Pancreaticoduodenectomy For Pancreatic Ductal Adenocarcinoma Research Articles

Metastatic lymph node ratio as an important prognostic factor in pancreatic ductal adenocarcinoma

BackgroundOverall five year survival following pancreaticoduodenectomy for ductal adenocarcinoma is poor with typical reported rates in the literature of 8–27%. The aim of this study was to identify the histological variables best able to predict long-term survival in these patients. MethodsA prospective database of patients undergoing pancreaticoduodenectomy between April 2002 and June 2009 was analysed to identify patients with histologically proven pancreatic ductal adenocarcinoma. Patients with ampullary tumours, cholangiocarcinoma, duodenal adenocarcinoma and neuroendocrine tumours were excluded. The histology reports for these patients were reviewed. Uni-variate and multi-variate survival analysis was performed to identify variables useful in predicting long-term outcome. Results134 patients underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma during this period. 5 year survival in this series was 18.6%. Uni-variate analysis identified nodal status and the metastatic to resected lymph node ratio as predictors of survival. Using multi-variate Cox Regression analysis a metastatic to lymph node ratio of >15% (p < 0.01) and the presence of perineural invasion (p < 0.05) were identified as independent predictors of patient survival. Metastatic to resected lymph node ratio is better able to stratify prognosis than nodal status alone with 5 year survival of those with N0 disease being 55.6% and 12.9% for N1 disease. However for those with <15% of resected nodes positive, 5 year survival was 21.7% and in those with >15% nodes positive it was 5.2% (p = 0.0017). ConclusionThe metastatic to resected lymph node ratio can provide significant prognostic information in those patients with node positive disease after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

Loss of E-cadherin expression and outcome among patients with resectable pancreatic adenocarcinomas

Only a minority of patients who undergo surgical resection for pancreatic ductal adenocarcinoma are cured. Since patient outcome is not reliably predicted using pathological factors (tumor stage, differentiation, and resection margin status) alone, markers of tumor behavior are needed. One candidate predictor of pancreatic cancer outcome is E-cadherin status. CDH1 is a tumor suppressor gene encoding an important cell adhesion molecule (E-cadherin). The aim of this study was to determine if, among patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, loss of E-cadherin expression was an independent predictor of poor outcome. We examined patterns of loss of E-cadherin by immunohistochemistry in tissue microarrays of 329 surgically resected pancreatic ductal adenocarcinomas. E-cadherin expression was then correlated with outcome. Kaplan–Meier analysis and Cox proportional hazards regression modeling were used to assess the mortality risk. One hundred forty-one pancreatic adenocarcinomas (43%) had partial or complete loss of E-cadherin expression within the analyzed tissue cores. In most instances (134 cases, 41%), this loss was partial. Patients whose pancreatic adenocarcinomas had either complete loss (n=7; median survival, 5.5 months) or partial loss (n=134; 12.7 months) of E-cadherin expression had significantly worse median survival than those with uniformly intact E-cadherin expression (n=188; 18.5 months) by univariate (P=0.002) and multivariate (P=0.006) analyses. In subgroup analysis, patients with poorly differentiated cancers had a worse prognosis if their cancers had partial loss of E-cadherin expression (P=0.02). Among patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, partial loss of tumoral E-cadherin expression is an independent predictor of poor outcome.

Preoperative Neutrophil‐to‐Lymphocyte Ratio (NLR) is Associated with Reduced Disease‐free Survival Following Curative Resection of Pancreatic Adenocarcinoma

Serological proinflammatory markers such as C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been associated with reduced survival for many different types of cancer. This study determined the prognostic value of the preoperative value of these markers in patients with resectable pancreatic adenocarcinoma. Consecutive patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma were entered into our database from 2001 to the present day. CRP, NLR, and PLR at the time of presentation were recorded as well as overall and disease-free survival. Seventy-four patients were identified. Overall median survival was 35.0 months and median disease-free survival was 27.0 months. Follow-up ranged from 1 to 125.8 months. Preoperative NLR was significantly greater in those patients who developed recurrence in the follow-up period (4.5 vs. 3.1). CRP and PLR were not found to differ significantly between the two groups. Kaplan-Meier survival analysis of patients with NLR > 5 demonstrated a disease-free survival of 12 months compared with 52 months for those patients with NLR < 5 (p < 0.001). Preoperative NLR offers important prognostic information regarding disease-free survival following curative resection of pancreatic ductal adenocarcinoma.

