National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma.

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

A prospective, real-world, multinational study of febrile neutropenia (FN) occurrence in oncology patients receiving chemotherapy with intermediate risk of FN: a MASCC Neutropenia, Infection, and Myelosuppression Study Group initiative.

PURPOSE: Limited knowledge is available on the incidence of febrile neutropenia (FN) in intermediate-risk patients and the rationale for use of granulocyte colony-stimulating factor (G-CSF) in these patients. We aimed to estimate the rate at which patients associated with intermediate risk (10-20%) of FN would develop ≥ 1 episode of FN with a commonly used chemotherapy regimen in clinical practice. METHODS: This prospective, real-world, observational, multinational, multicenter study (December 2016-October 2019) recruited patients with solid tumors or Hodgkin's/non-Hodgkin's lymphoma. Patients receiving chemotherapy with intermediate risk of FN, but not G-CSF as primary prophylaxis were included and observed for the duration of the chemotherapy (≤ 6 cycles and ≤ 30 days after the last chemotherapy administration). RESULTS: In total, 364 patients (median age, 56 years) with 1601 cycles of chemotherapy were included in the analysis. The incidence of FN was 5% in cycle 1, 3% in cycles 2-3, and 1% in cycles 4-6. The rate of patients with ≥ 1 episode of FN was 9%, and 59% of FN events were reported during cycle 1. The rate of grade 4 neutropenia in cycle 1 was 11%, and 15% of patients experienced ≥ 1 episode of grade 4 neutropenia. CONCLUSIONS: Overall, the incidence of FN was low, with a high incidence in cycle 1 and a decrease in the subsequent cycles. These results provide the real FN risk for common chemotherapy regimens in patients generally excluded from clinical trials. Prophylactic G-CSF in intermediate-risk patients could be considered as per clinician's judgement.

Clinical and psychosocial factors associated with quality of life in patients with head and neck cancer: an analytical cross-sectional study from a lower-middle-income country.

INTRODUCTION: The disease course of head and neck (H&N) cancer can severely impair patients' quality of life (QoL). In Pakistan, a South Asian lower-middle-income country (LMIC), psychosocial factors may impact QoL. We aimed to assess QoL and associated factors amongst patients with H&N cancer in Pakistan. METHODS: An analytical cross-sectional study was conducted amongst adult (≥ 18 years) patients with H&N cancer who were ≥ 4 weeks post-initiation of treatment. The survey assessed QoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaires), anxiety and depression (Hospital Anxiety and Depression Scale), and social support (Enriched Social Support Instrument). Multivariable linear regression was performed for analysis. RESULTS: A total of 250 patients (mean age: 51.6 years) were included. The majority of patients were married (87%) and living with multigenerational/extended family households (53%). On multivariable linear regression, ongoing cancer treatment (beta coefficient: -13.93), having a tracheostomy (-10.02), and receiving adjuvant chemoradiotherapy (-8.17) were significantly associated with poorer global QoL. Additionally, poorer QoL was associated with depression (-24.37) and anxiety (-13.34). However, having more household family members was associated with better global QoL (0.34). CONCLUSION: The QoL of patients with H&N cancer in Pakistan is affected by both the nature of cancer treatment as well as sociocultural factors such the number of household family members. Given that poorer QoL is associated with worse mental health outcomes, there is a need to develop and implement psychosocial interventions to improve the QoL of patients with H&N cancer in Pakistan, particularly during active treatment.

Psychosocial factors influencing quality of life in patients with primary brain tumors in Pakistan: an analytical cross-sectional study.

