World J. Surg., 2, 661-666, 1978
W rld Journal
Postoperative Acute Cholecystitis in Japan Yoh K a s a h a r a , M.D., H i r o y a U m e m u r a , M.D., Takeshi K u y a m a , M.D., and H i d e t a k a Oku, M.D. Second Department of Surgery and Department of Cardio-vascuology, Kinki University School of Medicine, Osaka, Japan
Postoperative acute cholecystitis following surgery unrelated to the biliary tract is a rare complication. Of 49 cases of this disease collected from the Japanese literature, including 3 of our cases, the ratio of males to females was 42:7, the ages ranged from 31 to 83 years, and 82% of the patients had no biliary calculi. The antecedent operation was performed for cancer of the stomach in 30 patients (61%), and for another type of cancer in an additional 10. Several pathogenetic factors that differ from those responsible for ordinary cholecystitis are considered to be contributory to this disease, among which impairment of the circulation to the gallbladder may be one of the most important. The overall mortality rate of postoperative cholecystitis was 32%. Although cholecystectomy is the preferred treatment, local findings or the condition of the patient should be considered in the decision regarding therapy. Early surgical intervention should not be delayed in the elderly patient, because there was a significant difference between the average age of survivors and those who died.
tion and, accordingly, we have reviewed 49 cases seen in Japan, including our own.
Three patients with p o s t o p e r a t i v e cholecystitis were treated in our institution in 1975, 1976, and 1977, respectively. T h e s e patients had no history of gallbladder disease and all of them underwent operations under general anesthesia.
Case 1 A 67-year-old male was admitted on August 1, 1975 with a history of h e m a t e m e s i s . Barium contrast xrays and e n d o s c o p y revealed esophageal varices, and transthoracic esophageal transection was performed on S e p t e m b e r 15, 1975. His postoperative course was uneventful except for p y r o t h o r a x , which drained for 18 days and subsided. On the 59th p o s t o p e r a t i v e day, the patient complained o f nausea and pain in the right u p p e r quadrant of the abdomen. Transient jaundice and t e m p e r a t u r e up to 102 ~ F were noted. He was treated c o n s e r v a t i v e l y and seemed to be recovering when, on the 75th p o s t o p e r a t i v e day, he d e v e l o p e d severe abdominal pain and distension. L a b o r a t o r y studies showed: hematocrit 32.8%; W B C 24,200; total serum bilirubin 7.5 mg/dl; serum alkaline p h o s p h a t a s e 73 IU.
Acute cholecystitis developing in the early postoperative period following surgery unrelated to the biliary tract was described as a definite entity by Glenn  in 1947, although a few sporadic cases had been reported previously. Since that time, this condition has received wider attention, and J6nsson and A n d e r s s o n  collected 346 cases, including 2 of their o w n in 1976. Recently, we treated 3 patients with postoperative acute cholecystitis in our institu-
Reprint requests: Yoh Kasahara, M.D., The Second Department of Surgery, Kinki University, School of Medicine, 380, Sayama-cho, Osaka 589, Japan.
0364-2313/78/0002-0661 $01.20 9 1978 Soci6t6 Internationale de Chirurgie 661
World J. Surg., Vol. 2, No. 5, September 1978
Abdominal tap showed numerous neutrophils. With the diagnosis of perforated peptic ulcer, an emergency laparotomy was performed which revealed a perforated necrotic gallbladder. Cholecystectomy and choledochotomy with T-tube drainage were performed because of the presence of a dilated common bile duct. He died 6 days after laparotomy. Autopsy showed cirrhosis of the liver, splenomegaly, and thrombosis of the portal venous system. Cholelithiasis was absent.
management with antibiotics and intravenous fluids was undertaken. The symptoms gradually subsided and the values of the laboratory studies returned to the normal range. Although a mild attack recurred 10 days after the first one, the mass in the right upper quadrant decreased in size and finally became nonpalpable, Oral cholecystography showed nonvisualization of the gallbladder. The patient has since been followed up in our outpatient department.