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.

Positive mobilization margins alone do not influence survival following pancreatico-duodenectomy for pancreatic ductal adenocarcinoma.

To determine the prognostic influence of residual tumor at or within 1 mm of the mobilization margins (R1Mobilization) compared with transection margins (R1Transection) following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). The prognostic strength of R1 status increases with frequency of margin positivity and is enhanced by protocol driven pathology reporting. Currently, margins are treated uniformly with tumor at or close to any margin considered of equal prognostic significance. The resection involves a mobilization phase freeing the posterior margin and anterior surface then a transection phase requiring lympho-vascular division forming the medial resection and pancreatic transection margin. The comparative assessment of the relative importance of tumor involvement of these different margins has not previously been investigated. Retrospective analysis of 148 consecutive resections for PDAC from 1996-2007 was performed. The individual (pancreatic transection, medial, posterior, and anterior surface) margins were separately identified and analyzed by a senior pathologist. An R1 resection was defined as microscopic evidence of tumor < or = 1 mm from a resection margin. R1Mobilization tumor extension included both R1Anterior and R1Posterior cases; while R1Transection included pancreatic neck/body transection, R1Medial and adjacent transection margins. R1 status was confirmed in 109 patients (74%). The medial (46%) and posterior (44%) margins were most commonly involved. R1 status was found to an independent predictor of poor outcome (P < 0.001). R1Mobilization involvement only (n = 48) was associated with a significantly longer median survival of 18.9 months (95% CI, 13.7-24.8) versus 11.1 months (95% CI, 7.1-15.0) for those with R1Transection tumor involvement (n = 61) (P < 0.001). There was no significant difference in the survival of the R1Mobilization compared with R0 group (P = 0.52). Following pancreaticoduodenectomy for PDAC, involvement of the transection margins in contrast to mobilization margins defines a group whose outcome is significantly worse. This may impact upon the allocation of adjuvant therapy within the setting of randomized controlled trials.

802 Peripancreatic Fat Invasion is an Independent Predictor of Poor Outcome Following Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma and Influences the Pattern of Recurrence

PURPOSE: Rectovaginal fistula (RVF) repair can be challenging. Additionally women may experience sexual dysfunction and psychosocial ramifications even after a successful repair. The aim of this study was to investigate variables looking for predictors of healing/failure and examine long-term quality-of-life (QOL) and sexual function in women with low RVF from obstetrical or cryptogladular etiology. METHODS: From June 1997-2009, 268 women underwent RVF repair. Of those, 100 with obstetric or cryptoglandular etiology agreed to participate in this study. Healing, type of procedure, use of seton or stoma, number of previous procedures, smoking, age, body mass index (BMI), dyspareunia, QOL using SF12, FIQL, IBD-QOL and Female Sexual Function Index was obtained from our prospective database and telephone contact. Fisher's-exact test, chi-square test, and MultivariableLogistic-Regression-Model were used to identify the variables associated with healing/failure. RESULTS: Mean follow-up was 45.8±39.2 months; mean age 42.7 ±10.5 years; and BMI was 28.8±7.6. Sixty (60%) fistulas were obstetric and 40 (40%) cryptoglandular. 68/100 patients (68%) healed. On multivariate analysis, treatment failure was related to a heavier BMI (p=0.001) and number of repairs (p=0.02). Looking at each type of repair, episioproctotomy had significant healing compared to the other choices (but was not significant on multivariate analysis). Forty-seven women were sexually active at follow-up. 12/47 (25.5%) reported dyspareunia. Fecal incontinence was reported preoperatively in 42 women, more often in those with obstetric related-RVF (73% vs. 28% p>0.05). Healing was not affected by age, smoking, co-morbidities, preoperative seton or stoma use. Fecal and sexual function and QOL were comparable between women with healed and unhealed RVF.CONCLUSION: Patients with higher BMI and more repairs had decreased healing rates following RVF repair. Despite surgical outcome, QOL and sexual function were surprisingly similar regardless of fistula healing.

