Table of Contents

 

Clinical Case (s)

Clinical Questions

Introduction

Acute Cholecystitis

Management of Acute Cholecystitis

Timing of Surgery

Estimation of Surgical Risk

Evidence for Optimal Timing of Surgery

Case Follow Up

Conclusions

 

Acute Cholecystitis and the Timing of Surgery:  When is it time to heal with steel?

 

  

Vincent C. Schooler, MD

Resident Grand Rounds

June 6, 2003

 

 

Clinical Cases   

 

Case 1:

 

80 year old female presents with 3 days of nausea, vomiting, and right upper quadrant pain. Patient has a history of cholelithiasis, diabetes mellitus, congestive heart failure, and hypertension. WBC is 17K (6% bands), Tbili 9.0, ALP 197, AST 699, ALT 650, Amylase 103, Lipase 19.  Abd. CT → Cholelithiasis with pericholecystic fluid and gallbladder distention.  HIDA scan → Cystic duct obstruction. 

 

Case 2:

 

48 year old male presents with progressive right upper quadrant pain for 2 weeks. Past medical history of diabetes mellitus, hypertension, and obesity. WBC 6.8, Tbili 0.8, ALP 88, AST 34, ALT 66. Abd. U/S → Cholelithiasis in the neck of the gallbladder, negative Murphy’s sign, and no common bile duct dilatation.

 

Both of these patients have acute cholecystitis and they also have significant comorbidities. The medical and surgical management of these types of patients is the basis for this discussion.  The following clinical questions arise when managing patients such as the two described above.

 

Clinical Questions

  1. What is the optimal time for laparoscopic surgery in a patient presenting with acute cholecystitis?

  2. What is the evidence that supports a laparoscopic approach to patients with acute cholecystitis?

  3. What clinical factors exist to predict a successful laparoscopic surgical outcome and what is the evidence supporting use of these factors in patients presenting with acute cholecystitis?

 

Introduction

 

In the last century the management of acute cholecystitis has rapidly advanced and changed as diagnostic technology such as ultrasound has improved.  During the first half of the 20th century the preferred treatment of acute cholecystitis was conservative therapy followed by delayed surgery. From the 1970’s until the mid-1980’s the procedure of choice cholecystectomy was safer and economically advantageous than delayed open cholecystectomy1.  Before these studies, it was generally accepted that a patient presenting with acute cholecystitis would be managed several days to several weeks with supportive care until the symptoms subsided, followed by an open cholecystectomy in four to twelve weeks. Several factors have created new debate about the optimal timing of surgery. First and foremost the development of laparoscopic surgery in the late 1980’s provided a less invasive option for management of cholecystitis.  In conjunction with this new technology, the elderly population in the United States dramatically increased.  With this increase the incidence of acute cholecystitis also has increased. This correlation was due to an increased incidence of gallstones in the elderly, diabetics, obese patients, and debilitated patients.  Acute cholecystitis is associated with gallstones in over 90% of cases1. With the widespread use of laparoscopy for elective cholecystectomies and the increase in the patient population with risk factors for surgical complications, came the rejuvenated interest in studies exploring the safety, benefit and timing of laparoscopic cholecystectomies for acute cholecystitis. An explanation about acute cholecystitis and the inflammatory response of acute cholecystitis is necessary prior to a discussion about the management of acute cholecystitis.

 

Acute Cholecystitis

 

Acute cholecystitis is traditionally thought of as a triad of right upper quadrant pain, fever, and leukocytosis.  However, this triad is not specific and must be accompanied by additional clinical manifestations to improve the predictive value for diagnosing this syndrome.  Many patients have nausea, vomiting, anorexia, pain that is steady and severe, and a temporal relationship between the ingestion of a fatty meal and the onset of pain at least an hour later.  The pain persists for longer than four hours unlike biliary colic, which typically reaches a crescendo over several hours and then resolves completely2.  Most of the time a gallstone lodges in the cystic duct and leads to distention and inflammation of the gallbladder. In acalculous cholecystitis, biliary sludge often blocks flow of bile at the level of the Heister valves. Patients with acute cholecystitis often show signs of local peritoneal inflammation and therefore, are often very tender on examination.  A “Murphy’s sign” is often present.  Although an elevation in serum aminotransferases, amylase, and hyperbilirubinemia are more common in patients who also have common bile duct obstruction, studies have shown these laboratory findings in patients with only calculous cholecystitis2.

Obstruction of the cystic duct occurs in both biliary colic and acute cholecystitis, but the latter involves damage to the gallbladder from inflammatory mediators and irritants to the mucosa. Lysolecithin and various prostaglandins are found in the bile of patients with acute cholecystitis. These agents escalate the gallbladder’s inflamed state and are not present in abnormal amounts in patients with biliary colic.

