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10.1245/s10434-006-9136-3
Annals of Surgical Oncology 14:50-60 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Predictors for Patterns of Failure after Pancreaticoduodenectomy in Ampullary Cancer

Hui-Ping Hsu, MD1, Ta-Ming Yang, MD2, Yu-Hsiang Hsieh, PhD3, Yan-Shen Shan, MD, PhD1 and Pin-Wen Lin, MD1

1 Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138, Sheng-Li Road, Tainan, 70428, Taiwan (ROC)
2 Department of Surgery, Tainan Municipal Hospital, Tainan, Taiwan
3 Department of Emergency Medicine, The Johns Hopkins University School of Medicine, 1830 E. Monument Street, Suite 6-100, Baltimore, Maryland 21205, USA

Correspondence: Address correspondence and reprint requests to: Yan-Shen Shan, MD, PhD; E-mail: ysshan{at}mail.ncku.edu.tw


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Ampullary cancer has the best prognosis in periampullary malignancy but unpredicted early recurrence after resection is frequent. The current study tried to find the predictors for recurrence to be used as determinative for postoperative adjuvant therapy.

Methods: Information was collected from patients who underwent pancreaticoduodenectomy with regional lymphadenectomy for ampullary cancer in high-volume hospitals between January 1989 and April 2005. Recurrence patterns and survival rates were calculated and predictors were identified.

Results: A total of 135 eligible patients were included. The 30-day operative mortality was 3%. Median followup for relapse-free patients was 52 months. Disease recurred in 57 (42%) patients, including 31 liver metastases, 26 locoregional recurrences, 9 peritoneal carcinomatoses, 7 bone metastases, and 6 other sites. Pancreatic invasion (P = 0.04) and tumor size (P = 0.05) were the predictors for locoregional recurrence, while lymph node metastasis was the sole predictor for liver metastasis (P = 0.01). The 5-year disease-specific survival rate was 45.7%; 77.7% for stage I, 28.5% for stage II, and 16.5% for stage III; and 63.7% for node-negative versus 19.1% for node-positive patients. Pancreatic invasion and lymph node involvement were both predictors for survival of patients with ampullary cancer.

Conclusion: Pancreaticoduodenectomy with regional lymphadenectomy is adequate for early-stage ampullary cancer but a dismal outcome can be predicted in patients with lymph node metastasis and pancreatic invasion. Lymph node metastasis and pancreatic invasion can be used to guide individualized, risk-oriented adjuvant therapy.

Key Words: Ampulla of Vater • Pancreaticoduodenectomy


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Carcinoma of the ampulla of Vater is a rare neoplasm accounting for 0.063%-0.210% of all routine autopsy cases1 and 12.7%-32.2% of surgical resectable periampullary carcinomas.2,3 The resection rate of ampullary cancer is about 76.5%-88.0%2,4 and pancreaticoduodenectomy with regional lymphadenectomy is the main treatment.4,5 However, pancreaticoduodenectomy with regional lymphadenectomy is a technically demanding procedure with high rates of morbidity and mortality. In the older literature, the 5-year survival rate ranges from 6% to 38%.2,4 After improvements in preoperative evaluation, surgical technique, and postoperative care, the last ten years now report a 5-year survival rate of 35.0%-62.7%.6,7 Even after apparently successful operations, some patients still relapse earlier without apparent causes or clinical clues. In the literature, we found that even postoperative adjuvant chemoradiotherapy does not improve long-term survival after radical surgery. The available postoperative histopathologic factors seem not to be able to give a reliable prognosis.8,9 Because the procedure varies greatly among surgeons, and hospital volume also influences in-hospital mortality, analysis of the outcome of ampullary cancer in relation to the various histopathologic factors and other indicators is complicated. Therefore, we collected information on ampullary cancer patients who underwent pancreaticoduodenectomy with regional lymphadenectomy by volume surgeon from high-volume hospitals who used the same surgical procedure to exclude the surgical factor and analyzed the predictors for recurrence and dismal survival as the indicators for future postoperative adjuvant therapy to improve outcome.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients with ampullary cancer who underwent pancreaticoduodenectomy and regional lymphadenectomy between January 1989 to April 2005 in National Cheng Kung University Hospital and Tainan Municipal Hospital, both in Tainan, Taiwan, were included in the study. Patients who underwent palliative procedures or medical treatments were excluded. Age, gender, clinical presentation, laboratory findings on admission and before operation, preoperative biliary drainage procedures, type of resection, operative findings, postoperative morbidity, operative mortality, histopathologic findings, recurrent patterns, and survival were recorded from a retrospective chart review. Percutaneous transhepatic biliary drainage or endoscopic nasobiliary drainage was used routinely to relieve obstructive jaundice before operation if the bilirubin level was higher than 10 mg/dl.

