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Biomedical subjects

P A Goldberg

Publications and source records attributed to P A Goldberg.

At least 19 recordsLinked to original sources
PubMed2006

Immunohistochemistry detects mismatch repair gene defects in colorectal cancer.

OBJECTIVE: The clinical management of colorectal malignancies that arise via the mismatch repair gene pathway may differ from those that arise from the more common loss of heterozygosity pathway. They respond differently to chemotherapy, have a different prognosis and are associated with a raised incidence of metachronous lesions if a germline mutation is present. Established methods of detecting mismatch repair gene defects require the testing for microsatellite instability. This is expensive and requires specialized molecular biological resources and staff. An immunohistochemical method is attractive because it is far cheaper, and can be performed by most anatomical pathology laboratories. The aim of this study was to determine the incidence of mismatch repair gene defects using immunohistochemistry in a group of patients who were aged < or = 45 years at the time of diagnosis of colorectal cancer and to compare the patient survival and pathological features of tumours with and without mismatch repair gene defects. METHODS: One hundred and four patients with colorectal cancer, diagnosed at 45 years or younger between January 1983 and December 2001, who had been managed at Groote Schuur Hospital, were identified from clinical records. Demographic and clinical data was collected from the clinical notes. The pathological reports were reviewed and the original histopathological slides retrieved. New tissue sections were cut from the original paraffin embedded tissue blocks to obtain both normal colonic mucosa and tumour on the same slide. There was insufficient tissue available or poor staining in 11 patients so 93 were available for the study. RESULTS: The mismatch repair status was detected by antibodies to hMLH1 and hMSH2 gene product using a standard immunohistochemical technique. Fifty-six (60%) of 93 tumours demonstrated normal expression of both hMLH1 and hMSH2 protein. Twenty-five (27%) tumours did not express hMLH1 and 12 (13%) hMSH2 proteins. Comparison of the histopathological features revealed that a greater proportion of tumours with absence of either the hMLH1 or hMSH2 product were right sided, mucinous and poorly differentiated when compared to those that expressed the gene product. There was no detectable difference in overall survival or in survival of patients with Duke's C carcinoma when the groups were separated by the presence or absence of gene product. CONCLUSIONS: This study found that 40% of patients who were < or = 45 years of age at the time of diagnosis of colorectal cancer seen at Groote Schuur Hospital have tumours which are related to the absence of expression of either hMLH1 or hMSH2 genes.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Should knee-length replace thigh-length graduated compression stockings in the prevention of deep-vein thrombosis?

OBJECTIVE: To compare knee-length with thigh-length graduated compression stockings for correct application and rate of compliance when they are prescribed for the prevention of deep-vein thrombosis in surgical patients. METHODOLOGY: Patients who were prescribed graduated compression stockings were prospectively studied in three surgical units at Groote Schuur Hospital from February to June 1997. Knee-length stockings were prescribed in the colorectal unit, while the thigh-length variety were prescribed in the hepatobiliary and trauma units. Patients were observed for the correct application and size of stockings, and the presence of compression bands. A total of 72 patients were studied. RESULTS: One patient in the knee-length group and 7 patients in the thigh-length group were not wearing their stockings. Twenty-one of 30 patients (70%) in the knee-length group and 15 of 42 (35.7%) in the thigh-length group had correctly applied stockings (P = 0.009). CONCLUSIONS: Knee-length are more likely to be correctly applied than thigh-length stockings. Knee-length should replace thigh-length stockings in general surgical patients.

Adolescent↗
PubMed2000

Variceal rebleeding and recurrence after endoscopic injection sclerotherapy: a prospective evaluation in 204 patients.