OBJECTIVE: Despite quality of life (QoL) being recognized as an important outcome in neuro-oncology, there is a lack of research from Pakistan where sociocultural differences may influence QoL. This study aimed to measure the QoL in patients with primary brain tumors (PBTs) and assess its association with mental health outcomes and social support. RESULTS: Our study included a total of 250 patients, with a median age of 42 years (range 33-54 years). The commonest brain tumors were glioma (46.8%) and meningioma (21.2). The mean global QoL of the sample was 75.73 ± 14.9. The majority of patients had high social support (97.6%) and were not depressed (90%) or anxious (91.6%). On multivariable linear regression, global QoL was inversely associated with no or low income (beta coefficients: -8.75 to -11.84), having hypertension (-5.53), currently using a urine catheter (-13.55), having low social support (-28.16) suffering from mild (-15.31) or symptomatic (-23.84) depression, or mild anxiety (-13.22).

Mean level of pretreatment neutrophil to lymphocyte ratio in patients with squamous cell carcinoma of the head and neck-Cross-sectional study.

Background: Squamous cell carcinoma of the head and neck have been characterized using various prognostic parameters. These include advanced age, lifestyle habits such as smoking, higher tumor stage at presentation & presence of metastasis. Many patients are diagnosed with head and neck cancers annually in Pakistan, but limited data is available for the prognosis of these patients. This study aims to investigate a new biomarker by estimating the mean level of pretreatment neutrophil to lymphocyte ratio (NLR) in patients with Squamous cell carcinoma of the head & neck. Methods: We conducted a cross-sectional study using non-probability consecutive sampling techniques for 222 biopsy-proven cases of head & neck squamous cell carcinoma. Clinical & pathological variables were analyzed, including the patient's profile and tumor characteristics. The NLR of each patient before treatment was calculated using the absolute neutrophil count divided by the absolute lymphocyte count in preoperative blood samples. An independent sample t-test was used to assess the mean difference. A p-value less than or equal to 0.05 was taken as statistically significant. Results: Of 222 patients, a male predominance was seen in the entire cohort. A median pretreatment NLR of 3.19 (2.47-4.97) was identified, and patients were classified into high and low NLRs based on this value. Data analysis revealed a statistically significant increase in NLR among patients with nodal metastasis. In addition, patients with NLR above the median cutoff value of 3.19 demonstrated that there was a significant increase in NLR values with high tumor (T) and nodal (N) classifications with a p-value of 0.001 and 0.003, respectively. Conclusion: Pretreatment neutrophil to lymphocyte ratio may be associated with increased nodal involvement. It may serve as a useful prognostic predictor for patients with squamous cell carcinomas of the head and neck. Identifying high-risk patients in the pretreatment phase with the help of such biomarkers will also facilitate early inclusion in clinical trials.

Factors affecting well-being in brain tumor patients: An LMIC perspective.

Introduction: Brain tumor is a devastating and often fatal diagnosis; quality of life and patient well-being are important goals of treatment. This study addresses the gap in culture-specific literature exploring the needs and coping strategies of brain tumor patients within an LMIC setting. Methodology: A qualitative approach was undertaken using an exploratory descriptive study design. In-depth interviews were conducted to capture the perspective of 250 brain tumor patients at a private tertiary center followed by extensive content analysis to identify major themes and sub-themes across responses. Results: The analysis identified three major themes: (i) Factors affecting the lives of brain tumor survivors (BTSs) and their impact (ii) What works to improve QoL according to the survivors' perspectives, and (iii) Coping tactics & fostering healthy relationships. The need for financial navigation strategies improved patient-physician relationships, and reinforcing positive coping strategies were emphasized. Conclusion: In our population, family support and spiritual connection played an important role in helping patients mitigate the psychosocial burden of illness. However, financial concerns were pervasive and need to be addressed for better overall well-being.

Cardiac sarcoma: A rare case of primary cardiac sarcoma.

