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Biomedical subjects

T A Stellato

Publications and source records attributed to T A Stellato.

At least 19 recordsLinked to original sources

Aberrant crypts in human colonic mucosa: putative preneoplastic lesions.

Aberrant crypts are recognized in methylene blue-stained, unsectioned, colonic mucosa by their increased size, elliptical lumenal opening, thicker epithelial layer, and increased pericryptal region. Aberrant crypt foci in rodents are observed as early as 2 weeks and for at least 9 months after a single dose of carcinogen, have a distribution that parallels that of tumors, and have an increased number of aberrant crypts per focus with time after the carcinogen dose. The ability to quantify these lesions in the entire colon of rodents in less than an hour suggests that aberrant crypts may provide a highly efficient in vivo bioassay for colon carcinogens. Since aberrant crypt foci appear to be the earliest identifiable putative precursors of colon cancer, they represent lesions that can be characterized further for the earliest genetic and biochemical alterations. In F344 rats, we have demonstrated that aberrant crypts have multiple histochemically-detectable enzyme alterations. Using similar techniques, we were the first to demonstrate aberrant crypts in unsectioned human mucosa. After embedding and sectioning, these microscopic aberrant crypts resemble rare lesions described earlier in the literature after extensive serial sectioning. In rats and humans, aberrant crypts may be histologically normal or display varying degrees of dysplasia and histochemically-detectable altered enzyme activities. These putative, preneoplastic lesions should reveal early changes that precede colon cancer and ways to alter their progression.

5'-Nucleotidase

History of laparoscopic surgery.

Laparoscopic surgery has a long and colorful history. Although most general surgeons, especially in the United States, have discovered this technology only recently with the advent of videolaparoscopy, extensive diagnostic and therapeutic laparoscopy has been accomplished throughout the twentieth century, especially in Europe. Since its origin in 1901 by Kelling to the development of the computer chip television camera in the late 1980s, the history of laparoscopy entails a chronicle of discovery, innovation, and rediscovery. An appreciation for this historical chronicle may actually provide surgeons with a secure foundation as they embark on the new era of videolaparoscopy.

History, 20th Century

Single dose cephalosporin prophylaxis in high-risk patients undergoing surgical treatment of the biliary tract.

During June 1985 through October 1986, 292 patients considered to be at high risk for having postoperative complications develop underwent cholecystectomy and were evaluated in a multicenter, randomized, prospective, double-blind study. Risk factors included age greater than 70 years, acute cholecystitis within the previous six months, obstructive jaundice, obesity and diabetes mellitus. One gram of cefamandole was administered intravenously to 144 patients and 148 patients received 1 gram of cefotaxime intravenously 30 minutes prior to skin incision. Culture-proved bactibilia was found in 55 patients and 11 of the patients had choledocholithiasis. Of the risk factors considered to place patients at high risk for postoperative infectious complications, obesity and acute cholecystitis proved to be the more common. However, age greater than 70 years, diabetes mellitus and obstructive jaundice were more significant risk factors predisposing to bactibilia. The most common organisms isolated from the bile and gallbladder intraoperatively were Staphylococcus, Streptococcus and Klebsiella species along with enterococcus, Escherichia coli and diphtheroids. Clinically significant postoperative infections occurred in eight patients, including six patients in the cefamandole group and two patients in the cefotaxime group. Antibiotic concentrations were measured in the serum, muscle, subcutaneous fat, gallbladder and bile, with cefamandole showing statistically significant greater concentrations in bile, gallbladder and muscle tissue. There was no statistical significance between the postoperative infection rates, total period of hospitalization or total hospital charges for each group. Therefore, there is no significant advantage between a single prophylactic dose of cefamandole versus cefotaxime for high-risk patients undergoing biliary tract operation.

Adolescent

Aberrant crypts: putative preneoplastic foci in human colonic mucosa.

Aberrant crypts were identified for the first time in whole-mount preparations of normal-appearing human colonic mucosa after staining with methylene blue. The foci of aberrant crypts varied from single altered glands to plaques of greater than 30 crypts. The mean proportion of colonic mucosa altered and the number of foci with aberrant crypts per cm2 of colonic mucosa were (a) higher in patients with colon cancer than in patients without colon cancer or predisposing conditions and (b) highest in our single case of Gardner's syndrome. Aberrant crypts are postulated to be the earliest identifiable potential precursors of colon cancer. Analysis of aberrant crypts may facilitate the study of the early pathological and molecular changes that precede colon cancer.