HYPOTHESIS: Eradication of esophageal varices by repeated injection sclerotherapy and maintenance of eradication using continued surveillance endoscopy may reduce recurrent variceal bleeding and death from esophageal varices. DESIGN: A prospective study of consecutive adult patients with endoscopically proved esophageal variceal bleeding. SETTING: A tertiary care university hospital in a metropolitan area. PATIENTS: Two hundred four patients (127 men and 77 women; mean age, 50.1 years; age range, 16-82 years) underwent 993 emergency and elective variceal endoscopic injection treatments with 5% ethanolamine oleate during 1992 endoscopy sessions. Most (166 [81.4%]) had cirrhosis, mainly due to alcohol abuse (131 [78. 9%]). The number of patients with each modified Pugh-Child risk grade was as follows: A, 30; B, 91; and C, 83. (The modified Pugh-Child classification comprises ascites, encephalopathy, serum albumin and bilirubin levels, and prothrombin time. Each variable is given a value of 1 to 3 with increasing impairment of liver function. Addition of the values leads to the Pugh-Child risk grades for each patient, with 5 and 6 giving grade A; 7 through 9, grade B; and 10 through 15, grade C, respectively.) RESULTS: Ninety-five patients (46.6%) rebled at a median of 17 days (range, 0-2583 days). Seventy-four patients (36.3%) had a total of 112 further bleeding episodes before eradication of varices. Varices were eradicated in 99 (87.6%) of 113 patients who survived longer than 3 months after a median of 5 injections and remained eradicated in 43 (mean follow-up after eradication, 38 months; range, 4-125 months). Rebleeding was markedly reduced after eradication of varices. Varices recurred in 56 patients, of whom only 10 rebled from recurrent esophageal varices. Cumulative survival by life table analysis was 55%, 41%, and 30% at 1, 3, and 5 years, respectively. One hundred thirty-seven patients (67.2%) died during follow-up. Liver failure was the most common cause of death. Minor complications (mucosal ulceration) occurred in 105 patients. Major complications, including a localized injection site leak (n = 9), esophageal stenosis (n = 25), and esophageal perforation (n = 5), occurred in 39 patients. CONCLUSIONS: Repeated injection sclerotherapy eradicated esophageal varices in most long-term patients. Complications related to injection sclerotherapy were mostly minor. Complete eradication of varices reduced rebleeding and death from esophageal varices.

Esophageal and Gastric Varices↗
PubMed2000

Radical excision of multifocal anal intraepithelial neoplasia: report of a case.

PURPOSE: The aim of this study was to describe the technique of radical excision of multifocal anal intraepithelial neoplasia and discuss controversial issues surrounding the management of this condition. METHOD: We describe the case of a 31-year-old female with previous vulval warts, vulval squamous carcinoma, and recent immunosuppression who had widespread anal intraepithelial neoplasia excised, and the resulting defect was split-skin grafted, including the anal canal. RESULTS: Excision and split-skin grafting was successful in removing the disease and left a satisfactory cosmetic and functional result. CONCLUSION: Diffuse, high-grade, anal intraepithelial neoplasia is rare. Excision of these lesions remains controversial but may be the best option.

Adult↗
PubMed2000

Molecular genetics improves the management of hereditary non-polyposis colorectal cancer.

BACKGROUND: The syndrome of hereditary non-polyposis colorectal cancer (HNPCC) can be diagnosed fairly accurately using clinical criteria and a family history. Identifying HNPCC helps to prevent large-bowel cancer, or allows cancer to be treated at an early stage. Once the syndrome has been diagnosed a family member's risk can be judged approximately from a family tree, or it can now be predicted accurately if the causative mutation is known. OBJECTIVE: This study involved attempts to improve the management of a family with HNPCC over a period of 10 years. Clinical diagnostic criteria, colonoscopic surveillance, surgical treatment, genetic counselling, molecular genetic research, and finally predictive genetic testing were applied as they evolved during this time. SUBJECTS AND METHODS: A rural general practitioner first noted inherited large-bowel cancer in the family and began screening subjects as they presented, using rigid sigmoidoscopy at the local hospital. At the time that the disorder was recognised as being HNPCC (1987), screening by means of colonoscopy at our university hospital was aimed primarily at first-degree relatives of affected individuals. After realising how many were at risk, screening was brought closer to the family. A team of clinicians and researchers visited the local hospital to identify and counsel those at risk and to perform screening colonoscopy. Family members were recruited for research to find the gene and its mutation that causes the disease, to develop an accurate predictive test and to reduce the number of subjects undergoing surveillance colonoscopies. RESULTS: There are approximately 500 individuals in this family. In the 10 years of this study the number of subjects who have been counselled for increased genetic risk or who have requested colonoscopic surveillance for HNPCC in this kindred has increased from 20 to 140. After the causative mutation was found in the hMLH1 gene on chromosome 3, a test for it has reduced the number of subjects who need screening colonoscopy by over 70%. A protocol has been devised to inform family members, to acquire material for research in order to provide genetic counselling for (pre-test and post-test) risk, and to test for the mutation. Eventually, identifying those with the mutation should focus surveillance accurately. CONCLUSIONS: The benefits of restricting screening to subjects with the mutation that causes colorectal cancer and of performing operations to prevent cancer are hard to measure accurately. However, it is likely that at least half the family members will be able to avoid colonoscopic screening, some deaths from cancer should be prevented, and the cost of preventing and treating cancer in the family should fall substantially.

