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.

Nasopharyngeal carcinoma - an update of treatment and acute radiation induced reactions from a tertiary-care hospital in Pakistan.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is a diverse entity with a multi-factorial etiology and a distinct racial and geographical distribution. It is curable if diagnosed and treated early. METHODS: This descriptive study covered 30 patients who underwent radiotherapy (RT) for nasopharyngeal malignancies during February 2006 till November 2010 at the Department of Radiation Oncology, Aga Khan University Hospital (AKUH), Karachi. RESULTS: Thirty cases of nasopharyngeal tumors were registered; a case of embryonal rhabdomyosarcoma and another of diffuse large B-cell lymphoma were not included in the final analyses. There were 20 (71.0%) males and 8 (29.0%) females, 2 and 5 being observed in adolescents. The mean age of the male and female patients was 43.7 [SD 20.1] and 30.3 years [SD 17.9], respectively. Nodal involvement was seen in 23 cases and cranial in 8. Almost two-thirds the patients presented with a stage IV disease and all but two received chemotherapy. Electrons or photons were used for 23 cases; low anterior neck field was used in 25 cases. The doses of radiotherapy delivered ranged between 2000cGy to 7400cGy, the lower ones being given for palliation only. Once spinal cord tolerance was reached, electron boost fields were used in order to treat the posterior neck. A nasogastric tube was required for feeding in 2 (10.0%) male and 2 (25.0%) female patients; gastrostomy was needed for 1 (5.0%) patient. Radiotherapy (RT) induced reactions were observed in 90% of the patients, but were mild in most cases. CONCLUSIONS: In the presence of clinician based expertise and technical constraints in Pakistan, nasopharyngeal tumors are still being treated optimally with the need of creating a better awareness in public for early detection.

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.

Lymphoma cases referred to the radiation oncology service of a tertiary referral university hospital in Karachi, Pakistan: a retrospective study.

INTRODUCTION: Radiation therapy is an important component of curative therapy for Lymphoma [Hodgkin's disease (HD) and non Hodgkin's Lymphoma (NHL)]. The current study was conducted to give us an overview of lymphoma patients presenting to a tertiary care hospital for complementary adjuvant RT. METHOD: Data of lymphoma patients who underwent radiotherapy during February 2006 till August 2009 at the department of radiation oncology, Aga Khan University, Hospital, Karachi was retrieved from the medical records and analyzed using SPSS (version 16.0). RESULTS: A total of 1,678 cancer patients were registered, 75 (0.45%) were lymphoma patients (25.3% HD; 74.7% NHL). HD and NHL were both seen predominantly in males, with a male:female ratio of 2 and 3 respectively. Nodal HD comprised 94.7% and nodal NHL comprised 41.1%. Extranodal NHL (EN-NHL) comprised 53.6% whereas 5.4% cases had both nodal and EN-NHL; 6.7% of EN-NHL were primary CNS lymphomas. Stages of presentation for HD were IIA (52.6%), 1A (21.1%), IIB (10.5%) and IB, IIIB and IVA collectively 15.9%. The ages of HD patients ranged from 11 to 54 years (median 23.5 years 13.2 SD). Response to therapy for HD was 52.6% complete remission, 36.8% partial response, and 5.3% each with stable and progressive disease. Almost all patients (94.7%) received radical treatment with radiation doses (between 1950 cG to 5404 cGy) with a median of 40 Grays.Stages at presentation for NHL were II (23.2%), IV (21.4%) and IE (17.9%); I, IIE, and III were found to be 12.5 %. NHL patients ranged from 15 to 88 years. It was more commonly observed amongst the elderly with 25% patients diagnosed in the fifth decade of life; 50% patients aged at or above 50 years, 41.1% belonged to the 25-49 years age group and 8.9% below 25 years of age. Majority of the cases were diffuse NHL (82.1%), follicular NHL (7.1%), Primary CNS unclassified type (8.9%), and unclassified other than CNS variety (1.8%). Response to chemotherapy for NHL was 51.8% complete remission, 25.9% progressive disease, 20.4% partial response. Forty (71.4%) patients with NHL received radical treatment with radiation doses between 2340 cG to 6600 cGy; 28.6% received palliative RT. CONCLUSION: Radiation therapy though important for curative lymphoma therapy, is relatively underutilized in our population, despite encouraging outcomes.

Cancer epidemiology in South Asia - past, present and future.

