Faculty Bibliography

BACKGROUND:Accurate assessment of complications is critical in analysing surgical outcomes. The post-operative morbidity index (PMI), derived from the Modified Accordion Severity Grading System and American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), is a quantitative measure of post-operative morbidity. This study utilizes PMI to establish the complication burden for a distal pancreatectomy (DP). METHODS:From 2005-2011, nine centres contributed ACS-NSQIP complication data for 655 DPs. Each complication was assigned an Accordion severity weight ranging from 0.11 for grade 1 to 1.00 for grade 6 (death). The PMI is the sum of complication severity weights divided by the total number of patients. RESULTS:ACS-NSQIP complications occurred in 177 patients (27.0%). The non risk-adjusted PMI for DP is 0.087. Bleeding/Transfusion and Organ Space Infection were the most common complications. Frequency and burden differed across Accordion grades. While grade 4-6 complications represented only 15.4% of complication occurrences, they accounted for 30.4% of the burden. Subgroup analysis demonstrates that the PMI did not vary based on laparoscopic versus open approach or the performance of a splenectomy. DISCUSSION/CONCLUSIONS:This study uses two validated systems to quantitatively establish the morbidity of a DP. The PMI allows estimation of both the frequency and severity of complications and thus provides a more comprehensive assessment of risk.

OBJECTIVE:Evaluation of the imaging features of pathology-proven acinar cell carcinomas (ACCs) of the pancreas using computed tomography (CT). METHODS:We reviewed the CT features, clinical presentations, and clinical outcomes of 15 patients (9 men, 6 women, mean age 62.3) with pathology-proven pancreatic ACCs. An abdominal radiologist retrospectively evaluated each patient's initial imaging study with respect to the lesion's size, location, attenuation (Hounsfield units) on arterial and venous phase images, peripancreatic lymphadenopathy, and distant metastases. Additional parameters studied included biliary and pancreatic ductal dilatation, intratumoral hemorrhage, calcification, the presence of cystic/necrotic components, and whether the tumor was intraparenchymal or exophytic. RESULTS:The ACCs in this series were evenly distributed between the head/uncinate and the tail, were predominantly exophytic (73%), tended to be large (average size 5.1 cm), and were mostly hypodense to the surrounding pancreas on both the arterial and venous phase images. A sizeable proportion demonstrated a cystic or necrotic component (53%) and/or an enhancing capsule (53%). Of those lesions in the head or uncinate process, very few resulted in pancreatic (28%) or biliary (14%) ductal dilatation. None of the lesions in this series showed internal calcification or intratumoral hemorrhage. CONCLUSION/CONCLUSIONS:While a prospective diagnosis is difficult, ACCs have several features which can differentiate them from ductal adenocarcinoma, including their large size, lack of biliary or pancreatic ductal dilatation, exophytic nature, and the presence of an enhancing capsule.

PURPOSE/OBJECTIVE:To facilitate a better understanding of incidentally noted cystic pancreatic lesions, since these lesions often pose a challenge regarding appropriate management. METHODS:This article reviews pathophysiology, prevalence, significance, and recommendations for management of the various pancreatic cystic lesions. Illustrative cases are demonstrated. RESULTS:Diagnostic benign lesions can be left alone. Cross-sectional imaging can be used to follow-up benign appearing lesions and to stage more aggressive ones. Endoscopic ultrasound with fine needle aspiration and cyst fluid analysis can be performed on certain indeterminate lesions. Lesions with high malignant potential should undergo resection. CONCLUSIONS:A better understanding of the variety of incidentally detected pancreatic cystic lesions can help direct appropriate management.

BACKGROUND:The median age of pancreatic ductal adenocarcinoma (PDAC) patients is 71 years. PDAC rarely affects individuals under the age of 45. We investigated features of PDAC occurring in young patients (≤45 years) who underwent surgical resection in order to determine if any difference exists in comparison to elderly patients (≥70 years). METHODS:A retrospective analysis of patients with PDAC who were ≤ 45 years on the date of surgery between 1975 and 2009 was performed. This cohort was compared with PDAC patients whose ages were over 70 years on the date of surgery over the same time interval. Information reviewed included demographics, Charlson Age-Comorbidity Index (CACI), pathological staging, surgical management, and death or last follow-up. RESULTS:Seventy five patients with PDAC of age ≤ 45 years at surgery were identified. The reference group consisted of 870 patients with a median age of 75. The most common symptoms of young patients were jaundice (45 %), abdominal pain (32 %), or weight loss (33 %). This did not differ significantly from older patients. Among the younger patients, 7 (9 %) underwent total pancreatectomy, 60 (80 %) underwent pancreaticoduodenectomy, and 8 (11 %) had distal pancreatectomy. The distribution of type of surgery was similar between two groups. Fifty-two of the young patients (69 %) had an R0 resection and this did not differ from the older age group (n = 616; 71 %). The rate of lymph node positivity was 68 % for younger patients and 74 % for older patients (p = 0.27). Of the younger patients, 11, 13, 49, and 2 were classified as stage I, IIA, IIB, and III, respectively, and did not differ from the older age group. The median overall survival for the young patients cohort was 19 months (95 % CI 15-22 months) which is longer than 16 months (95 % CI 14-17 months) of the older group (p = 0.007). The actual 5- and 10- year survival in young age group (24 and 17 %) was longer than that in old age group (11 and 3 %) (p < 0.05). The median CACI of the younger patients was 0.5 and was lower than 4.1 of the older patients (p < 0.0001). CONCLUSIONS:The demographic, pathologic, and treatment characteristics of PDAC patients younger than 45 years were similar to those older than 70 years. Younger patients had fewer complications after curative resections. The better survival among younger patients is likely related to fewer comorbidities in this group. These findings will be useful in counseling young patients with resectable pancreatic cancer.

