Overall survival peri-hilar cholangiocarcinoma: R1 resection with curative intent compared to primary endoscopic therapy.

BACKGROUND AND OBJECTIVES: Patients with peri-hilar cholangiocarcinoma who undergo R1 resection with curative intent will have an improved survival compared to patients who were not resected. METHODS: Review of a prospective hepatobiliary database identified 130 patients. Survival was compared using the log-rank test. RESULTS: Seventy-nine patients (61%) were resected while 51 (49%) patients were not. Forty-two patients (54%) had an R0 resection. There was no difference in mean age (69 vs. 67; P = 0.8), BMI (27.8 vs. 27.9; P = 1.0), gender (73% vs. 43% male; P = 0.1), presence of jaundice (77% vs. 64%; P = 0.5), vascular involvement on pre operative imaging (77% vs. 64%; P = 0.5), stent (73.1% vs. 64.3%; P = 0.72), and lobar atrophy (27% vs. 7%, P = 0.2) in the resected versus non-resected patients. All patients underwent chemotherapy and/or radiation therapy. After a median follow up of 35.6 months the median OSl for all peri-hilar patients was 16.2 months (95% CI = 11.2-23.4). The median OS for resected patients was 18.9 months (95% CI = 12.5-24.7) versus 5.0 months (95% CI = 0-6.9) for patients not resected (P < 0.001). The only pre-operative predictor of OS was resection (P = 0.041). Vascular invasion, lobar atrophy, and stent placement were not statistically significant predictors. CONCLUSION: Overall survival is improved in patients undergoing R1 resection and multi-modality therapy compared to patients not resected.

Dietary freeze-dried black raspberry's effect on cellular antioxidant status during reflux-induced esophagitis in rats.

INTRODUCTION: Esophageal cancer consists of two distinct types, esophageal adenocarcinoma (EAC) and squamous cell carcinoma, both of which differ significantly in their etiology. Freeze-dried black raspberry (BRB) has been consistent in its ability to modulate the biomarkers and reduce the incidence of carcinogen-induced squamous cell carcinoma in rats. In our previous studies in the esophagoduodenal anastomosis (EDA) model, we have shown that the early modulation of manganese superoxide dismutase (MnSOD) significantly correlates with the development of reflux-induced EAC in rats. In this study we looked at the short-term effects of a BRB-supplemented diet on the modulation of antioxidant enzymes in reflux-induced esophagitis. METHODS: Male SD rats (8 wk old; n = 3-5) were randomized into three groups--sham-operated, fed control AIN-93M diet (SH-CD), EDA operated and fed either control diet (EDA-CD) or 2.5% (w/w) BRB diet (EDA-BRB). The effect of both reflux and dietary supplementation was analyzed 2 and 4 wk after EDA surgery. RESULTS: Animals in the EDA groups had significantly lower weight gain and diet intake compared to SH-CD (P < 0.05). The sham-operated animals received an average esophagitis score of 0.1 ± 0.1; this increased significantly in EDA-CD animals to 1.8 ± 0.14 (P < 0.001 versus SH-CD) and in EDA-BRB group to 1.7 ± 0.06 (P < 0.001 versus SH-CD), with BE changes also present. However, dietary supplementation of BRB did not alter or ameliorate the grade of esophagitis or the induction of BE. BRB diet caused a 43% increase in MnSOD levels compared to EDA-CD (0.73 ± 0.16; P = 0.09); however, this effect was not statistically significant and at 4 wk, EDA-CD (0.58 ± 0.12) showed an increase in MnSOD expression compared to SH-CD (0.34 ± 0.01). CONCLUSIONS: In conclusion, our data suggest that dietary BRB does not increase the levels of cellular antioxidant enzymes or reduce the levels of lipid peroxidation compared to a control diet, in a short-term study of gastroesophageal reflux induction in the EDA animal model. However, it remains to be tested whether this is indicative of its ineffectiveness to inhibit reflux-induced EAC incidence over the long term.

The lower incidence of melanoma in women may be related to increased preventative behaviors.

