Correlation of intra-operative frozen section consultation with the final diagnosis at a referral center in Karachi, Pakistan.

BACKGROUND: The correlation of intra-operative frozen section diagnosis with final diagnosis on permanent sections is an integral part of quality assurance in surgical pathology laboratories. However, there is scant data on this topic from Pakistan. Similarly, no local study has looked at frozen section turnaround times. AIMS AND OBJECTIVES: To analyze indications, discrepancies and deferrals for all frozen sections performed or received at our institution over a 1-year period and to determine the turnaround time for frozen section diagnoses in our cases. DESIGN: A retrospective study, was undertaken, of all frozen sections reported at our institution between 1 st January 2006 and 31 st December 2006. The records of these cases were reviewed. The number and types of discrepancies, including sampling and interpretation errors were determined. The deferred cases and causes for deferral were also determined. The turnaround times of all cases were recorded. Agreement rates were calculated as percent agreement, sensitivity/specificity and positive and negative predictive values. RESULTS: A total of 356 specimens were received. Out of these, 14 cases (3.93%) were deferred to permanent sections. Of the remaining 342 cases, the discordant diagnostic frequency was 2.92% while the concordant diagnostic frequency was 97.08%. The most common pathological processes encountered were presence/typing of neoplasm (51.12%) and assessment of surgical margins (27.53%). The average turn-around time for frozen section diagnosis was 23 minutes; 60% of the cases were reported in 20 minutes or less. CONCLUSIONS: The accuracy of frozen section diagnosis at AKUH pathology department can be interpreted as comparable with most international quality control statistics for frozen sections. The overall error and deferral rates are within the range of previously published errors in pathology. Deferrals and errors in some sub-specialties were higher than in others. The results suggest specific measures should be taken to reduce the number of discrepancies. The overall goal is to reduce errors, reduce the number of deferrals and improve frozen section diagnosis turnaround times.

Comparison of ER, PR and HER-2/neu (C-erb B 2) reactivity pattern with histologic grade, tumor size and lymph node status in breast cancer.

INTRODUCTION: Carcinoma of the breast is the most common malignancy of women in Karachi. The current study was conducted with the objective of assessing estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu reactivity patterns of mammary cancers for correlation with histologic grade, tumor size and lymph node metastasis. MATERIALS AND METHODS: One hundred and fifty modified mastectomy specimens received at the section of histopathology, Aga Khan University Hospital, were selected using a non-probability sampling method. RESULTS: Mean age of the patients was 48.3 years (95%CI 46.5, 50.2). The left breast was more commonly involved (57%). Tumor size ranged from 0.3 to 15.0 cm; 12% were >2.0 and 35.3% were >5.0 cm in diameter. The predominant morphology was infiltrating ductal carcinoma (85.3%). The majority of the cases presented as grade II (55.3%) lesions with tumor necrosis (70%) and lymph node involvement (71.3%). ER and PR were positive in 32.7% and 25.3% cases respectively. HER-2/neu was positive (3+) in 24.7%. ER positivity increased and HER-2/neu positivity decreased with rising age. ER and PR expression was significantly lower in HER-2/neu positive as compared with HER-2/neu negative tumors (ER 83.8% vs 69.8%; PR 91.9% vs 77.8%). In the HER-2/neu positive tumors, ER and PR expression in high grade tumors was significantly decreased compared with intermediate grade tumors (ER 5.6% vs 10.5; PR 0% vs 5.3%). ER expression in the HER-2/neu positive, large sized tumors was also significantly decreased compared with smaller tumors (ER 6.3% vs 11.8). CONCLUSIONS: ER and PR expression in breast cancers in the current study was found to be comparable to published international data, but the frequency of HER-2/neu expression was higher, possibly reflecting a young age at diagnosis. Assessment of prognostic markers for the clinical management of breast cancer patients is strongly advocated to provide best therapeutic options.

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.

Extranodal non-Hodgkin's lymphomas--a retrospective review of clinico-pathologic features and outcomes in comparison with nodal non-Hodgkin's lymphomas.

