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H Bouzourene

Publications and source records attributed to H Bouzourene.

At least 19 recordsLinked to original sources
PubMed2007

A case of Muir-Torre syndrome associated with mucinous hepatic cholangiocarcinoma and a novel germline mutation of the MSH2 gene.

Muir-Torre syndrome (MTS) is a rare cancer-predisposing syndrome that is autosomal dominantly inherited and characterized by the development of sebaceous skin lesions (adenomas, epitheliomas, basaliomas and carcinomas). These lesions are typically associated with tumors that belong to the spectrum of hereditary nonpolyposis colorectal cancer (HNPCC) (i.e., tumors of the colorectum, endometrium, stomach or ovary). Biliary malignancy in association with MTS has only rarely been reported. We report a case of Muir-Torre syndrome associated with intrahepatic cholangiocarcinoma, a location not previously described, and associated with a novel missense mutation of the MSH2 gene (c.2026T > C), predicted to disrupt the function of the gene.

Adenocarcinoma, Mucinous↗
PubMed2006

CPT-11 and concomitant hyperfractionated accelerated radiotherapy induce efficient local control in rectal cancer patients: results from a phase II.

Patients with rectal cancer are at high risk of disease recurrence despite neoadjuvant radiochemotherapy with 5-Fluorouracil (5FU), a regimen that is now widely applied. In order to develop a regimen with increased antitumour activity, we previously established the recommended dose of neoadjuvant CPT-11 (three times weekly 90 mg m(-2)) concomitant to hyperfractionated accelerated radiotherapy (HART) followed by surgery within 1 week. Thirty-three patients (20 men) with a locally advanced adenocarcinoma of the rectum were enrolled in this prospective phase II trial (1 cT2, 29 cT3, 3 cT4 and 21 cN+). Median age was 60 years (range 43-75 years). All patients received all three injections of CPT-11 and all but two patients completed radiotherapy as planned. Surgery with total mesorectal excision (TME) was performed within 1 week (range 2-15 days). The preoperative chemoradiotherapy was overall well tolerated, 24% of the patients experienced grade 3 diarrhoea that was easily manageable. At a median follow-up of 2 years no local recurrence occurred, however, nine patients developed distant metastases. The 2-year disease-free survival was 66% (95% confidence interval 0.48-0.83). Neoadjuvant CPT-11 and HART allow for excellent local control; however, distant relapse remains a concern in this patient population.

Adenocarcinoma↗
PubMed2006

Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.

BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.

Adenocarcinoma↗
PubMed2006

Mixed testicular germ cell tumor presenting as metastatic pure choriocarcinoma involving the maxillary gingiva.

Gingival metastases are infrequent and invariably associated with a widespread disease and a poor prognosis. Because of their unremarkable clinical appearance, they can be difficult to distinguish from more common gingival hyperplastic or reactive lesions, such as pyogenic granuloma, peripheral giant cell granuloma, and peripheral ossifying granuloma. We are reporting here an unusual case of a 36-year-old man with a mixed testicular germ cell tumor presenting as a metastatic pure choriocarcinoma involving the maxillary gingiva, extending from the first left premolar to the left second maxillary molar, mimicking a 'benign looking' gingival mass. Gingival metastases may be the first manifestation of a widespread metastatic disease and therefore particular attention must be paid to gingival lesions associated with atypical clinical symptoms and/or signs.

Adult↗
PubMed2005

Digital image DNA cytometry: a useful tool for the evaluation of malignancy in biliary strictures.

