Paraduodenal pancreatitis (PP) represents a diagnostic challenge, especially in non-referral centers, given its potential imaging overlap with pancreatic cancer. There are two main histological variants of PP, the cystic and the solid, with slightly different imaging appearances. Moreover, imaging findings in PP may change over time because of disease progression and/or as an effect of its risk factors exposition, namely alcohol intake and smoking.

To describe multimodality imaging findings in patients affected by PP to help clinicians in the differential diagnosis with pancreatic cancer.

The systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analyses 2009 guidelines. A Literature search was performed on PubMed, Embase and Cochrane Library using (groove pancreatitis [Title/Abstract]) OR (PP [Title/Abstract]) as key words. A total of 593 articles were considered for inclusion. After eliminating duplicates, and title and abstract screening, 53 full-text articles were assessed for eligibility. Eligibility criteria were: Original studies including 8 or more patients, fully written in English, describing imaging findings in PP, with pathological confirmation or clinical-radiological follow-up as the gold standard. Finally, 14 studies were included in our systematic review.

Computed tomography (CT) findings were described in 292 patients, magnetic resonance imaging (MRI) findings in 231 and endoscopic ultrasound (EUS) findings in 115. Duodenal wall thickening was observed in 88.8% of the cases: Detection rate was 96.5% at EUS, 91.0% at MRI and 84.1% at CT. Second duodenal portion increased enhancement was recognizable in 76.3% of the cases: Detection rate was 84.4% at MRI and 72.1% at CT. Cysts within the duodenal wall were detected in 82.6% of the cases: Detection rate was 94.4% at EUS, 81.9% at MRI and 75.7% at CT. A solid mass in the groove region was described in 40.9% of the cases; in 78.3% of the cases, it showed patchy enhancement in the portal venous phase, and in 100% appeared iso/hyperintense during delayed phase imaging. Only 3.6% of the lesions showed restricted diffusion. The prevalence of radiological signs of chronic obstructive pancreatitis, namely main pancreatic duct dilatation, pancreatic calcifications, and pancreatic cysts, was extremely variable in the different articles.

PP has peculiar imaging findings. MRI is the best radiological imaging modality for diagnosing PP, but EUS is more accurate than MRI in depicting duodenal wall alterations.

Paraduodenal pancreatitis (PP), also known as groove pancreatitis, is a peculiar form of chronic pancreatitis characterized by an inflammatory mass-forming involvement of the duodenal wall in the so-called groove area, located between the head of the pancreas, the duodenum, and the common bile duct[1]. The inflammatory process may lead to a solid thickening of the duodenal wall and/or to the development of cystic changes centered in the groove area. PP has been subdivided into cystic or solid type, based on the presence or absence of cysts in the groove area at imaging or pathology. According to a large Italian study, two thirds of patients present the cystic type of PP and one third the solid one[2]; similar data were reported on a more limited series from India[3]. The inflammatory process, arising from the groove area, might also extend to the whole pancreas secondary to the compression and obstruction of the main pancreatic duct by the inflamed and thickened groove area, leading to obstructive chronic pancreatitis. No definitive epidemiological data have been published, but PP is a rare disease considering that in an observational study including 893 patients with chronic pancreatitis, PP prevalence was 6%[4]. On the other hand, a German study published in 2014 reported 3.5% of PP on 373 consecutive pancreatic resections in a single center[5].

Adsay et al[1] described the typical histological features of PP, namely dilated ducts in the duodenal wall with pseudocystic changes and granulation tissue, Brunner’s gland hyperplasia, dense myoid stromal proliferation and fibrosis of the pancreas and of the surrounding soft tissue of the groove area[1].

As reported by many previously published papers, patients suffering from PP are typically middle-aged men, heavy smokers, and drinkers[2-4,6-14]. Acute pancreatitis and abdominal pain have been described as the most frequent presenting symptoms, followed by symptoms related to duodenal obstruction (vomiting and weight loss) and to common bile duct obstruction (jaundice)[2,9-11]. Symptoms related to pancreatic insufficiency (diabetes and steatorrhea) are less frequent and generally reported in patients with advanced disease.