The issue of determining the best imaging study for a patient with acute cholecystitis is a constantly changing dilemma due to rapidly evolving technology.  Since an adequate discussion of this dilemma will take away from my stated goals concerning the timing of surgical management for acute cholecystitis, it will not be fully addressed. Imaging options include ultrasound, cholescintigraphy (HIDA scan), computed tomography, and magnetic resonance cholangiography (MRCP), although MRCP’s use in diagnosing acute cholecystitis is very limited.  Abdominal ultrasound is the preferred first choice, and evidence of gallbladder wall thickening or edema or a sonographic Murphy’s sign confirm the diagnosis of acute cholecystitis.

 

     Cleveland Clinic Journal of Med.3

 

Pathogenesis of Acute Cholecystitis

 

In order to understand why the timing of surgery is important for the resolution of acute cholecystitis, a brief explanation of the inflammatory response that it involves is necessary.  During the early stages of acute cholecystitis the connective tissue surrounding the gallbladder is edematous and hyperemia is diffuse. The edema during this initial stage facilitates view of the structures surrounding the gallbladder. In particular, the triangle of Calot which consists of the common hepatic duct, cystic duct, and the liver is a guide for resection of the gallbladder.  After 72 hours of inflammation, adhesions, hypervascularity, fibrosis, and necrosis develop.  These changes prevent adequate visualization of the triangle of Calot, and thus increase the chances for intraoperative complications.  The sequence of these inflammatory changes has led to the belief of performing surgery for acute cholecystitis during the first “golden 72 hours” of the onset of symptoms4.

 

Management

Once the diagnosis of acute cholecystitis is established, a patient must be appropriately managed to prevent complications. Before understanding the current recommendations for the management of acute cholecystitis, one must first know some historical principles that led to today’s method of improving patients with this disease entity. As early as the mid-1700’s a surgeon named Jean Petit was the first to use a trocar to percutaneously drain an inflamed gallbladder. Several prominent physicians following him expanded the knowledge base of cholecystitis and management of gallstones over the next 100 years. In 1886, the first cholecystectomy was performed in the U.S. by Justus Ohage5.  The management during the early to mid-part of the 20th century would be greatly changed by the revolution of imaging technology used to diagnose gallstones and gallbladder disease.  In addition to these technological advances, improvements in surgical techniques have occurred, which together have tremendously altered the management of acute cholecystitis.

For any patient, management of acute cholecystitis begins with supportive care.  Supportive care includes intravenous hydration, bowel rest, and antibiotics.  In one study 46% of patients with acute cholecystitis had positive bile cultures with Escherichia Coli (41%) being the most common organism followed by Enterococcus (12%), Klebsiella (11%), and Enterobacter (9%)2.   Although no studies have definitively shown a benefit to patients treated with antibiotics for acute cholecystitis, it is recommended by most physicians in order to attempt to reduce the postoperative complication rate. The antibiotic choice varies but it should be geared toward coverage against the previously stated organisms. Often a combination of ampicillin with an aminoglycoside or a third-generation cephalosporin is used during initial care for acute cholecystitis.  A nasogastric tube is inserted if the patient is vomiting, and analgesics are also initiated in some cases.  There is some evidence that analgesics such as rectally administered indomethacin can improve the course of acute cholecystitis. A randomized study by Thornell et al showed that indomethacin can improve fever, abdominal pain, white blood count and serum bilirubin much greater than placebo in patients diagnosed with acute cholecystitis. This study supported the hypothesis that nonsteroidal anti-inflammatory agents not only decrease the intraluminal gallbladder pressure, but also improve the clinical course of acute cholecystitis patients awaiting surgery6.

The cornerstone of management for acute cholecystitis is surgery, since supportive care alone will not prevent future episodes of cholecystitis or its complications.  Complications of ineffective treatment include development of gallbladder gangrene, perforation, cholecystenteric fistula, and emphysematous changes in the gallbladder.  These complications greatly increase the morbidity and mortality of affected patients.  To try and prevent these complications surgery should be undertaken for patients presenting with acute cholecystitis.  The timing of surgery is debatable due to the advent and subsequent mastery of laparoscopic techniques. The optimal timing for surgery in a patient with acute cholecystitis is not currently known. Some surgeons believe that a laparoscopic cholecystectomy should be done within 72 hours of admission or at least during the first episode of cholecystitis, while others believe that patients benefit from supportive care only during the initial attack followed by an elective cholecystectomy in 6-12 weeks.   There are advantages and disadvantages to either approach, which will be highlighted in the upcoming discussion of the clinical evidence.

