INDIANAPOLIS – Acute cholecystitis patients fared significantly better with early rather than delayed laparoscopic cholecystectomy in the largest-ever randomized trial addressing surgical timing for this common condition.

Patients assigned to early cholecystectomy – that is, surgery within 24 hours of presentation to the hospital – had one-third the morbidity, markedly shorter hospital lengths of stay, and correspondingly lower hospital costs compared with patients who underwent surgery on day 7-45, according to Dr. Markus W. Buchler of Heidelberg (Ger.) University.

"Early cholecystectomy in patients fit for surgery and in hospitals experienced in doing difficult laparoscopic cholecystectomies should become the standard of care in acute cholecystitis," he declared in presenting the results of the ACDC (Acute Cholecystitis: Early Versus Delayed Cholecystectomy) trial at the annual meeting of the American Surgical Association.

The optimal timing of surgical intervention in acute cholecystitis is a subject of long-standing controversy. The ACDC trial was conducted because in a Cochrane review of five smaller randomized trials totaling 451 acute cholecystitis patients, researchers concluded there was insufficient evidence to say which surgical strategy was best (Cochrane Database Syst. Rev. 2006 Oct 18;4:CD005440).

Dr. Buchler noted that surveys indicate many American surgeons prefer to delay laparoscopic cholecystectomy, while in Germany the surgical preference is for immediate surgery in patients with uncomplicated acute cholecystitis.

The ACDC trial involved 618 patients with uncomplicated acute cholecystitis who were placed on the same antibiotic – moxifloxacin – and randomized to early laparoscopic cholecystectomy or to delayed surgery on day 7-45. Pregnant patients were excluded from the trial, which was conducted at 35 European hospitals, including seven German university medical centers. All participating hospitals were staffed by surgical teams experienced in performing difficult laparoscopic cholecystectomies.

The primary endpoint was total morbidity within 75 days. This included cholangitis, pancreatitis, biliary leak, stroke, myocardial infarction, abscess, bleeding, peritonitis, infection, and renal failure. The rate was 11.6% in the early cholecystectomy group compared with 31.3% with delayed surgery. Among less challenging patients with an ASA score of 2 or less, the rates were 9.7% and 28.6%, respectively. Patients with an ASA score above 2 had an overall morbidity rate of 20% with early surgery compared with 47% with delayed laparoscopic cholecystectomy.

The rate of conversion to open surgery was 9.9% in the early laparoscopic cholecystectomy group and similar at 11.9% in the delayed surgery group. This came as a surprise to Dr. Buchler and his coinvestigators. They expected a significantly higher conversion rate in conjunction with delayed laparoscopic cholecystectomy.

"I think what this tells us is surgeons have gotten really good at laparoscopic cholecystectomy even in more difficult situations," he observed.

Total hospital stays averaged 5.4 days in the early surgery group compared with 10.0 days with delayed surgery. Mean total hospital costs calculated via the German DRG system were 2,919 euro in the early cholecystectomy group and 4,261 euro with delayed surgery.

Discussant Dr. Andrew L. Warshaw praised Dr. Buchler and his coworkers in the German surgical clinical trials study group for their "leadership in determining evidence-based standards of care."

"There’s no doubt in my mind that immediate cholecystectomy is superior in this patient population," said Dr. Warshaw, professor and chairman of the department of surgery at Harvard Medical School, Boston.

Noting that most acute cholecystitis patients are first seen by an internist or gastroenterologist who then makes the initial treatment decision, Dr. Warshaw asked Dr. Buchler if German internists and gastroenterologists have gotten on board this immediate surgery treatment pathway.

"Convincing internists and gastroenterologists will take a long time, at least in Germany," the surgeon replied. "It is much easier to convince the emergency department physicians to refer patients early to surgery; they’re much closer to the surgeons."

He noted that German surgical practice differs from that in the United States in several respects. For one, German patients routinely stay in the hospital longer, even if they don’t experience complications. That’s why the mean length of stay after cholecystectomy in ACDC was 4.68 days in the early surgery group and closely similar at 4.89 days in the delayed surgery group, even though the delayed surgery group had a threefold higher complication rate.

Another difference is that, unlike in this country, intraoperative cholangiography is rarely done in Germany.

"It’s the absolute exception that intraoperative cholangiography is used. It is used only when there’s a reason for it, such as jaundice. There was probably less than a 3% intraoperative cholangiography rate in this trial," said Dr. Buchler.

The ACDC trial was funded with government research grants. Dr. Buchler reported having no financial conflicts.

bjancin@frontlinemedcom.com

Early cholecystectomy beats delayed in acute cholecystitis