Analysis of Japanese Cases
A 62-year-old female was admitted on October 5, 1976 because of an attack of dyspnea and cough. Examinations revealed squamous cell carcinoma of the left lung. After irradiation therapy, total resection of the left lung was performed on November 16, 1976, revealing that the tumor had invaded into the pericardium, which was partially resected. On the second postoperative day, she complained of nausea and pain in the right upper quadrant of the abdomen, which lasted until the 8th postoperative day, when marked abdominal distension was noted. The chest x-ray showed free air under the right diaphragm. Temperature up to 102~ F was noted and laboratory studies showed: hematocrit 40.3%; WBC 25,600; total serum bilirubin 3.3 mg/dl; serum alkaline phosphatase 129 IU. With diagnosis of perforated peptic ulcer, the patient underwent laparotomy on November 24, 1976. A necrotic gallbladder was found and cholecystectomy was performed. There were no perforations of the gastrointestinal tract, although the small intestine and colon down to the splenic flexure were dark red in color and swollen. The patient died on the third day after laparotomy. Autopsy revealed invasion of the left vertricle of the heart by carcinoma and thrombi mixed with tumor cells occluding the superior mesenteric artery and celiac axis. No biliary calculi were present.
Since the first report of Itoh  in 1963, a total of 49 cases of acute postoperative cholecystitis in Japan have been reported in the literature up to 1977 (Table 1). The patients ranged in age from 31 to 83 years, with a mean age of 59.5 years; 86% were 50 years or older. There were 42 males (86%) and 7 females. Historical data were available in 33 cases. Only 1 patient had a past history of cholecystitis, and 32 had no previous biliary symptoms. Acute cholecystitis developed most frequently after operations for lesions of the esophagus and gastrointestinal tract. Of 43 patients who had alimentary tract operations, 40 underwent operations for malignant neoplasms, and 30 were operated on for gastric cancer (11 total gastrectomy, 15 partial gastrectomy, 4 unknown). Seven patients underwent radical resections for cancer of the esophagus, 2 had resections for carcinoma of the rectum, and 1 had excision of jejunal metastasis from gastric sarcoma. Three patients had operations for benign disease of the alimentary tract, and these included transthoracic transection of esophageal varices, repair of a perforated esophageal diverticulum, and lysis of a small bowel obstruction. Six patients had operations unrelated to the alimentary tract, including bilateral arthroplasty of the hips, reduction of a fracture of the right femoral neck, pneumonectomy for carcinoma of the left lung, extirpation of a pheochromocytoma, skin transplantation for extensive burns, and embolectomy of the right femoral artery. From the available data, 37 of 38 patients had abdominal pain, either in the epigastrium or right upper quadrant. This symptom was followed in incidence by febrile episodes in 33 patients (89%), a palpable abdominal mass in 13 (39%), and nausea and/or vomiting in 12 (32%). Leukocytosis was found in 25 of 38 patients (66%), with counts as high as 35,600. Onset of symptoms was observed within 1 week postoperatively in 10 patients, within 2 weeks in 17, and within 4 weeks in 8. The remaining 11 patients began to complain of symptoms between the 29th and 150th postoperative day.
An 83-year-old female was admitted on November 7, 1977 because of a fracture on the right femoral neck. Reduction of the fracture was performed on November 10, 1977. On the 16th postoperative day, she complained of pain in the right upper quadrant of the abdomen and nausea. On physical examination, a tender mass in the right upper quadrant and temperature up to 101~ F were noted. Laboratory studies showed: hematocrit 43.5%; WBC 15,600; serum alkaline phosphatase 120 IU. With the diagnosis of postoperative cholecystitis, conservative
Y. Kasahara et al.: Postoperative Acute Cholecystitis
Table 1. Characteristics of 49 patients with postoperative acute cholecystitis. No. patients Age 30-39 40-49 50-59 60-69 70-79 80-89 Unknown Sex Male Female Calculi Present Absent Unknown
2 5 13 19 4 1 5 42 7 6 28 13
No. patients Primary disease Cancer of stomach Cancer of esophagus Cancer of rectum Cancer of lung Other Treatment Cholecystectomy Cholecystostomy Abdominal drainage Nonoperative Unknown Outcome Recovered Died Unknown
30 7 2 1 9 15 20 3 7 2 30 14 5
