Search PubMed⌕ Search

Biomedical subjects

H S Stern

Publications and source records attributed to H S Stern.

At least 37 records · Page 2Linked to original sources

Long-term results of anterior resection using the double-stapling technique.

PURPOSE: This study was designed to determine the anastomotic leak rate, local recurrence rate, and survival of patients undergoing anterior resection with the double-stapling technique for rectal cancer. METHODS: Between 1981 and 1992, 189 patients underwent a curative (166) or palliative (23) anterior resection using the double-stapling technique. A chart review was performed, and follow-up information was obtained from the patient or family physician. Follow-up was complete in 186 patients (98 percent). RESULTS: There were five (2.6 percent) stapler-related complications, of which two patients required a defunctioning colostomy. Postoperative mortality was 1.6 percent, and clinical leak rate was 7.3 percent. Clinical leak rate was significantly higher in patients with lesions in the lower third (20 percent) compared with those in the middle and upper thirds (9 and 1 percent, respectively; P < 0.05). After a mean follow-up of 32 +/- 29 months, local recurrence rate was 9.1 percent but was significantly higher in patients more than 65 years old (14 vs. 1 percent; P < 0.005) and in patients with resection margins less than 2.0 cm (17 vs. 5.5 percent; P < 0.05). Five-year survival was 78 percent. CONCLUSIONS: Anterior resection performed with the double-stapling technique has an acceptable clinical leak rate, local recurrence rate, and survival rate. However, the clinical leak rate appears to be increased in patients with low tumors and, therefore, a defunctioning colostomy should be considered. Resection margins of more than 2 cm are necessary.

Adult↗

Free flaps in the management of intrathoracic sepsis.

Experience with 5 free flaps, 1 TRAM and 4 latissimus dorsi flaps, transferred intrathoracically for the management of chronic sepsis is described. Healing and elimination of sepsis was achieved in all cases despite the infection being resistant to all previous more traditional forms of treatment including thoracoplasty. The results were achieved with minimal morbidity and argue for the early consideration of free flaps in the management of chronic intrathoracic sepsis in appropriate circumstances. A review of the limited available literature concerning this topic is presented.

Adult↗

Fungating carcinoma of the stomach: en bloc multiple organ resection and abdominal wall reconstruction.

A patient with carcinoma of the stomach invading multiple adjacent organs and fungating through the anterior abdominal wall was treated by en bloc multiple organ resection and abdominal wall reconstruction. The patient is alive and well at the time of writing, six months after the operation. The rationale for embarking on multiple organ resection for gastric cancer is discussed. However, such an aggressive surgical approach should only be applied to carefully selected patients who are medically fit and have no evidence of widespread systemic metastases.

Abdominal Muscles↗

Somatic APC and K-ras codon 12 mutations in aberrant crypt foci from human colons.

Aberrant crypt foci (ACF) are microscopic lesions which have been postulated to precede the development of adenomatous polyps, the precursors to colorectal cancer. APC and ras gene mutations have been shown to be important early molecular events in the development of colorectal neoplasms. The objective of this study was to establish the nature and frequency of these two genetic alterations in ACF harvested from human colorectal resection specimens. One hundred and fifty-four ACF comprised of between 1 and 56 crypts were harvested from the grossly normal mucosa of colorectal resection specimens of 28 patients with varying pathological diagnoses. One hundred and twenty-five ACF from 20 colons were screened for the presence of K-ras codon 12 mutations with a polymerase chain reaction/restriction enzyme-based method. The APC gene mutation cluster region was screened in 65 ACF from 20 colons using a polymerase chain reaction/single strand conformation polymorphism technique. Putative mutations were confirmed by direct sequencing. K-ras codon 12 mutations were identified in 13% (16 of 125) of ACF. We also identified APC mutations in 4.6% (3 of 65) of ACF. The results of this study demonstrate that both APC and K-ras mutations occur in ACF. These observations support the role of the ACF as a colorectal cancer precursor and provide further insight into the early genetic changes which occur during colorectal tumorigenesis.

Adenomatous Polyps↗

Combined use of molecular and biomarkers for presymptomatic carrier risk assessment in familial adenomatous polyposis: implications for screening guidelines.

