INTRODUCTION: The use of neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision (TME) has shown promising results in the management of locally advanced rectal carcinoma, and is associated with improvement in local control, disease free survival (DFS) and overall survival (OS). However, these clinical endpoints cannot be properly assessed due to poor follow up among many patients. Other endpoints such as negative circumferential resection margins (CRM), pathologic complete response (pCR) and sphincter-preserving surgery (SPS) may serve as indirect means of assessing successful treatment. This study reports the experience of the Philippine General Hospital (PGH) Colorectal Polyp and Cancer (CRPoCan) Study Group in using neoadjuvant CRT and TME in the management of locally advanced rectal carcinoma, towards quality care.
METHODS: The Integrated Surgical Information System (ISIS) database of the Department of Surgery, PGH was queried for rectal cancer patients with pretreatment clinical stage II and III disease that underwent neo-adjuvant CRT followed by TME between January 2008 and December 2009. The final surgical pathology reports of the subjects were reviewed for treatment response. Response was categorized as: (1) positive or negative CRM; and (2) with or without pCR. The study assessed whether SPS was done.
RESULTS: Of 140 potential neoadjuvant CRT patients followed by TME, 82 patients completed the treatment. Thirty two of the patients who completed treatment (39%) were eligible since the other 50 patients (61%) had no post-operative histopathology results. Among those eligible, 10 patients (31%) had pCR. Only 1 patient had a positive CRM. Of the 14 patients whose tumor distance was ?5cm from the anal verge, only 1 patient underwent SPS. The small sample size was mainly attributed to low resources or treatment. Non-availability of post-operative histopathology results was due to poor record keeping.
CONCLUSION: The PGH CRPoCan Study Group's use of neoadjuvant CRT followed by TME for locally advanced rectal carcinoma has resulted in acceptable numbers of pCR and clear CRM but has not translated into an increased number of SPS. Despite the limitations of the study, the institutionalization of the multidisciplinary team in the PGH CRPoCan Study Group and the implementation of the ISIS database program are considered the first steps towards quality health care.

Human ; Male ; Female ; Neoadjuvant Chemoradiotherapy ; Total Mesorectal Excision ; Polyp ; Surgical Pathology ; Rectal Cancer

Objectives: The highly polymorphic nature of the CYP2D6 gene and its central role in the metabolism of commonly used drugs make it an ideal candidate for pharmacogenetic screening. This study aims to determine the prevalence of CYP2D6 polymorphisms among Filipinos and their association to lung cancer. Method: Forty seven single nucleotide polymorphisms (SNPs) of the CYP2D6 gene were genotyped from DNA samples of 115 cases with lung cancer and age- and sex-matched 115 controls. Results: Results show that 18 out of 47 polymorphisms have significant genotypic variability (>1% for at least 2 genotypes). No variant is associated with lung cancer. However, rs1135840, rs16947 and rs28360521, were found to be highly variable among Filipinos. Conclusion This study demonstrated that CYP2D6 polymorphisms are present among Filipinos, which, although not found to be associated with lung cancer, can be useful biomarkers for future pharmacogenetic studies. The SNP rs16947 is found to be associated with cancer and timolol-induced bradycardia; the SNP rs1135840, on the other hand, is only shown to be linked with cancer. The genetic variant rs28360521 is known to be associated with low-dose aspirin-induced lower gastrointestinal bleeding.
Pharmacogenetics ; Cytochrome P-450 CYP2D6 ; Lung Neoplasms ; Biomarkers

Objectives. Polymorphisms in metabolic genes which alter rates of bioactivation and detoxification have been shown to modulate susceptibility to colorectal cancer. This study sought to evaluate the colorectal cancer risk from environmental factors and to do polymorphism studies on genes that code for Phase I and II xenobiotic metabolic enzymes among Filipino colorectal cancer patients and matched controls. Methods. A total of 224 colorectal cancer cases and 276 controls from the Filipino population were genotyped for selected polymorphisms in GSTM1, GSTP1, GSTT1, NAT1 and NAT2. Medical and diet histories, occupational exposure and demographic data were also collected for all subject participants.Results. Univariate logistic regression of non-genetic factors identified exposure to UV (sunlight) (OR 1.99, 95% CI: 1.16-3.39) and wood dust (OR 2.66, 95% CI: 1.21-5.83) and moldy food exposure (OR 1.61, 95% CI:1.11-2.35) as risk factors; while the NAT2*6B allele (recessive model OR 1.51, 95% CI :1.06-2.16; dominant model OR 1.87, 95% CI: 1.05-3.33) and homozygous genotype (OR 2.19, 95% CI: 1.19-4.03) were found to be significant among the genetic factors. After multivariate logistic regression of both environmental and genetic factors, only UV radiation exposure (OR 2.08, 95% CI: 1.21-3.58) and wood dust exposure (OR 2.08, 95% CI: 0.95-5.30) remained to be significantly associated with increasing colorectal cancer risk in the study population.Conclusion. This study demonstrated that UV sunlight and wood dust exposure play a greater role in influencing colorectal cancer susceptibility than genotype status from genetic polymorphisms of the GST and the NAT` genes.
Colorectal Neoplasms ; Polymorphism, Genetic