Clinical and Pathologic Features Influencing Survival in Patients Undergoing Pancreaticoduodenectomy for Pancreatic Adenocarcinoma

Objective

The aim of the study was to determine the clinicopathological features that influence survival in patients with resected pancreatic ductal adenocarcinoma (PDA).

Methods

The study used a single institution retrospective review of patients undergoing pancreaticoduodenectomy (PD) for PDA from 1993 to 2010.

Results

Two hundred forty-six consecutive cases of resected PDA were identified: 128 males (52 %), median age 68 years. Median hospital length of stay was 8 days and 30-day mortality rate was 2.4 %. There were 101 (41.1 %) postoperative complications, 77 % of which were Dindo–Clavien Grade 3 or less. Overall survival was 85, 63, 25, and 15 % at 6 months, 1 year, 3 years, and 5 years, respectively, with a median survival of 17 months. Multivariate Cox proportional hazard modeling demonstrated lymph node ratio was negatively correlated with survival at all time points. Preoperative hypertension was a poor prognostic factor at 6 months, 3 years, and 5 years. The absence of postoperative complications was protective at 6 months whereas pancreatic leaks were associated with worse survival at 6 months. Abdominal pain on presentation, operative time, and estimated blood loss were also associated with decreased survival at various time points.

Conclusion

The strongest prognostic variable for short- and long-term survival after PD for PDA is lymph node ratio. Short-term survival is influenced by the postoperative course.     

Decreased Skeletal Muscle Volume Is a Predictive Factor for Poorer Survival in Patients Undergoing Surgical Resection for Pancreatic Ductal Adenocarcinoma

Background

The aim of this study was to investigate the impact of decreased skeletal muscle (SM) volume on survival outcomes in patients undergoing surgical resection for pancreatic ductal adenocarcinoma (PDAC).

Methods

Between March 2000 and February 2015, 323 patients who underwent upfront surgical resection for PDAC were identified from the Mayo Clinic SPORE in Pancreatic Cancer. Body composition data, including SM area, subcutaneous adipose tissue area, and visceral adipose tissue area were calculated using an abdominal computed tomography (CT) image at the third lumbar spinal level. The body composition data were normalized by patients’ height (e.g., SM index, cm²/m²) and analyzed as continuous variables. Clinicopathological findings and body composition data at initial diagnosis were evaluated for association with overall survival and recurrence-free survival.

Results

Because the median SM index was significantly different between males vs. females (49.9 cm²/m² [range, 32.0–70.3] vs. 39.4 cm²/m² [range, 29.2–66.2], P?<?0.001), it was standardized for each sex and used for further analyses. Parameters independently associated with a shorter overall survival were a larger tumor size (P?=?0.007), a greater tumor extent (P?=?0.037), a higher carbohydrate antigen 19–9 level (P?<?0.001), and a smaller sex-standardized SM index (P?=?0.011). Parameters independently associated with a shorter recurrence-free survival were female sex (P?=?0.029), a larger tumor size (P?<?0.001), a higher carbohydrate antigen 19–9 level (P?=?0.001), and a smaller sex-standardized SM index (P?=?0.007).

Conclusions

A smaller sex-standardized SM index is a predictive factor for shorter overall and recurrence-free survival in PDAC patients undergoing surgery.

     

Effects of Perioperative Red Blood Cell Transfusion on Disease Recurrence and Survival After Pancreaticoduodenectomy for Ductal Adenocarcinoma

Background

The premise that allogeneic red blood cell transfusion (RBCT) contributes to adverse oncologic outcomes after surgery remains controversial. We examined the effects of RBCT during and after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) on disease recurrence and survival.

Methods

A prospective database of 220 patients undergoing PD for PDAC from 2000 to 2008 was reviewed and transfusion data collected. Univariate and multivariate analyses were performed for factors influencing RBCT, recurrence-free survival (RFS), and overall survival (OS). The effect of amount and timing (intraoperative vs. postoperative) of RBCT was analyzed.

Results

One hundred forty-seven patients (67%) received RBCT: 70 (32%) received 1 to 2 units, and 77 (35%) received >2 units. Median RFS and OS for the entire cohort was 12 and 16 months, respectively. RBCT of >2 units was associated with reduced RFS (9 vs. 15 months; P = 0.033) and OS (14 vs. 20 months; P = 0.003). Stratified by timing of transfusion, postoperative RBCT was associated with shortened RFS and OS. Controlling for age, body mass index, comorbidities, tumor factors, and major complications, each incremental unit of postoperative RBCT was associated with reduced RFS (hazard ratio 1.10, 95% confidence interval 1.02–1.18) and OS (hazard ratio 1.08, 95% confidence interval 1.03–1.12). Low hemoglobin and presence of comorbidities were the only preoperative factors independently associated with RBCT.

