Concomitant-chemoradiotherapy-associated oral lesions in patients with oral squamous-cell carcinoma.

OBJECTIVE: : Oral squamous-cell carcinoma (OSCC) accounts for >90% of oral cancers affecting adults mostly between the fourth to seventh decades of life. The most common OSCC treatment is concomitant chemoradiotherapy (CCRT) having both loco-regional and distant control, but CCRT has acute and chronic toxic effects on adjacent normal tissue. This study aimed to determine the side effects of CCRT on the oral mucosa and to characterize the clinicopathology of oral lesions in patients with OSCC. METHODS: This descriptive, cross-sectional study was certified by the Ethical Review Committee (UHS/Education/126-12/2728) of the University of Health Sciences, Lahore, Pakistan. OSSC patients (n=81) with various histological subtypes, grades, and stages were recruited, and findings on their oral examination were recorded. These patients received 70, 90, and 119 Gy of radiotherapy dosages in combination with the chemotherapy drugs cisplatin and 5-fluorouracil. Data were analyzed using SPSS 20.0. RESULTS: : The most common presentation of OSCC was a nonhealing ulcer (63%) involving tongue (55.6%). Clinical findings included mucositis (92.6%) and xerostomia of mild, moderate, and severe degrees in 11.1%, 46.9%, and 35.8% cases, respectively. Ulcers (87.7%), palpable lymph nodes (64.2%), limited mouth opening (64.2%) and fistula (40.7%) were also observed. In females, the association of radiotherapy dosage with limited mouth opening, xerostomia, and histological grading was statistically significant (P<0.05). The association of chemotherapy drugs with xerostomia (P=0.003) was also statistically significant. CONCLUSIONS: : CCRT induced mucositis, xerostomia, and trismus in patients with OSCC.

MCM - 2 and Ki - 67 as proliferation markers in renal cell carcinoma: A quantitative and semi - quantitative analysis

ABSTRACT Introduction/Background: Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers from inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferation faction. This study was designed to assess the prognostic significance of MCM-2 by comparing it with Fuhrman nuclear grade and Ki-67. Material and Methods: n=50 cases of various ages, stages, histological subtypes and grades of RCC were selected for this study. Immunohistochemical staining using Ki-67(MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal antibody, Thermo) was performed on the paraffin embedded blocks in the department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore. Labeling indices (LI) were determined by two pathologists independently using quantitative and semi-quantitative analysis. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade, and Pearson's correlate was used to determine correlation between the two proliferation markers. Results: Labeling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67(median=13.05%). Both markers were significantly related with grade (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67(r=0.0934;p=0.01 with Pearson's correlate). Results of semi-quantitative analysis correlated well with quantitative analysis. Conclusion: Both Ki-67 and MCM-2 are markers of proliferation which are closely linked to grade. Therefore, they can act as surrogate markers for grade in a manner that is more objective and reproducible.

MCM - 2 and Ki - 67 as proliferation markers in renal cell carcinoma: A quantitative and semi - quantitative analysis.

INTRODUCTION/BACKGROUND: Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers from inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferation faction. This study was designed to assess the prognostic significance of MCM-2 by comparing it with Fuhrman nuclear grade and Ki-67. MATERIAL AND METHODS: n=50 cases of various ages, stages, histological subtypes and grades of RCC were selected for this study. Immunohistochemical staining using Ki-67(MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal antibody, Thermo) was performed on the paraffin embedded blocks in the department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore. Labeling indices (LI) were determined by two pathologists independently using quantitative and semi-quantitative analysis. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade, and Pearson's correlate was used to determine correlation between the two proliferation markers. RESULTS: Labeling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67(median=13.05%). Both markers were significantly related with grade (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67(r=0.0934;p=0.01 with Pearson's correlate). Results of semi-quantitative analysis correlated well with quantitative analysis. CONCLUSION: Both Ki-67 and MCM-2 are markers of proliferation which are closely linked to grade. Therefore, they can act as surrogate markers for grade in a manner that is more objective and reproducible.

CLINICO-PATHOLOGICAL PATTERN, CLASSIFICATION AND STAGING OF URINARY BLADDER CARCINOMAS--A FIVE YEARS EXPERIENCE AT A TERTIARY CARE HOSPITAL IN CENTRAL PUNJAB. .

