Higher colon cancer tumor proliferative index and lower tumor cell death rate in mice undergoing laparotomy versus insufflation

BACKGROUND: Our laboratory has previously shown that tumors are established more easily and grow larger after laparotomy than after laparoscopy. To characterize these differences in tumor growth further, the tumor cell death rates and tumor proliferation rates were compared in vivo after full sham laparotomy versus carbon dioxide (CO2) insufflation. METHODS: Female Balb/C mice (n = 36) were inoculated intradermally in the dorsal skin with 106 C-26 colon adenocarcinoma cells in 0.1 ml of culture media no more than 1 h before interventions. The mice then were randomized to one of three groups: anesthesia control, CO2 insufflation, or sham laparotomy. The anesthesia control group underwent no procedure. The insufflation group underwent CO2 pneumoperitoneum (4-6 mmHg) for 20 min via a 20-gauge angiocatheter. The laparotomy group underwent a midline incision from xiphoid to pubis, which was closed after 20 min. Tumors were excised from half the mice in each group on postoperative day 7, and from the remaining mice on postoperative day 14. Sections of tumors were made then stained separately for free 3? hydroxyl ends of genomic deoxyribonucleic acid (DNA) using fluorescein-deoxyunidine triphosphate (dUTP), and immunohistochemically for proliferating cell nuclear antigen (PCNA). Apoptosis was measured by quantitating DNA strand breaks in individual cells using fluorescence microscopy. Fluorescein-positive cells in five random high-power fields (x200) were counted in a blinded fashion. The proliferative index of each tumor was determined by averaging PCNA positive cells in five high-power fields (x450) counted in a blinded fashion with the aid of an optical grid. RESULTS: On postoperative day 7, there was no significant difference in the proliferative index or apoptotic rates among the three groups. On postoperative day 14, the proliferative index in the laparotomy group was significantly higher than in either the insufflation or control group (p < 0.001). The proliferative index in the insufflation group also was significantly higher than in the control group (p < 0.05). Inverse differences in apoptotic rates were found. The apoptotic rate in the laparotomy group was significantly lower than in either the insufflation (p < 0.05) or control group (p < 0.001). The apoptotic rate in the insufflation group was significantly lower than in the control group (p < 0.001). CONCLUSIONS: We have demonstrated that there is a significantly higher rate of tumor cell proliferation and a significantly lower rate of tumor cell death with the C-26 colon adenocarcinoma tumor line after laparotomy than after insufflation or anesthesia alone on post-operative day 14. The mechanisms of these phenomena are unclear. It appears that certain factors postoperatively stimulate tumors to proliferate at a higher rate, causing tumor cells to die at a lower rate in the laparotomy group than in the insufflation group.     

Potential Influence of Acute CT on Inpatient Costs in Patients with Ischemic Stroke

RATIONALE AND OBJECTIVES: Patients presenting with ischemic brain symptoms have widely variable outcomes dependent to some degree on the pathologic basis of their stroke syndrome. The purpose of this study was to determine the cost implications of the emergency use of a computed tomographic (CT) protocol comprising unenhanced CT, head and neck CT angiography, and whole-brain CT perfusion. MATERIALS AND METHODS: By using a retrospective patient database from a tertiary care facility and publicly available cost data, the authors derived the potential savings from the use of CT angiography. CT perfusion, or both at hospital arrival by means of a cost model. The cost of the CT angiography-CT perfusion protocol was determined from Medicare reimbursement rates and compared with that of traditional imaging protocols. Cost savings were estimated as a decrease in the length of stay for most stroke patients, whereas the most benign (lacunar) strokes were assumed to be managed in a non-acute setting. Misdiagnosis cost (erroneously not admitting a patient with nonlacunar stroke) was calculated as the cost of a severe complication. Sensitivity testing included varying the percentage of misdiagnosed patients and admitting patients with lacunar stroke. RESULTS: The nationwide net savings that would result from the adoption of the CT angiography-CT perfusion protocol are in the $1.2 billion range (-$154 million to $2.1 billion) when patients with lacunar strokes are treated nonacutely and $1.8 billion when those patients are admitted for acute care. CONCLUSION: The results demonstrate the potential effect of implementing a CT angiography-CT perfusion protocol. In particular, prompt CT angiography-CT perfusion imaging could have an effect on the cost of acute care in the treatment of stroke.     