The correct diagnosis of postoperative acute cholecystitis was made in 4 of 6 patients who had operations outside the alimentary tract, and in 13 of 43 patients whose antecedent operation involved the alimentary tract. In the other patients, the initial diagnosis was peritonitis in 4, ruptured duodenal stump in 4, intra-abdominal abscess in 4, perforated peptic ulcer in 2, anastomotic leakage in 1, and acute appendicitis in 1. One patient was incidentally discovered to have a gangrenous gallbladder when he developed a wound dehiscence. In 13 cases the initial diagnosis was not mentioned in the literature. Postoperative acute cholecystitis was treated by operation in 42 patients; 14 had cholecystectomy, 20 had cholecystostomy, and 3 had simple abdominal drainage. One patient underwent choledochotomy with cholecystectomy. In 4 patients, the operative procedure was not clearly described. Seven patients had supportive measures. Biliary calculi were found in only 6 of 34 patients (17.6%). One patient of the 6 also had choledocholithiasis. Although emergency surgery was done in the majority of cases, 3 patients underwent elective procedures after remission of acute symptoms. Pathologic examinations revealed 5 cases of mild cholecystitis, 26 of gangrenous or necrotic cholecystitis, 3 of perforation, 3 of empyema, and 2 of associated cholangitis. In the other 10 cases, pathologic findings were not described in detail. Eleven patients died within 28 days of surgical intervention for acute cholecystitis. Six died in the first week, 2 in the second week, and 3 in the third week after surgery. Two patients died 50 and 70 days after operation, respectively. One patient treated with supportive measures died 30 days after the onset of the symptoms. The overall mortality
rate was 32% (14 of 44 patients). The outcome of 5 patients was not reported. The average age of survivors was 56.3 years and of those who died was 65.1 years.
Recognition of acute cholecystitis in the postoperative period unrelated to surgery of the biliary tract may be difficult. The symptoms of gallbladder disease are frequently mistaken for other postoperative complications. The disease has been preceded by all varieties of gastrointestinal surgery as well as by surgery in remote areas. No single antecedent operation has been observed with a statistically significant frequency . However, it is noteworthy that of the 49 cases in Japan, postoperative acute cholecystitis was preceded by surgery for gastric carcinoma in 30 (61%) and by surgery for esophageal carcinoma in 7 (14%). Postoperative cholecystitis has several characteristics. It rarely occurs in patients under the age of 50 years, the mortality rate is high, there is usually no past history of symptoms of biliary tract disease, there is a high incidence of acalculous gallbladder, and the incidence of males is higher than females [5-101. There is general agreement that the usual form of acute cholecystitis is nearly always due to obstruction of the cystic duct by an impacted stone. Cystic duct obstruction may be caused by other agents, such as angulation of the duct, adhesions, an adjacent peptic ulcer and, rarely, by viscid, inspissated bile. Glenn and Wantz  emphasized the importance of concentration of bile in the gallbladder during the fasting period after surgery in the pathogenesis of postoperative acute cholecystitis. They proposed that contraction of the gallbladder after resumption of oral intake might impact stones or viscid bile in the cystic duct. However, several authors report that a relationship between the resumption of oral intake and the onset of symptoms could not be demonstrated [6, 9, 10]. In our collective review, there was no distinctive relationship between eating and symptoms, although 3 patients developed the onset of symptoms within 1-3 days of resumption of food intake. The pathogenetic factors in postoperative cholecystitis are uncertain. Factors often present in the postoperative period and known to be contributory to the stasis of bile are fasting, anesthesia, dehydration, fever, and use of narcotics for relief of pain. Increased absorption of water through the gallbladder wall causes concentration and increased viscosity of bile. Fever and disturbed fluid balance may also increase the concentration and viscosity
World J. Surg., Voi. 2, No. 5, September 1978
