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Carcinoma of the papilla of Vater is classified as periampullary cancer; 5% of all gastrointestinal tract malignant. Early and accurate diagnosis is important for those patients with tumor of the papilla as the prognosis is more favorable than others periampulary neoplasms. Endoscopically obtained biopsies from suspicious papillas can establish an early and immediate preoperative diagnosis, although even for skilled pathologists it is difficult to distinguish carcinomas from non-invasive lesions on the basis of forceps biopsies. The purpose of this study was to asses the preoperative diagnostic accuracy of duodenoscopy appearance and biopsy in all suspicious of tumor. Thirty patients with suspicious of carcinoma of the papilla of Vater and with final diagnosis established by Whipple’s procedure were included in this retrospectively study. In each case, a comparison was made between endoscopic biopsy and duodenoscopy appearance. A final diagnosis was established by surgical specimen. After surgery the resected tumors of the papilla of Vater were definitely diagnosed as adenocarcinomas in 96.7% (29 patients) and inflammatory non-neoplastic lesion in 3.3% (01 patient). Duodenoscopic appearance accuracy for malignancy was 83,32%. One case
Endoscopy diagnosis in carcinoma of the papilla of Vater
Michelle Lucinda Gonçalves de Oliveira, MD, Assistent Surgeon from Division of Gastrointestinal Surgery, Federal University of São Paulo.
Gaspar de Jesus Lopes Filho, MD, Ph.D, Professor from Division of Gastrointestinal Surgery, Federal University of São Paulo.
Tarcisio Triviño, MD, Ph.D, Professor and Head from Division of Gastrointestinal Surgery, Federal University of São Paulo.
Department of Surgery, Division of Gastrointestinal Surgery Escola Paulista de Medicina
Federal of Sao Paulo University (UNIFESP-EPM)
Grant Support: FADA/UNIFESP, CAPES
Address: Rua Pedro de Toledo 1222,134 Vila Clementino, São Paulo-SP Brazil
Zip code:04039003
Telephone: 55 11 55713626 Email:michellelgo@uol.com.br
all gastrointestinal tract malignancy. Early and accurate diagnosis is important for those patients with a tumor of the papilla as the prognosis is more favorable than in other periampullary neoplasms. Endoscopically obtained biopsies from suspicious papillas can establish an early and immediate preoperative diagnosis, although even for skilled pathologists it is difficult to distinguish carcinomas from non-invasive lesions on the basis of forceps biopsies.The purpose of this study was to assess the preoperative diagnostic accuracy of duodenoscopy appearance and biopsy in all cases with suspicion of tumor. Thirty patients with suspicions of carcinoma of the papilla of Vater and with final diagnosis established by Whipple’s procedure were included in this retrospective study. In each case, a comparison was made between endoscopic biopsy and duodenoscopic appearance. Duodenoscopic appearance sensitivity and accuracy for malignancy was 86.2% and 83,3%. Endoscopic biopsy sensitivity and accuracy was 65.5% and 66.6%. Preoperative diagnosis of carcinoma of the papilla of Vater is mandatory for making therapeutic decisions. In this series, endoscopic biopsy was more limited than endoscopic appearance in preoperative diagnosis of carcinoma of the papilla of Vater.
Key words: endoscopic biopsy, digestive endoscopy, carcinoma, tumors of the papilla of Vater
Carcinoma of the papilla of Vater represents about 1% of all epithelial malignancies and 5% of all carcinomas in the gastrointestinal tract1. In clinical practice, four types of tumors are described as periampullary neoplasms: carcinoma of the papilla of Vater; cancer at the head of the pancreas, cancer of the distal bile duct and cancer of the duodenum. As in the colon, it appears that carcinomas of the papilla of Vater arise from precancerous lesions. Many reports have indicated the premalignant nature of adenomas and the high rate of association with focal cancer1,2,3,4. The neoplasm in the papilla of Vater can be diagnosed early and, unlike other periampullary neoplasms, has a good prognosis after surgical therapy5,6,7. However, an accurate preoperative diagnosis is essencial to select the right patients and the most appropriate treatment8 because after a complete surgical resection the five-year survival rate can be expected to be approximately 40%6,9. Endoscopically
obtained biopsies from suspicious papillas can establish an early and immediate preoperative diagnosis, although even for skilled pathologists it is difficult to distinguish carcinomas from non-invasive lesions on the basis of forceps biopsies8,10,11. The purpose of this review was to assess the preoperative diagnostic accuracy of duodenoscopic appearance and endoscopic biopsy in all cases with a suspicion of tumor.
