Cholelithiasis and cholecystitis (an appraisal of clinico-surgical experiences with 228 cases).
Cholelithiasis and cholecystitis are fairly common diseases beset with serious complications. The clinical presentations are varied, diagnosis is at times hazy and the treatment often problematic. This paper presents the pitfalls and challenges in the management of these twin diseases.
Two hundred and twenty-eight cases of cholecystitis and/or cholelithiasis operated by the author at the Sir Hurkisondas Nurottamdas Hospital over the last fitteen years are analysed. Clinical features are not elaborated upon but some facets which influence the therapy, or which dispel some hazy concepts are stressed.
Age and sex [Table - 1]
The disease was commoner in the females. The F: M ratio for the whole group was 1.3:1; it was 2.3:1 in patients under 50; however, in patients over 50, the F: M ratio was 0.82:1. The peak incidence was observed in the fifth and sixth decades; the youngest patient was a girl aged 13 years and the oldest, a 93 year old woman.
Clinical presentations [Table - 2]
The commonest presentation was chronic cholecystitis (109 cases) with all its varied clinical manifestations. Sixty-three patients presented with acute cholecystitis. In 15 instances, gall bladder disease was detected on a routine survey of the biliary tree in patients who presented with pancreatitis.
Of the 24 who presented with icterus, 12 suffered from cholangitis. In eleven cases, cholelithiasis as the cause of jaundice was discovered at operation for persistent jaundice of indeterminate etiology.
In addition to the 24 cases in whom icterus was the presenting symptom (12 cases of cholangitis, 1 case of chronicpancrestitis and 11 cases of gall stones diagnosed at operation) jaundice was observed in 9 cases with acute cholecystitis, patients being unaware of it. In all, thirty patients admitted to history of jaundice in the past, but the cause of this jaundice (hepatitis, gall stones, or others) was not clear in some of these.
In 16 cases, cholelithiasis was found at laparotomy for other diseases.
Flat roentgenogram of the abdomen revealed radio-opaque stones in 93 cases (41%), radio-luscent stones in 125 cases and no stones in 10 cases (as proved at subsequent operation). Double dose oral cholecystography revealed no function or poor function in the gall bladder in 147 cases; interestingly, in 43 cases gall bladder functioned well and in many of these normal ductal anatomy was demonstrated on post-fatty meal film. Oral cholecystogram, was not done in 38 cases (4 cases of emergency operation, 18 cases who were operated for persistent jaundice and 16 cases of gall stones discovered at laparotomy for some other disease). Intravenous cholangiography was carried out in 91 cases, and revealed ductal stones and/or dilatation in 17. In icteric patients neither oral nor intravenous cholangiography was attempted till the serum bilirubin was normal.
Associated diseases (diagnosed clinically, or on investigations, or at laparotomy)
In addition to the frequently present medical problems like hypertension, myocardial ischaemia, chronic bronchitis, and emphysema, 36 patients suffered from diabetes mellitus. In 15 of these, the magnitude of hyperglycemia decreased following surgery on biliary tract disease.
As mentioned earlier, 15 patients presented with pancreatitis; 8 others were found to have chronic pancreatitis at laparotomy.
Peptic ulcer was found in 18 cases (two of these had haematemesis) and hiatus hernia in 13. Cirrhosis of liver was present in 17 and chronic hepatitis in two. In two patients, the liver harbored hydatid cyst.
Ventral scar hernia and congenital spherocytosis were present in two cases each; whereas, non-cirrhotic portal fibrosis, haemangioma of liver, fatty liver, tuberculous ileal stricture, miliary peritoneal tubercles, carcinoid of small intestine, T.B. cecum, and inguinal hernia were present in one case each.
Carcinoma of gall bladder.
This was found in 8 (3.5%) of the 228 cases. In only 3 of these could the gall bladder be resected.
Endoscopic retrograde cholangiopancreaticography (FRCP) was carried out in 4 and/or laparoscopy in three jaundiced patients. Stones were demonstrated by FRCP, and chronic cholecystitis, by laparoscopy. Liver scans with radioiodinated rose-Bengal with delayed films for extrahepatic biliary tree was carried out in four cases.
