Megan Winner

Incidence and Predictors of Bowel Obstruction in Elderly Patients With Stage IV Colon Cancer: A Population-Based Cohort Study

IMPORTANCE 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 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 Patients 65 years or older with stage IV colon cancer (n = 12 553). MAIN OUTCOMES AND MEASURES 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 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.

Quality of life in patients after total pancreatectomy is comparable with quality of life in patients who undergo a partial pancreatic resection

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.

MRCP is not a cost-effective strategy in the management of silent common bile duct stones.

BackgroundFew formal cost-effectiveness analyses simultaneously evaluate radiographic, endoscopic, and surgical approaches to the management of choledocholithiasis.Study DesignUsing the decision analytic software TreeAge, we modeled the initial clinical management of a patient presenting with symptomatic cholelithiasis without overt signs of choledocholithiasis. In this base case, we assumed a 10 % probability of concurrent asymptomatic choledocholithiasis. Our model evaluated four diagnostic/therapeutic strategies: universal magnetic resonance cholangiopancreatography (MRCP), universal endoscopic retrograde cholangiopancreatography (ERCP), laparoscopic cholecystectomy (LC), or laparoscopic cholecystectomy with universal intraoperative cholangiogram (LCIOC). All probabilities were estimated from a review of published literature. Procedure and intervention costs were equated with Medicare reimbursements. Costs of hospitalizations were derived from median hospitalization reimbursement for New York State using diagnosis-related groups (DRG). Sensitivity analyses were performed on all cost and probability variables.ResultsThe most cost-effective strategy in the diagnosis and management of symptomatic cholelithiasis with a 10 % risk of asymptomatic choledocholithiasis was LCIOC. This was followed by LC alone, MRCP, and ERCP. LC was preferred only when the probability that a retained CBD stone would eventually become symptomatic fell below 15 % or if the probability of technical success of an intraoperative cholangiogram (IOC) was less than 35 %. Universal MRCP and ERCP were both more costly and less effective than surgical strategies, even at a high probability of asymptomatic choledocholithiasis. Within the tested range for both procedural and hospitalization-related costs for any of the surgical or endoscopic interventions, LCIOC and LC were always more cost-effective than universal MRCP or ERCP, irrespective of the presence or absence of complications. Varying the cost, sensitivity, and specificity of MRCP had no effect on this outcome.ConclusionsLC with routine IOC is the preferred strategy in a cost-effectiveness analysis of the management of symptomatic cholelithiasis with asymptomatic choledocholithiasis. MRCP was both more costly and less effective under all tested scenarios.

Bowel obstruction in elderly ovarian cancer patients: A population-based study

PURPOSE Bowel obstruction is a common pre-terminal event in abdominal/pelvic cancer that has mainly been described in small single-institution studies. We used a large, population-based database to investigate the incidence, management, and outcomes of obstruction in ovarian cancer patients. PATIENTS AND METHODS We identified patients with stages IC-IV ovarian cancer, aged 65 years or older, in the Surveillance, Epidemiology and End Results (SEER)-Medicare database diagnosed between January 1, 1991 and December 31, 2005. We modeled predictors of inpatient hospitalization for bowel obstruction after cancer diagnosis, categorized management of obstruction, and analyzed the associations between treatment for obstruction and outcomes. RESULTS Of 8607 women with ovarian cancer, 1518 (17.6%) were hospitalized for obstruction subsequent to cancer diagnosis. Obstruction at cancer diagnosis (HR=2.17, 95%CI: 1.86-2.52) and mucinous tumor histology (HR=1.45, 95%CI: 1.15-1.83) were associated with increased risk of subsequent obstruction. Surgical management of obstruction was associated with lower 30-day mortality (13.4% in women managed surgically vs. 20.2% in women managed non-surgically), but equivalent survival after 30 days and equivalent rates of post-obstruction chemotherapy. Median post-obstruction survival was 382 days in women with obstructions of adhesive origin and 93 days in others. CONCLUSION In this large-scale, population-based assessment of patients with advanced ovarian cancer, nearly 20% of women developed bowel obstruction after cancer diagnosis. While obstruction due to adhesions did not signal the end of life, all other obstructions were pre-terminal events for the majority of patients regardless of treatment.

Management and Outcomes of Bowel Obstruction in Patients with Stage IV Colon Cancer: A Population-Based Cohort Study

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: This was a retrospective cohort study. SETTING AND PATIENTS: 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: 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: 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.

Neoadjuvant therapy for non-metastatic pancreatic ductal adenocarcinoma.

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.

Intraductal Papillary Mucinous Neoplasms of the Pancreas: Clinical Surveillance and Malignant Progression, Multifocality and Implications of a Field-Defect

Intraductal papillary mucinous neoplasms (IPMNs) are a heterogeneous group of mucin producing cystic tumors that involve the main pancreatic duct and/or branch ducts and may be associated with invasive carcinoma. Predicting the risk of malignant transformation of an IPMN lesion can be challenging. The Sendai criteria, based in large part on radiographic imaging features, help guide surgical intervention based on the stratification of cysts into high and low risk lesions for malignancy. Invasive carcinoma may develop in the index IPMN lesion or in a separate site within the pancreas, supporting the concept of a field defect in IPMN tumorigenesis. This stresses the importance of evaluation of the entire pancreas upon diagnosis of IPMN and continued surveillance of the residual pancreas following resection. Herein, the authors summarize the data presented at the 2012 ASCO Gastrointestinal Cancers Symposium regarding prevalence and site of invasive carcinoma detected in patients undergoing surveillance for IPMN (Abstract #152).

The Role of Molecular Analysis in the Diagnosis and Surveillance of Pancreatic Cystic Neoplasms

CONTEXT 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 Students t or the Mann-Whitney U test for continuous variables and the Fishers 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.

An update on surgical staging of patients with pancreatic cancer.

Accurate staging of pancreatic adenocarcinoma is a crucial step in determining the appropriate therapeutic approach to pancreatic cancer and to maximizing life expectancy. Despite the availability of high-quality abdominal imaging, the use of multi-modality imaging and of diagnostic laparoscopy, a portion of surgically explored patients fail to undergo resection secondary to metastatic disease. This review is an update from the 2012 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium of new developments in the staging of localized pancreatic adenocarcinoma. (Abstracts #168, #177, and #212).

Su1497 MRCP is Not a Cost Effective Strategy in Management of Common Bile Duct Stones

trans-well filters apically and basally supplemented with keratinocyte serum-free media with 0.6mM Ca+2. This stratified epithelium shows epithelial barrier function and expresses squamous specific genes like GRHL-1, K10, KDAP, DSG1, and IVL. Moreover, when exposed to bile acids at pH5 in short pulses, EPC1 cells demonstrate reduction in the stratification layers and in the expression of squamous specific genes. The epithelium also exhibits loss of barrier function possibly due to disruption of desmosomal junctions and phosphorylationactivation of epidermal growth factor receptor (EGFR) and down-stream pathways. In addition, the epithelium starts expressing columnar specific transcription factor CDX2 as early as day 3 of treatment. These results indicate that bile acid at low pH is responsible for skewing the differentiation status of stratified squamous esophageal epithelium In Vitro to a more columnar type possibly by initiating a mucosal restitution response through activation of EGFR signaling.