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ACUTE CHOLECYSTITIS: DIAGNOSIS AND TREATMENT




B Navez , MD , Hôpital Saint Joseph, Gilly, Belgium
D Mutter , MD , PhD , Hôpitaux Universitaires de Strasbourg, Strasbourg, France




1. Introduction

2. Diagnosis

3. Clinical presentation

4. Medical treatment

5. Cholecystectomy

6. References


1. Introduction

While in the elective setting, a laparoscopic cholecystectomy has become the standard of care, the laparoscopic approach to acute cholecystitis remains controversial ( Kiviluoto et al., 1998 ).
Early publications list acute cholecystitis as a relative or absolute contraindication to a laparoscopic approach. This continues to be the case in certain centers ( Hashizume et al., 1998 ). On the other hand, the laparoscopic approach to acute cholecystitis is preferred in practice by a large number of experienced teams ( Navez et al., 2001 ).
Such an approach can nowadays be considered safe if the intervention is performed in a timely fashion (a maximum of 72 hours after the onset of symptoms).
A conversion rate of 20% demonstrates that the procedure is only pursued when felt to be safe ( Hunter, 1998 ).
Figure
Figure 1

1.1. Pathophysiology

Impaction of a stone in the cystic duct will result in bile stasis in the gallbladder.
Acute cholecystitis results from inflammation of the mucosa of the gallbladder which may secondarily become infected. This inflammation can then evolve to hydrops of the gallbladder and gallbladder abscess.
Complications (necrosis, perforation, phlegmon or peritonitis) can result in a dramatic clinical presentation.

In certain cases, acute cholecystitis can be acalculous (in less than 10% of the cases), especially in diabetic patients or in the immediate postoperative period following other surgical interventions ( Hashizume et al., 1998 ).

1.2. Bacteriology

An infectious agent is identified in less than 50% of cases of confirmed cholecystitis ( Thompson et al., 1990 ). These infections are polymicrobial in 30 to 80% of the cases. A transient bacteremia is frequently associated with biliary infections. Bacteremia is present in 21 to 71% of patients with acute cholangitis.
Figure
Figure 1.2

Table 1.2: Most frequent organisms identified in biliary infections ( Leung et al., 1994 )
Organism
Infected bile (%)
Bacteremia (%)
Escherichia coli
27
 71
Klebsiella
17
 14
Enterococcus
17
 0
Enterobacter
8
 5
Streptococcus
8
 0
Pseudomonas
7
 4
Candida
4
 0
Citrobacter
3
 2
Proteus
3
 0
Staphylococcus
2
 3
Clostridium
2
 0
Bacteroides
1
 1
Acinetobacter
1
 0




1. Introduction

2. Diagnosis

3. Clinical presentation

4. Medical treatment

5. Cholecystectomy

6. References


2. Diagnosis

2.1. Physical examination

Acute cholecystitis is distinguished from biliary colic by the presence of at least 2 of the following signs ( Hashizume et al., 1998 ):
  • right upper quadrant pain lasting longer than 24 hours;
  • fever greater than 37°C;
  • the presence of a palpable distended gallbladder implying gallbladder hydrops or purulent cholecystitis;
  • an elevation of the WBC count greater than 10.000/mm3;
  • ultrasonographic findings demonstrating thickening of the gallbladder wall >4 mm;
  • pericholecystic fluid.

2.2. Ultrasonography

Ultrasonography is the main radiologic examination used in these cases:
  • it confirms the presence of cholelithiasis;
  • it demonstrates signs of stasis and inflammation:
  • gallbladder distension (8 cm in length or 4 cm in diameter) ( Yang and Hodgson, 1996 );
  • gallbladder wall thickening to greater than 4 mm;
  • emphysema of the gallbladder wall,
  • pericholecystic fluid.
Figure
Figure 2.2

2.3. Laboratory examinations

The complete blood count demonstrates an elevation of the white blood cell count (WBC) to 10.000 to 12.000/mm3 with a leftward shift.
Serum chemistries demonstrate abnormalities of the liver enzymes in cases of compression of the common bile duct by the distended and inflamed gallbladder. In these cases, a mild cholestasis can be demonstrated. This hyperbilirubinemia is often very moderate in the absence of common bile duct lithiasis.

2.4. Additional examinations

When the diagnosis of acute cholecystitis is confirmed by the above findings, no additional examinations are necessary before the treatment is initiated.



