Faculty Bibliography

BACKGROUND:The objective of the current study was to characterize the prevalence of the expectation that surgical resection of lung or colorectal cancer might be curative. The authors sought to assess patient-level, tumor-level, and communication-level factors associated with the perception of cure. METHODS:Between 2003 and 2005, a total of 3954 patients who underwent cancer-directed surgery for lung (30.3%) or colorectal (69.7%) cancer were identified from a population-based and health system-based survey of participants from multiple US regions. RESULTS:Approximately 80.0% of patients with lung cancer and 89.7% of those with colorectal cancer responded that surgery would cure their cancer. Even 57.4% and 79.8% of patients with stage IV lung and colorectal cancer, respectively, believed surgery was likely to be curative. On multivariable analyses, the odds ratio (OR) of the perception of curative intent was found to be higher among patients with colorectal versus lung cancer (OR, 2.27). Patients who were female, with an advanced tumor stage, unmarried, and having a higher number of comorbidities were less likely to believe that surgery would cure their cancer; educational level, physical function, and insurance status were not found to be associated with perception of cure. Patients who reported optimal physician communication scores (reference score, 0-80; score of 80-100 [OR, 1.40] and score of 100 [OR, 1.89]) and a shared role in decision-making with their physician (OR, 1.16) or family (OR, 1.17) had a higher odds of perceiving surgery would be curative, whereas patients who reported physician-controlled (OR, 0.56) or family-controlled (OR, 0.72) decision-making were less likely to believe surgery would provide a cure. CONCLUSIONS:Greater focus on patient-physician engagement, communication, and barriers to discussing goals of care with patients who are diagnosed with cancer is needed.

CONTEXT/BACKGROUND:Molecular analysis of pancreatic cyst fluid obtained by EUS-FNA may increase diagnostic accuracy. We evaluated the utility of cyst-fluid molecular analysis, including mutational analysis of K-ras, loss of heterozygosity (LOH) at tumor suppressor loci, and DNA content in the diagnoses and surveillance of pancreatic cysts. METHODS:We retrospectively reviewed the Columbia University Pancreas Center database for all patients who underwent EUS/FNA for the evaluation of pancreatic cystic lesions followed by surgical resection or surveillance between 2006-2011. We compared accuracy of molecular analysis for mucinous etiology and malignant behavior to cyst-fluid CEA and cytology and surgical pathology in resected tumors. We recorded changes in molecular features over serial encounters in tumors under surveillance. Differences across groups were compared using Student's t or the Mann-Whitney U test for continuous variables and the Fisher's exact test for binary variables. RESULTS:Among 40 resected cysts with intermediate-risk features, molecular characteristics increased the diagnostic yield of EUS-FNA (n=11) but identified mucinous cysts less accurately than cyst fluid CEA (P=0.21 vs. 0.03). The combination of a K-ras mutation and ≥2 loss of heterozygosity was highly specific (96%) but insensitive for malignant behavior (50%). Initial data on surveillance (n=16) suggests that molecular changes occur frequently, and do not correlate with changes in cyst size, morphology, or CEA. CONCLUSIONS:In intermediate-risk pancreatic cysts, the presence of a K-ras mutation or loss of heterozygosity suggests mucinous etiology. K-ras mutation plus ≥2 loss of heterozygosity is strongly associated with malignancy, but sensitivity is low; while the presence of these mutations may be helpful, negative findings are uninformative. Molecular changes are observed in the course of cyst surveillance, which may be significant in long-term follow-up.

Treatment of pancreatic cancer is increasingly multimodal, with patients receiving chemotherapy, radiation, and surgical extirpation in hope of long-term cure. There is ongoing debate over the timing, sequence, and necessity of these treatments as they pertain to the spectrum of local-regional disease. Current guidelines support a neoadjuvant strategy in patients with locally advanced and borderline resectable disease. Although there is currently no high-level evidence to recommend neoadjuvant therapy for all patients, there are data to suggest that wider application of neoadjuvant therapy may be beneficial. Random-assignment prospective trials are ongoing. In this review we examine the literature addressing a neoadjuvant approach to potentially resectable, borderline resectable, and locally advanced pancreatic cancer and highlight the outcomes of preoperative emergence of latent metastatic disease, attempted resection rates, margin negative resection rates, and pathologic response to treatment.

