Investigating vertical transmission and maternofoetal outcomes in pregnant women with COVID-19: a case-control study from Pakistan.

Objectives: To estimate the frequency of severe acute respiratory syndrome coronavirus-2 among pregnant women, the impact in terms of obstetrical and clinical outcomes and vertical transmission to the neonates. METHODS: The prospective, case-control study was conducted at Zainab Panjwani Memorial Hospital, Karachi, from March to December 2021, and comprised pregnant women regardless of gestational age who exhibited symptoms or had a suspicion of exposure to any confirmed coronavirus disease-2019 individual. They were screened for severe acute respiratory syndrome coronavirus-2 infection using polymerase chain reaction or serology. Those who tested negative were designated as control group A, while who had a positive serology result along with a negative polymerase chain reaction were taken as recovered case group B1, and those who tested positive for polymerase chain reaction were called the positive case group B2. Groups B1 and B2 were followed up till delivery. The clinical presentation of coronavirus disease-2019 infection in pregnancy and its obstetrical and neonatal outcomes was assessed. Products of conception were tested for the detection of the severe acute respiratory syndrome coronavirus-2 genome. The viral genome from group B2 cases was sequenced to confirm vertical transmission. Data was analysed using GraphPad Prism V8. RESULTS: Of the 139 pregnant women, 74(53.2%) were in group A with mean age 25.87±6.90 years, 49(35.3%) were in group B1 with mean age 25.53±7.02 years, and 16(11.5%) were in group B2 with mean age 27.12±5.03 years. The gestational age at which termination of pregnancy occurred was 38.3±1.26 weeks in group B1 and 38.3±1.85 weeks for group B2. There were 96 neonates across the 3 groups. Of the 11(11.45%) neonates in group B2, 1(9.09%) had postnatal transmission of severe acute respiratory syndrome coronavirus-2 and this mother-neonate case was taken as the Indexed case. The severe acute respiratory syndrome coronavirus-2 genome isolated from the neonate showed similar mutations as the viral strain infecting the mother. Conclusion: The risk of vertical transmission was found to be low. The severe acute respiratory syndrome coronavirus-2 genome was the same for both the mother and the neonate.

Mesenchymal Stem Cell-Derived Extracellular Vesicles Protect Rat Nucleus Pulposus Cells from Oxidative Stress.

BACKGROUND: Oxidative stress (OS) is mainly associated with the pathogenesis of intervertebral disc (IVD) degeneration; it causes nucleus pulposus cells (NPCs) to undergo senescence and triggers autophagy and apoptosis. This study aims to evaluate the regeneration potential of extracellular vesicles (EVs) derived from human umbilical cord-mesenchymal stem cells (hUC-MSCs) in an in vitro rat NPC-induced OS model. DESIGN: NPCs were isolated from rat coccygeal discs, propagated, and characterized. OS was induced by hydrogen peroxide (H2O2), which is confirmed by 2,7-dichlorofluorescein diacetate (H2DCFDA) assay. EVs were isolated from hUC-MSCs and characterized by analyzing the vesicles using fluorescence microscope, scanning electron microscope (SEM), atomic force microscope (AFM), dynamic light scattering (DLS), and Western blot (WB). The in vitro effects of EVs on migration, uptake, and survival of NPCs were determined. RESULTS: SEM and AFM topographic images revealed the size distribution of EVs. The phenotypes of isolated EVs showed that the size of EVs was 403.3 ± 85.94 nm, and the zeta potential was -0.270 ± 4.02 mV. Protein expression analysis showed that EVs were positive for CD81 and annexin V. Treatment of NPCs with EVs reduced H2O2-induced OS as evidenced by a decrease in reactive oxygen species (ROS) levels. Co-culture of NPCs with DiI-labeled EVs showed the cellular internalization of EVs. In the scratch assay, EVs significantly increased NPC proliferation and migration toward the scratched area. Quantitative polymerase chain reaction analysis showed that EVs significantly reduced the expression of OS genes. CONCLUSION: EVs protected NPCs from H2O2-induced OS by reducing intracellular ROS generation and improved NPC proliferation and migration.

Karachi Cancer Registry (KCR): Consolidated Data of 5-years 2017-2021.

