Differential stromal and epithelial localization of cyclooxygenase-2 (COX-2) during colorectal tumorigenesis.

The purpose of the following study is to describe the localization of COX-2 protein and COX-2 mRNA during human colorectal tumorigenesis and to identify potential cellular targets for COX-2 inhibition in chemopreventive strategies. Immunohistochemistry with digital image analysis was used to determine COX-2 protein expression in histologic sections containing synchronous normal colorectal mucosa, adenomas and carcinomas, from 17 previously untreated patients. Epithelial and stromal COX-2 mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), on laser-capture microdissected samples from the same histologies. The stromal compartment in normal colorectal mucosa and adenomas showed higher levels of COX-2 protein expression compared to colorectal carcinomas (p < .0001). Conversely, epithelial COX-2 protein was significantly increased only after development of the invasive phenotype (p < .0001). RT-PCR demonstrated higher stromal COX-2 mRNA expression compared to that within the epithelium for colorectal adenomas and carcinomas. In conclusion, stromal COX-2 may be the target for chemopreventive agents in the early stages of colorectal carcinogenesis.

Premature peripheral vascular disease: clinical profile and abnormal lipid peroxidation.

The aim of this study was to determine any biochemical differences between early-onset peripheral vascular disease and typical onset atherosclerosis, and age-matched controls. A subset of patients present at a young age ( < 50 years) with peripheral vascular disease which pursues an aggressive course. As lipid oxidation seems important in atherosclerosis, total lipid peroxides, oxidized subfractions, and Trolox equivalent antioxidant capacity (TEAC) were studied in patients with premature peripheral vascular disease. Charts were reviewed of patients operated on for vascular occlusive disease over a 5-year period. Patients with early-onset peripheral vascular disease (group I) were evaluated for biochemical abnormalities and compared with typical onset atherosclerotics (group II) and age-matched controls (group III). Sixteen patients with early-onset peripheral vascular disease underwent biochemical evaluation. Conventional lipid profiles did not differ statistically from those of age-matched controls, except for mild elevations in LDL and VLDL in patients with vascular occlusive disease (207 and 195 mg/dl in groups I and 11 versus 157 mg/dl in group III). Total oxidative potential was significantly elevated (P = 0.006) 3.04, 2.15 and 2.04 nmol/ml in groups I, II and III, respectively. Levels of oxidized LDL and VLDL were even more significantly elevated (P = 0.0009) for premature peripheral vascular disease, (1.2, 0.58 and 0.47 nmol/ml in groups I-II). TEAC values did not differ significantly between groups (0.83, 0.82, 0.82 nmol/ml) and did not correlate with total lipid peroxide values for individual patients. In conclusion, lipid peroxides were significantly elevated in patients with premature peripheral vascular disease, the most marked changes being seen in oxidized LDL and VLDL subfractions. Lipid peroxides were elevated when standard lipid profiles were only mildly abnormal. The poor long-term prognosis in these patients suggests the need for aggressive evaluation and treatment of lipid abnormalities.

Long-term follow-up of patients with early atherosclerosis.

PURPOSE: Patients with premature peripheral vascular disease may respond differently than their older counterparts. To determine the impact of early onset of atherosclerosis on outcome, we decided to compare a group of these patients with a group of patients with typical onset of atherosclerosis with regard to early complications, indications for intervention, site of disease at initial presentation (aortoiliac, infrainguinal, or cerebrovascular), and long-term outcomes (secondary revascularization, amputation, and death). METHOD: All patients younger than 50 years old requiring operative intervention between 1987 and 1992 were retrospectively compared with a group of patients greater than 60 years old, randomly selected from patients who underwent operation during the same time period. Patients were evaluated and compared for indications, risk factors, and early and late outcomes. RESULTS: Patients with early onset atherosclerosis at the aortoiliac or infrainguinal level had a higher late amputation rate (17% versus 3.9%, p = 0.02) and poorer overall outcome than their older cohorts. Patients with cerebrovascular disease in both cohorts had similarly good prognoses. CONCLUSION: Aortoiliac or infrainguinal disease diagnosed in patients less than 50 years of age portends a poorer outcome than does similar disease in an older patient population.

Carotid exploration for acute postoperative thrombosis.