Predictive carrier testing for the inherited disorder of familial adenomatous polyposis (FAP) can be conducted using DNA markers linked to the FAP locus. The presence of characteristic hypertrophic retinal lesions has been advocated as useful biomarkers for FAP. We have compared molecular linkage and retinal screening techniques by evaluating the presymptomatic carrier risk of 40 at-risk individuals from 15 FAP families. Linkage analysis was informative in all and retinal lesion analysis in 25 cases. For informative at-risk population, predictive diagnosis by both techniques was completely concordant and identified 15 members at "high" and 10 at "low" risk of inheriting FAP. Because of the unique advantages offered by each technique, a strategy integrating both techniques will increase the number of FAP families that can be screened presymptomatically. Identification of individuals at high risk of polyposis will improve their clinical surveillance and further reduce the incidence of colorectal cancer in FAP families.

Adenomatous Polyposis Coli↗

Comparative dual label study of first and second generation antitumor-associated glycoprotein-72 monoclonal antibodies in colorectal cancer patients.

Radiolabeled first-generation anti-tumor-associated glycoprotein-72 (TAG-72) monoclonal antibody (MAb), B72.3, has proven useful in detecting primary and secondary colorectal carcinoma. It has been anticipated that the development of second-generation, higher affinity, anti-TAG-72 MAbs, CC49 and CC83, would be of greater use in cancer detection and of value in radioimmunotherapy of human cancer. We compared the pharmacokinetics, biodistribution, and immune responses of 131I-labeled CC49 and CC83 to 125I-labeled B72.3 by preoperatively coninjecting dual-labeled MAbs into 16 colorectal cancer patients. The imaging properties of radiolabeled CC49 and CC83 were also assessed. Pharmacokinetics of all three MAbs were identical, and there were no differences in the uptake of any of three MAbs in tumor and normal tissues. Maximum tumor uptake was 0.0041% of the injected dose/g for 125I-B72.3, 0.0024% for 131I-CC49, and 0.0029% for 131I-CC83. Radiolabeled CC49 and CC83 detected most known tumor sites on scintigrams without any clear advantage for either MAb. Nonspecific splenic and testicular uptake was frequently observed. Anti-idiotypic human anti-mouse antibody responses were seen more frequently with B72.3 than with CC49 or CC83. We conclude that higher affinity, radiolabeled anti-TAG-72 MAbs can detect colorectal cancer but do not penetrate these tumors more effectively than B72.3. Improvements in tumor detection and radioimmunotherapeutic strategies will likely require the administration of smaller fragments of MAb molecules or novel delivery systems rather than the continued development of higher affinity MAbs.

Adult↗

K-ras mutations in aberrant crypt foci, adenomas and adenocarcinomas during azoxymethane-induced colon carcinogenesis.

Ras mutations are an important early event in a number of carcinogen-induced rodent tumors. Colon carcinogenesis induced in rats by azoxymethane is a useful model as it mimics the adenoma-carcinoma sequence observed in humans. In addition, aberrant crypt foci develop in the rat and these lesions appear to be potentially important precursors to adenomas in colorectal cancer. Recent studies have shown that specific K-ras codon 12 and 13 mutations are present in up to 66% of carcinogen-induced rat colon adenocarcinomas. We studied the frequency of these mutations during the aberrant crypt focus-adenoma-carcinoma sequence in azoxymethane-induced Fisher F344 rats. K-ras codon 12 GAT and codon 13 GAC mutations were detected with a sensitive assay based on the amplification of DNA using the polymerase chain reaction. No mutations were present in normal mucosa. Of 27 aberrant crypt foci, K-ras mutations were identified in 2 lesions containing 5 and 10 aberrant crypts, respectively. Mutations were present in 1 of 23 and 10 of 27 adenomas and adenocarcinomas, respectively. These data suggest that K-ras mutations play a role during the stages of carcinogenesis in azoxymethane-induced rat colon cancer. The demonstration of a genetic mutation in aberrant crypt foci provides further evidence for the significance of these lesions as precursor markers of malignant potential during colorectal tumorigenesis.

Adenocarcinoma↗

Colonic epithelial proliferation indices before and after colon cancer removal.

Rectal mucosal (epithelial) proliferation labeling indices (LI) have been widely used as a risk marker for colorectal cancer and as an intermediate end-point in chemoprevention studies. The purpose of this study was to determine whether the presence of cancer preoperatively altered the LI and whether these LI could be used over the long term as a marker for colon cancer. We studied 25 patients (18 with colorectal cancer and 7 with benign colonic diseases) who were admitted for colonic resection. Biopsies for thymidine LI were taken before, during, and 4 and 7 months after the operation. The preoperative LI of cancer patients was higher, but not significantly, than that of noncancer patients (5.22 +/- 3.54 and 4.11 +/- 1.34%, respectively, p = 0.28). The intraoperative LI was significantly higher than the preoperative LI (8.08 +/- 4.00 and 4.90 +/- 3.07%, respectively; p = 0.004). After 4 and 7 months, the LI was not significantly different from the preoperative LI (p = 0.60 and 0.89, respectively). Resection of a colonic segment did not affect the level of proliferation over time. Therefore, it is unlikely that LI can be used as a marker to predict local recurrence after curative resection of colorectal cancer.

