RAS/RAF/MAPK Pathway Mutations as Predictive Biomarkers in Middle Eastern Colorectal Cancer: A Systematic Review.

Background: This review article aims to investigate the prevalence and spectrum of rat sarcoma (RAS) and V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations, and their connection with geographical location, clinicopathological features, and other relevant factors in colorectal cancer (CRC) patients in the Middle East. Methods: A systematic literature review, employing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, was conducted to investigate the association between the frequency of relevant mutations and the descriptive clinicopathological characteristics of CRC patients. Multiple electronic databases, including PubMed, Science Direct, Web of Science, Scopus, and Google Scholar, were searched to analyze the relevant literature. Results: A total of 19 eligible studies comprising 2960 patients with CRC were included in this review. A comprehensive analysis of the collected literature data as well as descriptive and methodological insights is provided. Men were predominant in reviewed studies for the region, accounting for 58.6%. Overall, RAS mutation prevalence was 38.1%. Kirsten RAS Viral Oncogene Homolog (KRAS) mutations were the most common, accounting for 37.1% of cases and distributed among different exons, with the G12D mutation being the most frequent in exon 2 (23.2%) followed by G12V (13.7%), G13D (10.1%), G12C (5.1%), G12A (5.04%), and G12S (3.6%). Neuroblastoma RAS Viral Oncogene Homolog (NRAS) mutations were identified in 3.3% of tumor samples, with the most common mutation site located in exons 2, 3, and 4, and codon 61 being the most common location for the region. The total mutation frequency in the BRAF gene was 2.6%, with the V600E mutation being the most common. Conclusion: The distribution patterns of RAS and BRAF mutations among CRC patients exhibit notable variations across diverse ethnic groups. Our study sheds light on this phenomenon by demonstrating a higher prevalence of KRAS mutations in CRC patients from the Middle East, as compared with those from other regions. The identification of these mutations and geographical differences is important for personalized treatment planning and could potentially aid in the development of novel targeted therapies. The distinct distribution patterns of RAS and BRAF mutations among CRC patients across different ethnic groups, as well as the regional variability in mutation prevalence, highlight the need for further research in this area.

Clinical Significance of Somatic Mutations in RAS/RAF/MAPK Signaling Pathway in Moroccan and North African Colorectal Cancer Patients.

BACKGROUND: Mutations in RAS (KRAS, NRAS) and BRAF genes are the main biomarker predicting response to anti-EGFR monoclonal antibodies in targeted therapy in colorectal cancer (CRC). OBJECTIVE: Our study aims to evaluate the frequencies of KRAS, NRAS and BRAF mutations and their possible associations with clinico-pathological features in CRC patients from Morocco. METHODS: DNA was extracted from 80 FFPE samples using the QIAamp DNA FFPE-kit. RAS and BRAF mutations were assessed by pyrosequencing assays using Qiagen, KRAS Pyro®kit 24.V1, Ras-Extension Pyro®kit 24.V1 and BRAF Pyro®Kit 24.V1, respectively, and carried out in the PyroMark-Q24. RESULTS: RAS mutations were identified in 57.5% (56.2% in KRAS, 8.8% in NRAS). In KRAS gene, exon 2 mutations accounted for 93.3% (68.9% in codon 12, 24.4% in codon 13). Within codon 12, G12D was the most prevalent mutation (37.7%), followed by G12C (13.4%), G12S (8.9%) and G12V (6.6%). Within codon 13, the most frequently observed mutation was G13D (22.3%). The mutation rates of exon 3 and 4 were 15.6% and 13.3%, respectively. In exon 3 codon 61, 2.3% patients were detected with two concurrent mutations (Q61R, Q61H), and 4.4% with three concurrent mutations (Q61R, Q61H, Q61L). In NRAS gene, the mutation rates of exon 2, 3 and 4 were 57.1%, 28.6%, and 14.3%, respectively. G13A and Q61H were the most common mutations, accounting for 42.9% and 28.5%, respectively. There were 13% patients with concurrent KRAS/NRAS mutation and 4.3% wt KRAS with NRAS mutations. No mutations were identified in BRAF gene. In both sexes, KRAS codon 12 mutations were associated with higher stage III/IV tumors. Moreover, Patients whose tumor is in the proximal colon (56.3%) are more likely to harbor KRAS mutations than those tumor located in rectum (25%). CONCLUSION: RAS mutations could be useful in future target anti-EGFR therapy and molecular CRC screening strategy in Morocco.