Ultrasound echosonogram was available in five patients with no false positive results.
Complications of gall stone disease
Apart from cholecystitis, serious complications of gall stone disease encountered,. in the present series were: (1).Gholangitis 15, (2) Jaundice 33, (and perhaps some of the 30 with history of jaundice in the past), (3) Pancreatitis 23, (4) Enterobiliary fistula 2.
For chronic cholecystitis, operation was carried out soon after the diagnosis was made with the necessary pre-operative preparation. If the gall stones are incidentally discovered at a laparotomy for spine other disease, cholecystectomy is always carried out unless there is a cogent contraindication.
Acute cholecystitis was managed conservatively and surgery was carried out three to six weeks later. However, four cases required a semi-emergency operation for persistent pain, pyrexia and a lump. ,In two of these a cholecystostomy was done at a first stage, of empyema of the gall bladder and at a second stage, the viscus was removed.
The fifteen patients with recurrent cholangitis were laparotomised in between the febrile episodes.
Surgery in the 33 icteric patients was deferred till the serum bilirubin normalised. (15 cases) or reached- the lowest possible level (18 cases). The maximum waiting period was two to .six weeks, being shorter if there was cholangitis: In13 of these 18- cases, the serum bilirubin was less than 5 mg. % at the time of operation and in another four, it was 5-10 mg.%; one patient required emergency surgery with bilirubin level of 15.8 mg.% because he also had torrential hematemesis from an associated preexisting peptic ulcer.
Eleven patients with acute pancreatitis of biliary etiology were advised gallbladder surgery four to six weeks after the attack. Patients with chronic pancreatitis and gall stone disease were operated upon soon after the diagnosis was made.
Associated diseases were treated or stabilised prior to surgery. Many of the patients, especially the older ones, were in a state of chronic hypovolemia; during the week or two preceding the operation their fluid intake was increased to 3-4 litres per day. Antibiotics were routinely administered twenty-four to forty-eight hours prior to surgery (ampicillin and/or gentamycin being preferred for reasons discussed later). Jaundiced patients were administered intra-musular vitamin K for three to five days to normalise prothrombin time; they were also infused intravenous mannitol 300 millilitres per day for three days prior to surgery to minimise the risk of renal shutdown. Oral neomycin and protein withdrawal for twenty-four hours pre-operatively were used to obviate post-operative hepatic coma.
Apart from removing the diseased gall bladder and clearing the biliary tree, other surgically correctable diseases were looked for and the requisite additional operative procedures were carried out Table 3]. The most frequently associated disease requiring surgery were peptic ulcer and/or hiatus hernias. A thorough visual and palpatory assessment of all the abdominal viscera and especially of common bile duct, pancreas and liver is mandatory.
Upto 1970, an operative cholangiogram was obtained only when there were some specific indications and the dye for the cholangiogram was injected through the common bile duct. An exploration of the common bile duct was a necessary finale to the roentgenogram. But since 1970, the intra-operative radiogram has been done routinely. If an obvious indication for the ductal exploration existed, the cholangiogram was obtained through the common bile duct as mentioned above. In all other cases, the dye was pushed through a cannula positioned via the cystic duct; this is technically more difficult, but has certain advantages.
In all, 169 operative cholangiograms were done, 49 through the common bile duct and 120 through the cystic duct.' In 11 additional cases, an attempt at transcystic duct cholangiogram failed because of technical difficulties. In 67 cases, abnormal biliary ducts requiring an exploration were discerned; stones with or without dilatation of the duct were detected in 45 and dilatation without lithiasis in 21. In one patient a false negative shadow resulted in an exploration of normal duct.
Eighteen of the 67 patients who required exploration of the choledochus were not icteric in the past or at the time of operation; eleven of these had choledochal stones, five had pancreatitis and two, sphincteric stenosis. On the other hand, in 13 instances with history of jaundice (more than once in two of these), the transcystic cholangiogram showed a normal common hepatic and bile duct.
In 34 cases, the pancreatic duct was visualised in the cholangiographic films. In absence of pancreatitis and in absence of other abnormalities, this was of no consequence.
