Curative Pancreaticoduodenectomy Research Articles

Surgical Strategy and Outcome in Patients Undergoing Pancreaticoduodenectomy After Gastric Resection: A Three-Center Experience with 39 Patients.

Stomach cancer is the second most commonly diagnosed cancer in Korea. Although the long-term survival outcome has improved, secondary primary tumors from periampullary regions are increasing inevitably and pancreaticoduodenectomy (PD) following gastrectomy is challenging. This study evaluates the surgical outcomes of PD following gastrectomy and suggests the optimum method for reconstruction. Patients who underwent curative PD with a history of gastric resection between 2005 and 2015 were assessed retrospectively. PD was performed according to the standard fashion, with the aim of creating a new pancreaticobiliary limb with sufficient length (40-50cm). Different reconstructive methods were employed during PD according to the previous gastrectomy type. A total of 3064 patients underwent PD, 39 of whom had previous gastrectomies including 12 with Billroth I gastrectomy, 20 with Billroth II gastrectomy, and seven patients with total gastrectomy (TG). In patients with Billroth I gastrectomy, all of the previous gastroduodenostomy site was resected for specimen retrieval. All previous esophagojejunostomy site was preserved in seven patients who had TG. In the Billroth II patients, the gastrojejunostomy site was preserved in 17 patients. Re-operation after PD was required in two patients, and 14 patients (36%) developed pancreatic fistula and five (13%) of grade B or higher. Our study has been the largest report so far of PD following gastric resection, and we were able to confirm the safety and the feasibility of PD procedure. We therefore suggest standardizing the reconstruction method for PD following gastrectomy based on the type of previous gastrectomy.

Which patients with para-aortic lymph node (LN16) metastasis will truly benefit from curative pancreaticoduodenectomy for pancreatic head cancer?

In patients with cancer of the pancreatic head, metastasis to para-aortic lymph nodes (LN16) is considered distant metastasis and a poor prognostic marker. However, the incidence of LN16 involvement in pancreatic head cancer is high, and it is unclear whether all such patients have poor surgical outcomes. We investigated the significance of LN16 involvement in resectable pancreatic head cancer by retrospectively analyzing 579 ductal adenocarcinoma patients treated with para-aortic lymph node dissection at two high-volume Chinese centers. Depending upon tumor location, the incidence of LN16 metastasis and the correlation between LN16 involvement and involvement of Group 1 or 2 lymph nodes significantly differed. Metastasis to LN16 indicated a high serum tumor burden and a poor prognosis, though LN16-positive patients with a lymph node ratio (LNR) < 0.25 may still benefit from radical surgery. Survival analysis of LN16-positive patients with resectable pancreatic head cancer revealed that tumor size, tumor differentiation, and tumor location are independent prognostic factors. We also found that preoperative serum CA125 < 18.62 U/ml and the level of JAK2 signaling are both indicators of who may benefit from curative surgical resection for pancreatic head cancer.

Prognostic Value of Excision Repair Cross-Complementing Gene 1, Dihydropyrimidine Dehydrogenase, and Human Equilibrative Nucleotide Transporter 1 Expression and Their Implications for Adjuvant Treatment in Patients With Ampullary Carcinoma.

The purpose of this study was to characterize the intratumoral expression profiles of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), and human equilibrative nucleotide transporter 1 (hENT1) in ampullary carcinomas (ACs) to evaluate their prognostic values and better tailor adjuvant chemotherapy for individual patients with AC after surgery. This study included 49 patients with AC who underwent a curative pancreaticoduodenectomy. Various clinicopathological factors, including ERCC1, DPD, and hENT1, were analyzed in relation to postoperative disease recurrence and the patients' survival. The median recurrence-free survival and overall survival were 24.5 months and 32.4 months, respectively. Multivariate Cox regression analysis of recurrence-free survival identified a DPD expression (hazard ratio [HR], 8.18; 95% confidence interval [CI], 2.00-34.8; P = 0.003) and combined ERCC1/DPD expression (HR, 134.8; 95% CI, 11.8-1920; P < 0.001) as independent predictors of disease recurrence. Multivariate Cox regression analysis of overall survival also identified a DPD expression (HR, 8.48; 95% CI, 1.71-46.3; P = 0.008) and combined ERCC1/ DPD expression (HR, 135.6; 95% CI, 11.8-1940; P < 0.001) as independent predictors of survival. The DPD and ERCC1 expression profile could potentially serve as a useful prognostic biomarker and therapeutic target for surgically resected patients with AC.