INTRODUCTION AND IMPORTANCE: Primary cardiac sarcoma is a rare malignancy with a poor prognosis because of diagnostic delay, therapeutic difficulties, and high metastatic potential. The therapeutic approach includes surgery, chemotherapy, and radiation therapy, alone or in combination. However, there is a lack of evidence to guide the treatment. CASE PRESENTATION: We present a case of primary cardiac sarcoma. Our patient was presented in the department of emergency medicine (ED) in our institute with shortness of breath on exertion associated with orthopnea. Based on the history and cardiovascular examination, he underwent an echocardiogram, which revealed a sizeable echogenic density in the right ventricular outflow tract. He underwent surgical resection of the cardiac mass via median sternotomy and total cardiopulmonary bypass approach. The patient was eventually diagnosed with primary cardiac sarcoma, confirmed by tissue biopsy after surgical intervention. CLINICAL DISCUSSION: Through this report, we highlight the rarity of primary cardiac sarcomas, the importance of multidisciplinary tumor board (MDT) discussion and provide evidence of surgical excision being the treatment of choice, followed by systemic chemotherapy in selected cases. CONCLUSION: Cardiac sarcoma is a rare but highly malignant tumor with a poor prognosis. However, early diagnosis and surgical resection of a primary cardiac sarcoma can significantly increase the patient's survival and quality of life. Therefore, physicians should keep a high suspicion of a patient with clinical features suggestive of cardiac sarcoma, and echocardiography should be the diagnostic modality of choice in such patients.

Psychometric properties of the Urdu version of the EORTC QLQ-H&N35 (European organization for research and treatment of cancer head and neck module) quality of life tool.

BACKGROUND: We translated and validated the Urdu version of the European Organization for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire's Head and Neck (H&N) Cancer Module (EORTC QLQ-H&N35) and assessed its convergent and discriminant validity by examining correlations of QoL with depression, anxiety, and resilience. METHODS: We translated the EORTC QLQ-H&N35 according to EORTC instructions. Patients at a tertiary care hospital in Pakistan completed a survey consisting of Urdu versions of EORTC QLQ-C30 (core QoL tool), QLQ-H&N35, Hospital Anxiety and Depression Scale, and Wagnild and Young Resilience Scale (RS-14). Content validity, convergent validity, discriminant validity, and reliability (using Cronbach's alpha) of the EORTC QLQ-H&N35 were assessed. RESULTS: Our sample comprised 250 patients with H&N cancer, most commonly oral (82%). The Urdu translations were comprehensible for all patients. The Cronbach alpha for QLQ-H&N35 multi-item domains ranged from 0.75 to 0.98 (acceptable to excellent), barring "Senses Problems", which was less than the generally acceptable level (0.50). The patient-reported content validity index (CVI) scores for relevance and clarity of the Urdu version of the QLQ-H&N35 were 0.93 and 0.92, respectively (both excellent). Our results revealed weak bidirectional correlations of the QLQ-H&N35 with resilience, depression, and anxiety, showing good discriminant validity. A weak-to-moderate but significant negative correlation (r: - 0.185 to - 0.613; p < 0.01) was seen between the QLQ-H&N35 and the global QoL measure of the QLQ-30. CONCLUSION: Our Urdu translation of the EORTC QLQ-H&N35 demonstrated validity comparable to previous studies, with good discriminant construct validity when measured against resilience, depression, and anxiety. An issue of concern is the poor internal consistency of the "Senses Problems" domain. Nevertheless, the Urdu translation produced in this study serves as a valid and reliable measure to measure QoL in H&N cancer in clinical or research settings in Pakistan.

Spectrum of germline pathogenic variants using a targeted next generation sequencing panel and genotype-phenotype correlations in patients with suspected hereditary breast cancer at an academic medical centre in Pakistan.

