Mohamed Ichou

Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan Population

Worldwide variation in the distribution of BRCA mutations is well recognised, and for the Moroccan population no comprehensive studies about BRCA mutation spectra or frequencies have been published. We therefore performed mutation analysis of the BRCA1 gene in 121 Moroccan women diagnosed with breast cancer. All cases completed epidemiology and family history questionnaires and provided a DNA sample for BRCA testing. Mutation analysis was performed by direct DNA sequencing of all coding exons and flanking intron sequences of the BRCA1 gene. 31.6 % (6/19) of familial cases and 1 % (1/102) of early-onset sporadic (< 45 years) were found to be associated with BRCA1 mutations. The pathogenic mutations included two frame-shift mutations (c.798_799delTT, c.1016dupA), one missense mutation (c.5095C>T), and one nonsense mutation (c.4942A>T). The c.798_799delTT mutation was also observed in Algerian and Tunisian BC families, suggesting the first non-Jewish founder mutation to be described in Northern Africa. In addition, ten different unclassified variants were detected in BRCA1, none of which were predicted to affect splicing. Most unclassified variants were placed in Align-GVGD classes suggesting neutrality. c.5117G>C involves a highly conserved amino acid suggestive of interfering with function (Align-GVGD class C55), but has been observed in conjunction with a deleterious mutation in a Tunisian family. These findings reflect the genetic heterogeneity of the Moroccan population and are relevant to genetic counselling and clinical management. The role of BRCA2 in BC is also under study.

Is there any advantage to combined trastuzumab and chemotherapy in perioperative setting her 2neu positive localized gastric adenocarcinoma

We report here a 44-year-old Moroccan man with resectable gastric adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2) by immunohistochemistry who was treated with trastuzumab in combination with chemotherapy in perioperative setting. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, and capecitabine. Afterwards, he received total gastrectomy with extended D2 lymphadenectomy without spleno-pancreatectomy. A pathologic complete response was obtained with a combination of trastuzumab and oxaliplatin and capecitabine. He received 3 more cycles of trastuzumab containing regimen postoperatively.We conclude that resectable gastric carcinoma with overexpression of the c-erbB-2 protein should ideally be managed with perioperative combination of trastuzumab with chemotherapy. Further research to evaluate trastuzumab in combination with chemotherapy regimens in the perioperative and adjuvant setting is urgently needed.

Endometrial stromal sarcoma: prognostic factors and impact of adjuvant therapy in early stages

BACKGROUND AND OBJECTIVES Endometrial stromal sarcomas (ESS) are rare uterine neoplasms. surgery remains the cornerstone of treatment for early stages and consists of an abdominal hysterectomy with bilateral salpingo-oopherectomy. Despite appropriate surgical treatment, relapse rates are high (18% to 45%) and the value of adjuvant therapies is not clear. We evaluated prognostic factors and the impact of adjuvant treatment on localized ESS (stages I and II). DESIGN AND SETTING Retrospective, case-control study conducted at the National Institute Of Oncology in Rabat, Morocco over 10 years from 2000 to 2009. PATIENTS AND METHODS twenty-one cases of localized ESS were included in the analysis. RESULTS standard surgery was performed in 71.4% of our patients. Myometrial invasion was noted in 57.1% of cases. Mitotic activity was considered high in five patients. Adjuvant treatment was given to 52.3% of patients: endocrine therapy in five patients and radiotherapy in six. Survival was significantly longer in the group of patients who underwent standard surgical treatment (P=.0007), in the absence of deep myometrial invasion (P=.0248) in cases with a low mitotic index (P<.0001) and in patients who received adjuvant therapy (hormone or radiotherapy) (P=.0048). In a multivariate analysis independent risk factors for monitoring were inadequate surgical treatment and absence of adjuvant treatment. CONCLUSIONS Myometrial invasion and mitotic index appear to be important prognostic factors. the reference surgery is hysterectomy with bilateral salpingo-oopherectomy. Lymph node dissection does not appear to provide a benefit. finally adjuvant treatment may carry a significant survival benefit.

