Association of positive transection margins with gastric cancer survival and local recurrence.

PURPOSE: To examine the association between positive resection margins and survival and local recurrence in patients with gastric cancer undergoing resection with curative intent. METHODS: Patients who underwent curative intent resection for gastric carcinoma from 1985 to 2010 were identified from a prospectively maintained database. Positive margins were defined as disease present at the line of luminal transection. Clinicopathological features and outcome of patients undergoing gastrectomy with negative and positive margins were compared. RESULTS: Among 2384 patients undergoing curative intent resection, 108 (4.5 %) had positive margins. Positive margins were associated with higher American Joint Committee on Cancer (AJCC) stage, T stage, N stage, median number of positive nodes, diffuse Lauren type, and poorly differentiated tumors. Treatment of positive margins consisted of: observation (39 %), chemoradiotherapy (26 %), chemotherapy (20 %), repeat resection (10 %), radiotherapy (4 %), and unknown (1 %). Multivariate analysis of the entire cohort demonstrated margin status, T stage, N stage, grade, and perineural invasion to be independent predictors of survival. Margin status was an independent predictor of survival in patients with ≤3 positive nodes or T1-2 disease but was not in patients with >3 positive nodes or T3-4 disease. Local recurrence occurred in 16 % of patients with a positive margin. We identified no factors predictive of local recurrence in patients with positive margins. CONCLUSIONS: Positive resection margin is associated with advanced AJCC stage and aggressive tumor biology but remains an independent predictor of worse survival. The significance of a positive margin in gastric cancer is confined to patients with nontransmural disease and/or limited nodal involvement.

Indications for and efficacy of splenectomy for haematological disorders.

BACKGROUND: Splenectomy is performed for a variety of indications in haematological disorders. This study was undertaken to analyse outcomes, and morbidity and mortality rates associated with this procedure. METHODS: Patients undergoing splenectomy for the treatment or diagnosis of haematological disease were included. Indications for operation, preoperative risk, intraoperative variables and short-term outcomes were evaluated. RESULTS: From January 1997 to December 2010, 381 patients underwent splenectomy for diagnosis or treatment of haematological disease. Some 288 operations were performed by an open approach, 83 laparoscopically, and there were ten conversions. Overall 136 patients (35·7 per cent) experienced complications. Postoperative morbidity was predicted by age more than 65 years (odds ratio (OR) 1·63, 95 per cent confidence interval 1·05 to 2·55), a Karnofsky performance status (KPS) score lower than 60 (OR 2·74, 1·35 to 5·57) and a haemoglobin level of 9 g/dl or less (OR 1·74, 1·09 to 2·77). Twenty-four patients (6·3 per cent) died within 30 days of surgery. Postoperative mortality was predicted by a KPS score lower than 60 (OR 16·20, 6·10 to 42·92) and a platelet count of 50,000/µl or less (OR 3·34, 1·25 to 8·86). The objective of the operation was achieved in 309 patients (81·1 per cent). The success rate varied for each indication: diagnosis (106 of 110 patients, 96·4 per cent), thrombocytopenia (76 of 115, 66·1 per cent), anaemia (10 of 16, 63 per cent), to allow further treatment (46 of 59, 78 per cent) and primary treatment (16 of 18, 89 per cent). CONCLUSION: Splenectomy is an effective procedure in the diagnosis and treatment of haematological disease in selected patients.

Downstaging in pancreatic cancer: a matched analysis of patients resected following systemic treatment of initially locally unresectable disease.

BACKGROUND: Patients with locally unresectable pancreatic cancer (AJCC stage III) have a median survival of 10-14 months. The objective of this study was to evaluate outcome of initially unresectable patients who respond to multimodality therapy and undergo resection. METHODS: Using a prospectively collected database, patients were identified who were initially unresectable because of vascular invasion and had sufficient response to nonoperative treatment to undergo resection. Overall survival (OS) was compared with a matched group of patients who were initially resectable. Case matching was performed using a previously validated pancreatic cancer nomogram. RESULTS: A total of 36 patients with initial stage III disease were identified who underwent resection after treatment with either systemic therapy or chemoradiation. Initial unresectability was determined by operative exploration (n = 15, 42%) or by cross-sectional imaging (n = 21, 58%). Resection consisted of pancreaticoduodenectomy (n = 31, 86%), distal pancreatectomy (n = 4, 11%), and total pancreatectomy (n = 1, 3%). Pathology revealed T3 lesions in 26 patients (73%), node positivity in 6 patients (16%), and a negative margin in 30 patients (83%). The median OS in this series was 25 months from resection and 30 months since treatment initiation. There was no difference in OS from time of resection between the initial stage III patients and those who presented with resectable disease (P = .35). CONCLUSIONS: In this study, patients who were able to undergo resection following treatment of initial stage III pancreatic cancer experienced survival similar to those who were initially resectable. Resection is indicated in this highly select group of patients.

Resveratrol is an effective inducer of CArG-driven TNF-alpha gene therapy.

We report the anticarcinogenic, anti-aging polyphenol resveratrol activates the radio- and chemo-inducible cancer gene therapy vector Ad.Egr.TNF, a replication-deficient adenovirus that expresses human tumor necrosis factor alpha (TNF-alpha) under control of the Egr-1 promoter. Like ionizing radiation or chemotherapeutic agents previously shown to activate Ad.Egr.TNF, resveratrol also induces Egr-1 expression from its chromosomal locus with a possible role for Egr-1 promoter CC(A+T)richGG sequences in the expression of TNF-alpha. Resveratrol induction of TNF-alpha in Ad.Egr.TNF-infected tumor xenografts demonstrated antitumor response in human and rat tumor models comparable to that of radio- or chemotherapy-induced TNF-alpha. Although sirtuins are known targets of resveratrol, in vitro inhibition of SIRT1 activity did not abrogate resveratrol induction of Egr-1 expression. This suggests that SIRT1 is not essential to mediate resveratrol induction of Egr-1. Nevertheless, control of transgene expression via resveratrol activation of Egr-1 may extend use of Ad.Egr.TNF to patients intolerant of radiation or cytotoxic therapy and offer a novel tool for development of other inducible gene therapies.