[Evaluation of the practice of prescribing oral chemotherapy type "Capecitabine" by medical oncologist: A first study from Morocco]. / Évaluation de la pratique de prescription d'une chimiothérapie orale type « capécitabine ¼. Résultats de la première enquête auprès des oncologues médicaux marocains.

INTRODUCTION: Oral anticancer therapy is becoming increasingly developed; their prescription has become a common practice in oncology. However, there is a variability and diversity in prescription practice. Its magnitude has been very little studied in scientific literature. To our knowledge, this is the first study in Morocco and North Africa to evaluate the practice of prescribing oral chemotherapy. METHODS: The authors conducted a national exhaustive cross-sectional survey, to evaluate the practice of the oral chemotherapy "Capecitabine" type prescription by Moroccan oncologists and to identify strategies to promote an adherence to oral anti-neoplasic therapy. RESULTS: Ninety-one medical oncologists answered out of 118, from public oncology centres (29.7%), Hospital University (58.2%), and private sector (12.1%). Thirty-four of the oncologists replied by email, 33 through phone conversation and 24 by filling paper questionnaires. In total, 32% of the cases were handwritten prescriptions, and 51.6% electronically generated. Forty-six percent of medical oncologists dedicated more time to the oral chemotherapy type Capecitabine prescription versus its intravenous equivalent 5FU. However, 33% medical oncologists take less time to this prescription, and 20.9% of them take the same time. Adherence to oral chemotherapy was evaluated by simply questioning of patients in most of the cases (94%) and 4% of medical oncologist declared that they did not evaluate this adherence. In total, 87.9% of Moroccan medical oncologists revealed that they have not received any specific training in the therapeutic education of the patient with oral anti-cancer treatment. CONCLUSION: In Morocco, there is a great variability in prescription and follow-up practice for patients receiving oral chemotherapy. There is a lack of a national standardization with regards to the procedures of prescribing and monitoring patients to ensure the quality and safety of the oral chemotherapy prescription.

When tyrosine kinase inhibitor sunitinib can be discontinued in metastatic renal cell carcinoma to pancreas: a case report.

BACKGROUND: Long-term survival with durable response remains possible in the area of targeted therapies. Discontinuation of sunitinib could improve quality of life and reduce treatment costs in metastatic renal cell carcinoma with long-term disease stabilization. We discuss a case of successful interruption of antiangiogenic therapy in a patient with persisting evidence of metastases. The discontinuation of antiangiogenic therapy seems to be an option, even in indolent oligo-metastatic renal cell carcinoma with long disease stabilization before sunitinib. This observation contributes important data to the ongoing discussion on the discontinuation of treatment with kinase inhibitors in selected patients with metastatic renal cell carcinoma. CASE PRESENTATION: We report a case of an 80-year-old Moroccan man treated for renal clear cell carcinoma with multiple pancreatic metastases. He was not on any other medications. He underwent active surveillance with deferred sunitinib at disease progression. He showed significant disease control on sunitinib therapy demonstrating partial response with stable disease after a total of 28 months of therapy. He experienced toxicities which were manageable with supportive care and dose adjustments. Our patient asked for a break of the sunitinib administration, and the treatment was stopped. The disease remained stable after 13 months' discontinuation of sunitinib therapy. The patient was in excellent overall health. CONCLUSIONS: All available agents for metastatic renal cell carcinoma have side effects, which may become serious in a minority of patients. Clinicians and patients must therefore carefully balance the goals of maximal efficacy with minimal toxicity. Sunitinib can be discontinued without negatively impacting outcomes in indolent disease. Further research is needed to characterize the molecular determinants of response and resistance to targeted therapy.