OBJECTIVE:  To collect and analyse epidemiologic data of all malignancies by age group and gender for the Karachi population to estimate the cancer incidence of 5-years (2017-2021) and identify major risk factors for setting priorities towards cancer control programs. STUDY DESIGN: Observational study. Place and Duration of the Study: Karachi Cancer Registry (KCR) Secretariat, Pakistan Health Research Council (PHRC), JPMC, Karachi, from 2017-2021. METHODOLOGY: Cancer data of seven tertiary care hospitals of Karachi submitted to KCR during the study period were analysed including age, gender, date of first contact, primary site and ICD coding. All the data was cleaned, merged, and analysed. All patients 0-14 years were classified as 'children', all aged 15-19 years were classified as 'adolescents', and those age 20-years and above as 'adults'. Age standardised incidence rates (ASIR) were determined for both genders. RESULTS: During the last five years (2017-2021), a total of 65,886 malignant cases were received. The distributions seen amongst males and females were 33,510 (51%) and 32,376 (49%), respectively with 60,145 (91.3%) tumours found in adults (≥20 years), 4844 (7.3%) in children, and 897 (1.4%) in adolescents. The three most common tumour sites were oral, liver, and colorectal in males; breast, oral and ovary in females; bone, brain and connective tissue in adolescents; and leukaemia, brain and bone in children. The overall ASIR (%) in males was 89.20 for adults, 9.19 for children, and 1.61 for adolescents. The overall ASIR (%) in females was 93.44 for adults, 5.45 for children, and 1.11 for adolescents. CONCLUSION: Oral cancer, a largely preventable cancer is the leading cancer in males while breast cancer is the leading cancer in females followed by oral cancer. In adolescents and children, the incidence closely matches most of the world. KEY WORDS: Karachi, Cancer registry, Oral cancer, Breast cancer, Age-standerdised ratio.

Human umbilical cord-derived mesenchymal stem cells and their chondroprogenitor derivatives reduced pain and inflammation signaling and promote regeneration in a rat intervertebral disc degeneration model.

Intervertebral disc (IVD) degeneration is an asymptomatic pathophysiological condition and a strong causative factor of low back pain. There is no cure available except spinal fusion and pain management. Stem cell-based regenerative medicine is being considered as an alternative approach to treat disc diseases. The current study aimed to differentiate human umbilical cord-mesenchymal stem cells (hUC-MSCs) into chondrocyte-like cells and to elucidate their feasibility and efficacy in the degenerated IVD rat model. Chondrogenic induction medium was used to differentiate hUC-MSCs into chondroprogenitors. Rat tail IVD model was established with three consecutive coccygeal discs. qPCR was performed to quantify the molecular markers of pain and inflammation. Histological staining was performed to evaluate the degree of regeneration. Induced chondroprogenitors showed the expression of chondrogenic genes, SOX9, TGF-ß1, ACAN, BMP2, and GDF5. Immunocytochemical staining showed positive expression of chondrogenic proteins SOX9, TGF-ß1, TGF-ß2, and Collagen 2. In in vivo study, transplanted chondroprogenitors showed better survival, homing, and distribution in IVD as compared to normal MSCs. Expression of pain and inflammatory genes at day 5 of cell transplantation modulated immune response significantly. The transplanted labeled MSCs and induced chondroprogenitors differentiated into functional nucleus pulposus (NP) cells as evident from co-localization of red (DiI) and green fluorescence for SOX9, TGF-ß1, and TGF-ß2. Alcian blue and H & E staining showed standard histological features, indicating better preservation of the NP structure and cellularity than degenerated discs. hUC-MSCs-derived chondroprogenitors showed better regeneration potential as compared to normal MSCs. The pain and inflammation genes were downregulated in the treated group as compared to the degenerated IVD.

Is COVID-19 Fatality Rate Associated with Malaria Endemicity?

COVID-19 (coronavirus disease 2019) is a disease caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). COVID-19 has yielded many reported complications and unusual observations. In this article, we have reviewed one such observation: an association between malaria endemicity and reduced reported COVID-19 fatality. Malaria-endemic regions have a significantly lower reported COVID-19 fatality rate as compared to regions where malaria is non-endemic. Statistical analyses show that there is a strong negative correlation between the reported SARS-CoV-2 fatality and endemicity of malaria. In this review, we have discussed the potential role of CD-147, and potential malaria-induced immunity and polymorphisms in COVID-19 patients. Noteworthy, the results may also be due to underreported cases or due to the economic, political, and environmental differences between the malaria endemic and non-endemic countries. The study of this potential relationship might be of great help in COVID-19 therapy and prevention.

Karachi Cancer Registry (KCR): Age-Standardized Incidence Rate by Age-Group and Gender in a Mega City of Pakistan.

