Second-Look Operation for Unresectable Pancreatic Ductal Adenocarcinoma at a High-Volume Center

Background The value of re-exploration for pancreatic ductal adenocarcinoma after the initial diagnosis of unresectability is unclear. Methods In this study, we analyzed 33 patients who were re-explored after an initial diagnosis of unresectability. Results At the time of reoperation, a resectable tumor was found in 18 patients: therefore, 15 pancreaticoduodenectomies, two total pancreatectomies and one left resection were performed with three vascular resections. Morbidity and mortality rates for the cohort were 6/33 and 1/33, without significant differences between resectable and nonresectable patients. Length of stay, duration of operation, and blood loss were significantly increased in the resection group. Kaplan–Meier survival analysis demonstrated increased median survival for resected patients (1078 days after the initial operation versus 547 days in the group of unresectable patients; p = 0.018). Analysis of the reasons against initial resection showed that, if the patients had been sent to a tertiary referral center for pancreatic surgery, a different decision in favor of resection would probably have been made in 14 out of 33 patients. A review of 10 published reports on reoperation for pancreatic cancer revealed results comparable to our study in terms of low morbidity and mortality as well as a survival benefit. Conclusions Reoperation for pancreatic ductal adenocarcinoma that is initially deemed unresectable can be safely performed in a selected group of patients by experienced surgeons, supporting the concept of patient centralization in pancreatic surgery. Resection at the second operation may confer a survival benefit even when the initial findings preclude a potentially curative approach.     

Preoperative Platelet Count and Survival Prognosis in Resected Pancreatic Ductal Adenocarcinoma

BACKGROUND: High platelet counts are associated with an adverse effect on survival in various neoplastic entities. The prognostic relevance of preoperative platelet count in pancreatic cancer has not been clarified. METHODS: We performed a retrospective review of 205 patients with ductal adenocarcinoma who underwent surgical resection between 1990 and 2003. Demographic, surgical, and clinicopathologic variables were collected. A cutoff of 300,000/mul was used to define high platelet count. RESULTS: Of the 205 patients, 56 (27.4%) had a high platelet count, whereas 149 patients (72.6%) comprised the low platelet group. The overall median survival was 17 (2-178) months. The median survival of the high platelet group was 18 (2-137) months, and that of the low platelet group was 15 (2-178) months (p = 0.7). On multivariate analysis, lymph node metastasis, vascular invasion, positive margins, and CA 19-9 > 200 U/ml were all significantly associated with poor survival. CONCLUSIONS: There is no evidence to support preoperative platelet count as either an adverse or favorable prognostic factor in pancreatic ductal adenocarcinoma. Use of 5-year actual survival data confirms that lymph node metastases, positive margins, vascular invasion, and CA 19-9 are predictors of poor survival in resected pancreatic cancer.     

Preoperative Therapy and Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: a 25-Year Single-Institution Experience

Journal of Gastrointestinal Surgery - The purpose of this study was to evaluate a single-institution experience with delivery of preoperative therapy to patients with pancreatic ductal...     

A Pilot Study Evaluating Serum MMP7 as a Preoperative Prognostic Marker for Pancreatic Ductal Adenocarcinoma Patients

Background

Current preoperative risk stratification modalities for pancreatic ductal adenocarcinoma (PDA) patients are inadequate. Elevated serum matrix metalloproteinase 7 (MMP7) is associated with metastatic PDA. We evaluated preoperative MMP7 level as a prognostic marker in patients with resectable PDA.

Methods

From a prospectively maintained database, we identified PDA patients who underwent operation with curative intent from 2004 to 2008 and had serum collected preoperatively. MMP7 was measured by enzyme-linked immunosorbent assay. Patients were defined as having advanced disease if they were found to be unresectable at the time of operation or had nodal involvement on final pathology.

Results

Preoperative serum samples were available for 134 patients. Using a cutoff of 13.5 ng/mL, MMP7 was highly predictive for advanced disease. For patients who underwent R0 resection, MMP7?>?13.5 ng/mL was strongly associated with N1 status, T3/T4 stage, moderate/poor differentiation, and perineural invasion. The median recurrence-free survival was 5.0 months in patients with MMP7?>?13.5 ng/mL versus 9.9 months for patients with lower values (P?=?0.004).