Adult

A critical analysis of the largest reported mass fecal occult blood screening program in the United States.

Fecal occult blood testing for the detection of colon cancer remains controversial. We performed a mass screening program from January 24, 1988, to February 19, 1988, with intensive media promotion, including 121 minutes of televised air time. A total of 5,000 primary practitioners were notified by mail. Hemoccult-II tests were distributed to 156,000 individuals; 55,051 (35%) were returned. Ninety-five percent of the respondents were informed of the program by television. A total of 3,375 persons (6%) tested positive for fecal occult blood; of these, 2,469 (73%) informed the center that they saw their physician to initiate a work-up. Information from physicians regarding work-ups was returned on only 1,356 (55%) patients. Diagnostic tests numbered 2,227 (1.6 tests per patient). However, 5% had no testing, 16% had a repeat Hemoccult only, and 35% had neither a barium enema nor colonoscopy performed. Thirty-six colorectal cancers and 212 polyps were identified. The predictive value (i.e., number of cancers per number of patients who tested positive) increased directly by decade. Thirty-three of 36 patients (92%) with cancer underwent either a barium enema or colonoscopy versus only 185 of 438 (42%) patients with a "negative" work-up. Cancers found were carcinoma in situ in 10 patients (29%), Dukes A in 12 (35%), Dukes B in 4 (12%), and Dukes C in 8 (24%); distant metastases were not found in any participant. Thirty-six percent of the tumors were located in either the right or transverse colon. We conclude that: (1) Screening identified early cancers. All were potentially curable and 64% were limited to the bowel wall. (2) Massive Hemoccult distribution was possible over a short interval, but patient and physician compliance was disturbingly low. (3) Total colonic evaluation is mandatory, since at least 36% of tumors were beyond the reach of the flexible sigmoidoscope. (4) Many work-ups were unnecessary (repeat Hemoccults) or inadequate, indicating a need for physician education.

Adult

Pelvic abscesses: CT-guided transrectal drainage.

Percutaneous drainage of pelvic abscesses has been performed by using a number of approaches, including transabdominal, transgluteal, and transrectal. The authors present a technique for the drainage of pelvic abscesses by a transrectal route with use of computed tomographic (CT) guidance. Equipment for the technique included a plastic introducer tube, standard needle, angiographic guide wire, and pigtail catheters. The pelvic abscesses of 10 patients (six after appendectomy, three after colon resection, one secondary to diverticulitis) were successfully drained by using the new technique. No complications or recurrences were experienced. After initial catheter placement, patients were treated with use of gravity drainage and appropriate antibiotics. Success of drainage was determined with sequential CT scans. Compared with the transgluteal approach, the transrectal approach offered increased patient comfort and minimal risk of potential complications such as injury to the sciatic nerve or tracking of the abscess. Use of the plastic introducer tube promoted operator safety by protecting the guiding finger. On the basis of this initial series, CT-guided transrectal drainage appears to be an effective and well-tolerated method for the drainage of pelvic abscesses.

Abscess

Endoscopic and radiographic evaluation of the murine colon.

Endoscopic and radiographic techniques have not been widely applicable in the evaluation of chemically induced murine colon cancer. The authors investigated methods of cleansing the rat colon and refined endoscopic and radiographic techniques. They compared total colonoscopy (TC) and air-contrast (ACBE) and single-contrast barium enema (SCBE) findings with those obtained at necropsy in rats with 1,2-dimethylhydrazine (DMH)-induced colon cancer. Gastrograffin enemas with bisacodyl suppositiories showed complete evacuation of solid feces. Sprague-Dawley rats treated with DMH had their colons cleansed and then underwent TC (5.0-mm Olympus bronchoscope) and either SCBE or ACBE. Colonoscopy and ACBE were equally sensitive (81.5% and 76.3%, respectively), although SCBE was significantly insensitive in identifying lesions (P less than 0.001). This study demonstrates that: (1) mechanical cleansing of the rat colon is feasible, (2) TC and barium radiology can be done routinely after mechanical cleansing, and (3) TC and double-contrast BE are sensitive in identifying colon lesions. These techniques will provide a means for manipulation of murine tumors and in vivo surveillance.