BACKGROUND AND AIMS/OBJECTIVE:Endoscopic placement of enteral self-expandable metallic stents is an alternative to surgical gastrojejunostomy (GJ) for palliation of malignant gastric outlet obstruction (GOO). Factors associated with clinical outcomes are not known. The aims of this study are to compare the overall complication rate and effectiveness (duration of oral intake) between endoscopic stenting (ES) and GJ in patients with GOO and identify predictors of clinical outcomes. PATIENTS AND METHODS/METHODS:This was a retrospective cohort study at a single tertiary academic center. Patients who underwent ES or GJ for treatment of GOO between 1/2001 and 12/2010 were identified using an institutional claims database. The electronic medical records for each patient were reviewed. Univariate and multivariate logistic regression analyses were performed to study the association of treatment outcomes with patient factors and cancer therapy. RESULTS:120 patients had ES while 227 had GJ. Technical success was higher for GJ (99 vs. 96 %, p = 0.004). Complication rates were higher in the GJ group (22.10 vs. 11.66 %, p = 0.02). Reintervention was more common with ES [adjusted odds ratio (OR) 9.18, p < 0.0001]. Mean length of hospital stay (LOHS) was shorter (adjusted p = 0.005) in the ES compared with the GJ group. However, mean hospital charges, including reinterventions, were greater in the ES group (US $34,250 vs. US $27,599, p = 0.03). ES and GJ had comparable reintervention-free time in patients who had reintervention (88 vs. 106 days, respectively, p = 0.79). Chemotherapy [adjusted hazard ratio (HR) 3 > 0.57, p = 0.04] and radiation therapy (adjusted HR 0.35, p = 0.03) were associated with significantly longer duration of oral intake after ES or GJ. CONCLUSION/CONCLUSIONS:ES is associated with fewer complications, shorter LOHS, but higher reintervention rates and overall charges.

OBJECTIVE:We sought to quantify the use of and analyze factors predictive of receipt of surgical therapy for early hepatocellular carcinoma (HCC). BACKGROUND:The incidence of HCC is increasing, and the options for surgical therapy for early HCC have expanded, but the use of surgical therapy for early HCC has not been examined in a modern cohort. METHODS:A retrospective cohort study was performed using data from the 1998-2007 Surveillance, Epidemiology, and End Results-Medicare linked database. Data were analyzed for patients 66 years of age and older with early HCC (tumors ≤5 cm without metastatic disease, nodal metastasis, extrahepatic extension, or major vascular invasion). Both Surveillance, Epidemiology, and End Results and Medicare data were used to ascertain receipt of therapy as well as comorbidity burden and other patient and hospital variables. Multivariable logistic regression models were used to analyze factors associated with receipt of therapy. RESULTS:Our selection criteria identified 1745 patients for this study. Most patients had tumors between 2 and 5 cm in size (n = 1440, 83%). Solitary tumors (n = 1121, 64%) were more common than multiple tumors (n = 624, 36%). A total of 820 patients (47%) with early HCC received no surgical therapy. Among 741 patients with solitary, unilobar tumors and microscopic confirmation of HCC, 246 (33%) received no surgical therapy. Of 535 patients with no liver-related comorbidities, 273 (51%) did not receive surgical therapy. In multivariable analysis, patient age, income, tumor factors, liver-related comorbidities, and hospital factors were associated with receipt of surgical therapy. CONCLUSIONS:Although some patients with early HCC may not be candidates for surgical therapy, these data suggest that there is a significant missed opportunity to improve survival of patients with early HCC through the use of surgical therapy.

