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Jaundice in patients with acute cholecystitis
Jaundice in Patients with Acute Cholecystitis Its Validity as an indication for Common Bile Duct Exploration Laurence Y. Cheung, MD, Salt Lake City, Utah J. Gary Maxwell, MD, Salt Lake City, Utah
Since retained common bile duct stones may cause serious complications such as cholangitis and biliary cirrhosis, detection and elimination of stones within the common bile duct are major objectives of surgery for gallbladder disease. However, choledochotomy may be difficult in the presence of acute inflammation and edema; therefore, routine exploration of the common bile duct in the course of treatment of acute cholecystitis may result in higher morbidity, such as injuries to the extrahepatic biliary ductal system or hepatic artery [I]. Surgeons have used various parameters to identify patients likely to have ductal stones. Jaundice has been a classical indicator for the presence of choledocholithiasis; however, the significance of its presence in patients with acute cholecystitis is disputed. Some have called jaundice a strong indication for exploration [1,2], whereas, others have suggested that mild to moderate jamdice alone is an unreliable indication for the presence of ductal stones in patients with acute cholecystitis [3,4]. Since 1968, intravenous cholangiography was performed in many of our patients because we have found it valuable in the diagnosis of acute cholecystitis [5]. It has also been our policy to recommend early operation in nearly all patients and operative cholangiography in those with relative indications for ductal exploration. We have found frequent association of normal ductal system in preoperative or operative cholangiograms and the presence of jaundice during this period. To evaluate the validity of jaundice as a criteria for choledochotomy, we reviewed our experience with acute cholecystitis with particular regard to (1) incidence of jaundice, (2) incidence of choledocholithi-
asis, (3) the association of jaundice and ductal stones, and (4) causes of jaundice other than choledocholithiasis. Material The hospital records of 102 patients with the clinical diagnosis of acute cholecystitis at the University of Utah Medical Center and Salt Lake Veterans Administration Hospital from 1968 through 1974 were examined. Cases were excluded when the clinical diagnosis was not confirmed by gross and microscopic findings of acute inflammation of the gallbladder. Patients with preexisting liver disease were also excluded from this study. Thus, forty-one cases were acceptable for study. All patients had acute manifestations including biliary pain and right subcostal tenderness and gross and microscopic confirmation of acute cholecystitis. White blood cell count was elevated in thirty-three patients and fever was noted in twenty-six. Cholecystectomy was performed in all but three who had tube cholecystostomy. Two of these three patients were readmitted for cholecystectomy at a later time, and the third patient died of sepsis. The patients ranged in age from twenty-five to eighty-nine years with a median of fifty-four years, and the male to female ratio was three to one. Among these forty-one patients, thirty-three had preoperative serum bilirubin determinations, and the other eight had emergency cholecystectomy before liver chemistry was measured. The presence or absence of common bile duct stones was evaluated by preoperative intravenous and/or operative cholangiography in twenty-five patients, and ductal exploration in seven. The remaining nine patients had clinical follow-up to two to five years including their liver chemistry. Liver biopsies were taken during surgery in five patients who had jaundice but normal ductal system on cholangiography.
Results From the Department of Surgery, University of Utah College of Medicine, Veterans Administration Hospital, Salt Lake City, Utah Reprint requests should be addressed to Laurence Y. Cheung. MD, Department of Surgery, University of Utah College of Medicine. 50 North Medical Drive, Salt Lake City, Utah 84132. Presented at the Twenty-Seventh Annual Meeting of the Southwestern Surgical Congress, Las Vegas, Nevada, April 21-24. 1975.
