External auditory canal as an unusual site for metastasis of breast cancer: A case report.

Metastatic breast cancer is one of most common cause of death in women worldwide. The estimated incidence of breast cancer to be metastatic at diagnosis is 6%, with a five year survival rate of about 21%. There are three types of breast cancer recurrence: local, regional and distant metastasis mainly to the lung, liver, bone or brain. Review of literature indicate a relatively few reported cases about metastatic breast cancer to soft tissue. We present a case of metastatic breast cancer to left external auditory canal.

Breast cancer molecular subtypes in oman: correlation with age, histology, and stage distribution - analysis of 542 cases.

BACKGROUND: Breast cancer (BC) is one of the most common malignancies and a foremost health issue throughout world. BC accounted for 23.1% of cancer cases diagnosed in Oman in 2009. BC is a heterogeneous disease, and immuno-histochemical (IHC) markers are used to further classify it into distinct subtypes, which are biologically discrete and display different behaviors. IHC testing of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2); can sub-classify BC into 4 principal molecular subtypes. These subtypes are luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), basal like (BCL - ER-, PR-, HER2-), and Her2/neu (ER-, PR-, HER2+). Previous studies have shown preliminary evidence and high probabilities of molecular differences across ethnic and geographic groups which may be responsible for disparities in presentation, biological behavior, treatment response and outcome. PATIENTS AND METHODS: BC data from 2006-2010 at the National Oncology Center - The Royal Hospital, Oman were retrospectively retrieved from the electronic patient record system (Al-Shifa). Data were analyzed with respect to ER, PR, and Her-2 status and tumours were classified on molecular basis. Molecular subtypes were correlated with age, histology and treatment outcome. The results were compared with published regional and international data. RESULTS: There were 542 cases of BC accessible for evaluation. Luminal A subtype was the most common and the BCL subtype was highest among Omani females. Age was a significant factor in basal-like (63.8% younger than 50 years vs. 36.2% older than 50 years) and Her2 +ve tumours (60.9% vs. 39.1%). High grade tumors were mostly observed (41%) in basal tumors and were lowest in luminal A (19%). A higher stage at presentation (Stage III and IV) was observed in Her2+ tumours (59%), and a higher (22.4%) mortality was detected in basal like/TN tumours. CONCLUSIONS: The molecular classification and sub-typing of BC have revealed ethnic and geographic variation. Luminal A subtype is the most common among Omani female breast cancers but it is less common than in Western females. BCL subtype is highest among Omani females compared with Western females. These differences may have diagnostic, therapeutic and prognostic implications. Large scale and multi-centre studies may confirm these findings and can be translated and incorporated to pertinent management strategies. Key Words: Molecular subtypes, breast cancer, Oman, Royal Hospital.

The Dilemma of Serum Tumor Marker (STM) Flares.

UNLABELLED: Serum tumor marker (STM) estimation is often used in clinical practice in monitoring response to treatment and as a predictor of treatment failure and relapse. However, there are pitfalls in interpretation, particularly in the immediate post treatment period, when a rise in titre could be observed, the phenomenon being termed as "flare". A literature search was done to examine this phenomenon for some of the commonly used serum tumor markers in malignancies. This phenomenon has been documented with respect to AFP, beta HCG, CEA, AC 15.3, PSA, CA 19.9 and CA 125 with or without other evidence of progression. Based on this review, a practical approach is suggested so that the clinician is not misled into changing a potentially effective treatment regime. A practical approach would be to correlate serum tumor marker values with other clinical and radiological parameters, and not to rely exclusively on serum marker values to guide therapy. KEYWORDS: serum, tumor markers, flares, STM, pseudoprogression.

BRCA1 gene Molecular Alterations in Omani Breast Cancer Patients.