BACKGROUND: Breast cancer is the most common malignancy in women, affecting over 1.5 million women every year, which accounts for the highest number of cancer-related deaths in women globally. Hereditary breast cancer (HBC), an important subset of breast cancer, accounts for 5-10% of total cases. However, in Low Middle-Income Countries (LMICs), the population-specific risk of HBC in different ethnicities and the correlation with certain clinical characteristics remain unexplored. METHODS: Retrospective chart review of patients who visited the HBC clinic and proceeded with multi-gene panel testing from May 2017 to April 2020. Descriptive and inferential statistics were used to analyze clinical characteristics of patients. Fisher's exact, Pearson's chi-squared tests and Logistic regression analysis were used for categorical variables and Wilcoxon rank-sum test were used for quantitative variables. For comparison between two independent groups, Mann-Whitney test was performed. Results were considered significant at a p value of < 0.05. RESULTS: Out of 273 patients, 22% tested positive, 37% had a VUS and 41% had a negative genetic test result. Fifty-five percent of the positive patients had pathogenic variants in either BRCA1 or BRCA2, while the remaining positive results were attributed to other genes. Patients with a positive result had a younger age at diagnosis compared to those having a VUS and a negative result; median age 37.5 years, IQR (Interquartile range) (31.5-48). Additionally, patients with triple negative breast cancer (TNBC) were almost 3 times more likely to have a positive result (OR = 2.79, CI = 1.42-5.48 p = 0.003). Of all patients with positive results, 25% of patients had a negative family history of breast and/or related cancers. CONCLUSIONS: In our HBC clinic, we observed that our rate of positive results is comparable, yet at the higher end of the range which is reported in other populations. The importance of expanded, multi-gene panel testing is highlighted by the fact that almost half of the patients had pathogenic or likely pathogenic variants in genes other than BRCA1/2, and that our test positivity rate would have only been 12.8% if only BRCA1/2 testing was done. As the database expands and protocol-driven referrals are made across the country, our insight about the genetic architecture of HBC in our population will continue to increase.

Translation and validation of the Urdu version of the European organization for research and treatment of cancer core quality of life questionnaire (EORTC QLQ-C30) and brain module (QLQ-BN20) in primary brain tumor patients.

INTRODUCTION: This study translated and validated the Urdu version of the European Organization for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) and Brain Module (QLQ-BN20) amongst patients with primary brain tumors (PBT) in Pakistan, and assessed the correlation of QoL with resilience, depression, and anxiety. METHODS: Translation of the EORTC QLQ-C30 and QLQ-BN20 was performed as per EORTC guidelines. A survey comprising of Urdu translations of EORTC QLQ-C30, QLQ-BN20, Wagnild and Young Resilience Scale (RS-14) and Hospital Anxiety and Depression Scale was administered to patients with PBT at a tertiary care hospital in Pakistan. Reliability (via Cronbach alpha), content validity index (CVI) scores, construct validity, and inter-scale correlations were assessed. RESULTS: Our sample consisted of 250 patients with PBT, most commonly glioma (46.8%) and meningioma (21.2%). All patients were able to understand the Urdu translations. The Cronbach alphas for the QLQ-C30 and the QLQ-BN20 were 0.860 and 0.880, respectively. The CVI scores for clarity and relevance were high for both the EORTC QLQ-C30 (0.98 and 0.96, respectively) and the QLQ-BN20 tool (0.81 and 0.95, respectively). The global QoL domain (EORTC QLQ-C30) showed significant positive correlations with resilience (r = 0.422), and significant negative correlations with depression (r = - 0.541) and anxiety (r = - 0.502). Strong inter-scale correlations were observed between physical functioning and insomnia (r = - 0.690) and role functioning and insomnia (r = - 0.641). CONCLUSION: Our study confirms the Urdu versions of the EORTC QLQ-C30 and QLQ-BN20 as valid clinical tools for the measurement of QoL in primary brain tumors patients within the cultural and socioeconomic context of Pakistan.