746
Figure 1 illustrates the preoperative serum bilirubin level in thirty-three patients. Of these, twenty-four (72 per cent) had elevated total bilirubin (greater than 1.2 mg/lOO ml). The elevation was mild (1.2 to 3 mg/lOO ml) in sixteen patients,
TheAmerkan
Journal of Surgery
Acute Cholecystitis
moderate (3 to 6 mg/lOO ml) in six, and severe (greater than 7 mg/lOO ml) in two. Of all forty-one patients, only one was found to have ductal stones and his preoperative serum bilirubin level was 5.6 mg/lOO ml. Six patients had negative ductal exploration and twenty-five patients had normal ductal systems as determined by either preoperative and/or operative cholangiography. The remaining nine patients had neither clinical nor laboratory evidence of choledocholithiasis in the preoperative workup and postoperative follow-up period of two to five years. In one patient, preoperative cholangiograms demonstrated narrowing of the common bile duct, possibly by pressure from a distended gallbladder. The common bile duct was explored in that patient and no stone was found. Postoperative cholangiography revealed normal ductal system. Liver biopsy showed periductal and hepatocellular inflammation in three patients and fatty infiltration in two. ‘I’he cause of jaundice without choledocholithiasis in many patients was unknown. One patient died of sepsis for an operative mortality of 2.5 per cent. Morbidity included hematoma in one patient, subphrenic abscess in one patient, and wound infection in one patient. Comments
The two common complications of gallstone disease are acute cholecystitis and cholangitis secondary to choledocholithiasis. Acute cholecystitis is due to an obstruction of the cystic duct or the neck of the gallbladder by an impacted stone in 90 to 95 per cent of the cases [4]. Obstruction not only prevents the egress of bile but causes an accumulation of normal secretion within the gallbladder. This, in turn, may result in distention of the gallbladder, vascular insufficiency, ischemic necrosis, and perforation. However, clinically it is usually difficult to differentiate acute cholecystitis from cholangitis secondary to choledocholithiasis. Gross appearance of the gallbladder during surgery in patients with acute cholecystitis may also be similar to that found in choledocholithiasis with bile duct obstruction. Furthermore, the individual surgeon may have different criteria for gross diagnosis of acute cholecystitis during surgery. Therefore, studies [1-31 that use clinical criteria alone may include some patients who did not have acute cholecystitis but rather had (1) cholangitis secondary to choledocholithiasis and (2) simple biliary colic in chronic cholelithiasis and cholecystitis. For example, of 7,019 patients with disease of the gall-
Volume 130. December 1975
14 0 0
z
:
0 -
C. D. STONES
0
0 -
NO C.D.
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z 0 0
I ! O-l.2
I
1.2-2
I
2-3
TOTAL
0
I
I
3-4
4-5
SERUM
6 I
5-6 BILIRUBIN
I
6-7
6 I
I 0 __-----&-
7-8
13-14
(rngV.1
Figure 1. Preoperative total serum bilirubin level In thirtythree patients.
bladder and biliary tract (exclusive of neoplasms and trauma) seen at the University of Michigan, a diagnosis of acute cholecystitis was made in 338 by review of the clinical records alone [6]. However, only 109 patients had histopathologic confirmation of the diagnosis. Elevation of serum bilirubin was present in 72 per cent of our patients who had preoperative serum bilirubin determination. This is higher than figures reported in other studies, which ranged from 6 to 43 per cent [2,4]. However, most of our patients had only mild to moderate elevation of serum bilirubin. Severe bilirubinemia (greater than 7.0 mg/lOO ml) was found in only two of forty-one patients (5 per cent). Only one patient (2.5per cent) in the present series had common bile duct stones. This result was slightly lower than that reported by Lester [3]. Several reports have shown much higher incidence of choledocholithiasis in patients with acute cholecystitis. In a series of 134 patients with acute cholecystitis, Dunphy and Ross [7] have found choledocholithiasis in 21 per cent. Watkin and Thomas [2] reported 25 per cent incidence of choledocholithiasis in 107 patients with acute cholecystitis. Since none of these reports defined the diagnosis of acute cholecystitis with histopathologic confirmation, different criteria for selection of patients may account for this discrepancy. It is also possible that clinicians using normal intravenous or operative cholangiography have overlooked stones in some patients since the common bile duct was not explored in the majority of patients. However, none of these patients have later shown any evidence of jaundice, pancreatitis, or cholangitis due to choledocholithiasis in a follow-up period as long as five years.
