Abstract
Objective
This study was conducted to investigate the imaging information, laboratory data, and clinical characteristics of duodenal papillary malignancies, aiming to contribute to the early diagnosis of these diseases.
Methods
The clinical characteristics, laboratory data, and computed tomography (CT) findings of 17 patients with adenoma of the major duodenal papilla (the adenoma group) and 58 patients with cancer of the major duodenal papilla (the cancer group) were retrospectively analyzed. The measurement data were analyzed using t test and expressed as mean ± standard deviation. The counting data were analyzed using the χ2 test and expressed in n (%). Pearson correlation analysis was also conducted, and a scatter plot was drawn.
Results
There were significant differences in the diameter, shape, margin, and target sign of the major duodenal papilla, pancreatic duct diameter, common bile duct diameter, enhancement uniformity, fever, direct bilirubin, total bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9, and jaundice between the adenoma group and the cancer group (P < .01). The enhancement magnitude of the duodenal papilla was correlated with the lesion size, and the venous phase CT value of the enhanced scan was correlated with the duodenal papilla diameter (P < .05). Additionally, 12 patients in the cancer group suffered from malignant transformation of adenomas.
Conclusion
Firstly, CT is of high value in the diagnosis of duodenal papilla diseases. Secondly, the enhancement magnitude of the duodenal papilla is correlated with the lesion size. Thirdly, patients with duodenal papilla adenomas have a risk of progression into adenocarcinoma, thereby requiring close follow-up.
Keywords
Introduction
There are 2 mastoids in the middle part of the duodenum, which can be anatomically divided into the minor duodenal papilla (visible in some people) and the major duodenal papilla. More specifically, the minor duodenal papilla is the opening of the accessory pancreatic duct; while the major duodenal papilla is the common pathway of the opening of the common bile duct and pancreatic duct. The major duodenal papilla covers a variety of epithelial types and can regulate the excretion of pancreatic juice and bile.1,2 Therefore, the major duodenal papilla is an important anatomical structure and it is commonly referred to as duodenal papilla.1,2 Duodenal major papilla adenoma is a rare and benign tumor with the potential for malignant transformation, presenting an incidence of about 0.04 - 0.12. 3 Duodenal major papilla adenoma can be considered a precancerous lesion of duodenal major papilla carcinoma.4-7 Cancer of the major duodenal papilla occurs in the duodenal papilla part, which consists of the common duct connecting the bile duct and the pancreatic duct, adjacent sphincter muscle, and papillary bulge of the duodenal mucosa. 8 Duodenal major papilla carcinoma is the rarest gastrointestinal malignancy type, with an incidence of 0.2%. 9 In addition to occasional papillary carcinoma, adenosquamous carcinoma, or mucinous adenocarcinoma, duodenal papilla carcinoma is dominated by adenocarcinoma; however, the etiology remains unclear. 10
The symptoms are not obvious in the early stage of duodenal major papilla adenoma and duodenal major papilla carcinoma. However, symptoms such as abdominal pain, jaundice, and weight loss can manifest after the biliary outlet is blocked by the tumor. It is difficult to conduct an early clinical diagnosis for these diseases because the duodenal papilla is surrounded by the pancreas, bowel, and adjacent ducts. At present, timely surgical treatment is recommended after the diagnosis is confirmed. Meijer et al 11 found that, compared with tumors in other parts of the duodenum, early lesions of duodenal papillary tumors were more common, which can be diagnosed at an early stage of tumor development and can be completely resected at an early stage with a better prognosis. Therefore, duodenal papillary tumors should be detected and treated as early as possible. Li et al 12 suggested that different treatment methods should be selected for duodenal papillary tumors at different stages. The pathological stage of the tumor is an important factor affecting the prognosis, and surgical treatment may achieve better outcomes for early-stage cancers. However, comprehensive consideration should be given to the treatment plan for progressive cancers. At present, the diagnosis of duodenal papillary lesions is mainly made by enhanced computed tomography (CT), enhanced magnetic resonance imaging (MRI), endoscopic retrograde cholangiopancreatography (ERCP) and other examinations, and there is no sufficient evidence to corroborate that 1 examination method is significantly superior to the others. Given these facts, this study was conducted to investigate the imaging information, laboratory data, and clinical characteristics of duodenal papillary malignant diseases, thus achieving the early diagnosis of these diseases.
Materials and Methods
The clinical data of 75 patients were retrospectively collected. Patients who were diagnosed by pathological examinations in our hospital between January 2011 and December 2020 were divided into the cancer group and the adenoma group according to pathological types.
