• Asian-Australasian Journal of Animal Sciences
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• v.20 no.9
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• pp.1361-1366
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• 2007

In this project, ovarian size and activity during the peak (November-April) and the low (May-October) breeding seasons in young and adult camels were studied. Ovaries of 92 camels (Camelus dromedarius), with clinically normal reproductive tracts, aged 3-15 years and slaughtered at Faisalabad or Lahore abattoirs over a period of 24 months, were collected. Jugular blood was collected from each animal before slaughter; the serum was separated and analyzed for oestradiol concentration. The size (length, width and thickness) and weight of each ovary were measured. Grossly observable Graafian follicles were counted and their diameter was measured using Vernier Calipers. The camels having ovaries presenting follicles more than 5 mm in diameter were taken as having active ovaries. The results showed that ovarian length, width and weight were significantly higher (p<0.05) during the peak than the low breeding season. The percentage of active ovaries was also significantly higher (p<0.01) during the peak than the low breeding season. However, the effect of season on ovarian thickness was non-significant. Similarly, the ovarian length, width, thickness, weight and activity did not vary significantly between young (3-7 years old) and adult (8-15 years old) animals. Serum oestradiol concentrations were significantly higher (p<0.05) during the peak ($67.70{\pm}1.36$ pg/ml) than the low breeding season ($15.25{\pm}1.54$ pg/ml). It was concluded that in Pakistani camels ovarian size and activity were higher during the peak than the low breeding season. However, age of the camel (from 3 to 15 years) had no effect on these parameters.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1049-1052
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• 2016

Background: Myelodysplastic syndrome (MDS) is a clonal disorder of hemopoeitic stem cells, characterized by infective hematopoiesis, peripheral cytopenias along with hypercellularity of marrow and marked dysplastic features. Our aim was to study the spectrum of the WHO classification in adult Pakistani patients with MDS at disease presentation. Materials and Methods: This retrospective descriptive study was conducted at Liaquat National Hospital and Medical College, extending from January 2010 to December 2014. Patient data were retrieved from the maintained archives. Results: Overall, 45 patients were diagnosed at our institution with de novo MDS during the study period. There were 28 males and 17 females. Age ranged between 18 and 95 years with a mean of $57.6{\pm}17.4years$. The male to female ratio was 1.7:1. According to the WHO classification, 53.3% had refractory cytopenia with multilineage dysplasia, 22.2% had refractory cytopenia with unilineage dysplasia, 4.4% each had refractory anemia with excess of blasts-1 and II and 15.5% had MDS unclassified. The main presenting complaints were generalized fatigue (60%), fever (33.3%), dyspnea (15.5%), bleeding (13.3%) and weight loss (11.1%). Physical examination revealed pallor in 37.7%, followed by petechial and purpuric rashes in 20% of patients. Hemoglobin was <10 g/dl in 41 (91.1%). Pancytopenia and bicytopenia were noted in 18 (40%) and 14 (31.1%) respectively. Conclusions: MDS in our patients presents at a relatively young age. Refractory c ytopenia with multilineage dysplasia was the dominant disease variant in our setting.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1053-1055
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• 2016