The use of either standard (SPD) or pylorus-preserving pancreaticoduodenectomy (PPPD) was determined by the surgeons. The surgical techniques have been described previously.10,11 In the SPD, the vagus nerves were preserved and the distal two-thirds of the stomach was transected. In PPPD, the right gastric artery was preserved, unless the artery restricted the mobility of the stomach. The duodenum was dissected and divided at least 2 cm distal to the pylorus. Reconstruction was accomplished by single-layer end-to-side choledochojejunostomy without T-tube drainage and end-to-side pancreaticojejunostomy with appropriate pediatric nasogastric tube as a diversion stent in the pancreatic duct for three weeks. The resected lymph nodes included the anterior and posterior pancreaticoduodenal lymph nodes, nodes along the right lateral aspect of the superior mesenteric artery and vein, and nodes in the lower hepatoduodenal ligament. If local invasion of the portal vein or superior mesenteric vein was encountered during the operation without further macroscopic distant metastasis, resection of the vein with end-to-end reconstruction was performed. After completing reconstruction, one or two suction drains were placed through separate skin incisions in the right upper quadrant of the abdomen relative to the pancreatic and biliary anastomoses. During the operation, pancreatic consistency was evaluated by the surgeon. The diameters of the stumps of the pancreatic duct and common bile duct (CBD) were measured at the stump end. Operative time, intraoperative blood loss, and units used for blood transfusion were recorded precisely. Only eight patients received adjuvant postoperative chemoradiotherapy. Four patients received intravenous fluorouracil-based chemotherapy (fluorouracil/leucovorin + mitomycin or fluorouracil + epirubicin + mitomycin) and two patients took oral tegafur (Futraful, FT-207®).

Morbidity and Mortality
All general and procedure-related complications were recorded. Pancreatic fistula was defined as amylase-rich fluid with drain fluid volume greater than 10 ml/day, persistent elevation of the drain amylase level, and three times higher than the serum level for longer than seven days.12 A biliary fistula was defined as the presence of bile drainage that persisted after postoperative day 7. Postoperative pancreatitis was defined as an increase in serum lipase with clinical presentation. Intra-abdominal abscess was defined as when drainage fluid was dirty with positive bacterial culture. Hemorrhagic complications included intra-abdominal bleeding after surgical dissection and gastrointestinal tract bleeding due to marginal ulcer. Delayed gastric emptying was defined as occurring when the nasogastric tube was left in place for ten days or more, plus one of the following: (1) emesis after removal of the nasogastric tube, (2) reinsertion of a nasogastric tube, or (3) failure to progress with diet.13 Wound infection was defined as a positive wound culture and the presence of pus necessitating opening of the wound. The pulmonary complications included pneumonia, pleural effusion, empyema, or respiratory failure. The operative mortality was defined as 30-day mortality, but hospital mortality included those who died from other causes associated with hospitalization, even more than 30 days after the operation.

Histopathology
All surgical specimens were checked by a pathologist. The site of the tumor’s origin was determined at the time of gross and histolopathologic examinations. Only adenocarcinoma originating in the ampulla of Vater was included. Histologic differentiation was recorded as well, moderately, or poorly differentiated. Tumor size was measured from surgical specimen before formalin fixation. Tumor stage and TNM stage were defined according to the American Joint Committee on Cancer (AJCC) classification of 2002.14 Pancreatic invasion was defined as a tumor nest that invaded the parenchyma of the pancreas grossly or microscopically. The lymphovascular/perineural invasion or morphologic type of intestinal or pancreaticobiliary mucosa was not routinely recorded by a pathologist and was not included in study.

Followup
Followup at three-month intervals comprised physical examination and laboratory tests for tumor markers (carcinoembryonic antigen, CEA; cancer antigen 125 and 199, CA-125 and CA-199). Abdominal sonography was done every three months in the first year and then every six months in the second year. The computerized tomography of the abdomen was done annually or if there was suspicion of intra-abdomnal metastasis. Radiography of the thorax, bone scan, and computerized tomography of the brain were performed if clinical examination reported suspicion of metastasis.