747
Cheung and Maxwell
Our study has shown that mildly or moderately elevated serum bilirubin may be considered only a relative indication for the presence of ductal stones. Preexploratory cholangiography should obviate negative exploration in a number of these patients. This has also been shown in patients undergoing elective cholecystectomy in several recent series [8,9]. Because common bile duct stone was found in only one patient whose serum bilirubin level was 5.6 mg/lOO ml, we cannot correlate the level of serum bilirubin with the likelihood of choledocholithiasis. However, it has been suggested by other studies that a serum bilirubin level greater than 5 to 7 mg/lOO ml renders the presence of a ductal stone more likely [4,8]. The cause of jaundice in patients with acute cholecystitis without common bile duct stones remains unknown. We have found that three of the five liver biopsies performed show periductal and hepatocellular inflammation. This has also been reported by Lyon and Goldman [IO], who found similar pathologic changes in the liver biopies of six of ten patients with acute cholecystitis without choledocholithiasis. Compression of the common bile duct by pressure from a distended gallbladder was suggested as a mechanism in one of our patients, and in three patients reported on by Nolan and Espiner [II]. Spasm of the choledochal sphincter is also a possibility.
Summary
Our study demonstrates that (1) mild to moderate jaundice is frequently seen in patients with acute cholecystitis; (2) severe degrees of jaundice were seen in two patients without the presence of common duct stone or recognizable obstruction of the common bile duct; (3) only one of forty-one patients with acute cholecystitis had common bile duct stone; (4) jaundice does not appear to be a compelling reason for choledochotomy; and (5) less invasive technics such as intravenous and intraoperative cholangiography should suffice to exclude the possibility of common bile duct stone in patients with acute cholecystitis.
References 1. Boyden AM: Acute gallbladder disease and the common duct. Arch Surg 70: 374, 1955. 2. Watkin DFL, Thomas GG: Jaundice in acute cholecystitis. Bf J Surg 58: 570, 1971.
748
3. Lester W: Acute cholecystitis with special reference to the occurrence of jaundice. Surgery 21: 875, 1947. 4. Berk JE, Monroe LS: Gastroenterology, vol 11, 2nd ed (Bockus HL, ed). Philadelphia, WB Saunders, 1983, p 700. 5. Chang FC: Intravenous cholangiography in the diagnosis of acute cholecvstitis. Am J Surq 120: 587, 1970. 8. Buxton RW, Ray DK, Collar Fi Acute cholecystitis. JAMA 148: 301, 1951. 7. Dunphy JE, Ross FP: Studies in acute cholecystitis. Surgery 26: 539, 1949. 8. Way LW. Admirand WH, Dunphy JE: Management of choledocholithiasis. Ann Surg 176: 347, 1972. 9. Colcock BP. Perev B: Exploration of the common bile duct. Surg Gynkcol dbstet 1 i8: 20, 1964. 10. Lvon CG. Goldman L: Acute cholecvstftis in a municipal hospital. Am J Surg 98: 283, 1959. _ 11. Nolan DJ. Espiner HJ: Compression of the common bile duct in acute cholecystitis. Br J Radio/ 45: 82 1, 1972.
Nathaniel M. Matolo (Davis, CA): The incidence of choledocholithiasis in the authors’ cases was small as compared with other centers, perhaps because their number of cases of acute cholecystitis was only fortyone. However, the paper does emphasize several more important points. One, routine choledochotomy is not necessary in all patients with jaundice associated with acute cholecystitis. Secondly, mild jaundice is an unreliable indication of stone. Thirdly, the use of intravenous as well as operative cholangiography for evaluating biliary duct system can reduce the number of unnecessary explorations. Do the authors recommend routine intravenous or operative cholangiograms in patients with acute cholecystitis with jaundice and have they experienced any complications with intraoperative cholangiography? Biliary scanning with technetium 99m-pyridoxine glutamate can be used to evaluate the biliary tract system. Lawrence W. Way (San Francisco, CA): I wondered why the incidence was lower in your patients. This questions the reliability of intravenous cholangiography as a test to rule out the presence of common bile duct stones. I would suspect the quality of intravenous cholangiograms, even using tomography, in patients whose serum bilirubin levels are between 1.2 and 3.0 mg/lOO ml. You can expect false-negative results to be fairly frequent. Did any of these patients have acalculus acute cholecystitis? Laurence Y. Cheung (closing): I am not advocating routine intravenous cholangiography in all patients. Operative cholangiogram in patients with jaundice is a necessity. The reason our study shows such a low incidence of choledocholithiasis is perhaps the nonuniform way acute cholecystitis is defined. That is the reason we use histopathologic confirmation. We have not had any patients with acalculus acute cholecystitis.
