Faculty Bibliography

BACKGROUND:Intraperitoneal chemotherapy is used to treat peritoneal surface-spreading malignancies. We sought to determine whether volume and surface area of the intraperitoneal chemotherapy compartments are associated with overall survival and posttreatment glomerular filtration rate (GFR) in malignant peritoneal mesothelioma (MPM) patients. METHODS:Thirty-eight MPM patients underwent X-ray computed tomography peritoneograms during outpatient intraperitoneal chemotherapy. We calculated volume and surface area of contrast-filled compartments by semiautomated computer algorithm. We tested whether these were associated with overall survival and posttreatment GFR. RESULTS:Decreased likelihood of mortality was associated with larger surface areas (p = 0.0201) and smaller contrast-filled compartment volumes (p = 0.0341), controlling for age, sex, histologic subtype, and presence of residual disease >0.5 cm postoperatively. Larger volumes were associated with higher posttreatment GFR, controlling for pretreatment GFR, body surface area, surface area, and the interaction between body surface area and volume (p = 0.0167). DISCUSSION/CONCLUSIONS:Computed tomography peritoneography is an appropriate modality to assess for maldistribution of intraperitoneal chemotherapy. In addition to identifying catheter failure and frank loculation, quantitative analysis of the contrast-filled compartment's surface area and volume may predict overall survival and cisplatin-induced nephrotoxicity. Prospective studies should be undertaken to confirm and extend these findings to other diseases, including advanced ovarian carcinoma.

BACKGROUND:Few formal cost-effectiveness analyses simultaneously evaluate radiographic, endoscopic, and surgical approaches to the management of choledocholithiasis. STUDY DESIGN/METHODS:Using 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. RESULTS:The 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. CONCLUSIONS:LC 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.

BACKGROUND:Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) would correlate with the pharmacokinetic advantage of HIPEC. Because oxaliplatin is administered in 5 % dextrose, we hypothesized that BSA would correlate with glycemia. METHODS:We collected blood and peritoneal perfusate samples from ten patients undergoing HIPEC with a BSA-based dose of 250 mg/m(2) oxaliplatin, and measured drug concentrations by inductively coupled plasma mass spectrophotometry. We monitored blood glucose for 24 h postoperatively. Areas under concentration-time curves (AUC) were calculated by trapezoidal rule. Pharmacokinetic advantage was calculated by (AUC[peritoneal fluid]/AUC[plasma]). We used linear regression to test for statistical significance. RESULTS:Higher BSA was associated with lower plasma oxaliplatin AUC (p = 0.0075) and with a greater pharmacokinetic advantage (p = 0.0198) over the 60-minute duration of HIPEC. No statistically significant relationships were found between BSA and blood glucose AUC or peak blood glucose levels. CONCLUSIONS:Higher BSA is correlated with lower plasma drug levels and greater pharmacokinetic advantage in HIPEC, likely because of increased circulating blood volume with inadequate time for equilibration. Plasma glucose levels after oxaliplatin HIPEC were not clearly related to BSA.

PURPOSE/OBJECTIVE: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/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/CONCLUSIONS: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.

PURPOSE/OBJECTIVE:We evaluated the efficacy and safety of capecitabine and temozolomide (CAPTEM) in patients with metastatic neuroendocrine tumors (NETs) to the liver. This regimen was based on our studies with carcinoid cell lines that showed synergistic cytotoxicity with sequence-specific dosing of 5-fluorouracil preceding temozolomide (TMZ). METHODS:A retrospective review was conducted of 18 patients with NETs metastatic to the liver who had failed 60 mg/month of Sandostatin LARâ„¢ (100%), chemotherapy (61%), and hepatic chemoembolization (50%). Patients received capecitabine at 600 mg/m(2) orally twice daily on days 1-14 (maximum 1,000 mg orally twice daily) and TMZ 150-200 mg/m(2) divided into two doses daily on days 10-14 of a 28-day cycle. Imaging was performed every 2 cycles, and serum tumor markers were measured every cycle. RESULTS:Using RECIST parameters, 1 patient (5.5%) with midgut carcinoid achieved a surgically proven complete pathological response (CR), 10 patients (55.5%) achieved a partial response (PR), and 4 patients (22.2%) had stable disease (SD). Total response rate was 61%, and clinical benefit (responders and SD) was 83.2%. Of four carcinoid cases treated with CAPTEM, there was 1 CR, 1 PR, 1 SD, and 1 progressive disease. Median progression-free survival was 14.0 months (11.3-18.0 months). Median overall survival from diagnosis of liver metastases was 83 months (28-140 months). The only grade 3 toxicity was thrombocytopenia (11%). There were no grade 4 toxicities, hospitalizations, opportunistic infections, febrile neutropenias, or deaths. CONCLUSIONS:CAPTEM is highly active, well tolerated and may prolong survival in patients with well-differentiated, metastatic NET who have progressed on previous therapies.

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.