BACKGROUND: In Pakistan, urinary bladder carcinoma is the 8th commonest malignancy while being the fourth commonest cancer in men. The relative occurrence of a particular histological type of bladder carcinoma depends on the clinical setting. Both grade and stage of these cancers are highly correlated with recurrence, progression and patient survival rates. METHODS: This cross- sectional study comprised of 122 patients with newly diagnosed operable primary bladder carcinomas who underwent cystoscopy associated transurethral resection of bladder tumour at the Urology Department of Punjab Employees Social Security Hospital, Lahore. All participants completed a detailed questionnaire and underwent an in-depth interview to obtain data. The surgical specimens were referred to the Pathology department. Gross observations of the tumour recorded. RESULT: A total of 114 cases, classified according to WHO/ISUP criteria, low-grade papillary lesions, comprising Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP) and Papillary Low Grade carcinomas, accounted for 43% of tumours. Male to female ratio being 5.3:1 (74%). Lateral walls were involved in 44%, posterior wall in 25.3%, trigone in 10.7%, bladder neck in 7.2%, dome in 5.8%, ureteric orifice in 4.13%, anterior wall in 2% and left ureter in 0.87% cases. Tumour staging revealed an overall 11.5% of tumours with stage Ta and 31.5% with stage T3-4. About 29% tumours were non invasive. About n=13 of low-grade carcinomas and n=68 of high-grade carcinomas were invasive. For tumours classified by WHO/ISUP criteria, the percentage of women was larger for PUNLMP than for the other categories of urothelial tumours (p-value 0.006); no statistically significant difference was found by age or gender with respect to tumour stage (p-value 0.138 and 0.452). CONCLUSION: Transitional Cell Carcinoma (TCC) is the commonest among middle aged men.

Immune mechanisms in type-2 diabetic retinopathy.

OBJECTIVE: To enumerate CDR+CD25+ Treg cells and determine serum IL-6 and IL-17 in type 2 diabetes mellitus patients with retinopathy. METHODS: The case-control study was conducted at the Department of Immunology, University of Health Sciences, Lahore, from November 2009 to January 2012 and comprised diabetic patients and healthy controls who were divided into three groups. Group 1 had controls, while Group 2 had diabetic patients without retinopathy and Group 3 had diabetic patients with retinopathy. Flowcytometre and enzyme-linked immunosorbent assay were used for CD4+CD25+ Tregs and serum IL-6 and IL-17 respectively. SPSS 20 was used for statistical analysis. RESULTS: Of the 212 subjects in the study, 30(14%) were Group 1, 30(14%) in Group 2 and 152(72%) in Group 3.There were 25 (83%) women in Group 2 and 101 (66%) in Group 3 compared to 9 (30%) in Group 1. Higher mean age was in Group 3 (50.88 ± 8.9 years) and Group 2 (49.46 ± 9.94 years) compared to Group 1 (34.66 ± 8.78 years) while longer mean disease duration was in Group 3 (10.51 ± 5.24 years) than Group 2 (7.76 ± 4.14 years). Highest median ratio of IL- 6 was in Group 1 (1468.62) (Q1-Q3: 1229.9-1543.35), followed by Group 2 (1455.32) (Q1-Q3:1214.22-158.9) and Group 3 (469.84) (Q1-Q3: 206.53-1231.33) whereas IL-17 was the highest in Group 1 (339.38) (QT-Q3: 159.89- 1174.93), followed by Group 3 (216.60) (Q1-Q3:141.87-410.25) and Group 2 (174.17) (Q1-Q3: 138.77-458.17). Higher percentage of Tregs was in Group 2 (3.07 ± 0.43) followed by Group 1 (2.91 ± 0.04) and Group 3 (2.88 ± 0.38). Significant difference was observed in gender, age, disease duration, level of IL-6 and IL-17 (p < 0.05 each), while no difference was found in glycated haemoglobin, CD4+CD25+ and Tregs (p > 0.05 each). CONCLUSION: Age, gender and duration of diabetes contributed to diabetic retinopathy, while CD4+CD25+ T cells and Treg cells did not. Serum IL-6 and IL-17 were inversely associated with diabetic retinopathy.