The role of lymph nodes in predicting the prognosis of ampullary carcinoma after curative resection.

BackgroundLymph node involvement is one of the well-demonstrated prognostic factors in ampullary carcinoma. The aim of this study is to clarify the role of lymph nodes in predicting the survival outcome of ampullary carcinoma.MethodsA cohort of consecutive curative pancreaticoduodenectomies for ampullary carcinoma from 1999 to 2014 was retrospectively analyzed. The effect of node-associated variables, including lymph node status, positive lymph node number, total harvested lymph node (THLN) number, and lymph node ratio (LNR) was examined using univariate and multivariate analyses for survival outcome prediction.ResultsIn 194 evaluable patients, univariate analysis demonstrated that stage, cell differentiation, perineural invasion, and nodal status were significant conventional prognostic factors. Concerning the node-associated variables, positive nodal status, positive lymph node number ≥2, THLN number <14, and LNR ≥0.15 were significantly associated with poorer survival outcomes, with a 5-year survival rate of 20.3, 38.9, 25.4, and 18 %, respectively. By multivariate analysis, nodal status and THLN number were two independent predictors of survival. The most favorable 5-year survival rate was 84.4 % in patients with negative nodal involvement and THLN number ≥14, compared with the poorest 5-year survival rate of 16.1 % in those with positive nodal status and THLN number <14.ConclusionsTumor biology reflected by lymph node status is the most important independent prognostic factor; nevertheless, surgical radicality based on THLN number also plays a significant role in the survival outcome for patients with ampullary carcinoma after curative pancreaticoduodenectomy.

Prognostic impact of M2 macrophages at neural invasion in patients with invasive ductal carcinoma of the pancreas

BackgroundNeural invasion is a characteristic pattern of invasion and an important prognostic factor for invasive ductal carcinoma (IDC) of the pancreas. M2 macrophages have reportedly been associated with poor prognosis in various cancers. The aim of the present study was to investigate the prognostic impact of M2 macrophages at extrapancreatic nerve plexus invasion (plx-inv) of pancreatic IDC. MethodsParticipants comprised 170 patients who underwent curative pancreaticoduodenectomy for pancreatic IDC. Immunohistochemical examination of surgical specimens was performed by using CD204 as an M2 macrophage marker, and the area of immunopositive cells was calculated automatically. Prognostic analyses of clinicopathological factors including CD204-positive cells at plx-inv were performed. ResultsPlx-inv was observed in 91 patients (53.5%). Forty-eight patients showed a high percentage of CD204-positive cell area at plx-inv (plx-inv CD204%high). Plx-inv CD204%high was an independent predictor of poor outcomes for overall survival (OS) (P<0.001) and disease-free survival (DFS) (P<0.001). Patients with plx-inv CD204%high showed a shorter time to peritoneal dissemination (P<0.001) and locoregonal recurrence (P<0.001). In patients who underwent adjuvant chemotherapy, plx-inv CD204%high was correlated with shorter OS (P=0.011) and DFS (P=0.038) in multivariate analysis. ConclusionsPlx-inv CD204%high was associated with shortened OS and DFS and early recurrence in the peritoneal cavity and locoregional space. The prognostic value of plx-inv CD204%high was also applicable to patients who received adjuvant chemotherapy. High accumulation of M2 macrophages at plx-inv represents an important predictor of poor prognosis.

