David Neufeld

Magnetic resonance imaging using gadolinium labeled monoclonal antibody

Gadolinium was attached to antibodies and tested in vitro and in vivo for its effect on proton relaxation enhancement. Using the cyclic anhydride method, diethylenetriaminepentaacetic acid (DTPA) was attached to albumin, IgG and anti-CEA monoclonal antibody. Gadolinium (Gd) was then chelated to the protein complexes forming protein-DTPA-Gd complex. With this technique approximately 9 atoms of Gd could be attached to each albumin molecule, 4 to each IgG molecule and 1.5 to each monoclonal antibody molecule. The minimal in vitro concentration of Gd in the form of IgG-DTPA-Gd necessary to produce proton relaxation enhancement at 0.35 tesla was 10(-1) mM. An in vivo experiment using anticarcinoembryonic antigen (CEA) monoclonal antibody-DTPA-Gd in hamsters implanted with human colon carcinoma resulted in a tumor concentration of Gd of less than 10(-4) mM. No enhancement of the tumors was detected at that concentration. For monoclonal antibodies to function as selective MR contrast agents, substantial advances in technology must occur.

Severe complication of rubber band ligation of internal hemorrhoids.

In light of recent reports describing severe and even fatal complications, the authors would like to report good results in two patients with massive edema and one with localized necrosis following rubber band ligation of internal hemorrhoids, which were recognized early and treated aggressively. The potential for severe complications emphasizes the need for determining other causes of rectal symptoms before ligation of hemorrhoids is undertaken

Octreotide Treatment in Patients with Severe Acute Pancreatitis

We investigated the effect of octreotide in the treatment of severe acute pancreatitis in a case–control study. Experimental and clinical studies on the effect of octreotide in the treatment of acute pancreatitis have shown controversial results. Since January 1992, we have been conducting a prospective randomized study on the effect of octreotide in severe acute pancreatitis, in three hospitals in Israel. The entering criteria included three or more of the Ranson prognostic signs and CT findings of severe pancreatitis. Patients were randomly assigned to conservative treatment either with or without octreotide (0.1 mg subcutaneously three times a day). The end points of the study included: complication rate (ARDS, sepsis, renal failure, pseudocyst, fistula, and abscess), length of hospital stay, and mortality. From January 1992 to December 1996, 60 patients entered the study. After evaluating the files, 10 patients were excluded due to failure to meet the entering criteria, incomplete data, or incorrect diagnosis. Of the remaining 50 patients, 25 were assigned to octreotide (treatment group) and 25 to conservative treatment only (control group). The two groups matched with regard to age, sex, etiology, and severity of the disease. The complication rate was lower in the treatment group with regard to sepsis (24% vs 76%, P = 0.0002) and ARDS (28% vs 56%, P = 0.04). The hospital stay was shorter in the treatment group (20.6 vs 33.1 days, P = 0.04). Two patients died in the treatment group and eight in the control group (P < 0.019). These results suggest that octreotide may have a beneficial effect in the treatment of severe acute pancreatitis.

Enema-induced perforation of the rectum in chronically constipated patients

INTRODUCTION: The use of retrograde irrigation enemas is common in the treatment of chronic constipation, especially in the elderly. Perforation of the rectum and sigmoid colon caused by cleansing enemas, used by chronically constipated patients, has not been previously described. METHODS: We reviewed all patients with colorectal perforations caused by irrigation enemas admitted to our service in the three-year period between January 1995 and December 1997. RESULTS: Thirteen patients were treated by our surgical service because of perforations of the rectum and sigmoid colon related to a previous retrograde irrigation enema. Ten of these patients came from nursing homes, and the other three lived at home. The relevant information relating the enema administration to the patients condition was given in only two of the ten patients referred to the emergency room by the institutions nursing or medical staff. In the other eight the information was vague and sometimes misleading. The diagnosis of colorectal performation was made by history, plain abdominal x-rays, and CT scan with or without meglumine diatrizoate enemas. Ten patients survived, regardless of age, previous diseases, or operative findings. In all of them, diagnosis was made within 36 hours from the perforation. The three deaths occurred in patients in whom the diagnosis was made late. CONCLUSIONS: Awareness of the possible injury from enemas administered to chronically constipated patients should be stressed. A high degree of suspicion by the attending physician is extremely important, because prompt diagnosis and early surgical treatment carries a relatively good prognosis.