OBJECTIVE: The primary objective of this study was to analyze the anatomic distribution, clinical features and outcome of Diffuse large B-cell lymphoma (DLBCL) patients according to the primary site (extranodal vs. nodal) with applicability of International Prognostic Index (IPI). METHODOLOGY: A retrospective review (1988 to 2004) of 557 cases of DLBC. RESULTS: The median age was 48.7 +/- 15.3 years; M:F ratio was 2:1. The distribution according to the primary site was: lymph node (N-NHL), 322 cases (58%) of which 145(44%) were stage IV, 76(23%) stage III, 60 (18%) stage II and 47 (15%) stage I. The extra nodal sites (EN-NHL) 235 (42%) cases included gastro-intestinal tract (44%), upper aerodigestive tract (19%), bones (8%), spine (5%), and unusual sites less than 3% each as breast, CNS, testis, lungs and skin. The median survival rate was 4.8 years and 6.3 years in N-NHL and EN-NHL respectively. In the latter this varied greatly depending on the primary site and stage of disease at presentation. In the univariate analysis factors associated with good prognosis were: age less than 60 years, early stage (I-II), extranodal involvement primarily gastric or bone, 0-1 extranodal site, 0-1 performance status, lack of B symptoms and normal LDH level. In the multivariate analysis age, performance status, stage of disease and level of LDH were the main variables predicting overall survival; no nodal or extranodal site maintained their prognostic value. CONCLUSION: Patients with EN-NHL present more frequently with early stage disease then those with N-NHL; overall survival in both groups largely depended on IPI and not on the site of origin of the malignancy.

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.

Factors influencing in-hospital length of stay and mortality in cancer patients suffering from febrile neutropenia.

INTRODUCTION: Febrile neutropenia (FN) is a major complication of chemotherapy, costly in terms of morbidity, mortality and associated financial expenditure. The present study was conducted with the goal of highlighting FN as a serious problem in Pakistan, with the longer term objective of improved cancer survival, reduction in length of stay (LOS) in hospital, morbidity, mortality and costs in our existing developing country scenario. METHODS: A cross-sectional descriptive study was conducted on patients, > or =18 years, admitted with FN as a consequence of chemotherapy at a referral hospital in Karachi from 1st September 2006 to 30th April 2007. RESULTS: A total of 80 patients [43 (53.8%) males and 37 (46.2%) females] were selected. The mean age was 47.4 (SD +/-16.6; range 18-79) years. Sixty eight patients (86%) were < or = 65 years, 50% were < or = 50 years. Overall, inhospital mortality was 11%; 4% for patients on granulocyte colony stimulating factor (G-CSF) prophylaxis as against 20% for those without. The cause of death was either pneumonia or septic shock. Mean LOS was 7.53 (SD +/-3.8; range 2-17) days. Hematological malignancies, older age, severity of dehydration, pneumonia and culture positivity were significantly associated with LOS and death. Those above 50 years of age were 1.5 times as likely to be hospitalized longer and > three times as likely to die. Bacteremia conferred a 5-fold and pneumonia an 8-fold increase in the risk of death. CONCLUSION: The results of this study indicate that age, vital instability, dehydration, high creatinine, culture positivity and hematological malignancies are high risk factors in chemotherapy induced FN. Identification of FN risk factors with poor outcomes may help in devising protocols for modified dosage or including GCFs initially. This may help reduce the cost of cancer care as well as mortality and morbidity. Prospective studies of FN in multiple centers in Pakistan may be beneficial in evaluating these risk factors further.

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.

Primary gastrointestinal malignancies in childhood and adolescence--an Asian perspective.