CONTEXT/BACKGROUND: Of the 200 million adults worldwide who undergo noncardiac surgery each year, more than 1 million will die within 30 days. OBJECTIVE:To determine the relationship between the peak fourth-generation troponin T (TnT) measurement in the first 3 days after noncardiac surgery and 30-day mortality. DESIGN, SETTING, AND PARTICIPANTS/METHODS: A prospective, international cohort study that enrolled patients from August 6, 2007, to January 11, 2011. Eligible patients were aged 45 years and older and required at least an overnight hospital admission after having noncardiac surgery. MAIN OUTCOME MEASURES/METHODS: Patients' TnT levels were measured 6 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We undertook Cox regression analysis in which the dependent variable was mortality until 30 days after surgery, and the independent variables included 24 preoperative variables. We repeated this analysis, adding the peak TnT measurement during the first 3 postoperative days as an independent variable and used a minimum P value approach to determine if there were TnT thresholds that independently altered patients' risk of death. RESULTS: A total of 15 133 patients were included in this study. The 30-day mortality rate was 1.9% (95% CI, 1.7%-2.1%). Multivariable analysis demonstrated that peak TnT values of at least 0.02 ng/mL, occurring in 11.6% of patients, were associated with higher 30-day mortality compared with the reference group (peak TnT≤0.01 ng/mL): peak TnT of 0.02 ng/mL (adjusted hazard ratio [aHR], 2.41; 95% CI, 1.33-3.77); 0.03 to 0.29 ng/mL (aHR, 5.00; 95% CI, 3.72-6.76); and 0.30 ng/mL or greater (aHR, 10.48; 95% CI, 6.25-16.62). Patients with a peak TnT value of 0.01 ng/mL or less, 0.02, 0.03-0.29, and 0.30 or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively. Peak TnT measurement added incremental prognostic value to discriminate those likely to die within 30 days for the model with peak TnT measurement vs without (C index = 0.85 vs 0.81; difference, 0.4; 95% CI, 0.2-0.5; P < .001 for difference between C index values). The net reclassification improvement with TnT was 25.0% (P < .001). CONCLUSIONS:Among patients undergoing noncardiac surgery, the peak postoperative TnT measurement during the first 3 days after surgery was significantly associated with 30-day mortality.

Pancreatic cysts are being identified with increasing frequency due to a combination of increased awareness and more frequent use of cross sectional imaging. Cystic neoplasms of the pancreas range from completely benign to frankly malignant. Identifying pre-malignant cysts offers the opportunity to prevent the development of pancreatic cancer. This article reviews the presentation, workup, and non-operative and operative management of premalignant and malignant pancreatic cysts.

PURPOSE/OBJECTIVE:TNFerade biologic is a novel means of delivering tumor necrosis factor alpha to tumor cells by gene transfer. We herein report final results of the largest randomized phase III trial performed to date among patients with locally advanced pancreatic cancer (LAPC) and the first to test gene transfer against this malignancy. PATIENTS AND METHODS/METHODS:In all, 304 patients were randomly assigned 2:1 to standard of care plus TNFerade (SOC + TNFerade) versus standard of care alone (SOC). SOC consisted of 50.4 Gy in 28 fractions with concurrent fluorouracil (200 mg/m(2) per day continuous infusion). TNFerade was injected intratumorally before the first fraction of radiotherapy each week at a dose of 4 × 10(11) particle units by using either a percutaneous transabdominal or an endoscopic ultrasound approach. Four weeks after chemoradiotherapy, patients began gemcitabine (1,000 mg/m(2) intravenously) with or without erlotinib (100 to 150 mg per day orally) until progression or toxicity. RESULTS:The analysis included 187 patients randomly assigned to SOC + TNFerade and 90 to SOC by using a modified intention-to-treat approach. Median follow-up was 9.1 months (range, 0.1 to 50.5 months). Median survival was 10.0 months for patients in both the SOC + TNFerade and SOC arms (hazard ratio [HR], 0.90; 95% CI, 0.66 to 1.22; P = .26). Median progression-free survival (PFS) was 6.8 months for SOC + TNFerade versus 7.0 months for SOC (HR, 0.96; 95% CI, 0.69 to 1.32; P = .51). Among patients treated on the SOC + TNFerade arm, multivariate analysis showed that TNFerade injection by an endoscopic ultrasound-guided transgastric/transduodenal approach rather than a percutaneous transabdominal approach was a risk factor for inferior PFS (HR, 2.08; 95% CI, 1.06 to 4.06; P = .032). The patients in the SOC + TNFerade arm experienced more grade 1 to 2 fever and chills than those in the SOC arm (P < .001) but both arms had similar rates of grade 3 to 4 toxicities (all P > .05). CONCLUSION/CONCLUSIONS:SOC + TNFerade is safe but not effective for prolonging survival in patients with LAPC.