Colorectal cancer among young native Indonesians: A clinicopathological and molecular assessment on microsatellite instability.

Aim: To obtain clinicopathological characteristics of colorectal cancer among young native Indonesians and to assess MLH1, MSH2, and SMAD4 protein expressions, comparing them with a matched population of colorectal cancer patients aged 60 years old and older. Methods: Medical records of colorectal cancer patients aged 40 years or younger and 60 years or older from several hospitals in three Indonesian cities – Jakarta, Makassar, and Bandung - were reviewed. The “native” ethnic groups were selected from those originating from Java, Makassar (South Celebes), Miinangkabau (West Sumatra). Ethnicity of 121 colorectal carcinoma patients was confirmed by fulfilling requirements in a questionnaire. Tumor specimens of those patients underwent evaluation for histopathology, tumor grading as well as immunohistochemical analysis to assess MLH1, MSH2 protein expressions to detect microsatellite instability mutation pathway and SMAD4 protein expression to reconfirm that the specimens were not microsatellite instability origin. Results: There were 121 colorectal carcinoma cases of Sundanese, Javanese, Macassarese and Minangkabau ethnic group. This study indicated that colorectal cancer has statistically different grade (p = 0.001) between the young and the older patients. Immunohistochemical staining for MSH2 protein and MLH1 were done for 92 and 97 specimens respectively. There was no significant difference between the expressions of MLH1 and MSH2 on tumor grading, indicated there was no correlation between microsatellite instability and tumor grading in this study. Conclusion: Colorectal cancer in young native Indonesian patients (40 years old or less) was not different in clinicopathological characteristics compared to older patients (60 years old or more) in similar ethnic groups. There was also no difference in MSH2 and MLH1 protein expressions, important indicators of microsatellite instability and.

Expression of NF-kB and COX-2 in Young Versus Older Patients with Sporadic Colorectal Cancer.

Aim: to distinguish the expression of NF-kB and COX-2 between young and older group of sporadic colorectal cancer patients. Methods: this was a comparative study between sporadic CRC patients aged 40 years or younger and patients aged 60 years or more. Expression of NF-kB and COX-2 were assessed by immunohistochemical method using rabbit polyclonal antibodies against human p65 NF-kB and COX-2 proteins. Results: there were 98 cases of sporadic colorectal cancers between 1999 and 2007 obtained from the Department of Anatomical Pathology, Faculty of Medicine University of Indonesia, Jakarta and Department of Anatomical Pathology, Faculty of Medicine Padjajaran University, Bandung. There were 60 patients aged 60 years or more and 38 patients aged 40 years or less. Most tumors were located in the distal colon. Positive expression of NF-kB was found in 72 (73.5%) cases, whereas COX-2 expression was found in 48 (49.0%) cases. No significant difference of NF-kB and COX-2 expression between young and older patients. Conclusion: the expression of nuclear factor kB (NF-kB) in Indonesian patients with sporadic colorectal cancer was high. However, cyclooxygenase-2 (COX-2) was only expressed in half of patients. There was no significant difference of NF-kB and COX-2 expressions between patients aged 40 years or less and patients aged 60 years or more. Further studies are needed to elaborate the role of inflammation in sporadic colorectal carcinogenesis.

Cytogenetics in oncology: From hematologic malignancies to solid tumors.

Although presently known as an environmentally-related disease and appears mostly sporadic, cancer is regarded as a genetic disease based on the presence of genetic mutation as a consistent factor. The “Philadelphia Chromosome” found consistently among chronic myeloid leukemia (CML) patients was the first significant finding of a chromosomal abnormality specifically related to a particular disease. Starting from this point, cytogenetics as the study of chromosomes has become a valuable tool in the assessment of cancer – as an aid in diagnosis, thus guiding therapy, and as a prognostic marker. Chromosomal abnormalities are found mostly in hematological malignancies and the findings are more pathognomonic. The situation is different in solid tumors, which when visible to the naked eye already have complex chromosomal changes and thus pose technical difficulties to the cytogeneticist. However, the scientists believe that the shift in chromosomal studies from conventional cytogenetics to molecular cytogenetics will provide further information regarding solid tumors.

The influence of calorie restriction during the Ramadan fast on serum fructosamine and the formation of beta hydroxybutirate in type 2 diabetes mellitus patients.

AIM: To determine whether the Ramadan fasting can improve metabolic control evaluated from serum fructosamine and beta hydroxybutirate in patients with Type 2 diabetes mellitus. METHODS: This was a prospective one group before and after study (self-controlled study). Twenty four patients from the outpatient clinic of the Metabolic Endocrinology Division of the Department of Internal Medicine, Faculty of Medicine, University of Indonesia/ Cipto Mangunkusumo General Hospital who were well under control underwent assessment for serum fructosamine at weeks -1, 4, and 6 (2 weeks after the Ramadan fast) and beta hydroxybutirate formation at week 4. RESULTS: The mean serum fructosamine on weeks -1, 4, and 6 were 334.2 +/-45.7; 303.9 +/-34.5 dan 313.6 +/-45.9 umol/L. The beta hydroxybutirate level was 0.3 mmol/L. CONCLUSION: The Ramadan fasting in patients with well-controlled and medium-controlled type 2 diabetes mellitus could cause a reduction in serum fructosamine and does not cause formation of beta hyroxybutirate.

Beta-hydroxybutirate levels as a determinant for the success of diabetic ketoacidosis management.

AIM: To obtain a greater understanding of the diagnosis and evaluation of success in diabetic ketoacidosis management. METHODS: A prospective observational study was performed on patients with diabetic ketoacidosis at the Emergency Unit of Cipto Mangunkusumo General Hospital. All patients that were admitted were had their blood glucose, beta-hydroxybutirate, acetoacetate, pH, pCO2, HCO3, anion gap and consciousness levels serially monitored on upon admittance (0 hour) and the 2nd, 6th, 12th, 18th and 24(th) hours. The correlation coefficient of each examination was also calculated. The benefit of serial examination of each variable was also determined for each ketoacidosis undergoing the study. RESULTS: Out of the 19 available samples, a strong negative correlation was found between beta-hydroxybutirate and pH with a value of r>0.5 (from -0.524 to -0.833 with p<0.05) for 24 hours, compared to acetoacetate with the lowest r of -0.515 to -0.731 lasting up to 12 hours. Blood glucose and pH is correlated only at 0 hour, the same with the correlation between beta-hydroxybutirate and HCO(3). pCO2 and anion gap is better compared to that of blood glucose and acetoacetate. There is no correlation between the three and the level of consciousness. Significant serial examinations to perform are blood glucose, beta-hydroxybutirate, and HCO(3). CONCLUSION: beta-Hydroxybutirate has a stronger correlation compared to blood glucose and or acetoacetate towards pH, pCO2, HCO(3), and anion gap. Patients with ketoacidosis are recommended to undergo blood beta-hydroxybutirate examination. Serial examination should be performed for blood glucose, beta-hydroxybutirate, and bicarbonate.