Conclusions

Very elevated serum MMP7 was highly predictive of unresectable disease and nodal involvement despite favorable preoperative cross-sectional imaging. MMP7 should be further evaluated as a biomarker to risk-stratify PDA patients prior to operation.

     

Preoperative Resolution of Jaundice Following Biliary Stenting Predicts More Favourable Early Survival in Resected Pancreatic Ductal Adenocarcinoma

Introduction  Despite the widespread use of endoscopic biliary stenting in patients presenting with potentially resectable pancreatic cancer, there is no general consensus regarding whether this represents a superior management approach over expeditious surgical intervention. The objective of this study was to investigate the influence of preoperative biliary stenting and resolution of jaundice on subsequent postoperative survival following resection for pancreatic cancer. Methods  155 patients undergoing partial pancreatoduodenectomy for pancreatic ductal adenocarcinoma between January 1997 and August 2007 were identified from a prospectively maintained database. Results  There was no survival difference when comparing patients undergoing preoperative biliary drainage (n = 130) with those who did not (n = 25) (log rank, P = 0.981). When analysing individual prognostic factors as continuous variables in univariate Cox analysis, lower albumin levels (P = 0.016), elevated alkaline phosphatase levels (P = 0.011) and elevated CRP levels (P = 0.021) were associated with poorer overall survival. Multivariable Cox regression demonstrated that both albumin (P = 0.008) and CRP (P = 0.038) remained significant independent predictors of overall survival alongside lymph node ratio (P = 0.018). Although preoperative bilirubin levels were not associated with overall survival when analysed as a continuous variable (Cox, P = 0.786), the presence of jaundice (i.e., bilirubin >35 μmol/l) at the time of surgery was a significant adverse predictor of early survival in patients undergoing preoperative biliary drainage (Breslow–Gehan–Wilcoxon, P = 0.013) and remained a significant predictor of early survival when included in a further Cox analysis with censoring of cases who survived beyond 6 months (Cox, P = 0.017). Conclusion  These results suggest that the presence of jaundice at the time of resection has an adverse impact on early, but not overall, postoperative survival in pancreatic cancer patients undergoing preoperative biliary drainage.     

Pancreatic Ductal Adenocarcinoma is Associated with a Distinct Urinary Metabolomic Signature

Background

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis in part due to the lack of early detection and screening methods. Metabolomics provides a means for noninvasive screening of tumor-associated perturbations in cellular metabolism.

Methods

Urine samples of PDAC patients (n = 32), healthy age and gender-matched controls (n = 32), and patients with benign pancreatic conditions (n = 25) were examined using ¹H-NMR spectroscopy. Targeted profiling of spectra permitted quantification of 66 metabolites. Unsupervised (principal component analysis, PCA) and supervised (orthogonal partial-least squares discriminant analysis, OPLS-DA) multivariate pattern recognition techniques were applied to discriminate between sample spectra using SIMCA-P⁺ (version 12, Umetrics, Sweden).

Results

Clear distinction between PDAC and controls was noted when using OPLS-DA. Significant differences in metabolite concentrations between cancers and controls (p < 0.001) were noted. Model parameters for both goodness of fit, and predictive capability were high (R ² = 0.85; Q ² = 0.59, respectively). Internal validation methods were used to confirm model validity. Sensitivity and specificity of the multivariate OPLS-DA model were summarized using a receiver operating characteristics (ROC) curve, with an area under the curve (AUROC) = 0.988, indicating strong predictive power. Preliminary analysis revealed an AUROC = 0.958 for the model of benign pancreatic disease compared with PDAC, and suggest that the cancer-associated metabolomic signature dissipates following RO resection.

Conclusions

Urinary metabolomics detected distinct differences in the metabolic profiles of pancreatic cancer compared with healthy controls and benign pancreatic disease. These preliminary results suggest that metabolomic approaches may facilitate discovery of novel pancreatic cancer biomarkers.

     

Pancreatic Ductal Adenocarcinoma is Associated with a Distinct Urinary Metabolomic Signature

Background

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis in part due to the lack of early detection and screening methods. Metabolomics provides a means for noninvasive screening of tumor-associated perturbations in cellular metabolism.

