '24'34. However, the typical features may be overshadowed by the concomitant illness or be masked in injured postoperative patients who are heavily sedated and mechanically ventilated. Abdominal pain, commonly in the right upper quadrant, fever and vomiting are the symptoms most frequently reported. Physical signs include abdominal tenderness, distension, loss of bowel sounds and occasionally jaundice. It is important to remember that AAC may present purely as a persistent unexplained fever or as a sudden deterioration in general health. Leucocytosis, hyperamylasaemia and abnormal liver function tests may occur, but they are neither constant nor specific features6'34. A high index of clinical suspicion is therefore needed if this potentially lethal condition is to be diagnosed before the onset of complications.

Diagnostic Tests
The plain abdominal film is unhelpful in the diagnosis of AAC, while oral cholecystography is inappropriate in acutely ill patients who may be nauseated and vomiting. Ultrasonography is non-invasive and safe. It can also be performed at the bedside using a portable machine. Thickening of the gallbladder wall, gallbladder distension, subserosal oedema, pericholecvsticabscess, biliary sludge and wall fragmentation are all helpful clues5'1. Individual signs vary in sensitivity and specificity. Wall thickening, for example, occurs in 81-90 per cent of cases of AAC 5'51 but is also found in non-biliary conditions including hepatitis, hypoproteinaemia, heart failure, renal disease and myeloma52. Experienced operators may be able to differentiate between the mural oedema of a hypoproteinaemic state and the inflammatory thickening of cholecystitis53. Serial scans allow luminal distension and wall thickening to be closely monitored.
Cholescintigraphy involves the intravenous injection of a technetium-labelled derivative of iminoacetic acid. Non-visualisation of the gallbladder despite good hepatic uptake and isotope entry into the intestine indicates gallbladder disease.
Free intraperitoneal spill of isotope suggests perforation 5'5(55. Impaired hepatic function may vitiate the test. The sensitivity and specificity of both ultrasonography and scintigraphy have been assessed by several groups. Mirvis reported a sensitivity of 92 per cent and a specificity of 96 per cent in the ultrasonic diagnosis of AAC56, but other workers using different criteria reported lower sensitivities varying from 36-89 her cent 6'57-By contrast, the sensltlwty of sclntgraphy n the dagnoss of AAC IS 57 60 consistently high, figures of 83-100 per cent being reported Yet, specificitYsseems to be a problem, with up to 54 per cent of abnormal scans being false positive v. The specificity of scintjgr..aphy in the diagnosis of acute calculous cholecystitis is much better (81-96%)'z.
In a small series of 15 patients, computerised axial tomography was found to be 100 per cent sensitive and specific in the diagnosis of AAC56, but these results obviously need confirmation. Other techniques of potential value in the diagnosis of AAC include percutaneous aspiration of bile from the gallbladder and indium-labelled leucocyte scanning 56'63'6 Preoperative diagnosis is certainly more difficult in AAC than it is in calculous disease, and this difficulty must contribute to the high prevalence of complications.
In one large series, for example, 48 per cent of patients showed areas of gangrene while perforation occurred in 8 per cent and empyema in 6 per cent24. In another large series, 50 per cent of patients with AAC had gangrenous gallbladders6, and 40 per cent of 35 gallbladders perforatin during the course of acute cholecystitis had inflammation in the absence of stonesvJ. Johnson recently reported that perforation occurred five times more frequently if operation was delayed until 48 hours after the onset of symptoms than if no delay in surgical treatment occurred66.

