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Biomedical subjects

H S Goh

Publications and source records attributed to H S Goh.

At least 37 records · Page 2Linked to original sources
PubMed1996

The investigation of chronic constipation for surgical management.

AIMS: This study was conducted to ascertain the incidence of patients requiring surgery for intractible constipation. We also aimed to determine the anorectal physiology findings which influenced the surgery, and the outcome of surgical intervention. METHODS: A prospective study was done on 217 patients (34 men, 183 women; mean age 59 years [SD 17.7]) managed in a tertiary referral centre. Physiological tests consisting of transit marker studies, anal manometry, electromyography (EMG) and synchronised mano-myo-cinedefaecography (SMC), were then performed where appropriate. Surgical management was based on the results of these investigations. The mean follow-up was 19.6 months (SD 9.3). RESULTS: Eighteen patients (8.3 percent) underwent surgery: 2 for Hirschsprung's disease, 8 for colonic inertia (CI) and 8 for obstructed defaecation (OD). CI patients were younger than the OD patients (p = 0.03). Transit marker studies were abnormal but manometry was not different from the OD patients. The latter were identified on SMC to have rectoceles, sigmoidocele or rectal intussusception. The stool frequency significantly improved after surgery (before = 1.9 bowel motions a week [SD 0.9], after = 8.8 bowel motions a week [SD 1.2]; p = 0.003). There were no complications. CONCLUSIONS: A small but significant proportion of constipation patients require surgery. Good results are obtainable when surgery is directed by the findings of anorectal physiology investigations.

Adult↗
PubMed1996

Surgery for inflammatory bowel disease in Singapore.

Inflammatory bowel disease is uncommon in Asians and reports of surgery in these populations are rare. Eighty-two patients with inflammatory bowel disease were seen in the Department of Colorectal Surgery over a five-year period (1989-1994). Twenty-three patients underwent surgery for their disease. There were 12 males and 11 females with 16 Chinese, 4 Indians and 3 Malays. Twelve had Crohn's disease and 11, ulcerative colitis. The majority of patients with Crohn's disease had emergency surgery for bleeding, perforation, abdominal masses and intestinal fistulae. Fifty percent of these had the diagnosis made intraoperatively or post-operatively. Surgery for ulcerative colitis was indicated because of multiple relapses, non-response to medical treatment, side effects of therapy or malignant change. The median age at surgery of patients with Crohn's disease and ulcerative colitis was 39 years (range 24-84) and 40 (range 18-60) respectively. The median follow-up was 22.4 months (range 9-50). The results of surgical therapy in these patients show that surgery when indicated can be done with minimum morbidity and mortality.

Adult↗
PubMed1996

Overexpression of the c-myc proto-oncogene in colorectal carcinoma is associated with a reduced mortality that is abrogated by point mutation of the p53 tumor suppressor gene.

The survival of 119 colorectal cancer patients was analyzed in the light of the overexpression status of the c-myc proto-oncogene mRNA and the point mutation status of the p53 tumor suppressor gene in the primary adenocarcinoma. The presence of >3 fold overexpression of c-myc mRNA in the primary tumor was found to be associated with a better prognosis than patients who evinced no overexpression (P = 0.02, log rank analysis). Point mutation of the p53 tumor suppressor gene was found to be associated with a poorer patient prognosis (P = 0.007, log rank analysis). Endogenous levels of c-myc and point mutation of p53 both contributed independently toward a poorer patient prognosis in Cox regression modeling. The better prognosis seen in patients who overexpress c-myc was offset when c-myc overexpression was coupled with a point mutated p53 gene. These results suggest that in colorectal adenocarcinoma c-myc deregulation leads to increased apoptotic death, but that this response may be modulated by a more downstream event such as point mutation of the p53 gene.

Adult↗
PubMed1995

p53 point mutation and survival in colorectal cancer patients.