 

Introduction to Timing of Surgery

 

The essence of this discussion on the timing of surgery involves the definition of early versus delayed surgery. Early surgery typically means within 72 hours of admission and delayed surgery means occurring anytime after 72 hours of admission. In some studies ‘early surgery’ may refer to performance of the operation within a specified time frame beginning from the time of admission not the onset of symptoms.  Delayed surgery usually refers to supportive care only during the initial presentation followed by discharge upon resolution of symptoms and readmission 6-12 weeks later for a laparoscopic cholecystectomy.   Many physicians may ask, ‘Why operate in the acute setting when you can do it at a time when a patient is symptom-free?’ However, this day and age of cutting costs has led to numerous studies examining whether the use of laparoscopic cholecystectomies during an initial presentation with acute cholecystitis reduces hospital costs, procedural and patient complications, operative time, conversion to open cholecystectomy, and the duration of the hospital stay.    

 

Risk Stratification for Surgery

 

Traditionally the timing of surgery is based on a patient’s overall risk of surgery.  Determining this risk is often done using a scale by the American Society of Anesthesiologists (ASA)7.  Traditionally, low-risk patients are considered those in classes I and II and should undergo early cholecystectomy, unlike classes III and above, which are classified as high-risk. The evidence that follows will help clarify whether the traditional approach is the best course of action in acute cholecystitis.   

 

Feigal et al.7

 

 

Evidence: Laparoscopic vs. Open Cholecystectomy

 

A study by Kiviluoto et al in Lancet evaluated in a randomized trial the benefits of laparoscopic versus open cholecystectomy for patients with acute cholecystitis. Prior to this trial, the favored use of laparoscopic cholecystectomy for acute cholecystitis was based only on retrospective studies8. The demographics of the 63 patients in the trial were comparable including a mean age in the laparoscopic and open group of 61 and 59, respectively.  Patients from ASA III-IV were present in over 35 % of the patients in the open cholecystectomy group and over 47% of the patients in the laparoscopic cholecystectomy group.  At the end of the trial the complication rate of the laparoscopic group compared to the open group was 3% vs. 42%, respectively. Also, there was no increase in mortality in the laparoscopic group.  Both groups in this study underwent surgery within 5 days of the onset of their symptoms.  This study showed that laparoscopic surgery is safer than open cholecystectomy, but the timing of surgery was not addressed.

A study by Jarvinen et al in 1980 performed a randomized trial comparing early open cholecystectomy with delayed open cholecystectomy. In this study, 165 patients were randomized to either receive surgery within 7 days of the onset of symptoms or be discharged upon resolution of the acute attack and readmitted two to four months later for elective surgery.   Fifteen percent of patients, who subsequently had delayed surgery, had recurrent symptoms before the scheduled surgery, and 13% of the patients randomized to delayed group required emergent surgery prior to the scheduled readmission9. This study was one of the first to show that the performance of early surgery for acute cholecystitis was associated with lower costs and no increase in mortality or morbidity. 

To the practicing internist, determination of the best time for surgery has numerous advantages for their patients.  For patients that are treated with the delayed approach, some have a recurrence of symptoms prior to their scheduled elective procedure and fail conservative treatment during this second episode. This failure often leads to emergent surgery and increased chance of morbidity and mortality.  Due to this event , it seems that the early approach would be preferred.  However, the early approach may lead to conversion from a laparoscopic procedure to an open procedure, which potentially could increase morbidity and mortality. The decision on which approach to take is a challenging one that surgeons face, but it should be helped by the available evidence addressing this issue.  Another component of properly managing these patients involves the use of laboratory data preoperatively.  Some researchers believe that the use of preoperative clinical factors, especially certain lab data, may help determine the safest surgical management to use for patients with acute cholecystitis. 

 

Evidence: Timing of Surgery

 

Chandler et al: Prospective Evaluation of Early versus Delayed Laparoscopic Cholecystectomy (LC) for Treatment of Acute Cholecystitis10

 

Objective:  To compare the safety and efficacy of early versus delayed laparoscopic cholecystectomy in acute cholecystitis

 

Study Design: 

  • 43 patients at Olive View-UCLA Medical Center during June 1996-June 1998 were randomized to early vs. delayed treatment. 

  • Early treatment group had laparoscopic surgery within 72 hours of admission.

  • Delayed treatment group had laparoscopic surgery either after resolution of their symptoms or after 5 days of treatment, whichever occurred first.