The inclusion criteria included patients with complete clinical and laboratory data, CT findings, and pathologic findings of duodenal papillary lesions and those without a history of other malignant tumors.
This study was conducted in accordance with the Helsinki Declaration of the World Medical Association. This study was approved by the ethical review board of our institution. No. ZN-20240703-0237-01. Written informed consent to participate in this study was provided by the patients, for their anonymized information to be published in this article.
Data Collection
1. The general condition and clinical presentation data included age, gender, fever, abdominal pain, and jaundice. 2. The laboratory examination data included white blood cell count, total bilirubin, direct bilirubin, and tumor markers (CEA, CA19-9, and CA125). 3. Radiological examination (CT).
The direct signs on CT included the major duodenal papilla diameter, shape, margin, enhancement uniformity, and CT value in each phase)
The indirect signs on CT included the pancreatic duct diameter, common bile duct diameter, pancreatic duct dilatation, choledochectasia, presence of calculus at the lower end, pancreas divisum, metastasis, and target sign)
CT Scan
The abdominal plain scan and three-phase enhanced scan were performed using the Siemens 64-row spiral CT scanner. Specifically, 100 mL of ioversol contrast agent (350 mg/mL) was injected at a rate of 3-4 mL/s through elbow vein puncture. The arterial, venous, and delayed phase images were obtained at 25 s, 65 s, and 110 s after injection.
Statistical Analysis
The data were processed with the aid of SPSS 22.0. The measurement data were analyzed by the t test and expressed as mean ± SD. The counting data were analyzed by the χ2 test and expressed in n (%). As the CT value of the plain scan and enhanced scan showed a normal distribution with the nodule diameter, the Pearson correlation analysis was conducted, and the scatter plot was drawn. P < .05 was considered statistically significant.
The reporting of this study conformed to the guidelines of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement. 13 All patient details had been de-identified.
Results
The Adenoma Group
General Situation, Clinical Manifestations and Laboratory Findings of Adenoma of the Major Duodenal Papilla Group and Cancer of the Major Duodenal Papilla Group.
(A) Abdominal CT: enlarged major duodenal papilla in the intestinal lumen of the descending duodenum, which was nearly regular in shape with regular edges, and homogeneous enhancement. (B) Abdominal CT: dilatation of common bile duct. (C) Pathology: (staining, H&E; magnification, ×200) duodenal villous adenoma, mild or moderate dysplasia, infiltrating the duodenal papilla and ampulla.
The laboratory and clinical parameters included age (66.14 ± 10.28) years old, jaundice (11.76%, 2/17), fever (23.53%, 4/17), abdominal pain (23.53%, 4/17), total bilirubin 15.8 (13.5, 18.9) umol/L, direct bilirubin 2.9 (1.85, 5) umol/L, white blood cell count 6.5 (4.8, 8) × 109/L, tumor marker CEA 2.5 (1.3, 3.5) ug/L, CA19-9 5.4 (2.75, 47.15) ku/L, and CA125 13.3 (6.3, 16.35) ku/L (Table 1).
The Direct Signs on CT for Adenoma of the Major Duodenal Papilla
Direct Signs on CT of Adenoma of the Major Duodenal Papilla Group and Cancer of the Major Duodenal Papilla Group.
Indirect Signs on CT of Adenoma of the Major Duodenal Papilla Group and Cancer of the Major Duodenal Papilla Group.
The Cancer Group
A total of 58 patients with cancer of the major duodenal papilla were included in this study, including 46 patients with adenocarcinoma of the duodenal major papilla. Among these patients, there were 16 females and 30 males, and the ages of these patients ranged from 43 to 84 years old, with an average age of 66.67 ± 9.79 years old. Additionally, 12 patients suffered from the malignant transformation from adenomas, including 4 females and 8 males (age range: 46-87 years old, with an average age of 64.08 ± 12.21 years old). The pathological data and CT scan are shown in Figure 2. (A) Abdominal CT: enlarged major duodenal papilla in the intestinal lumen of descending duodenum, which was abnormal in shape with partly ulcer-like lesions, and nearly homogeneous enhancement. (B) Abdominal CT: dilatation of pancreatic duct and common bile duct. (C) Pathology: (staining, H&E; magnification, ×200) major duodenal papilla moderate differentiated adenocarcinoma, infiltrating the muscularis propria.
The laboratory and clinical parameters included age (66.14 ± 10.28) years old, jaundice (75.86%, 44/58), fever (24.14%, 14/58), abdominal pain (25.86%, 15/58), total bilirubin 82 (33, 147.75) umol/L, direct bilirubin 39 (8.025, 87.1) umol/L, white blood cell count 6.9 (5.6, 10.2) × 109/L, CEA 3.4 (2.7, 5.45) ug/L, CA19-9 85.45 (23.175, 374.75) ku/L, and CA125 14.8 (8.4, 21.3) ku/L (Table 1).