Lymph node ratio predicts local recurrence for periampullary tumours

To better define the prognostic role of nodal disease, evaluation of metastatic lymph node ratio (MLR) has been performed, and this method has recently gained prominence in various gastrointestinal cancers. The present study attempts to identify prognostic factors and evaluate the independent prognostic influence of MLR in patients who have undergone curative pancreaticoduodenectomy. In our institution within the study period, 111 patients received curative pancreaticoduodenectomy for periampullary cancers. Clinicopathologic data were collected and MLR was calculated for each of the patients. Patients were then divided into four groups based on MLR value: MLR 1 = 0; MLR 2 = 0.01-0.2; MLR 3 0.21-0.4; and MLR 4 >0.4. Increasing MLR correlates with high recurrence rate and lower overall survival (OS) with significance (P < 0.001, P < 0.001). The recurrent group showed significantly lower OS than the non-recurrent group (P < 0.001). In the multivariate analysis for recurrence, MLR was identified as the only independent prognostic factor (P < 0.001). The simple and easily obtainable MLR is well qualified as a prognostic factor in patients who undergo curatively radical resection for periampullary cancer. Furthermore, MLR can overcome the limitations of evaluation of lymph nodes status, allowing it to be used as a potential prognostic factor.

Metastasis to the skin at the drain site after complete resection of the lower bile duct cancer: report of a case

There are extremely few reports of metastases from a lower cholangiocarcinoma to the skin except for metastatic seeding in a percutaneous transhepatic biliary drainage catheter tract. This report presents a rare case of metastases to the skin after the removal of a drain following curative pancreaticoduodenectomy for lower bile duct cancer (LBDC). A 73-year-old female had undergone subtotal stomach-preserving pancreaticoduodenectomy. Skin metastasis was noted at the site where the drain from the lower border at pancreaticojejunostomy had been removed 22 weeks postoperatively, and it was en bloc resected with the abdominal wall without exposing the carcinoma. Multiple nodules were confirmed in the axilla and chest wall 40 weeks after the initial operation. Careful discussion is necessary to avoid this mode of metastasis. The surgical field should not be exposed to pancreatic juice, even with LBDC. Nevertheless, this case is rare. Therefore, the risks and benefits of using such drains must be considered.

Postoperative morbidity is an additional prognostic factor after potentially curative pancreaticoduodenectomy for primary duodenal adenocarcinoma

The aims of this paper were to evaluate the clinical features of patients with primary duodenal adenocarcinoma and to address the prognostic relevance of different surgical and pathological variables after potentially curative pancreaticoduodenectomy. Patients with primary duodenal adenocarcinoma observed from 2000 through 2009 were identified from a single-institution electronic database. Univariate and multivariate analyses were performed to identify factors associated with survival. The study population consisted of 37 patients. Of these, 25 underwent pancreaticoduodenectomy, while the remaining 12 were not amenable to resection and underwent bypass operations or were given best supportive care. Overall survival after radical resection (R0) was significantly longer than after palliative surgery (180 versus 35months, p = 0.013). On multivariate analysis, tumor grade (hazard ratio (HR) = 1.345, 95% CI = 1.28-1.91, p = 0.03) and the occurrence of postoperative or abdominal complications (HR = 1.781, 95% CI = 1.10-2.89, p = 0.037; HR = 1.878, 95% CI = 1.21-3.08, p = 0.029) were found to be significant prognostic factors for survival in patients undergoing potentially curative resection. In particular, median survival was 180months in patients with an uneventful postoperative course and 52months in those with abdominal complications. The 5-year overall survival rates were 100 and 60%, respectively. According to the present findings, the development of postoperative complications may be an additional prognostic factor after potentially curative pancreaticoduodenectomy for primary duodenal adenocarcinoma. This emphasizes the need for centralization to high-volume centers where an appropriate postoperative care can be delivered.