1. Introduction

2. Diagnosis

3. Clinical presentation

4. Medical treatment

5. Cholecystectomy

6. References


3. Clinical presentation

Uncomplicated cholecystitis accounts for approximately 50% of all cases of acute cholecystitis ( Eldar et al., 1999 ). The natural history of cholecystitis is highly variable.

3.1. Resolution

An attack of acute cholecystitis can resolve spontaneously or following medical treatment.
A cholecystectomy can be performed in a delayed fashion or after the acute inflammation has subsided.

3.2. Subacute cholecystitis

Subacute presentations of acute cholecystitis are often associated with significant right upper quadrant pain and can mimick pancreatitis or perforated ulcer.

3.3. Hydrops of the gallbladder

Hydrops of the gallbladder is defined as distension of the gallbladder with clear and sterile white bile secondary to chronic obstruction of the cystic duct by a stone.
The clinical presentation of this hydrops is one of right upper quadrant pain with no fever and a large palpable gallbladder in the right upper quadrant. It is present in approximately 10% of cases of acute cholecystitis ( Eldar et al., 1999 ).

3.4. Purulent cholecystitis

Purulent cholecystitis is defined as a gallbladder abscess.
The gallbladder is filled with frank pus secondary to obstruction of the cystic duct with a stone, with superinfection of the bile.

3.5. Jaundice

In the absence of choledocholithiasis, acute cholecystitis may cause jaundice by compression of the extrahepatic biliary tree due to the inflammation and the local distension of the gallbladder. This is called the Mirizzi syndrome.

Depending on its severity, it can be classified into 4 types ( Nagakawa et al., 1997 )
Type I: stenosis of the common bile duct by an impacted stone in the cystic duct
Type II: fistula into the common bile duct
Type III: stenosis of the common bile duct by an impacted stone at the confluence of the cystic duct / common bile duct junction
Type IV: stenosis of the common bile duct by acute cholecystitis without impacted stone.

3.6. Complicated forms of acute cholecystitis

These are due to a local evolution of the inflammatory process in the right upper quadrant. They include:
  • the right upper quadrant phlegmon with localized peritonitis and adhesions involving the omentum, the colon or the duodenum in direct contact with the gallbladder;
  • biliary peritonitis secondary to perforation of the gallbladder into the peritoneal cavity;
  • right upper quadrant abscess;
  • and gangrenous cholecystitis.
Figure
Figure 3.6.a

Gangrenous cholecystitis represents a severe form of acute cholecystitis. It accounts for 20% of cases of acute cholecystitis ( Eldar et al., 1999 ). It is associated with hyperthermia (>38,5°C) and a higher WBC count than uncomplicated cholecystitis and a normal bilirubin level (less than 10 mg/L).
During the surgical intervention, the gallbladder wall is friable and perforates much easier than in other presentations of acute cholecystitis leading to spillage of bile and stones intraperitoneally. Operative time is typically longer with a higher conversion rate (40% vs 12% for abscess cases) ( Eldar et al., 1998 ).
Figure
Figure 3.6.b

3.7. Acalculous cholecystitis

Acalculous cholecystitis is present in approximately 18% of patients in the 11 days following a major trauma (operative or not). It accounts for approximately 6% of cases of acute cholecystitis.
The diagnosis is somewhat difficult to establish: physical examination findings are atypical as the patients are often receiving analgesics in the postoperative period or following trauma. Ultrasonographic findings are atypical (lack of cholelithiasis, absence of Murphy’s signs because of analgesic intake). This combination of factors leads to a delayed diagnosis in approximately 42% of cases ( Yang and Hodgson, 1996 ).
Laparoscopic exploration allows confirmation of the diagnosis as well as treatment of the underlying pathology, by realizing a cholecystectomy.



1. Introduction

2. Diagnosis

3. Clinical presentation

4. Medical treatment

5. Cholecystectomy

6. References


4. Medical treatment

Medical therapy must be taylored to the general medical condition of the patients and must address secondary septic complications related to the acute inflammatory process in the right upper quadrant.

Antibiotic therapy alone is insufficient for the treatment of acute cholecystitis as it only favors the formation of abscesses or chronic cholecystitis. This can eventually lead to complications such as fistulae with a nearby organs (colon, duodenum).

Initial medical therapy of acute cholecystitis includes ( Lo et al., 1996 ):
  • fluid and electrolyte resuscitation;
  • nasogastric decompression in cases of duodenal obstruction;
  • antibiotic therapy: the benefit of an antibiotic therapy versus no such treatment has been demonstrated in complicated cholecystitis as well as cases involving patients at high medical risk ( Meijer et al., 1990 ).

