Metastatic breast cancer in Kenya: survival, prognosis and management at a tertiary referral centre.

There has been an increase in breast cancer in Africa with up to 77% of patients diagnosed with advanced disease. However, there is little data on survival outcomes and prognostic factors affecting survival in patients with metastatic breast cancer (MBC) in Africa. The study objective was to establish the survival of patients with MBC at a single tertiary health facility, the clinical and pathological characteristics affecting survival and describe the treatment modalities used. This was a retrospective descriptive study conducted at Aga Khan University Hospital, Nairobi of patients diagnosed with MBC between 2009 and 2017. Survival data was collected on metastatic free survival, survival time between diagnosis of first metastasis and death and overall survival. Data on patient's age, menopausal status and stage at diagnosis, tumour grade, receptor status, site of metastasis and treatment given was also collected. The Kaplan-Meier Estimator was used to estimate survival. Prognostic factors for survival outcomes were analysed using univariate analysis. Standard descriptive statistics were used to describe patient characteristics. A total of 131 patients were included in the study. The median survival was 22 months. The 3 and 5-year survivals were 31.3% and 10.7%, respectively. On univariate analysis, the Luminal A molecular subtype was a significant positive prognostic factor hazard ratios (HR 0.652 95% confidence interval (CI) 0.473-0.899) while metastasis to the liver or brain were significant negative prognostic factors (HR 0.615 95% CI 0.413-0.915 and HR 0.566 95% CI 0.330-0.973, respectively). A large proportion (87.0%) received some treatment for metastatic disease. Our study concluded that survival rates for patients diagnosed with MBC were lower compared to studies from Western countries but higher than in studies from Sub-Saharan Africa. Luminal A molecular subtype was found to be a positive prognostic factor and metastasis to the liver or brain were found to be negative prognostic factors. Improved access to adequate treatment for MBC is required in the region.

Tumour Infiltrating Lymphocytes (TILs) and immune composition in breast cancer patients from Kenya: Spatial distributions and associations with risk factors and tumour characteristics.

BACKGROUND: The immune landscape of breast cancer (BC) in patients from Sub Saharan Africa is understudied. Our aims were to describe the distribution of Tumour Infiltrating Lymphocytes (TILs) within the intratumoural stroma (sTILs) and the leading/invasive edge stroma (LE-TILs), and to evaluate TILs across BC subtypes with established risk factors and clinical characteristics in Kenyan women. METHODS: Visual quantification of sTILs and LE-TILs were performed on Haematoxylin and eosin -stained pathologically confirmed BC cases based on the International TIL working group guidelines. Tissue Microarrays were constructed and stained with immunohistochemistry (IHC) for CD3, CD4, CD8, CD68, CD20, and FOXP3. Linear and logistic regression models were used to assess associations between risk factors and tumour features with IHC markers and total TILs, after adjusting for other covariates. RESULTS: A total of 226 invasive BC cases were included. Overall, LE-TIL (mean = 27.9, SD = 24.5) proportions were significantly higher than sTIL (mean = 13.5, SD = 15.8). Both sTILs and LE- TILs were predominantly composed of CD3, CD8, and CD68. We found higher TILs to be associated with high KI67/high grade and aggressive tumour subtypes, although these associations varied by TIL locations. Older age at menarche (≥ 15 vs. < 15 years) was associated with higher CD3 (OR: 2.06, 95%CI:1.26-3.37), but only for the intra-tumour stroma. CONCLUSION: The TIL enrichment in more aggressive BCs is similar to previously published data in other populations. The distinct associations of sTIL/LE-TIL measures with most examined factors highlight the importance of spatial TIL evaluations in future studies.

Supporting Kenyan women with advanced breast cancer through a network and assessing their needs and quality of life.

