1. Management of periampullary tumor What are the options for ampullary adenoma?
Joint Hospital Surgical Grand Round (July 2017)
Presented by Dr. Sin Kar Yan, PMH

2. Case Study Miss Wong F/64 Hepatitis B carrier Asymptomatic patient
OGD for screening for varices
No varices
Incidental finding of ampulla mass 4x2cm

3. Case Study What to do next? Biopsy: Tubular adenoma Hb normal
LFT normal
Referral to surgery
What to do next?

4. Introduction Periampullary tumors
Neoplasms that arise within 2cm of the ampulla of Vater
Origins
Pancreas
Distal CBD
Ampulla
Duodenum
Ampulla of Vater
Duodenal aspect of sphincter of Oddi muscle
Surround confluence of distal CBD and main pancreatic duct and papilla of Vater
Ampullary and periampullary tumors are infrequent, but have malignant rate of >90%
Periampullary tumor: 5% of all GIT malignancy.
Ampullary tumor: 1% of GIT malignancy.
Origins
Pancreas 60%
Distal CBD 10%
Ampulla 20%
Duodenum 10%
Image: Netter, Frank Henry, and Sharon Colacino. Atlas of human anatomy. Ciba-Geigy Corporation, 1989.

5. Differential Diagnosis
Benign
Tubular adenoma, tubulovillous or villous adenoma
Prevalence: 0.04% to 0.12%
Rate of transformation to carcinoma: 30%
Hemangioma
Leiomyoma
Leiomyofibroma
Lipoma
Lymphangioma
Neuroendocrine tumor
Malignant (>90%)
Adenocarcinoma
Ddx - The benign pathology we must rule out upon examining the ampullary and periampullary region is also diverse: choledocholithiasis or microlithiasis, chronic pancreatitis, dysfunction of the sphincter of Oddi and the presence of alterations in biliopancreatic drainage as a periampullary diverticulum, choledochocele or pancreas divisum.
30% transformation rate to carcinoma
Adenoma - Associated with FAP and HNPCC
Baker HL, Caldwell DW. Lesions of the ampulla of Vater. Surgery. 1947;21:523–531.
Sato T, Konishi K, Kimura H, Maeda K, Yabushita K, Tsuji M, Miwa A. Adenoma and tiny carcinoma in adenoma of the papilla of Vater--p53 and PCNA. Hepatogastroenterology. 1999;46:1959–1962.
Seifert, Erwin, Ferdinand Schulte, and Manfred Stolte. "Adenoma and carcinoma of the duodenum and papilla of Vater: a clinicopathologic study." American Journal of Gastroenterology 87.1 (1992).

6. Presentations of Periampullary Tumors
Asymptomatic as incidental finding
Symptomatic
Jaundice
Abdominal pain
Palpable gallbladder
Acute pancreatitis
UGIB / obstruction
Jaundice intermittent due to erosion / intermittent permeability of bile duct
Prevalence x in patients with FAP (80% can develop SB polyps) / HNPCC

7. Investigations Blood investigations Imaging and endoscopy
Complete blood count
Liver function test
CA 19.9
Imaging and endoscopy
Ultrasound CT
MRCP
Duodenoscopy
ERCP
EUS
CA19.9
Pancreas / NET
Biliary (GB, cholangio, ampullary CA)
HCC
Gastric, ovarian, colorectal
Lung, breast, uterus
Benign: cholangitis, cirrhosis
Ultrasound
Dilated CBD down to level of ampulla.
Assess liver metastasis, LN, ascites. CT
Locoregional spread and vascular involvement
MRCP
Less invasive than ERCP for investigation of OJ
ERCP
Both diagnostic and therapeutic
Biopsy / cytology
Biliary drainage
EUS
Transmural information / depth of tumor invasion
Peripancreatic LN assessment
FNAC
Helps to assess small tumors that cannot be assessed by CT

8. Duodenoscopy / ERCP Visualization of ampulla
Assessment of biliary system
± biliary drainage if obstruction
Benign and malignant ampullary tumors may not be distinguished on appearance alone
Suspicious ampullary lesions should be biopsied before endoscopic resection is attempted.
ampullary adenoma is
suspected if discolored lobular or pine cone– like lesions
are detected.
Forceps bx – 30% false negative
Malignant
Benign