Background: Polycythemia rubra vera (PV), being a primary polycythemia, is caused by neoplastic proliferation of erythroid, megakaryocytic and granulocytic lineages which result in panmyelosis. PV patients have a somatic acquired mutation in the Janus kinase (JAK2) pathway, rendering cell proliferation independent of the normal regulatory mechanisms that regulate erythropoiesis. The rational of this study was to determine the prevalence of the JAK-2 V617F mutation in Pakistani patients with PV. Materials and Methods: In this cross sectional study, 26 patients with PV were enrolled from January 2010 to December 2014. Patients were diagnosed based on WHO criteria for PV. All were screened for G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by an allele specific PCR. Results: The mean age was $53.4{\pm}9.31years$ (range 36-72) and the male to female ratio was 2:1. The frequency of JAK2 V617F positivity in our PV patients was found to be 92.3%. Overall 30.7% of patients were asymptomatic and remaining 69.3% presented with symptomatic disease. The mean hemoglobin was $18.1{\pm}1.9g/dl$ with the mean hematocrit of $55.6{\pm}8.3%$. The mean total leukocyte count was $12.8{\pm}7.1{\times}10^9/l$ and the platelet count was $511{\pm}341.9{\times}10^9/l$. A positive correlation of JAK2 V617F mutation was established with high TLC count (P=0.01). No correlation of JAK2 V617F could be established with age or gender (P>0.05). Conclusions: The JAK2 V617F mutation frequency in our PV patients was similar to those reported internationally. Screening for the mutation in all suspected PV cases could be beneficial in differentiating patients with reactive and clonal erythrocytosis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7893-7895
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• 2015

Background: Acute promyelocytic leukemia (APL) is a distinctive clinical, biological and molecular subtype of acute myeloid leukemia. However, data from Pakistan are scarce. Therefore we reviewed the demographic and clinical profile along with risk stratification of APL patients at our center. Materials and Methods: In this descriptive cross sectional study, 26 patients with acute promyelocytic leukemia were enrolled from January 2011 to June 2015. Data were analyzed with SPSS version 22. Results: The mean age was $31.8{\pm}1.68years$ with a median of 32 years. The female to male ratio was 2:1.2. The majority of our patients had hypergranular variant (65.4%) rather than the microgranular type. The major complaints were bleeding (80.7%), fever (76.9%), generalized weakness (30.7%) and dyspnea (15.38%). Physical examination revealed petechial rashes as a predominant finding detected in 61.5% followed by pallor in 30.8%. The mean hemoglobin was $8.04{\pm}2.29g/dl$ with the mean MCV of $84.7{\pm}7.72fl$. The mean total leukocyte count of $5.44{\pm}7.62{\times}10^9/l$; ANC of $1.08{\pm}2.98{\times}10^9/l$ and mean platelets count were $38.84{\pm}5.38{\times}10^9/l$. According to risk stratification, 15.3% were in high, 65.4% in intermediate and 19.2% in low risk groups. Conclusions: Clinico-epidemiological features of APL in Pakistani patients appear comparable to published data. Haemorrhagic diathesis is the commonest presentation. Risk stratification revealed predominance of intermediate risk disease.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7125-7128
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• 2014

Background: Acquired genetic alterations and presence of sensitizing mutations in the tyrosine kinase domain of EGFR and other signaling molecules have been found in different subsets of primary lung adenocarcinoma. The commonest EGFR mutations are small in frame deletions of exon 19 and a point mutation (L858R) in exon 21, having a combined occurrence of around 90%. The objective of this study was to determine the frequency and types of EGFR mutations in primary lung adenocarcinomas in Pakistan. Materials and Methods: EGFR mutations in tumor samples were screened by multiplex real time PCR. Briefly, DNA from formalin fixed paraffin-embedded tissue was amplified with primers and probes specific to 43 different EGFR mutations in a Cobas z 480 instrument. The assay detects mutations in four exons (18-21) of the EGFR gene. Results: Out of 94 patients, 65 were males and 29 females with a M:F ratio of 2.2: 1. The median age was 62 years (range, 28 - 85 years). In our biopsy samples 70 (74%) cases were of primary lung adenocarcinoma, whereas 24 (26%) were confirmed metastatic adenocarcinoma of primary lung origin. EGFR mutation was positive in 29% of the patients. The highest frequency of L858R was observed in 48% of these, followed by deletion in exon 19 (44%). In addition, other rare mutations such as compound G718X:S768I and insertions in exon 20 insertion were detected in approximately 4% of the patients. Conclusions: This study showed that Del 19 and L858R are the most frequent mutations in Pakistani lung adenocarcinoma patients and around 29% of the patients were found eligible for erlotinib therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2195-2199
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• 2014