CT Direct Signs in Cancer of the Major Duodenal Papilla
Most patients with cancer of the major duodenal papilla had a tumor with an irregular shape, accounting for 65.52%, (20/58). The diameter of the major duodenal papilla was 19.10 ± 4.65 mm. The proportion of enhanced uniformity was 51.72% (30/58), and that of clear margins was 56.90% (33/58). The plain CT value was 38.53 ± 4.42 HU, the enhanced venous phase CT value was 76 (69.75, 90.75) HU, and the enhanced arterial phase CT value was 78.69 ± 14.63 HU (Table 2). Indirect signs: The diameter of the pancreatic duct was 5 (2, 7.25) mm, and that of the common bile duct was 19 (15.75, 21) mm. The proportion of pancreatic duct dilatation was 63.79% (37/58), and that of choledochectasia was 96.55% (56/58). The proportion of patients with a target sign was 63.79%, (37/58), and that of patients with pancreatic division was 18.97% (11/58). The proportion of patients with metastasis was 15.52% (9/58), and that of patients with a diverticulum was 6.90% (4/58). The proportion of patients with a calculus at the lower end was 10.34%, (6/58) (Table 3).
There were significant differences in duodenal papilla enhancement uniformity and fever between the adenoma group and the cancer group (P < .05) (Tables 1 and 2). There were significant differences in the diameter, shape, margin, and target sign of major duodenal papilla, pancreatic duct diameter, pancreatic duct dilatation, common bile duct diameter, choledochectasia, direct bilirubin, total bilirubin, CEA, CA19-9, and jaundice between both groups (P < .01) (Tables 1–3). There was no significant difference in gender, age, plain CT value, venous CT value, arterial CT value, metastasis, diverticulum, pancreatic division, lower end with calculus, abdominal pain, white blood cell count, and CA125 (all P > .05) (Tables 1–3). The enhancement magnitude of the duodenal papilla was correlated with the lesion size, and the venous phase CT value of the enhanced scan was correlated with the diameter of the duodenal papilla (P < .05) (Figure 3). In the cancer group, 12/58 patients suffered from the malignant transformation from adenomas. Hence, patients with duodenal papilla adenomas had a risk of progression into adenocarcinoma. Pearson correlation analysis: the venous phase CT value of enhanced scan was correlated with the size of duodenal papilla.
Discussion
The lesions of the duodenal papilla are common in inflammation and tumors, of which the adenoma is the most common benign tumor in this area (70%), 14 and the adenocarcinoma is the most common malignant tumor. 15 Due to the small size of the adenoma of the major duodenal papilla and malignant tumors in the early stage, there is generally no obvious clinical manifestation and effective detection methods. Some scholars have proposed that endoscopic retrograde cholangiopancreatography (ERCP) is the optimal technique to evaluate ampullary lesions.16,17 However, this technique is invasive, expensive, and time-consuming, which is not conducive to the early screening of ampullary lesions without obvious clinical symptoms. This contributes to selecting appropriate and effective diagnostic methods to make an accurate diagnosis and reduce the burden on patients. 18 In addition, some scholars have published the comparison of computed tomography (CT), laboratory, and clinical characteristics between patients with adenoma of the major duodenal papilla and those with cancer of the major duodenal papilla. Magnetic resonance imaging plus computed tomography (MRCT) can be employed to reveal the imaging features, clinical characteristics, and laboratory examination results of major duodenal papilla diseases and the comparison between benign and malignant lesions in detail through thin-layer scanning, so as to accurately detect cancer of the major duodenal papilla at an early stage and provide more significant information for the clinical diagnosis of these diseases.
It has been reported that cancer of the major duodenal papilla is mainly sporadic and often occurs in elderly males (the ratio of males to females is about 1.48:1), with a peak age of 70 years old and a mean onset age of 50 years old.1,6 Adenoma of the major duodenal papilla often occurs in females, with a mean onset age of 50-70 years old. 19 In this study, there was no statistical difference in age and gender between the 2 groups, which was consistent with previous reports. Kumar et al confirmed that cancer of the major duodenal papilla had nonspecific clinical symptoms. Jaundice may occur after a blockage in the common hepatic duct. 20 Gupta et al maintained that jaundice may appear early among various clinical characteristics, and such symptoms as abdominal pain, anemia, and emaciation may be aggravated with the progression of the disease. 15 Adenoma of the major duodenal papilla can be asymptomatic or present with abdominal pain or nausea. 21 Clary et al found that the occurrence of obstructive jaundice indicated the possibility of malignancies.22,23 In this study, there were differences in fever and significant differences in jaundice between the adenoma group and the cancer group. However, there was no statistical difference in abdominal pain between the 2 groups, which was consistent with previous reports.
