Therapeutic approach to tumors of the ampulla of Vater

The American Journal of Surgery 192 (2006) 161–164

Clinical surgery–International

Therapeutic approach to tumors of the ampulla of Vater Akihiko Kobayashi, M.D., Masaru Konishi, M.D.*, Toshio Nakagohri, M.D., Ph.D., Shinichiro Takahashi, M.D., Taira Kinoshita, M.D., Ph.D. Surgery Division, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa City, Chiba, Japan 277-8577 Manuscript received April 28 2004; revised manuscript March 19, 2005

Abstract Background/Aim: Indications for local resection for tumors of the ampulla of Vater have not been established. The present study evaluated suitable treatments for tumors of the papilla of Vater. Patients and Methods: Clinicopathological factors were reviewed for 53 patients with tumors of the ampulla of Vater treated between February 1993 and August 2003. Results: Of 53 patients, 41 were treated surgically. Local resection was performed in 7 of these 41 patients, with a histologically involved margin evident in 4 patients. Lymph node metastasis was identified in 20 patients who received radical resection, including 1 patient with pT1 cancer. Conclusion: Given the presence of some positive surgical margins, local resection is indicated as a therapeutic approach to tumors of the papilla of Vater only for benign tumors or some malignant tumors that cannot undergo pancreaticoduodenectomy (PD). © 2006 Excerpta Medica Inc. All rights reserved. Keywords: Tumors of the ampulla of Vater; Cancer; Therapy; Surgery; Local resection

Ampullary carcinoma displays clinical patterns similar to those of carcinoma involving the head of the pancreas. These tumors require pancreaticoduodenectomy (PD) with regional lymph node dissection for cure. Optimal surgical technique for PD has recently been largely established. Curative resection rate has thus increased to 80% to 90%, while operative mortality has decreased to 5% [1,2]. However, patients with carcinoma of the ampulla of Vater display far better prognosis after resection than patients with ductal carcinoma of the pancreatic head [3,4]. Patients with benign ampullary tumor can be treated with local resection, but this procedure for ampullary carcinoma carries a high risk of local recurrence [5–7]. Accurate determination of tumor malignancy would allow limited resection for ampullary tumors with fewer complications and functional disorders than observed after PD. The present study evaluated suitable treatments for patients with tumors of the ampulla of Vater, and the implications for surgical treatment of such tumors are discussed.

* Corresponding author. Tel.: ⫹81 4 7133 1111; fax: ⫹81 4 7131 4724. E-mail address: [email protected]

Patients and Methods Between February 1993 and August 2003, a total of 53 patients with tumor of the ampulla of Vater were treated at the National Cancer Center Hospital East Japan. Clinicopathological factors were reviewed for these 53 patients and the following factors were analyzed: surgical procedure, surgical stress, resection margin, local recurrence, lymph node metastasis, and prognosis. All staging was assigned using tumor-node-metastasis (TNM) classifications as described by the International Union Against Cancer (UICC) [8]. Diagnosis was confirmed preoperatively in all patients using endoscopy and biopsy. To evaluate depth of tumor invaTable 1 Postoperative pathology for 41 resected cases Operation

Ampullectomy PSD PD

No. of patients

Permanent sections Adenoma

CIS

Carcinoma

6 4 31

1 1 0

4 2 0

1 1 31

CIS ⫽ carcinoma-in-situ; PSD ⫽ pancreas-sparing duodenectomy; PD ⫽ pancreaticoduodenectomy.

0002-9610/06/$ – see front matter © 2006 Excerpta Medica Inc. All rights reserved. doi:10.1016/j.amjsurg.2006.05.002

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Table 2 Result of minimal surgery Operation

Positive resected margin (%)

Local recurrence

MST (range)

Ampullectomy (n ⫽ 6) PSD (n ⫽ 4)

3 (50) 1 (25)

0 0

24 mo (8–51) 71 mo (64–79)

PSD ⫽ pancreas sparing duodenectomy; MST ⫽ median survival time.

sion, endoscopic ultrasonography (EUS) was used in 15 patients, computed tomography (CT) in 41 patients, and endoscopic retrograde cholangiopancreaticography (ERCP) or magnetic resonance cholangiopancreaticography (MRCP) in 38 patients. Local resection was indicated for patients diagnosed preoperatively with adenoma or T1 cancer with poor surgical risk. Other patients with malignant tumor underwent major oncological resection by means of pylorus-preserving PD (PPPD) or subtotal stomach-preserving PD (SSpPD). Survival rates were calculated using Kaplan-Meier analysis on the basis of overall survival. The significance of differences between groups was ascertained using the logrank test. A P value of ⱕ.05 was considered statistically significant.

Results Of the 53 patients, 41 (77%; 26 men, 15 women) displayed resectable tumors, while 12 (23%) were unresectable. Unresectable cases involved liver metastasis (n ⫽ 7), stenosis of the celiac axis (n ⫽ 1), direct tumor invasion to the proper hepatic artery (n ⫽ 1), or poor general condition (n ⫽ 3). Mean age of the 41 patients who underwent surgery was 61.8 years (range 41 to 80 years). The 7 patients with adenoma confirmed by preoperative biopsy were treated by local resection with ampullectomy (n ⫽ 4) or pancreassparing duodenectomy (PSD; n ⫽ 3). Postoperative pathology revealed carcinoma in situ or carcinoma in 5 of the 7 adenoma patients (71%). The 34 patients with adenocarcinoma confirmed by preoperative biopsy were treated using PD (PPPD or SSpPD; n ⫽ 31) with lymph node dissection, or local resection (ampullectomy, n ⫽ 2; or PSD, n ⫽ 1) in cases of poor surgical risk (Table 1). Histologically involved margins were evident in 3 ampullectomy cases and 1 PSD case, but no local recurrence has been encountered (Table 2). One patient who underwent

