Displaying publications 21 - 26 of 26 in total

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  1. Liew NC, Gee T, Sandra K, Gul YA
    Med J Malaysia, 2003 Dec;58(5):766-8.
    PMID: 15190666
    Perforation with extravasation of barium is a rare complication of contrast enema examination of the large bowel with a high associated mortality rate. The experience of performing a re-laparotomy in a patient previously exposed to barium peritonitis is even less common. We describe an elderly male patient with a Hartmann's procedure performed a year previously, presenting with peritonitis following barium enema evaluation of the proximal colon via an end descending colon stoma. Emergency laparotomy, segmental bowel resection and liberal peritoneal toilet resulted in a satisfactory outcome. The patient had a subsequent successful reversal of his Hartmann's procedure nine months later despite the presence of dense barium induced adhesions. This potentially preventable iatrogenic complication is discussed in this report, which is supplemented by a brief review of the English literature.
  2. Jabar MF, Halim ME, Gul YA
    Asian J Surg, 2004 Jan;27(1):26-31.
    PMID: 14719511
    The aim of this study was to determine the appropriateness of colonoscopy in relation to its diagnostic yield, with reference to the guidelines set by the American Society of Gastrointestinal Endoscopy (ASGE). A prospective 90-day audit was performed at Hospital Kualal Lumpur, which is a tertiary referral centre in Malaysia, to examine the appropriateness of colonoscopy by indication. During that time, 257 colonoscopies were performed in 244 patients. The predominant indications for colonoscopy were altered bowl habit (37%) and rectal bleeding (18%). Of the 257 colonoscopies, 216 (84%) were judged to be appropriate by ASGE guidelines. Only 43% of all colonoscopies had positive findings. Positive findings were found in 93% of cases judged appropriate compared with only 7% found in cases deemed inappropriate. There were statistically significant relationships between appropriateness and overall positive yield and between appropriateness and neoplastic findings (p < 0.05). Colonoscopy performed for appropriate indications yield more significant findings, this, we advocate the use of accepted guidelines to maintain or improve the standard colonoscopy services.
  3. Khor TO, Gul YA, Ithnin H, Seow HF
    Cancer Lett, 2004 Jul 16;210(2):139-50.
    PMID: 15183529
    The enhancement of cell proliferation and promotion of cell survival via the inhibition of apoptosis is thought to be the key to the initiation and progression of cancers. The phosphatidylinositol-3 kinase (PI3K)/Akt is an important survival signal pathway that has been shown to be crucial in the regulation of balance between pro-apoptotic and survival (anti-apoptotic) signal. In this study, the expression of phosphorylated Akt at Thr308 and Ser473, BCL-2-antagonist of cell death (BAD) at Ser136 and glycogen synthase kinase-3beta (GSK-3beta) at Ser9 in 47 paraffin-embedded human colorectal carcinoma (CRC) tissues were determined by immunohistochemical staining in order to dissect the alterations in the signal transduction pathways in CRC. Our results showed that there was a significant increase in the expression of these biomolecules in CRC tissues compared to the apparently normal adjacent tissues. The frequency of increased expression in tumor colonic mucosa were as follows: p-Akt1/2/3 (Thr308) = 16/47 (34%); p-Akt1 (Ser473) = 21/47 (44.7%); phospho-BAD (p-BAD) Ser136 = 27/47 (57.4%) and phospho-GSK-3beta (p-GSK-3beta) = 21/47 (44.7%). Analysis of the total p-Akt1 (Ser473), p-Akt1/2/3 (Thr308), p-GSK-3beta (Ser9) and p-BAD (Ser136) score found that there was a statistically significant relationship with each other. A statistically significant positive linear relationship was found between total p-Akt (Ser473) score and total p-GSK-3beta (Ser9) score as well as with total p-BAD (Ser136) score. On the other hand, total p-Akt1/2/3 (Thr308) scores had a statistically significant positive linear relationship with p-GSK-3beta (Ser9) only. The Akt targets, p-GSK-3beta (Ser9) and p-BAD (Ser136) were positively correlated to each other. There was no significant correlation between clinico-pathological data with total p-Akt1 (Ser473), p-Akt1/2/3 (Thr308), p-GSK-3beta (Ser9) and p-BAD (Ser136) score except for age. The total scores of p-GSK-3beta were found to be higher in patients in the age group of greater than 60. This is the first report of p-Akt1/2/3 (Thr308) and p-BAD (Ser136) expression in primary colorectal tumor tissue. Our data further supports the role of PI3K/Akt signaling pathways in the pathogenesis of CRC and contributes to the identification of target molecules in the signal transduction pathway for cancer therapy.
  4. Ching-Shian Leong V, Jabal MF, Leong PP, Abdullah MA, Gul YA, Seow HF
    Cancer Genet. Cytogenet., 2008 Dec;187(2):74-9.
    PMID: 19027487 DOI: 10.1016/j.cancergencyto.2008.07.005
    Somatic mutations of phosphoinositide-3-kinase, catalytic, alpha; PIK3CA gene have been reported in several types of human cancers. The majority of the PIK3CA mutations map to the three "hot spots" - E542 K and E545 K in the helical (exon 9) and H1047R in the kinase (exon 20) domains of the p110alpha. These hot spot mutations lead to a gain of function in PI3 K signaling. We aimed to determine the frequency of PIK3CA mutations in the three most common Malaysian cancers. In this study, we assessed the genetic alterations in the PIK3CA gene in a series of 20 breast carcinomas, 24 colorectal carcinomas, 27 nasopharyngeal carcinomas (NPC), and 5 NPC cell lines. We performed mutation analysis of the PIK3CA gene by genomic polymerase chain reaction (PCR) and followed by DNA direct sequencing in exons 9 and 20. No mutations were detected in any of the 24 colorectal and 27 NPC samples, but one hot spot mutation located at exon 20 was found in a NPC cell line, SUNE1. Interestingly, PIK3CA somatic mutations were present in 6/20 (30%) breast carcinomas. Two of the six mutations, H1047R, have been reported previously as a hot spot mutation. Only one out of three hot spot mutations were identified in breast tumor samples. The remaining four mutations were novel. Our data showed that a higher incidence rate of PIK3CA mutations was present in Malaysian breast cancers as compared to colorectal and nasopharyngeal tumor tissues. Our findings also indicate that PIK3CA mutations play a pivotal role in activation of the PI3 K signaling pathway in breast cancer, and specific inhibitors of PIK3CA could be useful for breast cancer treatment in Malaysia.
  5. Hong SK, Gul YA, Ithnin H, Talib A, Seow HF
    Asian J Surg, 2004 Jan;27(1):10-7.
    PMID: 14719508
    BACKGROUND: Promising new pharmacological agents and gene therapy targeting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) could modulate treatment of colorectal cancer in the future. The aim of this study was to elucidate the expression fo beta-catenin and teh presence of COX-2 and iNOS in colorectal cancer specimens in Malaysia. This is a useful prelude to future studies investigating interventions directed towards COX-2 adn iNOS.

