Clinical Pancreatology for Practising Gastroenterologists and Surgeons. Группа авторов
following his observation of this phenomenon in an autopsy case (duct obstruction hypothesis) [11]. In the same year, he also postulated the “common channel hypothesis” which states that impaction of gallstones at the papilla of Vater creates a common channel between bile duct and pancreatic duct allowing bile to reflux into the pancreatic duct [12]. However, anatomical studies have shown that the common channel is less than 6 mm which is too short to permit reflux of bile into the pancreas, and a stone at the papilla of Vater is likely to obstruct both the ducts [13]. Also, pressure in the pancreatic duct is higher than that in the bile duct, which should preclude bile reflux into the pancreas [14]. Experiments performed on American opossum, an animal model well suited to test the common channel hypothesis, showed that obstruction of the pancreas rather than bile reflux resulted in pancreatitis [15]. In an elegant study, Acosta and Ledesma [16] showed that small stones could be recovered by sieving the stool samples of patients with gallstone pancreatitis. This observation suggested that small stones migrating from the gallbladder to the biliary tract transiently obstructed the papilla during their onward journey to the duodenum and thus caused pancreatitis.
Rise in liver enzymes within the first 24 hours of onset of AP is suggestive of a biliary etiology, with a sensitivity of 85–90% [17,18]. Elevations of alanine aminotransferase (ALT) levels to threefold or more alone has a positive predictive value of 95% as shown in a meta‐analysis and increases to 100% if combined with abdominal ultrasound [19,20]. However, elevation of ALT also occurs in alcoholism, nonalcoholic steatohepatitis, and viral hepatitis. Hence, we recommend monitoring hepatic transaminase levels to document its rapid decline to baseline within a few days for predicting biliary pancreatitis.
Table 2.1 Causes of acute pancreatitis.
| Obstructive Gallstonea Tumor Benign: ampullary adenoma, ampullary GIST Malignant: periampullary carcinoma, pancreatic ductal adenocarcinoma, other pancreatic neoplasms Biliary parasites Ampullary stenosis Toxin and drugs Alcohola Scorpion venom Organophosphorus poisoning Tobacco (smoking)b Drug (list is not exhaustive) [8] Definite: L‐asparaginase, azathioprine, codeine, carbamazepine, cisplatin, co‐trimoxazole, cytarabine, dapsone, didanosine, enalapril, erythromycin, estrogens, furosemide, hydrochlorothiazide, interferon alfa‐2b, itraconazole, lamivudine, mercaptopurine, mesalamine, methyldopa, olanzapine, opiates, pentamidine, simvastatin, steroids, sulfasalazine, sulindac, tamoxifen, tetracycline, valproic acid Probable: didanosine, doxycycline, ifosfamide, imatinib, liraglutide, orlistat, oxaliplatin, rifampicin, secnidazole, sitagliptin, sorafenib, tigecycline, vildagliptin Metabolica Hypertriglyceridemia Hypercalcemia Diabetes mellitusb Traumatica Post‐ERCPa Balloon enteroscopy Hereditary/familial/geneticb Infections Viruses, e.g. mumps, hepatitis B and E, coxsackievirus, cytomegalovirus, varicella‐zoster virus, SARS‐CoV2 Bacteria, e.g. Salmonella, Mycoplasma pneumoniae, Legionella Parasites: ascariasis, Clonorchis sinensis Vascular disorders Vasculitis: microscopic polyangiitis, Wegener’s granulomatosis Hypotension/ischemia Embolic occlusion Congenital anomaliesb Annular pancreas Choledochocele Pancreas divisum Anomalous pancreatobiliary union Uncertain causes: sphincter of Oddi dysfunction Idiopathica |
a Common causes of acute pancreatitis.
b May be a cofactor rather than cause.
ERCP, endoscopic retrograde cholangiopancreatography; GIST, gastrointestinal stromal tumor.
Abdominal ultrasonography (USG) should be performed in all patients with AP to look for gallstones [21]. A biliary etiology should be suspected in patients with AP who have gallstones and a dilated bile duct with or without choledocholithiasis on abdominal USG. Abdominal USG has a very high sensitivity and specificity for cholecystolithiasis, but a lower sensitivity for choledocholithiasis [22–24]. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) have similar high sensitivity (91–100%) and specificity (85–98%) for detection of common bile duct stones [23,25,26]. In a prospective study which considered endoscopic extraction of a biliary stone as the gold standard, the sensitivity of abdominal USG, computed tomography (CT), MRCP, endoscopic retrograde cholangiopancreatography (ERCP) and intraductal endosonography was 20, 40, 80, 90, and 95%, respectively, for detecting bile duct stones [24]. The presence of gallstones alone might suggest a biliary etiology, but it is not conclusive. Biochemical and radiological investigations are needed to differentiate it from other etiologies. If there is suspicion of a common bile duct stone in view of persistently deranged liver function tests, then either MRCP or EUS should be done to look for bile duct stones. If suspicion of biliary pancreatitis remains, repeat USG is recommended after recovery [27,28].
Microlithiasis
Microliths are gallstones less than 3 mm in size and which cannot be detected on abdominal USG. Because of the lithogenic bile, microliths generally grow in size. Patients with suspected microlithiasis have been shown to develop gallstones on follow‐up abdominal USG in up to 75% of cases [29,30]. Microliths are different from biliary sludge. Biliary sludge is seen as low‐amplitude echoes in the gallbladder without acoustic shadowing on USG and layer in the dependent part. Microliths are best diagnosed on EUS with a sensitivity of 96% [35].
Earlier studies had shown a high prevalence of microlithiasis in patients with idiopathic AP; however, recent studies have shown a much lower prevalence (Table 2.2). One of the reasons could have been the reliance in earlier studies on duodenal bile microscopy to detect biliary crystals, an indirect method, in order to diagnose microlithiasis. This has largely been supplanted by EUS which detects microliths directly. Microlithiasis should be considered as a cause of pancreatitis in the presence of abnormal liver function tests within the first 24–48 hours of onset of AP as mentioned above in the context of gallstones [36].
Once a patient develops gallstone pancreatitis, cholecystectomy should be advised. Endoscopic sphincterotomy alone might prevent the recurrence by not allowing the small stone to obstruct the papilla of Vater. In a study of 5079 patients, recurrence of biliary AP in those treated with endoscopic sphincterotomy occurred in 6.7%; cholecystectomy was able to reduce this rate to 4.4%, while cholecystectomy followed by endoscopic sphincterotomy further reduced the rate to 1.2% [37].
Table 2.2 Frequency of biliary microlithiasis in recurrent acute pancreatitis.
| Study | Frequency of microlithiasis |
|---|---|
| Older studies | |
| Ros et al. 1991 [29] | 37/51 (73%) |
| Lee et al. 1992 [30] | 21/29 (72%) |
| Sherman et al. 1993 [31] | 7/13 (54%) |
| Kaw et al. 1996 [32] | 15/25 (60%) |
| Newer studies | |
| Garg et al. 2007 [33] | 10/75 (13%) |
| Wilcox et al. 2016 [34] | 20/200 (10%) |
Alcoholic Pancreatitis
In 1878, Cawley [38] first described the association by using the term “drunkard pancreatitis.” A case–control study from Japan showed that the odds ratio for development of pancreatitis increased after consumption of more than 20 g/day of alcohol. With subsequent incremental dose of alcohol intake, the odds ratio increased further to 6.4