Quality of life (QoL) is an important facet of well-being for patients with primary brain tumors (PBTs), as these individuals face significant distress during the course of their illness and treatment. It is important to have valid and reliable tools to accurately measure the QoL of patients with PBTs. The EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) and its brain tumor-specific module EORTC QLQ-BN20 (EORTC QLQ-Brain Neoplasms 20) are exactly that.However, the use of the EORTC QLQ-C30 and QLQ-BN20 is limited in Pakistan, where the national language is Urdu, and the majority of patients are of low socioeconomic backgrounds. Since no Urdu translations of the EORTC QLQ-C30 and QLQ-BN20 exist, we aimed to translate and validate these tools to enable their applicability in Pakistan.The Urdu versions of the EORTC QLQ-C30 and QLQ-BN20 demonstrated good validity amongst patients with PBTs. Thus, our study confirms the EORTC QLQ-C30 and QLQ-BN20 as valuable clinical tools for the measurement of QoL in primary brain tumors patients within the linguistic, cultural and socioeconomic context of Pakistan.

Resilience and its associated factors in head and neck cancer patients in Pakistan: an analytical cross-sectional study.

INTRODUCTION: The study aimed to assess resilience and its associated factors in head and neck cancer patients, post-treatment in a low middle income country (LMIC) such as Pakistan. METHODS: An analytical cross-sectional study was conducted from November 2019 to May 2020 among head and neck cancer patients aged at least 18 years at the largest private tertiary care hospital, in Karachi, Pakistan. Information regarding their resilience scores was collected through Wagnild and Young's Resilience scale that comprises of 14 items (RS-14). Moreover, depression and anxiety were also assessed via Hospital Anxiety and Depression Scale (HADS) and social support was assessed by Enriched Social Support Instrument (ESSI). RESULTS: The data was analyzed by linear regression modeling. Unadjusted and adjusted beta coefficients with 95% CI were reported. A total of 250 head and neck cancer patients were recruited, 79% of them were males. Mean age of the patients was 51.59 years with 93% having high social support and only 8% having severe depression and 3% having severe anxiety. After adjusting for the covariates in multivariable analysis resilience was associated with severe depression (- 17[- 20.98,-12.93]) or borderline depression (- 4[- 8.41,-0.39]), severe anxiety (- 11 [- 17.88,-4.18]), low social support (- 6[- 9.62,-1.71]), having family members of > 6 in the household (- 2[- 4.31,-0.29), smokeless tobacco users post- treatment (10[5.79, 14.45]), and those who underwent tracheotomy (- 4[- 7.67,-0.21]). There was a significant interaction between education and role in the family (decision maker). CONCLUSION: In Pakistan, a South Asian LMIC, collectivist culture prevails, family ties are greatly promoted thus resilience and social support is highly prevalent in head and neck cancer patients resulting in lower prevalence of depression and anxiety. Our study highlights that higher resilience is prevalent among small families less than six members, as the welfare of the individual is prioritized over multiple needs of the family. Formal Education and role in household/decision making power are effect modifiers in our study, demonstrating its protective effect on the mental health of head and neck cancer patients. High resilience scores were reported among current smokeless tobacco users as compared to quitters post treatment. Resilience-building interventions should be formulated to aid head and neck cancer patients to cope with the disease and its sequel.

A multidisciplinary approach to triage patients with breast disease during the COVID-19 pandemic: Experience from a tertiary care center in the developing world.

BACKGROUND: The COVID-19 pandemic has created a need to prioritize care because of limitation of resources. Owing to the heterogeneity and high prevalence of breast cancers, the need to prioritize care in this vulnerable population is essential. While various medical societies have published recommendations to manage breast disease during the COVID-19 pandemic, most are focused on the Western world and do not necessarily address the challenges of a resource-limited setting. AIM: In this article, we describe our institutional approach for prioritizing care for patients presenting with breast disease. METHODS AND RESULTS: The breast disease management guidelines were developed and approved with the expertise of the Multidisciplinary Breast Program Leadership Committee (BPLC) of the Aga Khan University, Karachi, Pakistan. These guidelines were inspired, adapted, and modified keeping in view the needs of our resource-limited healthcare system. These recommendations are also congruent with the ethical guidelines developed by the Center of Biomedical Ethics and Culture (CBEC) at the Sindh Institute of Urology and Transplantation (SIUT), Karachi. Our institutional recommendations outline a framework to triage patients based on the urgency of care, scheduling conflicts, and tumor board recommendations, optimizing healthcare workers' schedules, operating room reallocation, and protocols. We also describe the "Virtual Blended Clinics", a resource-friendly means of conducting virtual clinics and a comprehensive plan for transitioning back into the post-COVID routine. CONCLUSION: Our institutional experience may be considered as a guide during the COVID-19 pandemic, particularly for triaging care in a resource-limited setting; however, these are not meant to be universally applicable, and individual cases must be tailored based on physicians' clinical judgment to provide the best quality care.

