Comparison of sentinel lymph node micrometastatic tumor burden measurements in melanoma.

BACKGROUND: Multiple methods have been proposed to classify the micrometastatic tumor burden in sentinel lymph nodes (SLN) for melanoma. The purpose of this study was to determine the classification scheme that best predicts nonsentinel node (NSN) metastasis, disease-free survival (DFS), and overall survival (OS). STUDY DESIGN: A single reviewer reanalyzed tumor-positive SLN from a multicenter, prospective clinical trial of patients with melanoma ≥ 1.0 mm Breslow thickness who underwent SLN biopsy. The following micrometastatic disease burden measurements were recorded: Starz classification, Dewar classification (microanatomic location), maximum diameter of the largest focus of metastasis, maximum tumor area, and sum of all diameters. Univariate and multivariate models and Kaplan-Meier analysis were used to evaluate each classification system. RESULTS: We reviewed 204 tumor-positive SLNs from 157 patients. On univariate analysis, all criteria except Starz classification were statistically significant risk factors for NSN metastasis. On multivariate analysis, including Breslow thickness, ulceration, age, sex, and NSN status, maximum diameter (using a cut-off of 3 mm) was the only classification system that was an independent risk factor predicting DFS (hazard ratio 2.31, p = 0.0181) and OS (hazard ratio 3.53, p = 0.0005). By Kaplan-Meier analysis, DFS and OS were significantly different among groups using maximum diameter cut-offs of 1 and 3 mm. CONCLUSIONS: Maximum tumor diameter outperformed other measurements of metastatic tumor burden, including microanatomic tumor location (Dewar classification), Starz classification, maximum tumor area, and sum of all diameters for prediction of survival. Maximum tumor diameter is a simple method of assessing micrometastatic tumor burden that should be reported routinely.

Impact of post-operative complications on quality of life after pancreatectomy.

CONTEXT: Pancreatectomies for malignant and benign diseases are increasingly being performed worldwide. Recent studies, that have evaluated quality of life in pancreatectomy, have reported conflicting outcomes. OBJECTIVE: This study was undertaken to analyze the quality of life changes reported by patients with pancreatic cancer undergoing pancreatectomy. DESIGN: Post-hoc analysis was performed of a clinical trial examining the safety of intraoperative autotransfusion during oncologic resections. MAIN OUTCOME MEASURES: Perioperative (90-day) complications were graded prospectively using a validated 5-point scale. Quality of life parameters were recorded prospectively by a single trained interviewer preoperatively, at the first post-operative outpatient visit, and at 6 weeks, 3 months, and 6 months follow-up using the EORTC QLQ-C30 and FACT-An instruments. RESULTS: Pancreatectomy for adenocarcinoma was performed in 34 patients with a median follow-up of 2 years (range: 1-1.5 years). Major (grade≥3) complications occurred in 12 (35.3%) of patients. Early (<6 month) recurrence was noted in 2 patients (5.9%). Increased severity of fatigue, pain, dyspnea, and loss of appetite over baseline were noted at initial follow-up (P<0.05); however, symptom scores normalized at 6-week follow-up, and remained stable at 6 months. No significant difference was noted in quality of life metrics between patients with or without major complications (P>0.11). A significant (P=0.023) decline in cognitive function vs. baseline was noted at 6-month follow-up after pancreatectomy. Using a repeated-measures generalized linear model, neither age, nor complication occurrence, nor adjuvant therapy, nor early recurrence accounted for this cognitive decline (P>0.10). CONCLUSION: Quality of life metrics tend to normalize to preoperative levels after pancreatectomy at 6 weeks post-operatively. The occurrence of major complications does not predict a decreased quality of life. The decrease in self-reported cognitive function at six months in this cohort merits further study.

Differences between bipolar compression and ultrasonic devices for parenchymal transection during laparoscopic liver resection.

OBJECTIVES: In laparoscopic liver resection, multiple options for parenchymal transection techniques exist; however, none have emerged as superior. The aim of this study was to compare operative characteristics and outcomes between bipolar compression and ultrasonic devices used for parenchymal transection during laparoscopic liver resection. METHODS: A review of a prospective hepatopancreatobiliary database from December 2002 to August 2009 identified 54 patients who underwent laparoscopic liver resection with parenchymal division using either a bipolar compression (n= 35) or an ultrasonic (n= 19) device. Operative data, histology and 90-day complication rates were compared between the groups using analysis of variance (anova) and Pearson's chi-squared test. RESULTS: The two groups did not differ significantly in terms of age, body mass index, parenchymal steatosis/inflammation or number of segments resected. A shorter time of parenchymal transection was noted for the bipolar compression device (median: 35 min; range: 20-65 min) vs. the ultrasonic device (median: 55 min; range: 29-75 min) (P < 0.001). Median total operative time was also shorter using the bipolar compression device (130 min) than the ultrasonic device (180 min) (P= 0.050). No significant differences between device groups were noted for estimated blood loss, complications of any type or liver-specific complications. CONCLUSIONS: Bipolar compression devices may offer advantages over ultrasonic devices in terms of decreased transection time and total operative time. No differences in postoperative complications in laparoscopic liver resection emerged between patients operated using the devices.

