Placebo Controlled Trials: Interests of Subjects versus Interests of Drug Regulators

The use of placebo-controlled trials in situations where established therapies are available is considered ethically problematic since the patients randomised to the placebo group are deprived of the beneficial treatment. The pharmaceutical industry and drug regulators seem to argue that placebo-controlled trials with extensive precautions and control measures in place should still be allowed since they provide necessary scientific evidence for the efficacy and safety of new drugs. On the other hand, the scientific value and usefulness for clinical decision-making may be much higher if the new drug is compared directly to existing therapies. As such, it may still be unethical to impose the burden and risk of placebo-controlled trials on patients even if extensive precautions are taken. A few exceptions do exist. The use of placebo-controlled trials in situations where an established, effective and safe therapy exists remains largely controversial.

Median Survival Time of Endometrial Cancer Patients with Lymphovascular Invasion at the Hospital Universiti Sains Malaysia

Background: Endometrial cancer is the most common gynaecologic malignancy among females worldwide. The purpose of this study was to determine the median survival time of endometrial cancer patients at the Hospital Universiti Sains Malaysia (USM). Methods: A list of 121 endometrial cancer cases registered at Hospital USM between 2000 until 2011 was retrospectively reviewed. The survival time of the endometrial cancer patients was estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare the survival of the patients based on socio-demographics and clinical presentation. Results: Only 108 patients, 87.0%, were included who were of Malay ethnicity. Previous history included menopause in 67.6% of patients and diabetes mellitus in 39.8% of patients; additionally, 63.4% of patients were nulliparous. Tumour staging was as follows: 24.5% stage I, 10.8% stage II, 26.5% stage III and 38.2% stage IV. The overall median survival time of the endometrial cancer patients was 70.20 months (95% confidence interval (CI): 51.79, 88.61). The significant factors were age, the presence of lymphovascular invasion and treatment received. Conclusion: The overall survival of endometrial cancer was low. A prospective study needs to be carried out to discover more effective and accurate tests for the early detection of endometrial cancer.

Informed Consent Template and Guidelines on the Ethical Practice in Human Genetics and Human Genomic Research; Initiatives of the Universiti Sains Malaysia

Malaysia is advancing and nearly on pace with the international scientific community in human genetics and human genomics research. However, this research poses unique challenges. Although Malaysia already regulates medical genetic services, these regulations are insufficient for coping with the ethical issues emerging from recent genomic technologies. The Universiti Sains Malaysia recently created in-house guidelines and an informed consent template for genetic and genomic research. This article presents these guidelines and the informed consent template and discusses the justification and the background of the initiative. We also propose recommendations pertaining to local social studies and regulatory arrangements.

Review of the Medicinal Effects of Tualang Honey and a Comparison with Manuka Honey

Tualang honey (TH) is a Malaysian multifloral jungle honey. In recent years, there has been a marked increase in the number of studies published in medical databases regarding its potential health benefits. The honey is produced by the rock bee (Apis dorsata), which builds hives on branches of tall Tualang trees located mainly in the north-western region of Peninsular Malaysia. This review collates the results of the various studies of TH that range from research on tissue culture to randomised control clinical trials. Findings thus far show that, TH has antimicrobial, anti-inflammatory, antioxidant, antimutagenic, antitumor, and antidiabetic properties, in addition to wound-healing attributes. Some of its properties are similar to the well-researched Manuka honey (New Zealand and/or Australian monofloral honey). Distinct differences include higher phenolics, flavonoids, and 5-(hydroxymethyl) furfural (HMF). Compared with Manuka honey, TH is also more effective against some gram-negative bacterial strains in burn wounds.