INTRODUCTION: Primary gastrointestinal (GI) malignancies are a rarity in childhood and adolescence, with limited information from Asian populations. This study was conducted with the objective of identifying the existence of malignant GI tumors in the young population of Pakistan and to determine high risk geographical areas of the country. METHODOLOGY: Pediatric and adolescence (<or=14 years; <or=19 years) gastrointestinal malignancies, ICD-10 categories C15-20 registered at the surgical pathology department of the Aga Khan University Hospital during 1st March 2004 to 30th April 2006 were included in the cross-sectional study. RESULTS: Sixty cases in <or=19 year age group were studied. The mean age was 16.2 years (SD+/-4.56). Carcinoma comprised 47 cases (78.3%; 32 boys and 15 girls.) and lymphoma 13 cases (21.7%; 12 boys and 1 girl). All cases presented as advanced malignancies. Categorization of carcinoma by site was colon (85.1%), stomach (6.4%) and esophagus (8.5%). Lymphoid malignancies were diffuse large B-cell lymphoma (30.8%), Burkitt lymphoma (46.1%) and Burkitt-like lymphoma (23.1%). The mean age at presentation was 11.1 years (SD+/- 4.6). CONCLUSION: This study has identified a substantial number of GI malignancies in the <or=19 year Pakistani population, involvement of esophagus, male predominance, preponderance of carcinoma versus lymphoma and a high signet ring cell and mucinous colo-rectal carcinoma. It has identified Baluchistan as a high risk region for esophageal cancer and diffuse large B-cell lymphoma and NWFP for Burkitt and Burkitt-like lymphoma. Most findings in the present study did not concur with published western data, indicating the need to study cancer in the Asian population.

Pediatric brain tumours at a tertiary care hospital in Karachi.

The objectives of this study were to determine the epidemiology of brain tumors during infancy and childhood and to define and segregate childhood brain tumors vis-a-vis their morphological characteristics. The present study includes pediatric brain tumors, ICD-10 category C71 encountered during 10 years (January 1989 through December 1998) at a tertiary care hospital in Karachi. Eighty one cases were included, 58 (71.6%) in males and 23 (28.4%) in females with a male to female ratio of 2.5:1. The cases were divided into 3 age groups each covering five years of life (0-4, 5-9, 10-14 years), with the greatest number in the second age group i.e. 5-9 years followed by the third age group and the 0-4 year age group. The mean age for all cases, both genders was 8.8 years (95% CI 7.9; 9.6) with a marginal variation for cases occurring in the cerebrum and cerebellum. The malignancies occurred at a younger age in the males for each subcategory by site and morphology. The morphological distribution of cases was astrocytoma (28 cases, 34.6%), primitive neuroectodermal tumor or PNET (40 cases; 49.4%), ependymoma (8 cases, 10%), mixed glioma (4 cases; 5%) and a case of oligodendroglioma. The 81 malignancies included in this study were further categorized by site into two groups, supratentorial (27 cases; 33.3%) and infratentorial (54 cases; 66.7%). The morphological categorization of supratentorial tumors was astrocytoma (17 cases; 63%), ependymoma (5 cases; 18.5%), mixed glioma (2 cases; 7.4%). PNET with rhabdoid differentiation, oligodendroglioma and pinealoblastoma comprised 1 case (3.7%) each. The 17 supratentorial astrocytoma were sub-categorized as follows - pilocytic astrocytoma (5 cases; 29.4%), grade II astrocytoma (6 cases; 35.3%); grade III astrocytoma (2 cases; 11.8%), anaplastic astrocytoma (1 case; 5.9%) and glioblastoma multiforme (3 cases; 17.7%). The morphological categorization of infratentorial tumors was astrocytoma (11 cases; 20.4%), medulloblastoma (38 cases; 70.4%), ependymoma (3 cases; 5.6%) and mixed glioma - astroependymoma (2 cases, 3.7%). The morphological sub-categorization of infratentorial astrocytoma was pilocytic astrocytoma (7 cases, 63.6%), with gemistocytic astrocytoma, grade II, grade III and anaplastic astrocytoma comprising 1 (9.1%) case each. The morphological categorization of medulloblastoma was classical medulloblastoma (15 cases; 39.5%), desmoplastic medulloblastoma (8 cases; 21.1%), medulloblastoma with astrocytic differentiation (12 cases; 31.5%), medulloblastoma with neural differentiation (2 cases; 5.3%), and neuroblastic medulloblastoma (1 case; 2.6%). The pediatric brain tumors in Karachi reflect a developing country scenario, with a strong male predisposition and a late presentation with a peak in the 5-9 year age group. There is a predominance of medulloblastoma and a paucity of astrocytomas. The current study is a single institution study and needs cautious interpretation. Population-based studies are required to determine the cancer burden due to pediatric malignancies of the brain in this population and for the morphological categorization of brain tumors in Karachi.