INTRODUCTION: Metastatic breast cancer (MBC) patients have several unmet needs. The needs and quality of life of MBC women living in sub-Saharan Africa (SSA) are understudied. Facilitating the interaction of various caregivers is beneficial in addressing the needs. Internet-based resources play an important role in reaching out to these patients. We aimed to bring the various stakeholders into a joint network force, create a web-based portal, understand the needs of MBC patients, and assess the utilization of web-based resources for women from Kenya. METHODS: A network of various stakeholders considered crucial in the care of Kenyan women with MBC was created. We conducted educational camps and assessed their needs, quality of life (QoL), and knowledge. We assessed the impact of utilizing web-based resources by MBC patients from here. RESULTS: We formed a network involving partners and launched the first dedicated website for MBC from Kenya. The website has received 13,944 visits and 310,379 hits in 2 years. One hundred fourteen women living with MBC were interviewed, and our findings show that psychological needs (63%), physical support needs (60%), and health care system needs (55%) are leading areas of needs that increase with rural residence (p = 0.001), less education (p = 0.003), and aggressive treatments (p = 0.008). Quality of life (QoL) confirmed better scores with urban residence (p = 0.002), internet access (p = 0.010), and stable disease (p = 0.042). CONCLUSIONS: Creating a network of caregivers provides opportunities for cohesive efforts in understanding the psychosocial and medical needs of patients with MBC. Internet-based resources are an effective way of reaching out to them. Kenyan patients show extremely good uptake of internet-based resources.

Breast cancer risk factors in relation to molecular subtypes in breast cancer patients from Kenya.

BACKGROUND: Few studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations. METHODS: We conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based, and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors. RESULTS: The median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3, and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER-positive tumors, ER-negative patients were more likely to have higher parity (OR = 2.03, 95% CI = (1.11, 3.72), p = 0.021, comparing ≥ 5 to ≤ 2 children). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR = 0.45, 95% CI = 0.23, 0.87, p = 0.018, comparing ≥ 5 to ≤ 2 children); HER2-enriched patients were less likely to be obese (OR = 0.36, 95% CI = 0.16, 0.81, p = 0.013) or older age at menopause (OR = 0.38, 95% CI = 0.15, 0.997, p = 0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes. CONCLUSIONS: In Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies is needed to develop population and subtype-specific risk prediction/prevention strategies.

Comparative analysis of triple-negative breast cancer transcriptomics of Kenyan, African American and Caucasian Women.

PURPOSE: Triple-negative breast cancer (TNBC) patients of various ethnic groups often have discrete clinical presentations and outcomes. Women of African descent have a disproportionately higher chance of developing TNBCs. The aim of the current study was to establish the transcriptome of TNBCs from Kenyan (KE) women of Bantu origin and compare it to those TNBCs of African-Americans (AA) and Caucasians (CA) for identifying KE TNBC-specific molecular determinants of cancer progression and potential biomarkers of clinical outcomes. PATIENTS AND METHODS: Pathology-confirmed TNBC tissues from Kenyan women of Bantu origin (n = 15) and age and stage range matched AA (n = 19) and CA (n = 23) TNBCs of patients from Alabama were included in this study. RNA was isolated from paraffin-embedded tissues, and expression was analyzed by RNA sequencing. RESULTS: At clinical presentation, young KE TNBC patients have tumors of higher stages. Differential expression analysis identified 160 up-regulated and 178 down-regulated genes in KE TNBCs compared to AA and CA TNBCs. Validation analyses of the TCGA breast cancer data identified 45 KE TNBC-specific genes that are involved in the apoptosis (ACTC1, ERCC6 and CD14), cell proliferation (UHRF2, KDM4C, UHMK1, KCNH5, KRT18, CSF1R and S100A13), and Wnt signaling (BCL9L) pathways. CONCLUSIONS: In this study, we identified biomarkers that are specific for KE TNBC patients of Bantu origin. Further study with a larger sample size of matched tumors could confirm our findings. If biologically confirmed, these molecular determinants could have clinical and biological implications and serve as targets for development of personalized therapeutics for KE TNBC patients.

Follow-Up Care for Breast and Colorectal Cancer Across the Globe: Survey Findings From 27 Countries.

