Clinical pattern and spectrum of endometrial pathologies in patients with abnormal uterine bleeding in Pakistan: need to adopt a more conservative approach to treatment.

BACKGROUND: Abnormal uterine bleeding (AUB) is one of the most common debilitating menstrual problems and has remained one of the most frequent indications for hysterectomy in developing countries. Approximately in 40% of hysterectomy specimens, no definite organic pathology could be established. The problem is common worldwide but causes may vary from one region to another. This study may help gynecologists in our population to improve their therapeutic strategies by promoting minimally invasive uterus sparing modalities such as endometrial ablation and hysteroscopic resection of early proliferative lesions. METHODS: It was a prospective, cross-sectional study conducted at Liaquat National Hospital from 15(th) January 2010 till 14(th) July 2011 over a period of 18 months. Women who underwent dilatation and curettage for endometrial sampling with complaints of AUB were included in the study and histopathologic spectrum was determined. RESULTS: Polymenorrhea was the most common presenting pattern (30%, 72/241) with reproductive age women being the most susceptible (49.3%,119/241). The commonest histopathological spectrum was normal menstrual pattern (34%, 82/241) and the commonest pathology was hormonal imbalance (27%, 65/241), followed by endometrial polyp (14%, 34/241), chronic endometritis (12%, 28/241), atrophic endometrium (6%, 15/241), endometrial hyperplasia (5%, 12/241), and endometrial carcinoma (2%, 5/241). Chronic endometritis was commonly seen in reproductive age (18%, 21/119); hormonal imbalance (45%, 35/77) and endometrial hyperplasia (6.5%, 5/77) in perimenopausal age; endometrial polyp (35.5%, 16/45) and endometrial carcinoma (9%, 4/45) in postmenopausal age. CONCLUSION: Frequency of benign endometrial pathology is quite high in AUB, 236 participants (98%, 236/241). Histopathological spectrum in patients with AUB is quite variable with respect to age. The most common pattern of AUB was polymenorrhea. The most common pathology was hormonal imbalance. It is suggested that age was associated with more progressive lesions found in peri and postmenopausal age group such as endometrial hyperplasia and endometrial carcinoma. Yet endometrial polyp was the most common pathology found in postmenopausal women. Therefore, the management strategy should be individualized, as in most cases a restrictive approach is appropriate in order to avoid unnecessary hysterectomies.

Extensively drug-resistant tuberculosis, Pakistan.

Frequency of extensively drug-resistant tuberculosis in Pakistan increased from 1.5% in 2006 to 4.5% in 2009 (p<0.01). To understand the epidemiology, we genotyped selected strains by using spoligotyping, mycobacterial interspersed repetitive units-variable number of tandem repeats, and IS6110 restriction fragment length polymorphism analysis.

Frequency of intestinal parasitic infestation in children of 5-12 years of age in Abbottabad.

BACKGROUND: Worm infestation is a major problem in children from developing countries due to bad hygienic conditions. It produces nutritional deficiencies and anaemia in children, especially when hookworm infestation is present. METHODS: This cross-sectional study deals with investigation of the frequency of intestinal parasitic infestation in children between the ages 5-12 years. A total of 283 subjects were tested and screened for different intestinal parasites at of Department of Physiology, Ayub Medical College, Abbottabad. Negative cases were re-examined and if found free of intestinal pathogenic parasites were labelled as negative. RESULTS: Of the 283 children examined, 230 tested positive for various intestinal parasites. The frequency of helminthic infestation was found to be above 81%. There were 8 different species of helminths and protozoa found in the specimens. By far the highest frequency of 48% was noted for Ascaris lumbricoides while 6.9% (16 cases) of the specimens examined had mixed infestation. The mean Haemoglobin (Hb) level was found to be 9.82 g/dl in males and 9.0 g/dl in females. Virtually no Hookworm infestation was found which may be the reason of not so low Hb level of the subjects. CONCLUSIONS: A very high percentage (81%) of children from suburbs of Abbottabad have intestinal worm infestation and majority of them (48% of positive cases) have Ascaris lumbricoides. Children were not very severely anaemic because of virtually no hook worm cases.

A large parosteal ossifying lipoma of lower limb encircling the femur.

INTRODUCTION: Lipoma is a benign soft tissue neoplasm that may contain mesenchymal elements, as a result of metaplastic process. Ossification in benign and malignant soft tissue tumors can also manifest due to metaplastic process. CASE PRESENTATION: A 45 year old woman presented with a large thigh mass. The mass was developed one and a half year ago which insidiously increased in size and was associated with movement restriction. Radiological findings revealed soft tissue neoplasm on antero-medial aspect of thigh encircling the femur and displacing adjacent muscles. Fine trabeculations were seen in neoplasm suggestive of ossification. Excision of the mass was performed and histopathology revealed adipocytes with mature bony trabeculae possessing prominent osteoblastic rimming suggestive of ossifying lipoma. CONCLUSION: It is important to recognize this variant of lipoma as it is associated with a better clinical outcome in contrast to most of the deep seated soft tissue neoplasms. Secondly it should also be differentiated from myositis ossificans and heterologous differentiation in other soft tissue neoplasms. We suggest an algorithmic approach to the diagnosis of ossifying soft tissue neoplasms histopathologically. Mature bony trabeculae with prominent osteoblastic rimming in a soft tissue lesion are due to a metaplastic process and should not be confused with osteosarcoma.

Morphologic spectrum of glial tumors: an increased trend towards oligodendroglial tumors in Pakistan.