After exploration and choledocho-lithotomy, the sphincter of Oddi was probed, and if necessary dilated, and then the duct was drained by a T-tube; a per operative T-tube cholangiogram was obtained to ensure against a missed stone or pathology at the sphincter.
An operative elimination of the sphincter of Oddi was deemed essential in 34 cases. This was achieved by a transduodenal sphincteroplasty (never sphincterotomy) in 23 cases with impacted ampullary stones, sphincteric stenosis and/or multiple stones, with a choledochus less than 2 cm in diameter. In 11 cases with the duct dilated to 2 cm or more, a choledochoduodenostomy was carried out.
During operative cholangiography, the bile was aspirated from the common bile duct. This bile as well as the bile obtained from the excised gall bladder were cultured and an antibiotic sensitivity test was carried out. A positive growth was obtained in 42 cases. Mixed growth was seen in 8 cases. The commonest organisms were E. coli (31 cases) and Klebsiella (11 cases). Pseudomonas, Aerobacter aruginosan, Steptococcus hemolytieus and Salmonella typhi were cultured in two cases each.
The most efficacious antibactorial drugs in vitro were ampicillin, gentamycin and co-trimoxazole.
Post operative complications and deaths
The significant morbidity problems were bronchopulmonary complications (5 cases), wound sepsis (2 cases), pancreatitis (4 cases), temporary leakage of bile (5 cases) and myocardial infarction (3 cases). Other post-operative complications seen were subdiaphragmatic abscess (1 case), wound dehiscence (1 case), hepatic coma (2 cases), uremia (1 case) and haemobilia (1 case). There were seven deaths, three from myocardial infarction, one from acute pancreatitis, two from hepatic coma and one from uraemia. Five of the 67 patients who required ductal exploration succumbed post-operatively, whereas only two out of 161, who did not require a choledochostomy, died.
One hundred and fifty patients have been followed up for 1-10 years. Two patients developed Australia antigen positive jaundice two to three months after the operation. One patient with transduodenal sphincteroplasty developed recurrence of common bile duct stones and required choledochoduodenostomy. Another patient following ductal exploration developed recurrent cholangitis which responded to antibiotics; sonographic studies demonstrated normal calibered duct without stones in this patient. Two patients in the earlier part of the series developed ventral scar hernia which was repaired.
Cholecystitis and cholelithiasis occur together so often that when a patient is said to have cholecystitis, concomitant cholelithiasis is assumed. However, one does encounter noncalculous cholecystitis, as seen in 10 of the 228 cases in the present series. In the literature the frequency of acalculous cholecystitis amongst patients with gall bladder disease is reported to be 4 to 6%, , 
This is usually suspected clinically and confirmed by investigations.
Clinical features and complications of gall stone disease.
The clinical presentation of acute and chronic cholecystitis, cholangitis and jaundice due to cholelithiasis are too well known to merit repetition. However, certain features need emphasis. The text book patient of cholelithiasis viz. a fat, fertile, flamboyant, female in forties accounts for less than 40% of the cases. Though the females outnumber males, the males suffer from the disease more frequently than is otherwise thought; also the disease occurs with significant frequency in younger age group. With advancing age the relative frequency of females to males decreases., ,  In fact in this series there were more males than females in the group after the age of 50 years.
The pain is not always experienced in the right hypochondrium. Patients often complain of pain in the epigastrium, or right lumbar region and at times all over the abdomen. Occasionally, pain may be felt only in the back. Similarly, tenderness may be elicited in the epigastrium or in the right lumbar region instead of subcostal region. Every patient with persistent upper abdominal dyspepsia should have evaluation of biliary system, pancreas, upper gastro-intestinal system and the liver, as diseases at these sites frequently coexist.