PURPOSE: The purpose of this study was to describe follow-up care for breast and colorectal cancer survivors in countries with varying levels of resources and highlight challenges regarding posttreatment survivorship care. METHODS: We surveyed one key stakeholder from each of 27 countries with expertise in survivorship care on questions including the components/structure of follow-up care, delivery of treatment summaries and survivorship care plans, and involvement of primary care in survivorship. Descriptive analyses were performed to characterize results across countries and variations between the WHO income categories (low, middle, high). We also performed a qualitative content analysis of narratives related to survivorship care challenges to identify major themes. RESULTS: Seven low- or /lower-middle-income countries (LIC/LMIC), seven upper-middle-income countries (UMIC), and 13 high-income countries (HICs) were included in this study. Results indicate that 44.4% of countries with a National Cancer Control Plan currently address survivorship care. Additional findings indicate that HICs use guidelines more often than those in LICs/LMICs and UMICs. There was great variation among countries regardless of income level. Common challenges include issues with workforce, communication and care coordination, distance/transportation issues, psychosocial support, and lack of focus on follow-up care. CONCLUSION: This information can guide researchers, providers, and policy makers in efforts to improve the quality of survivorship care on a national and global basis. As the number of cancer survivors increases globally, countries will need to prioritize their long-term needs. Future efforts should focus on efforts to bridge oncology and primary care, building international partnerships, and implementation of guidelines.

Metastatic Breast Cancer in Kenya: Presentation, Pathologic Characteristics, and Patterns-Findings From a Tertiary Cancer Center.

PURPOSE: The purpose of this research was to describe the sociodemographic and clinical characteristics of Kenyan women with metastatic breast cancer diagnosed and treated at Aga Khan University Hospital in Nairobi, Kenya from 2012 to 2018. PATIENTS AND METHODS: We reviewed charts of Kenyan women with metastatic breast cancer and analyzed sociodemographic data, breast cancer risk factors, and tumor characteristics associated with stage at diagnosis, receptor status (ie, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 [HER2]), and site of metastasis using χ2, analysis of variance, two-sample t tests, and logistic regressions. RESULTS: A total of 125 cases with complete medical records were included in the analysis. Forty women (32%) had metastases at diagnosis. Of the others, those diagnosed in stage III developed metastases sooner than those diagnosed in stage II (P < .001). Fifty-eight percent of patients had metastases to bone, 14% to brain, 57% to lungs, and 50% to liver. Seventy-four percent of patients presented with more than one metastatic site. Metastases to bone were associated with greater age at diagnosis (P = .02) and higher parity (P = .04), and metastases to the brain were associated with early menopause (P = .04), lower parity (P = .04), and lack of breastfeeding (P = .01). Patients whose tumors were triple negative (estrogen receptor-negative, progesterone receptor-negative, and HER2 negative) were more likely to develop brain metastases (P = .01), and those whose tumors were HER2 positive were more likely to develop liver metastases (P = .04). CONCLUSION: Although our data on patterns of metastases and pathologic subtypes are similar to those in published literature, some unique findings concerning hormonal risk factors of women with metastatic breast cancer and specific metastatic sites need additional exploration in larger patient populations.

Mammographic Breast Density and Breast Cancer Molecular Subtypes: The Kenyan-African Aspect.

INTRODUCTION: Data examining mammographic breast density (MBD) among patients in Sub-Saharan Africa are sparse. We evaluated how MBD relates to breast cancer characteristics in Kenyan women undergoing diagnostic mammography. METHODS: This cross-sectional study included women with pathologically confirmed breast cancers (n = 123). Pretreatment mammograms of the unaffected breast were assessed to estimate absolute dense area (cm2), nondense area (cm2), and percent density (PD). Relationships between density measurements and clinical characteristics were evaluated using analysis of covariance. RESULTS: Median PD and dense area were 24.9% and 85.3 cm2. Higher PD and dense area were observed in younger women (P < 0.01). Higher dense and nondense areas were observed in obese women (P-trend < 0.01). Estrogen receptor (ER) positive patients (73%) had higher PD and dense area than ER-negative patients (P ≤ 0.02). Triple negative breast cancer (TNBC) patients (17%) had lower PD and dense area (P ≤ 0.01) compared with non-TNBCs. No associations were observed between MBD and tumor size and grade. CONCLUSIONS: Our findings show discordant relationships between MBD and molecular tumor subtypes to those previously observed in Western populations. The relatively low breast density observed at diagnosis may have important implications for cancer prevention initiatives in Kenya. Subsequent larger studies are needed to confirm these findings.

