PERIAMPULLARY CANCERS: Are There Differences?

doi:10.1016/S0039-6109(05)70142-0

Surgical Clinics of North America

Volume 81, Issue 3, 1 June 2001, Pages 543-555

https://doi.org/10.1016/S0039-6109(05)70142-0 Get rights and content

By definition, periampullary cancers arise within 2 cm of the major papilla in the duodenum. They encompass four different types of cancers: ampullary (ampulla of Vater), biliary (intrapancreatic distal bile duct), pancreatic (head–uncinate process), and duodenal (mainly from the second portion). Although these tumors have different origins, the complex regional anatomy and their proximation within that confined region generally dictate a common operative approach. Radical resections, such as the Whipple procedure ⁶² or its variant with preservation of the pylorus with or without extended regional lymphadenectomy,⁵⁸ have been the main treatments for these cancers, especially with the currently low morbidity and mortality rates.⁶⁷ Although the perioperative outcomes for these different cancers are similar, the long-term survival has traditionally varied. Consequently, because exact tumor origin is often difficult to clinically ascertain, surgeons have favored an aggressive approach toward resection to benefit those patients harboring cancers with a better prognosis. This observation has intrigued physicians managing patients with these cancers. It is unknown why outcome should vary for adenocarcinomas arising from different anatomic sites in such close proximity. Indeed, if survival does vary significantly for these cancers as clinical impression suggests, clearly, factors other than anatomy alone must be involved.

This article explores whether there are differences in the clinical behavior of the periampullary cancers and defines which of these factors, if any, affect outcome. Moreover, it is important to determine which factors are valuable clinically so that they can be used to improve overall survival rates.

Section snippets

Epidemiologic Considerations Prevalence Of Periampullary Cancers

Overall, periampullary cancers account for 5% of all gastrointestinal tract malignancies. Pancreatic cancer occurs most often among the periampullary cancers. They account for 3% of all gastrointestinal cancers. Cancers of the ampulla of Vater occur more frequently than distal common bile duct cancer with a ratio of 1:12.⁵ In autopsy studies, the overall prevalence of periampullary cancers is between 0.063% and 0.21%.5, 42, 65 Considered separately, carcinoma of the ampulla of Vater has been

Outcome Studies Support Variable Survival

Representative outcome after pancreaticoduodenectomy for each type of periampullary cancers are shown in Tables 1 to 4. Overall perioperative morbidity and mortality for each cancer are similar. Overall perioperative mortality ranges from 0% to 15%. Overall perioperative morbidity also is similar among periampullary cancers and ranges from 30% to 50%. Postoperative diabetes after Whipple procedure is infrequent and does not occur more frequently with any of the periampullary cancers.¹

Embryology

Can the embryology of the specific anatomic sites of the periampullary region explain the perceived differences in cancer behavior? The caudal foregut and the cranial midgut generate the duodenum. The origin of the bile duct, the pancreas, and the ampulla of Vater arise from the foregut just above its junction with the midgut. By the end of the fourth week, the dorsal pancreatic primordium arises from the dorsal duodenal diverticulum. Concurrently, the ventral duodenal diverticulum

Outcome Influences: Histology and Other Factors

Accurate histologic classification of periampullary cancers can be notoriously difficult. Not uncommonly, careful pathologic review of resected specimens alters the original clinical diagnosis. Two practical points are useful in defining the origin of these cancers, which can significantly improve diagnostic clinical accuracy: (1) the predominant site of the mass of the cancer and (2) the presence of any component of carcinoma in situ. Nevertheless, some periampullary cancers will evade an

CLINICAL PRESENTATION

Clinical presentation often differs among patients with cancers primarily located in the distal portion of the biliary duct (biliary and ampullary), close to it (pancreatic), and those involving the ampullary complex, at least in early stages (duodenal). The main clinical difference is the timing of the onset of jaundice related to constitutional cancer symptoms. In patients in the former group, jaundice is always the most common symptom, and it usually precedes nausea, vomiting, or abdominal

Early vs Late Jaundice.