Assessment of the Interface Between Retroperitoneal Fat Infiltration of Pancreatic Ductal Carcinoma and the Major Artery by Multidetector‐Row Computed Tomography: Surgical Outcomes and Correlation with Histopathological Extension

Precise assessment of retroperitoneal invasion is clinically important to allow the achievement of negative margin resections. The clinical records of 132 patients who underwent macroscopic curative pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas between 2004 and 2008 were retrospectively examined. The clinicopathological factors, including retroperitoneal fat infiltration classified into four groups by multidetector-row computed tomography (MDCT), were analyzed. The relationship between the grade of retroperitoneal fat infiltration and surgical outcomes, as well as various histopathological factors, was also investigated. The 5 year survival rate was 55.6 % for grade 0 infiltration (n = 8), 38.7 % for grade 1 (n = 54), 16.4 % for grade 2 (n = 49), and 0 % for grade 3 (n = 21). There were significant differences in survival in each group. Extrapancreatic nerve invasion and the surgical margin status were significantly associated with retroperitoneal fat infiltration demonstrated on MDCT. According to the grading classification among the 43 patients with pathological portal vein invasion, the 5 year survival rate was 45.9 % for patients with grade 1, which was significantly better survival that those with grade 2 (P = 0.007). The grading criteria for retroperitoneal fat infiltration may be useful as a predictor of survival after pancreaticoduodenectomy for pancreatic head carcinoma. Pancreaticoduodenectomy with portal vein resection could provide favorable survival in patients with grade 1 retroperitoneal fat infiltration, even if histopathological portal vein invasion is present.

Long-term results of pancreaticoduodenectomy and endoscopic resection in the treatment of early stage carcinoma of the ampulla of Vater: case series and review of the literature

We retrospectively evaluated 6 cases to explore the role of curative pancreaticoduodenectomy and endoscopic resection of ampulla of Vater tumors. Six patients diagnosed with stage 1 ampullary tumors at Ankara University Hospital between January 1994 and September 2009 were analyzed retrospectively. Icterus was the cardinal symptom in all patients. The median time for the symptoms caused by the lesion of the papilla was 7 weeks in patients with carcinoma. The diameters of the visualized tumors were less than 20 mm. Diabetes mellitus was observed in 2 patients. When the patients were classified according to TNM staging, all patients were in stage 1. Endoscopic resection was performed in 3 patients, and the other 3 patients underwent curative pancreaticoduodenectomy. The mean ages in the curative pancreaticoduodenectomy group and endoscopic resection group were 54.3 and 80.3 years, respectively. Tumor recurrence was not observed in any patient. Among the endoscopic resection group, there was no sign of tumor recurrence for 72 months in 1 patient, 6 months in another patient, and 46 months in the last patient. One of the patients died 46 weeks after endoscopic ampullectomy. This patient also had diabetes mellitus and cardiac problems. Radical pancreaticoduodenectomy is presently the most common method for resecting malignant ampullary tumors. Endoscopic resection of carcinoma of the ampulla of Vater appears to be an alternative to surgical therapy, particularly in patients for whom surgical approach carries a high risk.

Carcinoma of the Ampulla of Vater: Patterns of Failure Following Resection and Benefit of Chemoradiotherapy

Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. We performed a single-institution outcomes analysis to define the role of concurrent chemoradiotherapy (CRT) in addition to surgery. A retrospective analysis was performed of all patients undergoing potentially curative pancreaticoduodenectomy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1976 and 2009. Time-to-event analysis was performed comparing all patients who underwent surgery alone to the cohort of patients receiving CRT in addition to surgery. Local control (LC), disease-free survival (DFS), overall survival (OS), and metastases-free survival (MFS) were estimated using the Kaplan-Meier method. A total of 137 patients with ampullary carcinoma underwent Whipple procedure. Of these, 61 patients undergoing resection received adjuvant (n = 43) or neoadjuvant (n = 18) CRT. Patients receiving chemoradiotherapy were more likely to have poorly differentiated tumors (P = .03). Of 18 patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response (pCR). With a median follow-up of 8.8 years, 3-year local control was improved in patients receiving CRT (88% vs 55%, P = .001) with trend toward 3-year DFS (66% vs 48%, P = .09) and OS (62% vs 46%, P = .074) benefit in patients receiving CRT. Long-term survival rates are low and local failure rates high following radical resection alone. Given patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered.

Carcinoma of the ampulla of Vater: Patterns of failure after resection and benefit of adjuvant radiotherapy.