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.

Cancer profile of Larkana, Pakistan (2000-2002).

This present study was conducted with the objective of providing the cancer profile of Larkana, the fourth largest city of Sindh, Province. The study included two sets of patients. The first set included the incident cancer cases, residents of Larkana, who reached Karachi for diagnosis or treatment. The second set consisted of the incident cancer cases registered at the Aga Khan University (AKU) Pathology collection points at Larkana during 1st January 2000 to 31st December 2002. The age-standardized rates (ASR) for cancer (all sites) were 134.2/100,000 in males and 110.3/100,000 in females. The most common malignancies in males were lymphoma, oral cavity, prostate, liver, and urinary bladder. Cancers in females were breast, oral cavity, lymphoma, skin and thyroid. Tobacco-associated cancers accounted for approximately 35.0% of the tumors in males and 18.6% in females. The gender ratio was 1.5, the mean age of cancer all sites was 45.5 years (95% CI 34.6; 56.4) in males and 42.9 years (95% CI 33.6; 52.2) in females. This is the first attempt to determine the cancer incidence pattern of Larkana and should serve as a guideline for estimation of the cancer burden of Pakistan and the cancer control program of the country. The data must be interpreted with care, as they are largely pathology-based with approximately 15-30% population-wise under-registration. However, the chances of selective collection bias were minimized as the AKU pathology specimens were collected from 2 centers within the city, Each collection centre provided diagnostic service to several health centres giving wide population coverage, thus ensuring adequate sampling from the entire city.

Phylloides tumors in adolescent girls and young women in Pakistan.

The objective of this study was to determine the frequency of phylloides tumor (PT) in adolescent girls and young women (less than and equal to 25 years of age) and to define the clinico-pathological features of PT in this unusual clinical setting. This descriptive study was carried out at the Aga Khan University Hospital (AKUH) pathology department. All consecutive cases of PT diagnosed during the last sixteen years in the section of histopathology from 1st January 1990 to 31st June 2005 were included. Selection of cases was restricted to patients up to 25 years of age. A total of 42 cases of PT in up to 25 years of age were diagnosed. This comprised 11% of the total PT cases (total n=363). The number of benign (BPT), borderline (BLPT) and malignant (MPT) was identical i.e. 14 (33.3%) each. Clinically all cases presented with a solid, mobile, palpable mass. The mean age was 19.1 years (95% CI, 16.7-21.6), 21.9 years (95% CI, 20.7-21.9) and 19.7 years (95% CI, 17.2-22.3) in BPT, BLPT and MPT respectively. In majority of cases the surgical procedure performed was lumpectomy (50% of BPT, 78% of BLPT and 64% of MPT). High grade PT (BLPT and MPT) is an uncommon mammary tumor in adolescent girls and young women but seems to be occurring with increased frequency in the study population. This observation may indicate the biological behavior of PT in a high risk population, though chances of referral bias are also present. In view of the rarity of the disease, larger population studies are suggested to confirm our findings.

Metaplastic carcinoma of the breast, an intriguing rarity.