Hepatectomy after hepatic arterial therapy with either yttrium-90 or drug-eluting bead chemotherapy: is it safe?

BACKGROUND: The use of hepatic arterial therapy (HAT) with either yttrium-90 or drug-eluting bead therapy for initially unresectable hepatic malignancies has risen significantly. The safety of hepatic resection after hepatic arterial therapy (HAT) is not established. OBJECTIVE: The present study evaluates the safety profile for hepatic resection after HAT. METHODS: We identified 840 patients undergoing hepatectomy for primary or metastatic lesions. Forty patients underwent HAT before hepatectomy (pre-HAT). A 1:4 case-matched analysis compared three groups: (i) pre-HAT and pre-operative chemotherapy (n=40); (ii) pre-operative chemotherapy (n=160); and (iii) no pre-operative therapy (n=640). Controls were matched for age, resection type, maximal tumour size and magnitude of resection. Morbidity and mortality among groups were compared using a graded complication scale. RESULTS: There were no differences in post-operative complications, grade of complication or liver-specific complications among the groups. A proportional hazards model for all patients did not demonstrate any association between increased complications and either pre-HAT or pre-operative chemotherapy when compared with patients without pre-operative therapy (P=0.7). CONCLUSIONS: Pre-HAT demonstrated similar morbidity, liver-specific morbidity and intra-operative complications when compared with patients undergoing pre-operative chemotherapy alone or without pre-operative chemotherapy. These results suggest that pre-HAT is safe and should not preclude hepatectomy in carefully selected patients.

Phase II comparison study of intraoperative autotransfusion for major oncologic procedures.

BACKGROUND: Intraoperative autotransfusion (IOAT) has been avoided in oncologic surgery because of possible tumor cell dissemination. Through a prior Phase I study, we demonstrated that malignant cells are not present in blood filtered for IOAT. We hypothesized that autotransfusion could be safely used for patients undergoing major oncologic procedures and reduce the need for allogeneic blood. MATERIALS AND METHODS: A Phase II, IRB-approved, prospective evaluation was conducted of patients undergoing gastrointestinal oncologic procedures. All procedures were conducted with blood salvaged for IOAT, and the collected volume was autotransfused if it was >100 ml. Quality of life (QoL) was assessed by questionnaire at regular intervals. RESULTS: A total of 92 patients were enrolled with median age of 56 years. The most commonly performed procedures were hepatectomy (47%) and pancreaticoduodenectomy (26%). The median preoperative hemoglobin (Hgb) was 13.1 (range, 9-16), and the median estimated blood loss was 350 ml (range, 20-4000 ml). Of the 92 total patients, 32 (35%) received IOAT with a median volume of 255 ml (range, 117-1499 ml). Multivariate analysis identified that patients with preoperative Hgb >11 g/dl (P = .02), and blood loss of 400-900 ml (P = .03) benefited from IOAT with a reduction in postoperative blood transfusion rate. Patients with discharge Hgb >10 g/dl showed higher mean QoL scores throughout their recovery. At a median follow-up of 18 months, the rates of recurrence in the IOAT and the non-IOAT groups were equivalent (38 vs. 39%, P = .9). CONCLUSIONS: Intraoperative autotransfusion can be used safely and effectively for major oncologic procedures. Furthermore, degree of discharge anemia is associated with lower quality of life in patients undergoing oncologic gastrointestinal surgery.

Chemoprotective effects of curcumin in esophageal epithelial cells exposed to bile acids.

AIM: To investigate the ability of curcumin to counteract the impact of bile acids on gene expression of esophageal epithelial cells. METHODS: An esophageal epithelial cell line (HET-1A) was treated with curcumin in the presence of deoxycholic acid. Cell proliferation and viability assays were used to establish an appropriate dose range for curcumin. The combined and individual effects of curcumin and bile acid on cyclooxygenase-2 (COX-2) and superoxide dismutase (SOD-1 and SOD-2) gene expression were also assessed. RESULTS: Curcumin in a dose range of 10-100 micromol/L displayed minimal inhibition of HET-1A cell viability. Deoxycholic acid at a concentration of 200 micromol/L caused a 2.4-fold increase in COX-2 gene expression compared to vehicle control. The increased expression of COX-2 induced by deoxycholic acid was partially reversed by the addition of curcumin, and curcumin reduced COX-2 expression 3.3- to 1.3-fold. HET-1A cells exposed to bile acid yielded reduced expression of SOD-1 and SOD-2 genes with the exception that high dose deoxycholic acid at 200 mumol/L led to a 3-fold increase in SOD-2 expression. The addition of curcumin treatment partially reversed the bile acid-induced reduction in SOD-1 expression at all concentrations of curcumin tested. CONCLUSION: Curcumin reverses bile acid suppression of gene expression of SOD-1. Curcumin is also able to inhibit bile acid induction of COX-2 gene expression.