The need for extended intensive care after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma

Pancreaticoduodenectomy (PD) is standard for patients with resectable pancreatic ductal adenocarcinoma (PDAC) in the pancreatic head, neck, and uncinate process, but it is associated with a relatively high morbidity. This study aimed to identify risk factors for extended postoperative intensive care unit (ICU) admission and assess the impact of ICU treatment on patient survival. Between October 2001 and June 2008, patients that underwent PD for PDAC in the pancreatic head were identified from a prospective database. Patients admitted to the ICU after an initial recovery period were compared to those not admitted regarding comorbidities, intraoperative parameters, resection size, and tumor biology. Five hundred and forty patients were included. Of these, 17.8% required extended postoperative ICU admission (immediate, 9.3%; delayed, 7.6%). Immediate ICU admission was most frequently required for increased intraoperative blood loss and fluid management. Delayed ICU treatment was most frequently required for hemorrhage, respiratory insufficiency, or pancreatic fistula. Morbidity and 30-day mortality rates were 54.2% and 2.6%, respectively. ICU admission correlated with significantly lower survival rates compared to no ICU admission (P = 0.0155). Multivariate risk factors for ICU admission included a history of diabetes mellitus and heart failure (NYHA I-III), an intraoperative blood transfusion, and a longer operating time. The need for extended ICU admission is associated with higher in-hospital mortality and reduced long-term outcome. The highest mortality was observed after delayed ICU admission. Preoperative diabetes, heart failure and long operations, and intraoperative blood transfusions substantially increased the risk for ICU requirement.

Pancreaticoduodenectomy of Pancreatic Ductal Adenocarcinoma in the Elderly

PurposePancreatic ductal adenocarcinoma has the highest incidence between the ages of 60 and 70 years. As the elderly population has been increasing in the last several decades, the proportion of patients older than 70 years of age with resectable pancreatic cancer is expected to increase in our society. This retrospective observation was performed to evaluate surgical value of pancreaticoduodenectomy for the elderly patients with pancreatic ductal adenocarcinoma.Materials and MethodsFrom January 1990 to June 2005, among the patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, the elder patients older than 70 years of age were retrospectively reviewed. Perioperative surgical outcomes, including general clinicopathologic features, morbidity, mortality, and survival outcomes, were investigated based on available medical records.ResultsSeventy-seven patients underwent pancreaticoduodenenctomy (PD) for pancreatic ductal adenocarcinoma. Among them, 11 patients (14.3%) were 70 years older. More frequent incidences of morbidity (8 out of 11 vs. 25 out of 65, p = 0.049), especially delayed gastric emptying (3 out of 8 vs. 3 out of 66, p = 0.035), were observed and overall length of hospital stay was also longer in the elderly (49.2 ± 13.9 days vs. 36.1 ± 13.2, p = 0.012). However, no significant differences in mortality rate and survival outcomes were noted when comparing with those of the younger patients (p > 0.05).ConclusionWe agree with the opinion that age factor can not be absolute contraindication for pancreaticoduodenectomy, however, appropriate preoperative evaluations, proper patient selection considering life expectancy, advanced surgical techniques and detailed perioperative management are mandatory to guarantee the safety of pancreaticoduodenectomy performed in the elderly with pancreatic ductal adenocarcinoma.