PP diagnosis may be challenging since patients often present with symptoms mimicking pancreatic cancer, such as abdominal pain, vomiting, weight loss or jaundice, and, especially in the solid type, also at imaging the differential diagnosis with pancreatic cancer can be extremely difficult. Therefore, a significant proportion of patients (reported between 5% and 21%, even in referral centers) undergo demolitive pancreatic surgery because of misdiagnosis or malignancy suspicion[2,6,15,16].

Many different therapeutic strategies have been proposed for symptoms’ management in PP and, nowadays, no definitive data have been published about the best choice between medical treatment and endoscopic or surgical interventions. A step-up approach should probably be considered, starting with medical treatment based on pain control, alcohol consumption cessation, and smoke cessation. Endoscopic treatment might be considered in the case of bile duct stenosis and surgery should be reserved for patients with intractable pain, duodenal obstruction, or recurrent bile duct obstruction and cholangitis.

Despite the rarity of the disease, a precise radiological and clinical diagnosis is crucial for patients’ management and a multidisciplinary approach is needed to reduce the risk of misdiagnosis and of inappropriate surgical resections. Therefore, the aim of our study was to conduct a systematic literature review to show the multimodality imaging appearance of PP and to assess imaging performance in the differential diagnosis between PP and pancreatic cancer.

Our systematic review included 14 original articles showing multimodality imaging findings in PP. Imaging was the main topic in eight of the included articles, whereas it was ancillary in six of them; in these latter articles, imaging findings were not always extensively and accurately described. A total of 22 different imaging features were considered by the Authors in the included articles, with a mean of 4,4 imaging features per article. Surprisingly, the most frequently described imaging features were not directly correlated with PP appearance and were in the presence of main pancreatic duct dilatation (reported in 13 studies), presence of biliary duct dilatation (11 studies) and presence of pancreatic calcifications (10 studies). Presence of duodenal wall thickening and of duodenal walls cysts were also frequently assessed in the included studies (10 and 8 studies, respectively).

Typical imaging findings in PP are second duodenal portion wall thickening (88.8% of the cases), which is usually eccentric (81.8%), associated with the presence of duodenal wall cysts (82.6%) and second duodenal portion increased wall enhancement (76.3%). Duodenal wall cysts were more frequently single (65.8%) and showed a mean maximum diameter of 13 mm. The above-described imaging findings detection rates varied largely according to the adopted imaging modality. For example, duodenal wall thickening prevalence was 96.5% at EUS (Figure 2A), 91.0% at MRI and 84.1% at CT, and, similarly, duodenal wall cysts prevalence was 94.4% at EUS, 81.9% at MRI and 75.7% at CT. These differences are probably the consequence of the increased tissue contrast resolution of EUS over MRI and of MRI over CT (Figures 2B and 3). Consequently, the prevalence of cystic and solid subtypes of PP can be extremely variable and depends on the patients’ population characteristics (solid subtype prevalence increases in the surgical series, given to the difficulty in differential diagnosis with pancreatic cancer, and decreases in the gastroenterological series) and from the adopted imaging modality (cystic subtype prevalence is higher in MRI and EUS series in comparison to CT series).

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Figure 2 Endoscopic ultrasound. A: Endoscopic ultrasound (EUS) clearly shows second duodenal portion wall thickening in a patient with chronic alcohol abuse history and abdominal pain, findings suggestive of solid subtype of paraduodenal pancreatitis; B EUS shows mild second duodenal portion wall thickening and a large duodenal wall cyst (star), findings pathognomonic for paraduodenal pancreatitis.

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Figure 3 A 49-year-old male patient with weight loss and abdominal pain. A: Axial 3 mm thick multiplanar reconstruction of portal venous phase computed tomography acquisition shows a hypodense mass in the groove region with patchy enhancement (arrow); B: Axial T2-weighted magnetic resonance imaging image acquired 2 mo later clearly shows eccentric second duodenal portion wall thickening (line) with cystic component (dotted arrow).