  • Eligible patients received the same supportive care preoperatively: IVFs, antibiotics (Piperacillin 2g IV Q6hours), bowel rest, NG suction prn

  • Indomethacin (50mg per rectum Q12hours) given to delayed treatment group

  • Antibiotics continued for 24 hours postoperatively

 

Inclusion:  RUQ pain with localized tenderness; WBC ³ 10K or fever > 38°C, and U/S evidence of AC (gallstones, thickened gallbladder wall, pericholecystic fluid, or positive Murphy’s sign)

 

Exclusion: History of peptic ulcer disease, evidence of gallbladder perforation, or uncertainty of diagnosis

 

 

Chandler et al.10

 

Results:  Conversion rate in early vs. delayed treatment group was 24% and 36%, respectively. Operative time, blood loss, conversion rate, %gangrenous, total hospital days and charges were all increased in the delayed treatment group.  No significant reduction in complication rate in delayed treatment group.

 

Conclusions:  Delay in operation until resolution of symptoms showed no advantage with regard to operative time or complication rate.

 

Limitations:  Small study group, average patient population less than 40 years old

 

Eldar et al: Laparoscopic Cholecystectomy for Acute Cholecystitis:Prospective Trial11

 

Objective:  To determine the optimal timing of laparoscopic cholecystectomy for acute cholecystitis and to evaluate preoperative and operative factors associated with conversion from laparoscopic to open cholecystectomy

 

Study Design:

  • 137 pts at Bnai Zion Medical Center in Haifa, Israel were treated for clinical acute cholecystitis between Jan 1994 and Dec 1995

  • 130 of these 137 patients evaluated in this prospective, non-randomized study

  • 80 patients having (58%) 1st attack, 57 patients (42%) had previous biliary attacks

  • All pts underwent laparoscopic cholecystectomy as soon as the diagnosis was established

  • All pts started on admission on Cephazolin 1g IV Q8 hours and antibiotics were discontinued 24-48 hrs. postoperatively if afebrile

  • Data sheets generated with preoperative, operative, and postoperative factors

 

Exclusion:  7 patients with choledocholithiasis

 

Results:

  • 37 (28%) of 130 patients required conversion from laparoscopic to open cholecystectomy

  • Patients who had laparoscopic cholecystectomy with a delay of greater than 96 hours from onset of disease had a higher conversion rate: 47% vs. 23% (p=0.022)

  • 23/77 patients (23%) in earlier operated group versus 14/16 patients (47%) converted in delayed group (> 96 hours)

 

 

 

Figure 1: Conversion Rate of Laparoscopic Cholecystectomy for Acute Cholecystitis.  Comparison between groups with delay periods of up to and including 96 hours and longer from onset of complaints.  Shaded box = no conversion; unshaded box = conversion.   Eldar et al.11

 

 

Laparoscopic group

Converted group

Mean Age

                    50

                      60

Complication Rate (%) (p=0.013)

                   8/93 (8.5%)

10/37 (27%)

Postop Hospital Stay (days)

                     2

                       6

Table 1      Eldar et al.11

 

Independent Factors

Odds Ratio

p value

Age > 65 years

10.5

0.048

WBC > 13K

15.25

0.0108

Acute gangrenous cholecystitis

630.8

0.0001

History of biliary disease

12.4

0.0250

Nonpalpable gallbladder

111.2

0.0008

Table 2:  Independent factors associated with conversion from laparoscopic cholecystectomy.   Eldar et al.11

 

Independent Factors

Odds Ratio

p value

Gender

8.9

0.078

WBC > 13K

13.7

0.0028

Bilirubin > 0.8mg/dl

9.1

0.0068

Presence of large bile stones

8.5

0.0072

Table 3:  Independent factors associated with complications of attempted laparoscopic cholecystectomy.  Eldar et al.11

 

Conclusions: 

  • Older pts, history of biliary disease, a nonpalpable gallbladder, elevated WBC (>13K), and acute gangrenous cholecystitis were independent factors associated with a higher conversion rate

  • Male patients, serum bilirubin > 0.8mg/dl, WBC > 13K, and presence of large bile stones were independent factors associated with a higher complication rate

 

Limitations:  Small study; randomized trial needed to show whether presence of these factors should change management strategy; inferences made using odds ratios

 

Lai et al: Randomized Trial of Early versus Delayed Laparoscopic Cholecystectomy for Acute Cholecystitis 12

 

Objective:  To define the optimum management between early and delayed laparoscopic cholecystectomy for patients with acute cholecystitis

 

Study Design:

  • 145 patients had acute cholecystitis during the time period of Jan. 1993 – Dec. 1995 at Prince of Wales Hospital in Hong Kong and randomized to early versus delayed treatment