Treatment
Although patients with AAC are sometimes given a trial of medical treatment, the attendant toxicity and the risk of complications mean that early laparotomy is essential unless there is rapid clinical improvement. Because gangrene is so common, except in children, cholecystectomy is usually a better option than cholecystostomy. Subtotal  Although biliary colic is a symptom that clearly implicates the gallbladder, the same may not be true for dyspepsia. Price found that dyspepsia was just as common in women with normal cholecystograms as it was in those with gallstones76. By contrast9 Rhind described good symptomatic relief of dyspepsia following cholecystecto.m.y7. Although most authors suggest that CAC can cause dyspeptic symptoms/-, patients with biliary colic are more likely than others to benefit 81 from cholecystectomy From historical reports it appears that cholecystitis is frequently asymptomatic. In a series ofmacroscopically normal gallbladders resected in patients with non-biliary disorders, many neutrophils were observed histologically in 48 per cent82. Likewise, in an autopsy series in which only 8 per cent of deaths were attributable to gallbladder disease, 62 per cent of gallbladders were macroscopically diseased while a further 13 per cent were macroscopically normal but histologically inflamed83. Conversely a healthy gallbladder can theoretically cause pain if there is obstruction to bile flow. Grossly thick-walled gallbladders may turn out to be histologically 84 normal though criteria for the histological diagnosis of chronic cholecystitis seem to vary between observers78. The pathological appearances of cholecystectomy specimens cannot be distinguished between patients with and without persistent symptoms84.
The symptoms of CAC overlap with those of cholelithiasis84; physical examination and laboratory tests are similarly unhelpful in differentiating between the two conditions. The oral cholecvstogram in CAC may be normal or show impaired opacification or filling defects4. The findings on ultrasonography and scintigraphy are equally non-specific. Ultrasound examination, for example, is only 29 to 62 per cent sensitive for CAC58'59'79'85, while scintigraphy can be normal in as many as 60 per cent of cases79'86.
Irrespective of whether clinical or histological criteria are used (and in contrast to AAC), most series of CAC show a marked female preponderance with a sex ratio varying from 2.5" to 10:179,80,87.