Pakistan, India, Sri Lanka, Bangladesh, Nepal and Bhutan, with their total population of more than 1,500 million, make up the subcontinent of South Asia. Despite massive diversity across the region, there are sufficient similarities to warrant a collective approach to chronic disease control, including development of cancer control programs. Cancer is already a major problem and there are general similarities in the prevalence patterns. In males, oral and lung cancer are either number one or two, depending on the registry, with the exceptions of Quetta in the far north, Larkana and Chennai. Moderately high numbers of pharyngeal and/or laryngeal cancer are also consistently observed, with prostate cancer now becoming visible in the more developed cities. Breast and cervical cancer share first and second place except in Muslim Pakistan, where oral cancer generally follows breast. The ovary is often included in the five most prevalent types. Markedly increasing rates for breast cancer and distribution shifts in other cancers suggest that, despite improvement in cervical and oral rates, the overall burden will only become heavier over time, especially with increasing obesity and aging of what are still youthful populations. Coordination of activities within South Asia is a high priority for cancer control in the region.

Cancer survival in Africa, Asia, and Central America: a population-based study.

BACKGROUND: Population-based cancer survival data, a key indicator for monitoring progress against cancer, are not widely available from countries in Africa, Asia, and Central America. The aim of this study is to describe and discuss cancer survival in these regions. METHODS: Survival analysis was done for 341 658 patients diagnosed with various cancers from 1990 to 2001 and followed up to 2003, from 25 population-based cancer registries in 12 countries in sub-Saharan Africa (The Gambia, Uganda), Central America (Costa Rica), and Asia (China, India, Pakistan, Philippines, Saudi Arabia, Singapore, South Korea, Thailand, Turkey). 5-year age-standardised relative survival (ASRS) and observed survival by clinical extent of disease were determined. FINDINGS: For cancers in which prognosis depends on stage at diagnosis, survival was highest in China, South Korea, Singapore, and Turkey and lowest in Uganda and The Gambia. 5-year ASRS ranged from 76-82% for breast cancer, 63-79% for cervical cancer, 71-78% for bladder cancer, and 44-60% for large-bowel cancers in China, Singapore, South Korea, and Turkey. Survival did not exceed 22% for any cancer site in The Gambia; in Uganda, survival did not exceed 13% for any cancer site except breast (46%). Variations in survival correlated with early detection initiatives and level of development of health services. INTERPRETATION: The wide variation in cancer survival between regions emphasises the need for urgent investments in improving awareness, population-based cancer registration, early detection programmes, health-services infrastructure, and human resources. FUNDING: Association for International Cancer Research (AICR; St Andrews, UK), Association pour la Recherche sur le Cancer (ARC, Villejuif, France), and the Bill & Melinda Gates Foundation (Seattle, USA).

Staging of prostatic adenocarcinoma with radical prostatectomy specimens in Pakistan.

OBJECTIVES: Data for pathological staging of radical prostatectomy specimens reported in the Section of Histopathology of a large tertiary care hospital in Pakistan were compared with sextant biopsy findings to determine whether clinically localized disease is actually localized pathologically. DESIGN: A study was conducted of radical prostatectomy specimens reported in the Section of Histopathology from Jan 2001 to July 2008, with cases staged according to the pathologic TNM staging system. Other variables such as amount of tumor in prostatectomy specimens and lobes affected were also determined. RESULTS: Out of 65 cases, 83.3% were clinical stage TIc. 29.2% were pT3a, 24.6% were pT3b and 3.1% were pT4. Therefore, in the majority of cases, disease was not localized to the prostate and perineurial invasion was seen in all. Comparison with biopsy results showed Gleason's grade to be altered in 20% cases. CONCLUSIONS: The large majority of prostatic carcinomas in Pakistan are advanced cancers with pathologic stage more advanced than evident on clinical staging. On average, tumors involved 35-40% of the prostate with a particular preponderance in posterior lobes.

Clinico-pathological features and outcomes in chronic phase chronic myeloid leukemia patients treated with hydroxyurea.