OBJECTIVES: To estimate the cancer incidence by age group and gender for the population of Karachi Division by analyzing the Karachi Cancer Registry data of 2017-19. SETTINGS: The population of Karachi division is 16.1 million according to national census 2017. 'Karachi Cancer Registry' which is a part of 'National Cancer Registry' is collecting data from eight major hospitals in Karachi since 2017. For outcome measures, cancer counts and the age standardized incidence rates (ASIR) per 100,000 population were computed for age groups (0-14, 15-19 and ≥20 years), in both genders and all cancer site/type. METHODS: The population denominators were based on the population of Karachi division estimated at 16.1 million in the population census, 2017. Counts and age-standardized incidence rates (ASIR) were calculated for each of the three age categories. RESULTS: From Jan 2017 till Dec 2019 a total of 33,309 malignant cases were recorded in KCR database comprising 17,490 (52.5%) females and 15,819 (47.5%) males. ASIRs in age groups 0-14, 15-19 and ≥ 20 years, among female were 11.5, 2.4 and 223.6 and in males were 17.6, 3.2 and 216.7 respectively. The commonest diagnosis in children, adolescent and adults were (1) among females: children; bone (3.12),  leukemia (2.09) brain/CNS (1.26); in adolescents: bone (0.78), brain/CNS (0.27), connective and soft tissue (0.11), in adults: breast cancer (76.07), oral cancer (16.68) and ovary (10.89) respectively, and (2) among males: children; bone (4.56),  leukemia (2.79) and brain/CNS (1.88); in adolescent; bone (1.19), brain/CNS (0.31) and leukemia (0.21) and in adults: oral cancer (42.83), liver (16.10) and bone (13.37) respectively. CONCLUSION: Oral Cancer, a largely preventable cancer is the leading cancer in Karachi adult males while in female adults Breast Cancer is the leading cancer followed by Oral Cancer. In children and adolescents Bone, Leukemia and Brain/CNS malignancies are most common.
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Awareness and Attitude of Undergraduate Medical Students towards 2019-novel Corona virus.

OBJECTIVE: To assess the knowledge, awareness and attitudes of medical students towards recently discovered coronavirus disease-19 (COVID-19). METHODS: This was a cross sectional study conducted on medical students in CMH Lahore Medical College,(LMC), Institute of Dentistry (IOD). A questionnaire containing demographic information, 14 knowledge and eight attitude items was completed by 384 participants. RESULTS: Overall, >90% people were aware about the etiology, mode of transmission and possible symptoms; however, very few of them knew about the in-depth details. Knowledge score revealed that 80% of participants had sufficient knowledge about coronavirus. MBBS students and nursing Students had significantly better knowledge in comparison with other students. In terms of attitude, >80% of students showed positive attitudes among which the nursing students were dominant. CONCLUSION: The medical students of CMH LMC showed a satisfactory level of awareness and attitudes towards COVID-19 with an obvious difference with regard to disciplines. More educational efforts with periodic educational interventions are still needed about the current pandemic.

Correlation Between Peak Expiratory Flow Rate, Markers of Adiposity, and Anthropometric Measures in Medical Students in Pakistan.

Obesity has been defined as the excessive deposition of fats on the body. It presents a very significant risk to humanity, with debilitating consequences for healthcare systems worldwide. It has multiple effects on the body, including grave consequences on the cardiovascular and respiratory systems. Our project explores the latter. There are multiple studies available in the scientific literature that attempt to explain this phenomenon, all with limited success and conflicting results. This cross-sectional exploration of the topic was done on medical undergraduates to pick up on any correlations between peak expiratory flow rate (PEFR) and the markers of obesity (body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist to hip ratio (WHR)). In general, we found that male participants had sizably higher PEFR values than females (r=0.540, p<0.01). Appropriate BMI is mandatory for the physiologic functioning of the human body. This work also statistically demonstrates a negative overall correlation between lung health and various parameters of obesity. Our work suggests a positive correlation between WHR and PEFR (r=0.325, p<0.01), BMI and PEFR (r=0.573, p=0.02), along with weight and PEFR (r=0.464, p<0.01). Maintaining a BMI and WHR in the normal range is essential for optimal physiological functioning and physical well-being.

Incidence, trends and morphology of ovarian cancer in Karachi (1995-2002).

INTRODUCTION: Cancer ovary is the third most common malignancy diagnosed in women in Karachi, a moderate to high risk region for the disease. MATERIALS AND METHODS: Three hundred and thirty seven cases of ovarian cancer registered at the Karachi Cancer Registry for the years 1995-2002 were reviewed. RESULTS: The age- standardized incidence rate (ASR) world per 100,000, crude incidence rate per 100,000 (CIR) and frequency of ovarian malignancies in 1995-1997 were 10.9, 5.9 and 6.2% respectively. Corresponding figures for 1998-2002 were 8.1, 5.1 and 4.8%. The mean age at presentation in 1995-1997 was 45.7 years (95%CI 42.9, 48.4; SD∓15.9), range 95 (3 to 98) years and in 1998-2002 it was 45.0 years (95%CI 42.8, 47.3; SD±16.1), range 79 (3 to 82) years. Eleven (3.3%) cases of childhood cancers, 13 (3.9%) adolescent cases, 126 (37.4%) reproductive age (20-44 years) and 187 (55.5%) cases in the 45+ age group were registered. Epithelial malignancies were the most common cancers above the age of 20 years (78.4%), the commonest amongst these was serous adenocarcinoma (33.3%). Germ cell tumors were more common (5.6%) in children and adolescents. Microscopic confirmation was 99.0%. Presentation was of a moderately differentiated (grade 2) malignancy with a regional or distant spread of disease in three fourths of the cases. CONCLUSIONS: The incidence of cancer ovary, though stable in Karachi, involves a relatively younger age group with a strong family history in a fourth of the cases. The disease presents at an advanced stage. An ageing population over time may translate into a higher incidence of ovarian cancer. The current incidence of cancer ovary in Karachi is an enigma and belies reproductive protective factors. Studies focused on the genetic risk factors in this population are recommended.

