Chemoprevention of metaplasia initiation and carcinogenic progression to esophageal adenocarcinoma by resveratrol supplementation.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol found in the skin of the grape and red wine, has been found to have chemopreventitive effects in some carcinogenic models. The effects of resveratrol on the initiation of Barrett's metaplasia and the carcinogenic progression to esophageal adenocarcinoma have not been evaluated. The aim of this study was to evaluate the effects of resveratrol on the transition from reflux esophagitis to Barrett's metaplasia to dysplasia to esophageal adenocarcinoma in an established rat model. Male Sprague-Dawley rats underwent esophagoduodenal anastomosis as per institutional approved protocol. They were then treated twice weekly with intraperitoneal injection of 7 mg/kg of resveratrol or saline. Additional nonoperated rats served as controls. The rats in each group were assigned to 1, 3, or 5-month subgroups. The distal esophagus was preserved for blinded histopathological examination at the time of harvest. Thirty-one animals in the 5-month resveratrol group showed a decreased severity of esophagitis (P<0.0001), incidence of intestinal metaplasia (P = 0.3567), and incidence of carcinoma (P = 0.4590) as compared with both the saline and nonoperated control groups. In conclusion, morphological characteristics consistent with decreased esophagitis and incidences of metaplasia and esophageal adenocarcinoma were seen on histopathology in the resveratrol group. Resveratrol resulted in a small diminution of the carcinogenic effects and progression to metaplasia, and further human studies are designed to explore the potential anticarcinogenic mechanism.

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.

Administration of glutamine after hemorrhagic shock restores cellular energy, reduces cell apoptosis and damage, and increases survival.

BACKGROUND: Hemorrhagic shock causes a rapid depletion of adenosine triphosphate (ATP) and an increase of the terminal metabolite xanthine. Free radicals generated from xanthine oxidase play a major role in cell injury. Programmed cell death, apoptosis, is a major pathway causing reperfusion injury. During apoptosis, cytosolic cytochrome-c is released from damaged mitochondria, and it further initiates activation of apoptosis as evidenced by the appearance of caspase-3. The bcl-2 protein serves as an antiapoptosis found on the mitochondrial membrane. Glutamine has been known as a conditionally essential nutrient and seems to have beneficial effects in critically ill patients. The hypothesis of the present study is that glutamine administered during resuscitation following hemorrhagic shock would restore the depletion of hepatic ATP, reduce cellular apoptosis, and increase survival. METHODS: Male Sprague-Dawley rats were randomly assigned to 3 groups for resuscitation after the same pattern of hemorrhagic shock: Ringer's lactate (LR 21 ml/kg); Alanine-glycine (LR with alanine 0.15 gm/kg and glycine 0.18 gm/kg); and glutamine (LR with glutamine 0.3 gm/kg). Hepatic ATP and xanthine was measured at different time periods. Hepatic apoptosis was measured and the levels of cytosolic cytochrome-c, caspase-3 and bcl-2 were analyzed. Another group of rats were used for survival study. RESULTS: Glutamine administered during resuscitation following hemorrhagic shock partially restored the depletion of hepatic ATP, reduced cellular apoptosis, and increased survival. CONCLUSIONS: Glutamine administration during resuscitation significantly protected the liver from tissue damage caused by hemorrhagic shock. Glutamine supplementation may offer opportunities for therapeutic intervention during and after shock.

Effect of DHEA on the hemodynamic response to resuscitation in a porcine model of hemorrhagic shock.

BACKGROUND: Hemorrhagic shock is a major cause of death from trauma. Pharmacologic treatment has not been satisfactory. The objective of this study was to use a porcine model of hemorrhagic shock and resuscitation to access the hemodynamic effects of dehydroepiandrosterone (DHEA), an adrenal steroid hormone reported to improve cardiac function in patients. METHODS: Hemorrhagic shock was produced in 20- to 30-kg male Yorkshire pigs anesthetized with 2% isoflurane by withdrawing blood through a carotid cannula to a mean arterial pressure (MAP) of 40 to 45 mm Hg and maintaining that level for 60 minutes by further removals of blood. Resuscitation was with 21 mL/kg Ringer's lactate (LR), with (n = 6) or without (n = 6) DHEA (4 mg/kg) dissolved in propylene glycol. The animals were killed after 7 days. Continuous cardiac output (CCO) was recorded using a modified Swan-Ganz catheter system. MAP, heart rate (HR), central venous pressure (CVP), and pulmonary arterial pressure (PAP) were measured every 5 minutes until 60 minutes postresuscitation. From MAP, CCO, HR, and CVP, we calculated total peripheral resistance (TPR), stroke volume (SV), and left ventricular stroke work (SW). RESULTS: The MAP, CCO, SV, and SW decreased significantly during hemorrhagic shock, and then gradually increased to baseline levels during and 1 hour after resuscitation. The TPR was increased during hemorrhagic shock, and then gradually decreased to baseline levels during and after resuscitation. DHEA administration was associated with no significant improvement. CONCLUSION: DHEA when added to standard fluid resuscitation showed no added benefit as resumed by the hemodynamic response.