BACKGROUND: Breast cancer (BC) is the most common cancer reported in females in Oman and usually occurs at a relatively younger age, presents at an advanced stage and behaves aggressively. BC occurs in hereditary and sporadic forms. Although germ-line mutations in BRCA1 and BRCA2 genes are rare in sporadic cases compared with hereditary cases, molecular alterations, such as loss of heterozygosity, and CpG methylation, are common. In this study, we investigated the types of molecular alterations associated with hereditary and sporadic BRCA1-associated BC in Omani patients. METHODS: We obtained clinical data and samples from 43 sporadic BC patients. The selection of cases was made based on the following criteria: aged ≤ 40 years, or bilateral breast cancer, or estrogen and progesterone receptor negative status, and HER-2/neu negative (Triple Negative phenotype) status. Screening for molecular alterations was performed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA). RESULTS: Genomic deletions and duplication in the BRCA1 gene were identified in four female patients. Two patients carried exon 1 and 2 deletions and two showed exon 1 and 2 duplication. Screening for mutation by direct sequencing revealed three polymorphisms in exon 11. Two of these polymorphisms are nonsynonymous (rs1800704, rs799917) and one is synonymous (rs1800740). CONCLUSION: The current pilot study detected previously described gene rearrangements and polymorphisms involving the BRCA1 gene and no seemingly pathogenic missense mutations were elucidated. KEYWORDS: BRCA1, breast cancer, mutation, polymorphism, Omani, Arab.

Rapid rituximab infusion, local center experience.

UNLABELLED: Rituximab, a chimeric monoclonal antibody (MoAb) targeting CD20 has been widely used in the management of B-cell lympho-proliferative disorders.(1-3) The usual recommended schedule of regular administration over 3 to 4 hours requires considerable healthcare resources and oftentimes inconvenient for patients. Literature shows the availability of published reports proving the safety and feasibility of rapid infusion of rituximab. This study explored the safety and tolerability of rituximab infusion over a shorter total infusion time. A total of 24 patients diagnosed with CD20+ Non-Hodgkin's lymphoma and planned to receive rituximab at a dose of 375mg/m2 in combination with standard chemotherapy regimens were included in the study from January 2009 to December 2009. The administration of first rituximab dose was unaltered and given as per standard practice of 3-4 hours infusion. The second and subsequent doses were delivered over a total infusion time of only 90 minutes (20% of dose in the first 30 minutes, remaining 80% over the next 60 minutes). These patients, aged between 15 and 79 years, received a total of 152 rituximab infusions with an average of 6.33 (+/-2.37) infusions per patient. Grade 1 infusion related toxicity was reported in 5 infusions (3.2%), and there were no acute reactions or G3/4 toxicity in any infusion episode. A rapid infusion of rituximab is well tolerated, feasible and safe when administered as second and subsequent infusions in the course of therapy for those who tolerate the first dose without significant infusion related toxicity. This shortened infusion method results in a substantial reduction in resource utilization. Our institution has now adopted this as a routine practice. KEYWORDS: Rituximab, Short infusion, Oman.

Renal Cell Carcinoma metastasizing to larynx: a case report.

Renal Cell Carcinoma (RCC) is a malignant tumor occurring in 5th-6th decade of life with an increasing incidence reported in the US but stable in Europe. The metastasis of RCC to head and neck region is infrequent and very rarely seen in larynx. Very few cases of RCC metastasizing to larynx are reported in literature. We report a case of RCC in a middle aged male with metastasis to larynx, 7 years after initial diagnosis and nephrectomy. These unusual tumor metastases have unique pathobiology and route of metastasis, and there can be a long interval from initial diagnosis of primary tumor. The diagnosis of metastatic RCC in unusual locations is often not easy. Treatment options include metastasectomy, radiotherapy and systemic chemotherapy but with a poor outcome. A differential diagnosis should always be considered in metastatic head and neck tumors. The need for prompt accurate diagnosis, risk stratification at initial primary diagnosis, surveillance, and long term regular follow up is emphasized.

Prognostic significance of cyclooxygenase-2, epidermal growth factor receptor 1, and microvascular density in gastric cancer.