Incidence and current trends of colorectal malignancies in an unscreened, low risk Pakistan population.

INTRODUCTION: Karachi falls into a low risk region for colorectal cancer (CRC). The incidence rate is known but detailed epidemiology and pathology data regarding the disease are not available. The aim of this study was to describe CRC with reference to incidence, gender, topographic sub-site, tumor morphology, grade and stage at diagnosis and to determine the trends of incidence. MATERIALS AND METHODS: Four hundred and seventy three cases of colorectal cancer submitted to the Karachi Cancer Registry for Karachi South, years 1995-2002 were reviewed. Cases were analyzed in two time periods (1995-7 and 1998-2002) to facilitate the study of time trends. RESULTS: A total of 151 CRC cases were registered during period one [86 (57%) males; 65 (43%) females] and 322 cases [210 (65%) males; 112 (35%) females] in period two. Age standardized rate (ASR) world per 100,000, crude incidence rate (CIR) and relative frequency in period one were 5.3, 3.2 and 4.1% in males and 5.5, 3.2 and 3.2% in females respectively. Corresponding figures for period two were 7.1, 4.5 and 4.7% for males and 5.2, 2.8 and 2.7% in females. The male, female ratio was equal for colon (1:1). Men had more rectal cancers (2:1) and overall CRC (1.7:1). The mean age of the patients varied with sub-site and gender from 43.7 years to 51.2 years. Cancers of the rectum presented at a relatively earlier age. Less then 5% of the cases were diagnosed in adolescents, 50% above 50 years of age and only 30% above 60 years. The ratio under-40 to above-40 for CRC patients was 0.3, which is much higher than the international average, indicating a younger age group at risk. The first cases were observed in adolescents (15-19 years) and a peak was observed in the seventh decade. Colon to rectum ratio was 1:1 in males and 2:1 in females. Most cases presented with advanced disease, though some down staging was observed in period 2 (1998-2002). CONCLUSION: The current low but increasing incidence (especially in men), the younger age and advanced stage of CRC at diagnosis reflects a low risk, unscreened population. With existing prevalence of high risk factors in Pakistan, the low CRC incidence may be an artifact. There are concerns that an aging population over the next decade and changing lifestyle patterns may translate into a higher CRC incidence. Screening must be considered as part of the health sector planning for the future and include the high risk younger age groups.

Trends and morphology of central nervous system malignancies in Karachi.

INTRODUCTION: This study was conducted to assess the patterns of primary central nervous system (CNS) malignancies in Karachi South (KS), a moderate risk population in Asia. MATERIALS AND METHODS: Data for 321 registered cases were reviewed and analyzed in two periods 1995-1997 (111 cases, 75 (67.6%) male (M); 36 (32.4%) female (F)) and 1998-2002 (210 cases, 124 (59.1%) M; 86 (40.9%) F). RESULTS: Age standardized incidence rate per 100,000, crude incidence rate and relative frequency in 1995-1997 were 3.5, 2.8 and 3.5% (M) and 1.8, 1.6 and 1.7% (F). Corresponding figures for 1998-2002 were 3.3, 2.7 and 2.7% (M) and 3.3, 2.7 and 2.1% (F). Mean age of male and female patients during 1995-1997 was 33.3 years (SD± 20.4) and 30.7 years (SD±19.6). Mean ages for 1998-2002 were 33.2 years (SD±19.5) and 28.7 years (SD±18.5) for males and females respectively. In males, 199 malignancies were reported, 106 (86.9%) cases in the brain, 10 (5.5%) in meninges and 12 (6.0%) in the spinal cord; 122 cases were observed in females, 177 (89%) cases in the brain, 8 (6.6%) each in the meninges and spinal cord. The most common morphology was astrocytoma (72 (36.2%) (M); 40 (32.7%) (F)). Mean age of low grade astrocytoma was 27.8 years (M) and 27.0 years (F); anaplastic astrocytomas, 40.5 years (M), 34.1 years (F) and glioblastoma, 45.7 years (M) and 38.3 years (F). Youngest cases were registered for cerebellum and brain stem. CONCLUSION: The incidence of CNS malignancies is stable in males and gradually increasing in females. Astrocytoma is the commonest morphology; they affect a younger age group and show an age gradient in proportion to tumor grade. The mean age varied by sub-site and histology. Focus should be directed towards the understanding the biological nature and risk factors prevalent in this population.

Incidence and trends of prostate cancer in Karachi South, 1995-2002.