Background: Despite being rare in incidence, malignant tumors of major salivary glands show diverse histological variation. There are limited data on major salivary gland tumor management and outcome from Pakistan. The objective of this study was to share our experience with management of malignant tumors of major salivary glands. Materials and Methods: Patients who received treatment at Shaukat Khanum Cancer Hospital and Research Center from July 2002 to June 2011 with an underlying diagnosis of a major salivary gland malignancy were included. Patient characteristics and treatment modalities were assessed. Local, regional and distant failures were determined. Disease free survival (DFS) and overall survival (OS) were calculated using Kaplan Meier curves and the Log rank test was used to determine statistical significance. Univariate and multivariate analyses were performed using Cox proportional hazard regression. Results: The parotid gland was the primary site of origin in 104 (80%) patients. Mucoepidermoid carcinoma (43%) and adenoid cystic carcinoma (24%) were the most common histological types. Surgery followed by adjuvant radiation remained the mainstay treatment modality with 81 (62%) patients. Nineteen (15%) patients were treated with surgery alone and 30 (23%) patients with locally advanced surgically inoperable tumors received radiation only. Forty one (32%) patients failed the treatment (local 12, regional 11, locoregional 5, distant 13). The expected 5 year DFS and OS were 65% and 74% respectively. On multivariate analysis, grade was the only independent predictor of DFS and nodal involvement was the only independent predictor of overall survival. Conclusions: Employing existing standards of treatment, comparable survival can be achieved in Pakistani population with major salivary gland malignancies as elsehwere in the world.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2307-2309
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• 2016

Background: Acute lymphoblastic leukemia (ALL) is a malignant disease in which early lymphoid precursors proliferate and replace the normal hematopoiesis. It has distinctive clinical and biological features. In respect to adult ALL, available data from Pakistan are limited. Therefore we reviewed the demographical and clinicohematological profiles along with FAB stratification of adult patients with ALL presented at our hospital. Materials and Methods: In this cross sectional study, 51 adults (${\geq}15years$) patients with ALL were enrolled from January 2010 to December 2014. Results: The mean age was $23.8{\pm}12.9years$ with the median age of 18.0 years. The male to female ratio was 2:1. The major complaints were fever (60.7%), generalized weakness (47.0%), overt bleeding (19.6%) and weight loss (13.7%). Physical examination revealed lymphodenopathy as a predominant finding detected in 43.1% followed by splenomegaly and hepatomegaly in 23.5% and 21.5%, respectively. The mean hemoglobin level was $9.0{\pm}2.75g/dl$ with a mean MCV of $82.2{\pm}15.4fl$, a mean total leukocyte count of $31.1{\pm}64.0{\times}10^9/l$, a mean ANC of $2.1{\pm}3.0{\times}10^9/l$ and a mean platelet count of $71.7{\pm}85.7{\times}10^9/l$. According to FAB classification, 47.1% were L1 type, 45.1% L2 and 7.8% L3 variant. Conclusions: Clinico-pathological features appeared comparable to published data. Febrile illness associated with lymphodenopathy was the commonest presentation. FAB classification revealed a predominance of ALL-L1 variant in Pakistani adult patients with ALL.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3005-3010
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• 2013

