Proportion of cancer in a Middle eastern country attributable to established risk factors.

BACKGROUND: Providing an estimate of the percentage of cancer in Lebanon by 2018 that is due to the exposure to risk factors in 2008. Factors include: smoking, body mass index (BMI), physical inactivity, dietary factors, alcohol consumption, infections, and air pollution in adults. METHOD: Population Attributable Fraction (PAF) was calculated using the proportion of the population exposed and relative risks for each risk factor from meta-analyses. The PAF estimates the proportion of cases in which exposure may have played a causal role. RESULTS: Smoking caused most cancer cases, and it will further add a total of 1800 new cases by 2018. Among many other cancers, lung cancer had the largest proportion attributable of around 75%. BMI is expected to increase colorectal, liver and gastric cardia carcinoma specifically in males. High physical activity has a an average of 15% protection rate on cancer on colorectal cancer. Minimal adherence to Mediterranean diet will affect gastric cancer incidence by 7%. Cases of oropharyngeal and esophageal cancer will be the result of alcohol consumption mainly in males. H.Pylori infection is expected to result in half of the gastric cases by 2018. The high exposure to air pollution is expected to contribute by 13% to lung cancer cases in 2018. CONCLUSION: The highest benefits can be achieved by controlling tobacco smoking. Interrelated and small changes in weight, physical activity and healthy diet with limited alcohol consumption can protect against several GI cancers in the long run. These results can be used to determine public health interventions that target important risk factors in the general population.

Lymph node ratio is an independent prognostic factor after resection of periampullary malignancies: data from a tertiary referral center in the middle East.

OBJECTIVE: The prognostic impact of nodal involvement in resected pancreatic carcinoma and biliary malignancy has been relatively well established. It has been suggested that lymph node ratio (LNR) may be a more informative way of stratifying patients with node positive disease. Our retrospective review aimed to investigate the significance of such variables and test for independent prognostic factors for survival. METHODS: One hundred eighty-three pancreatic and periampullary malignancy cases were registered at the American University of Beirut Medical Center from 1990 to 2004. Of those, 80 had complete data on lymph node status. We analyzed the impact of the number of lymph nodes resected, the number of positive lymph nodes retrieved and LNR using Kaplan-Meier and Cox proportional hazard models. The measured outcome in the KM model was the survival probability at 1, 3, and 5 years while the Cox model was used to measure the hazard ratio (HR) of the previously identified predictors on survival. RESULTS: For the 80 patients included in this analysis, overall survival rates were 65% (54 to 78), 32% (18 to 47), and 21% (8 to 34) were alive at 1, 3, and 5 years, respectively. The median number of resected lymph nodes was 9. In the node positive patients, those who had >12 nodes examined were found to have a significantly better survival (HR=0.24; P=0.013). On multivariate analysis, our model showed the following factors to be significant: age 60 years or older (HR=5.92; P=0.018), poorly differentiated tumors (HR=21.87; P=0.018), number of lymph nodes examined <12 LN (HR=6.77; P=0.022), 3 or more metastatic LN (HR=7.21; P=0.028), and LNR≥0.2 (HR=7.12; P=0.007). CONCLUSIONS: After pancreaticodudonectomy for adenocarcinoma of the pancreas and biliary malignancies, ratio-based lymph node staging is an independent and powerful prognostic factor.

A phase II study of lipoplatin (liposomal cisplatin)/vinorelbine combination in HER-2/neu-negative metastatic breast cancer.