The American Journal of Surgery
Since retained common bile duct stones may cause serious complications such as cholangitis and biliary cirrhosis, detection and elimination of stones within the common bile duct are major objectives of surgery for gallbladder disease. However, choledochotomy may be difficult in the presence of acute inflammation and edema; therefore, routine exploration of the common bile duct in the course of treatment of acute cholecystitis may result in higher morbidity, such as injuries to the extrahepatic biliary ductal system or hepatic artery [I]. Surgeons have used various parameters to identify patients likely to have ductal stones. Jaundice has been a classical indicator for the presence of choledocholithiasis; however, the significance of its presence in patients with acute cholecystitis is disputed. Some have called jaundice a strong indication for exploration [1,2], whereas, others have suggested that mild to moderate jamdice alone is an unreliable indication for the presence of ductal stones in patients with acute cholecystitis [3,4]. Since 1968, intravenous cholangiography was performed in many of our patients because we have found it valuable in the diagnosis of acute cholecystitis [5]. It has also been our policy to recommend early operation in nearly all patients and operative cholangiography in those with relative indications for ductal exploration. We have found frequent association of normal ductal system in preoperative or operative cholangiograms and the presence of jaundice during this period. To evaluate the validity of jaundice as a criteria for choledochotomy, we reviewed our experience with acute cholecystitis with particular regard to (1) incidence of jaundice, (2) incidence of choledocholithi-
asis, (3) the association of jaundice and ductal stones, and (4) causes of jaundice other than choledocholithiasis. Material The hospital records of 102 patients with the clinical diagnosis of acute cholecystitis at the University of Utah Medical Center and Salt Lake Veterans Administration Hospital from 1968 through 1974 were examined. Cases were excluded when the clinical diagnosis was not confirmed by gross and microscopic findings of acute inflammation of the gallbladder. Patients with preexisting liver disease were also excluded from this study. Thus, forty-one cases were acceptable for study. All patients had acute manifestations including biliary pain and right subcostal tenderness and gross and microscopic confirmation of acute cholecystitis. White blood cell count was elevated in thirty-three patients and fever was noted in twenty-six. Cholecystectomy was performed in all but three who had tube cholecystostomy. Two of these three patients were readmitted for cholecystectomy at a later time, and the third patient died of sepsis. The patients ranged in age from twenty-five to eighty-nine years with a median of fifty-four years, and the male to female ratio was three to one. Among these forty-one patients, thirty-three had preoperative serum bilirubin determinations, and the other eight had emergency cholecystectomy before liver chemistry was measured. The presence or absence of common bile duct stones was evaluated by preoperative intravenous and/or operative cholangiography in twenty-five patients, and ductal exploration in seven. The remaining nine patients had clinical follow-up to two to five years including their liver chemistry. Liver biopsies were taken during surgery in five patients who had jaundice but normal ductal system on cholangiography.
Results From the Department of Surgery, University of Utah College of Medicine, Veterans Administration Hospital, Salt Lake City, Utah Reprint requests should be addressed to Laurence Y. Cheung. MD, Department of Surgery, University of Utah College of Medicine. 50 North Medical Drive, Salt Lake City, Utah 84132. Presented at the Twenty-Seventh Annual Meeting of the Southwestern Surgical Congress, Las Vegas, Nevada, April 21-24. 1975.