4.1. Evaluation of the medical risk

Medical therapy using antibiotics is justified in cases of elevated medical risk.
The patients are placed in an elevated medical risk category if one of the following criteria is met ( Meijer et al., 1990; Wetsphal and Brogard, 1999 ):
  • surgical intervention for acute cholecystitis or emergent cholecystitis (within 4 weeks of the postoperative state)
  • documented choledocholithiasis or surgical exploration of the extrahepatic biliary tree;
  • jaundice at the time of the surgical intervention;
  • age > 60 years;
  • prior history of biliary tree surgery;
  • morbid obesity;
  • diabetes.

4.2. Types of antibiotic therapy

Prophylactic antibiotics
In the absence of a documented infection, the use of antibiotic therapy at the time of the surgical intervention is considered to be prophylactic. The choice of the antibiotic to be used is dictated by economic as well as public health criteria (prevention of resistance strains).
In the absence of specific isolated organisms, the clinical benefits of the use of third or fourth generation cephalosporins or of multiple antibiotics has not been demonstrated (meta-analysis of 42 controlled studies including 4,125 patients; Meijer et al., 1990; Wetsphal and Brogard, 1999 ). The use of a single antibiotic such as Cefazoline, Cefuroxime or quinolone seems to be more appropriate in this setting ( Wetsphal and Brogard, 1999 ).

Therapeutic antibiotics
The presence of one of the criteria for elevated medical risk mandates the use of therapeutic antibiotics. Despite the fact that biliary infections are common and associated with a high morbidity , there are very few prospective randomized trials evaluating standardized approaches to the antibiotic therapy of these conditions.

4.3. The choice of antibiotics

It is preferable to use antibiotics with a high penetration into bile.
Classically, a combination penicillin-aminoglycoside has always been considered to be the standard treatment. However, their insufficient coverage against anaerobic germs, the emerging resistance of several Gram negative bacilla, and the nephrotoxicity of the aminoglycosides has led to their falling out of favor.
The ureidopenicillins have a broad spectrum of action and seem to be particularly adapted to the use in the setting of biliary tree infections. Monotherapy with these agents (Mezlocilline or Piperacilline) has been proven in prospective studies to be more efficacious than the combination ampicilline-aminoglycoside ( Gerecht et al., 1989; Muller et al., 1987 ).
The use of quinolones as single agents (ciprofloxacine 2 x 200 mg/day) has also been shown to be efficacious in the usual presentations of infections of the biliary tree ( Wetsphal and Brogard, 1999 ).
In cases of severe infections or of documented bacterial resistance ( Escherichia coli or Klebsiella for example) or in cases of pseudomonas-associated infections (peritonitis, pneumonitis), the association of Piperacilline-Tazobactam seems to be an interesting alternative ( Wetsphal and Brogard, 1999; Jaccard et al., 1998 ). The dose of these agents is Piperacilline / Tazobactam 4 g / 500 mg every eight hours.

4.4. Prophylactic antibiotics in the setting of ERCP

A large number of controlled studies have failed to demonstrate the clinical benefit of systematic use of prophylactic antibiotics prior to ERCP.
However, the severity of complications related to the failure of ERCP in decompressing the biliary tree or the presence of specific risk factors indicates the use of prophylactic antibiotics in specific settings ( Motte et al., 1991 ). These specific risk factors are:
  • history of or failure of biliary drainage;
  • cholangitis;
  • cholestasis;
  • cholangiocarcinoma;
  • elevation of WBCs.

In such cases, the use of a monotherapy is sufficient such as Cefotaxime ( Niederau et al., 1994 ) or Piperacilline ( Byl et al., 1995 ) and leads to a significant reduction in septic complications.
Current recommendations favor the administration of a single agent of one of the following antibiotics ( Wetsphal and Brogard, 1999 ):
  • Ciprofloxacine 750 mg,
  • Cefazoline 1 g,
  • Cefuroxime 1.5 g.
This antibiotic therapy must be continued if a partial or complete residual obstruction remains after ERCP.