Fig. 1. Frequency of lymph node metastasis. Posterior pancreaticoduodenal (PPD) lymph nodes were positive in all pT1 cases. CBD ⫽ common bile duct lymph nodes.

ampullectomy died of esophageal carcinoma, but the other patients were alive without tumor recurrence as of time of writing. Lymph node metastasis was identified in 20 patients who received radical resection (64.5%; Table 3), and all displayed positive posterior pancreaticoduodenal (PPD) lymph nodes. Other sites of lymph node metastasis were the proximal mesenteric nodes (n ⫽ 2), common bile duct nodes (n ⫽ 2), and para-aortic nodes (n ⫽ 2) (Fig. 1). Prognosis was worse in patients with lymph node metastasis than in other patients (Fig. 2). Factors representing surgical aggression are listed in Table 4. Among patients who received ampullectomy, postoperative complications (wound infection) were observed in only 1 patient, and postoperative hospital stay was shorter than in other patients. The most frequent postoperative complication was pancreatic fistula due to radical lymphadenectomy. Almost all patients were treated conservatively, but 1

Table 3 Result of radical surgery Primary tumor

pT1 Other

Regional lymph nodes pN0

pN1

2 9

1 19

Fig. 2. Survival curves of patients who underwent radical resection, stratified by lymph node status. Survival rate was significantly worse in patients with lymph node metastasis than in patients without (P ⫽ .026).

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Table 4 Factors representing surgical stress Operation

Operation time (mean)

Blood loss (mean)

Morbidity (%)

In-hospital mortality (%)

Postoperative hospital stay (mean)

Ampullectomy (n ⫽ 6) PSD (n ⫽ 4) PD (n ⫽ 31)

147 min 212 min 420 min

181 mL 424 mL 1663 mL

1 (17) 3 (75) 20 (65)

0 0 1 (3)

14 days 43 days 48 days

PSD ⫽ pancreas sparing duodenectomy; PD ⫽ pancreaticoduodenectomy.

patient who received PPPD died 45 days after surgery, following postoperative hemorrhaging due to pancreatic fistula. Tumor recurrence occurred in 12 cases, as hematogenous recurrence only (n ⫽ 5), hematogenous and lymphogenous recurrence (n ⫽ 6), or local recurrence (n ⫽ 1).

Comments The detection rate for tumor of the ampulla of Vater has increased over the years with developments in diagnostic techniques. EUS provides a precise diagnosis with regard to the extent of tumor invasion [9,10]. CT and magnetic resonance imaging represent additional important diagnostic modalities for assessing tumor invasion into the pancreas and bile duct [11]. When choosing a therapeutic approach to ampullary tumors, distinguishing between benign and malignant neoplasms by tumor biopsy is indispensable. Reliable preoperative diagnosis in patients with benign ampullary tumor allows local resection and avoids unnecessary radical resection. Conversely, failure to recognize malignancy can lead to inadequate local resection with subsequent reintervention for radical resection or high risk of tumor recurrence. However, endoscopic biopsy fails to identify adenoma in 40% to 60% of cases [12,13]. Sauvanet et al. [14] reported that endoscopy with forceps biopsies, endoscopic sphincterotomy, and EUS, even combined, are not accurate enough to differentiate benign and malignant ampullary tumors, with a false-negative rate for malignancy of 20%. The procedure for local resection of ampullary tumors was first described by Halsted in 1899 [15]. Since then, patients displaying adenoma with carcinoma in situ or pT1 cancer of the ampulla have undergone local resection as one surgical option [5,6]. Recently, endoscopic snare excision of benign adenomas of the papilla of Vater has been proposed as an adequate treatment [7,16,17]. PSD represents a practical intervention for nonmalignant duodenal lesions where the pancreas is not involved by the disease process [18]. Ryu et al. [19] reported segmental resection of the duodenum including the papilla of Vater for focal cancer in adenoma. They insisted that this method ensures resection of all layers of the duodenum and excision of the bile and pancreatic duct outside the duodenum and pancreas, does not damage the pancreas, and ensures reliable resection of the papilla of Vater, including the bile and

pancreatic ducts. We performed PSD in 4 cases, and all operations were safely completed. Positive resection margins were identified in 1 case of advanced cancer with poor surgical risk. The remaining 3 patients were still alive without tumor recurrence as of time of writing. We therefore consider PSD as a suitable surgical option for ampullary tumors. Indications for local resection of malignant ampullary tumor remain controversial. According to van Gulic et al. [20], local resection of even limited ampullary carcinoma is inadvisable due to lymphatic dissemination of the tumor, resulting in inadequate clearance. Progression of benign epithelial ampullary tumors to papillary adenocarcinoma after local resection has also been reported [21]. In this series, 5 of the 7 cases of adenoma confirmed by preoperative tumor biopsy displayed focal cancer. Local resection was performed in 10 patients, with pathologically positive margins identified in 4 patients (adenoma, n ⫽ 2; pT1 cancer, n ⫽ 1; pT2 cancer with poor surgical risk, n ⫽ 1). Lymph node metastasis was evident in the patient with pT1 cancer. Although none of the 4 patients with incomplete resection have experienced local recurrence in the years since surgery, local resection should be proposed in patients with preoperatively confirmed benign tumor or T1 cancer for whom general conditions indicate a special risk for radical resection. In conclusion, since positive surgical margins exist in some cases and lymph node metastasis can be present even in patients with pT1 cancer, local resection as a therapeutic approach to tumors of the ampulla of Vater is indicated only for patients with preoperatively diagnosed benign tumors or in patients with malignant tumors who cannot withstand PD.

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