BACKGROUND:Positron emission tomography (PET) as an adjunct to conventional imaging in the staging of pancreatic adenocarcinoma is controversial. Herein, we assess the utility of PET in identifying metastatic disease and evaluate the prognostic potential of standard uptake value (SUV). METHODS:Imaging and follow-up data for patients diagnosed with pancreatic adenocarcinoma were reviewed retrospectively. Resectability was assessed based on established criteria, and sensitivity, specificity, and accuracy of PET were compared to those of conventional imaging modalities. RESULTS:For 123 patients evaluated 2005-2011, PET and CT/MRI were concordant in 108 (88 %) cases; however, PET identified occult metastatic lesions in seven (5.6 %). False-positive PETs delayed surgery for three (8.3 %) patients. In a cohort free of metastatic disease in 78.9 % of cases, the sensitivity and specificity of PET for metastases were 89.3 and 85.1 %, respectively, compared with 62.5 and 93.5 % for CT and 61.5 and 100.0 % for MRI. Positive predictive value and negative predictive value of PET were 64.1 and 96.4 %, respectively, compared with 75.0 and 88.9 % for CT and 100.0 and 91.9 % for MRI. Average difference in maximum SUV of resectable and unresectable lesions was not statistically significant (5.65 vs. 6.5, p = 0.224) nor was maximum SUV a statistically significant predictor of survival (p = 0.18). CONCLUSION/CONCLUSIONS:PET is more sensitive in identifying metastatic lesions than CT or MRI; however, it has a lower specificity, lower positive predictive value, and in some cases, can delay definitive surgical management. Therefore, PET has limited utility as an adjunctive modality in staging of pancreatic adenocarcinoma.

BACKGROUND:Quality of life after total pancreatectomy (TP) is perceived to be poor secondary to insulin-dependent diabetes and pancreatic insufficiency. As a result, surgeons may be reluctant to offer TP for benign and premalignant pancreatic diseases. METHODS:We retrospectively reviewed presenting features, operative characteristics, and postoperative outcomes of all patients who underwent TP at our institution. Quality of life was assessed using institutional questionnaires and validated general, pancreatic disease-related, and diabetes-related instruments (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30 and module EORTC-PAN26], Audit of Diabetes Dependent Quality of Life), and compared with frequency-matched controls, patients after a pancreaticoduodenectomy (PD). Continuous variables were compared using Student t-test or analysis of variance. Categorical variables were compared using χ(2) or Fisher exact test. RESULTS:Between 1994 and 2011, 77 TPs were performed. Overall morbidity was 49%, but only 15.8% patients experienced a major complication. Perioperative mortality was 2.6%. Comparing 17 TP and 14 PD patients who returned surveys, there were no statistically significant differences in quality of life in global health, functional status, or symptom domains of EORTC QLQ-C30 or in pancreatic disease-specific EORTC-PAN26. TP patients had slightly but not significantly higher incidence of hypoglycemic events as compared with PD patients with postoperative diabetes. A negative impact of diabetes assessed by Audit of Diabetes Dependent Quality of Life did not differ between TP and PD. Life domains most negatively impacted by diabetes involved travel and physical activity, whereas self-confidence, friendships and personal relationships, motivation, and feelings about the future remained unaffected. CONCLUSIONS:Although TP-induced diabetes negatively impacts select activities and functions, overall quality of life is comparable with that of patients who undergo a partial pancreatic resection.

BACKGROUND:Pancreatic surgery with vascular reconstruction is increasingly performed to offer the benefits of surgical resection to patients with locally advanced disease. The short- and long-term patency rates and the clinical significance of thrombosis of such reconstructions are unknown. METHODS:We reviewed pancreatectomies requiring venous reconstruction from 1994 to 2011. We sought to identify predictors of acute (within 30 days) and late thrombosis. We compared survival of patients with thrombosis to patients with patent reconstructions. RESULTS:Of 203 pancreatectomies requiring venous reconstruction, acute thrombosis occurred in nine (4.4 %) cases and was associated with increased perioperative mortality (22.2 versus 4.6 %, p = 0.023). Even when nonfatal, acute thrombosis was associated with decreased median survival (7.1 versus 15.9 months, p = 0.011) and increased hazard of death (hazard ratio 8.6, confidence interval 3.7-19.9, p < 0.001). A late loss of patency was seen in 31.2 % of cases at a median of 9.5 months. Later loss of patency was not associated with decreased median survival or increased hazard of death. CONCLUSIONS:Acute thrombosis of the portal venous reconstructions after pancreatectomy is associated with increased perioperative mortality and, even when nonfatal, is associated with decreased survival. Late loss of patency occurs in one-third of patients but does not affect survival.