The so-called "silent" stone is a myth. Even if the stone is silent at a given point of time, more than 50 per cent of such patients, in course of time develop symptoms and/or complication., ,  Various complications of the stones in gall bladder (where majority of the stones originate), apart from acute cholecystitis, are choledocholithiasis, jaundice, pancreatitis, cholangitis, cholecysto or choledochointestinal fistula, and carcinoma. The incidence 'of complications rises with advancing age., , , 
Ten to 25 per cent of patients with acute or chronic cholecystitis have stones in common bile duct,, , ,  (but not all of them necessarily suffer from jaundice). In the present series; organisms (mostly E. coli and Klebsiella) were grown on culture n 42 cases. The bacterial invasion is more frequent if there are stones in the common bile duct., , 
Jaundice complicating gall stone disease may be due to choledocholithiasis or cholangitis. About 20% of patients with acute pancreatitis have jaundice. In acute cholecystitis, icterus may result due to pressure of oedematous Hartman's pouch or pressure of stone impacted in Hartman's pouch on the choledochus.
Pancreatitis and biliary tract disease are causally related, though. the mechanism of the relationship is not clear. The coexistence is not uncommon , ,  The exact incidence of pancreatitis in various series of cholelithiasis and cholecystitis reported from India is not clear. In the present series it was 10 per cent. About 10 to 30% of acute or chronic pancreatitis are due to biliary tract diseases., , , , , ,  Thus in every patient with pancreatitis, biliary tree must be thoroughly assessed and vice versa.
The incidence of carcinoma of gall bladder at operation for cholelithiasis varies from 0.2 to 5.0% in different series., , , ,  Much work has been done to elucidate the causal relationship between cholelithiasis-cholecystitis and carcinoma of gall bladder. Such relationship is suggested (but not yet proven) by their frequent co-existence.
Recently it has been shown that severe nausea, vomiting, abdominal pain and/or distension of common bile duct may decrease coronary 'blood flow in patients with coronary artery disease., 
Plain roentgenogram of abdomen by itself does not suffice to rule out biliary pathology as nearly half the number of patients have radioluscent stones. Oral cholecystography (always double dose technique) is the minimum essential investigation. In the absence, of vomiting, diarrhoea, liver disease, and jaundice, nonvisualisation of the viscus strongly suggests gall bladder disease. But if no radio-opaque stones are- discerned, it is prudent either to repeat the cholecystogram or better, to resort, to ultrasound echosonography which demonstrates stones as small as 5 mm in diameter. Intravenous cholangiography is a useful adjunct but with limitations (and is never a substitute for per-operative cholangiogram). Often it does not delineate focal pathologies like stones. However, it well indicates the diameter of the choledochus, 3-10 mm. being considered normal. However, at times the duct is very faintly visualised. If in a patient suspected to be suffering from acute or chronic cholecystitis, intravenous cholangiogram outlines the common bile duct without filling gall bladder, cystic duct obstruction is assumed.
The oral cholecystogram as well as intravenous cholangiogram will not demonstrate any part of biliary tree in presence of jaundice, irrespective of its etiology. In a jaundiced patient, various biochemical tests may indicate obstructive nature of the jaundice. Occasionally the routine radiology (plain roentgenogram as well as the barium meal studies) delineate the pathology. Recently, the E.R.C.P. and ultrasound echosonography have pinpointed the cause of jaundice accurately and expeditiously. If the course of jaundice is not established and if the icterus does not diminish in four to six weeks (earlier if there is associated pyrexia), a laparotomy is resorted to. A percutaneous transhepatic cholangiography may be carried out just prior to surgery.
As emphasized earlier, cholecystitis and cholelithiasis are essentially surgical problems.
Chenodeoxylic acid therapy is useful only for pure cholesterol stones in a gall bladder whose wall is not diseased and, whose function is well preserved, a situation not often encountered. Even under these circumstances, this drug treatment is very prolonged and expensive, with a success rate of about 50 percent. Hence inspite of chenodeoxylic acid being available in the market for over 10 years, it has. not found wide use.
For "silent" or asymptomatic stones, operation is always insisted upon (unless there are contraindications) because long term longitudinal follow up of these patients have revealed that more than 50 per cent of them develop symptoms and or complications.,  The group of patients with complications are older and also the surgery in these older patients with complications carries higher morbidity and mortality, , , , 
However, in any patient with gall stone disease, timing of surgery is very important. For chronic cholecystitis and for silent stones no delay is brooked except to correct any associated problems like diabetes. The time schedule for cholangitis- and jaundice has already been outlined.