Adequacy of cellular material in split-sampling of cervical scrapings for routine cancer screening: an analysis of 702 smears

Objective: The aim of this study was to examine cells (split-sample) that were retained on sampling devices used to collect conventional Pap smears (primary smears) in order to evaluate specimen adequacy and cytological diagnosis of scrapings that are routinely discarded. Study design: Cervical scrapings from women attending routine cervical cancer screening were obtained using a cervical brush. Following primary conventional smear preparation, the same sampling devices were rinsed in Preservcyt solution (Cytyc) for subsequent monolayered thin smear (split-sample/discarded sample). The smears (conventional and ThinPrep® monolayer) were examined independently by pathologists and classifi ed using the Bethesda System. The diagnoses from discarded samples (splitsample smears) were then compared with the diagnoses made on primary conventional Pap smears. Results: 702 samples were studied. Cell abnormalities was found in 14/702 conventional smear and 12/702 split-sample thin smear. The adequacy of sampling in primary smears was 94.7% compared to 88.9% in split-sample smears. Six cases of Human Papillomavirus infection was found in splitsample smear, whereas only 5 cases found in primary smear. Cohen’s Kappa was 0.61 showing substantial agreement between both sampling cytological results. Conclusion: The cervical brush discarded after conventional smear retain adequate number of cells for diagnostic purposes.

Sternocleidomastoid intramuscular lipoma

Lipoma is the most common benign soft tissue tumour with most located in the superficial subcutaneous plane. However, some are located in the deeper plane. Location in the head and neck regions are less common compared to the other part of the body. Deep seated lipomas are either inter-muscular or intramuscular. We present a case of a simple subcutaneous neck lipoma in a 60-year-old Malay man which turned out to be an intramuscular sternocleidomastoid lipoma.

Kimura’s Disease: A Rare Cause of Nephrotic Syndrome with Lymphadenopathy

Kimura’s disease is a rare condition and typically presents as non-tender subcutaneous swellings in the head and neck region, usually in the pre-auricular and submandibular areas. It is associated with lymphadenopathy (both local and distal), marked peripheral eosinophilia, and an elevated IgE level. It can easily be mistaken for a malignant disorder. Fine needle aspiration can be misleading, and a diagnosis is established only by histopathological examination. Renal involvement, which may affect up to 60% of patients, is the only systemic manifestation. We report a case of Kimura’s disease in a Malay patient who was associated with steroid-responsive nephrotic syndrome.

Correlation of Nuclear Morphometry and AgNOR Score with Radiation Response in Squamous Cell Cancers of the Head and Neck: A Preliminary Study

Background: Prediction of radiation response before the completion of the radiotherapy schedule is challenging. Information about radiation response could help oncologist to choose the appropriate combination and sequence of therapies in the multidisciplinary management of cancer. Methods: The study involved 26 patients with squamous cell cancers of the head and neck region who received radiotherapy to a dose of 30 Gy in 10 fractions over a 2-week period as part of a split-course technique. Fine-needle aspiration cytology was performed on day 1 and day 5 of the schedule. The silver staining of the nuclear organiser region (AgNOR) and nuclear morphometric study were done on both days. Results: The median age of the patients was 44 years old. The primary tumours were distributed in the nasopharynx (n = 11), larynx and hypopharynx (n = 5), metastatic node (n = 4), and miscellaneous tumours were found in the head and neck sub sites (n = 6). The mean initial AgNOR score was 3.0, range 1.2–7.0. The median of nuclear and nucleolar diameters were 11.07 μm, range 7.70–16.6 μm, and 2.92 μm, range 1.09–11.66 μm, respectively. Patients with a pre-radiotherapy AgNOR score of greater than 2.5 were associated with disease progression and metastasis. However, the increased of nuclear diameter on day 5 compared with baseline predicted a good radiation response in patients (P = 0.016). Conclusion: Intra-radiotherapy nuclear morphometry combined with baseline AgNOR score could be a simple and useful tool for the prediction of radiation response in head and neck cancers.