1,2-Dimethylhydrazine

Enzyme-altered foci in colons of carcinogen-treated rats.

The distal colon and rectum from male F344 rats treated with 15 mg/kg 1,2-dimethylhydrazine.2HCl (DMH) for 20 weeks were analyzed for focal areas of enzyme alteration. Tissues were embedded in methacrylate at 4 degrees C and cut in 2- to 4-micron serial sections. In DMH-treated rats, 8.8 +/- 2.4 foci/cm2 of examined mucosa were observed at 20 weeks and 7.7 +/- 1.1 foci/cm2 at 31 to 52 weeks, compared with 1.2 +/- 0.6 foci/cm2 in control rats (P = 0.01). The number of foci at 31 to 52 weeks compared with 20 weeks did not change significantly, but the area of altered rectal mucosa increased from 0.22 +/- 0.2% at 20 weeks to 1.47 +/- 0.6% at 31 to 52 weeks (P = 0.051). Most foci had decreased N-acetyl-beta-D-glucosaminidase, alpha-naphthyl butyrate esterase, and mucin in epithelial cells and increased gamma-glutamyl transpeptidase in the stroma. Morphologically, the foci varied from normal to overtly dysplastic. Grossly, tumors were identified in 5 of 20 DMH-treated rats killed at 31 to 52 weeks but not in 12 DMH-treated rats killed at 20 weeks or 30 control rats killed at 20 to 52 weeks. These data suggest but do not establish that enzyme-altered foci are putative preneoplastic lesions in the colon.

1,2-Dimethylhydrazine

Role of surgery in antibiotic-induced pseudomembranous enterocolitis.

With the increased use of prophylactic and broad-spectrum antibiotics, pseudomembranous colitis has emerged as a significant clinical problem. Management with specific anti-Clostridium difficile therapy (vancomycin or metronidazole) has reduced mortality to less than 2%. Nevertheless, the disease may progress to a fulminant toxic colitis or colonic perforation. Additionally, another subset of patients will present with a dramatic clinical picture, suggesting acute peritonitis, eventuating in unnecessary laparotomy. This report reviews both the medical and surgical literature during the past 15 years of patients treated for pseudomembranous colitis. Analysis of this clinical data has provided us with the opportunity to both define the role of surgery in this disorder and illustrate the necessity for a combined medical and surgical cooperative approach in the early management of this iatrogenic disease.

Enterocolitis, Pseudomembranous

Taking the laparoscope to the laboratory for ventilatory research.

Chronic ventilatory support by phrenic nerve stimulation has been accomplished, but potential permanent phrenic nerve injury has limited its therapeutic use. Prior work from the authors' laboratory has demonstrated that direct muscle stimulation can be safely performed for prolonged periods. Thus, in 1983, a laparoscopic technique was devised for the direct implantation of diaphragm pacing electrodes in the canine. During the subsequent four years, 16 animals (10 acute and 6 chronic) have undergone diaphragm pacing. Under general anesthesia, diaphragm pacing electrodes loaded into 19-gauge needles were implanted under direct laparoscopic visualization in both hemidiaphragms. In each animal, tidal volume, transdiaphragmatic pressure, arterial blood gas, impedence, cardiac activation, and histology of electrode placement site have been evaluated. Chronically paced animals were subjected to daily 8- to 24-hr per day pacing. The longest paced animal has been 179 days with continuous 24-hour per day pacing. In both acute and chronic experiments, maximal evoked tidal volume has approached 400 per cent of resting tidal volume. Cardiac ectopy has not occurred. This work has demonstrated the safety and feasibility of direct muscular diaphragm activation using the laparoscope. It has provided the basis for embarking upon a clinical study of this modality as a method of chronic ventilatory support. The laparoscopic technique of electrode placement may have a variety of other potential applications.

Animals

Antibiotics in elective colon surgery. A randomized trial of oral, systemic, and oral/systemic antibiotics for prophylaxis.