Adult↗
PubMed1998

In a resource-poor country, mutation identification has the potential to reduce the cost of family management for hereditary nonpolyposis colorectal cancer.

PURPOSE: Colonoscopic surveillance of family members at risk of hereditary nonpolyposis colorectal cancer is difficult in a resource-poor country because of its expense. For family members who live in remote areas, poor communication and limited access to sophisticated medical care make surveillance even more difficult. The identification of the mutation causing the disease will simplify surveillance. Our aim was to assess the impact of mutation analysis on the management of a South African family with more than 150 members at risk for hereditary nonpolyposis colorectal cancer. METHODS: We studied a family that met the Amsterdam criteria for hereditary nonpolyposis colorectal cancer. Colorectal cancer affected 27 members in three generations (evidence from histology in 12, barium enema in 1, and family statements in 14 family members). Leukocyte DNA from family members was tested for linkage to candidate loci for colorectal cancer, and DNA from formalin-fixed cancers from six family members was studied for microsatellite instability. DNA from all available family members was then screened for mutations in the hMLH1 gene. The number of individuals at 50 percent risk was calculated by family pedigree and compared with the number who have the mutation. RESULTS: A disease-causing mutation in exon 13 of hMLH1 segregated with the disorder in members of this kindred. Test results of 100 chromosomes from population-matched controls were negative. Sixty family members between the ages of 16 and 50 years are at 50 percent risk for colon cancer by pedigree analysis, but of these, only 26 (43 percent) have the mutation. CONCLUSION: A mutation in the DNA repair gene hMLH1 was found in family members with hereditary nonpolyposis colorectal cancer and in some unaffected relatives previously at 50 percent risk, but not in unrelated subjects. The blood test for the mutation will simplify management, counseling, and surveillance and help to establish prophylactic colectomy.

Chromosome Segregation↗
PubMed1997

End stage renal transplant failure: allograft appearances on CT.

INTRODUCTION: Failed renal allografts often are left in situ in patients who revert to chronic dialysis therapy or who undergo retransplantation. These patients may be investigated with computed tomography (CT) imaging for allograft-related or other abdominopelvic disease. This study describes the appearances of failed renal transplants on CT. METHODS: A retrospective study was made of the clinical records and CT findings on 25 studies in 14 patients, 5-156 months (average, 44 months) following allograft failure. CT studies were reviewed for allograft position, size, shape, attenuation value, calcification, cyst formation, related abdominopelvic findings and the presence of other allografts. Correlation was made with clinical findings in all patients and with pathological findings in six. RESULTS: Global shrinkage was noted in eight failed allografts, all of which were asymptomatic. Enlargement of two failed allografts was due to symptomatic acute infarction of the allograft in one patient and subacute haemorrhagic infarction simulating a tumour mass in another. CT attenuation values in individual allografts varied markedly due to fatty replacement, hydronephrosis, haemorrhage or dense calcification. Both a failed longstanding and a functioning more recently placed renal allograft were present in seven patients, four of whom had acute complications related to the more recently transplanted kidney. Two of six calcified allografts were mistaken for opacified bowel on CT. CONCLUSION: A wide spectrum in size, shape and attenuation values may be detected in failed renal allografts by CT. These organs may be the site of acute disease despite their lack of physiological function or may be diagnostically confusing findings in patients with acute disease related to more recently transplanted organs.