  • 31 patients excluded before randomization leaving 104 patients for randomization

  • Early group had laparoscopic cholecystectomy within 24 hours of randomization

  • Delayed group had conservative treatment then laparoscopic cholecystectomy 6-8 weeks later

  • Average age 55.8 in early group vs. 56.1 in delayed group

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Inclusion:  Right upper quadrant tenderness, temperature > 37.5 C, WBC > 10K, U/S showing gallstones in a thickened and edematous gallbladder, positive sonographic Murphy’s sign and pericholecystic fluid collections

 

Exclusion:  Symptoms > 1 week; previous upper abdominal surgery; significant medical diseases that created contraindications for laparoscopic surgery; coexisting common bile duct stones with ductal dilatation, acute cholangitis or acute pancreatitis.

 

Results:

  • No major bile duct injuries in either group

  • No statistically significant difference in conversion rate, postop. pain, or postop. complications

  • Conversion Rate: 21% (early) vs. 24% (delayed) but not statistically significant

  • Early group:

    • Shorter hospital stay compared to delayed group (7.6 days vs. 11.6 days)

    • Postoperative complication rate of 9% vs. 8% in delayed group

  • Delayed group:

    • 16% of these patients failed conservative treatment or had a recurrent attack prior to the scheduled follow-up surgery

    • Mean total hospital stay 11.6 days (longer than early group) but mean postop. stay lower in delayed group (3 days vs. 4.8 days in early group)

 

Conclusions:  The higher conversion rate in the delayed group due to an increase in dense adhesions around the GB and porta hepatis after initial conservative treatment. The data suggest that early laparoscopic cholecystectomy is better than a delayed one, because it offers definitive treatment during the same admission and avoids the problems of failed conservative treatment and the increased conversion rate of delayed surgery.

 

Limitations:  8/145 patients (6%) were excluded from study because symptoms were present for longer than 1 week.  This exclusion eliminates patients that have been shown in other studies to have a very high conversion rate when operated on laparoscopically. This elimination creates selection bias with regard to the outcomes of the study.

 

Lo et al:  Prospective Randomized Study of Early Versus Delayed Laparoscopic Cholecystectomy for Acute Cholecystitis 13

 

Objective:  To compare early with delayed laparoscopic cholecystectomy (LC) for acute cholecystitis.

 

Study Design:

  • 141 consecutive patients admitted to Queens Mary Hospital in Hong Kong between November 1994 – December 1996 with a diagnosis of acute cholecystitis

  • 42 patients were excluded before randomization due to contraindications to the surgery

  • 99 patients were randomly assigned to early LC (within 72 hours of admission) or delayed LC (treated conservatively, discharged when the acute attack subsided and readmitted for elective LC 8-12 weeks later)

  • All pts. received supportive care (IVF, Cefuroxime, etc)

  • 44 % of pts. in trial had symptoms for 3 days or more before surgery

  • Median age in both groups of 60 years old

 

Inclusion:  RUQ tenderness, fever >37.5 C, WBC > 10K, U/S evidence ( thickened gallbladder wall, edematous gallbladder wall, presence of gallstones, positive Murphy’s sign, and pericholecystic fluid collection

 

 

Lo et al.13

 

Results:

  • Conversion rate (from LC to Open Cholecystectomy):  Early vs. delayed group of 11% vs. 23%(reasons for conversion: difficulty in gallbladder exposure and difficulty in dissection of Calot’s triangle.

  • 16% of patients in delayed group (8/50) failed to respond to conservative therapy and underwent urgent LC at a median of 63 hours (3 had spreading peritonitis and 5 had persistent fever)

  • Complication rate of 13% (6/45) in early group vs. 29% (12/41) in delayed group

  • Total hospital stay and total recuperation period 5 days less and 7 days less, respectively in early vs. delayed group (p < 0.001)

 

Conclusions:  The delay from onset of symptoms to admission is patient driven and cannot be controlled, therefore, the “golden 72 hours” rule is not feasible in most cases of acute cholecystitis.  The delay from admission to surgery is controllable and is the factor being studied in this trial to determine the optimal timing of surgery. The presence of dense fibrotic adhesions, which were more common in the delayed group renders a successful LC impossible and at times unsafe.  Conversion rate and morbidity of patients with acute cholecystitis are not reduced by a period of initial conservative treatment. There are definite socioeconomic benefits for early LC over delayed LC.  The optimal timing of LC for acute cholecystitis is as soon after diagnosis as possible, preferably within 72 hours of admission for physicians with adequate experience performing laparoscopic surgery.