4.5. Medical therapy alone of acute cholecystitis

Medical therapy of acute cholecystitis consists in fluid and electrolyte ressuscitation associated with prolonged antibiotic course aiming at sterilization of the infectious process.
Such treatment is indicated in the presence of absolute contraindications to a surgical intervention such as age greater than 75 years associated with poor general medical condition of the patient (cardiac or respiratory insufficiency, severe hypertension, acute myocardial infarction, psychiatric trouble, gallbladder carcinoma, etc.).
Such a therapy however is contraindicated in case of severe complications of acute cholecystitis (peritonitis, cholangitis, perforation of the gallbladder). If a course of medical therapy is chosen, the duration of the antibiotic therapy must be 10 to 28 days.
The persistance of an infectious syndrome 48 hours after the initiation of antibiotic therapy is a good indicator of the failure rate of medical therapy ( Wetsphal and Brogard, 1999 ). This failure rate is high: it ranges from 20% after median duration of 63 hours (32-142) ( Lo et al., 1998 ) to 46 % ( Margerit et al., 1994 ).

Percutaneous cholecystostomy
The use of percutaneous drainage of the gallbladder could allow for the acute episode to resolve and permit a more elective surgical intervention ( Hashizume et al., 1998 ).




1. Introduction

2. Diagnosis

3. Clinical presentation

4. Medical treatment

5. Cholecystectomy

6. References


5. Cholecystectomy

Cholecystectomy is the treatment of choice for acute cholecystitis. The laparoscopic approach is favored at the start of the case.
Despite the fact that operative principles are identical to those of elective cholecystectomy, local inflammatory changes significantly increase the difficulty of the dissection. A high level of expertise is required to perform the procedure and a higher conversion rate than for elective cholecystectomy should be accepted. Under such conditions, laparoscopic cholecystectomy in the setting of acute cholecystitis can be considered safe.
Figure
Figure 5

5.1. Timing of cholecystectomy in the setting of acute cholecystitis

At least 3 prospective randomized trials have attempted to define the optimal timing of the surgical treatment of acute cholecystitis by laparotomy. All 3studies have concluded that the ideal time for the surgical intervention is within 48 to 72 hours of the appearance of symptoms ( Järvinen and Hastbacka, 1980; Saltzstein et al., 1983; Norrby et al., 1983 ). Since the advent of laparoscopy, several studies have similarly confirmed the benefit of an early intervention.

Laparoscopic cholecystectomy, when performed early, leads to reduction in ( Koo and Thirlby, 1996 ):
  • operative difficulty;
  • conversion rate;
  • operative time;
  • cost;
  • recovery time.

One of the major determining factors is the conversion rate, an indicator of the actual difficulty of the procedure. Numerous studies have demonstrated a significantly lower conversion rate when the procedure is performed within the first 72 hours of the onset of symptoms as opposed to a delayed procedure after this period: 13% vs 30% ( Koo and Thirlby, 1996 ), 11% vs 23% ( Lo et al., 1996 ), 17% vs 30% ( Lo et al., 1998 ), 1.8% vs 31.7% ( Garber et al., 1997 ). The only study that did not demonstrate such a difference was the study by Lai et al. (1998).
These studies have also demonstrated that the hospital stay is shorter when the surgical intervention is undertaken promptly:

The cholecystectomy must be performed at the latest 48 to 96 hours after the onset of symptoms ( Estes et al., 1996; Navez et al., 2001 ) or 48 hours after admission to the hospital ( Rattner et al., 1993 ).

In case of an interval cholecystectomy following medical therapy, it must be performed within a period of 8 to 12 weeks ( Hunter, 1998 ). It is nonetheless associated with a higher morbidity rate than in early intervention.

5.2. Cholecystectomy during pregnancy

Cholecystectomy is relatively contraindicated during pregnancy due to the potentially adverse side effects on the fetus ( Hashizume et al., 1998 ).
However, when complications arise, a surgical intervention becomes mandatory. This intervention is ideally performed during the second trimester of pregnancy where the operative risks are considered to be the lowest.
Laparoscopic cholecystectomy during pregnancy has been reported in a series of over 40 patients in the elective as well as the acute setting (in rare cases), with no specific complications related to the laparoscopic approach ( Gurbuz and Peetz, 1997 ). The laparoscopic approach therefore does not seem to confer a particular added risk to this procedure.

5.3. Drainage after cholecystectomy for acute cholecystitis

Systematic drainage following cholecystectomy for acute cholecystitis should not be used. The decision to drain should be one on a case-by-case basis depending on the local conditions (quality of hemostasis and bilistasis) ( Mutter et al., 1999 ).
The use of drainage could in certain cases (difficult intervention with postoperative biliary leakage) prevent a generalized peritonitis in the postoperative period ( Hashizume et al., 1998 ).
Figure
Figure 5.3




1. Introduction

2. Diagnosis

3. Clinical presentation

4. Medical treatment

5. Cholecystectomy

6. References


6. References

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