Recurrence was categorized as either locoregional or metastatic. Disease relapse was defined as biopsy-proven disease or radiologic evidence of recurrence. Local recurrence was defined as recurrent retroperitoneal mass or regional nodes. Metastasis was defined as relapse of disease at a distant site, either a visceral organ or nonregional lymph nodes. The endpoint of the study was death and the primary criterion of followup was survival time. The overall survival rate was defined as the total survival ratio in these patients, including those who died from causes other than ampullary cancer. The disease-specific survival rate was limited to the effect of ampyllary cancer.

Statistical Analysis
All statistical analyses were performed using SAS v9.13 (SAS Institute, Cary, NC). Univariate analysis was performed using the {chi}2 test or Fisher’s exact test for categorical variables. Statistical comparison between the two groups was done by independent-sample t test for continuous variables with normal distribution. Continuous variables that did not follow normal distribution were compared by a nonpara-metric two-independent-sample test. The association of categorical variables and survival was assessed using the Kaplan-Meier method, and significance was tested using the log-rank test. Those factors with P < 0.2 in univariate analysis were defined as significant. A multivariate analysis using Cox proportional hazards regression model was used to determine significant influence on survival. Risk factors associated with nonrecurrence or recurrence were determined by multivariate logistic regression. Each model included age and gender as covariates. The results were expressed as odds ratio (OR) with 95 percent confidence interval (CI) and corresponding two-tailed p values. Statistical significance was determined for P < 0.05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Demographic Data
There were 146 patients diagnosed with adenocarcinoma of ampulla of Vater. A total of 135 patients who underwent pancreaticoduodenectomy with regional lymphadenectomy were included, the resection rate was 93%. Table 1Go. shows the demographic data comparing survivor and nonsurvivor patients. There were no statistical differences in age, gender, operative methods, stump of common bile duct, and consistency of pancreas between the two groups. Higher levels of preoperative bilirubin and tumor markers were noted in nonsurvivor patients (P < 0.05). Nonsurvivor patients had longer operative time, more blood loss and blood transfusion, and larger stump pancreatic duct size.


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  		TABLE 1. Demographics, preoperative data, and operative findings in this series of 135 patients with ampullary cancer who underwent pancreaticoduodenectomy: results of univariate analysis
 
Histopathologic Findings
The nonsurvivors had more advanced histopathologic conditions, including larger tumor size, higher ratio of pancreatic invasion and lymph node involvement, poorer differentiation, and more patients with T3/T4 lesions or stage III/IV disease (Table 2Go). The median tumor size was 2.0 cm (range = 0.5–8.0 cm). The size of the primary tumor associated with pancreatic invasion was significantly larger than the sizes of those without pancreatic invasion (median = 2.9 cm, range = 1.0–8.0 cm with pancreatic invasion; median = 2.0 cm, range = 0.5–7.0 cm without pancreatic invasion; P = 0.001). Also, the primary tumor size was correlated with lymph node status (median = 2.0 cm in two groups; P = 0.114). However, there was no association between tumor size and histologic differentiation (median = 2.0 cm in well- and moderately differentiated tumor and median = 1.75 cm in poorly differentiated tumors; P = 0.805). After further examination of the association of tumor size and clinical histopathology, the tumor size was not correlated with preoperative bilirubin level, diameter of pancreatic duct, operative time, intraoperative blood loss, or numbers of positive lymph nodes in graphs of scatterplots (data not shown).


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  		TABLE 2. Histopathologic findings in 135 patients with ampullary cancer who underwent pancreaticoduodenectomy: results of univariate analysis
 
After pancreaticoduodenectomy, a median of 9 lymph nodes (range = 0–39) were removed from each patient. In survivors, a median of 7 lymph nodes (range = 1–39) were removed compared with a median of 10 lymph nodes (range = 0–25) in non-survivors without statistical significance (P = 0.137). The median number of lymph nodes involved was zero in survivors (range = 0–8) and one in nonsurvivors (range = 0–9) with P < 0.0001. The median number of dissected lymph nodes did not have any significant difference between patients with or without liver metastases (median = 8 vs. 10.5 lymph nodes; P = 0.094). However, the patients with liver metastases had a higher ratio of lymph node metastases than those without liver metastases (median = 0 vs. 2 lymph nodes; P = 0.001). The median number of dissected and involved lymph nodes did not have any significant difference between patients with or without locoregional recurrence (median = 8 vs. 10 dissected lymph nodes; P = 0.235; median = 0 vs. 0 involved lymph node; P = 0.163).