Provocative Testing and Cholecystectomy
Since preoperative diagnosis of CAC is difficult and the symptomatic response to cholecystectomy unpredictable, provocative tests have been devised to try and identify patients who will benefit from operation. A provocative agent is administered, and one or more of the following are taken to imply gallbladder abnormality" 1) reproduction of abdominal pain, 2) impaired contraction of the gallbladder demonstrable by oral cholecystography, scintigraphy or ultrasonography, or 3) absence of gallbladder bile on duodenal aspiration or demonstration of pus cells, cholesterol or bilirubin crystals in the bile.
The most commonly used provocative agent is cholecystokinin (CCK). By stimulating contraction of the gallbladder and relaxation of the sphincter of Oddi, 88 89 this hormone produces gallbladder emptying in healthy individuals Ivy first noted that CCK administration could produce biliary colic in somefatients and 3 might therefore facilitate the diagnosis of acalculous biliary disease The pain typically occurred during emptying of the gallbladder and presumably arose from contraction of an inflamed viscus. Subsequently it was suggested that CCK also induced biliary pain in some patients with normal gallbladders in whom bile flow was impedeby pathological narrowing of the cystic duct, the so-called cystic duct syndromev-. Some authorities report that patients with aealculous biliary disease have reduced [94][95][96] gallbladder emptying in response to CCK when compared to healthy subjects 97 98 n but others do not This finding has been taken to "mply gallbladder disease eve 91 99 100 if abdominal pain is not reproduced It has been suggested that patients with a decreased gallbladder response to CCK are more likely to develop gallstones at 101 a later stage An alternative mechanism for biliary pain after CCK administration is through spasm of the sphincter of Oddi 102,103. Yet even in healthy subjects CCK can produce hypertonicity of the gallbladder infundibulum, with consequent delay in gallbladder evacuation and associated pain, especially if the hormone is administered too rapidly89'04. CCK has extra-biliary effects too, increasing motility in both small and large intestine 15 '16 A typical provocation test involves the intravenous administration of Ivy dog unit/Kg body weight of CCK over a period of 30 seconds to three minutes while the occurrence of abdominal pain is noted. Gallbladder emt)tying can be assessed by means of cholecystography7'8, ultrasonography 19 or scintigraphy92'11. The test can be refined by using a duodenal tube to aspirate bile for microscopic examin-ation99,111 Preparations of CCK produced by KabiVitrum and Boots have been used by most investigators. More recently, sincalide (an octapeptide of CCK) or ceruletide (a structurally.sj.m.i.lar.d..ecapeptide) have also been used; each agent produces gallbladder contraction'' z-o. Sincalide is more convenient and more effective by the intramuscular route than the intravenous route 112'117. A fatty meal has also been 11 used to produce CCK release and hence gallbladder contraction 8,119. Hopman and co-workers found fatty meals to be of equivalent potency to exogenous CCK in causing gallbladder contraction 120, but Park found fatty meals to be less effective2.
Certainly, the rate of gastric emptying is variable and different fatty meals have different potencies 122 It is generally acepted that these provocative tests are useful in selecting patients with suspected biliary pain but without demonstrable calculi for cholecystectomy. In most series 80 per cent or more of patients with positive CKK provocation tests have been improved by cholecystectomy ( Table 2). This result compares well with that of cholecystectomy for gallstone disease. At laparotomy the gallbladder could be either normal or inflamed on gross examination; the cystic duct was sometimes found to be narrow or tortuous. Microscopic examination of the gallbladder commonly showed chronic cholecystitis, but some patients have had normal gallbladders and a few others have had cholecystoses or calculous disease. Surprisingly the symptomatic response is indeoendent of the appearance of the gallbladder, 97 123 I27 whether operative or histological There are several drawbacks to the use of the CCK provocation test. Several authors have questioned its specificity, since CCK causes pain in some healthy individuals 97 98 possibly as a result of infundibular spasm In particular, Dunn and colleagues provoked biliary-type pain in 27 per cent of healthy controls 23. Both Dunn and 98,123 Nathan gave CCK over 15-45 seconds and such rapid injection may lead to s asm of the allbladder neck n 94 p g normal individuals.. Further, CCK is known to increase in2testinal motility and cause abdominal pain in patients with irritable bowel syndrome 8. Since irritable bowel syndrome is an important differential diagnosis to CAC in patients with otherwise unexplained abdominal pain, biliary pain might conceivably be confused with intestinal pain. Lastly, a positive CCK test is not always reproducible on repeat testing97, and radiological interpretation of impaired 123 gallbladder emptying is subject to considerable observer bias Proper evaluation of the CCK test would involve comparison of operative and conservative treatment in both positive and negative patients. Most authors, but not all, report that positive responders to the CCK test fare better with op.er.at.io.n.29t_hla prolonged conservative therapy ( Table 2) have been slightly inferior to those of cholecystectomy for positive responders, yet symptomatic benefit has still been reoorted in 80 per cent or more of such patients (Table 3)97 '111'123'125'126'131'134'135'137-142. Moreover, even negative responders to CCK seem to fare better after cholecystectomy than on conservative management alone. It may be that cholecystectomy has a non-specific effect on abdominal pain irrespective of the results of the CCK test. We therefore agree with 143 Sunderland and Carter and Berk 44 that routine use of the CCK test for selection of patients with suspected biliary pain for cholecystectomy is of unproven value, although no better test is currently available.
Non-surgical Treatment of CA C Hypertonicity of the gallbladder neck induced by CCK can be ameliorated by the use of amyl nitrite or glyceryl trinitrate39-'89. These antispasmodics, together with a low fat diet. have been used in patients with CAC with generally unsatisfactory re-sults93'94'127'129. It has recently been suggested that precipitation of cholesterol crystals in CAC may represent an early stage of calculous disease13'145. If this hypothesis were to be confirmed, dissolution therapy could in theory be an attractive proposition.

SECONDARY ACALCULOUS CHOLECYSTITIS
While most cases of acalculous cholecystitis are idiopathic, a small proportion can be clearly attributed to an underlying illness or agent (Table 4).

Specific infections and infestations
These are important causes ofacalculous cholecystitis in certain clinical-settings. In one report from India ascariasis was the aetiological agent in  Emphysematous cholecystitis, in which the infecting organisms (e.g| losstridia, coli- 5 15 forms) produce gas, is occasionally seen in the absence of gallstones The biliary tract can be involved by opportunistic infections in the acquired immunodeficiency syndrome. Presentation can be with abdominal pain, fever, jaundice, or merely with abnormal liver function tests. Both Candida albicans and cytomegalovirus have been reported to cause acalculous cholecystitis in this setting156-58. Acalculouscholangitis demonstrable .r.adiologically has also been attributed to superinfection with Cryptosporidium 159'u.

