H. S. Goh

Apoptosis and apoptosis related gene expression in normal conjunctiva and pterygium

BACKGROUND Pterygium is a relatively common eye disease in the tropics whose aetiology and pathogenesis remain uncertain. As such, interest has focused on understanding the underlying mechanism of pterygia development. METHODS 15 specimens of pterygia from 15 eyes were examined, together with normal conjunctival tissue from the same eyes for the pattern of gene expression of genes associated with the induction or repression of apoptosis (p53, bcl-2, and bax). In addition, the samples directly for apoptotic cells were examined by the terminal deoxynucleotide transferase (TdT) mediated nick end labelling (TUNEL) methodology. RESULTS In pterygia specimens apoptotic cells were found mainly confined to the basal layer of cells of the epithelial layer, situated immediately adjacent to the fibrovascular support layer. These cells were shown to express significant levels of p53 and bax, as well as the apoptosis inhibiting protein bcl-2. In contrast, normal conjunctival specimens displayed no bcl-2 expression and apoptotic cells were seen throughout the entire width of the epithelial layer, coupled with high levels of bax expression. CONCLUSION These results support a model whereby pterygia development is a result of disruption of the normal process of apoptosis occurring in the conjunctiva.

A simple and effective treatment for hemorrhagic radiation proctitis using formalin

Radiation proctitis is a common complication of radiotherapy for pelvic malignancy. In the more severe form, it leads to intractable or massive hemorrhage, which may require repeated hospital admissions and blood transfusions. Medical therapy in patients with radiation proctitis is usually ineffective, whereas surgery is associated with a high morbidity and mortality. Eight patients (seven females and one male) with hemorrhagic radiation proctitis were Treated over a six-month period with endoluminal formalin. The technique used ensured minimal contact with formalin. The median age of the patients was 68 years (range, 42–73 years). Seven patients had had cancer of the uterine cervix, and one patient had had cancer of the prostate treated with radiotherapy at a median time of 30 months (range, 9–46 months) previously. The median duration of time of symptomatic rectal hemorrhage before formalin therapy was eight months (range, 1–12 months). The median number of units of blood transfused previously per patient was four (range, 2–32). The time taken for formalin therapy was 20 minutes (range, 10–70 minutes). One patient required repeat formalin application at two weeks. Bleeding ceased immediately in seven patients after formalin treatment. No further bleeding was noted, nor was any blood transfusion needed, at follow-up at four months (range, 1–6 months). Formalin therapy is a simple, inexpensive, and effective treatment for hemorrhagic radiation proctitis.

Prospective, randomized trial comparing pain and clinical function after conventional scissors excision/ligation vs. diathermy excision without ligation for symptomatic prolapsed hemorrhoids

Forty-nine consecutive patients with symptomatic prolapsed hemorrhoids were prospectively randomized for conventional scissors excision with ligation (Group A; n = 16) or diathermy excision without ligation (Group B; n = 33). The median time taken to complete the procedure was 20 minutes (range, 10–40 minutes) and 10 minutes (range, 5–35 minutes) in Groups A and B, respectively (P<0.05). Length of hospital stay was similar in both groups, with a median of three days and a range of two to five days. The median length of follow-up was 35 weeks (range, 20–50 weeks) and 35 weeks (range, 20–51 weeks) for Groups A and B, respectively. There was no statistical difference in the severity of postoperative pain between the two groups. The use of postoperative oral analgesics was significantly lower in Group B (P<0.02), but there was no significant difference in the demand for intramuscular or topical analgesics. Diathermy excision of hemorrhoids is significantly faster than scissors excision, there is less bleeding, the vascular pedicles need not be ligated, and there is significant reduction in the requirement for oral analgesics postoperatively without any increase in early or late postoperative complications.

Bowel function survey after segmental colorectal resections.