Methods

Urine samples of PDAC patients (n = 32), healthy age and gender-matched controls (n = 32), and patients with benign pancreatic conditions (n = 25) were examined using ¹H-NMR spectroscopy. Targeted profiling of spectra permitted quantification of 66 metabolites. Unsupervised (principal component analysis, PCA) and supervised (orthogonal partial-least squares discriminant analysis, OPLS-DA) multivariate pattern recognition techniques were applied to discriminate between sample spectra using SIMCA-P⁺ (version 12, Umetrics, Sweden).

Results

Clear distinction between PDAC and controls was noted when using OPLS-DA. Significant differences in metabolite concentrations between cancers and controls (p < 0.001) were noted. Model parameters for both goodness of fit, and predictive capability were high (R ² = 0.85; Q ² = 0.59, respectively). Internal validation methods were used to confirm model validity. Sensitivity and specificity of the multivariate OPLS-DA model were summarized using a receiver operating characteristics (ROC) curve, with an area under the curve (AUROC) = 0.988, indicating strong predictive power. Preliminary analysis revealed an AUROC = 0.958 for the model of benign pancreatic disease compared with PDAC, and suggest that the cancer-associated metabolomic signature dissipates following RO resection.

Conclusions

Urinary metabolomics detected distinct differences in the metabolic profiles of pancreatic cancer compared with healthy controls and benign pancreatic disease. These preliminary results suggest that metabolomic approaches may facilitate discovery of novel pancreatic cancer biomarkers.

     

Preoperative Imaging for Clinical Staging Prior to Radical Cystectomy

The importance of patient selection for quality outcomes following radical cystectomy is critical. Clinical staging is one of the key elements necessary for patient selection, and staging relies on accurate preoperative imaging. Many imaging modalities are available and have been utilized for preoperative staging with published operating characteristics. In this update, we review recently published literature for advances in preoperative imaging prior to radical cystectomy.     

The Prognostic Effect of Clinical Staging in Pancreatic Adenocarcinoma

Background The importance of pancreatic cancer staging is uncertain. The aim of this report was to evaluate the accuracy of combined standard imaging techniques in predicting the pathologic stage and to evaluate the prognostic effect of clinical staging to identify patient groups in which laparoscopy and laparotomy could be beneficial.Methods Fifty-four patients were included in this analysis. The techniques used for clinical staging were endoscopic retrograde cholangiopancreatography, abdominal computed tomographic scan, and ultrasonography. All patients underwent both clinical and surgical/pathologic staging. A comparison was performed between presurgical stage and surgical/pathologic stage. The prognostic effect of different factors on survival was evaluated with both univariate (log-rank) and multivariate (Cox) analysis.Results Sensitivity and specificity for vascular involvement were 73.9% and 96.3%, respectively. Sensitivity and specificity for nodal involvement were 63.6% and 95.4%, respectively. A total of 33.3% of patients showed a higher than expected pathologic stage, and 3.7% showed a lower than expected pathologic stage, by comparing clinical and pathologic evaluation. A highly significant correlation was observed between clinical T stage (P = .0067) and tumor diameter (P = .0037) and patient survival. Maximal prognostic differentiation was observed by dividing patients into two groups based on imaging results: group A (favorable prognosis) and group B (unfavorable prognosis). The median survival was 25.1 and 8.0 months for group A and B, respectively. Five-year survival was 20.1% and 0%, respectively (multivariate analysis: P = .0007).Conclusions Integrated standard imaging studies achieved reasonable diagnostic accuracy in our analysis. A single classification based on clinical stage and tumor diameter evaluated by imaging predicts prognosis in patients with pancreatic carcinoma.     

Health Disparities Impact Expected Treatment of Pancreatic Ductal Adenocarcinoma Nationally

Background and Purpose

National adherence to treatment guidelines for pancreatic ductal adenocarcinoma (PDAC) is a concern. This study aims to evaluate national expected treatment (ET) adherence for all PDAC stages. We hypothesized that both patient and hospital demographics are associated with national ET disparities for PDAC.