Patients
Thirty patients with suspicion of carcinoma of the papilla of Vater and with final diagnosis established by Whipple’s procedure were included in this retrospective study. In each case, a comparison was made between endoscopic biopsy and duodenoscopic appearance. A final diagnosis was established by surgical specimen. All endoscopically obtained biopsies of the papilla of Vater were performed at the Hospital São Paulo-Federal São Paulo University between June 1981 and October 2002. Clinical data are show in Table 1.
Methods
Endoscopic procedures were carried out at the Endoscopy Sector of the Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM). The exams were done by the team of endoscopists of São Paulo Hospital, using a videoduodenoscope with a lateral vision (Pentax). In the presence of papilla alteration (Figure 1), such as irregularity of mucosa, dyschromy, areas of granulation, ulceration or vegetation, a biopsy was carried out, removing about five fragments, preferably from the edges and center of the lesion. Then the collected material was conditioned in a flask with 10% formol, identified and sent on to the department of pathological anatomy. A papillotomy was performed selectively in cases in which there was no plan for surgical treatment or when the patient developed colangitis.
material for making slides. All of the histological sections cut were stained with hematoxylin-eosin and examined by two pathologists responsible for the evaluation of histological degree and final diagnosis. These pathologists did not know the clinical data of the patients. Their diagnoses were independent and established on the basis of criteria generally used in pathological anatomy. To determine the diagnosis of malignancy in lesions of the major duodenal papilla, neoplasic invasion of the wall, presence of nuclear atypia, disturbance of the architecture and lymphatic and/or perineural invasion were considered.
Results obtained by duodenoscopy and endoscopic biopsy were analyzed to determine the accuracy and agreement and disagreement between them. The accuracy and sensitivity of the diagnostic methods was evaluated for malignancy. In addition, we calculed the concordance and discordance of diagnostic methods by Kappa’s test and Mc Nemar’s test respectively. The level of statistical significance was p< 0.05.
of the papilla, for 30 patients, the test was positive in 26, that is, the macroscopic appearance of the greater duodenal papilla was suggestive of cancer in 26 patients. However, the test gave a false positive in one case. The test was negative in 4 cases, meaning absence of macroscopic cancer, thus meaning false negatives in these cases. The table 2 shows these findings. Analysis of the data revealed the sensitivity of this diagnostic test to be 86,2%, the false negative to be 13,8, yielding a positive predictive value of 96% and accuracy of 83,3% (Mc Nemar p=0,375).
Concerning the comparative analysis of endoscopic biopsy and anatomopathological diagnosis for cancer of the papilla, the test was found to be positive in 19 patients, that is, a diagnosis of cancer of the greater duodenal papilla was confirmed, thus giving a true positive. In 11 patients, the test was negative, that is, did not confirm the diagnosis of cancer of the greater duodenal papilla. In fact, the test gave a false negative in 10 patients and a true negative in 1 case. The Table 3 shows these findings. Analysis of the results reveals a sensitivity of 65.5% , a false negative rate of 34,5% and accuracy of 66.6% (Mc Nemar p=0,002).
In the comparative analysis of the tests (Table 4), agreement was evaluated according to the Kappa test, resulting in agreement of 50% (K=0,243 p=0,102). In addition, distribution of disagreement was evaluated according to the Mc Nemar Test (p= 0, 118).
The importance of early diagnosis of cancer of the papilla rests in the fact that this type of cancer has high resectability and survival rates when compared with malignancies of the pancreas and biliary tree12,13. The duodenopancreatectomy (PD) with or without the preservation of the pylorus has shown a mortality rate of less than 5% in reference centers with the reduction in the rate of complications beginning in the 1990s13,14,15.
In clinical practice, surgeons seek a definitive preoperative diagnosis in identifying PD, however, histopathological diagnosis needed before surgery is limited and the possibility of obtaining an inconclusive biopsy continues to be a problem for the surgeon16,17. Until the 1980s, most tumors of the papilla were diagnosed during laparotomy or autopsy11. Nowadays the development of digestive endoscopy has contributed to the diagnosis of alterations in the greater duodenal papilla17,18,19. Endoscopy and biopsies from
a suspicious papilla can establish a preoperative diagnosis in that at times the tumor is not visualized, but an inflamed rounded papilla may be seen17. Ponchon et al.19 report that biopsies by snare resection improve biopsy quality, but can increase the chance of complications such as hemorrhaging. In addition, Bourgeois et al.20 point out that biopsies done after sphincterotomy may be necrotic and inconclusive. In a prospective study Menzel et al.8 observed that endoscopic biopsies obtained from tumors of the papilla of Vater prior to and after sphincterotomy do not allow for adequate prospective diagnosis. They recommend that biopsies be carried out on tumoral lesions of the papilla both on the surface and in the depths. In the presence of a negative biopsy with duodenoscopic evidence of
The result coming from endoscopic diagnosis and that from the histopathology of the endoscopic biopsy can disagree21,22. However the diagnostic accuracy of this procedure is variable11 and it has been reported to be from 45 - 85%21.