Background: To present the overall clinical and histological perspective of benign and malignant prostatic disease as seen in our practice in the Section of Histopathology, Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, Pakistan. Materials and Methods: All consecutive prostate specimens (transurethral resection or TUR, enucleation, needle biopsies) received between July 1, 2012 and December 31, 2012 were included in the study. Results: Of the total of 785 cases, 621 (79.1%) were TUR specimens, 80 (10.2%) enucleation specimens, and 84 (10.7%) needle biopsies. Some 595 (75.8%) were benign, while 190 (24.2%) were malignant. Mean weight of BPH specimens was 19 grams and 43 grams for TUR and enucleation specimens respectively. Almost 67% of adenocarcinomas were detected on TUR or enucleation specimens. Of the above cases, 41.7% were clinically benign while 58.3% were clinically malignant. The average volume of carcinoma in all cases ranged between 60 to 65%. The average number of cores involved in needle biopsies was 5. In general, higher Gleason scores were seen in TUR/enucleation specimens than in needle biopsies. Overall, in all types of specimens, commonest Gleason score was 7, seen in 74 (38.9%) cases, followed by Gleason score 9 seen in 47 (24.7%) cases. Out of the 63 needle biopsies with carcinoma, radical prostatectomy was performed in 16 cases (25.4%). Conclusions: Benign prostatic hyperplasia (BPH) is extremely common and constitutes the bulk of prostate specimens. TMajority of prostatic carcinomas are still diagnosed on TUR or enucleation specimens. These included both clinically benign and clinically malignant cases. The volume of carcinoma in these specimens was quite high indicating extensive disease. Gleason scores were also generally high compared with scores from needle biopsies. Commonest Gleason score in all type of specimens was 7. Pathologic staging was possible in very few cases since radical prostatectomies are rarely performed.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3309-3314
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• 2013

Spleen tyrosine kinase (SYK) is a non-receptor type cytoplasmic protein and a known tumor suppressor gene in breast cancer. Polymorphisms in SYK have been reported to be associated with cell invasion/cell morality and an increased risk of cancer development. In this case control study, all exons of the SYK gene and its exon/ intron boundaries were amplified in 200 breast cancer cases and 100 matched controls and then analyzed by single stranded conformational polymorphism. Amplified products showing altered mobility patterns were sequenced and analyzed. Twelve variations were identified in exonic and intronic regions of DNA encoding SH2 domain and kinase domain of the SYK gene. All of these mutations are novel. Among them, 5 missense mutations were observed in exon 15 while one missense mutation was found in exon 8. In addition to these mutations, six mutations were also identified in intronic regions. We found a significant association between SYK mutations and breast cancer and observed that Glu241Arg, a missense mutation is associated with an increase risk of ~7 fold (OR=6.7, 95% CI=1.54-28.8), Thr581Pro (missense mutation) is associated with increased risk of ~16 fold (OR=15.5, 95%CI=2.07-115.45) and 63367 T>G (missense mutation) is associated with increased risk of ~13 fold (OR=12.8, 95%CI=1.71-96.71) for breast cancer. Significant associations were observed for each of these variations with both late menopause (p<0.01) and early menarche (p<0.005) cases when compared to controls. Our findings suggest that the polymorphic gene SYK may contribute to the development of breast cancer in at least the Pakistani population. This study provides an insight view of SYK which may provide a significant finding for the pharmaceutical and biotechnology industry.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3631-3635
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• 2016

Background: Breast lymphomas constitute a rare disease entity. To date, limited relevant data have been reported. We therefore here present a review of breast lymphoma patients treated at a single center over a 20 year period, focusing on histological types, treatment modalities and outcomes. Materials and Methods: We identified patients who were diagnosed and treated for breast lymphoma at a single center from January 1995 to January 2014 and extracted data regarding patients' demographics and clinical data. Results: Twenty-seven patients with breast lymphoma were identified, of which 3 were males. The median age at diagnosis was 37 years (range: 22-76 years). Chemotherapy was the main stay of treatment and 55.6% patients also received radiation to the affected breast. At our institute, only 3 patients, all with progressive disease, had surgery performed to achieve local palliation. Complete response after chemotherapy was seen in 63% patients and partial response in 7.4%, while 26% patients demonstrated disease progression. The mean follow up was 46.8 months. Seven patients (33.3%) who were alive at last follow up, as well as 1 patient who died, survived more than 5 years after diagnosis. Conclusions: Patients with breast lymphoma should receive aggressive treatment, with combination of chemotherapy and radiation therapy. Surgery should be limited for diagnosis and palliation of local symptoms in cases of progressive disease.