254 Background: Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. To define the role of radiation therapy and chemotherapy with surgery, we performed a single institution analysis of treatment- related outcomes. Methods: A retrospective analysis was performed of all patients undergoing potentially curative therapy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1975 and 2009. Local control (LC), overall survival (OS), disease-free survival (DFS), and metastases-free survival (MFS) were estimated using the Kaplan-Meier Method. Results: One hundred thirty-seven patients with ampullary carcinoma underwent potentially curative pancreaticoduodenectomy. Sixty-one patients undergoing resection received adjuvant (n= 43) or neoadjuvant (n=18) radiation therapy with concurrent chemotherapy (CRT). Patients receiving radiotherapy were more likely to have poorly differentiated tumors. Median radiation dose was 50 Gy. Median follow up was 8.8 years. Of patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response. Three-year local control was significantly improved in patients receiving CRT (88% vs. 55% p= 0.001) with trend toward a 3-year OS benefit in patients receiving CRT (62% vs. 46% p=0.074). Despite this, there was no significant difference in 3-year DFS (66% CRT vs 48% surgery alone p=0.09) or MFS (69% CRT vs 63% surgery alone p=0.337). Conclusions: Long term survival rates are low. Local failure rates are high following radical resection alone and improved with CRT. Despite more adverse pathologic features in patients receiving CRT, survival outcomes were at least equivalent with a trend toward statistical significance. Given the patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered. No significant financial relationships to disclose.

A Prospective Comparison of the Prognostic Value of Tumor- and Patient-Related Factors in Patients Undergoing Potentially Curative Surgery for Pancreatic Ductal Adenocarcinoma

Outcome prediction after resection with curative intent for pancreatic ductal adenocarcinoma remains a challenge. There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients undergoing resection for a variety of common solid tumors. Our aim was to prospectively evaluate the prognostic value of tumor- and patient-related factors including the systemic inflammatory response in patients undergoing potentially curative surgery for pancreatic ductal adenocarcinoma of the head of pancreas. The prognostic impact of tumor factors such as stage and host factors, including the systemic inflammatory response (modified Glasgow Prognostic Score [mGPS]), were evaluated in a prospective study of 135 patients who underwent elective pancreaticoduodenectomy for pancreatic ductal adenocarcinoma from January 2002 to April 2009. In addition to the established tumor-related pathological factors (in particular margin involvement; hazard ratio [HR] 2.82, 95% confidence interval [CI] 1.65-4.84, P < 0.001), an elevated mGPS (HR 2.26, 95% CI 1.43-3.57, P < 0.001) was independently associated with lower overall survival after pancreaticoduodenectomy. Additionally, in an adjuvant therapy subgroup of 74 patients, both margin involvement and an elevated mGPS remained independently associated with reduced overall survival. We have prospectively validated the influence of tumor-related and patient-related factors. Margin involvement and the preoperative mGPS were the most important determinants of overall survival in patients undergoing potentially curative pancreaticoduodenectomy. Furthermore, both had independent prognostic value in those patients receiving adjuvant chemotherapy. In the future, this may be considered a stratification factor for entry onto therapeutic trials.

Peripancreatic Fat Invasion Is an Independent Predictor of Poor Outcome Following Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma

BackgroundFollowing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC), identification of peripancreatic fat tumor invasion promotes a tumor to stage T3. We sought to understand better the impact of histological peripancreatic fat invasion on prognosis and site of recurrence in a cohort of patients with PDAC. MethodsWe analyzed the patient demographics, outcome, and recurrence data that had been prospectively collected in 189 consecutive PDAC undergoing potentially curative pancreaticoduodenectomy between 1996 and 2009. Pathological features were reassessed for all patients. Survival outcome was compared using Kaplan–Meier/Cox proportional hazards analysis. The primary site of recurrence was defined as either locoregional or distant metastases. ResultsThe median survival of this PDAC cohort was 18.9 months (95% confidence interval (CI) 15.7–22.2). Histological peripancreatic fat invasion was evident in 51 (27%) patients and was associated with lymph node metastases (p = 0.004) and larger tumor size (p = 0.015). The presence of peripancreatic fat invasion was associated with reduced overall survival following resection (12.4 months [95% CI 9.9–15.0]) when compared to those patients with no evidence of fat invasion (22.6 months [95% CI 18.5–26.7]; p < 0.0001). By multivariate survival analysis, independent predictors of overall survival included tumor grade (p = 0.002), lymph node involvement (p = 0.025), resection margin status (p = 0.003), venous invasion (p = 0.045), and peripancreatic fat invasion (p = 0.007). Invasion into the pancreatic fat was significantly associated with the primary site of recurrence being locoregional failure (p = 0.002). ConclusionsPeripancreatic fat invasion was identified as being an independent predictor of poor outcome following pancreaticoduodenectomy for PDAC. Additionally, the presence of peripancreatic fat invasion was associated with locoregional disease as the primary site of recurrence. This may have implications for the staging of PDAC and potentially require incorporation into future staging systems to improve outcome stratification.