Methods

Clinical stage I through IV PDAC patients were evaluated using the National Cancer Data Base from 2004 to 2013. ET was defined as surgery for stage I/II, chemotherapy or radiation for stage III, and chemotherapy for stage IV. Unexpected treatment (UT) was defined as no surgery for stage I/II, surgery for stage III, and radiation or surgery for stage IV. No treatment is denoted by NT.

Results

171,351 patients were identified, of whom 56,589 (33.0%) were stage I/II, 23,459 (13.7%) were stage III, and 91,303 (53.3%) were stage IV. Of patients, 48.4% received ET, 14.7% received UT, and 36.9% received NT. ET rates were 41.1% for stage I/II, 65.4% for stage III, and 48.5% for stage IV patients. On multivariable analysis, older age, non-White race, lower socioeconomic status, being uninsured or Medicaid, increased comorbidities, nonacademic centers, and low-volume hospitals were independent negative predictors of receiving ET (P?<?0.01). On subgroup analysis, high-volume academic centers had similar negative predictors of ET despite higher ET adherence overall (P?<?0.01).

Conclusions

Patient and hospital factors impact ET of PDAC on a national level. These treatment disparities for PDAC are concerning, even at high-volume academic centers. Future studies need to identify the causes of treatment disparities for PDAC with intervention measures aimed to relieve treatment disparities.

     

Surgery for Ductal Adenocarcinoma of the Pancreatic Head: Staging, Complications, and Survival after Regional versus Extended Lymphadenectomy

The purpose of this study was to evaluate the influence of regional versus extended lymphadenectomy on survival after partial pancreaticoduodenectomy for pancreatic cancer. From October 1988 to December 1991 (Department of Surgery, University of Hamburg) and from January 1992 to March 1998 (Department of Surgery, University of Kiel) 72 patients with histologically proven ductal adenocarcinoma of the pancreatic head were treated. Partial pancreaticoduodenectomy with regional lymphadenectomy was performed in 26 patients. In 46 patients lymphadenectomy was expanded to include extended retroperitoneal lymphatic and connective tissue clearance. Comparing these two groups and including only patients with R0 resections (n= 58) no significant differences in long-term survival could be shown. The following parameters were shown to have a significant or nearly significant influence on long-term survival: (1) stage of the disease: The 5-year survival of patients with stage I/II pancreatic head cancer was 63%, compared to 15% in patients with stage III/IV a + b of the disease (p= 0.0087). (2) Grading: The 1-year survival of patients with well or moderately differentiated tumors was 55%, compared to 0% for patients with poorly differentiated ductal adenocarcinoma (p= 0.0022). (3) N stage: The 5-year survival of patients in N0 stage was 46.9%, compared with 15% for N1 stage patients. The difference was not quite significant (p= 0.081). (4) Portal vein involvement: The 1-year survival was 0% in patients with R0 resections and histologically proven tumor infiltration of the portal vein, compared to 63% for patients with curative resections without portal vein involvement (p= 0.0063). In conclusion our data indicate that extensive retroperitoneal tissue clearance during pancreaticoduodenectomy for ductal pancreatic cancer does not improve survival compared to regional lymphadenectomy restricted to the right side of the mesenteric artery.     

Preoperative CA 19-9 and the Yield of Staging Laparoscopy in Patients with Radiographically Resectable Pancreatic Adenocarcinoma