INTRODUCTION: Cancer prostate (CaP) is a commonly diagnosed cancer in western men, but there is sparse information about the demographics of this malignancy in Pakistan. The study objective was to provide an overview of CaP in Karachi, Pakistan. METHODOLOGY: Epidemiological data of 282 incident CaP cases registered at Karachi Cancer Registry (KCR) during 1st January 1995 to 31st December 2002 were reviewed. Incidence and trends were studied in 2 time periods, 1995-7 and 1998-2002. RESULTS: In 1995-7, CaP accounted for approximately 3.4% of the cancers in males and ranked 8th in hierarchy with an age standardized incidence rate (ASR) world and crude incidence rate (CIR) per 100,000 of 6.0 and 2.8 respectively. During 1998-2002, CaP accounted 4.6% of the cancers, ranked 4th with an ASR world and CIR per 100,000 of 10.1 and 4.4. Thus an approximate 60% increase was observed between 1995 and 2002. Mean ages of the patients were 67.0 and 67.4 years. Age-specific curves showed a gradual increase in risk from the fifth decade onwards. A marginal down staging was also observed in period 2, more apparent in the more educated Mohajir and Punjabi ethnicities. CONCLUSION: Karachi falls into a low risk region for CaP, with a rapidly increasing incidence and a marginal down staging. The probable reasons for the lower incidence are a low life expectancy, lack of availability or accessibility to health care and lack of public awareness. Implementation of CaP screening and public health education is a necessity today. The low incidence of CaP in Pakistan may be an artefact!

Rising incidence of gastric malignancies in Karachi, 1995- 2002.

INTRODUCTION: South Asia is an enigma for gastric cancer, a low risk region with a contradictory high prevalence for Helicobacter pylori. PATIENTS AND METHODS: To examine the demographics, pathology and trends of gastric cancer in Pakistan, epidemiological data of 335 gastric malignancies, registered at Karachi Cancer Registry (KCR) for Karachi South (KS), during 1st January 1995 to 31st December 2002 were reviewed. Trends were studied by categorizing the cases into two time periods '1995-7' and '1998-2002'. RESULTS: Ninety six cases of gastric cancers were registered in the 1995-7 period, 61 in males and 35 in females. In males, the ASR (world), and crude incidence rate (CIR) per 100,000 were 3.9 and 2.3 respectively. In females, the values were 3.0 and 1.5. In the 1998-02 period 239 cases of gastric cancer were registered, 156 cases in males and 83 in females. The ASR and CIR per 100,000 were 6.0 and 3.4 in males and 3.6 and 2.1 in females. An 18% increase was observed in males and 14% in females during the seven year study period. The male to female ratio was 2:1.The mean age of male patients was 51.9 years (95% CI 45.8; 58.1; SD -/+17.9) in 1995-7 and 53.7 years (95% CI 51.6; 55.9; SD -/+14.0) in 1998-02. In females the mean age for the two periods was 48.8 years (95% CI 42.5; 55.0; SD -/+ 18.2) and 48.4 years (95% CI 45.4; 51.5; SD -/+13.9) respectively. Age-specific curves showed a gradual increase in risk from the second until the seventh decade. The majority of the cases presented as poorly or moderately differentiated distal (non-cardia) cancers with a regional spread. CONCLUSION: Gastric cancers in Karachi fall into the prototype of a low risk developing country pattern. The incidence is increasing, most marked in males above 40 years of age. Larger pathology-based studies are required to comment on the precise morphological sub-types of gastric adenocarcinoma. Etiological studies focused on different strains of H. pylori are required to address the gastric cancer enigma, whilst examining possible protective environmental or genetic factors.

Primary malignancies of bone and cartilage in Karachi.

INTRODUCTION: Primary sarcomas of bone and cartilage (BS) are a group of rare neoplasms, with limited information from Pakistan. The present population-based study was conducted with the objective of examining descriptive epidemiological characteristics of BS in Karachi. MATERIALS AND METHODS: Epidemiological data of 68 BS registered at Karachi Cancer Registry for Karachi South during 1st January 1995 to 31st December 1997 were reviewed. RESULTS: Forty-six (66.7%) cases were diagnosed in males and 23 (33.3%) in females. BS accounted for 2.2% and 1.1% of all cancers in males and females, respectively. The age standardized rate (ASR) world per 100,000 was 1.75 in males and 1.00 in females. Microscopic confirmation was 99.0%. The mean age of male and female patients were 26.7 years (SD-/+17.4) and 24.3 years (SD-/+16.0) respectively. In males 14 (30.4%) BS were diagnosed in the 0-14 year age group and 23 (50.0%) cases in the below 20 years age group. The distribution in females was 31 (67.4%) and 8 (34.8%) cases, respectively. Approximately half the cases (34.8% males; 47.8% females) were observed in the lower limbs. The most common morphology was osteosarcoma (30.5% males; 43.4% females), followed by Ewing's sarcoma (23.9%) in males and giant cell tumor (13.0%) in females. Age-specific curves showed a gradual increase in risk from the first until the fifth decade in males, and second to fourth decade in females. The age-specific curves were bimodal. In both genders the first peak was observed at 10-14 years but a second peak was observed at 70-74 years in males and 65-69 years in females. The cardinal symptoms that led to the diagnosis of bone tumors were pain (22 cases; 32.4%) and spontaneous fractures (45 cases; 66.2%). CONCLUSION: Karachi falls into a high risk region for BS, which were observed in a relatively younger population, with a male predominance and a high frequency of osteosarcoma. The underlying factors for BS in Karachi need to be addressed considering the overwhelming proportion of youngsters at risk and the late presentation.