746
Figure 1 illustrates the preoperative serum bilirubin level in thirty-three patients. Of these, twenty-four (72 per cent) had elevated total bilirubin (greater than 1.2 mg/lOO ml). The elevation was mild (1.2 to 3 mg/lOO ml) in sixteen patients,
TheAmerkan
Journal of Surgery
Acute Cholecystitis
moderate (3 to 6 mg/lOO ml) in six, and severe (greater than 7 mg/lOO ml) in two. Of all forty-one patients, only one was found to have ductal stones and his preoperative serum bilirubin level was 5.6 mg/lOO ml. Six patients had negative ductal exploration and twenty-five patients had normal ductal systems as determined by either preoperative and/or operative cholangiography. The remaining nine patients had neither clinical nor laboratory evidence of choledocholithiasis in the preoperative workup and postoperative follow-up period of two to five years. In one patient, preoperative cholangiograms demonstrated narrowing of the common bile duct, possibly by pressure from a distended gallbladder. The common bile duct was explored in that patient and no stone was found. Postoperative cholangiography revealed normal ductal system. Liver biopsy showed periductal and hepatocellular inflammation in three patients and fatty infiltration in two. ‘I’he cause of jaundice without choledocholithiasis in many patients was unknown. One patient died of sepsis for an operative mortality of 2.5 per cent. Morbidity included hematoma in one patient, subphrenic abscess in one patient, and wound infection in one patient. Comments
The two common complications of gallstone disease are acute cholecystitis and cholangitis secondary to choledocholithiasis. Acute cholecystitis is due to an obstruction of the cystic duct or the neck of the gallbladder by an impacted stone in 90 to 95 per cent of the cases [4]. Obstruction not only prevents the egress of bile but causes an accumulation of normal secretion within the gallbladder. This, in turn, may result in distention of the gallbladder, vascular insufficiency, ischemic necrosis, and perforation. However, clinically it is usually difficult to differentiate acute cholecystitis from cholangitis secondary to choledocholithiasis. Gross appearance of the gallbladder during surgery in patients with acute cholecystitis may also be similar to that found in choledocholithiasis with bile duct obstruction. Furthermore, the individual surgeon may have different criteria for gross diagnosis of acute cholecystitis during surgery. Therefore, studies [1-31 that use clinical criteria alone may include some patients who did not have acute cholecystitis but rather had (1) cholangitis secondary to choledocholithiasis and (2) simple biliary colic in chronic cholelithiasis and cholecystitis. For example, of 7,019 patients with disease of the gall-
Volume 130. December 1975
14 0 0
z
:
0 -
C. D. STONES
0
0 -
NO C.D.
STONES
z 0 0
I ! O-l.2
I
1.2-2
I
2-3
TOTAL
0
I
I
3-4
4-5
SERUM
6 I
5-6 BILIRUBIN
I
6-7
6 I
I 0 __-----&-
7-8
13-14
(rngV.1
Figure 1. Preoperative total serum bilirubin level In thirtythree patients.
bladder and biliary tract (exclusive of neoplasms and trauma) seen at the University of Michigan, a diagnosis of acute cholecystitis was made in 338 by review of the clinical records alone [6]. However, only 109 patients had histopathologic confirmation of the diagnosis. Elevation of serum bilirubin was present in 72 per cent of our patients who had preoperative serum bilirubin determination. This is higher than figures reported in other studies, which ranged from 6 to 43 per cent [2,4]. However, most of our patients had only mild to moderate elevation of serum bilirubin. Severe bilirubinemia (greater than 7.0 mg/lOO ml) was found in only two of forty-one patients (5 per cent). Only one patient (2.5per cent) in the present series had common bile duct stones. This result was slightly lower than that reported by Lester [3]. Several reports have shown much higher incidence of choledocholithiasis in patients with acute cholecystitis. In a series of 134 patients with acute cholecystitis, Dunphy and Ross [7] have found choledocholithiasis in 21 per cent. Watkin and Thomas [2] reported 25 per cent incidence of choledocholithiasis in 107 patients with acute cholecystitis. Since none of these reports defined the diagnosis of acute cholecystitis with histopathologic confirmation, different criteria for selection of patients may account for this discrepancy. It is also possible that clinicians using normal intravenous or operative cholangiography have overlooked stones in some patients since the common bile duct was not explored in the majority of patients. However, none of these patients have later shown any evidence of jaundice, pancreatitis, or cholangitis due to choledocholithiasis in a follow-up period as long as five years.