Visceral Crisis Means Short Survival Among Patients With Luminal A Metastatic Breast Cancer: A Retrospective Cohort Study.

BACKGROUND: Patients with visceral crisis from luminal metastatic breast cancer (mBC) are often treated with palliative chemotherapy. No studies have analyzed the aggressiveness of the care in visceral crisis from luminal mBC patients. The objective of this study was to assess practices in this setting in a university medical oncology department. METHODS: This retrospective study included all patients who were managed for luminal mBC between January 2013 and April 2016. The analysis focused on the characteristics of the patients, the modalities of cancer treatment and delays between visceral crisis and death. RESULTS: Thirty-five patients pre-treated with two hormonal therapy lines were enrolled retrospectively. Worse performance status and a higher proportion of severe organ dysfunction for luminal mBC were observed among patients with visceral crisis. Sixty-five percent of patients received cytotoxic treatment. One cycle of chemotherapy was administrated in the majority of patients. Palliative care was performed in 35% of patients. Chemotherapy did not have any significant effect on patient outcome in the present study. The mean time between visceral crisis and death was 4.7 weeks (standard deviation = 1.9). CONCLUSION: Our study showed that visceral crisis in patients with luminal mBC is a complex problem. We need more comprehension of molecular pathogenesis to visceral crisis disease to propose efficacious treatments for these patients and to identify subgroup of patients who need chemotherapy followed by maintenance endocrine therapy.

Renal damage induced by pemetrexed causing drug discontinuation: a case report and review of the literature.

BACKGROUND: Pemetrexed maintenance therapy holds tremendous potential in improving the survival of patients with advanced pulmonary adenocarcinoma. Major side effects include myelosuppression and cutaneous reactions. However, little data are available on pemetrexed nephrotoxicity. Our case describes clinically relevant renal events leading to treatment discontinuation in routine practice. CASE PRESENTATION: We report a case of a 69-year-old Moroccan man treated for metastatic non-small cell lung cancer. He was not on any other medications and he did not receive any nephrotoxic agents. He was exposed to intravenously administered contrast from thoracoabdominal computed tomography in the week of his last pemetrexed treatment. He developed kidney disease related to pemetrexed. He was submitted to renal biopsy, which showed acute tubular damage and interstitial fibrosis. His kidney function remained impaired, but stable, after discontinuation of pemetrexed therapy. He died 5 months later. CONCLUSIONS: Medical oncologists should be aware of renal adverse events for patients with advanced non-small cell lung cancer eligible for pemetrexed maintenance therapy. Suggestions for mitigating the risk for renal toxicities (dehydration, non-steroidal anti-inflammatory drugs and zoledronic acid, radiocontrast agents) during pemetrexed maintenance should be followed to enable early detection and management of this adverse event.

A Case of Well-Differentiated Papillary Mesothelioma of the Male Peritoneum: Successful Treatment by Systemic Chemotherapy.

Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare subtype of epithelioid mesothelioma, which is usually seen in young women without a history of asbestos exposure, and generally, has an indolent course. The relative rarity of this neoplasm in males prompted us to report this case of a well-differentiated papillary mesothelioma of the peritoneum in a 36-year-old man. The patient, who had no history of asbestos exposure, presented with abdominal pain and ascites of unknown etiology. Computed tomography showed abundant ascites with nodules of the peritoneal cavity. Laparoscopic examination revealed a large number of white miliary nodules diffusely covering the peritoneum. Pathology revealed a diagnosis of well-differentiated papillary mesothelioma of the peritoneum, based on histomorphology and immunohistochemistry. The patient started chemotherapy with cisplatin and pemetrexed. After six cycles of chemotherapy, the effectiveness of this chemotherapy was checked by only the computed tomography. PET scan was not used because it is not routinely recommended in WDPMP. Few data are currently available in the literature regarding the performance of the PET scan in WDPMP. Nine months later, the patient was free of symptoms. Based on reviewing the literature and our observations in this case, consultation of other pathologists is highly recommended to discern WDPMP from other disseminated peritoneal diseases, in order to offer the most effective and safe therapeutic strategy. Chemotherapy should be strongly considered if the tumor is unresectable and accompanied by symptoms. Cisplatin and pemetrexed chemotherapy could be a promising therapeutic choice.