We have examined the relationship between point mutation of the p53 tumor suppressor gene and survival in colorectal cancer patients. We found that patients with tumors harboring mutated p53 genes showed a significantly poorer prognosis than did those patients with genes without point mutations, and, moreover, patient response to postoperative therapies depended significantly on mutation status in both adjuvant and palliative treatment cohorts. However, not all point mutations were the same functionally; point mutations within the conserved domains of the p53 tumor suppressor gene were inherently more aggressive than tumors with point mutations outside of these domains, and mutations of codon 175 were particularly aggressive. These results suggest that knowledge of a patient's p53 status, both with respect to the presence of point mutations and to the specific nature of the lesion, may be required to accurately predict both the course of the disease and the response of the disease to postoperative therapeutic interventions, especially those therapies based on the induction of apoptosis in the neoplastic cell.

Adenocarcinoma↗
PubMed1995

Increased mRNA expression of the receptor-like protein tyrosine phosphatase alpha in late stage colon carcinomas.

The protein tyrosine phosphatase alpha (PTP alpha) mRNA level in paired samples of late stage (Dukes' D) colorectal tumors and adjacent normal colon mucosa was quantified by RNase protection assays. After normalization against 18S RNA or beta-actin mRNA level, a 2-10-fold increase in PTP alpha mRNA was detected in 10 of 14 tumors (approximately 70%) compared to mucosa. In situ hybridization of digoxigenin-labelled antisense PTP alpha RNA to tumor and mucosa sections produced a signal only in neoplastic cells of the tumor sample, consistent with the high increase in PTP alpha mRNA detected by RNase protection assays of some of the tumors. This is the first report suggesting an association of a protein tyrosine phosphatase with colorectal carcinoma. PTP alpha is a receptor-like PTP thought to be involved in regulating cell proliferation. Its oncogenic properties when overexpressed in cultured fibroblasts suggest that PTP alpha overexpression could contribute to the tumorigenic process in colon carcinoma.

Adenocarcinoma↗
PubMed1995

Haemorrhoidectomy and disordered rectal and anal physiology in patients with prolapsed haemorrhoids.

The effect of haemorrhoidectomy on rectal and anal physiological abnormalities was studied in 24 consecutive patients (12 men and 12 women of mean (s.e.m.) age 39.1 (2.4) years) and compared with results in 13 sex- and age-matched controls. Before operation those with haemorrhoids had significantly higher resting anal pressures (P < 0.005), lower rectal compliance (P < 0.05) and more perineal descent (P < 0.05). Following haemorrhoidectomy there were significant decreases in the maximum resting (P < 0.05) and maximum squeeze anal (P < 0.001) pressures to within normal values 3 months after operation. Rectal compliance also increased significantly (P < 0.05), to that of normal controls. The abnormalities found in patients with prolapsed piles reverted to the normal range within 3 months of haemorrhoidectomy. These physiological changes are therefore more likely to be an effect, rather than the cause, of enlarged anal cushions.

Adult↗
PubMed1995

Prospective randomized trial comparing J colonic pouch-anal anastomosis and straight coloanal reconstruction.

Twenty patients (13 men) with low rectal cancer, median (range) age 64.5 (38-83) years were prospectively randomized to undergo ultra-low anterior resection with a J colonic pouch-anal anastomosis (median (range) distance of anastomosis from the anal verge 3 (1-4) cm). Another 20 patients (15 men), median (range) age 62.5 (44-86) years) with low rectal cancer were randomized to a straight coloanal anastomosis (median (range) distance of anastomosis from the anal verge 3.25 (2-5) cm). There were no significant differences in operative time or complications between the two groups. There was significantly better postoperative anal function in patients who underwent pouch-anal anastomosis at 1, 6 and 12 months after ileostomy closure. At 12 months all patients (19 of 19) with a pouch reconstruction had regained normal continence compared with 14 of 20 of those who had a straight coloanal anastomosis. No patient complained of severe constipation requiring enema or intubation to evacuate.

Adenocarcinoma↗
PubMed1995

Prospective randomized controlled trial of a micronized flavonidic fraction to reduce bleeding after haemorrhoidectomy.