Endorectal sliding flap repair of complicated anterior anoperineal fistulas

This report presents experience with a safe and effective form of treatment for anal fistulas that involve a significant portion of the sphincter mechanism. The technique includes removal of the involved crypt, closure of the internal opening with a sliding endorectal flap, and counter drainage of the fistula tract. This series includes eight patients treated over a five-year period with a follow-up of up to five years. This limited series had no complications and one case of early recurrence. Most of these patients had had previous failed attempts at correction of the fistula. The main advantage of this mode of treatment is preservation of the integrity of the sphincter muscle, thus avoiding the high risk of incontinence that is inherent especially with anteriorly located fistulas in females. It is proposed that, because it does not transect the sphincter anteriorly, this technique is safer than the placement of setons, as has been previously advised for management of anterior fistulas. The different treatment techniques for anal fistulas, including complications, recurrence rates, surgical techniques, and indications for types of management are reviewed.

Long-term results of fibrin glue treatment for cryptogenic perianal fistulas: a multicenter study.

BACKGROUND: Instillation of fibrin glue, a simple and safe procedure, has been shown to have a moderate short-term success rate in the treatment of cryptogenic perianal fistulas. OBJECTIVE: This study aimed to assess the long-term outcome of this procedure. DESIGN: This study included a retrospective chart review and telephone interviews. SETTINGS: This study was conducted at 4 university-affiliated medical centers. PATIENTS: Patients were included who underwent fibrin glue instillation for complex cryptogenic fistula between 2002 and 2003 within a prospective trial and had successful healing. INTERVENTIONS: Fibrin glue was instilled for complex cryptogenic fistula. MAIN OUTCOME MEASURES: The main outcome measure was long-term fistula healing. RESULTS: Sixty patients participated in the initial trial; the fistulas in 32 of these patients were healed at 6 months. We have located and interviewed 23 (72%) of those patients. Seventeen (74%) patients remained disease free at a mean follow-up of 6.5 years. Six (26%) patients had variable degrees of recurrence; 4 needed further surgical intervention and 2 were treated with antibiotics only. Recurrent disease occurred at an average of 4.1 years (range, 11 mo to 6 y) from surgery, and on several occasions was at a different location in the perianal region. None of the patients experienced incontinence following the procedure. LIMITATIONS: The retrospective nature of this long-term follow-up was a limitation. Twenty-eight percent of the potentially eligible patients were lost to long-term follow-up. CONCLUSIONS: Short-term success of fibrin glue in the treatment of cryptogenic perianal fistula is predictive of long-term healing, but a quarter of those healed in the short term may develop recurrent symptoms in the long run. Injection of fibrin glue remains a safe and simple procedure and may preclude extensive surgery.

Endoscopic management of anastomotic colon strictures with electrocautery and balloon dilation

regarding colonic dilation. l ,3,8 Previously, the treatment of benign stenosis was a matter for surgery, and only strictures of the distal rectum and anal region were successfully treated by Regar dilating tubes. Fiberoptic endoscopy allows a conservative alternative approach if the stenosis is benign, cicatricial, and short, even in segments distant from the anus. Nevertheless, the procedure is not without risk and requires technical skill. Moreover, we believe that in some cases it should be complementary rather than an alternative to surgery. In fact, dilation can sometimes be diagnostic, showing a recurrent neoplasia above the stricture which was believed to be cicatricial by biopsy. In these cases dilation may be the first step of a second look operation. In conclusion, we believe that endoscopic dilation can become a routine technique in the diagnosis and treatment of colonic stenosis. With more experience its limits will be better defined, but in our early

Tumor localization and radioimaging with mixtures of radioiodinated monoclonal antibodies directed to different colon cancer associated antigens

After demonstrating enhanced tumor cell binding with a mixture of monoclonal antibodies (MAbs) in vitro, biodistribution and immunoscintigraphy studies with 3 radioiodinated anti-colon cancer MAbs and a non-specific control MAb (MOPC) were conducted in a human colon cancer (GW-39)-hamster model system. Each of the specific MAbs, but not MOPC, demonstrated extensive tumor binding and in scintigrams affected visualization of all large tumors (greater than 0.85 g) over background. Using single MAbs, few small tumors (0.19-0.50 g) were defined above background (0-29%). However, with combinations of these specific MAbs small tumors were more frequently defined in scintigrams (43-67%). Radioimages using higher doses of MAbs and small, younger tumors more clearly demonstrated the superiority of a MAb mixture. These results confirmed that combinations of MAbs to different antigens can detect smaller tumors with better tumor localization when compared to component MAbs used singly. This study supports the concept that tumor targeting and detection may be enhanced with appropriate mixtures of MAbs.