9. Duodenoscopy / ERCP Characteristics of malignant lesions
Induration / rigidity
Ulceration
Suspicious lesions should be biopsied before endoscopic resection
False negative rate up to 30%
Comparison of cytologic and histologic results showed the following sensitivity and specificity: DB, 40% and 97%, respectively;
AB, 100% each; BB, 75% and 93%, respectively.
Ref:
Diagnostic value of brush cytology
Yamaguchi, Koji, Munetomo Enjoji, and Katsutoshi Kitamura. "Endoscopic biopsy has limited accuracy in diagnosis of ampullary tumors." Gastrointestinal endoscopy 36.6 (1990):

10. Endoscopic Ultrasound
Identify small lesions
Assess intraductal extension and extension beyond muscularis propia
Obtain tumor biopsy
Assess lymph node status + biopsy
Intraductal ultrasounds
Precise of T staging
Assess depth of involvement
AdenoCA: hypoechoic and heterogenous
Ref:
Role of endoscopy
The courses of lymphatic drainage of the papilla and the periampullary region move toward the chains of the posterior and anterior pancreatoduodenal arteries, the hepatic artery and the superior mesenteric artery. The lymph nodes which are furthest away, the splenic ones or those of the celiac trunk, are considered distant metastases
Ddx – inflammatory pseudotumors, chronic pancreatitis, periampullary diverticulum, choledochocele, pancreatic divism
Adler, Douglas G., et al. "The role of endoscopy in ampullary and duodenal adenomas." Gastrointestinal endoscopy 64.6 (2006):
Onkendi, Edwin O., et al. "Adenomas of the ampulla of Vater: a comparison of outcomes of operative and endoscopic resections." Journal of Gastrointestinal Surgery 18.9 (2014):

11. Endoscopic Ultrasound
Who should undergo EUS?
No consensus
Lesions >1cm
Lesions with suspicion of malignancy

12. Narrow Band Imaging Imaging features Irregular villous arrangement
Irregular villous size
Disappearance of ridges
Demarcation of normal villi
Abnormal microvasculatures

13. Narrow Band Imaging
Features of irregular villous arrangement + abnormal microvasculatures
Diagnose adenocarcinoma with a sensitivity of 69% and specificity of 100%
Irregular villi size, disappearance of the ridge, and
demarcation of villi could not predict the diagnosis of
ampullary tumor in multivariate analysis, even though
they were detected more frequently in ampullary tumors
than in infl ammatory diseases
All adenoCA has the two features
All adenoma has one or both of the NBI features
Irregular villous arrangement + abnormal microvasculatures:
sensitivity of 69% and specificity of 100%, PPV, NPV, and accuracy of 69%, 100%, 100%, 85%, and 89%, respectively.
Ref:
Usefulness in whitelight imaging guided NBI
Park, Jin-Seok, et al. "Usefulness of white-light imaging–guided narrow-band imaging for the differential diagnosis of small ampullary lesions." Gastrointestinal endoscopy 82.1 (2015):

14. Narrow Band Imaging Guide target biopsy site
Not suitable as a screening tool due to the low sensitivity
Role of NBI is still being investigated
Large scale prospective study is required

15. Treatment: Ampullectomy

16. Ampullectomy Surgical ampullectomy Transduodenal local excision
Involves reimplantation of the distal CBD and pancreatic duct within the duodenal wall
Endoscopic ampullectomy
“papillectomy”
Resection of mucosa and submucosa of the duodenal wall, in the area of the anatomical attachments of the ampulla of Vater, including the tissue around the bile duct and the pancreatic-duct orifices

17. Surgical Ampullectomy
Classic treatment for ampullary adenoma
Schneider, Lutz, et al. "Surgical ampullectomy: an underestimated operation in the era of endoscopy." HPB: the official journal of the International Hepato Pancreato Biliary Association 18.1 (2016): 65.

18. Surgical Ampullectomy
Laparotomy
Kocharization of duodenum
Longitudinal duodenotomy of D2
Lesion excised
Reimplantation of CBD and PD
Duodenotomy with ampullary adenoma exposed
Reimplantation of CBD and PD
Ángel, José Manuel Ramia, et al. "Ampulectomía transduodenal como tratamiento del adenoma de ampolla de Vater." Cirugía Española 87.3 (2010):