BACKGROUND: Men have a higher lifetime incidence of melanoma than women. METHODS: Data from the 2005 Health Interview Survey were analyzed for sex differences in response to sun exposure and reported preventive measures among adults. RESULTS: There were 31,428 people surveyed representing the US population. Although women were more likely to burn after 1 hour of sun (8.7% vs 5.4%), they also reported fewer sunburns than men (mean .7 vs .9). Women were also more likely stay in the shade (11.2% vs 6.2%) and always use sunscreen. However, women used a tanning bed more than men (2.1 vs .6 times per year) and were less likely to wear protective clothing when in the sun than men. After controlling preventive behaviors, men were 1.4 times more likely to have had a sunburn during the last 12 months. CONCLUSIONS: Although men more often wear protective clothing and are less likely to use a tanning bed, women are more likely to avoid sun exposure and use sunscreen. The higher incidence of melanoma in men may be explained, in part, by an increased incidence of preventive measures taken by women.

Colocalization of MnSOD expression in response to oxidative stress.

The loss of manganese superoxide dismutase function has been associated with increased incidence of Barrett's esophagus and esophageal adenocarcinoma. In previous studies, we have demonstrated that loss of MnSOD resulted in severe esophageal damage by both endogenous and exogenous bile. However, the alterative manner of MnSOD in esophageal epithelium is largely unknown. In this study, we investigated the expression and localization of MnSOD in response to the exposure to bile salts in an esophageal epithelial cell line. Het-1A cells were seeded at 5 x 10(5) and 10(7) and incubated with taurocholate, cholate, glycocholate, deoxycholate, and the mixture of these bile salts. Mitochondria and cytoplasma were separated, and the expression and localization of MnSOD was determined by Western blot and immunocytochemical assay. Proliferation rates were strongly inhibited in the groups with taurocholate and bile salts mixture at 4 h, with 0.367 +/- 0.042 and 0.396 +/- 0.046, respectively, compared to 0.684 +/- 0.054 in untreated groups (P < 0.05). An increased apoptotic rate compared to untreated group (3.65 +/- 0.59) were significantly increased in taurocholate group and in bile salts mixture group were 33.62 +/- 10.25 and 31.52 +/- 8.97 at 4 h, respectively (P < 0.05). The protein level of MnSOD in mitochondria was increased at 4 h, but with a decreased enzymatic activity after bile salts treatment. Cytoplasmic MnSOD was detected in the cells with bile salts treatment. Immunocytochemical staining demonstrated that esophageal epithelial cell underwent morphological alteration and MnSOD relocalization after bile salts treatment. This is the first study to demonstrate cellular cytosolic MnSOD expression and that this relocalization to the cytosol is a cause for decreased MnSOD enzymatic activity. This suggests that bile salts may contribute to the dysfunction of mitochondria, by enzymatically inhibiting of MnSOD localization and thus activation in the mitochondria.

Should hepatic metastatic colorectal cancer patients with extrahepatic disease undergo liver resection/ablation?

BACKGROUND: Surgical therapy has been proven to be the mainstay of treatment for hepatic metastases from colorectal cancer (CRM) in the appropriate patient. Previous contraindications were patients with extrahepatic disease (EHD) do not benefit from liver resection or ablation. We hypothesized that the survival of patients with EHD who receive aggressive multimodality care would be the same as those without EHD. METHODS: A review of our 1305 patient prospective hepato-pancreatico-biliary database from August 1995 to April 2008 identified 383 patients with surgical management of metastatic CRM to the liver. RESULTS: A total of 39 patients with limited EHD underwent liver resection/ablation vs 344 patients without EHD. There were no significant differences in hepatic disease burden (mean clinical risk score of 2.3 and 2.1 in patients with and without EHD, P=.19, and median number of hepatic metastases of 2 in each group, P=.88) or size of the largest lesion (mean 4.6 vs 4.5 cm with and without EHD, P=.84). EHD consisted of lung metastases in 33%, nodal metastases in 21%, peritoneal in 15%, unknown in 15%, and other in 15%. There was no difference in patients with and without EHD undergoing surgical with resection only in 41% vs 48%, ablation only in 31% vs 30%, and combined resection and ablation in 28% vs 22% (P=.61). Overall survival in patients with EHD was not significantly different (median survival 24 vs 33 months, P=.06). CONCLUSIONS: A thorough understanding of the biology of disease and appropriate multimodality care can lead to improved survival in patients with EHD, when compared with chemotherapy alone.