Mechanical Obstruction
Rarely, acalculous cholecystitis can result from cystic duct obstruction by tumour.
Primary carcinoma of the gallbladder61 or cystic duct162, as well as secondary breast carcinoma 163, can each tresent as AAC. Obstruction by secondary melanoma 64 and Hodgkin's disease 1"65 can cause CAC. Another patient with acquired immunodeficiency syndrome developed fever and jaundice owing to obstruction of the cystic duct by Kaposi's sarcoma157.
Torsion of the gallbladder is a rare cause of necrotizing AAC. It .typically occurs in elderly women, but any age group can beaffected 66'. The age at presentation may be related to the underlying anatomy. Thus two anomalies that 92 permit gallbladder torsion have been described 168. In the first variety, presumably acquired, the gallbladder is suspended by a mesentery that is postulated to elongate because of visceroptosis in elderly subjects. In the second type, presumably congenital, the gallbladder is free-floating on the cystic duct and artery with no attachment to the liver. Exceptionally, torsion can be confined only to the fundus 168 or affects only one half of a double gallbladder169. In another case a floating gallbladder became incarcerated within an epigastric hernia 17. Sudden onset of upper abdominal pain and vomiting are the typical features of torsion, pain often radiating to the back. A rare variant is that of partial recurrent torsion 66. Since torsion of the gallbladder presents like severe acute cholecystitis, precise preoperative diagnosis is almost never achieved. Sonographic and computed tomographic appearances are non-specific17. Gangrene and perforation are almost inevitable in torsion, so prompt operation is needed in any patient with presumed acute cholecystitis who fails to settle. The use of ceftriaxone, a third generation cephalosporin, has recently been associated with the development of allbladder sediments in up to 40 per cent of patients 182 rn receiving high-dose therapy Biliary sympto s may or may not be present. Both symptoms and ultrasonographic appearances are reversible on cessation of therapy.
We have lately seen AAC in one patient after injection of lipiodol into the hepatic artery to demonstrate liver tumour.

ACALCULOUS CHOLECYSTITIS IN INFANCY AND CHILDHOOD
Cholecystitis is much more commonly acalculous in young children than it is in adults. Thus 13 of 16 children (81%) with acute cholecystitis in one series had no gallstones 183. Literature reviews suggest that approximately 40 oer cent of cases of 184.185 acute cholecystitis in the paediatric age group are acalculous By contrast, in another series gallstones were found in 87 per cent of patients, but these were mainly older children u to age 20186. Young children with acalculous cholecystitis are predominantly male 5.
Sixty per cent of children with AAC have had a preceding systemic illness such 45,148 as leptospirosis, scarlet fever or non-specific diarrhoea Mucocutaneous lymph node syndrome is another recognised cause in this age group 174. In other cases cholecystitis could be related to congenital malformation of the bile ducts45'187. As in adults, the aetiology is generally obscure. Bile stasiscould follow dehydration or total parenteral nutrition. Mechanical blockage could result from congenital stenosis of the cystic duct or ductal occlusion by enlarged lymph nodes. The gallbladder can vary from bein distended but non-inflamed (i.e.acute hy-188 drops) to necrotizing cholecystitis ,189, but gangrene and perforation are said to be uncommon45. Bile culture may either be sterile or yield one of a wide range of pathogens.
The clinical presentation of AAC in children is similar to the adult disease. Abdominal pain is present in almost all cases 45'183 and can be localised or diffuse. Vomiting is frequent, and physical signs include tenderness, fever, mass and jaundice. Preoperative diagnosis is not always possible, b..u.t.abdominal ultrasound examination is of particular value in this age group '9'191. Although acute hydrops of the g.aJl.bladder may resolve spontaneously, perforation and biliary peritonitis can occurl, so decompression is recommended. Simple percutaneous aspiration of the gallbladder may be sufficient treatment. Percutaneous cholecystostomy is another recommended approach 45 and should be followed by secondary cholecystectomy if indicated by cholangiographic findings; primary cholecystectomy also has its advocates45'19. The mortality rate can reach 20 per cent 192 in neo.na.te.s. but two lrger series totalling 23 (mainly older) children included no deaths, l.