Morbidity and Mortality
Operative morbidity was 59% without any significant difference between SPD and PPPD (53% vs. 66%). There was more subjective delayed gastric emptying developed in PPPD patients. Incidence of pancreaticojejunostomy leakage was 10.7% (11 patients) in our series. In these 11 patients, the pancreaticojejunostomy leakage caused intra-abdominal fluid accumulation or abscess, which could be drained percutaneously, i.e., no surgical intervention needed. There was no mortality associated with pancreaticojejunostomy leakage in our series. Thirty-day operative mortality was 3% and hospital mortality was 6%. Mortality did not correlate with the operative method. In the patients with 30-day operative mortality or hospital mortality, the most frequent causes of mortality were pulmonary complications and intra-abdominal abscess. No one had evidence of pancreaticojejunostomy leakage.

Recurrence Patterns
Fifty-seven patients (42%) had disease recurrence during followup, including 31 (23%) liver metastases, 26 (19%) locoregional recurrences, 9 (7%) peritoneal carcinomatosis, 7 (5%) bone metastases, and 6 (4%) metastases at other sites (Table 3Go). There were 10 patients who developed liver metastasis and locoregional recurrence simultaneously. In the univariate analysis of risk factors for recurrence, preoperative CA-125 level, diameter of the common bile duct stump, tumor size, pancreatic invasion, tumor stage, lymph node involvement, and AJCC TNM stage were statistically significant (data not shown). We further analyzed the risk factors for liver metastasis and local recurrence. In univariate analysis, liver metastasis was associated with preoperative bilirubin level and tumor marker, operative time and blood loss, diameter of the common bile duct stump, and lymph node involvement (Table 4Go). In multivariate analysis, only lymph node involvement had statistical significance to liver metastasis (Table 5Go). Patients with locoregional recurrence had different risk factors. Gender, tumor size, pancreatic invasion, tumor stage, and AJCC TNM stage had statistical significance in univariate analysis, but only pancreatic invasion was significant in multivariate analysis. Tumor size had borderline significance to locoregional recurrence (P = 0.05) (Tables 4Go and 5Go).


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  		TABLE 3. Recurrence patterns in 135 patients with ampullary cancer who underwent pancreaticoduodenectomy
 

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  		TABLE 4. Univariate analysis of risk factors in different recurrence patterns in 135 patients with ampullary cancer who underwent pancreaticoduodenectomy
 

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  		TABLE 5. Multivariate analysis of risk factors in different recurrence patterns in 135 patients with ampullary cancer who underwent pancreaticoduodenectomy
 
Survival
During followup, 30 patients received chemoradiotherapy for recurrent disease. Six patients received intravenous fluororacil-based chemotherapy, four patients received gemcitabine-based chemotherapy, and two patients received another regimen. Only one patient received radiotherapy for locoregional recurrence. The overall 5-year survival rate in the series was 40.9% and the actuarial disease-specific 5-year survival rate was 45.7% (Table 6Go). There was no difference in the 5-year survival rate between patients with or without postoperative adjuvant therapy or between those with or without chemoradiotherapy for recurrent disease. For patients alive at the time of the followup study, the mean followup was 56 ± 39 months (median = 52 months, range = 5–145 months). Kaplan-Meier disease-specific survival curves were drawn according to histopathologic factors (Figs. 1Go–4GoGoGo). According to the AJCC staging system, the survival rate after 5 years was 77.7% for patients with stage I disease and decreased to 28.5% in stage II and 16.5% in stage III. The two patients with stage IV disease survived 6 and 12 months, respectively (Fig. 4Go). The differences in survival rates between stage I and stage II, stage I and stage III, and stage I and stage IV were highly significant (P < 0.05).


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  		TABLE 6. Histopathologic factors and impact on disease-specific survival in 135 patients with ampullary cancer who underwent pancreaticoduodenectomy
 

Figure 1
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  		FIG. 1. Kaplan-Meier disease-specific survival curves by lymph node status.