Intuitively, patients with cancers directly involving the distal bile duct should present with jaundice at an earlier stage of disease. Current data suggest that most ampullary, duodenal, and distal bile duct tumors present without lymph node metastases, and consequently when resected are associated with a better prognosis than pancreatic cancer. Although bile duct cancers should present early and should be associated with a prognosis equivalent to ampullary cancers, the fact that survival is

ALTERNATIVE SURGICAL TREATMENT

Currently, pancreaticoduodenectomy (classic or pylorus-preserving) remains the treatment of choice for invasive periampullary cancer; however, more limited resections of nonpancreatic periampullary cancers have been used selectively because of patient infirmity from comorbidity, early cancer stage (Tis), or both. Some patients with small (1 cm) ampullary or distal bile duct cancers are candidates for transduodenal ampullectomy, and selected patients with duodenal cancers not involving the

SUMMARY

Our review supports the clinical impression that periampullary cancers vary in outcome after resection. Overall survival after pancreaticoduodenectomy is greatest for patients with ampullary and duodenal cancers, intermediate for patients with bile duct cancer, and least for patients with pancreatic cancer. Moreover, survival for each tumor stage is greater for nonpancreatic periampullary cancers than for pancreatic cancers. Invasion of the pancreas by nonpancreatic periampullary cancers is a

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Cited by (129)