BACKGROUND: Glial tumors are most common brain tumors in our population. While the exact etiology and pathogenesis is unknown, the evaluation of current trends in the frequency and morphology of glial tumors is imperative to constitute better diagnostic and treatment protocols. Data pertaining to frequency and spectrum of glial tumors is scarcely available in our population. The aim of this study was to determine the morphologic spectrum of glial tumors prevalent in our population. METHOD: 126 cases of glial tumors were retrospectively analyzed over a period of 5 years. Patients from all age groups and both genders were included in this study. Glial tumors were classified and graded according to WHO classification. RESULTS: Glial tumors were more common in males with a sex ratio of 2:1 and mean age of 38.26 years. Astrocytomas were most common glial tumors (51.6%) followed by oligodendrogliomas (23%). Glioblastoma was the most frequent astrocytic tumor and was incomparably frequent in older age group. CONCLUSION: In our study, Oligodendrogliomas and mixed oligoastrocytomas represent major pattern of disease in comparison with available regional data. Knowledge of these changing trends and patterns of glial tumor morphology and frequency can help in improvements and applications of newly emerging diagnostic and treatment modalities.

Ki67 index in breast cancer: correlation with other prognostic markers and potential in pakistani patients.

INTRODUCTION: Breast cancer aggressiveness can be correlated with proliferation status of tumor cells, which can be ascertained with tumor grade and Ki67 indexing. However due to lack of reproducibility, the ASCO do not recommend routine use of Ki67 in determining prognosis in newly diagnosed breast cancers. We therefore aimed to determine associations of the Ki67 index with other prognostic markers like tumor size, grade, lymph node metastasis, ER, PR and HER2neu status. METHODS: A total of 194 cases of newly diagnosed breast cancer were included in the study. Immunohistochemical staining for ER, PR, HER2neu and Ki67 was performed by the DAKO envision method. Associations of the Ki67 index with other prognostic factors were evaluated both as continuous and categorical variables. RESULTS: Mean age of the patients was 51.7 years (24-90). Mean Ki67 index was 26.9% (1-90). ER, PR, HER2neu positivity was noted in 90/194 cases (46.4%), 74/194 cases (38.1%) and 110/194 cases (56.70%) respectively. Significant association was found between Ki67 and tumor grade, PR, HER2neu positivity and lymph node status, but no link was apparent with ER positivity and tumor size. There wasan inverse relation between Ki67 index and PR positivity, whereas a direct correlation was seen with HER2neu positivity. However, high Ki67 (>30%) was associated with decreased HER2neu positivity as compared to intermediate Ki67 (16-30%). The same trend was established with lymph node metastasis. CONCLUSION: Our study indicates that with high grade tumors, clinical utility of ki67 is greater in combination with other prognostic markers because we found that tumors with Ki67 higher than 30% have better prognostic profile compared to tumors with intermediate Ki67 level, as reflected by slightly lower frequency of lymph node metastasis and HER2neu expression. Therefore we suggest that Ki67 index should be categorized into high, intermediate and low groups when considering adjuvant chemotherapy and prognostic stratification.

Accuracy of frozen section analysis of sentinel lymph nodes for the detection of Asian breast cancer micrometastasis - experience from Pakistan.

BACKGROUND: Intraoperative sentinel lymph node biopsy has now become the standard of care for patients with clinically node negative breast cancer for diagnosis and also in order to determine the need for immediate axillary clearance. Several large scale studies confirmed the diagnostic reliability of this method. However, micrometastases are frequently missed on frozen sections. Recent studies showed that both disease free interval and overall survival are significantly affected by the presence of micrometastatic disease. The aim of this study was to determine the sensitivity and specificity of intraoperative frozen section analysis of sentinel lymph nodes (SLNs) for the detection of breast cancer micrometastasis and to evaluate the status of non-sentinel lymph nodes (non-SLNs) in those patients subjected to further axillary sampling. MATERIALS AND METHODS: We performed a retrospective study on 154 patients who underwent SLN biopsy from January 2008 till October 2011. The SLNs were sectioned at 2 mm intervals and submitted entirely for frozen sections. Three levels of each section submitted are examined and the results were compared with further levels on paraffin sections. RESULTS: Overall 40% of patients (62/154) were found to be SLN positive on final (paraffin section) histology, out of which 44 demonstrated macrometastases (>2mm) and 18 micrometastases (<2mm). The overall sensitivity and specificity of frozen section analysis of SLN for the detection of macrometastasis was found to be 100% while those for micrometastasis were 33.3% and 100%, respectively. Moreover 20% of patients who had micrometastases in SLN had positive non-SLNs on final histology. CONCLUSIONS: Frozen section analysis of SLNs lacks sufficient accuracy to rule out micrometastasis by current protocols. Therefore these need to be revised in order to pick up micrometastasis which appears to have clinical significance. We suggest that this can be achieved by examining more step sections of blocks.

Cancer stem cells and resistance to chemo and radio therapy.

Cancer stem cells (CSCs, or tumor initiating cells) are responsible for tumor initiation. If cancer treatment kills most of cancer cells in the stage of transit amplifying and differentiation without killing the stem cells, the surviving CSCs will eventually lead to recurrence of tumors. Studies have suggested that CSCs may be the primary mediators of resistance to chemo- and radio-therapy, leading to failure in cancer therapy. Numerous targets are being investigated for their potential involvement in the self-renewal and chemo- and radio-resistance of cancer cells. However, despite the intensive efforts invested into characterizing the role of cancer stem cells, there is a sense of uncertainty regarding the identity and number of these cells as well as the implications in cancer treatment. In this review, we will discuss the identification of CSCs by cell surface markers, the biology of CSCs, and the role of CSCs in resistance to radio- and chemo-therapy. This review will discuss the advances in targeting CSCs to improve the efficacy of chemo- and radio-therapy.