Synchronous Primary Renal Cell Carcinoma and Pancreatic Ductal Adenocarcinoma: Case Report and Literature Review.

Synchronous primary cancers involving the pancreas and kidney are extremely rare and poorly documented. We report the first case of this association treated with chemotherapy and tyrosine kinase inhibitor. A 70-year-old woman presented with a 2-month history of epigastric pain with weight loss of 12 kg. Two weeks previously, she had presented with jaundice and pelvic pain. A computed tomography (CT) scan of the body revealed the presence of an irregular mass in the body of the pancreas, encasing the celiac trunk, with dilatation of the biliary tract. CT also revealed a heterogeneously right renal mass with bone metastasis in the left acetabular cup and the left iliac wing. A biliary metallic prosthesis was performed with a pancreatic mass biopsy. Histology revealed a moderately differentiated pancreatic ductal adenocarcinoma. Another biopsy was performed in the right iliac wing. Pathological examination with immunohistochemistry confirmed the diagnosis of bone metastasis from clear cell renal cell carcinoma. The patient was treated with a combination of gemcitabine, sunitinib, and denosumab. She had a stabilization disease and a prolonged progression-free survival of 9 months. Side effects were manageable and included grade 2 fatigue and grade 2 hypertension. The patient died at 13 months from diagnosis after disease progression. This report suggests that the appropriate treatment for this association in metastatic or unresectable disease is chemotherapy for pancreatic cancer and tyrosine kinase inhibitor for kidney cancer. We also review the appropriate literature concerning that association.

Triple malignancy in a single patient including a squamous cell carcinoma of the cervix, a colloid adenocarcinoma of the colon and a lung adenocarcinoma: A case report and literature review.

INTRODUCTION: The association of two cancers in the same patient is unusual but has been widely reported in the literature, while triple malignancy in the same patient is exceptional. Indeed, only very rare cases have been described. CASE PRESENTATION: A 70-year-old woman treated in our institute in 2006 for a tumor of the cervix. She underwent extrafascial hysterectomy. Pathology revealed a well differentiated squamous cell carcinoma of the cervix (pT1N0M0). No external pelvic radiation or brachytherapy were done. The patient remained in good control until 2013 when she presented a tumor of the ascending colon. A right hemicolectomy was made. Pathology confirmed a colloid adenocarcinoma (pT3N0M0). No adjuvant chemotherapy was given. Three years later, a Computed tomography scan of the chest revealed a nodule of the lower lobe of the left lung. Biopsy was made. Histology with immunochemistry revealed the diagnosis of lung adenocarcinoma. Positron emission tomography scan showed abnormal fluorodeoxyglucose uptake in the lung nodule with no anomaly in mediastinal nodes and no metastasis. A left lower lobectomy was performed with lymph node dissection. Pathology confirmed the diagnosis of 2.5 cm lung adenocarcinoma without node invasion (pT1N0M0). No chemotherapy was given. After 14 months, the patient remained in good control. CONCLUSIONS: Triple malignancy in a single patient is exceptional. The management depend on stages. Surgery is the standard of care in localized cancers.

Metachronous pancreatic metastases from renal cell carcinoma: is there a place of Active-Surveillance before deferred deliberately Molecular Target Agent?