In the present study when we compare diagnostic tests using the Kappa test, we found agreement between duodenoscopy and endoscopic biopsy (perhaps reflecting sample size) to be no significant (P=NS). When we checked test disagreement, we found that the proportions of cancer and of inflammatory process do not significantly disagree between the duodenoscopic and endoscopic biopsy diagnostic tests according to the Mc Nemar test (P=NS).
Kimchi et al.11 evaluated the accuracy of the duodenoscopic exam and of endoscopic biopsy. In relation to the diagnosis of the presence of carcinoma in 21 patients, duodenoscopy was more accurate than endoscopic biopsy (90% versus 81%). Another study revealed that the sensitivity of endoscopic biopsy for cancer diagnosis was 70.5%, where false negatives by diagnosis of inflammatory process show up as inconclusive due to the presence of necrotic tissue23.
In our study, duodenoscopy was the instrument with better accuracy in the diagnosis of cancer of the papilla when compared with endoscopic biopsy (83.3% versus 66.6%). The false negative rate and sensitivity of the duodenoscopic exam were respectively 13.8% and 86.2%. This result has had an impact on clinical practice in our service. Even using other diagnostic methods, we still find ourselves with the same problem reported by other earlier
positive and a histopathological biopsy negative for cancer of the papilla. The analysis of the surgical specimen established the absence of cancer. The absence of a definitive preoperative diagnosis can lead to undue interventions.
Despite the development of endoscopic techniques, it would appear that the accuracy of endoscopic biopsy remains limited. An error in the interpretation of the diagnostic instrument can yield inadequate patient treatment8,18.
In conclusion, preoperative diagnosis of carcinoma of the papilla of Vater is requisite for making therapeutic decisions. In this series of cases, endoscopic biopsy proved more limited than endoscopic appearance in the preoperative diagnosis of carcinoma of the papilla of Vater.
The authors are grateful to Ricardo Artigiani Neto, MD from Department of Pathology and Nelson Sato, MD from Division of Gastrointestinal Endoscopy. They would also like to thank to FADA/UNIFESP and CAPES for financial support.
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5. Yamaguchi K, Nagai E, Ueki T, Nishihara K, Tamaka M. Carcinoma of the ampulla of Vater. Aust N Z J Surg 1993;63:256-262.
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diagnosis by intraampullary biopsy during endoscopic cannulation. Gastroenterology 1982;83:459-464.
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No. Jaundice
Weight
loss Pain Pruritis Fever Nausea Anemia Hepatomegaly 1 - + - - + - + 6cm 2 + + - + - - - - 3 + + - + - - - 10cm 4 - + + - - + + - 5 + + - - - + + 5cm 6 + + - - - 10cm 7 + + - + - - - 4cm 8 + + + - - - - - 9 + + + + + + + 3cm 10 + - - - 2cm 11 + + - - - + - 1cm 12 + + + + + + - - 13 + + - + - - - - 14 - + + - + - - 6cm 15 + + + + - - - 4cm 16 + + - - - + - 4cm 17 + + + + - - + 5cm 18 + + + + - + - - 19 + + + - - - - 6cm 20 + + + - - + - - 21 - + + - - - - 1cm 22 + + + - - + - 4cm 23 + + + - - - + 6cm 24 + + - + - - + 6cm 25 + - + - - + - - 26 + + + - - - - 2cm 27 + - + + - + - 4cm 28 + + - - - - 29 + + + - + + - 2cm 30 + + - + + - - -
Table 2 - Comparison of duodenoscopy and malignancy
Cancer of Papilla
Duodenoscopy Present Absent Total
Positive 25 1 26
Negative 4 0 4
Total 29 1 30
Table 3 – Comparison of endoscopic biopsy and malignancy
Endoscopic Cancer of the Papilla
Biopsy Present Absent Total
Positive 19 0 19
Negative 10 1 11
cancer inflam. Total Endoscopic Biopsy N % N % N % cancer 15 50,0 4 13,3 19 63,3 inflam. 11 36,7 0 0,0 11 36,7 Total 26 86,7 4 13,3 30 100,0 Inflam.= chronic inflammatory process
Figure 1 - Endoscopy appearance. An ulcerating tumor of the papilla of Vater.
Figure 2 – Histologic section of a lesion from the papilla of Vater obtained by endoscopic biopsy. Chronic inflammation and stromal fibrosis (hematoxylin and eosin, x100)
Figure 3 – Resection specimen showing carcinoma of the papilla of the Vater