Tolérance cardiaque du trastuzumab en adjuvant : revue à travers 53 observations

Trastuzumab has been a revolution in the treatment of breast cancer overexpressing HER. Its use as an adjuvant for a period of 1 year is currently an international standard. Its major toxicity is cardiac, where the systematic monitoring of the LVEF before and during treatment. To evaluate the cardiac safety for our patients, we conducted this retrospective case-control study. The average in LVEF before the start of trastuzumab was 62.5% (51-80), and at the end of treatment 60.55 (40-77), a decrease in absolute value by 2%. This difference is statistically significant with P<0.001. Eighty-three percent of our patients have completed treatment, of whom 26.4% with a provisional arrest because of a regressive fall in LVEF. A final arrest has been made in 17% cases due to either a nonregressive reduction in LVEF or the appearance of symptomatic heart failure found in two patients. Analysis of risk factors toxicity found in this group of patients with a cardiotoxicity persisting an average age and average number of treatments received anthracyclines higher than the rest of our sample, and diminished baseline LVEF. But all these differences were not statistically significants. During the period of monitoring of these patients, six (67%) had spontaneous recovery of their LFEV 5 months ± 2.01 after discontinuation of trastuzumab. For two cases of symptomatic heart failure, they had a clinical improvement under medical treatment in February but is still less than 40%. The cardiac safety in our study seems comparable with the literature data but located in the upper range of levels of toxicity. The lack of statistical power of our study does not exclude a greater cardiac toxicity of trastuzumab among Moroccan women and should prompt a more cautious use of this drug and the achievement of larger studies that could answer this question.

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.

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.

Primary Non-Hodgkin’s Lymphoma of the Colon: A Case Report and Literature Review

Adenocarcinoma is the most common colon cancer. The other histological types are rare, and primary non-Hodgkin’s lymphoma (NHL) of the colon is even more exceptional [1, 2]. The clinical, radiological and endoscopic signs are not specific and its histology that confirms the diagnosis. The treatment is not well defined and the prognosis remains unknown. In this paper, we report a case of a patient followed in our department for a primary NHL of the splenic flexion of the colon while discussing the different specificities of this disease.

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.

A Thumb Acrometastasis Revealing Lung Adenocarcinoma: A Case Reportand Review

Lung cancer is the commonest cause of acrometastatic disease to the fingers. Treatment of acrometastasis is palliative with radiation or amputation and the prognosis is poor. The authors report a case of phalangeal metastasis in a man aged 72 years old, diagnosed as a painful swelling of the thumb, revealing a bronchial adenocarcinoma. An amputation of the thumb was performed. Histology confirmed a metastasis from the lung adenocarcinoma. The patient died one month after discovery of the primary tumor.

Chemotherapy in the Treatment of Ovarian Psammocarcinoma: A CaseReport and Review of the Literature

Introduction: Psammocarcinoma is a rare form of epithelial serous ovarian carcinoma characterized by extensive formation of psammoma bodies, invasion of ovarian stroma, peritoneum or intraperitoneal viscera, and moderate cytological atypia. These tumors represent a real problem of the diagnostic, and the role of chemotherapy is not yet clearly demonstrated. Case presentation: We herein report a case of psammocarcinoma of ovary with peritoneal carcinosis in a forty year old Moroccan female. The patient underwent optimal surgical debulking and nine courses of chemotherapy with carboplatinum and paclitaxel with a complete response. The prognosis for this type of ovarian cancer is unclear, but it appears to be better than other forms of epithelial ovarian cancer. Conclusion: The psammocarcinome is a rare entity, majority of patients are diagnosed at an advanced stage. The role of chemotherapy is poorly defined; some authors have their patients treated by neoadjuvant or adjuvant chemotherapy. We currently lack evidence of increasing the benefits that can bring chemotherapy in the management of advanced ovarian psammocarcinomas. Only trials in wide yard can answer this question.