Ampullary Carcinoma Treatment & Management

Updated: Nov 10, 2016
  • Author: Ayana Allard-Picou, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Treatment

Surgical Care

The standard surgical approach is pancreaticoduodenal resection (Whipple procedure). The procedure involves en bloc resection of the following:

  • The gastric antrum and duodenum
  • A segment of the first portion of the jejunum, gallbladder, and distal common bile duct
  • The head and often the neck of the pancreas
  • Adjacent regional lymph nodes

In a review of 450 cases of surgical resection of ampullary adenoma or adenocarcinoma at Johns Hopkins, Winter et al found that 96.7% of the patients had undergone pancreaticoduodenectomy rather than local excision. These researchers concluded that pancreaticoduodenectomy should be the preferred approach for most ampullary neoplasms that require surgical resection, given that nearly 30% of the Johns Hopkins patients with T1 disease had lymph node metastases. [9]

Factors associated with the presence of lymph node metastasis included the following [9, 10] :

  • Tumor size ≥1 cm (odds ratio [OR] 2.1)
  • Poor histologic grade (OR 4.8)
  • Perineural invasion (OR 3.0)
  • Microscopic vessel invasion (OR 6.6)
  • Depth of invasion > pT1 (OR 4.3; all P < 0.05)
  • Specifically, risk of lymph node metastasis increased with T stage (T1, 28.0%; T2, 50.9%; T3, 71.7%; T4, 77.3%; P < 0.001)

Results after radical resection of ampullary of Vater carcinoma have been improving. During recent decades, 5-year survival rates have ranged from 20-61%, averaging higher than 35%. The reported mortality rates from this operation are decreasing. A summary follows in Table 2, below.

Table 2. Results of Pancreaticoduodenal Resection for Carcinoma of the Ampulla of Vater (Open Table in a new window)

Institution Year Patients, # Resected, # Mortality Rate, % 5-Year Survival Rate, %
Cleveland Clinic [11] 1950-1984 59 59 8 37
Leicester Royal Infirmary, United Kingdom [12] 1972-1984 52 24 13 56
University of Alabama [13] 1953-1988 24 24 13 61
Mayo Clinic [14] 1965-1989 104 104 5.7 34
Montebelluna Hospital, Italy [15] 1971-1990 36 31 3 56
Veterans Affairs hospitals [16] 1971-1993 123 64 14 20
Academic Medical Center, Amsterdam [17] 1984-1992 67 62 6 50
Hanover Hospital, Germany [18] 1971-1993 87 85 9 38
Johns Hopkins [19] 1969-1996 120 106 4 38
Memorial Sloan-Kettering [20] 1983-1995 123 101 5 44
Catholic University, Italy [21] 1981-2002 94 64 9 64

Resectability

In a review of more than 1100 patients published in a surgical series, Howe et al reported that the overall rate of resectability was 82%. [20] This most likely overestimates the true resectability rate because patients in whom radiologic studies identify unresectable disease often are not included in retrospective surgical series.

A review of cases from Veterans Affairs hospitals across the United States by el-Ghazzawy et al revealed that only 63% of presenting patients undergo surgery for cure. At disease presentation, 30-50% have involved lymph nodes. [16]

A few studies have been conducted on the pattern of lymphatic spread of ampullary cancer. These studies have been difficult to interpret because of the lack of standardized nomenclature for lymph node groups, variability in the degree of superior mesenteric lymph node dissection, and the small number of patients.

Shirai and colleagues meticulously reviewed 21 cases of ampullary cancer and documented the pattern of lymphatic spread. The site of greatest nodal involvement, the first echelon group, is the posterior pancreaticoduodenal nodal group. The nodal groups surrounding the inferior pancreaticoduodenal artery were the superior mesenteric lymph nodes involved most often. Finally, the para-aortic lymph node groups were involved in 3 patients with resectable disease. [22]

Kayahara reported that the inferior pancreaticoduodenal nodes (13b) and the superior mesenteric nodes (14) were the groups most often involved with metastatic carcinoma. [23]

Local excision

Because of the mortality and morbidity associated with pancreaticoduodenectomy, surgeons have studied local excision of cancers of the ampulla of Vater to avoid major resection. Transduodenal excision of ampullary tumors has been proposed as an intermediate option between radical resection and palliative bypass for high-risk patients. However, this approach remains highly controversial.

Local resection has generally been reserved for poor operative candidates (eg, elderly patients, those with other comorbid conditions) with favorable tumors (generally <2 cm, polypoid). Unfortunately, this approach compromises local control and has a higher risk of a positive margin, possibly requiring repeat excisions and resulting in higher local recurrence rates of up to 30% [24] . Additionally, lymph node metastasis may be present even in patients with T1 tumors and local resection does not include a regional lymphadenectomy, as is performed with pancreaticoduodenectomy.

Some have argued that local resection is simpler, is better tolerated and may have acceptable survival rates. In a series of 21 patients who underwent local resection of ampullary adenomas, Posner et al demonstrated overall survival of 85% and no tumor recurrence in 89% of the surviving patients (with average follow up of 38 months). However, this study was not limited to ampullary cancer; final pathology demonstrated 1 patient (5%) with invasive cancer, 2 (9%) with microinvasive cancer, 6 (28%) with high-grade dysplasia, and 1 (5%) with low-grade dysplasia. [25] .