    METHODS: A cross-section study using retrospective data over a 2-year period (1999-2000) involved 101 archival, formalin-fixed, paraffin-embedded tissue samples of colorectal cancers that were surgically resected in a tertiary referral.

    RESULTS: COX-2 production was detected in adjacent normal tissue in 34 sample (33.7%) and in tumour tissue in 60 samples (59.4%). More tumours expressed iNOS (82/101, 81.2%) than COX-2. No iNOS expression was detected in adjacent normal tissue. Intense beta-catenin immunoreactivity at the cell-to-cell border. Poorly differentiated tumours had significantly lower total beta-catenin (p = 0.009) and COX-2 scores (p = 0.031). No significant relationships were established between pathological stage and beta-catenin, COX-2 and iNOS scores.

    CONCLUSIONS: the accumulation of beta-catenin does not seem to be sufficient to activate pathways that lead to increased COX-2 and iNOS expression. A high proportion of colorectal cancers were found to express COX-2 and a significant number produced iNOS, suggesting that their inhibitors may be potentially useful as chemotherapeutic agents in the management of colorectal cancer.

  6. Gul YA, Prasannan S, Jabar FM, Shaker AR, Moissinac K
    World J Surg, 2002 Dec;26(12):1499-502.
    PMID: 12297939 DOI: 10.1007/s00268-002-6529-8
    Endoscopic thermal therapy and formalin are being increasingly recommended for the treatment of chronic hemorrhagic radiation proctitis. It may be too early, however, to discard pharmacologic agents from the management process, especially in medical institutions where specialized equipment is unavailable. We prospectively assessed the effectiveness of medical therapy in 14 consecutive patients with chronic hemorrhagic radiation proctitis from July 1999 to June 2001. All 14 subjects were women (mean age 56 years), 13 of whom had had radiotherapy for cancer of the cervix. The median time to onset of symptoms following irradiation was 16 months. Six patients had a hemoglobin level of < 8 g/dl, and blood transfusion was required in 11 patients. In five patients (36%) initially treated with hydrocortisone enemas prior to referral, this treatment continued; and the remaining nine patients were commenced on sucralfate enemas. Two patients given rectal hydrocortisone continued to bleed and were treated with sucralfate enemas and topical formalin, respectively. Rectal sucralfate suspension effectively procured symptomatic alleviation in all 11 patients. Rectal bleeding recurred in two patients who had been managed exclusively with hydrocortisone and sucralfate enemas, respectively, over a mean follow-up of 6 months. Both patients were managed with topical formalin, which controlled their symptoms. Even though the number of subjects in this study is small, sucralfate enema can be recommended as an effective first-line agent for managing patients with chronic hemorrhagic radiation proctitis. The use of more specialized therapy can therefore be reserved for cases where primary treatment failure occurs with sucralfate therapy.
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