Ethnicity and breast cancer characteristics in Kenya.

PURPOSE: There are no published data from specific regions of sub-Saharan Africa describing the clinical and pathological characteristics and molecular subtypes of invasive breast cancer by ethnic group. The purpose of this study was to investigate these characteristics among the three major ethno-cultural groupings in Kenya. METHODS: The study included women with pathologically confirmed breast cancer diagnosed between March 2012 and May 2015 at 11 hospitals throughout Kenya. Sociodemographic, clinical, and reproductive data were collected by questionnaire, and pathology review and immunohistochemistry were performed centrally. RESULTS: The 846 cases included 661 Bantus (78.1%), 143 Nilotes (16.9%), 19 Cushites (2.3%), and 23 patients of mixed ethnicity (2.7%). In analyses comparing the two major ethnic groups, Bantus were more educated, more overweight, had an older age at first birth, and had a younger age at menopause than Nilotes (p < 0.05 for all comparisons). In analyses restricted to definitive surgery specimens, there were no statistically significant differences in tumor characteristics or molecular subtypes by ethnicity, although the Nilote tumors tended to be larger (OR for ≥ 5 cm vs. < 2 cm: 3.86, 95% CI 0.77, 19.30) and were somewhat more likely to be HER2 enriched (OR for HER2 enriched vs. Luminal A/B: 1.41, 95% CI 0.79, 2.49). CONCLUSION: This case series showed no significant differences in breast cancer tumor characteristics or molecular subtypes, but significant differences in sociodemographic characteristics and reproductive factors, among the three major ethnic groups in Kenya. We suggest further evaluation of ethnic differences in breast cancer throughout the genetically and culturally diverse populations of sub-Saharan Africa.

Factors that influence advance directives completion amongst terminally ill patients at a tertiary hospital in Kenya.

BACKGROUND: An advance directive (AD) is a written or verbal document that legally stipulates a person's health care preference while they are competent to make decisions for themselves and is used to guide decisions on life-sustaining treatment in the event that they become incapacitated. AD can take the form of a living will, a limitation of care document, a do-not-resuscitate order, or an appointment of a surrogate by durable power of attorney. The completion rate of AD varies from region to region, and it is influenced by multiple factors. The objectives of this study were to determine the proportion of terminally ill patients with AD and to identify the factors that influence the completion of AD amongst terminally ill patients at a tertiary hospital in Kenya. METHODS: The study was a retrospective survey. All available records of terminally ill patients seen at Aga Khan University Hospital, Nairobi, between July 2010 and December 2015, and that met the inclusion criteria were included in the study. RESULTS: In total, 216 records of terminally ill patients were analyzed: 89 records were of patients that had AD and 127 records were of patients that did not have AD. The proportion of terminally ill patients that had completed AD was 41.2%. The factors that were associated with the completion of AD on bivariate analysis were history of ICU admission, history of endotracheal intubation, functional status of the patient, the medical specialty taking care of the patient, patient's caregiver discussing the AD with the patient, and a palliative specialist review. On multivariate regression analysis, discussion of AD with a caregiver and patient's functional impairment were the factors with statistically significant association with completion of AD. CONCLUSIONS: The proportion of terminally ill patients that had AD in their medical records was significant. However, most terminally ill patients did not have AD. Our data, perhaps the first on the subject in East Africa, suggest that most of the factors associated with AD completion mirrored those seen in other regions of the world. Discussion between patient and their physician and patient's functional impairment were the factors independently associated with completion of AD. Therefore, physicians need to be aware of the importance of discussions of AD with their patients.

Molecular targeting agents in cancer therapy: science and society.

The inception of targeted agents has revolutionized the cancer therapy paradigm, both for physicians and patients. A large number of molecular targeted agents for cancer therapy are currently available for clinical use today. Many more are in making, but there are issues that remain to be resolved for the scientific as well as social community before the recommendation of their widespread use in may clinical scenarios can be done, one such issue being cost and cost effectiveness, others being resistance and lack of sustained efficacy. With the current knowledge about available targeted agents, the growing knowledge of intricate molecular pathways and unfolding of wider spectrum of molecular targets that can really matter in the disease control, calls for only the just use of the agents available now, drug companies need to make a serious attempt to reduce the cost of the agents. Research should focus on agents that show sustained responses in preclinical data. More needs to be done in laboratories and by the pharmaceutical industries, before we can truly claim to have entered a new era of targeted therapy in cancer care.