Depression among adult patients with primary brain tumour: a cross-sectional study of risk factors in a low-middle-income country.

OBJECTIVE: The prevalence of depression among patients with primary brain tumour ranges from 15% to 40% globally. Several individual and clinical factors contribute to the development of depression. However, their association with depression in Pakistani setting has not yet been assessed. Thus, we aim to study the factors associated with depression among adult patients with primary brain tumour at a tertiary care hospital in Karachi, Pakistan. STUDY DESIGN: A prospective cross-sectional study. SETTING: This study was conducted at a tertiary care hospital of Karachi, Pakistan. PARTICIPANTS: This study included 132 patients with confirmed diagnosis of primary brain tumour (initially diagnosed on MRI of the brain with contrast and later confirmed on histology of surgical specimen) in various stages of treatment. PRIMARY OUTCOME: The primary outcome of this study was to assess depression and its associated factors among adult patients with primary brain tumour. Depression was assessed using a validated screening tool Patient Health Questionnaire-9 (PHQ-9). Scores of 10-27 on PHQ-9 were indicative of screen positive for depressive symptoms. A set of the structured pre-tested questions was used to evaluate patient-related, tumor-related and treatment-related factors. RESULTS: Fifty-one (39%, CI: 33.33-46.94) patients in our study screened positive for depressive symptoms on PHQ-9. There was a significant association between depressive symptoms and Karnofsky Performance Scores (KPS) (prevalence ratio: 3.25 and CI: 1.87-5.62) after controlling covariates. Propensity scores predicted a positive association between KPS (functional status) and unemployment, treatment stage, and tumour recurrence. Tumor-related and treatment-related factors including tumour grade, location, type and hemispheric lateralisation were found insignificant. CONCLUSION: Depression is common in patients with primary brain tumour. Impaired functional status has a direct impact on depression in these patients. Incorporating the psychosocial domain earlier in the course of treatment needs to be considered for better neuro-oncology management of patients with primary brain tumour.

Resilience and quality of life (QoL) of head and neck cancer and brain tumour survivors in Pakistan: an analytical cross-sectional study protocol.

BACKGROUND: Cancer is a devastating disease and has detrimental effects on the quality of life (QoL) of cancer survivors and interferes with their treatment compliance. The aim of the study is to assess resilience and QoL among cancer survivors and to evaluate the important factors affecting their resilience and QoL, with respect to the Pakistani cultural context. METHOD AND ANALYSIS: A cross-sectional study will be conducted at a tertiary care hospital in Karachi, Pakistan. A minimum sample size of 250 head and neck cancers and 250 brain tumour survivors with 10% inflation for non-response rate will be required. The SD of QoL and resilience will range from 16.5 to 40.8 for head and neck cancer, and 12.7 to 34.1 for brain tumour, at 5% level of significance, with 2.5 precision. QoL will be assessed by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-H&N35 and EORTC QLQ-BN20 and resilience will be evaluated by Wagnild and Young's 14-item scale. Mean±SD will be reported for resilience and QoL scores. Unadjusted and adjusted ß-coefficients, with 95% CI, will be reported by using multiple linear regression analysis. Correlation analysis will also be performed using Pearson or Spearman rank correlation coefficients. A p value of <0.05 will be considered significant. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Aga Khan University Pakistan's Ethical Review Committee. Written informed consent will be taken from the participants by trained research assistants. A trained psychologist will provide on-spot counselling to the participants and those identified with severe depression will be referred to a psychiatrist. The study materials will be kept under lock and key and the electronic data base will be password protected and will only be accessed by the research team. The study findings will be disseminated through publications conferences and workshops and research briefs. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov registry (NCT03466762).