Adult↗

The effect of lowering faecal pH on the rate of proliferation of the normal colonic mucosa.

Epidemiological and animal studies suggest that faecal pH may be a risk factor for colorectal cancer with low faecal pH associated with a lower incidence of the disease. The aim of this study was to determine whether faecal pH (or dietary fibre) affects the short-term risk factors for colon cancer. Sixty-nine normal volunteers were randomized into three equal groups (A-C). They provided food records, faecal specimens and submitted to rectal biopsy for thymidine labelling studies before and after a 2-week intervention. Group A received a placebo of fruit juice. Group B, approximately 3.0 g d-1 sodium sulphate in juice. Group C, 30 g d-1 supplementary dietary fibre as wheat bran in bread. Age, sex, weight, height and intake of macronutrients and minerals were similar in the groups prior to intervention. Faecal pH was similar for the three groups before and was reduced in Group B after intervention (P = 0.001) with a relative reduction of 0.5 pH units. The labelling index for the three groups was similar prior to intervention; after, it was lowest in Group B with a relative reduction of 0.5% points, although this difference was not statistically significant. The results thus do not support the hypothesis that an acidification of faecal pH leads to a reduction in risk markers for colon cancer.

Adult↗

Intra-rectal injection of tumour cells: a novel animal model of rectal cancer.

The purpose of this study was to develop an animal model of rectal cancer. Three murine-derived cell lines, B16 melanoma, CT26 and MCA38 colon carcinoma, as well as the human colon cancer cell line LS174T were injected into the submucosa of the mouse rectum. Subcutaneous CT26 anbd B16 tumours and intra-caecal CT26 tumours served as controls for tumourigenicity of the cell lines. B16 melanoma produced a locally aggressive rectal tumour as well as skin and para-aortic lymph node metastases. CT26 produced local tumour when injected intra-rectally and colon tumours and liver metastases when injected into the caecum. MCA38 and LS174T intra-rectal injections resulted in large rectal carcinomas without metastases. We believe that growth of a colon cancer cell line in the rectum approximates the human disease more closely than other models of colorectal cancer. We would expect that the model could similarly be utilized to assess the effects of novel adjuvant treatments for rectal cancer as well as in the study of the tumour biology of rectal cancer.

Adenocarcinoma↗

Colonic fermentation and markers of colorectal-cancer risk.

The aim of this study was to determine the effect of soluble fiber on indexes of colon-cancer risk in postpolypectomy and nonpolyp patients. Forty-five postpolypectomy and 49 nonpolyp volunteers completed 2-wk metabolic studies where half of the group received oat-bran supplements and the other half took wheat-brain supplements. Colonic biopsies taken before and after the intervention showed no difference in the index of thymidine colonic-crypt-cell labeling, thymidine-labeling pattern, or nuclear aberrations. Nevertheless, fecal pH was significantly reduced by 0.23 +/- 0.07 pH units (P less than 0.002) as an index of increased colonic fermentation on oat bran. This was not associated with increased basal breath hydrogen concentrations; fecal butyrate concentrations were higher on wheat bran. We conclude that soluble fiber as oat brain appears to have no advantage over wheat bran in modifying putative risk factors for colonic cancer.

Butyrates↗

Wheat-bran and oat-bran supplements' effects on blood lipids and lipoproteins.

To compare the effects of oat-bran fiber on blood lipids, we studied 84 healthy middle-aged men and women who were placed on metabolic diets, for 2 wk, that were supplemented with either wheat bran (n = 42) or oat bran (n = 42). Fiber supplementation was 1.6 micrograms dietary fiber/J (6.8 g dietary fiber/1000 kcal) to a maximum of 16.4 g fiber/d. Significantly greater decrease with oat than with wheat were seen in total cholesterol (0.56 +/- 0.08 mmol/L and 0.29 +/- 0.08 mmol/L, P = 0.022) and low-density-lipoprotein cholesterol (0.39 +/- 0.07 mmol/L and 0.15 +/- 0.07 mmol/L, P = 0.024). No significant differences were seen in high-density lipoprotein, apolipoproteins A-1 and B, or triglyceride. We conclude that oat bran has an advantage over wheat bran in lowering serum lipids when tested in metabolic diets on large numbers of individuals with an initial mean serum cholesterol concentration above the desirable range, at 5.61 +/- 0.16 mmol/L.