 

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  		FIG. 2. Kaplan-Meier disease-specific survival curves by histologic differentiation.

 

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  		FIG. 3. Kaplan-Meier disease-specific survival curves by pancreatic invasion.

 

Figure 4
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  		FIG. 4. Kaplan-Meier disease-specific survival curves by AJCC TNM stage.

 
In multivariate analysis, which included 14 covariates in univariate analysis, only pancreatic invasion, histologic differentiation, and lymph node status had significant influence on survival. For AJCC staging, the prognosis for patients with stage II and stage III disease was worse than for patients with stage I disease but did not reach statistical significance. Patients with stage IV had significantly worse prognosis than stage I (Table 7Go).


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  		TABLE 7. Multivariate analysis of prognostic factors for survival in 135 patients with ampullary cancer who underwent pancreaticoduodenectomy
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Ampullary cancer is the second most common periampullary carcinoma, but the 5-year disease-free survival rate after operation varies considerably.5–7 In this study we enrolled 135 patients with ampullary cancer who underwent pancreaticoduodenectomy with regional lymphadenectomy by two volume surgeons in high-volume hospitals. After a long median followup, the five-year survival rate was 45.7%, and 57 patients had different recurrent diseases. Lymph node involvement was the sole risk factor for liver metastasis and pancreatic invasion was the risk factor for local recurrence.

The predictors for recurrent patterns and survival in ampullary cancer patients vary greatly in the literature. The most common patterns of postoperative recurrence are liver metastasis and locoregional recurrence. From the complexity of anatomy in the periampullary region, the risk factors for recurrence pattern and survival should be correlated with lymphovascular invasion. Todoroki et al.15 reported that lymphatic vessel and venous invasion were significant predictors of distant failure in 66 ampullary cancer patients with surgical intervention. The microscopic venous and lymphatic vessel invasion significantly correlated with hematogenous metastases (liver, lung, bone metastases) and lymphogenous metastases (locoregional and distant nodes). The venous invasion significantly influenced liver metastasis and the lymphatic vessel invasion correlated significantly with distant node metastasis.15 However, in our series, the microscopic venous or lymphatic invasion was not routinely evaluated and only lymph node involvement was analyzed. We had different results after analysis; lymph node involvement was associated with liver metastasis and pancreatic invasion with locoregional recurrence.

Lee et al.16 reported that the risk of local recurrence was significantly higher in patients with a high-risk disease, including tumor invasion into the pancreas, a node-positive disease, higher T-stage, and a higher pathologic stage disease, while invasion of the duodenum was of borderline significance. Delcore et al.17 reported that tumor size was one of the independent factors for recurrence and 5-year survival, but Begar et al.18 showed that pancreatic invasion was the pivotal factor for survival and recurrence, not tumor size. In our series, both tumor size and pancreatic invasion had statistical significance for survival in univariate analysis and disease-specific survival rate. However, only pancreatic invasion was a predictor for survival and locoregional recurrence in multivariate analysis. We did find a relationship between large tumor size and pancreatic invasion. From the anatomical character of the ampulla of Vater, the pancreatic side of the duodenum has the lymphovascular supplement of the periampullar region, similar to Todoroki’s report. If the large tumor grows into duodenal lumen but not into the pancreas, subsequent metastasis will not develop. Therefore, the negative effect should come from pancreatic invasion not large tumor size.

There are several reports that discuss with the number of regional lymph nodes examined pathologically in a pancreaticoduodenectomy specimen.6,19 Monson et al.19 reported that a median of 7 (range = 1–21) regional lymph nodes, rather than the extent of lymph node involvement, was the significant prognostic factor. Böttger et al.6 reported that the extent of the lymph node dissection was the most important factor influencing the survival rate and they dissected a median of 10 regional lymph nodes (range = 5–34). Shirai et al.20 dissected a median of 32 lymph nodes (range = 13–73) by pancreaticoduodenectomy with radical lymphadenectomy. The 5-year survival rates of the pN0, "1–3 positive nodes," and "≥4 positive nodes" groups were 81%, 71%, and 0%, respectively. They suggested that radical lymphadenecto-my showed a limited degree in nodal disease.20 In our study, regional lymphadenectomy, not including paraaortic and distant nodes as in radical lymphadenectomy, was performed and a median of 9 lymph nodes (range = 0–39) were removed from each patient. Those patients with T1 primary tumors did not have any lymph node involvement, nor did patients with well-differentiated tumor or without pancreatic invasion (data not shown). Therefore, it was not the dissected number of lymph nodes, in either radical or regional lymhadenectomy, but rather the lymph node involvement that correlated with liver metastases and patient survival.