BACKGROUND: Metastatic renal cell cancer is a heterogeneous disease due to its diverse morphological features, the prognostic categories based on clinical criteria. Sometimes indolent course without any significant symptoms can be differentiated before the introduction of novel targeted agents. This observation led to interest in a strategy of deferring systemic therapy in the era of effective systemic therapies. CASE PRESENTATION: We report of a 78-year-old Moroccan man with pancreatic metastasis from renal cell carcinoma which occurred 14 years from right nephrectomy. Indolent disease based on body computed tomography imaging with 4 years follow-up was recognized. Active surveillance with deferred antiangiogenic multikinase inhibitor at disease progression was proposed. Nowadays, the patient is under oncological follow-up, he is in a good state of health, and he is disease-free for 48 months from the diagnosis of the tumor and for 20 months from the start of the treatment with Sunitinib CONCLUSIONS: Active surveillance before target therapy may be a suitable approach to ensure long progression-free survival with minimal side-effects and better quality of life in asymptomatic, low-volume, metastatic disease. Further prospective studies with biomarker validation are required to define the patients most likely to benefit from this approach.

Bone metastasis from malignant phyllodes breast tumor: report of two cases.

BACKGROUND: Phyllodes tumors are rare fibroepithelial tumors accounting for less than 1 % of all breast neoplasms. They are malignant in 20 % of cases. Only a few cases of malignant phyllodes tumors metastatic to bone have been reported. CASE PRESENTATION: Case 1: A 40 year-old white woman presented with three-week history of pain and functional impairment of the left lower limb. Her clinical past was remarkable for previous left mastectomy and radiotherapy for malignant phyllodes tumor performed one year ago. Computed tomography revealed a moth-eaten appearance of the left femoral head. The patient underwent computed guided femoral head biopsy. Pathological findings were consistent with metastatic malignant phyllodes tumor. The patient received ifosfamide and adriamycin chemotherapy. She is doing well without any evidence of progression on her imaging follow- up after 8 months. Case 2: A 48 year-old white woman, with history of bilateral mastectomy and radiotherapy for malignant phyllodes tumor performed one and two year ago, presented with four-week left lower quadrant abdominal pain. Computed tomography and magnetic resonance imaging revealed a solid aggressive osteolytic mass of the left iliac bone with extensive soft tissue invasion. Biopsy of the tumor was performed and showed a sarcomatous proliferation consistent with metastatic malignant phyllodes tumor. The patient received the same chemotherapy regimen as in the first case but without any response on her imaging follow up after 6 months. CONCLUSION: Malignant phyllodes tumor is a rare and aggressive fibroepithelial neoplasm. An accurate diagnosis of metastases should be based on clinicopathological correlation allowing exclusion of differential diagnoses. The goal of successful managing this tumor is early detection and complete resection prior to dissemination.

Whole-Genome Sequencing in Microbial Forensic Analysis of Gamma-Irradiated Microbial Materials.

Effective microbial forensic analysis of materials used in a potential biological attack requires robust methods of morphological and genetic characterization of the attack materials in order to enable the attribution of the materials to potential sources and to exclude other potential sources. The genetic homogeneity and potential intersample variability of many of the category A to C bioterrorism agents offer a particular challenge to the generation of attributive signatures, potentially requiring whole-genome or proteomic approaches to be utilized. Currently, irradiation of mail is standard practice at several government facilities judged to be at particularly high risk. Thus, initial forensic signatures would need to be recovered from inactivated (nonviable) material. In the study described in this report, we determined the effects of high-dose gamma irradiation on forensic markers of bacterial biothreat agent surrogate organisms with a particular emphasis on the suitability of genomic DNA (gDNA) recovered from such sources as a template for whole-genome analysis. While irradiation of spores and vegetative cells affected the retention of Gram and spore stains and sheared gDNA into small fragments, we found that irradiated material could be utilized to generate accurate whole-genome sequence data on the Illumina and Roche 454 sequencing platforms.

Tolerability profile of bevacizumab in metastatic colorectal cancer: about a Medical Department experience.