Neoadjuvant docetaxel-based chemoradiation for resectable adenocarcinoma of the pancreas: New neoadjuvant regimen was safe and provided an interesting pathologic response

Purpose To assess the safety and efficacy of a new neoadjuvant chemoradiation (CRT) docetaxel-based regimen in patients with resectable adenocarcinoma of the pancreatic head or body. Patients and methods 34 patients with histologically-confirmed resectable pancreatic adenocarcinoma were included in this prospective two-center phase II study. Radiotherapy was delivered at the dose of 45 Gy in 25 fractions of 1.8 Gy per fractions, 5 days/week, over 5 weeks. Docetaxel was administered as a 1-h intravenous (IV) infusion repeated every week during 5 weeks. The dose was 30 mg/m 2/week. All patients were restaged after completion of CRT. Results Tumor progression was documented in 11 patients (32%), stable disease was documented in 20 patients (59%), and partial remission was documented in 3 patients (9%). 23 patients still with local disease at restaging underwent explorative laparotomy. Of this, 17 patients (50%) had a curative pancreaticoduodenectomy with lymphadenectomy. Morbidity and mortality rates were 29% and 0%, respectively. Three patients (17%) had complete histological responses and 5 patients had minimal residual disease. All resected patients ( n = 17) underwent R0 resection. The median and five-year survival times for the resected patients were 32 months and 41%, respectively. Among the resected patients, ten (59%) died as a result of recurrent pancreatic cancer without local tumor bed recurrence. Conclusions Neoadjuvant docetaxel-based chemoradiation is well-tolerated. Resected patients had a prolonged survival time. Further studies are needed to confirm our findings and determine the role of such a neoadjuvant approach.

Lymph node involvement in ampullary cancer: The importance of the number, ratio, and location of metastatic nodes

Lymph node involvement significantly affects survival of cancer patients. The aim of this study was to evaluate the importance of the number, ratio, and location of metastatic lymph nodes in ampullary cancers. Medical records of 111 patients who underwent curative pancreaticoduodenectomy for ampullary carcinomas were reviewed. Metastatic lymph nodes were found in 52 (47%) patients and the median number of involved nodes was 3 (95% confidence interval (CI) 3-4; range 1-17). In the univariate analysis, gender, type of pancreaticoduodenectomy, depth of tumor invasion, perineural invasion, presence of metastatic nodes, their number, and ratio of metastatic nodes significantly correlated with patient survival. However, the location of metastatic nodes did not influence survival among patients with nodal involvement. Only four or more metastatic nodes (relative risk 7.35, 95% CI 3.34-16.17) and tumor invasion of peripancreatic soft tissues (relative risk 5.00, 95% CI 1.20-20.92) were the independent prognostic factors in the multivariate analysis. The number of metastatic nodes significantly affected patient survival. Although the location and ratio of metastatic nodes were not independent prognostic factors, these variables should be further evaluated with large-scale population data sets.