UNLABELLED: We assessed the efficacy and safety of a liposomal cisplatin (lipoplatin) and vinorelbine combination in metastatic breast cancer (MBC). Thirty-five patients were treated. The objective response rate was 53.1% and the median survival time was 22 months. Grade 3/4 neutropenia was observed in 44% of cycles, and febrile neutropenia was seen in 4 patients (11.4%). No grade 3/4 nephrotoxicity or neuropathy was noted. This combination is effective and well tolerated in patients with MBC and it warrants investigation as first-line treatment. BACKGROUND: Liposomal cisplatin (lipoplatin) has a mechanism of action similar to that of cisplatin, with reduced toxicities and enhanced or similar efficacy. We wanted to assess the efficacy and safety of a lipoplatin/vinorelbine combination in a phase II clinical trial in metastatic breast cancer (MBC). METHODS: Thirty-five patients with HER-2/neu-negative (HER-2/neu(-)) MBC were enrolled. Lipoplatin 120 mg/m(2) (days 1, 8, and 15) and vinorelbine 30 mg/m(2) (days 1 and 8) were administered in a 21-day cycle. RESULTS: Thirty-five patients were included in the intent-to-treat (ITT) analysis; 32 patients were evaluable for response. The objective response rate was 53.1%. Complete response (CR) was achieved in 3 patients (9.4%), partial response (PR) was seen in 14 patients (43.8%), stable disease (SD) was obtained in 12 patients (37.5%), and progressive disease (PD) was seen in 3 patients (9.4%). Median time to disease progression was 8 months (range 6-10 months). After a median follow-up of 15.5 months, 18 patients were still alive; the median survival time was 22 months (95% confidence interval [CI], 14-30). A total of 174 cycles were administered. Neutropenia was the most frequent hematologic toxicity, with grade 3/4 neutropenia observed in 44% of cycles. Febrile neutropenia was observed in 4 patients (11.4%). No grade 3/4 nephrotoxicity or neuropathy was noted. Grade 1/2 nephrotoxicity occurred in 8 patients (22.9%) and grade 3 vomiting was seen in 3 patients (8.6%). CONCLUSIONS: The results of this trial reveal that vinorelbine/lipoplatin is effective in treating patients with MBC. This regimen is well tolerated with no grade 3/4 nephrotoxicity or neuropathy. The investigation of this regimen as first-line treatment in MBC is warranted.

Is VEGF a predictive biomarker to anti-angiogenic therapy?

Tumor growth and metastasis are dependent on angiogenesis. Inhibiting angiogenesis has therapeutic potentials for treating cancer. Researchers have identified many of the pathways involved in angiogenesis and proposed selective targeted strategies. A high probability of benefit is desirable to justify the choice of anti-angiogenic therapy from an ever-expanding list of expensive new anticancer agents. However, biomarkers of response to anti-angiogenic agents are inconclusive for predicting benefit from these drugs. This paper reviews the most important biomarker of angiogenesis, namely VEGF, in relation to its expression in cancer and the treatment of these cancers through targeting VEGF and its pathways.

Metastasis of colorectal carcinoma to the testes: clinical presentation and possible pathways.

Distant metastasis from colorectal carcinoma most often occurs in the liver and lungs. Metastasis to bones, adrenals, lymph nodes, brain, and skin has also been reported. Metastatic colorectal carcinoma to the testes is very uncommon. Even more uncommon is testicular metastasis from rectal carcinoma. Researchers throughout the last few decades have not acquired a clear understanding of the lymphatic pathways involved in reported cases of testicular metastasis from primary colorectal carcinoma. These cases may present with testicular complaints after or even before the diagnosis of colorectal cancer; this is why it is crucial to differentiate between primary testicular tumor and a secondary one from a colorectal primary. We searched the English medical literature using the MEDLINE/PUBMED database from 1950 through January 2010. Our search yielded 33 cases of testicular metastasis from rectal or colonic carcinoma. These cases are reviewed and summarized. This paper reviews the literature for all cases of testicular metastasis from colonic and rectal adenocarcinomas shedding light on the possible pathways of metastasis. We recommend that physicians be aware of the risk of metastasis from the colorectal region to the testis in their evaluation of patients with testicular symptoms in the setting of colorectal carcinoma.

Platinum-based compounds for the treatment of metastatic breast cancer.

The role of platinum-based compounds (PBCs) in the treatment of metastatic breast cancer (MBC) has been extensively studied. As single agents, high response rates have been observed in first-line therapy, while results in pretreated patients were discouraging. Regimens containing cisplatin/carboplatin together with taxanes showed the highest efficacy and safety as both first-line and second-line therapy. When administered with vinorelbine, the combination was also active and well tolerated in anthracycline- and taxane-pretreated patients. Combining PBCs with etoposide or nucleoside analogues showed moderate activity, yet high toxicity in the case of etoposide. The overall results for the combination with anthracyclines were disappointing. Addition of trastuzumab to PBC combinations showed remarkable activity and good tolerability in patients with HER2/neu overexpression. The use of cisplatin or carboplatin alongside novel targeted therapeutics for patients with triple-negative MBC seems promising and is being further evaluated. The use of PBCs against MBC requires careful patient selection and combination with the right chemotherapeutic agent.

Ratio between positive lymph nodes and total excised axillary lymph nodes as an independent prognostic factor for overall survival in patients with nonmetastatic lymph node-positive breast cancer.

