Human antibodies targeting cell surface antigens overexpressed by the hormone refractory metastatic prostate cancer cells: ICAM-1 is a tumor antigen that mediates prostate cancer cell invasion

Transition from hormone-sensitive to hormone-refractory metastatic tumor types poses a major challenge for prostate cancer treatment. Tumor antigens that are differentially expressed during this transition are likely to play important roles in imparting prostate cancer cells with the ability to grow in a hormone-deprived environment and to metastasize to distal sites such as the bone and thus, are likely targets for therapeutic intervention. To identify those molecules and particularly cell surface antigens that accompany this transition, we studied the changes in cell surface antigenic profiles between a hormone-sensitive prostate cancer line LNCaP and its hormone-refractory derivative C4-2B, using an antibody library-based affinity proteomic approach. We selected a naïve phage antibody display library to identify human single-chain antibodies that bind specifically to C4-2B but not LNCaP. Using mass spectrometry, we identified one of the antibody-targeted antigens as the ICAM-1/CD54/human rhinovirus receptor. Recombinant IgG1 derived from this single-chain antibody binds to a neutralizing epitope of ICAM-1 and blocks C4-2B cell invasion through extracellular matrix in vitro. ICAM-1 is thus differentially expressed during the transition of the hormone-sensitive prostate cancer cell line LNCaP to its hormone-refractory derivative C4-2B, plays an important role in imparting the C4-2B line with the ability to invade, and may therefore be a target for therapeutic intervention

Management of Anal Incontinence.

Anal incontinence can be attributed to anatomic and physiologic alterations in the external sphincter, internal sphincter and puborectalis muscle. Altered compliance or changes in the sensory threshold are contributing factors. In addition to history and physical examination, anal manometry and radiologic examination of the anorectal angle are helpful in determining the exact causative factors. Depending on the cause, either medical therapy or surgical repair can control anal incontinence

Is Anorectal Surgery on Chronic Dialysis Patients Risky?

Patients on chronic hemodialysis for end-stage renal disease (ESRD) may develop anorectal problems necessitating surgery. From January 1984 to December 1987, 18 ESRD patients underwent anorectal surgery. During this period, a mean of 215 patients underwent dialysis. Patients with ESRD present with characteristic problems: chronic constipation, need for dialysis pre- and postoperatively with heparin infusion, anemia, anticoagulation secondary to the consequences of uremia, and significant medical problems including coronary artery disease, diabetes mellitus, hypertension, and chronic obstructive pulmonary disease (COPD). Two patients had concomitant anal fissure, two had fistula-in-ano, and one had an acute perianal abscess. In two patients, the postoperative course was complicated by hemorrhage and, in one patient, by abscess formation. There was no delay in wound healing compared with a cohort group. The essentials of perioperative management are discussed with respect to timing of dialysis, methods of anesthesia and pain management, coagulation screening, and complications. Patients on well-managed chronic dialysis will tolerate anorectal surgery without undue jeopardy

Management of Anorectal Horseshoe Abscess and Fistula.

Over a 10-year period 69 patients were treated consecutively for posterior and anterior horseshoe abscesses and fistulas. Fifty-nine patients had posterior and ten had anterior abscesses or fistulas. There were 52 patients with acute abscess. Treatment consisted of incision and drainage, incision and drainage with primary fistulotomy, incision and drainage with primary fistulotomy and counter-drainage, and incision and drainage with insertion of seton. Seventeen patients with chronic fistulas were treated by primary fistulotomy with curettage, or incision and drainage with insertion of seton. Patients were followed from three months to ten years with a mean follow-up of three years. No incidences of incontinence were reported in this series. The overall rate of recurrence was 18 percent, and included only patients with posterior abscesses and fistulas. Recurrence was related to the failure to maintain prolonged drainage in the midline after primary fistulotomy. The use of seton for delayed fistulotomy appears to promote wound drainage and precludes premature wound closure. More liberal use of the seton in the treatment of horseshoe abscesses and fistulas is advocated

Metronidazole vs. Erythromycin, Neomycin, and Cefazolin in Prophylaxis for Colonic Surgery.

A prospective, double-blind, randomized study was undertaken to compare perioperative parenteral metronidazole and erythromycin, One neomycin, and cefazolinhundred fifty-five patients were randomized into two groups by the pharmacy department. The resulting difference between the overall septic complication rate in patients receiving erythromycin, neomycin, and cefazolin (10.9 percent) and the rate in patients receiving metronidazole alone (31.9 percent) was significant. This indicates that an antibiotic to cover aerobic bacteria should be added to the regimen when metronidazole is used

Horseshoe Abscess Fistula. Seton Treatment.

A study was undertaken to analyze seton fistulotomy with counter drainage as a treatment modality for horseshoe abscess fistula. In a previous report of 27 patients with partial or complete horseshoe abscess fistula, 24 patients underwent primary fistulotomy and counter drainage with a recurrence rate of 28.6 percent. Two patients were treated by seton fistulotomy and counter drainage with no recurrence. Therefore, nine additional patients underwent this procedure. Recurrent horseshoe abscess fistula occurred in 2 of 11 patients (18.1 percent). Seton fistulotomy with counter drainage has become the authors\u27 operative procedure of choice for horseshoe abscess fistula. This method may prove more effective if the true primary abscess cavity is identified, the seton is removed appropriately, and postoperative care of the cavity is adequate. Method of management is discussed

Nephrocolic Fistula.

A patient with nephrocolic fistula secondary to perinephric abscess was treated successfully with nephrectomy, colonic resection, and colocolostomy

The Bacon Pull-through Procedure.

Twenty-eight patients who underwent the Bacon pull-through procedure for carcinoma of the midrectum were reviewed retrospectively. The results were comparable to low anterior resection and abdominoperineal resection. Although the indications are limited, it is a viable option in a highly selected group of patients