Tissue specific regulation of VEGF expression during bone development requires Cbfa1/Runx2.

Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis during development, but little is known about the factors that control its expression. We provide the first example of tissue specific loss of VEGF expression as a result of targeting a single gene, Cbfa1/Runx2. During endochondral bone formation, invasion of blood vessels into cartilage is associated with upregulation of VEGF in hypertrophic chondrocytes and increased expression of VEGF receptors in the perichondrium. This upregulation is lacking in Cbfa1 deficient mice, and cartilage angiogenesis does not occur. Finally, over-expression of Cbfa1 in fibroblasts induces an increase in their VEGF mRNA level and protein production by stimulating VEGF transcription. The results demonstrate that Cbfa1 is a necessary component of a tissue specific genetic program that regulates VEGF during endochondral bone formation.

Surgical therapy for Crohn's disease.

Recurrence of disease after restorative operation for Crohn's disease is the rule rather than the exception. In fact, studies using colonoscopic surveillance show that minute recurrent lesions appear early on after operation in the majority of patients. Radical extirpation of disease does not reduce the rate of recurrence but only predisposes to the development of short bowel syndrome. Unfortunately, although in preliminary studies some prophylactic drug regimens seem to delay recurrence, no agent has been shown to be sufficiently potent to change this basic picture. Cure is possible in many cases of predominately colonic disease, but this comes at the expense of a permanent ileostomy. Despite these gloomy statistics, 70% or more of patients require one or more operations during their course. This conundrum is managed by using conservative indications for operation and by bowel-conserving operative procedures. Thus employed and carried out, operation has a favorable impact on the quality of life of these patients. Similarly conservative surgical treatment of the perineal complications, which are frequent and devastating, can be of enormous benefit.

Use of a reperfusion catheter after angioplasty dissection for salvage of ischemic renal allograft: case report.

Percutaneous transluminal angioplasty was performed on a right common iliac artery stenosis presumed to be causing renovascular hypertension in a patient with a renal allograft anastomosis to the right external iliac artery. This was complicated by an obstructive dissection resulting in acute threatening renal allograft ischemia. Renal blood flow was restored by means of a transluminal reperfusion catheter until corrective surgery could be performed. This case is reported because such catheters can be acutely helpful to the interventionalist, and they have not been described in the radiology literature.

Aluminum hydroxide gel bezoar--CT diagnosis.

An obstructing aluminum hydroxide gel bezoar was first recognized on a retrograde gastrografin study through an ileostomy. In retrospect, a computed tomographic (CT) scan had demonstrated the bezoar as a high density intraluminal mass surrounded by somewhat less dense contrast material distending the bowel. A CT image of a phantom made of aluminum hydroxide gel surrounded by gastrografin was remarkably similar.

The long-term outcome of restorative operation in Crohn's disease: influence of location, prognostic factors and surgical guidelines.

The course of all 113 patients with Crohn's disease whose initial procedure involved an anastomosis operated upon from 1942 to 1972 was followed through 1980. The calculated cumulative 30-year total mortality was 23.4%, 16.7% disease-related. The cumulative recurrence rate was 29% at five years, 52% at ten years, 64% at 15 years and 84% at 25 years, with no important differences between disease locations and types of operation. Sex, age, duration, granulomas, enteral or perirectal fistulas and length of the resection, the disease, and the proximal resection margin had no significant influence on the rates of development of recurrent disease or on functional outcome. By far the most common site of recurrence was the neo-terminal ileum, but in ileocolitis compared with ileitis, recurrence was 5.2 times more likely (p = 0.0001) to involve the adjacent or remote colon as well. Moreover, only 1/63 ileitis patients eventually required ileostomy, whereas 15/47 patients with ileocolitis or colitis ultimately required this procedure (p less than 0.001). The current status of the patients was excellent or good in 64% and unwell or dead related in 24%. Urolithiasis developed in 19%.

Proctitis and colitis following diversion of the fecal stream.

Inflammation limited to excluded segments of the colon was observed in 10 patients without prior inflammatory bowel disease who had undergone colostomy or ileostomy for various indications. With the exception of 1 patient who complained of mucoid rectal discharge, the patients were asymptomatic when the lesion was discovered; 2 others subsequently developed mild symptoms. The proctoscopic findings were similar in appearance to those of mild ulcerative colitis. In 8 of 10 patients the inflammatory changes were confined to the distal few centimeters of the rectum, while in the remaining 2 patients the entire excluded segment was affected. Microscopic alterations were focal and included crypt abscesses, epithelial cell degeneration, acute and chronic inflammation in the lamina propria, and regenerative changes in the crypts. The inflammation persisted for as long as 8 yr in the 5 patients who did not have restoration of intestinal continuity, but subsided in the 5 patients whose colostomies were closed. The prior as subsequent clinical courses of these patients, together with the focal, nonspecific microscopic features, strongly suggest that the inflammation in these patients resulted from diversion of the fecal stream and was not a recognized form of specific or idiopathic colitis. Diversion-related colitis must not be confused with other forms of inflammation since this may result in improper therapy and/or delay in treatment of the condition for which the fecal diversion was performed.