For acute pancreatitis of biliary etiology, operation is carried out four : to six weeks after the attack. Here the clearance of biliary tree of its disease (cholecystectomy combined if necessary with choleductal exploration and sphincteric elimination) results in a cure of pancreatitis. In chronic pancreatitis, if there is associated biliary disease the surgical attack on pancreas must be combined with appropriate operation for gall stone diseases., 
For acute cholecystitis, conservative treatment rather than early or emergency operation is advocated because of the following considerations:
(a) Gangrene and perforation are rare complications and generalised peritonitis rarer still; 'hence the pathology does not- make emergency cholecystectomy mandatory.
(b) Diagnosis is not always. clear initially; even if it is clear; acute or subacute pancreatitis is not a rare concomitant disease.
(c) Many of the patients are aged, with various medical problems which need some pre-operative workup to make surgery safe for them.
(d) Early or emergency surgery often does not allow a proper evaluation of biliary tree and pancreas particularly since the hepato-duodenal ligament is oedematous and indurated.
(e) Morbidity and mortality of emergency surgery is higher.
Proponents of the conservative therapy include Dunphy, Buxton et al, Cole, Doubilet et al, Meagher and Campbell, and McCubbery and Thieme 
About four to six weeks after the acute attack elective surgery is carried out. However, a small number of patients with persistent pain, pyrexia, and lump (suggestive of empyema), need a semiemergency operation (four in the present series).
All abdominal viscera especially liver, gall bladder and bile duct, pancreas and upper gastro-intestinal tract need a thorough evaluation. The conventional criteria for exploration of common bile duct following a cholangiogram are:
(i) past history of jaundice or jaundice at the time of operation.
(ii) history of cholangitis or cholangitis evident at the time of operation,
(iii) dilatation of choledochus as discerned at the operation or on intravenous cholangiogram,
(iv) palpable stones in the ducts,
(v) wide cystic duct with multiple small gall stones,
Even when these Criteria do not exist, operative cholangiogram should always be carried out, through a cannula positioned via the cystic duct (as advocated by Neinhuis), as this adds to the visual and palpatory assessment of the biliary ducts. If no abnormality is found, the transcystic duct cholangiogram leaves the ducts virgin, whereas following transcholedochal cholangiogram it is prudent to drain the duct by a T-tube even if the duct is normal.
The incidence of ductal exploration ranges from 20 to 30 per cent of all cholecystectomics and stones recovered from 35 to 60 per cent of the ducts explored., , , , 
The incidence of false positive peroperative radiologic study is about 5 per cent.
Operative elimination of sphincter of Oddi to prevent recurrence of stones and/ or obstruction is required in cases where
(a) ductal dilatation is 2 cm or more
(b) ampulla of Vater is tight or stenosed
(c) a stone is impacted at the ampula
(d) there are multiple stones in the choledochus.
If the ductal diameter is 2 cm or more, a lateral choledochoduodenostomy is performed. A transduodenal phincteroplasty, which entails cutting of the sphincter for at least 1.5 cm followed by suturing of mucosa of the duct to that of the duodenum is preferred.
Following the exploration of the common bile duct and following transduodenal sphincteroplasty, the common bile duct is drained by a T-tube (which should never project into the duodenum, to minimise chances of post-operative pancreatitis due to blockage of the opening of the pancreatic duct by the tube). A per-operative T-tube cholangiogram is obtained to rule out missed stone or other pathology.
Routine culture of bile from gall bladder and/or choledochus yielded positive culture (usually E. coli or Klebsiella) in almost 20 per cent of the patients in the present series. Recent literature reports positive culture in 23 to 47 per cent., , , ,  Significantly a high incidence of positive culture is obtained in those with ductal pathology. This is a strong argument in favour of pre-operative use of antibiotics especially since many septic complications theoretically would derive from contamination by infected bile.
Post-operative morbidity and mortality
These are higher in patients who have had complications like jaundice, cholangitis etc. at the time of surgery , , , 
The author is grateful to Dr. H. I. Jhala, M.D., F.C.P.S., II.T.M., F.A.M.S., F.R.C.P., F.A.Sc., Medical Director, Sir Hurkisondas Nurottumdas Hospital, Bombay, (for his kind permission to use hospital record.)