Outcomes of High Risk Patients with Febrile Neutropenia at a Tertiary Care Center

Fever during chemotherapy-induced neutropenia continues to be a major cause of morbidity and mortality in cancer patients. Mortality depends on the duration and degree of neutropenia, bacteremia, sepsis, performance status, comorbidities and other parameters. The highest mortality rates in cancer patients hospitalized with febrile neutropenia (FN) are observed in those with documented infection. The objectives of the study were to present available tools for risk assessment, to review pathogens causing infections in adult FN patients and to assess outcomes. Methods: This cross sectional study was conducted on adult culture positive FN patients admitted to the Hematology/Oncology service at the Aga Khan University Hospital, Karachi, Pakistan from 1st January 2009 to 31st December 2012. Highrisk criteria were defined as profound neutropenia, short latency from a previous chemotherapy cycle, sepsis or clinically documented infection at presentation, severe co-morbidity and a performance status greater than or equal to 3. All types of organisms in blood culture and the outcomes of the patients were recorded on Proforma. Results: A total of 156 patients with culture-positive febrile neutropenia were identified during the study period. The mean age was 47 years with a slight male predominance of 54%. One hundred and sixteen patients fulfilled the criteria for the high risk group. Fifty two percent had a single high risk factor and 40 % had two. All patients harbored either single or multiple bacterial organisms including gram positive, gram negative or both types. Some 34% of patients had gram positive bacteremia, 57 % had gram negative and 9 % were infected with both. Among 73 gram positive cultures 44 % were Staphylococcus species and among 123 gram negative cultures 43 % were E. coli. One hundred and fifteen patients recovered uneventfully and could be discharged. Thirty two patients in the high risk and 9 in the low risk groups deceased with an overall mortality of 26 %. The mean hospital stays of patients with solid tumors and hematological malignancies were 7.58 and 15.0 days, respectively. Mortality was higher in the latter group, and also in high risk patients with both gram positive and negative bacteremia. Conclusion: We emphasize the importance of risk stratification and continuous surveillance of the spectrum of locally prevalent pathogens and their susceptibility patterns for formulation of therapeutic regimens for febrile neutropenic patients.

Knowledge, attitude and perceptions of Muslim cancer patients regarding cancer treatment during Ramadan: Results from a tertiary care hospital Karachi.

OBJECTIVE: To assess the knowledge and attitude of Muslim cancer patients regarding cancer treatment during Ramadan. METHODS: This cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from July to August 2015, and comprised cancer patients. .Adult Muslim cancer patients receiving active oncological treatment or on surveillance were included. Patients on only supportive treatment were excluded. SPSS 19 was used for data analysis. RESULTS: Of the 265 patients, 87(32.8%) were males and 178(67.2%) were females. The overall mean age was 49±13.87 years. Besides, 184(70.9%) patients belonged to the middle class. Breast cancer was the most common cancer 106(40.6%). Overall, 153(57.9%) patients had stage II disease. Further, 201(80%) patients had 0-1 performance status. Moreover, 180(72%) patients were receiving different forms of chemotherapeutic agents. It was found that 113(54.3%) patients sought advice regarding fasting. Most of the patients who observed fast, i.e. 214(81%), had an early stage disease and 19(7.1%) were on hormonal therapy. Patients who did not fast mostly attributed this to fatigue 69(26.3%). Conclusion: Only half of the patients sought advice on fasting and those having early disease more. CONCLUSIONS: Only half of the patients sought advice on fasting and those having early disease more frequently observed fast.