Adult↗
PubMed1997

Contribution of gastrointestinal transit and pouch characteristics in determining pouch function.

AIM: To determine the contributions of gastrointestinal transit and pouch characteristics to bowel frequency in patients with an ileoanal reservoir and no pouchitis. METHODS: Twenty one patients who had undergone restorative proctocolectomy, with ileostomy closure at least eight months previously, and who had no history of pouchitis were recruited. They were prospectively classified on the basis of their bowel frequency: 11 patients had good pouch function (bowel frequency less than six per day) and 10 had poor function (bowel frequency more than six per day). Gastrointestinal transit was studied using a dual isotope technique and anal and pouch physiological examination was performed on all patients. RESULTS: Lag phase, 25% and 50% gastric emptying, small bowel transit time, and 10% and 50% pouch filling times, all for solids and liquids, were not significantly different between patients with good and poor function. Anal manometry and pouch and anal electrical sensitivity were also similar in the two groups. The volume of air and water required to elicit an initial sensation and the urge to defaecate were similar in both groups, but the maximum tolerated volume to both air (525 v 245 ml, good v poor function, median values) and water (625 v 370 ml) infusion was significantly (both p < 0.02) lower in patients with poor function. CONCLUSION: Maximum tolerated volume in the pouch, which may reflect pouch size, sensitivity, compliance, or a combination of these is the major determinant of pouch function. Gastrointestinal transit does not seem to be an important determinant of function.

Adult↗
PubMed1996

A radiopaque marker technique for measuring gastrointestinal transit in subjects with an ileostomy.

We aimed to develop a simple, clinically useful technique for measuring gut transit time in patients with an ileostomy, in order to distinguish easily when patients have fast or slow transit. Seventeen healthy subjects (mean age, 55 years; range, 43-71 years; nine males) who had had a proctocolectomy for ulcerative colitis more than 1 year previously and without small intestinal resection were studied. Subjects were studied on 4 days after an overnight fast, two studies with and two without breakfast. A standard diet was used on all days. Twenty radiopaque markers were given at the start of each study day. Ileostomy effluent was collected over 24 hr and x-rayed to determine the number of retained markers. Studies with breakfast demonstrated greater intrasubject reproducibility. The mean transit time for passage of 50% of markers was 16.6 hr with, and 14.8 hr without, breakfast (p < 0.02). From the data obtained we suggest that the optimum time for taking a single abdominal radiograph in a patient with suspected fast transit is 6 hr after ingestion of markers, while the optimum time for a patient with suspected slow transit is 24 hr.

Adult↗
PubMed1996

Leucocyte typing, cytokine expression, and epithelial turnover in the ileal pouch in patients with ulcerative colitis and familial adenomatous polyposis.

BACKGROUND/AIMS: Conventional histopathology, leucocyte typing, cytokine mRNA expression, and crypt cell turnover were compared in ileal pouch biopsy specimens from patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP). METHODS: Biopsy specimens were taken from 17 patients with UC and seven with FAP at a median interval of 19 months (range 2-120) after ileostomy closure. All contained both epithelium and lamina propria. Cryostat sections were stained for lymphocyte subtypes (CD3, CD4, CD8), macrophages (CD68), common leucocyte antigen (CD45), and Ki-67, using a three stage immunoperoxidase reaction. Cytokine mRNA expression for interleukins 2 and 6, tumour necrosis factor alpha, and interferon gamma was studied using an in situ hybridisation technique. RESULTS: Lymphocyte subtype and macrophage populations in epithelium and lamina propria were similar in UC and FAP. The labelling index (Ki-67) was significantly increased in biopsy specimens from patients with UC (UC median = 43.3 (interquartile range (IQR) 38.9-48.2) v FAP 34.9 (29.9-35.2), p < 0.05). There was little or no epithelial mRNA expression for any cytokine in any of the specimens. Lamina propria mRNA expression for interleukin 2 was significantly increased in UC (UC median (IQR) 10.7 (5.4-14.2) cells per unit area v FAP 2.8 (1.5-6.6) p < 0.05) but not for tumour necrosis factor alpha, interleukin 6, and interferon gamma. CONCLUSIONS: While static morphological assessment (leucocyte type, conventional histopathological examination) was similar, tests of cell function (mRNA expression and labelling index) were different in ileal pouches in patients with UC compared with FAP. The study also showed that mRNA expression occurred almost entirely in the lamina propria.