Adult↗

Continuing evolution of the pelvic pouch procedure.

The results of the pelvic pouch procedure were reviewed to assess the surgical complication rate and outcome of patients who had had the procedure performed with a stapled ileo-anal anastomosis with and without a defunctioning ileostomy. Between December 1982 and March 1992, 483 patients underwent a pelvic pouch (PP) procedure. Patients were divided into three groups: group I consisted of 325 patients (178 men and boys and 147 women and girls) who underwent a PP procedure with a handsewn ileoanal anastomosis (IAA) with a defunctioning loop ileostomy. In group II, there were 87 patients (47 men and boys and 40 women and girls) who had a stapled IAA with a defunctioning ileostomy. Group III patients consisted of 71 patients (43 men and boys and 28 women and girls) who had a stapled IAA with no covering ileostomy. Assessment was made of the IAA leak rate, the surgical complications, the reoperation rate, and functional outcome. Early surgical complications included 40 (12%) IAA leaks in group I patients compared with only six (7%) leaks in group II patients who had a stapled IAA (p < 0.05). In group III patients, who had a stapled IAA but no covering ileostomy, there were 13 leaks (18%). Eleven of these 13 leaks healed spontaneously with tube drainage; one patient remains with a rectal tube in place 6 weeks after operation, and only one patient has required a reoperation (defunctioning ileostomy). Functionally, all patients with a healed IAA after a leak have had an excellent result comparable to those without a leak. Patients who were male, older than age 40, on steroids, and had had a true one-stage PP procedure, had a greater risk of developing an IAA leak. In two patients, there was intraoperative difficulty, and one of these patients had an IAA leak after operation. Disease activity at the resection margin and patient weight did not affect the leak rate. Our results suggest that the IAA leak rate is significantly reduced in patients with a stapled IAA with an ileostomy compared with those with a handsewn IAA. Omission of the defunctioning ileostomy is associated with a higher IAA leak rate, but spontaneous healing occurs in almost all patients without impairment of functional results. In patients in whom the ileostomy is omitted, the IAA leak rate is greatest in male patients who have undergone a true one-stage PP procedure, are on steroids, and are older than age 40.

Adenomatous Polyposis Coli↗

Progressive hemifacial atrophy associated with Lyme disease.

A case is described of progressive hemifacial atrophy occurring in a child with Lyme disease. Borrelial infection may have been an etiologic factor in the progressive hemifacial atrophy, which was ultimately treated with an SIEA free-flap transfer.

Adipose Tissue↗

Pilomatrix carcinoma of the scalp.

A matrical carcinoma (pilomatrix carcinoma) of the scalp is described--the first reported case in this site. This malignant hair follicle tumour must be distinguished histologically from benign pilomatricoma and proliferating trichilemmal tumour, which can have similar features.

Aged↗

Management of mesenteric desmoid tumours in familial adenomatous polyposis.

Intra-abdominal desmoids are locally invasive fibrous tumours within the mesentery of the intestine. They occur in 4% to 13% of patients with familial adenomatous polyposis (FAP). Of 498 patients registered in the Steve Atanas Stavro FAP Registry at the Mount Sinai Hospital, Toronto, 53 (11%) had desmoids and 40 of them had mesenteric desmoids. There were 23 women and 17 men, and the mean age was 31 years. Most tumours were diagnosed after colectomy for FAP. Of the 40 patients 7 (18%) died of desmoid-related complications. Surgical excision of desmoids is hazardous and was associated with a recurrence rate of up to 85% in this study. Current research is directed at the role of antiestrogens in the fundamental mechanisms of cell growth and are now the subject of clinical trials.

Abdominal Neoplasms↗

Colonic proliferation and colon cancer risk. A review of clinical studies.

The purpose of this review is to discuss some of the recent hypotheses regarding the dietary etiology of colorectal cancer. We will review some of the epidemiological background and animal studies that were performed to test these hypotheses. The use of the rectal mucosal proliferation rate as measured by thymidine labelling index as an intermediate endpoint for clinical studies is discussed, including the results of testing these hypotheses using this marker. We believe that all hypotheses must eventually be tested in the human model and that carefully controlled, sequential analyses of each acceptable hypothesis is the most prudent road to understanding the environmental causes of colorectal cancer.

Biomarkers, Tumor↗