Bile cultures: a guide to infectious complications after pancreaticoduodenectomy.

BACKGROUND: The aim of this study was to evaluate the utility of intraoperative bile cultures on the outcome of patients undergoing pancreaticoduodenectomy. STUDY DESIGN: A review of a hepato-pancreato-biliary database was performed to identify all patients who had a pancreaticoduodenectomy from 1/1998 to 8/2008. RESULTS: Two hundred twenty-eight patients were evaluated, with preoperative biliary stenting performed in 129 out of 229 patients (57%), with 63/129(49%) had bile cultures taken intraoperatively, 39/129(30%) having positive bile cultures. Neither preoperative biliary stenting (incidence of complication: 54% with stent vs. 51% without, P = 0.9) nor positive bile culture (incidence of complication: 54% with positive bile culture vs. 53% without, P = 0.9) were predictors of overall complications. Length of operating time, length of hospital stay, blood loss, blood transfusion, and severity of complications were similar in the group with and without stent. There were 19 different organisms identified with not a single species was a statistically significant predictor of neither severity of complication nor increased length of stay. CONCLUSIONS: Preoperative biliary stenting correlates with similar rate of biliary infections, however, intraoperative bile culture allows for early appropriate antibiotic use, which maintains a similar morbidity and infectious incidence as in patients without stents.

Second primary melanomas: incidence and outcome.

The objective of this study was to determine the incidence of multiple primary melanomas (MPM) and other cancers types among patients with melanoma. Factors associated with development of MPM were assessed in a post hoc analysis of the database from a multi-institutional prospective randomized trial of patients with melanoma aged 18 to 70 years with Breslow thickness 1 mm or greater. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis. Forty-eight (1.9%) of 2506 patients with melanoma developed additional primary melanomas. Median follow-up was 66 months. Except in one patient, the subsequent melanomas were thinner (median, 0.32 mm vs. 1.50 mm; P < 0.0001). Compared with patients without MPM, patients with MPM were more likely to be older (median age, 54.5 vs. 51.0 years; P = 0.048), to have superficially spreading melanomas (SSM) (P = 0.025), to have negative sentinel lymph nodes (P = 0.021), or to lack lymphovascular invasion (LVI) (P = 0.008) with the initial tumor. On multivariate analysis, age (P = 0.028), LVI (P = 0.010), and SSM subtype of the original melanoma (P = 0.024) were associated with MPM. Patients with MPM and patients with single primary melanoma had similar DFS (5-year DFS 88.7 vs. 81.3%, P = 0.380), but patients with MPM had better OS (5-year OS 95.3 vs. 80.0%, P = 0.005). Nonmelanoma malignancies occurred in 152 patients (6.1%). Ongoing surveillance of patients with melanoma is important given that a significant number will develop additional melanoma and nonmelanoma tumors. With close follow-up, second primary melanomas are usually detected at an early stage.

Hepatic resection for colorectal liver metastases.

Colorectal adenocarcinoma remains the third most common cause of cancer death in the United States, with an estimated 146,000 new cases and 50,000 deaths annually. Survival is stage dependent, and the presence of liver metastases is a primary determinant in patient survival. Approximately 25% of new cases will present with synchronous colorectal liver metastases (CLM), and up to one-half will develop CLM during the course of their disease. The importance of safe and effective therapies for CLM cannot be overstated. Safe and appropriately aggressive multimodality therapy for CLM can provide most patients with liver-dominant colorectal metastases with extended survival and an improved quality of life.

Nutritional management during neoadjuvant therapy for esophageal cancer.

Patients undergoing neoadjuvant therapy for esophageal cancer are at a high risk for malnutrition due to the effects of chemoradiation, dysphagia, and malignancy induced cachexia. Preparation for esophagectomy requires careful assessment of nutritional risk and adequate supplementation as indicated. Supplementation via the enteral route is preferred to the parenteral route but requires feeding tube placement. Endoscopically placed silicone stents have also shown promise as a means to alleviate malnutrition and avoid invasive feeding tubes.