Colorectal cancer is one of the most common cancers worldwide, and associated with high mortality rates in our country. The prognosis of patients diagnosed with metastatic colorectal cancer (mCRC) has improved markedly over the last 12 years, increasing from 5 months with best supportive care to almost 2 years with combination chemotherapy plus bevacizumab. Bevacizumab is well suited for use in combination with first or second line chemotherapy in the treatment of mCRC because its side effects are predictable and appear not to add to the incidence or severity of the side effects of chemotherapy. The aim of our small study is to explore the tolerability profile of bevacizumab used in daily clinical practice in patients with metastatic colorectal cancer (mCRC) in our department.

Spinal cord ischemia secondary to transcatheter arterial chemoembolization for hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma. Although considered relatively safe, TACE has been associated with several complications. Spinal cord ischemia secondary to TACE is an extremely rare but disastrous complication. We report a very rare case of spinal cord injuries after TACE, together with a literature review. During the procedure, the patient suddenly experienced sensory impairment below the T10 dermatome and bilateral lower extremity motor weakness. She was given high-dose steroids and supportive therapy. The sensory deficits nearly improved completely, but motor strength remained unchanged. Thereafter, a chest computed tomography scan showed tumor metastasis to the lungs. The patient is now receiving sorafenib and follow-up.

The single nucleotide polymorphism +936 C/T VEGF is associated with human epidermal growth factor receptor 2 expression in Moroccan breast cancer women.

The vascular endothelial growth factor (VEGF), a potent regulator of angiogenesis, is involved in the development and progression of breast cancer (BC). The functional +936 C/T polymorphism of the VEGF-A gene has been implicated in BC susceptibility; however, published data are conflicting. In the current case-control study, we analyzed the association of the +936 C/T polymorphism with BC risk and tumor markers expression, human epidermal growth factor receptor 2 (HER2/neu) and caner antigen 15.3 (CA 15.3) in Moroccan women. We genotyped the DNA of 70 BC patients and 70 healthy women by TaqMan SNP assays. The χ(2) test and Fisher's exact test were used for statistical analyses. The overall results revealed that there is no association between the +936 C/T polymorphism and BC risk [p = 0.8; OR 0.87, 95 % CI (0.32-2.42)]. However, when we stratified the group of patients according to the status of tumor markers, a statistical significant association of +936 C/T SNP and HER2/neu expression was observed (p = 0.009). In contrast, no association with the other tumor marker, CA 15.3, was found (p = 0.090). Thus, the +936 C/T polymorphism seems to have a correlation with HER/neu expression in BC disease.

An unusual case of isolated peritoneal metastases from lung adenocarcinoma.

INTRODUCTION: Peritoneal metastases from lung cancer are a rare event. In this paper, we report the case of a patient with adenocarcinoma of the lungs who had isolated peritoneal metastases at the time of diagnosis. CASE REPORT: We report a 55-year-old female who presented with shortness of breath, decreased effort tolerance, cough, and weight loss. Her initial chest X-ray and subsequent chest CT showed a 12 × 9 × 8 cm mass in the middle lobe of the right lung. The histopathological examination of her biopsy material was consistent with a thyroid transcription factor-1 positive lung adenocarcinoma. In the abdomen, a 5.3-cm mass was identified. A biopsy and immunohistochemistry revealed a lung adenocarcinoma. The patient was administered chemotherapy based on carboplatin-paclitaxel-bevacizumab, but only with a partial response. Six months later, the patient showed brain metastases. Therefore, a second-line treatment based on pemetrexed was administered for 9 courses, and a clinical and radiological response was observed. The chemotherapy was stopped and the patient did not exhibit any symptoms of progression while waiting for a new evaluation. DISCUSSION: The incidence of peritoneal involvement of lung cancer without metastases in other parts of the body is scarcely encountered in clinical practice. Out of the different types of lung cancers, adenocarcinoma and large cell carcinoma are most likely to metastasize in the peritoneum. Immunohistochemical staining patterns were important in the differential diagnosis with the other etiologies for peritoneal metastasis and the mesothelioma. Peritoneal metastases are indicative of a disseminated disease and prognosis is extremely poor.

Cardiac metastases of renal cell carcinoma revealed by syncope: diagnosis and treatment.