Conclusions

Allogeneic red blood cell transfusion after PD for PDAC is independently associated with earlier cancer recurrence and reduced survival, in particular when administered postoperatively and in larger quantities. Blood-conservation methods are especially indicated for patients with preoperative anemia and medical comorbidities.     

Metformin Use Is Associated with Improved Survival in Patients Undergoing Resection for Pancreatic Cancer

Preclinical evidence has demonstrated anti-tumorigenic effects of metformin. The effects of metformin following pancreatic cancer, however, remain undefined. We sought to assess the association between metformin use and survival using a large, nationally representative sample of patients undergoing surgery for pancreatic cancer. Patients undergoing a pancreatic resection between January 01, 2010, and December 31, 2012, were identified using the Truven Health MarketScan database. Clinical data, including history of metformin use, as well as operative details and information on long-term outcomes were collected. Multivariable Cox proportional hazards regression analysis was performed to assess the effect of metformin use on overall survival (OS). A total of 3393 patients were identified. The mean age of patients was 54.2 years (SD?=?9.1 years). Roughly one half of patients were female (n?=?1735, 51.1 %); 49.1 % (n?=?1665) presented with a Charlson comorbidity index of 3 or greater (CCI ≥3); and 19.6 % (n?=?664) had diabetes. At the time of surgery, 60.0 % (n?=?2034) of patients underwent a pancreaticoduodenectomy, 35.7 % (n?=?1212) a partial/distal pancreatectomy, while 4.3 % (n?=?147) had a total pancreatectomy. On pathology, 1057 (31.2 %) had lymph node metastasis. Metformin use was identified in 456 patients (13.4 %) and was more commonly administered among patients without locally advanced disease (14.3 vs. 11.6 %, p?=?0.038). While OS was comparable between patients within the first year of surgery (OS at 1 year 65.4 % [95 % confidence interval (CI) 63.4–67.3 %] vs. 69.2 % [95 % CI 64.2–73.4 %]), patients who received metformin demonstrated an improved OS beginning at 18 months following surgery. On multivariable analysis adjusting for patient and clinicopathologic characteristics, metformin use was independently associated with a decreased risk of mortality (hazard ratio [HR]?=?0.79, 95 % CI 0.67–0.93, p?=?0.005). Metformin use was associated with an improved overall survival among patients undergoing pancreatic surgery for pancreatic cancer. Further work is necessary to better understand its role in modifying cancer-specific and overall health outcomes.     

Osteopontin Expression is Associated with Improved Survival in Patients with Pancreatic Adenocarcinoma

Background

Osteopontin (OPN) is a secreted protein of the extracellular matrix. It has been used as a marker for tumor aggressiveness and correlated with clinical outcomes in several solid tumors, such as liver, lung, and breast. We determined the OPN expression and its influence on survival in patients with resected pancreatic adenocarcinoma.

Methods

Tissue microarrays were constructed from 245 resected pancreatic adenocarcinomas. Immunohistochemical staining for OPN was undertaken and compared to normal pancreas (n?=?12). OPN expression was then correlated with patient demographics, tumor size, grade, node, and margin status. Survival curves were created by the Kaplan?CMeier method and compared by log rank analysis.

Results

In total, 181 (74?%) of pancreatic adenocarcinoma tissues expressed OPN compared to 7 (58?%) of normal controls (p?=?0.004). Expression was observed predominantly in the cytoplasm of the tumor cells. The median and 2?year overall survival was longer when OPN was expressed (17.1 vs. 11.6?months, and 38 vs. 24?%, respectively, p?=?0.04). Multivariate analysis showed OPN expression and T stage to be independent predictors of overall survival, while other histopathologic factors such as tumor grade, tumor size, and nodal status were not.

Conclusions

These results suggest that the presence of OPN expression in pancreatic adenocarcinoma may have a protective effect independent of tumor stage. This emphasizes the importance of the interaction between pancreatic cancer cells and their stromal elements.     

Perioperative Care with Fast-Track Management in Patients Undergoing Pancreaticoduodenectomy

Background

It has been considered that allowing patients to return to daily life earlier after surgery helps recovery of physiological function and reduces postoperative complications and hospital stay. We investigated the usefulness of fast-track management in perioperative care of patients undergoing pancreaticoduodenectomy (PD).