Metaplastic carcinoma breast is categorized as a rare heterogenous neoplasm generally characterized by a mixture of adenocarcinoma with dominant areas of spindle cell, squamous and/or other mesenchymal differentiation. To determine the epidemio-demographic and histopathologic characteristics of this rare entity a retrospective study was conducted to review all cases at the Aga Khan University Hospital (AKUH) Karachi, received during 1st January 2000 to 31st August 2005. Twenty-four patients were identified with a mean age at diagnosis of 46.4 (+/-SD 3.8) years, and an age range of 28-68 years. The mean tumor size was 7.9 cm, range 2.0-17.0 cms (+/-SD 4.77). The specimens were mostly obtained by modified radical mastectomy(54.2%) followed by biopsy (29.2%), lumpectomy (8.3%), and total mastectomy (4.2%). Skin ulceration was found in 37.5% cases. Component sub-categorization showed 13 (54.2%) cases of infiltrating ductal carcinoma with squamous metaplasia, followed by 2 (8.3 %) cases with heterologous elements, 4 (16.7%) cases with spindle cell component, 2 cases of matrix producing carcinoma and one case of squamous cell carcinoma. The malignancy was high grade, modified Bloom Richardson's grade III (54.2 %) and grade II (12.5%). Such grading was not applicable to 4 cases of spindle cell component and 1 case with extensive chondroid areas. Twelve patients had information available on the nodal status. Five (41.6%) were node-negative, four (33.33%) had 1-3 lymph node involvement positive, and three (12.5%) had more than 3 lymph nodes positive. The median 3 year Event Free Survival (EFS) was 10% and overall survival was 30%. MCB is an aggressive disease with a poor prognosis. This aspect appears bleaker in our population either due to the biological characteristic of the malignancy in a high risk group or the lack of availability and accessibility of health coverage, resulting in a delayed presentation. MCB is an uncommon breast malignancy and due to the lack of sufficiently large studies there is limited knowledge as to the pathogenesis, progress, best treatment protocols and prognosis. Collaborative studies are therefore recommended to allow for better understanding of this intriguing neoplasm.

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.

Patho-epidemiology of lung cancer in Karachi (1995-2002).

The objective of the study was to provide an overview of the demographics of lung cancer, the number one cancer killer of men in Karachi South (1995-2002). Lung cancer cases recorded at Karachi Cancer Registry during 1st January 1995 to 31st December 2004 were analyzed. To allow for maximum data completion, cases recorded from 1st January 1995 to 31st December 2002 were included for final analysis. Trends were studied by analyzing the age standardized incidence rates (ASR)s in 2 time periods, 1995-1997 and 1998-2002. Odds ratio for sex, age-groups, ethnicity, religion, and residence by socio-economic categories were calculated by considering all malignancies (except tobacco-associated malignancies) for each group, registered at KCR for the same period as controls. Cancer of the lung ranked the most frequent malignancy in men in Karachi in the entire 1995-2002 period, though it did not feature amongst the first 10 malignancies in the females. In the 1995-1997 period, the ASR per 100,000 population for cancer of the lung was 21.4 and 2.9 in males (M) and females (F) respectively. The mean age of the patients was 60.4 years (95% CI, 59.1-61.7) M and 53.7 years (95% CI 48.9-58.5) F. In the 1998-2002 period the incidence rate increased to 25.5 per 100,000 (M) and 4.2 per 100,000 (F). Thus between 1995 and 2002, the incidence of lung cancer registered a 19% increase in men and almost 100% in women. The component of adenocarcinoma in females remained stable during 8 years, but increased 55% in males. Histologic confirmation was 80%; majority of cancer cases presented as grade 3 and grade 4 lesions (62.3%), and were discovered at advanced stages (stage III 35.7%; stage IV 55.8%).The odds ratio (OR) in men was 4.5 (95% CI 3.7; 5.4). The risk of developing lung cancer increased with age, the highest risk being observed in the 65+ age group. A marginally higher risk was observed in the higher socio-economic categories for men and in the lower socio-economic categories for women. A higher risk was also observed for men who were residing along the coastal belt, and for ethnicities belonging to Southern Pakistan (Sindhi and Mohajir) residing in Karachi South. In conclusion, Pakistan at present falls into a low risk lung cancer region in females and a moderate risk region for males and the highest registered increase between 1995 and 2002 was observed in the older age groups (65+). It is however a cause of concern that the overall lung cancer incidence rates continue to rise. The age specific rates though stable in the younger age groups (35-49 years), are at present equivalent to contemporary rates in high- risk countries. These rates correspond with the trends of smoking prevalence in the younger age groups in the last 2 decades. Published studies have given alerts to increase in the smoking habits of the present day youngsters and with an expanding population the country can expect a substantial increase in lung cancer. This threat can only be averted by implementation of stringent anti-tobacco rules and health education; prohibition of smoking in educational institutions at all levels and a ban on the sale of cigarettes to minors.