BACKGROUND: The status of the axillary lymph nodes in nonmetastatic lymph node-positive breast cancer (BC) patients remains the single most important determinant of overall survival (OS). Although the absolute number of nodes involved with cancer is important for prognosis, the role of the total number of excised nodes has received less emphasis. Thus, several studies have focused on the utility of the axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. However, most studies suffered from shortcomings, such as including patients who received neoadjuvant therapy or failing to consider the use of adjuvant therapy and tumor receptor status in their analysis. METHODS: We conducted a single-center retrospective review of 669 patients with nonmetastatic lymph nodepositive BC. Data collected included patient demographics; breast cancer risk factors; tumor size, histopathological, receptor, and lymph node status; and treatment modalities used. Patients were subdivided into four groups according to ALNR value (<0.25, 0.25-0.49, 0.50-0.74, 0.75-1.00). Study parameters were compared at the univariate and multivariate levels for their effect on OS. RESULTS: On univariate analysis, both the absolute number of positive lymph nodes and the ALNR were significant predictors of OS. On multivariate analysis, only the ALNR remained an independent predictor of OS, with a 2.5-fold increased risk of dying at an ALNR of ⩾0.25. CONCLUSIONS: Our study demonstrates that ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes.

Ratio between positive lymph nodes and total excised axillary lymph nodes as an independent prognostic factor for overall survival in patients with nonmetastatic lymph node-positive breast cancer.

BACKGROUND.: The status of the axillary lymph nodes in nonmetastatic lymph node-positive breast cancer (BC) patients remains the single most important determinant of overall survival (OS). Although the absolute number of nodes involved with cancer is important for prognosis, the role of the total number of excised nodes has received less emphasis. Thus, several studies have focused on the utility of the axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. However, most studies suffered from shortcomings, such as including patients who received neoadjuvant therapy or failing to consider the use of adjuvant therapy and tumor receptor status in their analysis. METHODS.: We conducted a single-center retrospective review of 669 patients with nonmetastatic lymph nodepositive BC. Data collected included patient demographics; breast cancer risk factors; tumor size, histopathological, receptor, and lymph node status; and treatment modalities used. Patients were subdivided into four groups according to ALNR value (<.25, .25-.49, .50-.74, .75-1.00). Study parameters were compared at the univariate and multivariate levels for their effect on OS. RESULTS.: On univariate analysis, both the absolute number of positive lymph nodes and the ALNR were significant predictors of OS. On multivariate analysis, only the ALNR remained an independent predictor of OS, with a 2.5-fold increased risk of dying at an ALNR of ≥.25. CONCLUSIONS.: Our study demonstrates that ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes.

Primary colorectal lymphoma.

This study aimed at investigating the incidence, presentation, patient and tumor characteristics, treatment, and outcome of primary colorectal lymphomas (PCL) at a tertiary care center in Lebanon over a 25-year period. The Dawson's criteria were used for selection of eligible cases. The medical records were reviewed for demographic variables, the presence of risk factors, presenting signs and symptoms, method of diagnosis, histologic type, type of therapy, and condition at last follow-up. Nine cases of PCL were identified (12.7% of gastrointestinal lymphomas and 0.1% of colorectal malignancies). The mean age at presentation was 44.2 years with male predominance noted. Abdominal pain was the most common presentation (77.8%). Colonoscopy was performed for eight patients with non-specific gross tumor characteristics. Three patients had Burkitt's and six had diffuse large B-Cell lymphomas. The most common site of involvement was the cecum (55.6%) with all cases presenting in stage I(E). Surgery was performed for six patients followed by chemotherapy except for one, and three patients had chemotherapy only. The median survival time was 25 months and the 2-year survival time was approximated at 60%. It is concluded that PCL is a rare malignancy with well-identified disease characteristics yet controversial ideal management plan.

Ratio between positive lymph nodes and total excised axillary lymph nodes as an independent prognostic factor for overall survival in patients with nonmetastatic lymph node-positive breast cancer.