Long-term complete response of multiple hepatic metastases from carcinoma of the papilla of Vater using intrahepatic infusion of 5-FU with low-dose cisplatin following pancreaticoduodenectomy

Of all distant metastases from carcinoma of the papilla of Vater (CPV), the liver is the most frequent site (more than 60%) and should be specifically targeted in the effort to improve the prognosis. However, the optimal chemotherapy regimen for nonresectable liver metastasis has not been clearly established. In this preliminary report, we note a patient with multiple hepatic metastases from CPV successfully treated using intrahepatic infusion of 5-fluorouracil (FU) with low-dose cisplatin. A 62-year-old woman underwent curative pylorus-preserving pancreaticoduodenectomy for CPV. Four months after surgery, followup computed tomography (CT) demonstrated multiple liver metastases. Weekly intrahepatic arterial infusion chemotherapy of 5-FU, 350 mg/m(2), with low-dose cisplatin (7 mg/m(2)) was started. Ten months after starting chemotherapy, a complete response was obtained. To date, the patient continues to receive this weekly hepatic arterial infusion chemotherapy without any side effects, and she has successfully maintained a long-term complete response for 20 months. The patient remains well and was able to proceed with daily activity at the last follow up 30 months after starting this chemotherapy regimen. This regimen is safe and effective and is recommended as one of the treatment choices for liver metastases from CPV.

Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome

Because autonomous proliferating cancer cells are often exposed to hypoxic conditions, there must be an alternative metabolic pathway, such as autophagy, that allows them to obtain energy when both oxygen and glucose are depleted. We previously reported finding that autophagy actually contributes to cancer cell survival in colorectal cancers both in vitro and in vivo. Pancreatic cancer remains a devastating and poorly understood malignancy, and hypoxia in pancreatic cancers is known to increase their malignant potential. In the present study archival pancreatic cancer tissue was retrieved from 71 cases treated by curative pancreaticoduodenectomy. Autophagy was evaluated by immunohistochemical staining with anti-LC3 antibody, as LC3 is a key component of autophagy and has been used as a marker of autophagy. The results showed that strong LC3 expression in the peripheral area of pancreatic cancer tissue was correlated with a poor outcome (P = 0.0170) and short disease-free period (P = 0.0118). Two of the most significant correlations among the clinicopathological factors tested were found between the peripheral intensity level of LC3 expression and tumor size (P = 0.0098) or tumor necrosis (P = 0.0127). Activated autophagy is associated with pancreatic cancer cells, and autophagy is thought to be a response to factors in the cancer microenvironment, such as hypoxia and poor nutrient supply. This is the first study to report the clinicopathological significance of autophagy in pancreatic cancer.

Preoperative gemcitabine (gem) and bevacizumab (bev)-based chemoradiation for resectable pancreatic adenocarcinoma

4630 Background: Over 80% of pts who undergo potentially curative pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PC) develop local or distant recurrence. Preoperative therapy maximizes...

Preoperative lymphocyte count as a prognostic factor in resected pancreatic ductal adenocarcinoma

Background and aims. Recognized prognostic factors for resected pancreatic ductal adenocarcinoma (PDAC) include tumour size, differentiation, resection margin involvement and lymph node metastases. A further prognostic factor of less certain significance is lymphocyte count. The aim of this study was to investigate whether preoperative lymphocyte count is a prognostic indicator in patients with PDAC. Material and methods. Patients who had undergone a potentially curative pancreaticoduodenectomy (PD) for PDAC between 1998 and 2005 were analysed. Standard prognostic factors, preoperative lymphocyte count, preoperative neutrophil count and survival data were collected. Results. Of the 44 patients studied, univariate analysis identified predictors of a poor survival as lymph node status (node positive (+ve) 10.3 [5.4–20.9] months versus node negative (−ve) 14.2 [10.9–31.4] months; p=0.038), posterior resection margin invasion (margin +ve 7.0 [5.1–15.0] months versus margin −ve 13.1 [10.0–28.3] months; p=0.025) and lymphocyte count below the reference range (<1.5×109/litre 8.8 [7.0–13.1] months versus ≥1.5×109/litre 14.3 [7.0–28.3] months; p=0.029). Low preoperative lymphocyte count (p=0.027) and posterior margin invasion (p=0.023) retained significance on multivariate analysis. Preoperative neutrophil to lymphocyte ratio was not a significant prognostic factor. Conclusion. Preoperative lymphocyte count is a significant prognostic factor in patients with PDAC.