Cancer profile of Hyderabad, Pakistan 1998-2002.

Hyderabad is the third largest city of Pakistan, the second largest city of Sindh Province and one of the oldest cities of the sub-continent. This administrative headquarter is located just east of the River Indus and is an important commercial and industrial center. Once a provincial capital, it is at a distance of approximately 200-km from Karachi. This present study was conducted with the objective of providing the cancer profile of Hyderabad, which has an urban population of 2,840,653 (52.2% M, 47.8% F) annual growth rate 1.13. The city is inhabited by all ethnicities of the country, however the predominant ethnicity is Sindhi, followed by Mohajirs (post-partition immigrants from India), and a lesser extent other ethnicities of Pakistan viz. Baluchs, Punjabis and Pathans. The study includes two sets of patients. First the incident cancer cases, residents of Hyderabad, who reached Karachi for diagnosis or treatment. Second the incident cancer cases registered at the Aga Khan University Pathology-based Cancer Registry (APCR) Pathology collection points at Hyderabad and subsequently registered at APCR, during 1st January 1998 to 31st December 2002. The pathology department of the AKU has 3 centers in Hyderabad, which provide diagnostic pathology especially oncopathology services to the city. The age-standardized rates (ASR) for cancer (all sites) 1998 to 2002 in Hyderabad were 91.6/100,000 in males and 96.0/100,000 in females. The most common malignancies (ASR per 100,000) in males were oral cavity (11.8), lymphoma (10.6), lung (8.0), urinary bladder (6.8), prostate (4.8), liver (4.4), pharynx (4.2), colo-rectum (3.6), larynx (3.2), and skin (3.2). The cancers in females (ASR per 100,000) were breast (22.4), oral cavity (11.5), gall bladder (4.8), esophagus (4.2), cervix (3.6), ovary (3.4), colo-rectum (3.4), lymphoma (3.4), uterus (3.4), and thyroid (2.4). Tobacco-associated cancers were responsible for approximately 40.0% of the tumors in males and 20.0% in females. Histological confirmation remained 96.3%, with 44.5% presenting in grade II or I, 55.5% presenting as stage III and IV. Information on grade and stage of malignancy was available in 70% and 50% of the cases respectively. Males comprised 53.1%, and females 46.9% of the cases. The mean age of cancer all sites, both genders was 45.2 years (95% CI 44.4; 45.9), males 45.4 years (95% CI 44.3; 46.5); females 44.9 years (95% CI 43.9; 45.9). Conclusions drawn from this database must be interpreted with care, as it may be identified as data from selected medical institutions. Chances of selective collection bias are minimized as the data of the AKU pathology is collected from multiple centers in the city of Hyderabad, dispersed at distances, which allows adequate sampling from the entire city. There is a slight preponderance of lymphomas in males which we feel is a true higher risk, yet it may indicate an over representation of easily accessible sites in pathology based-data. Nonetheless, this is the first attempt to determine the cancer incidence pattern of Hyderabad, and should serve as a guideline for estimation of the cancer burden and risk assessment statistics of Pakistan and the cancer control program of the country.

Increasing incidence of non-Hodgkin's lymphoma in Karachi, 1995-2002.

