biopsies from the ampulla of vater are usually essential to diagnose premalignant and malignant lesions in asymptomatic or symptomatic patients .
acute pancreatitis is an extremely unusual complication following non - thermal biopsy of the ampulla without attempted cannulation .
we present this case because of its rarity and the accompanying intense clinical manifestations without further severe consequences .
a 51-year - old man underwent two gastroscopies over the prior 2 years with the indication of intermittent dyspepsia . on the last endoscopy ,
the ampulla of vater was described as bulging ; biopsies were performed and histological examinations revealed mild chronic , nonspecific , inflammatory mucosal lesions of the ampulla and duodenum , with regional architectural disturbances , epithelial hyperplasia , accompanying mild nuclear stratification , and atypia , not fulfilling the diagnostic criteria for epithelial dysplasia .
the patient was referred to our clinic with persistent , intermittent epigastric discomfort and pain , and we therefore scheduled a repeat examination in order to exclude an ampullary tumor .
the extensive work - up after this episode did not reveal any aggravating factors for the embolism . in view of the results of the endoscopy
, we advised the patient to discontinue acenocoumarol and changed to low molecular weight heparin ( enoxaparin 40 mg / day ) .
the patient was heterozygous for sickle cell disease ( hemoglobin electrophoresis : hbs , 29.5% ; hbf , 0.6% ; hba2 , 3.6% ) .
a side - viewing scope ( olympus tjf-145 video duodenoscope ; olympus , tokyo , japan ) was used with the patient under conscious sedation ( midazolam 2 mg , propofol 60 mg ) .
eight biopsies were obtained from the area around the ampulla with a reusable oval - cup forceps ( olympus fb-26n-1 ; olympus ) . no excessive bleeding
one hour after the meal , the patient experienced an acute , severe ( eight out of 10 ) , persistent abdominal pain with recurrent , unrelieved vomiting .
he contacted his family doctor but refused hospital admission and was monitored on an outpatient basis . on the second day , the patient reported less vomiting , but the pain was still intense and he additionally became febrile to 38.5c .
he was advised to stop solid food intake and only take regular oral hydration . on day 3 , the symptoms improved with no vomiting , milder abdominal pain , and a temperature less than 37.8c .
serum and urine amylase levels were 845 u / l ( normal < 100 ) and 8,500 u / l ( normal < 460 ) , respectively .
kidney and liver tests showed normal results except for a slight elevation of the alanine aminotransferase level .
blood triglyceride level was 110 mg / dl ( normal < 150 ) and the calcium level was 9.2 mg / dl ( normal 8.5 to 10.2 ) .
a second abdominal ultrasound was unremarkable , while contrast - enhanced abdominal computed tomography ( ct ) revealed mild enlargement of the pancreatic head and stranding of the surrounding retroperitoneal fat ( fig .
eight tissue samples , with an approximate diameter of 1 to 3 mm each , were analyzed .
histological examinations revealed mild inflammatory mucosal lesions of the ampulla and duodenum , with regional gastric metaplasia , regional epithelial hyperplasia , and mild nuclear stratification , which did not meet the diagnostic criteria for epithelial dysplasia .
the majority of periampullary neoplasms are malignant , whereas benign neoplasms account for less than 10% of the cases . among benign lesions , adenomas are the most common , with a potential for malignant transformation .
although biopsies are essential in the diagnosis and follow - up of these lesions , the histological distinction between normal and pathological features of the ampullary mucosa is often difficult to make on endoscopically obtained samples .
acute pancreatitis is a well - recognized complication of endoscopic retrograde cholangiopancreatography , but is extremely rare after biopsy of the ampulla of vater without a previous attempt at cannulation .
however , an asymptomatic increase in amylase concentration has been reported in up to 30% of cases . in the case we present ,
the diagnosis of acute pancreatitis was based on symptomatology in combination with the increase in serum and urine amylase levels , as well as the ct findings . to our knowledge
, there are only three reported cases associating acute pancreatitis with endoscopic biopsies from the ampulla of vater .