Adenomatous Polyposis Coli↗
PubMed1996

Large-core biopsy guns: comparison for yield of breast tissue.

PURPOSE: To compare seven large-core, long-throw, 14-gauge biopsy guns for yield and quality of breast tissue obtained. MATERIALS AND METHODS: A two-phase, randomized and blinded study was performed. In the first phase, four fully automated 14-gauge biopsy guns (BIP, Manan, Biopsy, and ASAP) and one semiautomated device (Temno) were used to obtain breast cores from a cadaver. Samples were assessed for volume, number of fragments, and crush artifact. In the second phase, seven biopsy guns (previously mentioned guns plus Monopty and Ultra-Cut guns) were used to obtain cores from a breast parenchyma model. These cores were then evaluated for weight, volume, and number of fragments. RESULTS: The mean specimen volume of cadaveric breast tissue obtained was 17.9 mm3 for the BIP gun, 17.8 for the Manan gun, 14.9 for the Biopsy gun, 14.1 for the ASAP gun, and 9.9 for the Temno gun. The Temno gun obtained statistically significantly smaller volumes than all other guns. For the breast parenchyma model, mean obtained volumes were 24.5, 24.1, 16.2, 21.7, 17.5, 20.0, and 15.2 mm3, respectively. The BIP and Manan guns yielded statistically significantly larger cores than all other guns except the ASAP. CONCLUSION: Yields of breast tissue provided by each biopsy device differed statistically significantly. BIP and Manan biopsy guns yielded the greatest volume of core tissue, which may facilitate histopathologic diagnosis from breast biopsies performed with imaging guidance.

Animals↗
PubMed1995

Prediction of local recurrence and survival of carcinoma of the rectum by surgical and histopathological assessment of local clearance.

The surgeon and histopathologist were asked to assess whether clearance of the resected primary rectal tumour was complete or not. The results of each assessment were related to survival and recurrence rates. Of 478 patients entered, full information was available for 396 who were followed to death or for at least 5 years. The surgeon and pathologist agreed on the clearance in 341 of the 396 patients. The 5-year local recurrence rate was 15 per cent in the 331 patients with complete local clearance and 62 per cent in those with incomplete clearance. There was disagreement regarding 55 patients (14 per cent) (39 pathologist 'incomplete'/surgeon 'complete'; 16 surgeon 'incomplete'/pathologist 'complete'). Local recurrence occurred later where the pathologist assessed resection to be incomplete (log rank chi 2 = 11.0, 1 d.f., P = 0.001). Of 321 patients without metastatic disease, the surgeon and pathologist agreed in 290 that 284 had complete and six incomplete clearance. The 5-year survival rates were 53 and 0 per cent respectively. There was disagreement regarding 31 patients (10 per cent) (11 surgeon 'incomplete'/pathologist 'complete'; 20 pathologist 'incomplete'/surgeon 'complete'). The 5-year survival rates were 18 and 10 per cent respectively (log rank chi 2 = 1.5, 1 d.f., P = 0.2). Surgical and histopathological assessments of local clearance are important in determining local recurrence and survival.

Adenocarcinoma↗
PubMed1995

A study of a new osmotic purgative for colonoscopy. Is Golytely worth its salt?