Methods

Patients (n = 90) who received conventional perioperative management from 2005 to 2009 were included as the ‘conventional group’ (historical control group), and patients who received perioperative care with fast-track management (n = 100) from 2010 to March 2013 were included as the ‘fast-track group’. To evaluate the efficacy of perioperative care with fast-track management, the incidence of postoperative complications and the length of hospital stay were compared between the two groups (comparative study). For statistical analysis, univariate analysis was performed using the χ ² test or Fisher’s exact test.

Results

There was no significant difference between the two groups in sex, mean age, presence/absence of diabetes mellitus, preoperative drainage for jaundice, previous disease, operative procedure, mean duration of operation, or blood loss (p < 0.01). The incidence of surgical site infection in the conventional group and fast-track group was 28.9 and 14.0 %, respectively, with a significant difference between the two groups (p = 0.019). In addition, the incidence of pancreatic fistula (grade B, C) significantly differed between the two groups (27.8 % in the conventional group, 9.0 % in the fast-track group; p = 0.001). The mean postoperative hospital stay was 36.3 days in the conventional group and 21.9 days in the fast-track group (p < 0.001).

Conclusions

Perioperative care with fast-track management may reduce postoperative complications and decrease the length of hospital stay in patients undergoing PD.     

Zinc Deficiency in Patients Undergoing Pancreatoduodenectomy for Periampullary Tumors Is Associated with Pancreatic Exocrine Insufficiency

Background and purpose  

The present study was done to investigate the prevalence of zinc deficiency after pancreatoduodenectomy (PD) and its correlation with pancreatic exocrine insufficiency.     

Adverse Tumor Biology Associated with Mesenterico-Portal Vein Resection Influences Survival in Patients with Pancreatic Ductal Adenocarcinoma

Background

Although pancreatoduodenectomy (PD) with mesenterico-portal vein resection (VR) can be performed safely in patients with resectable pancreatic ductal adenocarcinoma (PDAC), the impact of this approach on long-term survival is controversial.

Patients and Methods

Analyses of a prospectively collected database revealed 122 consecutive patients with PDAC who underwent PD with (PD+VR) or without (PD?VR) VR between January 2004 and May 2012. Clinical data, operative results, and survival outcomes were analysed.

Results

Sixty-four (53 %) patients underwent PD+VR. The majority (84 %) of the venous reconstructions were performed with a primary end-to-end anastomosis. Demographic and postoperative outcomes were similar between the two groups. American Society of Anesthesiologists (ASA) score, duration of operation, intraoperative blood loss, and blood transfusion requirement were significantly greater in the PD+VR group compared with the PD?VR group. Furthermore, the tumor size was larger, and the rates of periuncinate neural invasion and positive resection margin were higher in the PD+VR group compared with the PD?VR group. Histological venous involvement occurred in 47 of 62 (76 %) patients in the PD+VR group. At a median follow-up of 29 months, the median overall survival (OS) was 18 months for the PD+VR group, and 31 months for the PD?VR group (p = 0.016). ASA score, lymph node metastasis, neurovascular invasion, and tumor differentiation were predictive of survival. The need for VR in itself was not prognostic of survival.

Conclusions

PD with VR has similar morbidity but worse OS compared with a PD?VR. Although VR is not predictive of survival, tumors requiring a PD+VR have more adverse biological features.     

Splenic Vein Thrombosis Is Associated with an Increase in Pancreas-Specific Complications and Reduced Survival in Patients Undergoing Distal Pancreatectomy for Pancreatic Exocrine Cancer