To determine the incidence of carotid reoperation and to document operative findings and clinical results, the records of patients requiring early reoperation (after less than 24 hours) during a 10-year period were analyzed with respect to operative findings, clinical outcome, and arterial patency. Endarterectomy was performed in 920 patients, with 27 strokes (3%) and 10 deaths (1%). Early re-exploration was required for 27 patients (3%) for either expanding hematoma (6 patients) or suspected thrombosis associated with a new neurologic deficit (21 patients). Two patients bled from the arteriotomy and 4 bled from surrounding tissues. Exploration for new postoperative neurologic events confirmed thrombosis in 19 cases (91%). Two patients with patent arteries and normal operative arteriograms were felt to have distal embolization, and the arteriotomy was not opened. Causes of thrombosis were intimal flap in 6 patients and closure stenosis in 11; the cause was unknown in 2 cases. All arteries were repaired over a shunt with a patch. Follow-up studies were available for 16 arteries, all of which remained patent. Of patients explored for hemorrhage, there was one death (from myocardial infarction), no neurologic events, and no late infections. Of 21 patients who underwent a second operation for neurologic deficits, 2 died, 8 were unchanged, 2 had minor residual deficit, and 9 had completely resolved deficits. Severe contralateral disease was more common among patients with residual deficits (10 of 12) compared with patients without residual deficits (0 of 9; chi-square = 8.23, P < 0.005). Carotid re-exploration is most commonly undertaken for a new neurologic deficit, usually associated with thrombosis at the operative site. Thrombosis is more often due to arterial narrowing than to an intimal defect. Prompt repair will restore patency and result in improvement in 50% of cases. Neurologic recovery is related to the status of the contralateral artery.

Failure of thrombolytic therapy to improve long-term vascular patency.

PURPOSE: Few data are available on long-term follow-up of arterial segments subjected to thrombolysis. We reviewed all cases of vascular occlusion treated with urokinase to identify early success and determine the influence of postlysis intervention and the nature of the thrombosed segment (i.e., artery vs graft) on long-term patency. METHODS: Data on 134 cases (58 arteries, 76 grafts) treated with high-dose urokinase infusion in the lower limbs over a 7-year period were analyzed. Limbs were divided into five groups on the basis of therapy after lytic infusion to determine long-term efficacy: group I, success with no additional therapy; group II, percutaneous angioplasty alone; group III, limited surgical procedure (operative angioplasty, jump graft); group IV, extensive procedure (new bypass); and group V, revascularization after lytic failure. Long-term results were assessed by life-table analysis and groups compared by log-rank test (Mantel-Haenszel). RESULTS: Initial patency was established in 87 (64.9%) of 134 cases with 5 deaths (3.7%), 11 amputations (8.2%), and 16 complications (11.9%). Follow-up was available in 68.6% of cases for a mean of 10.9 months. No difference was seen between grafts and native arteries. Patency was analyzed at 6, 12, 18, and 24 months. The 24-month patency rate after lysis alone (group I-25.9%) was inferior (p < 0.05) to results after lysis and any subsequent intervention (groups II, III, and IV). The type of intervention did not influence subsequent patency. Twenty-four-month patency of procedures performed after failed thrombolysis (group V, 41.4%) was not different from those after successful lysis (groups I to IV). Twenty-four-month patency in groups II and III (minor interventions, 62.9%) was not significantly different from that of groups IV and V (major interventions, 53.2%) (p > 0.25). CONCLUSIONS: Operative intervention is required to produce long-term arterial patency, even after successful thrombolysis. No statistically significant benefit of thrombolysis on vascular patency was seen in our series.

Late complications of revascularization for radiation-induced arterial disease.

During a 14-year period 23 patients underwent 25 revascularizations for radiation-induced arterial obstructive disease. An average of 5000 rads was delivered, 3 to 24 (mean 9) years before arterial insufficiency, for malignancies of the following origin: gynecologic (n = 9), lymphoma (n = 7), head and neck (n = 5), testicular (n = 1), and lower extremity sarcoma (n = 1). Arterial occlusive disease occurred in the aortic arch vessels (n = 8), visceral aortic vessels (n = 1), and aortofemoral vessels (n = 16). Presenting symptoms were claudication (n = 8), rest pain or nonhealing ulcers (n = 7), transient ischemic attacks (n = 6), asymptomatic bruit (n = 1), and renal insufficiency (n = 1). Reconstructive operations included anatomic bypass (n = 10), extra-anatomic bypass (n = 4), patch angioplasty (n = 5), endarterectomy (n = 3), and resection with interposition graft (n = 1). In this group of patients there were no major perioperative wound complications or other major radiation-associated morbidity. Five patients had late graft infections that manifested from 2 to 5 years after surgery. All occurred in anatomic regions where the bypass graft passed through previously irradiated tissues. Presenting symptoms of infection included a draining groin sinus (n = 3) or soft tissue abscess (n = 2). In all cases the graft had not incorporated into the surrounding tissues when passing through the irradiated area. Treatment included graft excision and extra-anatomic bypass through nonirradiated tissue. One patient died of systemic sepsis. Vascular reconstructive surgery can safely be performed for radiation-induced arterial disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Donor iliac angioplasty and crossover femorofemoral bypass.

We reviewed our experience with 99 patients who had 111 femorofemoral bypass grafts placed over a 10-year period. Mean follow-up was 36 +/- 28 months (range: 1 to 120 months). Bypass alone was performed in 89 cases (group 1). Preoperative donor iliac angioplasty was utilized in 22 cases (group 2). Overall graft failure was 21 of 89 in group 1 and 2 of 22 in group 2 (difference was not significant by chi 2: p greater than 0.05). Clinical success as calculated by life-table analysis was 95%, 83%, 75%, and 67% at 1, 3, 5, and 7 years, respectively, for group 1. Clinical success was 100% and 91% at 1 and 3 years, respectively, and 91% at 42 months for group 2. The success rates were not different for the two groups when analyzed by the log-rank test at 42 months (p greater than 0.30). We conclude that donor iliac angioplasty and femorofemoral bypass is an excellent option for patients with severe occlusive disease of one iliac artery and contralateral disease amenable to angioplasty.