There is no specific laboratory index for cancer of the major duodenal papilla. Beger et al demonstrated that the positive rate was not high, and carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were the tumor markers in patients with cancer of the major duodenal papilla. However, painless progressive jaundice may fulfill functions in the early diagnosis of cancer of the major duodenal papilla. 10 In this study, there was a significant difference in CEA and CA19-9 between the 2 groups. These laboratory indexes such as CEA and CA19-9 between the 2 groups were different from the results of Beger et al. In this study, the differences in total bilirubin and direct bilirubin were statistically significant between the 2 groups. Beger et al suggested that elevated bilirubin may be related to common hepatic duct obstruction caused by cancer of the major duodenal papilla. 24 There was no difference in blood routine white blood cell count and CA125 between the adenoma group and the cancer group.
CT can be employed to display detailed information and anatomical structures of the Vate ampulla. Although the duodenum is deep and may be affected by intestinal gas, it is an essential clinical diagnostic tool owing to its high diagnostic sensitivity and high accuracy in the localization diagnosis.25,26 The direct signs on CT images are elucidated as follows. The normal major duodenal papilla CT reveals the oval or semicircular soft tissue density shadow extending into the lumen from the inner wall of the descending segment of the duodenum. Ang et al proved that the diameter of the major duodenal papilla was generally <10 mm.3,27 Bolanaki et al found that the diameter of the normal duodenal papilla was smaller than that of duodenal papilla adenomatous lesions, which was smaller than that of the cancer of the major duodenal papilla.28,29 In this study, there were significant differences in the diameter of the major papilla between the 2 groups. Specifically, the diameter of the major papilla in patients with adenoma of the major duodenal papilla was smaller than that in patients with cancer of the major duodenal papilla, which was consistent with previous reports. Kim et al maintained that the normal major duodenal papilla had a cylindrical or conical nodular structure. 30 In this study, there were significant differences in the duodenal papilla margin and shape between the 2 groups. Specifically, the morphology of the duodenal papilla in cancer of the major duodenal papilla was abnormal with an unclear margin. In contrast, the papilla in the adenoma group was round with a clear margin. These results indicated that the diameter, margin, and shape of the major duodenal papilla were of great significance for the clinical diagnosis of these diseases. Iwashita et al concluded that there was no difference in the major duodenal papilla plain CT value, arterial CT value, and portal CT value between patients with cancer of the major duodenal papilla and individuals with normal duodenal papilla. 14 In this study, there was no statistical difference in each phase CT value between the 2 groups. Therefore, the benign and malignant lesions cannot be considered solely based on the intensity of CT enhancement. However, the results suggested that the magnitude of CT enhancement in cancer of the major duodenal papilla was positively correlated with the diameter of the mass. The enhancement magnitude increased with an increase in the volume of the lesion, and the liquefied necrotic areas may appear within the lesion with an increase in the enhancement magnitude. These liquefied areas may become blurry with time. However, all patients nearly will not appear in adenoma of the major duodenal papilla. Chang et al suggested that cancer of the major duodenal papilla showed homogeneous enhancement on CT in 75% of patients with major duodenal papillae, major duodenal papillary lesions cannot be diagnosed by the enhancement mode. 31 In this study, homogeneous enhancement was observed in 82.35% of patients with adenoma of the major duodenal papilla and 51.72% of patients with cancer of the major duodenal papilla, exhibiting a statistical difference between the 2 groups, which was inconsistent with the viewpoints of Chang et al.
The indirect signs on CT images are elucidated as follows. Clary et al concluded that intrahepatic and extrahepatic bile duct dilatation and common bile duct dilatation on CT in duodenal papilla tumors were highly indicative of malignancies. 22 Hawes et al proposed that patients with cancer of the major duodenal papilla had pancreatic duct and common hepatic duct dilatation and intrahepatic and extrahepatic bile duct dilatation on CT. 32 In this study, there were statistical differences in the diameter of the pancreatic duct and common bile duct, as well as pancreatic duct dilatation and common bile duct dilatation between the 2 groups, which was consistent with the results of Clary et al. Kim et al 33 revealed that enhanced axial CT findings included circular enhancement at the margin of the duodenal papilla and relatively low density in the center of the normal duodenal papilla and the cancer of the major duodenal papilla, which was shaped like a target ring and defined as a target sign. When the enhancement magnitude of the duodenal papillary mucosa on CT was inconsistent with that of the duodenal mucosal fold at the same level, it may cause changes. In this study, there was a statistical difference in the target sign between the 2 groups, which was consistent with the results of Kim et al. Therefore, the possibility of malignant transformation should be suspected after the occurrence of the target sign of abnormally enlarged duodenal papillae. There was no statistically significant difference in metastasis, diverticulum, pancreatic division, and calculus at the lower end between the 2 groups.