The use of bevacizumab among women with metastatic breast cancer: a survey on clinical practice and the ongoing controversy.

BACKGROUND: The US Food and Drug Administration's (FDA's) recent decision to remove the indication of bevacizumab for metastatic breast cancer (MBC) has fueled a debate in the breast cancer community. We conducted a survey to assess the perception of health care workers involved in the management of women with MBC on the FDA's decision to ascertain how it will affect practice and to determine how bevacizumab is commonly used in the community for MBC. METHODS: E-mails were sent out between September and November 2010 using a database of 3000 addresses maintained by the United Arab Emirates Cancer Congress. Individuals working for Roche or Genentech were excluded. The survey consisted of 22 questions that were divided into 3 parts addressing each participant's demographic profile, their opinion of the FDA's decision, and the typical use of bevacizumab in the community in the setting of MBC. RESULTS: A total of 564 participants were included in the final analysis, contributing to an 18.8% response rate. Of these participants, 14.6% were from the United States, 7.8% were from Canada, 31.1% were from Europe, 2.0% were from the United Arab Emirates, 11.1% were from Asia, and 33.3% were from other countries. The majority of participants believed progression-free survival to be a surrogate for overall survival, that cost played a role in the FDA's decision, and that the decision would adversely affect the future of newer drugs currently being investigated for MBC. The majority of participants indicated that they would use bevacizumab for triple receptor-negative MBC (46.5%), would use it in a first-line setting (44.7%), and would use it in combination with paclitaxel (51.9%). CONCLUSION: Our survey results highlight the discord between the opinion of community oncologists and the FDA's recent decision to withdraw the indication of bevacizumab for MBC.

Adjuvant Hormonal Therapy in Postmenopausal Women with Breast Cancer: Physician's Choices.

The choice of adjuvant hormonal therapy in postmenopausal women with hormone receptor positive breast cancer has remained a matter of controversy and debate. The variety of agents is available, with each claiming to be superior. This clinical survey was undertaken to get an impression of the physician's first choice of therapy in an attempt to find out what questions still need to be answered in the making of "standard of care." A web-based clinical survey was sent to the cancer physicians around the world, and 182 physicians responded to the survey. Most were medical oncologists in a tertiary care hospital. 36.3% preferred Anastrozole, 35.2% Tamoxifen, and 22.2% Letrozole as their first choice. Data support (67.8%) and safety concerns (30%) were given as the main reasons for the choice, 63.7% switched their therapy, and 24% had to switch because of side effects. 73.6% used 5 years of adjuvant hormonal therapy, 6.6% for 7 years, and 4.4% for 10 years. 61.5% follow their patients 3 times monthly, and 73.2% used laboratory and radiological assessment at each followup. Conclusion. Physicians show disagreement over the choice and duration of hormonal therapy in this patient population. Clinical trials leading to firm recommendations to set standards from which patients benefit the most are needed.

Incidence and impact of baseline electrolyte abnormalities in patients admitted with chemotherapy induced febrile neutropenia.