Radiofrequency ablation vs. resection for hepatic colorectal metastasis: therapeutically equivalent?

INTRODUCTION: The role of ablation for hepatic colorectal metastases (HCM) continues to evolve as ablation technology changes and systemic chemotherapy improves. Our aim was to evaluate the therapeutic efficacy of radiofrequency ablation (RFA) of HCM compared to surgical resection. METHODS: A retrospective review of our 1,105 patient prospective hepatic database from August 1995 to July 2007 identified 192 patients with only hepatic resection or only ablation for HCM. RESULTS: Patients who underwent RFA were similar to resection patients based on a similar Fong score (1.8 vs. 2.1 p = 0.28), presence of extrahepatic disease (15% vs. 9% p = 0.19), mean number of hepatic lesions (2.8 vs. 2.1 p = 0.14), and prior chemotherapy (67% vs. 60% p = 0.33). Median time to recurrence was shorter with ablation than resection (12.2 vs. 31.1 months; p < 0.001). Recurrence at the ablation-resection site was more common with ablation than resection occurring 17% vs. 2% (p < or = 0.001) of the time, respectively. Distant recurrence in the liver was also more common with ablation occurring in 33% of patients vs. 14% for resection (p = 0.002). CONCLUSIONS: Surgical resection is associated with a lower chance of recurrence and a longer disease-free interval than RFA and should remain the treatment of choice in resectable HCM.

Preoperative performance status predicts outcome following heated intraperitoneal chemotherapy.

BACKGROUND: Peritoneal carcinomatosis has a typical natural history of bowel obstruction and death. Significant evidence suggests that cytoreduction with heated intraperitoneal chemotherapy (HIPEC) improves long-term survival for these tumors. METHODS: A retrospective case series of patients who underwent initial HIPEC treatment was performed at 2 moderate-volume centers. Clinicopathologic data were reviewed and univariate analyses performed to determine predictors of periprocedural complications. RESULTS: Twenty-eight patients underwent HIPEC procedures. The most common pathologies were colonic adenocarcinoma and pseudomyxoma peritonei. The median preoperative peritoneal cancer index was 9.5. Thirteen patients had 34 complications, with no postoperative deaths. Pleural effusion and wound infection were the most common complications. Preoperative performance status and the extent of disease were predictive of complications. CONCLUSIONS: Cytoreduction and HIPEC can be done at moderate-volume centers with morbidity and mortality rates comparable with published results from large-volume centers. Preoperative performance status and the extent of disease predict postoperative complications.

Cerebral protection during carotid endarterectomy.

BACKGROUND: Perioperative stroke rates with carotid endarterectomy are 3.4% for asymptomatic and 5.2% for symptomatic patients. Several methods are used to limit perioperative stroke. METHODS: A retrospective chart review of consecutive carotid endarterectomies from January 1, 2000 to February, 28, 2003, was performed. Data were collected on patient demographics, operative procedure, intraoperative monitoring, and outcome. Comparative analysis of intraoperative monitoring and outcome was performed. RESULTS: Two hundred twenty-nine patients underwent 251 carotid endarterectomies. In 196 procedures decision to shunt was based on intraoperative monitoring, 129 by electroencephalogram (EEG), and 67 by stump pressures. Sixteen neurologic events occurred perioperatively, one transient ischemic attack and 15 strokes. The EEG group had 12 strokes, with a 38% event rate in procedures with EEG changes without shunting. The stump pressure group had one stroke. Stroke rate for intraoperative EEG monitoring was elevated (P = 0.02). CONCLUSIONS: Intraoperative EEG based decision to shunt may not be as effective as other methods for prevention of perioperative neurologic events. When EEG changes occur, shunting is necessary.