A prospective randomized controlled trial was carried out on the effects of Daflon 500 mg (a micronized flavonidic fraction containing diosmin 450 mg and hesperidin 50 mg) on bleeding after haemorrhoidectomy. In all, 228 consecutive patients with prolapsed irreducible piles were recruited. Elective haemorrhoidectomy was performed with a standardized diathermy excision method. Some 114 patients were randomized to receive Daflon 500 mg for 1 week after operation (group 1), and there were 114 controls (group 2). Postoperative analgesia and laxative prescription as well as hospital stay were otherwise the same. One patient (0.9 per cent) from group 1 and seven (6.1 per cent) from group 2 had postoperative bleeding (P = 0.03). All bleeding occurred from 6 to 15 days after haemorrhoidectomy. There were no side-effects from the use of Daflon 500 mg. The risk of secondary bleeding from haemorrhoidectomy is reduced with postoperative Daflon.

Adult↗
PubMed1995

The neurophysiological significance of perineal descent.

The establishment of a linear relationship between perineal descent (PD) and pudendal nerve motor terminal latency (PNMTL) is important in understanding the pathophysiology of pudendal neuropathy. The amount of stretching of the pudendal nerve resulting from the extent of PD, should correlate with the amount of injury sustained (PNMTL). The two key previous studies which used different techniques to measure PD, have differed on this vital issue. A prospective study was undertaken in 141 consecutive patients with PD (M:F = 57:84; mean age 46.3 SEM 1.6 years) to clarify this discrepancy. The patients had chronic constipation (81), neurogenic faecal incontinence (31), rectal mucosal prolapse (17) or female urinary stress incontinence (9). All underwent measurements of PD (by perineometry), anal sphincter pressures, single fibre anal sphincter electromyography and PNMTL. These variables, as well as age were analyzed for a linear relationship with PD by multiple regression analysis. Age was the only independent variable predicting PD at rest (T = -3.2; p < 0.005). PNMTL was the only independent variable predicting PD on straining (T = -3.0; p < 0.005). In conclusion, a linear relationship between PD on straining and PNMTL was confirmed, supporting the previous study which also measured PD by perineometry. The other study which refuted such a relationship measured PD radiologically, and it is likely that the difference was in the measurement technique.

Adult↗
PubMed1995

Unilateral anal electrosensation. Modified technique to improve quantification of anal sensory loss.

PURPOSE: Anal electrosensation is usually tested by an annular configured electrode that stimulates the circumference of the anus. In certain pelvic conditions, the right and left pudendal nerve function may be damaged separately and to different degrees. This may only be detected by a unilateral electrode testing each side independently. METHODS: Our study compares accuracy and sensitivity of annular and unilateral electrodes in assessing patients with hemorrhoids, perineal descent, incontinence, after low anterior resection, and constipation (107 subjects). RESULTS: In normal controls (n = 19), annular thresholds ranged from 0.5 to 2.7 mA and unilateral thresholds from 0.6 to 2.6 mA. In prolapsed hemorrhoids, unilateral was more sensitive than annular electrode in detecting deficits at the upper (P < 0.0001), mid (P < 0.005), and lower (P < 0.0005) anus. Patients with perineal descent had a sensory deficit in the upper anal canal, detected more consistently by unilateral electrode (P > 0.05). No significant abnormalities were found in neuropathic incontinence, after anterior resection and chronic constipation. Results of the unilateral electrosensory technique were found to be consistent with repeated measurements (r = 0.8878; P < 0.001). CONCLUSIONS: By being more sensitive than the annular technique, the unilateral electrode method may become, with refinement, a useful test for quantifying anal sensation.

Adult↗
PubMed1995

Solitary rectal ulcer syndrome: the clinical entity and anorectal physiological findings in Singapore.