 

Limitations:  Very small number of obese patients in the trial and no comparison of diabetics noted

 

Auguste et al:  Timing of Surgical Intervention for Acute Cholecystitis 14

 

Objective:  To determine the optimal timing for surgical intervention for acute calculous cholecystitis.

 

Study Design:

  • 204 consecutive patients were operated on for acute cholecystitis at Long Island Jewish Medical Center between January 1980 – December 1984 and their cases were reviewed retrospectively

  • Cases divided into 3 groups depending on timing of their surgery:

    • Group 1 (n=52) = surgery within 72 hours of onset of sxs

    • Group 2 (n=114) = surgery within 15 days of onset of sxs

    • Group 3 (n=37) = treated conservatively and readmitted for elective surgery in at least 4 weeks

 

Inclusion:  Acute cholecystitis defined as acute upper abdominal pain by history, RUQ tenderness or epigastric tenderness, and temp > 99 and/or WBC > 11K, radiologic evidence, and evidence of edema, thickening, and distention of the gallbladder at laparotomy

 

Exclusion:  Patients with biliary colic, acute cholangitis, or acute biliary pancreatitis

 

Results:

 

Group

Postoperative Morbidity (%)

Hospital Stay (days)

1

15/52 (29%)

9.5

2

24/115 (21%)

12.4

3

8/37 (22%)

15.0

                                                                                                                                                                    Auguste et al.14

 

Conclusions:  No significant difference in morbidity between the three groups. The timing of surgery did not affect morbidity or mortality rates.  

 

Koo et al:  Laparoscopic Cholecystectomy in Acute Cholecystitis4

 

Objective:  To review the results of LC in patients with AC with attention to cost and clinical outcome.

 

Study Design:

  • Retrospective review of 60 patients who underwent LC for acute cholecystitis

  • Patients divided into 3 groups based on timing of surgery

    • Group 1 (n=16) = LC attempted within 72 hours of onset of symptoms

    • Group 2 (n=19) = LC between the 4th and 7th day after symptom onset

    • Group 3 (n=25) = LC after 7 days of symptoms

 

Inclusion:  Signs and symptoms of acute cholecystitis along with ultrasound and laboratory evidence, laparoscopic evidence of acute inflammation, and histopathologic presence of acute inflammation in the resected gallbladders

 

Exclusion:  Patients with histopathologic evidence of acute cholecystitis secondary to pancreatitis or carcinomatosis and patients with no definite clinical symptoms or signs of acute cholecystitis were excluded

 

Results:

  • Conversion rates in patients operated on before and after 72 hours of symptoms were 13% and 30%, respectively

 

 

 

Koo et al.4

 

Conclusions:  No significant relation between white blood count levels or liver function tests levels with conversion rates or morbidity. No relation demonstrated between abnormal ultrasound findings and the conversion or morbidity rate.  Patients operated within 72 hours of the onset of symptoms (group 1) had lower conversion rates, less difficult, shorter and less costly operations, and statistically significant shorter convalescence times compared with the other 2 groups.  More severe inflammation noted in the gallbladders from patients in groups 2 and 3. The increase in conversion rate and prolonged operation time in groups 2 and 3 is due to the increased difficulty of a laparoscopic cholecystectomy after 72 hours from the onset of symptoms. In patients presenting after 72 hours from symptom onset, an interval cholecystectomy (elective procedure 6-8 weeks after the initial attack) may be a superior option.

 

Limitations:  Retrospective review subject to selection bias.  No discussion of demographics, such as average age or comorbidities of patients categorized into each group.

 

The majority of this evidence supports the use of early laparoscopic cholecystectomy for a patient presenting with acute cholecystitis, but the exact timing of this surgery has yet to be determined. Most surgeons with considerable laparoscopic experience will manage a patient with supportive care and opt for a laparoscopic cholecystectomy within 72 hours of admission.  At this time the consensus exists for laparoscopic cholecystectomy in a ‘low risk’ patient as soon as it is feasible after the initial presentation.   For patients in the ‘high risk’ category the experts disagree on the best course of action.

From the evidence, it seems that a surgeon with considerable laparoscopic experience should follow the same pathway for a ‘low risk’ patient as a ‘high’ risk patient, if their patient is hemodynamically stable and therefore, able to tolerate anesthesia. The evidence suggests that these patients have no increased morbidity or mortality and recover faster than patients that undergo open cholecystectomy or delayed laparoscopic surgery. The evidence is limited in most cases by the use of a small sample size and referral center-based patient population, which can create biases in the magnitude of the benefit. Also, several retrospective studies are used to support clinical decision making in regards to timing of surgery in these patients.