Comparison of DR. HPV Chip Kit with hybrid capture II assay for the detection of human papillomavirus in clinical samples: a preliminary study

Human papillomavirus (HPV) is well known as an etiological factor for the development of anogenital carcinomas. The aim of our study was to compare the performance of USFDA approved Hybrid II (HCII) Assay and recently introduced DR. HPV Chip Kit for the detection of HPV DNA in clinical cervical scrapings from 40 patients. HPV DNA testing was performed using the automated HCII Assay system and DR. HPV Chip Kit. Taking cytological results as gold standard, it was found that HCII was more sensitive (36.4%) than DR. HPV Chip Kit (18.2%) although specificity was 100% with the latter method. In addition, both these molecular methods had comparable negative and positive predictive values. It was concluded that both HCII and DR. HPV Chip Kit have comparable specificity. However, sensitivity for detection of HPV in clinical samples with HCII is almost double as compared to DR. HPV Chip Kit.

Prevalence of goblet cell metaplasia in endocervical and endometrial adenocarcinoma: A histochemical study

To determine the prevalence of goblet cell metaplasia in endocervical and endometrial adenocarcinomas by histochemial staining and to investigate the most sensitive histochemical staining method to detect this metaplasia, a total of 90 tissue blocks representing 30 non-neoplastic cervix, 30 non-neoplastic endometrium, 30 endocervical and endometrial adenocarcinoma cases were obtained for histochemical staining with Toluidine Blue (TB), Methylene Blue (MB), Mucicarmine (MUC), Periodic Acid Schiff before and after Diastase digestion (PAS, PAS-D), Alcian Blue pH 2.5 (AB), and Periodic Acid Schiff after Alcian Blue pH 2.5 (PAB). The cases were blinded and evaluated by a pathologist [NHO] for the presence of goblet cell metaplasia, the amount of goblet cells present and the histochemical differentiation of the goblet cells compared with its surrounding glandular epithelium. Goblet cell metaplasia was present in 2 out of 30 cases in non-neoplastic cervix, 0 out of 30 cases in non-neoplastic endometrium, 7 out of 15 cases in endocervical adenocarcinoma and in 2 out of 15 cases in endometrial adenocarcinoma. Relatively few goblet cells were seen in endometrial adenocarcinoma, few to moderate amounts were seen in endocervical adenocarcinoma and relatively more goblet cells were seen in non-neoplastic cervix. The differentiation of the goblet cells with its surrounding glandular epithelium was moderate to strong in non-neoplastic cervix and endocervical adenocarcinoma, while the differentiation in endometrial adenocarcinoma was weak to moderate. The various staining methods showed differences in presence, amount anddifferentiation of the goblet cells. Goblet cell metaplasia of the reproductive organs is not as rare as previously reported. There was no statistical difference in presence, amount and differentiation of goblet cells according to the various cases. The must optimum staining methods for staining goblet cells in non-neoplastic cervix, endocervical adenocarcinoma and endometrial adenocarcinoma were PAS, PASD and AB.

RET and p53 expression in thyroid follicular adenoma: a study of 52 cases with 14 years follow-up

Most previous studies on RET and p53 proteins have focused on thyroid papillary carcinoma. We investigated the role of RET and p53 protein expressions using immunohistochemistry on 52 cases of thyroid follicular adenomas and studied the follow-up records of these patients. The range of follow-up period was 3 to 14 years. The patients were between 15 and 71 years of age with a median age of 34.5 years. There were 46 females and 6 males. Except for 3 cases, all patients were Malays. The minimum volume of the tumour was 1000 mm3 and the maximum was 512,000 mm3 with a median of 270,000 mm3. Eleven (21.2%) cases showed RET expression. RET expression was not statistically significant when cross-tabulated against sex (p = 0.322), ethnicity (p = 0.518), age (p = 0.466) and symptom duration (p = 0.144). Six (11.5%) of 52 cases showed p53 immunopositivity. p53 expressions were also not significantly correlated to the clinical parameters above. There was no correlation between RET and p53 protein expressions. The only statistically significant finding was the association of tumour volume with duration of symptoms (p = 0.05). All patients are alive at the time of writing. 3 had recurrent goitre, 2 of these were diagnosed as colloid goitre while the third was a follicular lesion. One patient suffered from depression requiring anti-depressant treatment. In conclusion, unlike papillary carcinoma in which the roles of ret and p53 oncogenes are known, their roles in influencing the behaviour of follicular adenoma has not been ascertained.