Gallbladder cancer: Defining the indications for primary radical resection and radical re-resection.

BACKGROUND: The role of radical resection for gallbladder cancer is an ongoing area of debate. In this review, we present our experience managing gallbladder cancer at a tertiary center by using an aggressive surgical approach for T2 or greater disease, reserving simple cholecystectomy only for T1 lesions. METHODS: Seventy-six patients with histologically confirmed gallbladder cancer were identified from our cancer registry. Estimated survival distributions were calculated by the Kaplan-Meier method, and comparisons were made by using the log-rank test. The Cox proportional hazards model was used to determine the effect on survival of T stage, nodal status, age, and margins. RESULTS: Sixty-four patients were assessable for this study. Simple cholecystectomy was the only procedure performed in 10 T2 and 15 T3 cases. Radical cholecystectomy was performed as the primary procedure in two T2, two T3, and six T4 cases. Radical re-resection was accomplished in seven T2 and two T3 cases. Excluding the T4 group, there was a significant survival advantage (P = .007) for the radical resection group (n = 13; median survival not yet reached) compared with the simple cholecystectomy group (n = 25; median survival, 17 months; 95% confidence interval, 7-27 months). Analysis of the 13 T2 and T3 patients who underwent radical resections revealed that the radical re-resection group (n = 9) had an overall survival similar to that of the primarily resected group (n = 4). All T2N(+) and T3N(-) patients are still alive and disease free after 5 years of follow-up, whereas none of the T3N(+) or T4 patients survived beyond 24 months. Increasing T stage and age (>65 years) were independent predictors of a poor prognosis. CONCLUSIONS: Radical resection for T2 and T3 disease resulted in a significant survival advantage compared with simple cholecystectomy. Patients who undergo radical re-resection after an incidentally discovered gallbladder cancer experience the same survival benefit as primarily resected patients. Radical resection for T2N(-), T2N(+), and T3N0 cases can achieve long-term survival. Conversely, the prognosis for T3N(+) and T4 patients is poor, and improved outcome for this group will likely depend on the development of multi-institutional neoadjuvant clinical trials that can identify effective systemic regimens.

COX-2 expression in hepatocellular carcinoma is an initiation event; while EGF receptor expression with downstream pathway activation is a prognostic predictor of survival.

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is a leading cause of cancer mortality with over 90% of HCC patients succumbing to the disease. Current systemic therapies have had no measurable impact on survival in this disease; however there are small subsets of patients who benefit from systemic therapy who have been difficult to identify. Improvements in patient stratification and the development of biological therapies have resulted from the elucidation of the molecular mechanisms integral to tumor development and progression. Recent studies have found that COX-2 and EGFR are frequently inappropriately expressed in HCC compared to normal liver expression; however the presence of surface receptors does not always mean that the downstream pathway is active. In this study, we investigate the incidence and impact of activated EGFR downstream messengers phosphorylated akt (pakt) and/or phosphorylated MAPK (pMAPK) on survival in patients with HCC. METHOD: Thirty consecutive HCC patients treated at a single institution were retrospectively reviewed. Patient data including age, sex, Child's score, histological type, grade, stage, and survival were analyzed. Immunohistochemical staining was performed on formalin fixed, paraffin embedded tissues using monoclonal antibodies to COX-2, EGF receptor, pMAPK, and pakt. Histoscores were determined for each marker and evaluated for impact in survival, stage, and tumor grade. RESULTS: The median age was 67 years (39-83) and 67% of patients were male. Median survival was 9.8 months (1-47 months) for the whole group. COX-2 and EGFR expression was present in 90 and 67% of the tumors, respectively. Expression of activated downstream EGFR messengers was present in 53% of tumors (pMAPK 41%, pakt 31%). Median survival was significantly better in patients with downstream messenger expression, 24.4 months, compared to no expression, 4.7 months (P = 0.03). These groups were matched in age, stage, and Child's score. CONCLUSION: COX-2 and EGFR expression are commonly seen in HCC. Activated downstream EGFR expression is also common in HCC and is a predictor of improved survival. There may be a therapeutic role for EGFR tyrosine kinase inhibitors in this subset of patients and further investigation is warranted.

Should adjuvant therapy remain the standard of care for patients with resected adenocarcinoma of the pancreas?

Adenocarcinoma of the pancreas continues to be a formidable disease. In the United States, patients who have had resected disease are generally offered adjuvant chemoradiation. The current National Comprehensive Cancer Network practice guidelines uniformly support this practice. We reviewed seven selected series to evaluate the efficacy of adjuvant therapy for patients who had resected adenocarcinoma of the pancreas. Current evidence-based analysis demonstrates that an adjuvant therapy regimen as a standard of care is lacking. We, therefore, believe that it should be used judiciously because its benefit is confined to only a fraction of patients treated by complete resection (R0); patients with residual microscopic disease (R1) derived negligible benefits. Given the financial constraints and the small effect that current therapies have on this fatal disease, clinicians should concentrate on developing novel therapies and new paradigms to address this age-old problem.