This first population-based study of non- Hodgkin lymphoma (NHL) from any region in Pakistan, provides an overview of the incidence pattern and time trends in Karachi and generates hypotheses for future experimental research. Epidemiological data for 429 incident (1(st) Jan 1995 to 31(st) Dec 2002), microscopically verified nodal and extra-nodal NHL cases, registered at the Karachi Cancer Registry (KCR) for Karachi South, were reviewed. The age standardized incidence rate (ASIR) was 5.3/100,000 in males (M) and 4.1/100,000 in females (F), in 1995. A gradual increase in the annual incidence was observed during the study period, with NHL incidence rate increasing in 2002 to 8.4/100,000 in men and 6.5/100,000 in women, almost double the 1995 rates. NHL affected all age groups in both genders and for each group the ASIR was higher among men than women, with an overall gender ratio of 1.9. The mean ages of the patients were 41.5 years (95% CI 39.1; 43.8) in males and 44.0 years (95% CI 40.8; 47.1) in females. The adult to childhood ratios were 8.6 (M) and 10.7 (F). B-cell NHL comprised 81.0% of NHL in males and 87.3% in females. One fourth of the NHL cases were extra-nodal, the largest group was of gastrointestinal origin (54.1% M, 38.5% F). The gastric component was 21% M and 25.6% F. Odds Ratios for sex, age-groups, ethnicity, religion, and subdivision by socio-economic categories were calculated by considering all malignancies, except lymphoproliferative disorders as controls. The odds ratio (OR) in men was 2.2 (95% CI 0.6; 3.0). Children and adolescents were at the highest risk of developing NHL, especially the 5-9 year olds, in both genders. A marginally higher risk was observed for the lower socioeconomic categories and for ethnicities belonging to Northern and North Western Pakistan (Punjabi, Pushtu and Baluch) residing in Karachi South. The incidence rates of NHL registered in Karachi South are likely to be a reflection of non-AIDS-associated NHL. Estimated HIV/AIDS incidence was too low during the study period in this population to have an impact on NHL incidence. The preponderance of low and intermediate grade lymphomas, paucity of central nervous system NHL and a higher childhood NHL component support this hypothesis. As yet unpublished reports, however, are raising the alarm on rising HIV positivity. NHL correlation with HIV/AIDS status and studies identifying risk factors of non- HIV/AIDS associated NHL (childhood viral infections, Hepatitis C virus, and Helicobacter pylori) are potential areas for future experimental and epidemiological research.

Cancer of the oral cavity - trends in Karachi South (1995-2002).

The objective was to study the time trends in site-specific oral cancer incidence and to determine the age-and socio-economic profile over time in Karachi South. Oral cancer ranks second in this population, in both genders. The incidence is the highest reported worldwide. Incident oral cancer cases received at the Karachi Cancer Registry during 1(st) January 1995 to 30(th) June 2004 were reviewed. To ensure maximally complete data, cases registered between 1(st) January 1995 and 31(st) December 2002 were considered for the present study. Cases of lymphoma, leukemia and melanoma were not included. Trends were studied by grouping cases into two periods, 1995-1997 and 1998-2002. A total of 2253 cases of oral cancer were registered in Karachi South for the 8 year study period accounting for 8.8% of all cancer cases. Overall, the most common site was the mucosa cheek (55.9%), followed by the tongue (28.4%), palate (6.8%), gum (4.4%), lip (3.1%) and floor of the mouth (1.4%). About 30% of cases occurred in patients 40 years and younger and 23% occurred in patients 65 years and older. Sub-categories of oral cancer showed variation in trends, but an earlier onset of disease in period two was evident for all categories. The incidence of lip cancer in men decreased, the rates remained level in females. An increased incidence was observed for tongue, but a more dramatic increase in the cheek was evident in both sexes, despite no improvement during the past decade in detection of early, localized lesions. A strong socio-economic factor with a poorer, low literacy profile of oral cancer was apparent in the entire study period. The evidence that the largest increase in incidence has occurred in this population may unfavorably affect the mortality rates. Oral cancer trends are an interplay of prevalent risk factors, the level of prevalence, preventive education and intervention. Cost effective and efficient cancer control focused around the target populations would be beneficial for Pakistan. Educational campaigns should include information on oral hygiene, awareness of risk factors and symptoms and the importance of seeking early professional help when any of these are recognized. Audio-visual media involvement is imperative in view of the literacy status of the target population. Capacity building is required by the Government to increase the availability and accessibility of professionals. Population screening would reduce the incidence of oral cancer, but requires careful planning, and extensive financial resources. Mobilization of general practitioners, health visitors, volunteer organizations and medical students for early detection of oral cancer is the essential need of today.