Time trends in the incidence of cancer cervix in Karachi South, 1995-2002.

INTRODUCTION: The objective of the study was to determine the trends of cancer cervix in Karachi South during an eight (1995-2002) year period. METHODOLOGY: Cancer cervix cases recorded at Karachi Cancer Registry during 1st January 1995 to 31st December 2002 were analyzed. Trends were studied by analyzing the age standardized incidence rates (ASR)s in 2 time periods, 1995-97 and 1998-2002. RESULTS: Cancer cervix ranked sixth in the 1995-97 period the age standardized incidence rate (ASR) world and crude incidence rate (CIR) per 100,000 were 6.81 and 3.22. It reached the fifth ranking in the 1998-2002 period with an ASR and CIR of 7.5 and 4.0 per 100,000. Thus between 1995 and 2002, the incidence of cervical cancer registered an approximate 10% increase. The mean age of the cancer cases was 53.3 years (SD 11.6; 95% CI 50.58, 55.96; range 32-85 years) and 50.7 years (SD 11.7; 95% CI 48.8, 52.5; range 51 years) in period 1 and 2 respectively. The morphological components of squamous cell carcinoma and adenocarcinoma remained stable during this period, though a marginally higher component and increasing incidence of adenocarcinoma was observed throughout. A negligible down staging was observed in the 1998-2002 period. Localized malignancy was observed in 30.8% in period 2 as compared to 25.7% in period 1 and the component of carcinoma in situ increased from 0% percent in period 1 to 1.3% in the second period. Despite this two thirds of the cases still presented with a regional or distant spread of disease. CONCLUSION: Pakistan at present falls into a low risk cancer cervix region. The cause of concern is the steadily increasing incidence especially in the younger birth cohorts, the advanced disease at presentation; insignificant in-situ cancers and no preventive intervention or awareness practices in place.

Epidemiology of soft tissue sarcomas in Karachi South, Pakistan (1995-7).

INTRODUCTION: The present study was conducted with the objective of examining epidemiological characteristics of soft tissue sarcomas (STSs) in Karachi. PATIENTS AND METHODS: Epidemiological data of 96 (63 male and 33 female) incident STS cases registered at Karachi Cancer Registry (KCR) for Karachi South (KS), from 1st January 1995 to 31st December 1997, were reviewed. RESULTS: The age standardized rate (ASR) world per 100,000 were 3.3 (2.9%) and 2.1 (1.6%) in males and females, respectively, with mean ages of of 41.4 years (95% CI 35.77-46.97) and 40.2 years (95% CI 31.27-49.03). The age-specific curves showed a gradual increase in risk from the first until the eighth decade in both genders, with the highest peak at 75+ in females and 70-74 years in males. In males, 8 (12.7%) STS cases were diagnosed in the pediatric age group (0-14), 12 (19.1%) in adolescents and young adults (15-24 years), 19 (30.1%) in adults 25-49 years of age and 24 (38.1%) in the 50 years+ age group. In females the respective frequencies were 11%, 26%, 30% and 33%. The most common histological tumor was rhabdomyosarcoma, though the occurrence of the histological subtypes was age-dependent. Rhabdomyosarcomas and Ewing's sarcomas were more frequent in children and adolescents whereas fibrosarcomas, leiomyosarcomas, liposarcomas, malignant fibrous histiocytomas (MFHs) and schwannomas were encountered in the elderly. CONCLUSION: Karachi falls into a high risk region for STS, observed in a relatively younger population, with a male predominance, high frequency of rhabdomyosarcoma and advanced stage at diagnosis. Information on grading and staging remain incomplete for most cases, which negatively affect disease management and survival.

Patho-epidemiology of Cancer Cervix in Karachi South.