19. Surgical Ampullectomy
Frozen section can be performed
Conversion to radical pancreaticoduodenectomy if malignancy is found
Mortality 0-3%
Morbidity 42-45%
Complications
Bleeding
Cholangitis / pancreatitis
Anastomotic / duodenal leakage
Papillary stenosis
Frozen section
Margin analysis
Look for malignancy
Overall, the frozen section examinations correctly agreed with the final pathology in 75% of the cases.
The outcomes of the frozen section examinations in the detection of cancer are as follows: sensitivity—57%, specificity—100%, positive predictive value—100%, and negative predictive value—62%
false negative rate of 25%–56%
Transduodenal Resection of Peri-Ampullary Lesions
Dixon E; Vollmer CM Jr; Sahajpal A; Cattral MS; Grant DR; Taylor BR; Langer B; Gallinger S; Greig PD.
World Journal of Surgery. 29(5):649-52, 2005 May.
Ceppa, Eugene P., et al. "Endoscopic versus surgical ampullectomy: an algorithm to treat disease of the ampulla of Vater." Annals of surgery 257.2 (2013):
Grobmyer, Stephen R., et al. "Contemporary results with ampullectomy for 29 “benign” neoplasms of the ampulla." Journal of the American College of Surgeons (2008):

20. Endoscopic Ampullectomy
“papillectomy”
Minimally invasive
En bloc resection for small lesions
Piecemeal resection for large lesions may be required
Benign adenoma / carcinoma in situ / well or mod differentiated tumor T1N0M0
Free lateral and in-depth margin , no lymphovascular infiltration
<1cm inside CBD / P duct: Tissue invading to this level can be endoscopically exposed and ablated
Piecemeal if >2cm.
Pic:
*EP definition
Resection of the mucosa and submucosa of the duodenal wall, in the area of the anatomical attachments of the ampulla of Vater, including the tissue around the bile duct and the pancreatic-duct orifices.
SA definition
surgical “ampullectomy” which consists of resection of the ampulla of Vater, via a duodenotomy, including resection of pancreatic-head tissue, followed by separate reinsertion of the common bile duct and main pancreatic duct into the duodenal wall.
Ref: De Palma, Giovanni D. "Endoscopic papillectomy: indications, techniques, and results." World Journal of Gastroenterology: WJG 20.6 (2014): 1537.
Image: Bassan, Milan, and Michael Bourke. "Endoscopic ampullectomy: a practical guide." Journal of interventional gastroenterology 2.1 (2012): 23.

21. Endoscopic Ampullectomy
Patient selection
Lesion <4-5cm
Histology
Benign
High grade dysplasia is not a contraindication
EUS criteria
No invasion of duodenal muscularis propia
No tumor growth beyond 1cm inside CBD / pancreatic duct
Positive lifting sign
Lesion size is not corresponding to intraductal extension or presence of malignancy
Elevation after submucosal injection or presence of submucosal mass
Tis, focal T1 malignancy has been treated by EA, but long term results are still being investigated
Ref:
EA vs SA

22. Endoscopic Ampullectomy
De Palma, Giovanni D. "Endoscopic papillectomy: indications, techniques, and results." World Journal of Gastroenterology: WJG 20.6 (2014): 1537.

23. Endoscopic Ampullectomy
Techniques
Submucosal injection
Lift sign
Endoscopic snare and electrocautery
En bloc resection for small lesions
Piecemeal resection or multiple procedures may be required for larger lesions
Electrocautery injuries to tissue fragments can affect pathological analysis
Ablation (Argon plasma coagulation) if any residual lesion
Sphincterotomy
Helps pancreaticobiliary drainage after papillectomy
Stent placement
Not routine
Aim to prevent iatrogenic pancreatitis
Ablation
APC , laser, monopolar / bipolar
Destroy residual / recurrent adenoma
Sphinterotomy
- No consensus whether it is a must or when to do it
Stent placement is not a must
?prevent post-ERCP pancreatitis. (one RCT proved prophylactic pancreatic duct stent placement reduce post-papillectomy pancreatitis, 30 reduced to 10%)
Minimize stenosis of orifice PD, and safer use of coagulative tx
Some suggest only use stent if pancreatic duct drainage is suboptimal / difficult cannulation of PD after procedure
Most pancreatic stents will spontaneously migrate out of the pancreatic duct within 2 wk of insertion.