747
Cheung and Maxwell
Our study has shown that mildly or moderately elevated serum bilirubin may be considered only a relative indication for the presence of ductal stones. Preexploratory cholangiography should obviate negative exploration in a number of these patients. This has also been shown in patients undergoing elective cholecystectomy in several recent series [8,9]. Because common bile duct stone was found in only one patient whose serum bilirubin level was 5.6 mg/lOO ml, we cannot correlate the level of serum bilirubin with the likelihood of choledocholithiasis. However, it has been suggested by other studies that a serum bilirubin level greater than 5 to 7 mg/lOO ml renders the presence of a ductal stone more likely [4,8]. The cause of jaundice in patients with acute cholecystitis without common bile duct stones remains unknown. We have found that three of the five liver biopsies performed show periductal and hepatocellular inflammation. This has also been reported by Lyon and Goldman [IO], who found similar pathologic changes in the liver biopies of six of ten patients with acute cholecystitis without choledocholithiasis. Compression of the common bile duct by pressure from a distended gallbladder was suggested as a mechanism in one of our patients, and in three patients reported on by Nolan and Espiner [II]. Spasm of the choledochal sphincter is also a possibility.
Summary
Our study demonstrates that (1) mild to moderate jaundice is frequently seen in patients with acute cholecystitis; (2) severe degrees of jaundice were seen in two patients without the presence of common duct stone or recognizable obstruction of the common bile duct; (3) only one of forty-one patients with acute cholecystitis had common bile duct stone; (4) jaundice does not appear to be a compelling reason for choledochotomy; and (5) less invasive technics such as intravenous and intraoperative cholangiography should suffice to exclude the possibility of common bile duct stone in patients with acute cholecystitis.
References 1. Boyden AM: Acute gallbladder disease and the common duct. Arch Surg 70: 374, 1955. 2. Watkin DFL, Thomas GG: Jaundice in acute cholecystitis. Bf J Surg 58: 570, 1971.
748
3. Lester W: Acute cholecystitis with special reference to the occurrence of jaundice. Surgery 21: 875, 1947. 4. Berk JE, Monroe LS: Gastroenterology, vol 11, 2nd ed (Bockus HL, ed). Philadelphia, WB Saunders, 1983, p 700. 5. Chang FC: Intravenous cholangiography in the diagnosis of acute cholecvstitis. Am J Surq 120: 587, 1970. 8. Buxton RW, Ray DK, Collar Fi Acute cholecystitis. JAMA 148: 301, 1951. 7. Dunphy JE, Ross FP: Studies in acute cholecystitis. Surgery 26: 539, 1949. 8. Way LW. Admirand WH, Dunphy JE: Management of choledocholithiasis. Ann Surg 176: 347, 1972. 9. Colcock BP. Perev B: Exploration of the common bile duct. Surg Gynkcol dbstet 1 i8: 20, 1964. 10. Lvon CG. Goldman L: Acute cholecvstftis in a municipal hospital. Am J Surg 98: 283, 1959. _ 11. Nolan DJ. Espiner HJ: Compression of the common bile duct in acute cholecystitis. Br J Radio/ 45: 82 1, 1972.
Nathaniel M. Matolo (Davis, CA): The incidence of choledocholithiasis in the authors’ cases was small as compared with other centers, perhaps because their number of cases of acute cholecystitis was only fortyone. However, the paper does emphasize several more important points. One, routine choledochotomy is not necessary in all patients with jaundice associated with acute cholecystitis. Secondly, mild jaundice is an unreliable indication of stone. Thirdly, the use of intravenous as well as operative cholangiography for evaluating biliary duct system can reduce the number of unnecessary explorations. Do the authors recommend routine intravenous or operative cholangiograms in patients with acute cholecystitis with jaundice and have they experienced any complications with intraoperative cholangiography? Biliary scanning with technetium 99m-pyridoxine glutamate can be used to evaluate the biliary tract system. Lawrence W. Way (San Francisco, CA): I wondered why the incidence was lower in your patients. This questions the reliability of intravenous cholangiography as a test to rule out the presence of common bile duct stones. I would suspect the quality of intravenous cholangiograms, even using tomography, in patients whose serum bilirubin levels are between 1.2 and 3.0 mg/lOO ml. You can expect false-negative results to be fairly frequent. Did any of these patients have acalculus acute cholecystitis? Laurence Y. Cheung (closing): I am not advocating routine intravenous cholangiography in all patients. Operative cholangiogram in patients with jaundice is a necessity. The reason our study shows such a low incidence of choledocholithiasis is perhaps the nonuniform way acute cholecystitis is defined. That is the reason we use histopathologic confirmation. We have not had any patients with acalculus acute cholecystitis.
The American Journal of Surgery