An osmotic laxative containing polyethylene glycol and sodium sulfate (Golytely Braintree Laboratories, Inc., Braintree, MA) is widely used to clean the colon for colonoscopy. However, its salty taste makes the mixture unpalatable. We therefore tested the claim that a similar solution but without sodium sulfate (Golytely-RSS Braintree Laboratories, Inc., Braintree, MA) makes preparation of the colon more acceptable to patients in a double-blinded randomized controlled trial. Colonic preparation using polyethylene glycol with or without sodium sulfate was randomized in 100 patients due to undergo colonoscopy. The overall acceptability of the regimen was measured on a linear analogue scale and an estimate of symptoms was obtained. Body weight and serum electrolytes, urea, creatinine, hemoglobin and hematocrit were determined before and after preparation in order to assess fluid absorption. The efficacy of colonic cleansing was graded by the colonoscopist. Four patients did not complete the protocol, 47 received the regimen containing sodium sulfate and 49 received the regimen without it. The two groups did not differ in age or body mass. There was no statistical difference in the overall acceptability of the two regimens to the patients (median acceptability rating 74 for regimen with sodium sulfate, range 4-100 compared with 77 for regimen without, range 3-100, p = 0.32, Mann-Whitney test). Nor was there any difference in taste, nausea, vomiting, cramping or perianal discomfort or in the endoscopists' rating of the cleanliness of the colon. The serum sodium concentration rose slightly (mean 1.6 mmol/L) when the regimen with sodium sulfate was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Cathartics↗
PubMed1995

The outcome of familial adenomatous polyposis in the absence of a polyposis registry.

From 1964 to 1990, 70 patients with familial adenomatous polyposis were diagnosed at an institution without a polyposis registry. Those with symptoms at diagnosis were older (mean 34 v. 24 years) and more often had large-bowel cancer (7/30 v. 1/30, 23% v. 3%). The introduction of systematic screening significantly increased the number of cases diagnosed annually, from 2,3 to 5 per year, reduced the median age at diagnosis from 29 to 21 years and increased the proportion of cases diagnosed without symptoms from 52% to 90%. A colectomy with an ileorectal anastomosis achieved a low incidence of rectal cancer at 20 years (1/15, 7%) despite imperfect follow-up and annual sigmoidoscopy in only 40%. However, bowel cancer caused at least 35% of all deaths and 62% of deaths due to a known cause. A registry which maintained a screening programme should therefore prevent most large-bowel cancers and improve the life expectancy of patients with familial adenomatous polyposis who are managed at this institution. It might also refine the current method of screening by sigmoidoscopy alone, by facilitating the use of ophthalmoscopy and blood tests for DNA markers.

Adenomatous Polyposis Coli↗
PubMed1994

Long-term results of a randomised trial of short-course low-dose adjuvant pre-operative radiotherapy for rectal cancer: reduction in local treatment failure.

A prospective randomised multicentre trial compared pre-operative radiotherapy followed by surgery with surgery alone for rectal cancer < or = 12 cm from the anal verge. Of 468 patients (mean age 67 years, range 31-94, 273 males) who met the entry criteria, 228 were randomised to radiotherapy (3 x 5 Gy over 5 days within 2 days of operation) followed by surgery, and 239 to surgery alone. Randomisation was unknown in 1 patient. Follow-up to death or 5 years was achieved in 454 (97%) patients. 31 (7%) of the 468 patients died within 30 days of operation (radiotherapy and surgery 21 [9%], surgery alone 10 [4%]; P < 0.05). Cardiovascular and thromboembolic complications were more common after radiotherapy and surgery (30, 13%) than after surgery alone (8, 3%; P < 0.005). Of the 280 patients who had curative surgery, 52% of those who had radiotherapy and surgery and 56% of those who had surgery alone survived 5 years (P = 0.88). 395 patients attended outpatients clinics at least once. Local treatment failure was identified during follow-up in 82 patients [31/185 (17%) radiotherapy and surgery; 51/210 (24%) surgery alone; P < 0.05]. It occurred in 33 of the 258 patients who had a curative resection and attended outpatients [radiotherapy and surgery, 11/120 (9%), surgery alone, 22/138 (16%); P = 0.08]. Long-term survival was unaffected, but long-term local recurrence was reduced by the addition of low-dose radiotherapy to surgery. Peri-operative mortality was, however, increased.

Adult↗