 

Clinical Predictive Factors

 

The final question that remains in this investigation involves the presence of any clinical factors that may predict a successful laparoscopic surgical outcome. Three trials that have explored whether laboratory data or presence of certain specific symptoms could help determine when a patient would benefit most from laparoscopic surgery will now be briefly discussed.

 

Schafer et al:  Predictive Factors for the Type of Surgery in Acute Cholecystitis15

                                                                                      

Objective:  To define preoperative criteria to predict the surgical strategy for managing acute cholecystitis as well as the severity of inflammation

 

Study Design:

  • 236 patients with a mean age of 61 were admitted between Jan 1995-June 1999 with a diagnosis of acute cholecystitis

  • A non-randomized decision without strict preoperative criteria was made to perform laparoscopic cholecystectomy or open cholecystectomy and all surgery was performed within 48 hours of admission

  • ERCP done preoperatively if CBD stones suspected

  • Resected gallbladders classified into 3 subgroups based on the extent of inflammation

    • Type I = Mucosal inflammation only

    • Type II = Mucosal and submucosal inflammation (phlegmonous)

    • Type III = Gangrenous or necrotizing inflammation

 

Inclusion: RUQ tenderness and pain, fever, leukocytosis , increased CRP levels, and positive U/S (thickened gallbladder wall, pericholecystic fluid collection, positive Murphy’s sign)

 

 

Results:

 

Laparoscopic Cholecystectomy group:

  • 14 % classified as type III inflammation

  • 13 % postoperative complication rate

  • 6.3 days hospital stay

 

Converted (CON) group

  • 39% classified as type III inflammation

  • 16% postoperative complication rate

  • 9.7 days hospital stay

 

Open Cholecystectomy group:

  • 40% classified as type III inflammation

  • 35% postoperative complication rate

  • 14.1 days hospital stay

 

 

TYPE i  (n = 109)

tYPE ii (N = 63)

tYPE iii (N =64)

Mean Age

54.7

63.3

66.8

Preop Duration of Sxs

2.2 days

3.2 days

3.6 days

Mean WBC count (X109/L)

11.5

12.9

14.1

Mean CRP (mg/L)

42.1

91.0

146.4

Conversion Rate (%)

10

43

49

Complication Rate (%)

14

24

40

Table 2:  Comparison of different inflammatory stages of acute cholecystitis       (p < 0.05)  Schafer et al.15

 

  • Preoperative parameters determined to be predictors of the severity of inflammation:

    • C-reactive protein levels, duration of symptoms, white blood cell count, and male gender

  • Logistic regression analysis identified the following independent parameters that determine the treatment modality (LC or OC)

    • CRP levels and WBC counts on admission, ASA classification, duration of symptoms, and age

  • WBC counts rapidly increased with the occurrence of clinical symptoms but there was only a slight increase with advanced inflammation such as necrosis formation and perforation

  • CRP levels increased with the preop duration of symptoms and the highest levels were found in patients with gangrenous cholecystitis 

 

Conclusions:  The complication rate increased with the severity of inflammation. CRP levels > 100 mg/L are strongly associated with local tissue necrosis.  Risk of high CRP level is likely related to both the duration of symptoms and the presence of additional bacterial infections.  Percutaneous cholecystostomy should be an option only for patients unfit for surgery because 50% of patients undergoing this procedure still needed surgery at some point despite resolution of symptoms. Mortality from surgery with ASA IV was 5.5%-36% when post - percutaneous cholecystostomy. This study helped define a set of preoperative conditions that may help determine the safest method of surgery for acute cholecystitis.

 

Limitations:  Validation of markers needed with randomized trial. Selection bias in patients chosen for surgery.  Correlation needed between CRP levels and bacterial presence in the gallbladder wall (previous studies have bacterial infection rates of 80-85% in pts with CRP >100)

 

Rattner et al:  Factors Associated with Successful Laparoscopic Cholecystectomy for Acute Cholecystitis16

 

Objective:  To determine which preoperative data correlates with successful completion of a laparoscopic cholecystectomy in patients with acute cholecystitis

 

Study Design:

  • 20 of 281 patients had LC between June 1990-Feb. 1992 at Mass. Gen. Hosp.