Distal pancreatectomy and splenectomy (DPS) is the procedure of choice for the surgical treatment of pancreatic exocrine cancer localized to the body and tail of the pancreas. Splenic vein thrombosis (SVT) can occur in patients with malignant pancreatic exocrine tumors secondary to direct tumor invasion or compression of the splenic vein by mass effect. This study examines the effect of preoperative SVT on postoperative outcomes. In this retrospective cohort study, we queried our pancreatic surgery database to identify patients who underwent DPS from October 2005 to June 2011. These cases were evaluated for evidence of preoperative SVT on clinical records and cross-sectional imaging (CT, MRI, endoscopic US). Outcomes for patients with and without SVT were compared. From an overall cohort of 285 consecutive patients who underwent DPS during the study period, data were evaluated for 70 subjects who underwent surgery for pancreatic exocrine cancer (27 with SVT, 43 without SVT). The preoperative demographics and co-morbidities were similar between the groups, except the average age was higher for those without SVT (p?<?0.05). The median estimated blood loss was significantly higher in the SVT group (675 versus 250 ml, p?=?<0.001). While the overall morbidity rates were similar between the two groups (48 % SVT versus 56 % no SVT, p?=?NS), the group with SVT had a significantly higher rate of pancreas-specific complications, including pancreatic fistula (33 versus 7 %, p?<?0.01) and delayed gastric emptying (15 versus 0 %, p?<?0.02). Hospital readmission rates were similar between the groups (30 versus 28 %, p?=?NS). Patients without SVT had a trend toward longer median survival (40 versus 20.8 months), although the difference was not statistically significant (p?=?0.1). DPS for pancreatic ductal adenocarcinoma can be performed safely in patients with SVT, but with higher intraoperative blood loss, increased pancreas-specific complications, and a trend towards lower long-term survival rates. This paper was presented as a poster at the 53rd annual meeting of the Society for Surgery of the Alimentary Tract and at the 46th annual meeting of the Pancreas Club, San Diego, CA, May 2012.     

Positive Bone Marrow Biopsy Is Associated with a Decreased Disease-Free Survival in Patients with Operable Breast Cancer

Background  

Bone marrow (BM) biopsy has been suggested as an independent prognostic factor in patients with breast cancer.     

Impact of Obesity on Perioperative Outcomes and Survival Following Pancreaticoduodenectomy for Pancreatic Cancer: A Large Single-Institution Study

Background

To examine the effect of body mass index (BMI) on clinicopathologic factors and long-term survival in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma.

Methods

Data on BMI, weight loss, operative details, surgical pathology, and long-term survival were collected on 795 patients who underwent pancreaticoduodenectomy. Patients were categorized as obese (BMI?>?30 kg/m²), overweight (BMI 25 to <30 kg/m²), or normal weight (BMI?<?25 kg/m²) and compared using univariate and multivariate analyses.

Results

At the time of surgery, 14% of patients were obese, 33% overweight, and 53% normal weight. Overall, 32% of patients had preoperative weight loss of >10%. There were no differences in operative times among the groups; however, higher BMI was associated with increased risk of blood loss (P?<?0.001) and pancreatic fistula (P?=?0.01). On pathologic analysis, BMI was not associated with tumor stage or number of lymph nodes harvested (both P?>?0.05). Higher BMI patients had a lower incidence of a positive retroperitoneal/uncinate margin versus normal weight patients (P?=?0.03). Perioperative morbidity and mortality were similar among the groups. Obese and overweight patients had better 5-year survival (22% and 22%, respectively) versus normal weight patients (15%; P?=?0.02). After adjusting for other prognostic factors, as well as preoperative weight loss, higher BMI remained independently associated with improved cancer-specific survival (overweight: hazard ratio, 0.68; obese: hazard ratio, 0.72; both P?<?0.05).

Conclusion

Obese patients had similar tumor-specific characteristics, as well as perioperative outcomes, compared with normal weight patients. However, obese patients undergoing pancreaticoduodenectomy for pancreatic cancer had an improved long-term survival independent of known clinicopathologic factors.     

Impact of Obesity and Body Fat Distribution on Survival After Pancreaticoduodenectomy for Pancreatic Adenocarcinoma

Background

Epidemiologic studies have reported a positive correlation between body mass index (BMI) and pancreatic cancer risk, but clinical relevance of obesity and/or body fat distribution on tumor characteristics and cancer-related outcome remain controversial. We sought to assess the influence of obesity and body fat distribution on pathologic characteristics and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma.

Methods

Demographic and biometric data were collected on 328 patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. In a subset of patients, pancreatic fatty infiltration and fibrosis were assessed pathologically, and visceral fat area (VFA) was evaluated. Influence of BMI and body fat distribution on tumor characteristics and survival were evaluated.

Results

A significant positive correlation between BMI and VFA was observed, with a wide range of VFA value within each BMI class. According to BMI or VFA distribution, there were no significant differences in patient characteristics, intraoperative or perioperative outcome, or pathologic characteristics, with the exception of significantly higher blood loss in patients with an increased body weight or VFA. Unadjusted overall and disease-free survival between BMI class and VFA quartile were not significantly different.

Conclusions

In this study, obesity and body fat distribution were not correlated with specific tumor characteristics or cancer-related outcome.     