Background  Staging laparoscopy for patients with radiographically resectable pancreatic adenocarcinoma has been reported to yield an 8–15% finding of unresectable disease. Factors associated with the likelihood of subradiographic unresectable disease have not been clearly defined. Methods  A prospectively maintained pancreatic database was reviewed and patients were identified who underwent staging laparoscopy for radiographically resectable pancreatic adenocarcinoma between January 2000 and December 2006. Preoperative carbohydrate antigen 19-9 (CA 19-9) values were assessed for their association with the presence of subradiographic unresectable disease. Results  Four hundred ninety-one patients underwent staging laparoscopy. Resection was performed in 80% (n = 395). Of the 96 patients with unresectable disease, 75 (78%) had metastases either in the liver (n = 60) or peritoneum (n = 15). Preoperative CA 19-9 values were available for 262 of the 491 patients. Fifty-one of these patients had unresectable disease, of which 78% were due to distant disease. The median preoperative CA 19-9 value for patients who underwent resection was 131 U/ml versus 379 U/ml for those patients with unresectable disease (P = 0.003). A receiver operating characteristics (ROC) curve was developed for preoperative CA 19-9 value and tumor resectability. The statistically optimal cutoff value was determined to be 130 U/ml. Unresectable disease was identified in 38 of the 144 patients (26.4%) with a preoperative CA 19-9 ≥ 130 U/ml, and in 13 of the 118 patients (11%) with a CA 19-9 < 130 U/ml (P = 0.003). CA 19-9 values greater than 130 U/ml remained a predictor of tumor unresectability on multivariate regression analysis [hazard ratio (HR) 2.70, 95% confidence interval (CI) 1.34–5.44; P = 0.005]. Conclusion  In this study, preoperative CA 19-9 values were strongly associated with the identification of subradiographic unresectable disease. Preoperative CA 19-9 values may allow surgeons to better select patients for staging laparoscopy.     

Bariatric Surgery: Low Mortality at a High-Volume Center

BACKGROUND: The American Society of Bariatric Surgery has initiated a Bariatric Surgery Center of Excellence Program and the American College of Surgeons has followed with their Bariatric Surgery Center Network Accreditation Program. These programs postulate that concentration of weight loss operations in high-volume centers will decrease surgical mortality and improve outcomes. METHODS: The purpose of this study was to calculate the in-hospital mortality for bariatric operations accomplished at the highest volume bariatric surgery center in the state of New Jersey. After receiving Institutional Revew Board approval, the revised surgical schedule was used to identify all patients undergoing weight loss surgery (WLS) at Hackensack University Medical Center from 1998 through June, 2006. Data for these patients were then harvested from the hospital's electronic medical record. Step-wise and univariate logistic regression analysis tested the impact of various factors on hospital length of stay and in-hospital mortality. RESULTS: Between 1998 and June, 2006, 5,365 patients underwent WLS surgery: 2,099 open vertical banded gastroplasty-Roux en Y gastric bypass (VBG-RYGB); 2,177 laparoscopic Roux en Y gastric bypass (LRYGB); and 1,089 laparoscopic adjustable gastric banding (LAGB). 75.5% of patients were women. Median age was 41 years old (13-79), median weight 128 kg (81.2-290.3), and median body mass index 46.1 kg/m2 (35.0-92.6). Median total operating room time for VBG-RYGB was 115 min (33-328); LRYGB 155 min (53-493), and LAGB 92 min (33-274). Median length of stay for VBG-RYGB was 3 days (1-39 days), LRYGB 2 days (1-46 days), and LAGB 1 day (1-20). Seven patients died in hospital after the 5,365 WLS operations (0.13%): four after VBG-RYGB (0.19%); three after LRYGB (0.14%); and none after LAGB (0%). The characteristics of the patients who died did not significantly differ from the group as a whole. CONCLUSION: Surgeons at Hackensack University Medical Center, a high volume, accredited 1A American College of Surgeons Bariatric Surgery Center, achieved a 0.13% mortality among 5,365 patients undergoing weight loss operations between 1998 and June, 2006. This study supports the concept that high-volume centers perform bariatric operations with low mortalities.     

Short and Long-term Outcomes Among High-Volume vs Low-Volume Esophagectomy Surgeons at a High-Volume Center

Summary of ‘Short and Long-term Outcomes Among High-Volume vs Low-Volume Esophagectomy Surgeons at A High-Volume Center’.

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Prognostic Relevance of Extracapsular Lymph Node Involvement in Pancreatic Ductal Adenocarcinoma

Background  

In several malignancies extracapsular lymph node involvement (ECLNI) identifies a subgroup of patients with worse prognosis but no data are available on its significance in pancreatic ductal adenocarcinoma (PDAC). The aim of our study was to assess the prognostic relevance of ECLNI in resectable PDAC.     

Prognostic Impact of Para-aortic Lymph Node Metastasis in Pancreatic Ductal Adenocarcinoma

Background  

The aim of the present study was to clarify the prognostic impact of para-aortic lymph node metastasis in pancreatic ductal adenocarcinoma.     