Gastric cancer remains a significant global health burden with poor treatment outcome. New treatment modalities that target inflammation, proliferation, and angiogenesis have been used in various cancers, including gastric cancer. We sought to study the pattern of expression of two important proteins, cyclooxygenase-2 and epidermal growth factor receptor, and their association with microvascular density, clinicopathological features, and survival in Arab Omani patients with gastric cancer. Formalin-fixed, paraffin-embedded tumors were studied by immunohistochemistry using monoclonal antibodies to cyclooxygenase-2, epidermal growth factor receptor, and CD34. The immunohistochemical results were correlated with clinicopathological features and survival. In our study population, we found a male/female ratio of 72:43, a median age of 59 years, stage III and IV incidence of 66.9%, and a median follow-up of 96 months. Positive expression rates of cyclooxygenase-2 and epidermal growth factor receptor were 89.6 and 23.5%, respectively. The median microvascular density value was 52.5. When this value was determined as the cut-off point, 50% of patients were found to have high microvascular density. Epidermal growth factor receptor over-expression correlated with high microvascular density values, advanced lymph node involvement (N3), and TNM stage presentation (III and IV). Similarly, lymph node involvement was associated with cyclooxygenase-2 over-expression and high microvascular density. Univariate analysis showed that epidermal growth factor receptor over-expression, pathological T3 and T4 disease, and overall stage III and IV disease were adverse prognostic factors. On multivariate analysis using a Cox regression model, expression of epidermal growth factor receptor, and advanced TNM stage were significant adverse prognostic factors for overall survival. Expression of epidermal growth factor receptor in Arab Omani patients with gastric cancer correlates with aggressive tumor characteristics and is an independent prognostic factor. Further clinical studies are needed to evaluate the utility of epidermal growth factor receptor immunohistochemistry as a tool for gastric cancer treatment.

A short outpatient hydration schedule for cisplatin administration.

BACKGROUND: Cisplatin remains a principal chemotherapy agent in the treatment of many solid tumours. However because of its nephrotoxicity, inpatient hydration schedules have been utilized to ensure safe administration. In May 1995, due to significant load on in-patient bed availability, the Medical Oncology Department of the Cancer Therapy Centre, Liverpool Hospital, developed a short, intravenous fluid hydration protocol to be used on an out-patient setting. METHODS: Following an initial pilot program of the abbreviated hydration regimen, a retrospective study of all adult in-patients and out-patients who received cisplatin (60-100 mg/m2) from May 1995 to August 1998 was conducted. Biochemistry was performed prior to the start of chemotherapy, and a repeat serum creatinine level was taken immediately prior to each subsequent cycle of chemotherapy, unless clinically indicated at an earlier time. The in-patient hydration protocol was 6000 ml of normal saline with 60 mmol/L KCL, and 30 mmol/L MgSO4 over 24 to 28 hours, and the out-patient hydration was 4000 ml of normal saline over 6 hours. RESULTS: A total of 145 patients were included, 57 in-patient (39%) and 88 out-patients (61%), 95 males, and 50 females. The mean age was 56 years. The maximum mean percentage change in creatinine from baseline for all cycles of chemotherapy for in-patients was 32.5% ranging from -7% to 288% (95% CI=19.9-45.11), and for outpatients 19.9% ranging from -20% to 154% (95% CI=13.47-26.39). Although the mean increase was higher in the in-patient group by 12.6%, it was not statistically significant (p=0.079). CONCLUSION: In patient's eligible for cis-platinum therapy on the basis of good performance status and normal renal function, this agent can be safely administered in the out-patient setting with an abbreviated duration, moderate volume intravenous hydration regimen.

Measurement of circulating levels of VEGF-A, -C, and -D and their receptors, VEGFR-1 and -2 in gastric adenocarcinoma.

AIM: To analyze the serum levels and prognostic significance of vascular endothelial growth factor (VEGF) -A, -C, and -D, and their receptors, VEGFR-1 and -2 in gastric adenocarcinomas. METHODS: The serum levels of VEGF family members were measured in 76 control subjects and 76 patients with gastric adenocarcinoma using an enzyme-linked immunosorbent assay (ELISA). These measurements were correlated with clinco-pathological features and survival rates. RESULTS: The serum levels of VEGF-A and its receptor, VEGFR-1, were significantly higher in patients with gastric cancer than in healthy donors (t = 2.3, P = 0.02 and t = 4.2, P < 0.0001, respectively). In contrast, the serum levels of VEGF-D were significantly higher in control subjects than in patients (t = 2.9, P = 0.004). There was no significant difference in serum levels of VEGF-C and VEGFR-2 between patients and controls. VEGF-C was associated with advanced tumor stage and presence of metastasis. VEGFR-1 was associated with metastasis, advanced overall stage, tumor differentiation and survival. VEGFR-2 levels were associated with poor tumor differentiation. There was no significant prognostic value for any of the VEGF family members or their receptors except for VEGFR-1 where high levels were associated with a poor overall survival. CONCLUSION: Serum VEGF levels vary significantly in the same cohort of patients with variable clinico-pathological features and prognostic values. The simultaneous measurement of VEGF receptors levels in sera may overcome the limitations of a single biomarker assay.