The clinical pattern and physiological abnormalities in solitary rectal ulcer syndrome (SRUS) occurring in Singapore, were investigated. Since April 1989, 25 patients have presented with histologically proven SRUS. There were 13 males and 12 females (20 Chinese, 4 Malay and 1 Indian) with a mean age of 47.5 (+/- 3.1) years. Ninety-six per cent presented with rectal bleeding, 92% strained at stools, 40% had mucus discharge, 40% felt incomplete defecation and 32% digitated to defecate. Four had previous haemorrhoidectomies that did not cure their symptoms. The lesions were at a mean 6.8 (+/- 0.5) cm above the anal verge, usually anteriorly (64%) but one was circumferential. Anorectal physiology performed on 14 patients was compared with 13 age and gender matched normal controls. The measured mean resting perineum level in SRUS (1.4 +/- 0.3 cm) was significantly lower than in normals (P < 0.01). The mean anal electrosensory threshold (2.5 +/- 0.52 mV) was also significantly higher than in the controls (P < 0.05). Fifteen patients were successfully treated with a high fibre diet and avoidance of straining. Three patients required surgery and the most recent seven patients have responded well to biofeedback treatment. Awareness of this uncommon anorectal condition is necessary for early diagnosis and appropriate management. The physiological findings support a pelvic straining pathophysiology resulting in perineal descent, with less sensitive rectal mucosa prolapsing into, and raising, the anal canal electrosensory threshold. Treatment strategies aimed at correcting the straining have usually been successful.

Anal Canal↗
PubMed1995

Anal stricture following haemorrhoidectomy: early diagnosis and treatment.

Anal stricture is an uncommon but well recognized complication following haemorrhoidectomy. Twenty-seven (3.8%) out of 704 (500 elective and 204 emergency) cases of haemorrhoidectomy performed at the Singapore General Hospital over a 24 month period had clinical evidence of anal stricture post-haemorrhoidectomy. Of the 27 cases, 15 had haemorrhoidectomy as an elective procedure while 12 had it performed as an emergency procedure (chi 2 = 3.26, 1 d.f., P > 0.05, not significant). The mean interval between surgery and presentation of anal stricture was 6 weeks (range 3-12 weeks). Eighteen of the patients were managed by anal dilatation in the outpatient clinic combined with bulk laxatives and a local anaesthetic agent. The other nine patients required a minor surgical procedure comprising either a lateral internal sphincterotomy (five) or an anoplasty (four) procedure. All patients were well, following treatment. None of these patients developed a recurrent stricture at follow up 3 months after treatment. It was concluded that although anal stricture following haemorrhoidectomy is rare, it should be detected and treated early in order to avoid pain and suffering, and treatment is usually successful.

Adolescent↗
PubMed1995

Comparison study of DNA content of primary and metastatic lymph node lesions of colorectal cancer.

Abnormal DNA content or aneuploidy in cells usually indicates malignancy. In colorectal cancer aneuploidy has been shown to confer a poorer prognosis suggesting that aneuploid cancers are more aggressive. The mechanisms involved in the aggressive behaviour of an aneuploid tumour are still unknown. The aim of this study was to compare the patterns of aneuploidy of colorectal cancers and that of their corresponding lymph node metastases and to relate them to clinical outcomes. One hundred and one patients were studied, 81 (Dukes C) with lymph node metastasis only and 20 (Dukes D) with obvious distant metastasis as well. Forty-six (46.5%) of the tumours and an equal number of the lymph nodes were found to be aneuploid. Twenty-eight (60.9%) of the aneuploid tumours showed aneuploid metastasis and 18 (39.1%) showed diploid metastasis. Similarly, 37 (67.3%) of the diploid tumours showed diploid metastasis whereas 18 (32.7%) showed aneuploid metastasis. Local recurrence and distant metastasis were compared among the aneuploid and diploid primary tumours. Although there was no statistically significant difference, distant metastasis was more common in aneuploid tumour. Ploidy of the lymph node was not related to local recurrence or distant metastasis. We conclude that DNA ploidy by itself does not determine the metastatic potential of the tumour cell and that in about 50% of the tumours, the lymph node metastasis consists of clones of cells different from the primary tumours. We also conclude that the clinical outcome of the disease in terms of recurrence and metastasis cannot be predicted by the ploidy of the lymph node metastatic lesions.