of bile. Womack and Haffner  demonstrated that marked concentration and high viscosity of bile alone is sufficient to cause cholecystitis in animal experiments. An increased concentration and viscosity of bile may also be due to severe degradation of the blood after multiple transfusions in association with the primary operation [2, 12]. Sparkman  suggested that a sequence of hypotonicity of the gastrointestinal tract and functional obstruction of the biliary sphincter during anesthesia result in biliary stasis which might cause postoperative cholecystitis. Shirakawa et al.  suggested that insufficiency of the biliary sphincter might permit regurgitation of duodenal fluid which, in turn, might cause cholecystitis. Another factor that these patients have in common is that they have received narcotics for relief of pain. Virtually all analgesics increase the tonicity of the biliary sphincters and impair the evacuation of the gallbladder. Ischemic changes of the gallbladder wall without occlusion of the cystic duct may cause cholecystitis and this is considered by some to be the most important factor in the etiology of postoperative cholecystitis. According to Howard and Delaney , generalized hypoperfusion may be sufficient to cause ischemic injury to the gallbladder wall, particularly in elderly patients with impaired circulation. Animal experiments by Golden et al.  showed that shock with pronounced hypoperfusion caused focal necrosis of the mucosa of the gallbladder. Local hypotension in the liver and gallbladder may be sufficient to give rise to focal gallbladder necrosis . Thompson and Ferris  found thrombi in the blood vessels of the gallbladder and thought them to be a contributory factor in postoperative cholecystitis. The fact that more than 80% of the patients in our series had neoplasms and did not have biliary calculi, and yet developed acute cholecystitis is noteworthy. Some of these patients underwent serious operations for neoplastic disease and suffered from varying degrees of shock postoperatively, and others had considerable debility and inanition. These circumstances may provoke ischemic changes . The diagnosis of acute postoperative cholecystitis is not difficult when the initial operation has been extra-abdominal, or when the patient is known to have cholelithiasis. Otherwise, the gallbladder disease may be obscured by postoperative fever, ileus, and incisional pain . Since postoperative cholecystitis is rare, the diagnosis is not likely to head the list of possible causes of usual postoperative complications. Because the diagnosis is not suspected early in the postoperative course, and because there is general reluctance to consider a second diagnosis, it is not surprising that many of
the patients developed gangrene or localized perforation of the gallbladder by the time surgical therapy was instituted. Most of the patients had symptoms of fever and leukocytosis for more than 24 hours before the diagnosis was suspected . The correct diagnosis of this complication in our collected series was made in only 17 of 36 patients (47%). The high mortality rate of postoperative cholecystitis is apparently the result of the greater incidence of gallbladder gangrene and the contributory burdens of increased age and preceding illness and operations. The average age of survivors was significantly lower than in those who died in our series and in other reports . Although cholecystectomy is the treatment of choice, local findings or the condition of the patient should be considered in the decision regarding therapy. Cholecystostomy may be a preferable procedure in very sick patients. Three patients in our collective review underwent primary cholecystostomy and then had cholecystectomy 32, 40, and 60 days later. All of them recovered.
Acknowledgments The authors gratefully acknowledge the valuable guidance of Dr. Ryuzo Shioda of the Department of Surgery of the Japan Baptist Hospital.
R6sum6 La chol6cystite aigu6 postop6ratoire est une complication rare des op6rations ne portant pas sur l'arbre biliaire. Nous avons revu 49 cas publi6s dans la litt6rature japonaise, y compris 3 cas personnels. La proportion hommes/femmes est de 42/ 7. L'gtge va de 31 /~ 83 ans. I1 n'y avait pas de lithiase dans 82% des cas. L'op6ration d6clenchante avait 6t6 faite pour cancer de l'estomac dans 30 cas (61%) et pour un autre cancer dans 10 cas. Plusieurs facteurs pathog6nes, inexistants dans la chol6cystite classique, jouent un r61e: les alt6rations circulatoires v6siculaires sont probablement le plus important. La mortalit6 globale est de 32%. La chol6cystectomie est le meilleur traitement; mais la decision th6rapeutique doit d6pendre de l'6tat du malade et des conditions locales. L'intervention doit ~tre pr6coce surtout chez les malades fig6s: il y a une diff6rence d'~ge significative entre les survivants et les d6c6s.