A prospective, randomized double-blind study was undertaken to compare the efficacy of three prophylactic regimens (oral neomycin and erythromycin, intravenous cefoxitin, and a combination of both oral and intravenous antibiotics) in patients undergoing elective colorectal surgery. One hundred sixty-nine patients were randomized and 146 patients were evaluable. Septic complications occurred in 11.4 per cent of patients receiving oral antibiotics only, in 11.7 per cent of patients receiving intravenous cefoxitin alone, and in 7.8 per cent of patients receiving both oral and intravenous antibiotics. These differences were not statistically different. The greatest number of septic complications occurred in those patients with anastomotic disruptions. Two patients died (1.3%), both of whom had major anastomotic failures. There was no advantage between any of the groups in the incidence of wound infection (3.9-6.8%). Thus, no advantage could be identified in this study in the combination of oral and intravenous antibiotics in elective colorectal surgery.

Administration, Oral

Microcomputer image processing in gastrointestinal endoscopy.

A computer-based system was developed to handle information and endoscopic images in a clinical setting. The system is based on an 80286 AT computer whose topology includes a 16-bit color image capture/display graphics adapter and a 256 gray scale 8-bit digital image analysis processor. Using its color capabilities, one may initiate a picture database of patient's endoscopic images, x rays, and relevant clinical data. The computer-based imaging system allows instant access to this information and minimizes subjective evaluation, improving comparison and follow-up of treatments in a more objective manner. The image analysis components permit digital characterization of lesions, which allows online measurements and image enhancement. This is a cost-effective method of handling information and images in the clinical setting, facilitating endoscopic management and follow-up of the patient with gastrointestinal disease, as well as an effective research and teaching tool.

Computer Graphics

Correlation of stromal cells by morphometric analysis with metastatic behavior of human colonic carcinoma.

The cellular compositions of the inflammatory infiltrates in human colonic carcinoma in well-defined compartments have not been quantified previously. Morphometric analysis of this tissue revealed several relationships between the concentrations of different kinds of cells that may be an important first approach to understanding the nature of the host reaction in different groups of patients. Primary tumors without metastases differ from those with metastases in that those without metastases contain higher concentrations of plasma cells (P = 0.0019) and eosinophils (P = 0.0098) in sections taken at a location remote from the margin (tissue located greater than 1 cm from the margin) and increased concentrations of eosinophils (P = 0.0224) in sections of tumor contiguous to the margin (tissue 0-4.5 mm from the margin). In sections contiguous to the margin, the concentration of plasma cells is related to the concentrations of lymphocytes (R = 0.55, P = 0.0014), eosinophils (R = 0.46, P = 0.0085), fibroblasts (R = 0.47, P = 0.0075), and neutrophils (R = 0.63, P = 0.0001). In sections remote from the margin, the concentration of plasma cells is related to the concentration of lymphocytes (R = 0.36, P = 0.0442), eosinophils (R = 0.36, P = 0.0457), mast cells (R = 0.38, P = 0.0375), and neutrophils (R = 0.38, P = 0.0371).

Colon

Splenic injury: nonoperative management in three patients with infectious mononucleosis.

Three patients with infectious mononucleosis and splenic injury were managed nonoperatively. Mechanisms of injury included significant left upper quadrant trauma during a football game in a 17-year-old boy, a minor fall in a 16-year-old girl, and no apparent trauma in the remaining patient, a 28-year-old man. All had significant abdominal pain and two were hypotensive upon admission. All had computerized tomographic scan documentation of splenic enlargement, significant injury, and free peritoneal blood. Paracentesis was not performed. Only the first patient received transfused blood. The hospitalization period ranged from nine to 14 days. Gradual and finally complete healing (return to normal size) was documented in all three patients. Follow-up is 66, 14, and 10 months. Although clearly controversial and not free from danger, successful nonoperative management of the injured enlarged spleen in select patients with mononucleosis is possible in an appropriate setting.

Adolescent

Jejunostomy button as a new method for long term jejunostomy feedings.

The button jejunostomy provides long term access for jejunal feedings incorporating the benefits of the gastrostomy button device. Although this procedure requires a celiotomy, we believe the relative simplicity of the procedure and its advantages over other types of jejunostomies warrant its use in patients with clinically significant gastroesophageal reflux who require long term enteral nutrition.

Adult