Caudate lobe resection to reduce inferior vena caval hypertension prior to portacaval shunt.

Coexistent caval and portal hypertension was recognized on preoperative angiographic study of a patient with cirrhosis and variceal bleeding. This hemodynamic situation can preclude adequate reduction of portal hypertension by portasystemic shunt and can result in fatal postoperative bleeding. Resection of a very large caudate lobe effectively reduced caval pressure and allowed a direct solution to the problem by portacaval anastomosis, rather than by more complex shunts or by nonshunting procedures previously suggested as alternatives.

Thromboembolism after insertion of the Mobin-Uddin caval filter.

The occurrence, in one patient, of a life-threatening pulmonary embolus 3 days following insertion of a Mobin-Uddin umbrella filter promoted a review of our experience with this device. Over the past 5 years, 41 patients had umbrella filters inserted at the Beth Israel Hospital. Five patients (12%) had proven or probable pulmonary embolization following filer placement. In four of the seven autopsied patients, thrombus was found on the cardiac side of the umbrella, and in one of these patients a fresh embolus was also found in the pulmonary artery. We conclude that the standard (nonheparin-impregnated) Mobin-Uddin umbrella device offers incomplete protection against pumonary embolization in patients who cannot concurrently receive anticoagulant drugs.

Colonic exclusion bypass principle: its use in the palliative treatment of malignant duodenocolic and gastrocolic fistulas.

Two patients with malignant upper gastrointestinal-to-colon fistulas had palliative operations utilizing the exclusion bypass principle. This principle entails isolating the affected portions of the colon from the remaining large intestine and anastomosing it to itself. Exclusion bypass reduces bacterial contamination of the upper tract (which is the important mechanism for the unrelenting diarrhea and malnutrition), eliminates prograde shunting, which can contribute to symptoms in malignant fistulas, and avoids the potential for closed-loop obstruction.

Recurrence in Crohn's colitis: the numbers game.

There has been great controversy about the proper role of operation in the management of colonic Crohn's disease because of disagreement about the frequency of recurrence. Since, in our retrospective studies, the majority of patients with colonic Crohn's disease had a previous diagnosis of ulcerative colitis, accurate determination of the recurrence rate in colonic Crohn's disease requires review of all patients with colonic inflammatory bowel disease in order to define the population at risk. Using objective means for diagnosis and for the assessment of outcome, we have found that recurrent disease after ileostomy and colectomy occurred in a minority (approximately 16%) of the patients. Both Crohn's colitis and ulcerative colitis followed a generally favorable postoperative course after this procedure, since even those patients who developed recurrent disease usually were rehabilitated by one or more revisions of the ileostomy. We believe that needed operations should not be avoided solely because of a diagnosis of colonic Crohn's disease, since the high recurrence rates and poor prognoses reported in many studies are based on falsely low numbers of those at risk.

Ulcerative colitus and Crohn's disease of the colon - a comparison of the long term postoperative courses.

Patients with colitis and ileocolitis of unknown etiology from two previously reported series have been combined and the follow-up studies have been extended to compare the long term postoperative courses of ulcerative colitis (UC) and Crohn's disease of the colon (CDC). The combined and updated series of 176 patients, 99% of whom could be traced, provided a mean postoperative follow-up period for UC of 14 years (5 to 31) and CDC of 13.1 years (5 to 36). There were highly significant associations between generally accepted clinical and distributional features of UC and CDC and microscopic findings generally regarded as reliable for each. However, because of spectrum of features was found in each entity, neither clinical and distributional nor microscopic features alone are sufficient for diagnosis in every case. There were no differences in gross or disease-related mortality in UC and CDC whatever the method of diagnosis. After anastomotic procedures in CDC a recurrence rate of 73% was found. After proctocolectomy the ileostomy revision rate (considering all types of those which required further excision of ileum) was higher in CDC than UC whether the diagnoses were based on microscopic, clinical, or combined criteria, but the differences reached statistical significance only in the comparison of "clinical UC", with "clinical CDC". Moreover, after the first 2 postoperative years, the risk of having an ileostomy revision in UC and CDC (combined criteria) per patient year follow-up was virtually identical and there were no cases of short bowel syndrome. Differences in the clinical courses of UC and CDC after colectomy and ileostomy are of degree and do not reflect the ultimate course or potential for rehabilitation. Decisions regarding surgical therapy should be made independent of the diagnosis of UC or CDC.