A solid mass in the groove region was described in less than a half (40.9%) of patients with PP. At MRI, lesion signal intensity was quite variable on T1- and T2-weighted images. On the other hand, the included lesions were hypo- to iso-intense in comparison to a normal pancreas on high b-value DWI in 100% of the cases (Figure 4A) and were iso- to hyper-intense on the ADC map in 96.4%. Therefore, the presence of increased diffusivity restriction (i.e. hyperintensity on high b-value DWI and hypointensity on the ADC map) has high negative predictive value for the diagnosis of PP. The solid components typically (82.4%) appeared hypovascular in the arterial phase of the dynamic study and showed a progressive enhancement during the portal venous (57.1% iso- to hyper-intense/attenuating) and the delayed (100% iso- to hyper-intense/attenuating) phases (Figure 4B). The enhancement pattern during the portal venous phase was mainly described as “patchy” (78.3% of the cases). Both patchy enhancement during portal venous phase, which is the consequence of the presence of normal pancreatic tissue between the areas of inflammatory changes[9], and delayed phase enhancement, which is the direct consequence of the presence of fibro-inflammatory tissue, are useful in the differential diagnosis between PP and pancreatic cancer.

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Figure 4 Magnetic resonance imaging. A: Axial high b value (b = 800 s/mm²) diffusion weighted imaging image shows absence of increased diffusivity restriction in the thickened groove area (star) in comparison to adjacent “normal” pancreas, finding associated with paraduodenal pancreatitis and uncommon in pancreatic cancer; B: Axial delayed phase T1-weighted magnetic resonance imaging acquisition shows increased enhancement of the duodenal walls and of the groove region (arrow) in comparison to “normal” pancreas (star), finding often associated with paraduodenal pancreatitis.

Presence of radiological signs of obstructive chronic pancreatitis were reported with extremely variable prevalence in the included studies. For example, prevalence of main pancreatic duct dilatation ranged from 28.9% to 95.5%, prevalence of pancreatic calcifications from 20.0% to 100%, and prevalence of pancreatic cysts from 35.1% to 94.1%. The rationale of these wide differences is clearly explained in the work of de Pretis et al[2], which demonstrated that the prevalence of both pancreatic calcifications and main pancreatic duct dilatation significantly increases during the course of the disease. Therefore, despite the results reported by Boninsegna et al[22], signs of obstructive chronic pancreatitis should not be used for a differential diagnosis between PP and pancreatic cancer.

Given its expansile inflammatory nature, PP determines reactive alterations in the adjacent structures. The most frequently encountered finding was peripancreatic fat stranding, which was appreciable in 88.1% of the cases, often associated with enlarged reactive peripancreatic lymph nodes (65%). Gastroduodenal artery displacement, without infiltration or occlusion, must also be considered a common finding in PP (64.3%).

Given the central role of duodenal wall changes depiction in the differential diagnosis between PP and pancreatic cancer[21,22], MRI is mandatory if CT is inconclusive, and EUS must be performed if doubts remain even after MRI[23]. Moreover, EUS-guided fine needle aspiration/biopsy should be performed in inconclusive cases, warranting diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in differentiating PP from pancreatic cancer of 90%, 100%, 100%, 93%, and 96%, respectively[13].

The main strength of our study is that it is the first systematic literature review of imaging findings in PP. By systematically reviewing 14 different original articles dealing with imaging findings in PP, we have been able to bring together a total of 543 patients affected by PP. The article has also some weaknesses, mainly due to selection bias in the included articles and to the extreme variability of the evaluated and described imaging findings. Moreover, the differential diagnosis between PP and pancreatic cancer, which represents the main criticality, was only addressed in 4 Papers.

PP has peculiar imaging findings that enable differential diagnosis with pancreatic cancer, namely second duodenal portion eccentric wall thickening, increased enhancement, and cystic changes. Absence of increased diffusivity restriction in the groove area, patchy enhancement during the portal venous phase and delayed phase enhancement are also imaging features strongly correlated with PP. Signs of obstructive chronic pancreatitis and biliary obstruction are often present in advanced disease and must not be considered worrisome features.

CT can be considered the first line imaging modality in pancreatic pathologies and enables clinicians to perform a differential diagnosis between PP and pancreatic cancer in most of the cases. Given its higher tissue contrast resolution, MRI represents the second level imaging modality of choice in the case of inconclusive CT findings. EUS has higher accuracy than CT and MRI in depicting duodenal wall changes, offers the possibility of obtaining cyto-histologic samples, but is more invasive and less tolerated; therefore, EUS must be considered a problem-solving technique in difficult cases.