BACKGROUND: Febrile neutropenia (FN) and myelosupression remain a challenging oncologic medical emergency and dose limiting toxicity associated with chemotherapy for cancers. Various factors are known to affect the outcomes for patients diagnosed with FN. Electrolyte abnormalities have commonly been observed, but the real incidence and their impact has been only scarcely studied in literature. METHODS: This was a prospective, observational study. A total of two hundred and fifteen (215) patients admitted between January 2007 and August 2008 were included. Analysis of data was made using SPSS version16.0.Toxicity profile was graded according to CTC version 3.0. RESULTS: Almost equal number of FN was observed in both solid tumors and hematological cancers with almost equal gender distribution. Of all 83.5% patients demonstrated some electrolyte abnormalities. All grades combined, hypokalemia was seen in 48% of patients, with 51.4% having grade I, 33.3% grade III and 15.2% G IV (life threatening) hypokalemia. Hyponatremia of all grades was seen in 67.9% patients, of them 60.3% had Grade I, 33.3% grade III and 0.7% patients had grade IV hyponatremia. Hypomagnesaemia (70 patients assessed) was seen in 54.3% patient, 94.7% having grade I decline. Average length of stay for patients who received IV electrolyte replacement was 6.3 days compared to 4.9 days in those who did not. Out of 90 patients who required special care unit 75 had electrolyte abnormalities, of 15 patients who expired 13 had electrolyte abnormalities CONCLUSION: This analysis, which is first of its kind, suggests that decline in electrolyte levels is frequently observed in patients presenting with FN. These abnormalities can have independent negative impact on the outcome for such patients. Special attention should be paid to electrolyte imbalance right from the outset.

Acute lymphoblastic leukemia subsequent to temozolomide use in a 26-year-old man: a case report.

INTRODUCTION: We report the development of acute lymphoblastic leukemia in a patient in whom temozolomide was used for the treatment of a brain tumor. Unlike that of other alkylating agents, the leukemogenic potential of temozolomide is considered to be very low, and very rarely are such cases reported. CASE PRESENTATION: A 26-year-old Pakistani man who was treated for glioblastoma with temozolomide in an adjuvant setting was diagnosed to have acute lymphoblastic leukemia one year after stopping temozolomide. CONCLUSION: Temozolomide is a highly active agent, used in the management of high-grade brain neoplasms. The agent is generally regarded to be safe, with an acceptable safety profile. Very few cases of myelodysplasia associated with temozolomide use have been reported. We report here the first case of acute lymphoblastic leukemia, which developed in a young man about one year after he finished taking temozolomide. This should provide further insight into a possible toxicity profile of this alkylating agent. This finding should be of interest to physicians in general and to medical oncologists in particular.

Influence of patient's perceptions, beliefs and knowledge about cancer on treatment decision making in Pakistan.

INTRODUCTION: Cancer is a cause of major disease burden across the world and Pakistani data suggest that its incidence is increasing. Pakistan's socio-cultural history, social practices, religious beliefs and family systems differ in many ways from rest of the world. These factors make the practice of oncology a challenge. MATERIALS AND METHODS: A comprehensive questionnaire focusing on socio-cultural and religious aspects was administered to patients with a diagnosis of cancer and receiving chemotherapy at the Aga Khan University Hospital, Karachi, Pakistan. RESULTS: A total of 230 patients agreed to answer the questionnaire, with a mean age of 46 years and 63% were females. Obtaining some formal education was claimed by 87%, 75.2% had received some treatment before seeing an oncologist, including homeopathic physicians and faith healers. Of all 27 % thought that cancer is contagious, a fact observed more so in those who were illiterate, 27 % believed in some myth such as past sins, evil eye or God's curse as to be cause of their cancer, while 39.6% thought that cancer can be prevented by a regular religious activity. Some 30% thought that a meaningful life after diagnosis of cancer was not possible and 28%considered that they did not have proper information about chemotherapy. About 73% wanted to have their treatment related decision made by the treating physician. CONCLUSIONS: Patient related beliefs in myths and concerns are unique in the socio-cultural set up of Pakistan. If physicians are better aware of these factors, they may be able to handle patient related issues in a more effective way.

Demographics, pathologic patterns and long-term survival in operable colon cancers: local experience in Pakistan.