  • 10 / 20 had early surgery and 5 of these 10 required conversion to an open procedure

  • 10 / 20 had delayed surgery and 2 of these 10 required conversion

  • Average age of 57 years

 

Inclusion: Fever, Leukocytosis, RUQ tenderness, intraoperative findings of severe acute inflammation, pathology report showing acute cholecystitis

 

Exclusion:  Intraoperative findings of acute cholecystitis but no symptoms, signs or pathologic findings of acute cholecystitis

 

Results:

  • Clinical parameters associated with severe inflammation such as degree of leukocytosis, degree of ALP elevation, and the APACHE II scores were significantly associated with failure of the procedure

 

 

Rattner et al.16

 

 

Conclusions: Results suggest that a successful laparoscopic cholecystectomy is dependent on markers of inflammation as shown in table 1. Failure of LC is directly related to gangrenous changes in the gallbladder that occur as the inflammation progresses. Little evidence to show that a cooling-off period will reduce the rate of conversion to OC in patients with acute cholecystitis. Most important predictor of the success of LC is the timing of surgery with patients operated on within 48 hours of admission having successful procedures. Optimal timing of surgery is as soon as possible after diagnosing acute cholecystitis.

 

Limitations:  Retrospective, small patient population, no information on laparoscopic expertise of surgeons involved in cases, authors of study were the same surgeons who performed the reviewed procedures creating recall bias.

 

Bickel et al:  Laparoscopic Management of Acute Cholecystitis17

 

Objective: To studying prognostic factors that may lead to a better preoperative assessment in order to decrease operative injury and possibly increase success rates

 

Study Design:

  • 182 patient had surgery for acute cholecystitis between January 1992 and July 1994 with

  • 94/182 undergoing laparoscopic surgery and were reviewed retrospectively in nonrandomized fashion

  • Mean age 52 years old (LC) vs 61 in OC group

 

Inclusion:  Persistent RUQ pain and tenderness and fever, surgical and pathologic evidence of acute cholecystitis

 

Results:

  • Duration of RUQ pain > 96 hrs Þ higher conversion rate to OC from LC (p < 0.015)

  • Failure rate in LC increased as inflammatory changes worsened

  • Complication rate lower in LC vs. OC: 6.4 % vs. 24 %

 

Conclusions:  Duration of RUQ abdominal pain and the severity of the inflammatory process found to be significantly and independently correlated with increased conversion rate to open cholecystectomy.  Laparoscopic management of acute cholecystitis should be in the earlier stage of inflammation when edema and hyperemia allow identification of the triangle of Calot and adequate retraction of the gallbladder.

 

Limitations:  Non-randomized retrospective study, no demographic information given about the two groups (LC, OC) except for age.  Severity of inflammation factor not helpful for preoperative determination of the type of surgery to do since this finding was based on histopathologic examination

Case Follow-up

 

Case 1:

 

48 hours after admission patient had a laparoscopic cholecystectomy attempted that was converted to an open cholecystectomy due to omental and colonic adhesions in her right upper quadrant.  She also had necrosis of parts of her gallbladder wall so the procedure was converted to an open one.  Patient was diagnosed with acute obstructive cholecystitis and recovered well postoperatively.

Case 2:

Four days after admission patient had a laparoscopic cholecystectomy attempted that was also converted to an open cholecystectomy due to necrosis of the gallbladder and cystic duct junction.  Patient also had stones that were impacted in the cystic duct. Patient was diagnosed with acute necrotizing cholecystitis and recovered well postoperatively.

 

Conclusions

 

Summarizing the previous data into generalized statements that will benefit a certain patient population is very difficult.  Due to the various criteria defining the early group from the delayed group, applying the results to a particular patient population is very complicated and subject to biases. In general, most of the studies recommend that for patients diagnosed with acute cholecystitis, laparoscopic cholecystectomy should be done within 72 hours of admission. This time frame is beneficial for preventing increased conversions and postoperative complications, but is dependent on the availability of an experienced laparoscopic surgeon.  The duration of symptoms correlates with the severity of inflammation found in acute cholecystitis.  If symptoms have been present for more than 72 hours, then the evidence suggests that a laparoscopic cholecystectomy should be attempted with a low threshold used for conversion to an open procedure in order to reduce the chance of intraoperative complications.  The American Society of Anesthesiologists (ASA) scale is useful as a guide for determining who should undergo laparoscopic cholecystectomy, but it is a subjective marker and is therefore difficult to use in all cases.  A patient classified as ASA IV or V will likely have resolution of symptoms from use of a percutaneous cholecystostomy tube but 50% will still require a cholecystectomy at some point15.

With the steadily increasing elderly population, and the known association of age with the incidence of gallstones, the incidence of acute cholecystitis will continue to rise.  Management of the elderly as well as other patients at increased risk for acute cholecystitis, such as the obese and diabetics will continue to be a challenge. The consensus thus far is that these patients should undergo an attempted laparoscopic cholecystectomy within 72 hours of their admission.  Finally, more data is needed before a recommendation regarding the use of C-reactive protein levels or other laboratory data as a guide for successful laparoscopic cholecystectomy can be justified.

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