BACKGROUND: The status of the axillary lymph nodes in nonmetastatic lymph node-positive breast cancer (BC) patients remains the single most important determinant of overall survival (OS). Although the absolute number of nodes involved with cancer is important for prognosis, the role of the total number of excised nodes has received less emphasis. Thus, several studies have focused on the utility of the axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. However, most studies suffered from shortcomings, such as including patients who received neoadjuvant therapy or failing to consider the use of adjuvant therapy and tumor receptor status in their analysis. METHODS: We conducted a single-center retrospective review of 669 patients with nonmetastatic lymph node-positive BC. Data collected included patient demographics; breast cancer risk factors; tumor size, histopathological, receptor, and lymph node status; and treatment modalities used. Patients were subdivided into four groups according to ALNR value (< .25, .25-.49, .50-.74, .75-1.00). Study parameters were compared at the univariate and multivariate levels for their effect on OS. RESULTS: On univariate analysis, both the absolute number of positive lymph nodes and the ALNR were significant predictors of OS. On multivariate analysis, only the ALNR remained an independent predictor of OS, with a 2.5-fold increased risk of dying at an ALNR of >or= .25. CONCLUSIONS: Our study demonstrates that ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes.

Hypoxia-inducible factor in cancer angiogenesis: structure, regulation and clinical perspectives.

Tumor hypoxia is a common feature of many cancers. A master regulator of hypoxic response is the transcription factor hypoxia-inducible factor-1 (HIF-1). It functions as a master regulator of oxygen and undergoes conformational changes in response to varying oxygen concentrations. In this paper, we review what has been described about HIF-1: its structure, its regulation and target genes, its role in cancer, and its implication for cancer therapy.

Long-term outcome of adult acute lymphoblastic leukemia in Lebanon: a single institution experience from the American University of Beirut.

BACKGROUND AND OBJECTIVES: The most important studies about outcome of acute leukemia come from developed countries, whereas most of the patients with this disease are in developing countries. We report predictive and prognostic factors in patients with acute lymphoblastic leukemia (ALL) in a tertiary care center in a developing country. PATIENTS AND METHODS: We retrospectively reviewed the records of adult patients with acute leukemia who were referred to the American University of Beirut Medical Center between 1996 and early 2006. RESULTS: Of 105 patients, 36 (34%) patients were diagnosed with ALL, and included 19 (53%) males and 17 (47%) females with a median age of 34 years (range, 14-79 years). Induction chemotherapy with curative intent was administered to 34 (94%) patients. Twenty-seven patients received intrathecal chemotherapy as prophylaxis (n=24) or as treatment for CNS disease (n=3). Twenty-eight patients (82%) achieved complete remission (CR) after induction chemotherapy. The median overall survival (OS) time was 22 months and the five-year OS for ALL patients was 38%. The median disease-free survival (DFS) time was 12 months, while the five-year DFS was 38%. Multivariate analysis showed that age <40 years, WBC <30 X 109/L, achievement of CR after first induction, and CNS prophylaxis were predictive factors for OS and DFS. CONCLUSION: Despite limitations and the relatively low socioeconomic status of the Lebanese population, OS (38%) and DFS (38%) are quite similar to international data. Trends toward a higher CR and DFS in adults are due to intensified consolidation chemotherapy, the use of stem cell transplantation, and improvements in supportive care.

Incidence and prophylaxis of venous thromboembolic events in multiple myeloma patients receiving immunomodulatory therapy.

The diagnosis of multiple myeloma (MM) has been associated to an increased risk of venous thromboembolic events (VTE). Described risk factors that are not exclusive to MM include old age, chemotherapy, immobility, high levels of vascular endothelial growth factor, cancer procoagulant and paraproteinemia. Disease-specific risk factors unique to MM are production of procoagulant autoantibodies, a high incidence of acquired activated protein C resistance, increased levels of factor VIII and von Willebrand factor, and increased production of inflammatory cytokines, mainly IL-6, TNF and C-reactive protein. Treatment regimens that include thalidomide or related compounds such as lenalidomide combined with glucocorticoids and/or cytotoxic chemotherapy were associated with an increased risk of VTE. The risk appears to be particularly high when these immunomodulatory agents are combined with anthracyclines as treatment of newly-diagnosed disease. Combinations including thalidomide plus dexamethasone and/or alkylating agents are associated with an intermediate risk. The same regimens for relapsed/refractory myeloma seem to be associated with a lower risk. The use of newer immunomodulators such as brotezomib seem to reduce the thrombogenic potential. Several different thromboprophylaxis strategies have been effective in lowering the risk of VTE but the data are disputable. None of these VTE prevention strategies have been prospectively compared head-to-head.

Modified resistance to chemotherapy and trastuzumab by bevacizumab in locally recurrent breast cancer.