Margin Positive Pancreaticoduodenectomy Is Superior to Palliative Bypass in Locally Advanced Pancreatic Ductal Adenocarcinoma

Background

Pancreatic ductal adenocarcinoma is an aggressive disease. Surgical resection with negative margins (R0) offers the only opportunity for cure. Patients who have advanced disease that limits the chance for R0 surgical resection may undergo margin positive (MP) pancreaticoduodenectomy (PD), palliative surgical bypass (PB), celiac plexus neurolysis alone (PX), or neoadjuvant chemoradiation therapy in anticipation of future resection.

Objective

The aim of this study was to determine if there is a difference in the perioperative outcomes and survival patterns between patients who undergo MP PD and those who undergo PB for locally advanced disease in the treatment of pancreatic ductal adenocarcinoma.

Methods

We reviewed our pancreatic surgery database (January 2005–December 2007) to identify all patients who underwent exploration with curative intent of pancreatic ductal adenocarcinoma of the head/neck/uncinate process of the pancreas. Four groups of patients were identified, R0 PD, MP PD, PB, and PX.

Results

We identified 126 patients who underwent PD, PB, or PX. Fifty-six patients underwent R0 PD, 37 patients underwent MP PD, 24 patients underwent a PB procedure, and nine patients underwent PX. In the PB group, 58% underwent gastrojejunostomy (GJ) plus hepaticojejunostomy (HJ), 38% underwent GJ alone, and 4% underwent HJ alone. Of these PB patients, 25% had locally advanced disease and 75% had metastatic disease. All nine patients in the PX group had metastatic disease. The mean age, gender distribution, and preoperative comorbidities were similar between the groups. For the MP PD group, the distribution of positive margins on permanent section was 57% retroperitoneal soft tissue, 19% with more than one positive margin, 11% pancreatic neck, and 8% bile duct. The perioperative complication rates for the respective groups were R0 36%, MP 49%, PB 33%, and PX 22%. The 30-day perioperative mortality rate for the entire cohort was 2%, with all three of these deaths being in the R0 group. The median follow-up for the entire cohort was 14.4 months. Median survival for the respective groups was R0 27.2 months, MP 15.6 months, PB 6.5 months, and PX 5.4 months.

Conclusions

Margin positive pancreaticoduodenectomy in highly selected patients can be performed safely, with low perioperative morbidity and mortality. Further investigation to determine the role of adjuvant treatment and longer-term follow-up are required to assess the durability of survival outcomes for patients undergoing MP PD resection.     

Clinical Significance of Serum COL6A3 in Pancreatic Ductal Adenocarcinoma

Type VI collagen (COL6) forms a microfibrillar network often associated with type I collagen and constitutes a major component of the desmoplastic reaction in pancreatic ductal adenocarcinoma (PDA). We have demonstrated recently that the α3 chain of COL6, COL6A3, is highly expressed in PDA tissue and undergoes tumor-specific alternative splicing. In this study, we investigated the diagnostic value and clinical significance of circulating COL6A3 protein and mRNA in PDA. COL6A3 levels in sera from patients with PDA (n?=?44), benign lesions (n?=?46) and age-matched healthy volunteers (n?=?30) were analyzed by enzyme-linked immunosorbent assays (ELISA). Predictive abilities of COL6A3 were examined using receiver operating characteristic (ROC) curves from logistic regression models for PDA versus normal or benign serum levels. Expression levels were correlated with clinicopathological parameters. Real-time PCR was used to analyze the presence of COL6A3 mRNA containing alternative spliced exons E3, E4, and E6. Circulating COL6A3 protein levels were significantly elevated in PDA patients when compared to healthy sera (p?=?0.0001) and benign lesions (p?=?0.0035). The overall area under the ROC was 0.975. Log(COL6A3) alone provided good discrimination between PDA and benign lesions (area under the curve (AUC)?=?0.817), but combined with CA19-9 provided excellent discrimination (AUC?=?0.904). Interestingly, high COL6A3 serum levels were significantly associated with perineural invasion and cigarette smoking. Combined E3, E4, and E6 serum RNA values provided good sensitivity but low specificity. Our data demonstrate for the first time the potential clinical significance of circulating COL6A3 in the diagnosis of pancreatic malignancy.