24. Endoscopic Ampullectomy
Multiple sessions may be required
Mortality 0%
Morbidity 18%
Complications
Early: Pancreatitis, cholangitis, bleeding, perforation
Late: Papillary stenosis
Post-ampullectomy surveillance endoscopy required
3-12months for at least 2 years
More frequently in case of high grade dysplasia
Complications
Pancreatitis 8-15% , cholangitis 0-2%, perforation 0-4% , bleeding 2-13%
Papillary stenosis 0-8%
Death rare
Stent placement post-ERCP: pancreatitis rate decrease from 33% to 10%
Post-EA surveillance
perform endoscopic treatment every 2–3 months until there is no residual adenoma, with surveillance every 6–12 months for the next 2 years [9]. If recurrence is not identified, further patient follow-up should be individualized.
Surveillance
1 to 6 months after the index procedure followed by repeat examinations with a duodenoscope every 3 to 12 months thereafter for a period of at least 2 years with periodic examinations thereafter.
Closer monitoring if HGD
FAP - patients who have undergone proctocolectomy are still at high risk for development of ampullary lesions and should undergo periodic surveillance for duodenal and ampullary adenoma and carcinoma.
Surgical ampullectomy if not amendable to EA with no malignant features, abdominal exploration for another indication, or as palliative procedure for elderly precluding PD.
EA re-op: excise positive margin
SA re-op: due to complication of ampullectomy
free lateral and in-depth margins and the absence of lymphovascular compromise are required.
The histology should correspond to benign adenomas, in situ tumors (Tis) or early well or moderately differentiated type cancer T1N0M0.
Ceppa, Eugene P., et al. "Endoscopic versus surgical ampullectomy: an algorithm to treat disease of the ampulla of Vater." Annals of surgery 257.2 (2013):

25. EA vs SA
Endoscopic ampullectomy (EA) is superior to surgical ampullectomy (SA) in terms of:
Morbidity (18 vs 42%)
Length of stay (0.6 vs 10.1days)
Readmission rate (16 vs 34%)
Endoscopic ampullectomy (EA) is superior to surgical ampullectomy (SA) in terms of:
Morbidity (18 vs 42%)
Length of stay (0.6 vs 10.1)
Readmission rate (16 vs 34%)
*Reoperation 26 vs 15%
Ceppa, Eugene P., et al. "Endoscopic versus surgical ampullectomy: an algorithm to treat disease of the ampulla of Vater." Annals of surgery 257.2 (2013):

26. EA vs SA Positive margin and recurrence rate for EA are higher than SA
20 vs 10% (no statistical significance)
Re-intervention rate for EA is higher than SA
26% vs 15% (no statistical significance)
EA: mainly for margin re-excision
SA: mainly for complications
SA re-operation: wound dehiscence, incisional hernia, and feeding jejunostomy tube.
Ceppa, Eugene P., et al. "Endoscopic versus surgical ampullectomy: an algorithm to treat disease of the ampulla of Vater." Annals of surgery 257.2 (2013):

27. EA vs SA Endoscopic ampullectomy is preferred
Surgical Ampullectomy
Endoscopic Ampullectomy
Pros
Lower +ve margin rate
Lower recurrence rate
Frozen section available
Minimally invasive
Lower morbidity
Shorter LOS
Lower readmission rate
Cons
Need of GA
Higher morbidity
Longer LOS
Higher re-intervention rate
Higher +ve margin rate
Higher recurrence rate
Limitations
Not for adenomas with >1cm intraductal extension
Endoscopic ampullectomy is preferred
Surgical ampullectomy for lesions not feasible for endoscopic treatment

28. Back to our patient… EUS + endoscopic ampullectomy done
4.5cm lateral spreading ampulla tumor
No intraductal extension
Ampullectomy performed
CBD stent and pancreatic ductal stent inserted
Ampullectomy done
ESD, complete
Adrenaline + indocarmine

29. Submucosal injection
Post-ampullectomy
Ampullar tumor 45mm x 20mm

30. Back to our patient… Post-operative course was uneventful
Diet was resumed on the next day
No fever
LFT normal
Discharge home on day 4
Pathology:
Tubulovillous adenoma with low grade dysplasia
Lateral margin clear
Plan for surveillance endoscopy 3 months later

31. Conclusions Ampullary adenomas are rare
EUS has an important role in management decision
NBI may help improve diagnostic accuracy
More study would be needed to assess its efficacy
Endoscopic ampullectomy is a more favorable option than surgical ampullectomy
Minimally invasive, avoid GA
Lower morbidity
But the positive margin and recurrence rates are higher
Surgical ampullectomy
Treatment choice when EA is not feasible

32. The End