Telomere length assessment and molecular characterization of TERT gene promoter in periampullary carcinomas
2023, Gene
Genetic and epigenetic alterations of the telomere maintenance machinery like telomere length and telomerase reverse transcriptase (encoded by TERT gene) are reported in several human malignancies. However, there is limited knowledge on the status of the telomere machinery in periampullary carcinomas (PAC) which are rare and heterogeneous groups of cancers arising from different anatomic sites around the ampulla of Vater. In the current study, we investigated the relative telomere length (RTL) and the most frequent genetic and epigenetic alterations in the TERT promoter in PAC and compared it with tumor-adjacent nonpathological duodenum (NDu). We found shorter RTLs (1.27 vs 1.33, P = 0.01) and lower TERT protein expression (p = 0.04) in PAC tissues as compared to the NDu. Although we did not find any mutation at two reactivating hotspot mutation sites of the TERT promoter, we detected polymorphism in 45% (9/20) of the cases at rs2853669 (T > C). Also, we found a hypermethylated region in the TERT promoter of PACs consisting of four CpGs (cg10896616 with Δβ 7%; cg02545192 with Δβ 9%; cg03323598 with Δβ 19%; and cg07285213 with Δβ 15%). In conclusion, we identified shorter telomeres with DNA hypermethylation in the TERT promoter region and lower TERT protein expression in PAC tissues. These results could be used further to investigate molecular pathology and develop theranostics for PAC.
Controversies in the diagnosis and treatment of periampullary tumours
2022, Surgical Oncology
Citation Excerpt :
However, carcinomas located in the head of the pancreas may originate from the papilla of Vater, the distal part of the common bile duct, or the duodenum. Tumours of that region, within 2 cm of the major duodenal papilla, have been usually described as periampullary neoplasms [1]. Adenocarcinomas separated from the greater duodenal papilla (Vater) and located in the major pancreatic duct, common bile duct, or duodenum have been identified as ductal pancreatic carcinomas, distal bile duct carcinomas (cholangiocarcinomas) or duodenal carcinomas.
Most tumours in the head of the pancreas are adenocarcinomas of the exocrine pancreas. However, carcinomas located in the head of the pancreas may originate from the papilla of Vater, the distal part of the common bile duct, or the duodenum. Tumours of that region, within 2 cm of the greater duodenal papilla, have been usually described as periampullary neoplasms. Adenocarcinomas separated from the major duodenal papilla and located in the major pancreatic duct, common bile duct, or duodenum are identified as ductal pancreatic carcinomas, distal bile duct cholangiocarcinomas or duodenal carcinomas. Surgical treatment is the only chance for cure. Pancreatoduodenectomy is the procedure of choice. Regional lymphadenectomy and removal of at least 16 lymph nodes are necessary for optimal long-term outcomes. Indications for adjuvant chemotherapy remain controversial. This review evaluates the available data on the pathological assessment of periampullary tumours and discusses the controversies of therapeutic management, emphasising adjuvant treatment.
Oncologic management of ampullary cancer: International survey among surgical and medical oncologists
2022, Surgical Oncology
Ampullary adenocarcinoma (AAC) is a rare neoplasm which as a result is lacking specific treatment guidelines. This international survey study was performed to gain insight in the current daily practice of AAC.
Surgeons and medical oncologists, whom were members of the Dutch Pancreatic Cancer Group, International Study Group on Ampullary Cancer, International Hepato-Pancreato-Biliary Association, European and International Consortium on Minimally Invasive Pancreatic Surgery, or contributed to (peri)ampullary cancer research, were invited through email and newsletters between January and October 2021.
Overall, 217 surgeons and medical oncologists completed the survey. Most of the respondents work in Europe (60%), and in a pancreatic expertise center (86%). The majority of respondents (87%) stated that the histological AAC subtype (e.g. intestinal vs. pancreatobiliary) was determined in the resection specimen. Neoadjuvant treatment for resectable disease was considered by 24% and adjuvant therapy by 90% of the respondents, with 80% of them choosing adjuvant chemotherapy alone. The formation of multidisciplinary teams, improvement in resection procedures, increased availability of chemotherapy regimens, and increased knowledge on tumor biology were considered as the most important developments in the last five years. The necessity for randomized controlled trials was mentioned by 50% of the respondents.
This international survey highlights the existing variation in the management of patients with AAC, especially regarding the use of (neo)adjuvant therapy. More data from trials and international registries are needed to develop evidence-based guidelines on surgical and oncological management with the ultimate aim to improve outcomes for patients with AAC.
Treatment and overall survival of four types of non-metastatic periampullary cancer: nationwide population-based cohort study
2022, HPB
Periampullary adenocarcinoma consists of pancreatic adenocarcinoma (PDAC), distal cholangiocarcinoma (DC), ampullary cancer (AC), and duodenal adenocarcinoma (DA). The aim of this study was to assess treatment modalities and overall survival by tumor origin.
Patients diagnosed with non-metastatic periampullary cancer in 2012–2018 were identified from the Netherlands Cancer Registry. OS was studied with Kaplan–Meier analysis and multivariable Cox regression analyses, stratified by origin.
Among the 8758 patients included, 68% had PDAC, 13% DC, 12% AC, and 7% DA. Resection was performed in 35% of PDAC, 56% of DC, 70% of AC, and 59% of DA. Neoadjuvant and/or adjuvant therapy was administered in 22% of PDAC, 7% of DC, 7% of AC, and 12% of DA. Three-year OS was highest for AC (37%) and DA (34%), followed by DC (21%) and PDAC (11%). Adjuvant therapy was associated with improved OS among PDAC (HR = 0.62; 95% CI 0.55–0.69) and DC (HR = 0.69; 95% CI 0.48–0.98), but not AC (HR = 0.87; 95% CI 0.62–1.22) and DA (HR = 0.85; 95% CI 0.48–1.50).
This retrospective study identified considerable differences in treatment modalities and OS between the four periampullary cancer origins in daily clinical practice. An improved OS after adjuvant chemotherapy could not be demonstrated in patients with AC and DA.
Comparison of laparoscopic and open pancreaticoduodenectomy for the treatment of nonpancreatic periampullary adenocarcinomas: a propensity score matching analysis
2021, American Journal of Surgery
Citation Excerpt :
There was also no significant differences being observed between the LPD and OPD groups in OS (P = 0.065) (Fig. 1b). PD is the only feasible and effective treatment for periampullary carcinoma.5 However, for different types of periampullary cancer, the survival rate after PD treatment is different.
Use of laparoscopic pancreaticoduodenectomy (LPD) in place of open pancreaticoduodenectomy (OPD) remains controversial. Our aim was to evaluate the results of LPD versus OPD in non-pancreatic periampullary adenocarcinoma (NPPC), a less aggressive tumor.
Here, 488 NPPC patients who underwent LPD or OPD were analyzed in this study. The propensity score matching was used to balance the patients in two groups. Statistical analysis was conducted to investigate the differences between LPD and OPD in patients with NPPC.
The LPD group had shorter operative time, less intraoperative bleeding, and less postoperative hospital stay than OPD group. The 30- and 90-day mortality rates were significantly lower in LPD than in OPD group. There was no statistical difference in long-term survival between the two groups.
For NPPC, LPD may be the preferred surgical treatment due to its advantages over OPD in terms of intraoperative blood loss and short-term mortality.
A population-based study on incidence, treatment, and survival in ampullary cancer in the Netherlands
2021, European Journal of Surgical Oncology
Ampullary cancer is rare and as a result epidemiological data are scarce. The aim of this population-based study was to determine the trends in incidence, treatment and overall survival (OS) in patients with ampullary adenocarcinoma in the Netherlands between 1989 and 2016.
Patients diagnosed with ampullary adenocarcinoma were identified from the Netherlands Cancer Registry. Incidence rates were age-adjusted to the European standard population. Trends in treatment and OS were studied over (7 years) period of diagnosis, using Kaplan-Meier and Cox regression analyses for OS and stratified by the presence of metastatic disease.
In total, 3840 patients with ampullary adenocarcinoma were diagnosed of whom, 55.0% were male and 87.1% had non-metastatic disease. The incidence increased from 0.59 per 100,000 in 1989–1995 to 0.68 per 100,000in 2010–2016. In non-metastatic disease, the resection rate increased from 49.5% in 1989–1995 to 63.9% in 2010–2016 (p < 0.001). The rate of adjuvant therapy increased from 3.1% to 7.9%. In non-metastatic disease, five-year OS (95% CI) increased from 19.8% (16.9–22.8) in 1989–1995 to 29.1% (26.0–31.2) in 2010–2016 (logrank p < 0.001). In patients with metastatic disease, median OS did not significantly improve (from 4.4 months (3.6–5.0) to 5.9 months (4.7–7.1); logrank p = 0.06). Cancer treatment was an independent prognostic factor for OS among all patients.
Both incidence and OS of ampullary cancer increased from 1989 to 2016 which is most likely related to the observed increased resection rates and use of adjuvant therapy.