INTRODUCTION: The present study was conducted with the objective of examining descriptive epidemiological and pathological characteristics of cancer cervix in Karachi South, an all urban district population of Karachi, Pakistan. METHODOLOGY: A total of 74 cases of cancer cervix, ICD-10 (International Classification of Diseases 10th Revision) category C53 were registered at the Karachi Cancer Registry, for Karachi South, during a 3 year period, 1st January, 1995 to 31st December 1997. RESULTS: The age standardized incidence rate (ASR) world and crude incidence rate (CIR) per 100,000 were 6.81 (5.2, 8.43) and 3.22 (2.49 to 3.96). Cancer cervix accounted for approximately 3.6% of all cancers in females and was the sixth malignancy in hierarchy. The mean age of the cancer cases was 53.27 years [standard deviation (SD) 11.6; 95% confidence interval (CI) 50.58, 55.96; range (R) 32-85 years)]. The distribution by religion was Muslims (90.5%), Christians (8.1%) and Hindus (1.4%). There were no cases reported in Parsees. The frequency distribution by ethnicity was Urdu speaking Mohajirs (20.3%), Punjabis (17.6%), Gujrati speaking Mohajirs (4.1%), memon Mohajirs (8.1%), Sindhis (10.8%), Baluchs (8.1%), Pathans (5.4%) and Afghan migrants (2.7%). The ethnicity was not known in approximately a fourth (23.0%) of the cases. The socio-economic distribution was 27.0% financially deprived class, 24.4% lower middle class and 48.7% upper middle and affluent classes. The majority of the women were married (86.5%); a smaller number were unmarried (2.7%) or widows (10.8%). The age-specific curves showed a gradual increase in risk from the fourth up till the seventh decade, followed by an actual apparent decrease in risk after 64 years of age. The peak incidence was observed in the 60-64 year age group. The morphological categorization was squamous cell carcinoma (86.5%), adenocarcinoma (10.9%) and adenosquamous carcinoma (2.6%). The majority of cases presented with moderately differentiated or grade 2 lesions (45.9%). There were no in-situ cases. Approximately half the cancers (58.1%) had spread regionally and 8.1% to a distant site at the time of diagnosis. Odds ratios (OR) were calculated for socioeconomic residential categories, religion, ethnicity, age groups and education. The OR for socioeconomic residential categories ranged between 0.69 and 2.9 with a marginally higher risk in the lower [OR 2.09 (95% CI .97; 4.49)] and lower middle class [OR 2.08 (95%CI 0.95; 4.58)]. Hindus [OR 1.2 (95% CI 0.18; 2.2)] had a slightly higher risk then the Muslims [OR 0.14 (95% CI 0.17; 1.2)]. A higher risk was also observed for Christians [OR 7.76 (95% CI 1.74; 34.5)]. CONCLUSION: The incidence of cervical cancer in Karachi South (1995-97) reflects a low risk population with a late presentation and a high stage disease at presentation. It is suggested that cervical screening if implemented should focus on once a life time methodology involving 36-45 year old women. This should be combined with HPV vaccination for the young and public health education for all. A regular cervical screening program would require mobilization of considerable financial, structural and human resources along with training for personnel. This may burden the already stretched health resources of a developing country.

Patho-epidemiology of breast cancer in Karachi '1995-1997'.

OBJECTIVE: Provide an overview of the demographics and pathology of breast cancer in the female population of Karachi South during a 3 year period, 1995-1997. METHODS: Epidemiological data for 709 incident breast cancer cases, ICD-10 category C50 registered at Karachi Cancer Registry during 1st January 1995 to 31st December 1997 were reviewed. RESULTS: Breast cancer accounted for approximately one-third of the cancers in females. The age standardized incidence rate (ASR) world per 100,000 was 53.8, the crude incidence rate was 30.9. In KS 60% of the newly diagnosed breast cancers were observed in women below 50 years. The age-specific curves showed a gradual increase in risk from the third up till the seventh decade, followed by an actual/apparent decrease in risk. The socio-economic distribution was 24.9% in category I the financially deprived class, 38.9% in category II the middle class and 35.9% in category III, the affluent class. Microscopic confirmation of malignancies was 99%. Invasive breast cancers predominated with 99.4%, with in-situ cancers contributing to 0.6% of the malignancies. The morphology of cancers was tilted towards duct cell carcinoma (DCC), pure DCC (92%), combinations of DCC /Paget's disease (0.6%) and lobular carcinoma (0.4%). Approximately 45% of duct cell carcinoma were seen in the premenopausal age group (<45 years). All bilateral breast cancers were duct cell carcinoma with a family history of first degree relative with breast cancer. The majority of the cases presented as moderately differentiated or grade 2 lesions (59.0%). Approximately 56% cancers had spread to the regional lymph nodes and 8.3% to a distant site at the time of diagnosis. A family history of first degree relative with breast cancer was present in 3% and second degree relatives in 7% of the cases. Odds ratio (OR) for 680 breast cancer cases with complete demographic information was calculated with 675 gender matched controls. A slightly higher risk was observed in non-Muslims and migrant ethnicities: two to three fold elevation in the Indian migrants (Gujrati speaking Mohajirs OR 3.86 (95% CI 2.51; 5.92) Urdu speaking Mohajirs OR 2.85 (95% CI 2.05; 3.96), Memon Mohajirs OR 2.21 (95% CI 1.48; 3.29) and Afghan migrants [OR 2.99 (95% CI 11.20; 7.44)]. The risk was also high in the females of Punjabi ethnicity settled in KS [OR 2.73 (95% CI 1.87; 3.99)]. The risk seems much less for the ethnicities belonging to North Western Pakistan i.e. Pathans [OR 1.684 (95% CI 0.89; 3.17)] and Baluchs [OR 0.90 (95% CI 0.58; 1.39)]. A marginally higher risk was observed in the higher socio-economic categories. The risk of developing breast cancer increased gradually for each age category from illiterate [OR 1.2 (95% CI 0.94; 1.55)] to college graduates [OR 13.12 (95% CI 7.31; 23.73)]. CONCLUSIONS: The incidence of breast cancer in Karachi South (KS) for the period 1995-1997 was the third highest in Asia. The hallmarks were a high reproductive age malignancy involving a higher socio-economic class, an invasive duct cell carcinoma diagnosed at an advanced stage, in younger more educated females and a low in-situ malignancy. More studies are required to obtain a deeper insight into this breast cancer epidemic in Karachi. Implementation of breast cancer screening with stress on public health education is today a major responsibility of the government.