Antiangiogenic therapy is a valuable new approach in the treatment of breast cancer. Response rates ranging from 6.7% to 54% were reported using Bevacizumab (Avastin), anti-vascular endothelial growth factor, with chemotherapy. We report the first case of a patient, with a highly vascular breast cancer that recurred locally while on treatment with paclitaxel and trastuzumab combination, but showed complete clinical and pathological regression upon the addition of bevacizumab therapy to the same combination.

Effect of mucin production on survival in colorectal cancer: a case-control study.

AIM: To investigate the impact of mucin production on prognosis in colorectal cancer, in terms of overall survival (OS) and time to disease progression (TTP) in patients with mucinous compared to those with non-mucinous colorectal cancer (NMCRC), matched for age, gender, and tumor stage. METHODS: Thirty five patients with mucinous colorectal cancer (MCRC) were matched for age, gender, and tumor stage with 35 controls having NMCRC. OS and TTP were compared among 4 groups divided according to mucin content: group A (50%-75% mucin), group B (75%-100% mucin), group C or controls (<50% mucin). Group D consisted of all patients with tumors having <75% mucin (controls and groups A together). RESULTS: Median survival in MCRC and NMCRC groups was 46.2 and 112.9 mo, respectively (P=0.26). OS in groups A and B was 70.1 and 32.8 mo (P=0.46), and in groups B and D was 32.8 and 70.1 mo, respectively (P=0.143). TTP in MCRC and NMCRC was 50.17 and 44.77 mo, respectively (P=0.795). TTP in groups A, B, and D was 70.1, 24.8, and 65.5 mo, respectively. Twenty-eight percent of patients with MCRC had poorly differentiated adenocarcinoma versus 8.6% in NMCRC patients (P=0.028). CONCLUSION: MCRC is associated with a non-significant decrease in median survival and TTP, particularly when mucin content is >75% of tumor volume. However, it tends to be more poorly differentiated. A larger study matching for stage and grade is needed.

A novel genotype c.1228C>G/c.1448C-1498C (L371V/Rec-NciI) in a 3-year-old child with type 1 Gaucher disease.

Gaucher disease (GD) is an autosomal recessive inborn error of metabolism, resulting from a deficiency of the enzyme glucocerebrosidase, causing an accumulation of the glycolipid glucocerebroside within lysosomes of macrophages in the reticuloendothelial system. Three major clinical forms have been assigned and more than 200 gene mutations have been identified. We herein report a Lebanese boy born with a novel combined mutation L371V/Rec-NciI, who presented with moderate-severe type 1 GD. An overview of the clinical and biomarker improvement following enzyme replacement therapy with imiglucerase is described in a follow-up of 30 months. Imiglucerase seems to be efficacious in decreasing the severity of the disease associated with this mutation. However, a high dose may be required to achieve optimal growth, platelet count, and hemoglobin level.

Solitary mediastinal lymph node metastasis in rectosigmoid carcinoma: a case report.

INTRODUCTION: Colorectal cancer most commonly metastasizes to the regional lymph nodes, liver, bone, lung, and brain. Metastases to mediastinal lymph nodes is a rare entity which has never been reported to be solitary. CASE REPORT: We herein describe a 67-year-old male patient with a solitary mediastinal lymph node metastasis three years following the resection of his primary rectosigmoid carcinoma. Pathological characteristics of the metastatic tissue and technical limitations in imaging modalities resulted in incongruity between follow-up CT and PET scans. Diagnosis of this distant metastasis has been confirmed through a mediastinoscopic biopsy. CONCLUSION: Attention should be paid to the mediastinum when evaluating PET scan or CT films during follow-up of patients with colorectal cancer. Using PET/CT instead of separate morphological and functional data sets favors better detection. Questions still remain concerning the ideal management protocol of such a presentation, the two main options being locoregional or chemotherapeutic.

Burkitt's lymphoma of the colon and bronchi: three case reports.

INTRODUCTION: Burkitt's lymphoma is a form of non-Hodgkin's B-cell lymphoma with more than one identifiable variant. The sporadic form most commonly presents with abdominal lymph node involvement. CASE REPORTS: We herein report on three patients from our experience that presented with either endobronchial or colonic Burkitt's lymphoma. Their clinical presentation mimicked that of other syndromes. After confirmatory pathological diagnosis, the patients had complete remission through the use of an optimal treatment protocol. CONCLUSION: Our review of the cases and comparable reports warrants careful workup of such presentations to ensure early diagnosis and therapeutic planning of this highly aggressive disease.