Evaluation of the prevalence, pattern and management of cancer pain in Oncology Department, The Royal Hospital, Oman.

INTRODUCTION: Pain is under-treated in all parts of the world. Moderate to severe pain is experienced by the majority of patients with advanced disease. The aim of this study is to evaluate the prevalence, pattern and pain management in Oman. METHODS: A prospective study was carried out during a 3 months period. We evaluated all admitted patients and only patients who were complaining of pain were eligible. Assessment of pain intensity and pain relief were done using measuring scales. All patients received pharmacological treatment according to WHO analgesic ladder. RESULTS: A total of 335 admissions were recorded during the study period of which 100 patients (30%) were eligible for the study, 52% of cases were males. The mean age was 45 years +/- 16.2 years and the most common tumours were GIT and breast cancer. Sixty four patients had pain but did not complain about it. Forty-five patients (45%) had moderate pain but they did not routinely complain about it. The mean hospital stay was 3.5 days and the range 1- 10 days. CONCLUSIONS: Most cancer patients deny pain for various reasons. Thorough history and repeated pain assessment are very important. Following the WHO analgesic ladder is simple and effective.

The prognostic determinants of gastric cancer treatment outcome in Omani Arab patients.

BACKGROUND: Gastric cancer is the most common cancer in Oman and a leading cause of cancer death. The variation in survival rates between countries and ethnic groups has been attributed to early detection policies, differences in clinicopathological features, treatment approaches, and biological characteristics. There were no previous reports on gastric cancer from Oman and very few studies on Asian Arabs. AIM: To evaluate the impact of clinicopathological and treatment variables on the survival prospects of Omani Arab patients diagnosed with gastric cancer. METHODS: The medical records of 339 Omani Arab patients diagnosed with invasive gastric adenocarcinoma during the period 1993-2004 were retrospectively reviewed. The relative importance of clinicopathological features and surgical and medical treatments were assessed using univariate and multivariate analyses. RESULTS: Most patients had distal ulcerating-type gastric cancer and presented at advanced stages. The median survival time for the entire cohort was 12 months (95% CI 9.7-14.4) with a 5-year overall survival rate of 16.7%. On univariate analysis of 237 patients who underwent surgical resection, the following positive prognostic factors emerged as significant: early overall TNM stage, early T stage, negative lymph nodes, tumor size <5 cm, ulcerating macroscopic appearance, and curative surgical attempt. The independent prognostic factors on multivariate analysis were T stage and lymph node involvement. CONCLUSION: The overall T and N stages are the most important determining factor for survival in Omani Arab patients. More efforts need to be made for the early detection of gastric cancer in developing countries such as Oman, while continuing to employ the standard surgical and medical treatments.

The outcome of treatment of breast cancer in a developing country--Oman.

The aim of the present study was to evaluate the outcome of treatment of breast cancer in Oman with an analysis of clinico-pathological features, treatment modalities utilized, and prognostic factors. One hundred fifty-two breast cancer patients diagnosed between January 1996 and June 2002 were evaluated retrospectively. Their mean age was 48.5 (S.D. +/- 10.8) years, and 48% of the female patients were premenopausal. The mean tumor size according to pathology was 4.6 (S.D. 3.29)cm, and 34.9% and 15.8% of patients had stage III or IV disease, respectively. Only 26.3% of the patients had breast-conserving surgery, and neoadjuvant chemotherapy was underutilized. The overall 5-year relapse-free survival (RFS) and overall (OS) survival rates were 62% and 64%, respectively. On multivariate analysis, axillary lymph node involvement and tumor differentiation were predictive of RFS and OS, respectively. Thus, breast cancer patients in Oman present with advanced stages of the disease at younger ages than their counterparts in the West and have lower survival rates. Increasing awareness and the introduction of screening programs and of a multidisciplinary approach are essential in Oman and other developing countries to improve the outcome of treatment.

Primary central nervous system lymphoma and subcutaneous metastases.

Primary central nervous system lymphoma (PCNSL) is a rare disease with a poor prognosis. It usually remains confined to central nervous system (CNS). Reports of metastases outside of the CNS are rare. We report a patient with well-documented PCNSL who responded to treatment, but subsequently developed a histologically confirmed subcutaneous metastasis to the left leg without local failure.