the first case was reported in a patient with gardner syndrome , who developed acute progressive periumbilical pain radiating laterally to the back 4 hours after endoscopy , with temperature increasing up to 39.2oc on the following day , high serum amylase levels , and a ct scan that showed pancreatic enlargement and diffuse stranding of the peripancreatic fat .
another case of severe acute pancreatitis was attributed to endoscopic biopsies of the minor papilla in a patient with pancreas divisum and liver metastases due to colon cancer .
the third was also a case of severe pancreatitis with formation of a large pancreatic walled - off necrosis that was managed with ultrasonography - guided drainage .
in all the aforementioned cases , abdominal pain was the presenting symptom and occurred 4 hours after sampling of the papilla .
the clinical profile and course of our patient was similar to the case with gardner syndrome , with intense symptoms but still not a severe form of pancreatitis .
our patient was indeed on heparin up to 24 hours before the procedure , which in combination with the biopsy process could have led to the development of a small hematoma .
patients with sickle cell trait , especially african - americans , are more prone to manifest deep vein thrombosis and pulmonary embolism , although this remains a matter of debate .
vaso - occlusive phenomena have been described in patients with sickle cell trait ( splenic infarction or sequestration , hyphema , etc . ) .
the occurrence of a thrombotic event would have led to ischemic pancreatitis , which is also a very rare condition and is usually associated with a major circulatory event such as hemorrhagic shock .
mucosal edema due to biopsies is the most plausible mechanism for pancreatitis in our case .
we tried to direct the biopsies to the area around the orifice , but due to edema and bleeding after taking the first samples , it is sometimes very difficult to ensure that one or more biopsies are not directed towards the orifice .
this same mechanism is also proposed by ishida et al .   and morales and hixson , who reported cases of acute pancreatitis following endoscopic biopsy of the ampulla .
ishida et al .   additionally mentioned that the rise in the pancreatic duct pressure must have been low and of short duration , as no dilation of the pancreatic duct was observed . despite the clear chronological association between sampling of the ampulla and acute pancreatitis in our patient
no use of nonsteroidal anti - inflammatory drugs , paracetamol , proton pump inhibitors , antibiotics , or other commonly used medications were reported .
propofol has rarely been associated with pancreatitis if large doses are given in patients with coexistent hypertriglyceridemia .
when we reviewed both the patient s older and recent blood tests , no evidence of pathological values for lipids and/or calcium was found . to our knowledge
, there is no association of flumazenil with pancreatitis , whereas midazolam - induced pancreatitis reports has been scarcely reported and is not well - documented .
finally , it is worth mentioning that our patient recalled having substantial epigastric discomfort that lasted for 24 hours after a previous upper endoscopy when biopsies from the ampulla had been taken .
one can assume that mild forms of pancreatitis may occur more often than is actually reported in the literature . in conclusion , we present a case of acute pancreatitis following biopsy of the ampulla .
the case is significant for certain characteristics that have not been described in similar cases .
our patient s symptomatology was severe and not in parallel with the trivial laboratory and radiological pathology , and most importantly , with the excellent outcome .
the patient s medical history entails features of unknown importance for the pathogenesis of pancreatitis ( sickle - cell trait , previous use of anticoagulants , and repeat sampling ) , but these features may have contributed to the advent of pancreatitis ; therefore , this case may be worth reporting for future reference . finally , although pancreatitis after sampling of the ampulla is a rare complication , endoscopists should take it into consideration before the procedure and inform patients accordingly .
 a 51-year - old man underwent diagnostic work - up for an abnormal - appearing ampulla of vater . 
 three hours after biopsy of the ampulla , the patient presented with intense symptoms suggesting acute pancreatitis , which was later confirmed with laboratory and radiographic examinations . 
 other causes were excluded and the acute pancreatitis was considered a procedural complication . 
 this is a rarely reported complication that must be taken into consideration when biopsies are performed in the ampulla of vater . 