Aneuploidy↗
PubMed1995

Anorectal physiological parameters in chronic constipation of unknown aetiology (primary) and of cerebrovascular accidents--a preliminary report.

Chronic constipation may be secondary to dietary, metabolic or neurological causes such as cerebrovascular accidents (CVA). In certain patients, the cause is unknown (primary idiopathic constipation [PIC]). This study compared the anorectal physiological parameters of 15 PIC patients (all females; median age 40, range 32-48 years) with 7 CVA patients (M:F = 6:1; median age 58, range 51-67 years), to observe the influence of cerebral factors on the anorectal physiology of constipation. Twenty-five normal subjects (M:F = 13:12; median age 47, range 43-50 years) acted as controls. Transit marker studies showed decreased passage in both groups, but 9 of the PIC patients had a diffuse pattern (slow transit constipation [STC]) and 6 had a pelvic outlet obstruction pattern (PO). The CVA patients had a diffuse pattern of delayed transit. Rectal sensation was significantly impaired in STC (P < 0.05) but not in PO or CVA. Electromyographic evidence of paradoxical puborectalis contractions was significantly more common in PO only (P < 0.05). Therefore, CVA patients had a different anorectal physiological pattern of constipation from PIC patients.

Adult↗
PubMed1995

Association of activated proto-oncogenes ras and myc in colorectal carcinomas.

We have examined 60 colorectal carcinomas for activation of two proto-oncogenes, c-myc and c-Ki-ras. Over-expression of c-myc mRNA as determined by Northern analysis was found in 58% of cases (35/60). Activation of the c-Ki-ras gene by point mutations in codons 12 or 13 as determined by mismatch specific oligonucleotide hybridisation was found in 35% (21/60) of cases. There was a statistically significant association between activation of c-Ki-ras and over-expression of c-myc (P = 0.03), with 76% of tumours with an activated c-Ki-ras proto-oncogene showing over-expression of c-myc. The association was significant in left-sided colorectal tumours (P = 0.03) but not right-sided (P = 0.5). However, whereas only 59% of left side tumours showed at least one of the two changes (ras activation only, or myc activation only or both), 93% of right side tumours showed at least one of the changes (P = 0.01). Twenty-two percent of left side tumours showed both changes compared with 35% of right side tumours, although this result did not achieve significance (P = 0.2). These results suggest that in left-sided colorectal tumours ras and myc cooperate, as established in vitro, to produce neoplastic transformation while different pathway(s) are involved in right-sided tumours.

Base Sequence↗
PubMed1995

Allelic loss of the p53 gene in colorectal cancer.

The loss of specific chromosomal loci in cancers is indicative that the region contains a tumour suppressor gene. Allelic loss of chromosome 17p has been shown to occur in a wide variety of cancers such as lung, breast, colon, ovary and brain and, until recently, the gene believed to be involved was the p53 tumour suppressor gene. However, more recent studies have shown that the area deleted in some of these tumours does not include the structural gene for p53. For this reason it has been proposed that a tumour suppressor gene lying distal to p53 on chromosome 17p is the gene deleted in these cancers. As chromosome 17p has been shown to be deleted in approximately 75% of colorectal cancers, we set out to determine whether the target gene of these deletions was the structural gene for p53. Allelic loss was assessed by using restriction fragment length polymorphisms in 52 tumours. Deletions distal to p53 on chromosome 17p were assessed using the probe YNZ22.1 and allelic loss of p53 was assessed using probe pR4-2, a cDNA probe specific for the p53 gene. Out of the 21 tumours informative for both probes, 3 cases showed no allelic deletion of the chromosome 17p, 2 cases showed allelic deletion not encompassing the p53 gene and 16 cases (89%) showed allelic deletion including the p53 gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