Incidence of Venous Thromboembolism in cancer patients treated with Cisplatin based chemotherapy - a cohort study.

BACKGROUND: Cancer related thrombosis not only increases morbidity and mortality but also poses a significant financial burden on health care system. Risk of venous thromboembolism (VTE) in these patients substantially increases with the addition of chemotherapy. Lately, cisplatin has been implicated as an independent factor. There is little data estimating the risk of venous thromboembolism in patients receiving cisplatin based chemotherapy when compared to other chemotherapeutic agents. METHODS: Patients who had received chemotherapy between November 2010 and October 2012 were retrospectively identified from a single institute cancer registry. 200 patients who had received cisplatin based chemotherapy were identified as the exposed group while 200 patients who had received non-Cisplatin based regimens were identified as the non-exposed group. Patients were followed for development of VTE throughout the entire duration of therapy and one month thereafter. Cox proportional hazard model was used to compute relative risks with 95% confidence intervals. RESULTS: The baseline characteristics were similar in the two groups. Mean age for the entire cohort was 55.4 ± 10.7 years and male to female ratio was almost 1:1. On univariate analysis, cisplatin based chemotherapy, presence of central venous catheter, female gender, poor performance status, high risk stratification according to the Khorana model and use of granulocyte colony stimulating factor were all significantly associated with the development of VTE. The crude relative risk for the incidence of VTE in cisplatin group was 2.8 (95% CI, 1.4 - 4.2) times compared to the non-Cisplatin group. When the relative risk was adjusted for the above variables in multivariable analysis, it increased to 3.3 (95% CI, 1.6 - 6.8) compared to the control group. CONCLUSION: A high incidence of VTE in patients receiving cisplatin based chemotherapy was demonstrated in this study. Prospective studies are warranted to establish this observation with certainty and to explore the possible use of thromboprophylaxis in patients receiving cisplatin based chemotherapeutic regimens.

Metastatic Pancreatic Carcinoma and Experience with FOLFIRINOX - a Cross Sectional Analysis From a Developing Country.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer related death with median survival ranging from 3 to 6 months for metastatic disease. Palliative chemotherapy has been the backbone of treatment in advanced stage and has evolved over time. Data pertaining to the disease are scarce from our part of the world where treatment poses a significant challenge due to lack of resources. MATERIALS AND METHODS: A retrospective chart review was performed for all patients presenting with stage IV pancreatic carcinoma at a tertiary care hospital in Karachi, Pakistan between January 2008 and December 2012. Data were collected using a pre-designed, coded questionnaire looking at patient characteristics, treatment given and outcome. RESULTS: 101 patients were found to be eligible. Mean age was 56.7 ± 12.8 years, the male to female ratio was 2:1 and most patients had a good performance status. More than half of the tumors were located in the head (57%, n=58) and almost all were adenocarcinomas (95%, n=96). Some 58% (n=59) received first line chemotherapy of which 49% (n=29) received gemcitabine-based regimens and 39% (n=23) received FOLFIRINOX. The median progression free survival for gemcitabine based treatment was 2.9 months (IQR=1.6-5.6) as opposed to 7.3 months (IQR=4.5-9.2) for FOLFIRINOX (P=0.02). Median overall survival was 4.9 months (IQR=2.3-9.5) for first line gemcitabine based treatment and 10.5 months (IQR=7.0-13.2) for first line FOLFIRINOX therapy (P=0.002). Patients on FOLFIRINOX had better survival across all subgroups. Inpatient admissions and dose reductions were more frequent with FOLFIRINOX but the difference between the two regimens was not statistically significant. FOLFIRINOX could be successfully administered as outpatient therapy to a number of patients. CONCLUSIONS: FOLFIRINOX remains a suitable first line option in patients with metastatic pancreatic cancer with good performance status even in a resource-poor country where diagnostic and supportive care facilities may be less than optimal and cost is a limitation.