OBJECTIVE: To study the clinico-pathological features and major outcomes in patients with chronic myeloid leukemia, chronic phase, treated with hydroxyurea. METHODS: This is a single centre study extending from January 1997 to June 2003. Data were retrieved from the patients' records on predetermined performance and analyzed. Patients were primarily diagnosed on the basis of clinical findings, complete blood counts and leukocyte alkaline phosphate (LAP) scores. Bone marrow/trephine and genetic studies were conducted where appropriate. Patients were primarily treated with capsule hydroxyurea 30-50/ kg/day. RESULTS: One hundred and seventy six patients, 104 (59%) male and 72 (41%) females were included in the study. The median age at diagnosis was 39 years (range 11 to 66 years). The median delay in diagnosis was 156 days (range 30 to 360 days). Eighty four patients (47.7%) presented with pain/discomfort in the left hypochondrium. The mean hemoglobin, white blood cell count and platelet counts were 10.3 g/dl, 141,000/UL and 341,000/UL respectively associated with a low LAP score. Hyper-leucocytosis was observed in 19 (10.7%) cases. LDH values above 1,000 ug/l were observed in 38 (21.5%) cases and creatinine above 1.5 ug/l in 21 (12%) cases. All patients tested, were positive for Philadelphia chromosome and bcr-abl transcripts. At the close of the study, disease advancement was observed in 76 (43.2%) cases, of which 35 (20%) transformed to acute leukemia. One hundred and forty three patients (81%) were alive at the close of the study. One hundred and two (58.4%) patients were in chronic phase, 22 (12.5%) in accelerated phase and 19 (10.7%) in blast crisis. Disease progression remained the major cause of death and was seen in 29 (16.4%) patients. CONCLUSION: In the study population, CML was observed in a younger age group with significant delay in definitive diagnosis. Clinico-pathological features and major outcomes, however, appear comparable to published data.

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.

Age-standardized incidence rates for childhood cancers at a cancer hospital in a developing country.

BACKGROUND: Cancer registration is a neglected area in several developing countries of the world including Pakistan due to funding problems and apathy of most health professionals towards reporting of cancer data. METHODS: The epidemiologic review is the first of its type reporting cancers recorded at a cancer hospital in Lahore, Pakistan, in children less than 15 years of age, belonging to Lahore District, in a one year time period from January 1, 2008 to December 31, 2008. The results have been stratified by gender, 5-year age-groups (0-4, 5-9 and 10-14), and the International Classification of Childhood Cancers diagnostic groups. Crude- and age-specific-rates by age-groups were estimated and standardized by applying the direct method of age-standardization using the world standard of Segi (1960) to determine the incidence of childhood cancers per 100,000 population in one year. RESULTS: In order of ranking, the age-standardized incidence rates (ASR) per 100,000 were as follows: amongst boys, leukemias 1.3, lymphomas and reticuloendothelial neoplasms 1.3, CNS and miscellaneous intracranial/intraspinal tumors 0.7, malignant bone tumors 0.4, and soft tissue sarcomas 0.4; amongst girls, leukemias 0.7, lymphomas and reticuloendothelial neoplasms 0.5, malignant bone tumors 0.3, CNS and miscellaneous intracranial/intraspinal tumors 0.3, and renal tumors 0.3. CONCLUSION: The results represent one institution. However, as pediatric cancer care units are rare and specialized, hospital cancer registries in developing countries are likely to record a significant proportion of pediatric cases diagnosed in the area. Hence, it may be worthwhile to generate yearly incidence reports in an attempt to evaluate the trends in childhood cancers in Lahore.

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.

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.

Awareness of cancer risk factors among patients and attendants presenting to a tertiary care hospital in Karachi, Pakistan.

OBJECTIVE: To determine awareness of cancer risk factors in the patients and attendants of Out-patient Clinics at a University Hospital in Karachi, Pakistan. METHODS: A cross-sectional survey was conducted on 315 respondents reporting to a tertiary care hospital in Karachi, Pakistan, to assess their level of awareness regarding risk factors of cancer. RESULTS: The respondents belonged to an urban population with the mean time spent in Karachi of 29.1 years (SD +/- 13.94). There were 213 (67%) males and 102 (33%) females. All respondents had heard of the word 'cancer', while only 57.5% were aware of cancer risk factors. However, only 42.8% could identify age, 33% diet, 35% drugs and 31% obesity as risk factors for cancer. Even those who were aware of the risk factors were not able to appreciate personal risk of cancer. CONCLUSION: Despite awareness regarding some of the risk factors, the surveyed population was not aware of intrinsic risk factors for cancers like increasing age and obesity. It is important to create awareness through educational programs on cancer prevention, dissemination of knowledge pertaining to the preventable and avoidable cancer risk factors, the benefits of early diagnosis, and availability of screening tests.

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.

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.

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.

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.