BACKGROUND: Colon cancer is a common malignancy with its incidence reportedly rising in Asian countries, including Pakistan. There are no comprehensive data available from Pakistan which focus on associations of various factors with long-term survival of colon cancer. We therefore present an analysis of findings from our centre. METHODOLOGY: In this retrospective study adult patients with colon cancer diagnosed through 2000-2003 were included. A comprehensive questionnaire was filled for each individual through review medical and pathology reports. Long term survival data was collected from contactable patients or their relatives. RESULTS: A total of 93 patients were assessed, 57 males and 36 females (M: F= 1.58: 1). Mean age of diagnosis was 54 years. Of the total, 49.5% of the patients had right sided (mortality rate 51.6%), 10.8% had transverse colon, (mortality rate 37.5%), 7.5% had descending colon (mortality rate 66.7%) and 32.2% had sigmoid colon (mortality rate 40.9%) cancers. Stage I disease on diagnosis was found in 16%, stage II in 42.7 (mortality 40 %) and stage III in 41.3% (mortality 70 %). Tumors were well differentiated in 20.2% (mortality 42.9%), moderately differentiated in 61.9% (mortality 43%) and poorly differentiated in 17.9% (mortality 70%). In 36.3% of the patients less than 12 lymph nodes were removed (mortality 55% Vs 43% in patients with <12 lymph nodes removed). Margins were free in most patients but a radial margin was reported in only 44%. Most patients had pure adenocarcinoma while a mucinous type differentiation was seen in 19.7%, 3% had signet ring morphology, 1.5% adeno-squamous carcinoma and similar number with neuroendocrine differentiation. Overall 5 year all cause mortality for all stages combined was 46.9%. CONCLUSION: Colon cancer in Pakistan commonly presents at an advanced stage, there is a male preponderance, and relatively mean younger age at presentation for males is seen. Advanced stage and lymph node involvement along with poorly differentiated pathology, signet ring or mucinous morphology, location in descending colon, positive surgical margins and removal of less than twelve lymph nodes are factors associated with poor long term survival. There is a need to reinforce information about colon cancer and larger studies from the region are needed to confirm the factors analyzed here.

Clinical presentation and outcomes of patients with biliary malignancies: the Aga Khan University experience.

BACKGROUND: Gallbladder cancer (GBC) is a common malignancy in our country; however, very limited data exist on this malignancy in Pakistan. METHODS: This is a retrospective analysis of all the admitted patients diagnosed with GBC or cholangiocarcinoma in between 1st January 1995 to 31st December 2007. RESULTS: A total of 245 patients were admitted with diagnosis of GBC or cholangiocarcinoma. Sixty seven percent were females. Right hypochondrial pain (70.6%) and jaundice (49.8%) were the commonest symptoms, followed by nausea and vomiting (11.8%), weight loss (13%), fever (18.8%), anorexia (9.8%) and ascites (3.3%). Gallstones were seen in 132 (53.9%) patients. Pathological diagnosis was confirmed in 155 (63.2%) patients, adenocarcinoma (94.8%) being the predominant type. Metastasis was seen in 204 (83.3%) patients, with liver and abdominal lymph nodes being the frequent sites of metastasis. Most of the patients presented to the surgeons (42.9%) and gastroenterologists (35.9%) at their first visit. Only 89 (26.3%) patients were referred to medical oncologists and 42 (16.7%) of the patients actually received chemotherapy. The patients who received chemotherapy cisplatin and gemcitabine demonstrated partial responses (40%). Common bile duct stricture was seen in 78 patients and stenting was successful in 73 patients. Fourteen (5.7%) patients are alive to date, one is receiving chemotherapy, and another is alive with advanced disease while 10 patients had incidental diagnosis after surgery. Of all 53.9% of patients have died and 38% are lost to follow up. CONCLUSION: Most of the patients with biliary cancers present late with advanced disease at our referral tertiary care hospital. Minority of the patients received chemotherapy and most of responses were observed with cisplatin and gemcitabine combination or capecitbine based therapy.

Old disease, new targets--part-I, solid malignancies.

Targeted agents are now an integral part of treatment regimens for some cancers. Trastuzumab is established in treatment of human epidermal receptor 2 (Her2) positive breast cancers, with improvements in both, the disease free and over all survival. Monoclonal antibody (MoAB) against vascular growth factor receptor (VEGF), bevacizumab and cetuximab a MoAB against epidermal growth factor receptor (EGFR) are establishing their role in a many cancers after making their mark in colorectal cancer. Sorafenib and sunitinib have success stories in renal carcinoma. The Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial has established sorafenib role in advanced hepatocellular carcinoma, while in gastrointestinal tumors; imatinib and sunitinib have proven role. At this point in time side effect profile of all these agents appears relatively safe however cost for developing countries remains an issue.