Tumor Infiltration in the Medial Resection Margin Predicts Survival After Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma

Background

Microscopic tumor involvement (R1) in different surgical resection margins after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) has been debated.

Methods

Clinico-pathological data for 258 patients who underwent PD between 2001 and 2010 were retrieved from a prospective database. The rates of R1 resection in the circumferential resection margin (pancreatic transection, medial, posterior, and anterior surfaces) and their prognostic influence on survival were assessed.

Results

For PDAC, the R1 rate was 57.1?% (48/84) for any margin, 31.0?% (26/84) for anterior surface, 42.9?% (36/84) for posterior surface, 29.8?% (25/84) for medial margin, and 7.1?% (3/84) for pancreatic transection margin. Overall and disease-free survival for R1 resections were significantly worse than those for R0 resection (17.2 vs. 28.7?months, P?=?0.007 and 12.3 vs. 21.0?months, P?=?0.019, respectively). For individual margins, only medial positivity had a significant impact on survival (13.8 vs. 28.0?months, P?<?0.001), as opposed to involvement in the anterior (19.7 vs. 23.3?months, P?=?0.187) or posterior margin (17.5 vs. 24.2?months, P?=?0.104). Multivariate analysis demonstrated R0 medial margin was an independent prognostic factor (P?=?0.002, HR?=?0.381; 95?% CI 0.207?C0.701).

Conclusion

The medial surgical resection margin is the most important after PD for PDAC, and an R1 resection here predicts poor survival.     

Perioperative Blood Transfusion as a Prognostic Indicator in Patients with Hepatocellular Carcinoma

We studied the relation of perioperative blood transfusion and the outcomes in 175 patients with hepatocellular carcinoma (HCC) who underwent hepatic resection from 1986 to 1994 in our hospital. Hepatectomy was performed in 23 (13.1%) patients with and 152 (86.9%) without blood transfusions. The cumulative cancer-free survival rates for patients who had received blood transfusion was significantly lower than that for patients who had not received blood transfusions (p= 0.003). Further examinations revealed a significant difference in cancer-free survival rates for stage I–II patients (n= 75) of HCC (p= 0.02) but not for stage III–IV patients (n= 56) (p= 0.06). Cox regression analysis for recurrence revealed that blood transfusion was the most significant prognostic indicator (p= 0.001) for recurrence in stage I–II patients but not in stage III–IV patients (p= 0.99). These results suggest that a perioperative blood transfusion may be a significant prognostic indicator for patients with HCC who had underwent hepatectomy, especially in stage I–II patients of HCC.     

Resolution of Diabetes After Pancreaticoduodenectomy in Patients with and without Pancreatic Ductal Cell Adenocarcinoma

Background

New-onset diabetes mellitus (DM) is associated with pancreatic ductal cell adenocarcinoma (PDCA) and can resolve after pancreaticoduodenectomy (PD). Whether DM also resolves after PD in patients operated for disease other than PDCA remains to be determined.

Methods

We compared glycemic status before and after PD between patients with and without PDCA by review of a prospectively maintained database including all patients receiving PD from 2005 to 2011. New-onset DM was defined as diagnosis of DM less than 24 months before PD, and cases with DM diagnosis ≥24 months preceding PD were described as long-standing DM.

Results

Of 458 patients receiving PD, there were 146 (31.9 %) PDCA and 312 (68.1 %) non-PDCA, including 160 benign diseases, 113 ampulla cancer, 29 distal common bile duct cancer, and 10 duodenal cancer. Overall prevalence of DM was higher in PDCA group than non-PDCA group (37.7 vs. 25.6 %; P = 0.011). Resolution of new-onset DM after PD was observed in 9 (41 %) of 22 patients with PDCA and in 12 (63 %) of 19 patients without PDCA. Resolution of long-standing DM after PD was also observed in 3 (9.1 %) of 33 patients with PDCA and in 6 (9.8 %) of 61 patients without PDCA.

Conclusions

DM resolved after PD in some patients both with and without PDCA. These findings suggest that PD-associated anatomic change may play a role in resolution of DM after PD.     

Surgical Apgar Score Predicts Perioperative Morbidity in Patients Undergoing Pancreaticoduodenectomy at a High-Volume Center

Objectives  

Pancreaticoduodenectomy (PD) remains a procedure that carries considerable morbidity. Numerous studies have evaluated factors to predict patients at risk. The aim of this study was to determine whether the surgical Apgar score (SAS) predicts perioperative morbidity and mortality.