OBJECTIVES/OBJECTIVE:We examined long-term outcomes in patients with surgically treated intraductal papillary mucinous neoplasm (IPMN) to determine if any clinical or histologic features could predict risk of recurrent disease. METHODS:We reviewed 183 margin-negative surgical resections performed for IPMN between 1994 and 2011 with documented postoperative abdominal imaging. We calculated time to recurrent disease as indicated by radiographic change and created a multivariable Cox proportional hazards model to assess the relationship between patient characteristics and histopathologic tumor features and disease recurrence. RESULTS:Among patients with margin-negative resections and adequate imaging follow-up, we observed a recurrence rate of 13% over a median follow-up of 32.0 months. Individuals with invasive tumors on original pathology were more likely to recur (HR 5.2, 95% CI 2.2-12.2); however, original pathology did not predict disease severity on recurrence. Controlling for invasive pathology, no other histologic feature of the original tumor, including dysplasia at the surgical margin, predicted recurrence. Among non-invasive IPMN, pancreatitis was associated with disease recurrence (HR 3.6, 95% CI 1.2-10.7). CONCLUSIONS:The frequency of recurrent disease in this population and the inability to predict recurrence argues for universal and continuous surveillance after resection for IPMN. The relationship between pancreatitis and disease recurrence should be investigated further.

IMPORTANCE/OBJECTIVE:Research has been limited on the incidence, mechanisms, etiology, and treatment of symptoms that require palliation in patients with terminal cancer. Bowel obstruction (BO) is a common complication of advanced abdominal cancer, including colon cancer, for which small, single-institution studies have suggested an incidence rate of 15% to 29%. Large population-based studies examining the incidence or risk factors associated with BO in cancer are lacking. OBJECTIVE:To investigate the incidence and risk factors associated with BO in patients with stage IV colon cancer. DESIGN AND SETTING/METHODS:Retrospective cohort, population-based study of patients in the Surveillance, Epidemiology, and End Results and Medicare claims linked databases who were diagnosed as having stage IV colon cancer from January 1, 1991, through December 31, 2005. PATIENTS/METHODS:Patients 65 years or older with stage IV colon cancer (n = 12 553). MAIN OUTCOMES AND MEASURES/METHODS:Time to BO, defined by inpatient hospitalization for BO. We used Cox proportional hazards regression models to determine associations between BO and patient, prior treatment, and tumor features. RESULTS:We identified 1004 patients with stage IV colon cancer subsequently hospitalized with BO (8.0%). In multivariable analysis, proximal tumor site (hazard ratio, 1.22 [95% CI, 1.07-1.40]), high tumor grade (1.34 [1.16-1.55]), mucinous histological type (1.27 [1.08-1.50]), and nodal stage N2 (1.52 [1.26-1.84]) were associated with increased risk of BO, as was the presence of obstruction at cancer diagnosis (1.75 [1.47-2.04]). A more recent diagnosis was associated with decreased risk of subsequent obstruction (hazard ratio, 0.84 [95% CI, 0.72-0.98]). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:In this large population of patients with stage IV colon cancer, BO after diagnosis was less common (8.0%) than previously reported. Risk was associated with site and histological type of the primary tumor. Future studies will explore management and outcomes in this serious, common complication.

BACKGROUND:Bowel obstruction is a common complication of late-stage abdominal cancer, especially colon cancer, which has been investigated predominantly in small, single-institution studies. OBJECTIVE:We used a large, population-based data set to explore the surgical treatment of bowel obstruction and its outcomes after hospitalization for obstruction among patients with stage IV colon cancer. DESIGN/METHODS:This was a retrospective cohort study. SETTING AND PATIENTS/METHODS:We identified 1004 patients aged 65 years or older in the Surveillance, Epidemiology and End Results-Medicare database diagnosed with stage IV colon cancer January 1, 1991 to December 31, 2005, who were later hospitalized for bowel obstruction. MAIN OUTCOME MEASURES/METHODS:We describe outcomes after hospitalization and analyzed the associations between surgical treatment of obstruction and outcomes. RESULTS:Hospitalization for bowel obstruction occurred a median of 7.4 months after colon cancer diagnosis, and median survival after obstruction was approximately 2.5 months. Median hospitalization for obstruction was about 1 week and in-hospital mortality was 12.7%. Between discharge and death, 25% of patients were readmitted to the hospital at least once for obstruction, and, on average, patients lived 5 days out of the hospital for every day in the hospital between obstruction diagnosis and death. Survival was 3 times longer in those whose obstruction claims suggested an adhesive obstruction origin. In multivariable models, surgical compared with nonsurgical management was not associated with prolonged survival (p = 0.134). LIMITATIONS/CONCLUSIONS:Use of an administrative database did not allow determination of quality of life or relief of obstruction as an outcome, nor could nonsurgical interventions, eg, endoscopic stenting or octreotide, be assessed. CONCLUSIONS:In this population-based study of patients with stage IV colon cancer who had bowel obstruction, overall survival following obstruction was poor irrespective of treatment. Universally poor outcomes suggest that a diagnosis of obstruction in the setting of advanced colon cancer should be considered a preterminal event.