Total excision and extra-anatomic bypass for aortic graft infection.

Reports of high mortality and amputation rates following total excision and extra-anatomic bypass for aortic graft infection have prompted the use of alternate approaches including local antibiotics, partial resection, in situ revascularization, and graft excision without revascularization. Experience with aortic graft infection was reviewed to establish current morbidity and mortality rates and evaluate our bias in favor of total excision and extra-anatomic bypass. Aortic graft infection was identified in 32 patients, 8 with aortoenteric fistulas. The mean interval between graft placement and infection was 34 months. History of groin exposure (75%) or multiple prior vascular surgery (50%) was common. Clinical signs included fever and/or leukocytosis (23 patients), false aneurysm (9 patients), graft thrombosis (6 patients), groin infection (11 patients), and gastrointestinal hemorrhage (6 patients). Microbiologic data, available in 26 patients, demonstrated gram-positive organisms in 15 patients and gram-negative in 9. Multiple organisms were seen in 11 patients. Patients were treated by partial removal with (8 patients) or without (4 patients) revascularization or total removal with (18 patients) or without (2 patients) revascularization. Revascularization was by an extra-anatomic route, either simultaneous or staged. Overall morbidity/mortality was less in the revascularized groups (p = 0.01), while late complications were seen only after partial removal (p less than 0.01). The best results were found after total excision with revascularization. No patient in this group experienced late infection or amputation during a mean follow-up of 34 months (range: 1 to 168 months). Complications after total excision and extra-anatomic bypass for aortic graft infection are lower than generally appreciated. This approach should remain the standard to which other approaches are compared.

Superficial femoral artery as inflow for bypass to the proximal popliteal artery.

We have obtained long term follow-up on 58 patients in whom the superficial femoral artery was used as a donor site for bypass to the proximal popliteal artery. The indication for the reconstructive procedure was intermittent claudication 36%, rest pain 34%, and gangrene 26%. All patients had angiographic evidence of a patent proximal superficial femoral artery and many had relative indications for short bypass such as limited saphenous vein availability or compromised medical condition. There was a cumulative patency rate of 79% by life table method for the series with a six year follow-up. We have observed that the superficial femoral artery is a satisfactory inflow site for proximal popliteal bypass grafts in selected patients. The procedure can maximize use of a limited segment of vein with minimal operative time and morbidity. Inflow stenosis can be revised or long bypass procedures can be offered in the event of graft failure.

Aneurysmal dilatation in saphenous vein bypass grafts.

Three patients are reported who developed aneurysmal degeneration of a saphenous vein arterial bypass graft. All three had hypercholesterolemia and two had marked elevation of triglycerides. One bypass was for occlusive disease and two for popliteal aneurysm. There was a long lag, 3 to 7 years between graft implantation and aneurysmal degeneration. The pathology was similar for all three cases with lipid laden macrophages, loss of elastic lamina, and other atherosclerotic changes in the vein wall. While atheromatous changes and aneurysm formation in saphenous vein bypass grafts are rare, this may occur especially in patients with hypercholesterolemia and hypertriglyceridemia. Careful and prolonged follow-up plus vigorous management of the hyperlipidemic state is mandatory in these patients.

Single-layer anastomosis of the colon and rectum.

A total of 116 one-layer end-to-end anastomoses of the colon and the rectum in 112 patients were studied. Three patients died postoperatively (2.6 per cent). Significant disruption of anastomosis requiring a diverting colostomy occurred in five patients. The study is presented to draw attention to the safety of the single-layer anastomosis.

Experience with single-layer rectal anastomosis.

Anastomotic dehiscence following resection of the large intestine is a serious complication. Satisfactory results of single-layer anastomosis depend upon meticulous technique and a scrupulously clean colon. Out of 65 single-layer anastomoses involving the rectum, significant leakage occurred in 4 patients. The results are reported in order to draw attention to the safety and efficacy of one-layer anastomosis.

Cruveilhier-Baumgarten disease with associated splenic artery aneurysms.

Cruveilhier-Baumgarten Disease is a rare clinical entity. The distinction between C-B Disease and C-B syndrome rests solely on the liver morphology. In C-B Disease, the liver is morphologically normal. A case of a 27-year-old juvenile diabetic female with C-B Disease is presented. She manifested many of the metabolic and hemodynamic changes of cirrhosis including portal hypertension, encephalopathy, and a hyperdynamic cardiovascular state. There was also associated splenomegaly, hypersplenism, and splenic artery aneurysms. Splenectomy and splenic artery ligation were performed. Liver biopsies had normal morphology. The patient has had no recurrence of her symptoms. The pathogenesis of C-B Disease is unknown.