There are 3 types of adenoma of the major duodenal papilla, including tubular adenoma, villous adenoma, and tubular villous adenoma. Among them, the villous adenoma has the highest malignant transformation rate, which is more than 25%. 5 About 30%-90% of patients with duodenal papillary adenocarcinoma originate from adenoma of the major duodenal papilla. 7 Therefore, the adenoma of the major duodenal papilla can be considered as the precancerosis of cancer of the major duodenal papilla. In this study, there were 17 patients with adenoma of the major duodenal papilla, including 10 with tubular adenomas, 4 with tubular villous adenomas, and 3 with villous adenomas. Besides, 90% of patients with adenoma of the major duodenal papilla exhibited atypical hyperplasia, including 13 low-grade intratumoral transformations, 2 high-grade intratumoral transformations, and 2 without intratumoral transformations. The results of this study showed that there were 12 patients with adenomatous malignancies (20.69%, 12/58) in the cancer group, which was consistent with the results in previous studies.5,7 Additionally, only 17 patients with adenoma of the major duodenal papilla and 58 patients with cancer of the major duodenal papilla were included during the same period, and the incidence of the former was far lower than that of the latter. Moreover, adenomas were prone to atypical hyperplasia. Some patients with cancer of the major duodenal papilla may suffer from the malignant transformation from adenomas.
Nevertheless, there are some limitations in this study. Firstly, some patients had smaller lesion sizes in the major duodenal papilla, which was sometimes poorly displayed on some of the CT images. To solve this problem, we found the same location of the tissue structure on the images in different orientations, and the spatial localization cursor within the imaging system was applied to accurately locate the lesion. Secondly, Lauenstein et al have found that the CT enhancement characteristics of peripapillary carcinoma correlate with the cellular components of tumor histopathology. 34 ; however, we only investigated the clinical characteristics and diagnostic value of CT in patients with duodenal papillary diseases, and its relationship with histopathologic characteristics is not explored, which requires further investigation.
Conclusion
In conclusion, CT is of high value in the diagnosis of duodenal papilla diseases. CT may enable the early detection of duodenal papilla lesions and more intuitive observation of biliary and pancreatic duct anatomy, as well as adjacent intestinal walls, pancreas, and related spaces. Firstly, there are many similar manifestations in clinical characteristics, laboratory indicators, and CT findings between patients with cancer of the major duodenal papilla and those with adenoma of the major duodenal papilla. However, there are certain differences in the diameter, shape, margin, enhancement uniformity, and target sign of the major duodenal papilla, pancreatic duct diameter, common bile duct diameter, pancreatic duct dilatation, choledochectasia, total bilirubin, direct bilirubin, fever, jaundice, and tumor makers (CEA and CA19-9) between the 2 groups. Secondly, the enhancement magnitude of duodenal papillae was correlated with the lesion size, and the venous phase CT value of an enhanced scan was correlated with the diameter of duodenal papillae. Thirdly, patients with duodenal papilla adenomas have a risk of progression into adenocarcinoma, which requires close follow-up. Therefore, a comprehensive diagnosis should be performed according to the direct and indirect CT findings as well as clinical characteristics and laboratory examinations of the major duodenal papilla, thus increasing the diagnosis rate for cancer of the major duodenal papilla.
Footnotes
Author contributions
Ning Wang and Wenyan Wei: Conceptualization, Methodology, Formal analysis, Investigation, Writing - Original Draft. Jinyan Fang and Weixing Mo: Validation, Investigation, Writing - Review & Editing. Xianguo Qu and Qinghai Li: Statistical Analysis, Investigation.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Zhejiang Province Medical and Health Science and Technology Programme 2022KY241. Science and Technology Programme for Traditional Chinese Medicine in Zhejiang Province 2022ZA132. Major Project of Hangzhou Health Science and Technology Programme Z20220094. Hangzhou Medicine and Health Science and Technology Project A20241858.
Ethical Statement
Consent for Publication
All the authors agreed to publish.
Data Availability Statement
Corresponding authors can provide all data as needed.