Actually, there is no consistency in the role of lymph node involvement associated with poor prognosis in ampullary cancer. Matory et al.21 reported that only resectability was a significant predictor of survival in 69 ampullary carcinoma patients, and Allema et al.22 stated that involvement of section margins was the strongest prognostic factor for survival. In the Matory et al. and the Allema et al. series, residual tumor was the main cause of early recurrence, but survival time was too short to reveal the significance of lymph node status. In the series from the John Hopkins Medical Institute, lymph node involvement was a significant predictor for pancreas, distal bile duct, and duodenal adenocarci-oma but not for ampullary cancer.23 However, in patients after radical resection, regional lymph node involvement was the worst prognostic factor in most reports.3,5–7,12,18,24–29 The 5-year survival rate ranged from 0%-41% in patients with lymph node involvement and from 67%-81% in patients without lymph node involvement. Our series had similar results: 55 ampullary cancer patients with lymph node involvement had significantly short median survival (22 months) and 5-year survival (19.1%) when compared with 5-year survival of patients without lymph node involvement (63.7%).

Differentiation of the tumor was also a predictor for survival by univariate analysis in several reports, but not by multivariate analysis.4,17,18,29 The 5-year survival rate was reported at 82% in patients with well-differentiated tumor and at 37% in patients with moderate- to poorly differentiated tumor.29 In this series, 5-year survival rates were similar for those with well- or moderately differentiated tumor (54.6% vs. 41.1%, P > 0.05) but were dismal in those with poorly differentiated tumor (23.1%, P < 0.05). However, the differentiation had no influence on liver metastasis or local recurrence. Almost all patients with poorly differentiated tumor had a higher incidence of lymph node metastasis. Therefore, the impact of differentiation on survival or recurrence was negligible when counting the lymph node status.

The TNM staging system is a popular predictor for survival, but survival rates vary with different reports. By some reports, the 5-year survival rate was 76%–100% for patients with stage I disease, 21%–70% for stage II, 10%–27% for stage III, and 0% for stage IV.1,15,16,18 Under the American Joint Committee on Cancer (AJCC) classification of 2002, T1-3N1M0 was classified as stage IIB. In our series, the 5-year survival rate was 77.7% for stage I disease patients but it dropped to 28.5% for stage II patients, and the 5-year survival rates for stages III and IV patients were as bad as previous reports. As described above, the lymph node status is the determinant in patient outcome. Therefore, we recommend that lymph node status should be included in stage III of the TNM staging system.

Reports of the use of adjuvant therapy following radical resection of ampullary carcinoma are rare. Bakkevold et al.8 found that combined chemotherapy regimens (AMF) could postpone the incidence of recurrence in the first two years, but an increase in cure rate was not observed. A combination of intra-operative radiation and resection also did not benefit patients with ampullary cancer.30 However, Lee et al.16 and Willett et al.31 found that the combination of adjuvant chemotherapy and radiation therapy produced a trend toward better local control in high-risk patients but no improvement in survival.16,31 Mehta et al.32 proved that adjuvant chemoradio-therapy for ampullary cancer was well tolerated,32 but Sikora et al.9 found no improvement in long-term survival and no decrease in recurrence rates. From earlier studies, there was no known proper and adequate regimen of chemoradiotherapy for patients with ampullary cancer, so a prospective randomized study based on histopathologic or clinical predictors is necessary to elucidate the effect of adjuvant therapy on the high-risk patients.

In conclusion, lymph node status and pancreatic invasion were significant histologic predictors for survival in ampullary cancer patients. Lymph node involvement was a predictor for liver metastasis and pancreatic invasion and large tumor size were predictors for locoregional recurrence. We recommend postoperative regional therapy for patients with pancreatic invasion to decrease locoregional recurrence and systemic therapy for patients with lymph node metastasis to prevent later liver metastasis.

Received for publication June 16, 2006. Accepted for publication June 26, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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