INTRODUCTION: Cardiac metastases from renal cell carcinoma are very rare. In this report, we describe a case of ventricular metastases in the absence of vena cava or right atrial involvement. CASE REPORT: We report the case of a 60-year-old man who had a past history of heavy tobacco intake and well-controlled arterial hypertension. He experienced sudden-onset palpitations, lost consciousness and, as a result, was involved in an accident on the public highway. Cardiac arrhythmia was suspected and, therefore, transthoracic echocardiography was suggested, which revealed a large right ventricular mass. Chest and abdominal computed tomography demonstrated a mass in the right ventricle, but without contiguous vena cava involvement, and a right renal mass related to the probable neoplasm. An ultrasound-guided renal biopsy showed a clear-cell renal cell carcinoma. A bone scan revealed a metastatic bone disease. The patient was started on sunitinib treatment, which was well tolerated. However, approximately 8 months later, reevaluation showed pulmonary metastases. The patient was subsequently started on treatment with everolimus, which, however, was poorly tolerated. Two months later, the patient died due to terminal respiratory insufficiency. DISCUSSION: Based on the literature and our observations in this case, targeted antiangiogenic therapy should be considered as a viable therapeutic alternative to metastasectomy for patients with inoperable cardiac metastatic disease as long as there is no baseline systolic or diastolic dysfunction. The case also emphasizes the importance of a thorough history review and physical examination in the workup of patients with syncope.

Flagellate erythema secondary to bleomycin: a new case report and review of the literature.

Bleomycin is an antibiotic with antineoplastic properties. It is used in the treatment of different tumors in oncology. The mucocutaneous side effects of this drug include ulcers, scaly erythematous and bullous lesions, sclerosis, stomatitis, and pigmentary alterations. Flagellate erythema is a characteristic hyperpigmentation of bleomycin. We report a case of flagellate erythema following the administration of bleomycin in a 34-year-old woman with ovarian teratoma. She developed linear lesions two weeks after the first injection of bleomycin. Flagellate erythema is a specific reaction to bleomycin therapy, which occurs in susceptible individuals independently of dose, route of administration, and type of malignant disease treated.

Investigating the association of vascular endothelial growth factor polymorphisms with breast cancer: a Moroccan case-control study.

The main mediator of breast cancer (BC) angiogenesis is the vascular endothelial growth factor (VEGF). Variation of VEGF-A gene may influence the BC susceptibility. The present case-control study investigated the association of the four commonly studied single nucleotide polymorphisms (SNP) of VEGF-A, namely: -1154A/G (rs1570360), -2578C/A (rs699947), -634G/C (rs2010963) and -460T/C (rs833061) with BC susceptibility and aggressiveness in Moroccan women. After genomic DNA extraction, genotyping was performed by TaqMan SNP assays on 70 BC patients and 70 healthy women. The χ2 test was used to detect differences in the genotype frequencies of VEGF between the groups and to stratify genotypes by the clinico-pathological characteristics in patient's group. Women carriers of -1154AG + AA and -2578AC + AA VEGF genotypes had a reduced risk to develop BC [p = 0.018, OR 2.25 95 % CI (1.14-4.42) and p = 0.022, OR 2.26 95 % CI (1.12-4.58), respectively]. Carriers of -460CT and CT + CC genotypes had also a reduced risk to develop BC [p = 0.045, OR 2.63 95 % CI (1.19-5.84) and p = 0.043, OR 2.12 95 % CI (1.01-4.43), respectively]. Moreover, the A-1154A-2578G-634C-460 haplotype seems to have a protective effect against BC risk [p = 0.007, OR 2.41 95 % CI (1.27-4.55)]. Stratification for BC patients according to clinico-pathological characteristics reveals no association with any of VEGF-A SNPs. In conclusion, the data indicated significant associations of VEGF -1154A/G, -2578C/A and -460T/C polymorphisms with BC susceptibility in Moroccan individuals. These VEGF-A polymorphisms can be useful as predisposing genetic markers for BC. Further larger-scale studies are necessary to confirm our finding.