View all citing articles on Scopus

: Address reprint requests to David M. Nagorney, MD Mayo Clinic 200 First Street SW Rochester, MN 55905

^*: Department of Surgery, Mayo Clinic, Rochester, Minnesota

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PERIAMPULLARY CANCERS: Are There Differences?

Section snippets

Epidemiologic Considerations Prevalence Of Periampullary Cancers

Outcome Studies Support Variable Survival

Embryology

Outcome Influences: Histology and Other Factors

CLINICAL PRESENTATION

Early vs Late Jaundice.

ALTERNATIVE SURGICAL TREATMENT

SUMMARY

Surg Clin North Am

Hum Pathol

Am J Surg

Am J Surg

Am J Surg

Surgery

Eur J Oncol

Am J Surg

Surgery

Surgery

J Gastrointest Surg

Pancreatoduodenectomy for periampullary adenocarcinoma

J Am Coll Surg

What prognostic factors are important in duodenal adenocarcinoma?

Arch Surg

Tumor of the ampulla of Vater

Arch Surg

Clinicopathologic study for the assessment of resection for ampullary carcinoma

World J Surg

Diagnosis and therapy of ampullary tumors

World J Surg

Carcinoma of the ampulla of Vater: Prognostic factors after curative surgery: A series of 45 cases

Gut

Analysis of K-ras gene mutations in rare pancreatic and ampullary tumors

Eur J Gastroenterol Hepatol

Villous tumors of the duodenum: Reappraisal of local vs. extended resection

Gastroenterology

Locoregional dissemination and extended lymphadenectomy in pancreatic cancer

Dig Surg

Outcome of treatment for distal bile duct cancer

Br J Surg

Tumor size is the primary prognosticator for pancreatic cancer after regional pancreatectomy

Ann Surg

Wang I, Zhu Z, et al: Growth factor receptors are differently expressed in cancers of the papilla of Vater and pancreas

Ann Surg

Surgical treatment of ductal pancreatic carcinoma

Eur J Surg Oncol

Adjuvant therapy for pancreatic cancer

World J Surg

Pancreatic invasion is a prognostic indicator after radical resection for carcinoma of the ampulla of Vater

J Hepatobiliary-Pancreat Surg

Role of nodal involvement and the periductal soft tissue margin in middle and distal bile duct cancer

Ann Surg

Lymphatic flow in carcinoma of the distal bile duct based on clinicopathological study

Cancer

Carcinoma of the ampulla of Vater: Determinants of long-term survival in 94 resected patients

HPB Surg

Carcinoma of the pancreas and periampullary region: Palliation versus cure

Br J Surg

Cancer of the ampulla of Vater

Br J Surg

The case for parallel classification of biliary tract and pancreatic neoplasms

Mod Pathol

Radical resection for carcinoma of the ampulla of Vater

Arch Surg

Clinical study of lymphatic flow to the paraaortic lymph nodes in carcinoma of the head of the pancreas

Cancer

A clinical study on lymphatic flow in carcinoma of the pancreatic head area-peripancreatic regional lymph node grouping

Hepatogastroenterology