PURPOSE: Long-term bowel function after right hemicolectomy (RHC), extended right hemicolectomy (ERHC), left hemicolectomy (LHC), sigmoid colectomy (SC), and anterior resection (AR) was evaluated. METHOD: Three hundred fifteen patients (52.3 percent) replied to a questionnaire on stool frequency, fecal continence, and defecation problems. All patients had undergone surgery at least one year before questionnaire was sent to them. Patients with anastomotic leaks and recurrences were excluded. RESULTS: Stool frequency was one to two bowel movements per day in 78 percent of patients after RHC, 75 percent after ERHC, 57.6 percent after LHC, 64.3 percent after SC, and only 44.8 percent after AR (P=0.01). Continence affected lifestyle in 32 percent of patients after AR, but affected only up to 11.5 percent of patients who had had more proximal resections (P=0.001). Defecation problems occurred in less than 15.4 percent after RHC, ERHC, and LHC but were encountered more frequently after SC (25 percent) and AR (28.4 percent;P=0.009). CONCLUSIONS: Problems with postoperative bowel function were appreciably more common after SC and AR.

p53 and behaviour of colorectal cancer

The tumour suppressor gene p53 is altered in most colorectal tumours. We found that lymphatic dissemination was driven by the presence of mutated p53 whether or not the cell contained wild-type p53. In a total sample of 187 specimens, point mutation of the p53 gene occurred in 70% and 43% of cases with and without lymph-node involvement, respectively. By contrast, haematogenous dissemination was apparently the result of absent functional wild-type p53 (whether or not the cell contained mutated p53). These results are of potential importance in the prediction of the clinical behaviour of a tumour.

Clinical and physiologic effects of biofeedback in outlet obstruction constipation

PURPOSE: We report the results of biofeedback (BF) on patients with outlet obstruction defecation (OOC), including those with and without measurable paradoxical puborectalis contractions (PP). Clinical and anorectal physiologic parameters (ARP) were assessed one week before and after a standardized course of BF. METHODS: Sixty-two consecutive patients (24 men, 38 women; mean age, 48 (standard error of the mean, 2.3) years) were recruited. All had persistent constipation despite six weeks of dietary fiber supplements. Colonic inertia was excluded by transit marker studies. Defecating proctography excluded anatomic abnormalities causing outlet obstruction. Patients underwent four outpatient sessions of biofeedback, each session lasting one hour. RESULTS: After BF, 56 patients (90.3 percent) were subjectively improved. Frequency of spontaneous bowel movements were significantly increased (P=0.003). Frequency of laxative-induced (P=0.004) and enema-induced (P=0.005) stools were reduced. Anal resting (P=0.04) and squeeze (P=0.002) pressures were increased. Number of patients with PP was reduced from 40 to 31 (P=0.004). Presence of PP did not affect response to BF. There were no differences in ARP between the 56 patients who improved and the 6 who did not. There were no side effects or clinical regressions after a mean follow-up of 14.9 (standard error of the means, 0.9) months. CONCLUSIONS: BF effectively treated OOC in 90.3 percent, regardless of PP. Anal pressures were increased, and PP was decreased.

Performing internal sphincterotomy with other anorectal procedures

PURPOSE: A study was conducted to compare the outcome of combined anorectal procedures involving lateral internal sphincterotomy with lateral internal sphincterotomy alone to determine if the former results in increased complications. METHODS: Complications and anal function of 57 patients who underwent lateral internal sphincterotomy for chronic anal fissure in conjunction with another anorectal procedure (combined group) between April 1989 and June 1992 were compared with 57 other age- and sex-matched patients who underwent lateral internal sphincterotomy alone (control group). RESULTS: There was no statistical difference in the incidence of incontinence in the combined group (8.7 percent) and the control group (7 percent). None of the cases in either group had permanent incontinence. There were also no statistical differences in the incidence of postoperative bleeding, pruritus ani, mucus discharge, abscess formation, fistulation, and rates of fissure recurrence. CONCLUSIONS: Additional anorectal procedures performed at the same time as internal sphincterotomy do not increase the incidence of postoperative complications.

High frequency of allelic deletion on chromosome 17p in advanced colorectal cancer.

Background. Colorectal cancers often show alletic loss of chromosomes 5q and 17p, regions where the tumor suppressor genes p53 and adenomatous polyposis coli are known to reside. Currently, the inactivation of tumor suppressor genes and the activation of oncogenes are considered major events involved in tumor development. According to a recent genetic model, ras gene mutations and allelic deletion of chromosome 5q are early changes, whereas chromosome 17p and 18q deletions are late changes in colorectal tumorigenesis. It has been shown that 17p and 18q deletions are associated with an increased tendency of disease dissemination in colorectal cancer. Most of the studies on allelic deletion in colorectal cancer were undertaken with Western population cohorts. The authors examined the association of chromosomes 5q and 17p deletions with clinical parameters, including metastasis in a predominantly Chinese population with a high incidence of colorectal cancer.

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.