Biliary disease is the leading cause of AP in Western countries, and therefore cholecystectomy is the optimal therapy. However, the timing of laparoscopic cholecystectomy in patients with acute biliary pancreatitis has been a contentious issue. The concern of performing same‐admission, so‐called early, cholecystectomy is safety and prolonged length of stay. Conversely, issues associated with delayed laparoscopic cholecystectomy include when it should be performed post AP and determining the risks of recurrent AP and the occurrence of biliary events (i.e. colic, cholecystitis) in the interim. In addition, this timing issue only applies in patients with mild and possibly moderate AP as it is felt that patients with severe disease should undergo cholecystectomy once they recover from their organ failure. There is no consensus about the timing of cholecystectomy in patients with pancreatic necrosis with or without infection. Da Costa et al. [86] reported a randomized controlled trial comparing same admission versus delayed (so‐called interval) cholecystectomy for patients with mild gallstone pancreatitis. The risk of recurrent gallstone‐related complications occurred more frequently (17% in the delayed group vs. 5% in the early group). A systematic review by Lyu et al. [87] of 1833 patients found that gallstone‐related complications occurred in 25% of patients during the waiting period in the delayed cholecystectomy group.
The goal of cholecystectomy is prevention of recurrent AP and biliary events. Multiple societies have recommended cholecystectomy be performed during the initial admission rather than after discharge to prevent occurrence of these events [61]. Bilal et al. [88] reported the trends of same‐admission cholecystectomy in the United States and found a decrease in use of the procedure, from 48.7% in 2004 to 45% in 2014. Delayed cholecystectomy was found to be more common in patients with severe pancreatitis, sepsis, three or more Elixhauser comorbidities, and admission to small or rural hospitals [89] and in older patients [90]. Delayed cholecystectomy in these patients was likely related to the presence of severe pancreatitis with severe comorbidities. In these patients, as always, we must balance risks and benefits of early cholecystectomy.
A concern of early cholecystectomy is whether it is associated with increased operative complications (i.e. conversion of laparoscopy cholecystectomy to open cholecystectomy). Van Baal et al. [91] from the Dutch Pancreatic Group reported a systematic review and found no differences in operative complications, conversion to open cholecystectomy, or mortality between early (index) cholecystectomy and interval cholecystectomy. A follow‐up question in patients with mild acute biliary pancreatitis who are not undergoing early cholecystectomy is whether they should undergo ERCP with ES to prevent readmissions from RAP and biliary events. Ridtitid et al. [92] found that ERCP/ES performed in a delayed cholecystectomy group of AP patients was associated with a significantly lower rate of acute recurrent biliary pancreatitis (4% vs. 36% of those patients not undergoing ERCP/ES). ERCP/ES was associated with the occurrence of mild pancreatitis (4%) and with post‐sphincterotomy bleeding (5%). Bakker et al. [93] reported similar findings: in patients with mild biliary pancreatitis who did not have index cholecystectomy but underwent ERCP/ES, the procedure significantly decreased the occurrence of interval biliary events to 7.4% (compared with 18.4% in those who did not undergo ERCP/ES). This was primarily due to a reduced risk of biliary pancreatitis. Thus, ES is a temporizing measure in patients who are unfit for surgery. ES does not protect totally against biliary colic or acute cholecystitis [93]. The next issue is whether the patients who undergo ERCP/ES should subsequently undergo cholecystectomy, which could further decrease this 7.4% rate of biliary events. Zargar et al. [94] reported a randomized trial of cholecystectomy versus expectant management in patients with biliary AP who had undergone ERCP/ES and found that cholecystectomy significantly reduced the biliary complications in these high‐risk patients. Similar findings were reported by Khan et al. [95] in a systematic review and meta‐analysis that compared early cholecystectomy versus a “wait‐and‐watch” strategy after ES in high‐risk patients. They recommended that patients undergo laparoscopic cholecystectomy because it is associated with lower rates of subsequent recurrent cholecystitis, cholangitis, and biliary colic.
Long‐term Sequelae
The morbidity of a bout of AP persists in some patients after recovery. Long‐term assessment is addressed in Table 1.8. An episode of AP increases a patient’s risk of developing diabetes mellitus, progressing to chronic pancreatitis with EPI, and is associated with an increased risk of harboring or developing pancreatic cancer. Ventre et al. [96] reported that patients who had severe AP that required critical care were found to have a high risk for developing new‐onset diabetes mellitus. In addition, as expected, greater pre‐hospitalization comorbidity, as determined by the Charlson score, negatively influenced survival. Das et al. [97] conducted a systematic review of diabetes mellitus prevalence after AP and found pre‐diabetes mellitus in 16%; this is important, as 40% of patients with pre‐diabetes progress to diabetes over 5–10 years. Diabetes mellitus was found in 23% and requirement for insulin treatment in 15%. Newly diagnosed diabetes (so‐called type 3c diabetes) developed in 15% within 12 months after the first episode of AP. Interestingly, they found that there was no effect of disease severity on the risk of developing diabetes mellitus. Conversely, in a study of patients who had severe pancreatitis, of whom almost three‐quarters underwent open necrosectomy, new‐onset diabetes mellitus was found in 45%, and pancreatic insufficiency requiring pancreatic enzyme replacement was found in 25% [98].
Shen et al. [99] reported a cohort study that included almost 3000 patients with their first attack of AP and approximately 12 000 individually matched controls. The incidence of developing diabetes within the first three months after AP was 60.8 per 1000 person‐years in the AP group compared with 8.0 per 1000 person‐years in the control group (hazard ratio, HR, 5.9). The adjusted HR was 2.54 for developing diabetes mellitus beyond three months. Similar to other studies, the results for patients with mild AP were similar to those for all AP groups. We should therefore be aware that after AP of all severities, the risk of developing diabetes mellitus is increased, so‐called “diabetes of the exocrine pancreas” [100].
Table 1.8 Long‐term sequelae after resolution of acute pancreatitis.
| Chronic pancreatitis Exocrine pancreatic insufficiency Diabetes mellitus Pancreatic ductal adenocarcinoma Decreased quality of life |
Hollemans et al. [101] reported on the follow‐up of almost 1500 patients with AP at 36 months. They found a pooled prevalence of EPI of 27%. Using fecal elastase levels, EPI occurred significantly more often in patients with alcoholic pancreatitis than in those with other etiologies. EPI was significantly more common in patients with severe than mild AP [101]. The presence of pre‐diabetes and/or diabetes mellitus in patients after AP should necessitate a search for coexistent EPI. In patients after AP, Das et al. [102] found a prevalence of concomitant EPI of 40% in patients with newly diagnosed pre‐diabetes or diabetes.
Machicado et al. [103] reported the long‐term deleterious effect on physical health‐related quality of life using a physical‐ and mental health‐related quality of life telephone survey. Individuals who had experienced AP had a significantly lower physical component survey (PCS) score than did controls and this was associated with the presence of multisystem organ failure during hospitalization, which is similar to other ICU survivors. In addition, at time of follow‐up lower PCS scores were associated with abdominal pain, analgesic use, disability, and cigarette use. Thus, support to discontinue smoking and alcohol use and to control pain on discharge should be a focus of ongoing care.
The long‐term (median of 10.5 years) follow‐up of pancreatic function after the first episode of acute alcoholic pancreatitis was reported by Nikkola et al. [104]. As expected, 35% had one or more recurrent episodes of AP during a maximum follow‐up of 13 years. New pancreatogenic diabetes developed in 19%, all of which had recurrent AP. Exocrine pancreatic dysfunction occurred in 77 (24%)