Utility of left subclavian artery revascularization in association with endoluminal repair of acute and chronic thoracic aortic pathology

BACKGROUND: A rapidly increasing number of thoracic aortic lesions are now treated by endoluminal exclusion by using stent grafts. Many of these lesions abut the great vessels and limit the length of the proximal landing zone. Various methods have been used to address this issue. We report our experience with subclavian artery revascularization in association with endoluminal repair of acute and chronic thoracic aortic pathology. METHODS: Thirty (43%) of 70 patients undergoing thoracic endovascular stent-graft placement from January 2001 to August 2005 had lesions adjacent to or involving the origin of the subclavian artery. The mean age was 62 years (range, 22-85 years; 63% were men, and 37% were women). This subgroup of 30 patients had indications for repair that included thoracic aortic aneurysm (n = 15), traumatic transection (n = 6), chronic dissection with pseudoaneurysm (n = 5), and acute dissection with intramural hematoma (n = 4). All 30 patients had the subclavian origin covered by the stent graft. In eight cases (27%), no effort was made to revascularize the subclavian artery before or during the endograft placement procedure. Twenty-three (77%) of 30 patients underwent subclavian to carotid artery transposition (n = 21) or bypass (n = 2) before (n = 12; average of 14 days before stent-graft placement), concomitant with (n = 10), or after (n = 1) the endovascular procedure. Physical examination and computed tomography scans were performed after surgery at 1, 6, and 12 months and annually thereafter. The mean follow-up was 18 months (range, 1-51 months). RESULTS: Five acute complications occurred in the eight patients (63%) who had the subclavian artery covered without pre-endograft revascularization and included four patients who experienced stroke (accounting for the only death) and one patient who developed symptomatic subclavian-vertebral steal that necessitated transposition 7 months later. Two (9%) of the 23 patients who had subclavian revascularization experienced left-sided vocal cord palsies, and 1 patient (4%) developed lower extremity paraparesis secondary to spinal cord ischemia. No late endoleaks related to retrograde sac perfusion from the most distal great vessel have been identified in any patient. CONCLUSIONS: Subclavian revascularization procedures can be performed with relatively low risk. Complications are rare, and patient recovery is rapid. Although this is not necessary in all cases, we advocate subclavian to carotid transposition when the aortic lesion is within 15 mm of the left subclavian orifice to prevent type II endoleak or perfusion of a dissected false lumen when the ipsilateral vertebral artery is patent and dominant or when coronary revascularization using an ipsilateral internal mammary artery is anticipated and in cases that necessitate extensive coverage of intercostals that contribute to spinal cord perfusion. Carotid to subclavian artery bypass should be reserved for patients with a patent internal mammary artery conduit perfusing a coronary vessel and should be combined with proximal subclavian ligation.     

Results of randomized controlled trials of low-versus high-osmolality contrast media

The authors reviewed 100 randomized controlled trials (RCTs) conducted in humans to compare safety or efficacy of new low-osmolality contrast media (LOM) with that of high-osmolality contrast media (HOM). Findings of the 43 RCTs judged to be of the highest quality suggest that the efficacy of LOM in imaging is equal or superior to that of HOM for all routes of administration. Heat sensation occurred less often with LOM for all routes and pain occurred less often with LOM for intraarterial routes. No differences were seen in nephrotoxicity or in frequency of nausea, vomiting, urticaria, bronchospasm, laboratory test abnormalities, or neurologic events. Greater cardiovascular changes were seen with HOM, including increased or decreased heart rate, increased left ventricular end-diastolic pressure, decreased systolic pressure, and QT prolongation, depending on route of administration. To demonstrate whether a reduction in clinically significant adverse outcomes truly occurs with LOM, trials will need to enlist larger numbers of patients and employ appropriate outcome measures. Future trials should stratify patients according to their risk of adverse reactions to provide better information about benefits of LOM in low- versus high-risk patients.     

Protein-restricted diets in diabetic nephropathy

Low-protein diets in nondiabetic renal failure may slow the progressive loss of renal function in some patients, but few studies have detailed the nutritional consequences of these diets in patients with diabetic nephropathy. We studied 7 patients with insulin-dependent diabetes mellitus and chronic renal insufficiency [mean +/- SEM creatinine clearance (S, U): 28.3 +/- 6.5 ml/min (0.47 +/- 0.11 ml/s x 1.73/A)] for 15 weeks who were prescribed a diet of 0.6 g protein/kg ideal body weight. Midarm muscle circumference (24.1 +/- 1.8 at onset vs. 24.5 +/- 1.5 cm at completion), triceps skinfold thickness (21.6 +/- 3.1 vs. 21.0 +/- 1.5 mm), body weight (71.8 +/- 4.1 vs. 71.2 +/- 4.6 kg), and serum albumin [3.0 +/- 0.1 vs. 3.2 +/- 0.1 g/dl (30 +/- 1 vs. 32 +/- 1 g/l)] remained stable. Based on urinary nitrogen excretion, diet diaries overestimated the degree of dietary protein restriction; there was good adherence to the diet as evidenced by a reduction in urinary urea nitrogen (average 32%). Blood glucose control was maintained despite increased carbohydrate intake. On average, creatinine clearance did not change significantly, but proteinuria diminished slightly (1.8 +/- 0.2 vs. 1.5 +/- 0.6 g/day). These results indicate that 0.6 g/kg/day protein diets did not cause protein depletion in insulin-dependent diabetic patients. Longer-term studies are indicated to assess more fully the efficacy of these dietary regimens in reducing proteinuria or benefiting diabetic nephropathy.