References 1. Glenn, F.: Acute cholecystitis following the surgical treatment of unrelated disease. Ann. Surg. 126:411, 1947
Y. Kasahara et al.: Postoperative Acute Cholecystitis
2. J6nsson, P.-E., Andersson, A.: Postoperative acute acalculous cholecystitis. Arch. Surg. 111:1097, 1976 3. Itoh, T.: [A case of gallbladder necrosis after gastrectomy]. Arch. Jap. Chir. 32:320, 1963 4. Schein, C.J.: Acute Cholecystitis, 1st edition. New York, Harper & Row, 1972, pp. 213-215 5. Knuddsen, R.J., Zuber, W.F.: Acute cholecystitis in the postoperative period. N. Engl. J. Med. 269:289, 1963 6. Ottinger, L.W.: Acute cholecystitis as a postoperative complication. Ann. Surg. 184:162, 1976 7. Munster, A.M., Brown, J.R.: Acalculous cholecystitis. Am. J. Surg. 113:730, 1967 8. Glenn, F., Wantz, E.: Acute cholecystitis following the surgical treatment of unrelated disease. Surg. Gynecol. Obstet. 102:145, 1956 9. Levin, M.N.: Acute cholecystitis following surgery unrelated to the biliary tract. J.A.M.A. 177:644, 1961 10. Thompson, J.W., Ferris, D.O.: Acute cholecystitis
11. 12. 13. 14.
complicating operation for other diseases. Ann. Surg. 155:489, 1962 Womack, N.A., Haffner, H.: Cholesterolosis: its significance in the badly damaged gallbladder. Ann. Surg. 119:391, 1944 Lindberg, E.F., Grinnan, G.L.B., Smith, L.: Acalculus cholecystitis in Vietnam casualties. Ann. Surg. 171:152, 1970 Sparkman, R.S.: Abdominal emergencies following unrelated surgical procedures. Ann. Surg. 135:863, 1952 Shirakawa, Y., Matsumine, K., Takahashi, M.: [A case of acute acalculus cholecystitis due to insufficiency of the biliary sphincter]. Jap. J. Gastroenterol. 72:1064, 1975 Howard, R.J., Delaney, J.P.: Postoperative cholecystitis. Am. J. Dig. Dis. 17:213, 1972 Golden, G.T., Sears, H.F., Wangensteen, S.L.: Posttraumatic cholecystitis. Am. Surg. 37:371, 1971
Invited Commentary Per-Ebbe J6nsson, M.D. University of Lund, Lund, Sweden This paper reminds us again o f a rare postoperative complication, postoperative acute cholecystitis, which was first reported in 1844 by Duncan who wrote of a patient with gangrenous cholecystitis after surgery for femoral hernia . The well-known mortality o f this complication is confirmed by the present authors, in whose selected series the mortality rate was 32%. Acute cholecystitis after trauma, posttraumatic acute cholecystitis, has a similar etiological origin and pathological findings as postoperative cholecystitis and, therefore, should be discussed under the same heading. Posttraumatic acute cholecystitis has been mainly reported after multiple trauma and war injuries . This condition has not been discussed in the present paper. There are 2 characteristics that distinguish postoperative (posttraumatic) acute cholecystitis from ordinary acute cholecystitis, namely, the frequency of the acalculous form and the sex ratio. In ordinary acute cholecystitis, the frequency of the acalculous form is about 5-10% . Of published cases, 46% of postoperative acute cholecystitis and 92% o f the posttraumatic cases have been of the acalculous form . The male-to-female ratio, judged from a review of all published cases of postoperative cholecystitis, has been 7 to 1 for the acalculous
form and 1 to 1 for the calculous form . Ordinary acute cholecystitis is much more c o m m o n among women, but the sex difference decreases with increasing age and is nearly 1 to 1 in older patients. Therefore, it can be anticipated that surgery or trauma and accompanying calculous cholecystitis is just a coincidence. This has not been subjected to analysis by the authors. The diagnosis of postoperative acute acalculous cholecystitis can only be confirmed by surgery. In case 3 in the present paper, the diagnosis o f this form of cholecystitis was established by oral cholecystography. This cannot be considered sufficient. After trauma and surgery, patients surprisingly often show symptoms and signs simulating cholecystitis, which subside after about a week. In the Japanese material, there are 7 patients who are included without operatively confirmed diagnosis. Postoperative acalculous cholecystitis is mostly seen after abdominal surgery, particularly colon surgery . In the present review, about 75% of the cases occurred after esophageal and stomach surgery. This can depend on a difference in the proportion of surgical diseases compared with other countries. After extra-abdominal surgery, acalculous cholecystitis has mostly been observed in connection with orthopedic surgery, such as osteo-