Patho-epidemiology of cancer corpus uteri in Karachi South '1995-1997'.

AIM: To provide demographics and pathology of cancer of the uterine corpus in Karachi. METHODOLOGY: Data for 66 incident cases of cancer corpus uteri, ICD-10 category C54-5 registered at the Karachi Cancer Registry, for Karachi South, during a 3 year period, 1st January, 1995 to 31st December 1997 were reviewed. RESULTS: Cancer uterine corpus (1995-97) was the sixth most common malignancy, following breast, oral cavity, ovary, esophagus and cervix. The age standardized incidence rate (ASR) world and crude incidence rate (CIR) per 100,000 were 6.4 (4.73 to 8.01) and 2.9 (2.18 to 3.57). The mean age was 53.7 years (SD 15.6; range 6-90 years). Fifty eight cases were endometrial carcinoma with ASR world and CIR per 100,000 of 5.77 (4.20 to 7.33) and 2.53 (1.88 to 3.18) respectively. Sarcomas comprised 6% of the cases. Approximately a third of the females (28.8%) were below 50 years of age. The age-specific curves showed a gradual increase from the fourth till the seventh decade, followed by an actual apparent decrease in risk after 70 years. Peak incidence was observed in the 65-69 year age group. Presenting symptoms were post-menopausal bleeding (86.4%) and purulent discharge (4%). Associated pathologies included adenomyosis, adenomatous hyperplasia (12% each) or leiomyoma (8%). Associated clinical conditions were diabetes mellitus and hypertension (4% each). The majority of the cases presented as well differentiated (39.4%), localized (59.1%) lesions. CONCLUSION: The incidence of cancer corpus uteri in Karachi South reflects a moderate risk population, predominantly middle aged with a higher socio-economic status. On the average the malignancy is observed a decade earlier then reported elsewhere. This calls for in-depth investigation of risk factors and identification of underlying etiology.

Epidemiological review of head and neck cancers in Karachi.

Head and neck cancers, categories lip, oral cavity, pharynx and larynx are placed amongst the top ten malignancies globally. The cancers have a similar epidemiology, risk factors, morphology, and control measures. The geographical variations in incidence are indicative of the global differences in the prevalence of risk factors. The present study was conducted with the objective of reviewing descriptive epidemiological characteristics, incidence and time trends of head and neck cancers in Karachi (1995-2002). Head and neck cancers accounted for approximately one-fifth (21%) of the cancers in males and about one-tenth (11%) in females in the study period. The age standardized incidence rate (ASR) was 37.1/100,000 in males and 21.7/100,000 in females. In males, oral cavity and larynx were the commonly affected sites, followed by pharynx. In females, oral cavity was the preponderant site. The mean age of the patients was 53.0 years (95% CI 48.0; 58.0). A rising incidence was observed in both genders, more apparent in males. About 30% of oral cancer cases, 28.6% of the nasopharyngeal, 6.3% of the oropharyngeal, and 2.6% of laryngeal cancers occurred in patients 40 years and younger. The age specific incidence rates (ASIR) for oral cancer in males showed a gradual rise from 10 to 64+ years of age, for pharynx from 20 to 64+ and for larynx at 25+. The ASIR for oral cancer in females showed a gradual rise from 14 to 64+ years of age, for pharynx from 20 to 64+, a decade after the oral cancer rise and cancer larynx showed a rise at 25+, a decade and a half after the oral cancer rise. The peak incidence was at 64-69 years for all three cancer sites, in both genders. Pakistan falls into a high risk head and neck cancer geographical zone Presentation is late and treatment is not optimum. Recommendations, therefore for NCCP Pakistan, for short term benefits are selected community-based screening for the high risk population, early diagnosis, better treatment, rehabilitation and palliative care. These measures will improve survival and also contribute to a better quality of life. Primary prevention remains the only strategy for absolute cancer control.