Carcinoma in situ has been diagnosed with increasing frequency. It has been associated with polypoid growth and may be treated with endoscopic polypectomy. In these circumstances, the entire polyp should be removed and the base of the polyp should be carefully examined to ensure that no cancer is at the margin. In the case of an incomplete excision, a prompt pancreaticoduodenectomy is essential. Patients who undergo polypectomy only should be monitored endoscopically at yearly intervals to detect any recurrence.

Staging of ampullary cancer is critical to treatment. While ampullary polypectomy and ampullectomy have been performed successfully on some patients with ampullary cancer, local resection as a therapeutic approach is best reserved for patients with benign lesions, such as ampullary adenomas, or patients with carcinoma in situ or T1 tumors whose overall performance status makes the risks associated with a formal pancreaticoduodenectomy excessive. In general, for ampullary carcinoma, pancreaticoduodenectomy remains the gold standard and should be offered as long as the patient is able to tolerate the operation. [1]

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Adjuvant Therapy

Because local and systemic failures remain problematic, physicians continue to be interested in offering adjuvant therapy. The relative rarity of this disease limits research in this area. [26, 27]

Willett and colleagues summarized their experience with adjuvant radiotherapy for high-risk tumors of the ampulla of Vater (risk factors included invasion into the pancreas, poorly differentiated histology, involved lymph nodes, or positive resection margins). [28] Twelve patients received adjuvant radiotherapy (40-50.4 Gy) to the tumor bed and some received concurrent 5-fluorouracil (5-FU) as a radiosensitizer. Comparison of these patients with 17 patients who underwent surgical resection alone showed a trend toward better locoregional control with adjuvant radiotherapy, but there was no advantage in survival. Distant metastasis to the liver, peritoneum, and pleura was the dominant failure pattern in this group of patients.

Barton and Copeland reported on the M.D. Anderson Cancer Center experience of using postoperative chemotherapy for carcinoma of the ampulla of Vater. Seventeen patients received a variety of chemotherapeutic regimens (5-FU was used in combination with doxorubicin, carmustine, vincristine, methyl-lomustine, or mitomycin-C). Although no analysis was presented, the authors concluded that "no combination of drugs appeared to prolong life." [29]

Sikora and colleagues presented their experience from a hospital in India in a retrospective review. Patients who underwent a pancreaticoduodenectomy with adjuvant chemotherapy and radiation did not do any better than the group treated with surgery alone. [30]

Zhou et al reviewed the records of 111 patients at Johns Hopkins who underwent curative surgery for ampullary adenocarcinoma, 45% of whom also received adjuvant chemotherapy and radiation. In these patients, the improvement in survival with adjuvant treatment was not statistically significant (median overall survival: 21.6 vs. 13.0 months, P=0.092). [31]

In a retrospective review, Chan and colleagues reported that 13 patients who received adjuvant chemotherapy (predominantly involving 5-FU, mitomycin-C, and doxorubicin) had a significantly better survival than 16 patients who underwent resection only. [32]

Yeung and colleagues used neoadjuvant chemoradiotherapy for 20 patients with presumed carcinoma of the head of the pancreas, including 4 patients with duodenal/ampullary carcinomas. Interestingly, no residual tumor was found in pancreaticoduodenectomy specimens of the 4 patients thought to have had ampullary/duodenal carcinomas. [33]

At Stanford University, all cases of periampullary carcinoma are discussed and reviewed in detail by a multidisciplinary team that includes surgical oncologists, medical oncologists, radiation oncologists, a pathologist, a gastroenterologist, and a radiologist. All resected tumors are reviewed. Patients with tumors with poor prognostic features (eg, involved surgical margins, lymph nodes, invasion of the pancreas, perineural invasion, or poor histologic grade) are enrolled in a single-arm investigational protocol to receive adjuvant radiotherapy (45 Gy) and concurrent protracted venous infusion of 5-FU (225 mg/m2/d) during the entire treatment course.

Patients with carcinoma of the ampulla of Vater may benefit from recent advances in the treatment planning and delivery of adjuvant and definitive radiotherapy for patients with pancreatic cancer, which have produced modest gains in survival.

Pancreaticoduodenectomy is the procedure of choice for patients with resectable disease, but local recurrence plagues all surgical series, particularly when the pancreas has been invaded or lymph node metastases are discovered. In fact, whether major resection impacts survival in the setting of disease spread to the lymph nodes remains unclear. Postoperative irradiation of at least 45 Gy with 5-FU as a radiosensitizer is a reasonable treatment and reduces local recurrence in pancreatic cancer.

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Treatment of Unresectable Disease

For patients with unresectable ampillary carcinoma, endoscopic stenting to achieve biliary decompression is an appropriate palliative procedure. Endoscopic palliation may also be performed for duodenal obstruction with expandable metal stents. Similarly, a palliative bypass may be performed for tumors found to be unresectable intraoperatively.

No established answer exists to the question of further therapy. Very little has been published on adjuvant treatment for locally advanced and advanced ampullary carcinoma. Confining the therapeutic approach to relief of symptoms is reasonable.

Given the paucity of effective standard treatment options, encourage patients to enroll in clinical trials. Radiotherapy, chemotherapy, and chemoradiotherapy have been tried, but response rates probably are low, and an effect on survival is questionable.

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