BACKGROUND: Cytologic evaluation of the biliary tract strictures is nowadays widely used for distinguishing between benign and malignant lesions but remains a challenge for some problematic cases. Digital Image cytometry (DNA-cytometry) helps cytopathologists to resolve some unclear situations. METHODS: We have analysed 41 specimens of bile duct brushings obtained from patients during ERCP (11 benign cases, 7 suspicious for malignancy cases and 23 malignant cases) by DNA-cytometry and correlated them with the histological biopsy counterpart. RESULTS: All eleven cytological and histological benign cases were DNA-diploid and among 22 patients with malignant cytological and histological diagnosis 21 were DNA-aneuploid. One case considered malignant by the cytopathologist revealed DNA-aneuploid but malignancy could not be confirmed by histology. The analysis of the suspicious for malignancy cases revealed that all DNA-aneuploid cases were malignant and all DNA-diploid cases were benign referring to the follow-up of the patients. The comparison between cytology alone and cytology combined with DNA-cytometry related to the histological diagnosis (gold standard) resulted in a sensitivity of 100% and a specificity of 79% for cytology alone; a specificity of 94% and a sensitivity 92% for DNA-cytometry and a specificity of 93% and a sensitivity of 100% with combined analyses. The positive predictive value was 90% for cytology, 96% for DNA-cytometry and for both analyses. The negative predictive value showed 100% for cytology, 89% for DNA-cytometry and 100% for combined studies. CONCLUSIONS: Despite the limited number of patients involved in the study, the results obtained indicate an increased of specificity and of positive predictive value using DNA-cytometry. These results confirm the pertinence of these method for challenging cases, in conjunction with other available diagnostic tools.

Adult↗
PubMed2005

Irinotecan-induced colitis.

Irinotecan (CPT-11) is a chemotherapeutic drug used to treat tumors by acting on malignant cells through inhibition of DNA topoisomerase I and inducing premature apoptosis. Major toxic effects of Irinotecan are myelosuppression and gastrointestinal (GI) toxicity, which limits the dose of administration, particularly severe diarrhea with a delay of onset. However, according to the literature, serious GI side effects are uncommon, comprising 3% of the reported cases. The mechanism of Irinotecan-induced delayed diarrhea is unknown and unpredictable. To our knowledge, this is the first case of colitis associated with Irinotecan administration for temporal glioblastoma documented by biopsies. The histopathologic findings are described and the potential mechanisms inducing such lesions are discussed.

Aged↗
PubMed2004

Microscopic colitis with giant cells: a rare new histopathologic subtype?

Collagenous and lymphocytic colitis might be part of the same disease spectrum. In this report, we present a histopathologic subtype of microscopic colitis characterized by the presence of subepithelial multinucleated giant cells. This reaction is very unusual and not explicable by any underlying disease process or previous treatment. Among 490 cases of microscopic colitis (MC) diagnosed between 1992 and 2002, we found 2 cases with macrophages and giant cells (0.4%). One case of lymphocytic colitis (LC) and 1 case of collagenous colitis (CC) presented aggregates of macrophages and giant cells located in the superficial part of the lamina propria. Infectious or non-infectious colonic granulomatous diseases were excluded on histologic, clinical, and biological grounds. The recognition of this feature in an MC is important to avoid the diagnosis of granulomatous infectious or idiopathic colitis such as Crohn's disease. Even if very unusual, this subtype of MC evolves favorably since the 2 patients responded well to corticosteroid treatment.

Aged↗
PubMed2002

The natural history of a gastric low grade B cell MALT lymphoma followed during 11 years without treatment.

Low grade B cell mucosa associated lymphoid tissue (MALT) lymphoma of the stomach is usually an indolent tumour that remains localised for a long time before dissemination occurs. MALT appears in the stomach in response to infection by Helicobacter pylori, which is present in 80-90% of cases. The pathogenesis of the evolution from chronic gastritis to malignant lymphoma has not yet been fully explained and the exact role of H pylori in the pathogenesis and progression of gastric lymphoma remains unclear. This report describes the case of a 72 year old woman with a low grade B cell MALT lymphoma localised in the gastric fundus, who refused to be treated for eradication of H pylori. The histological diagnosis of B cell MALT lymphoma was supported by both immunohistochemical and molecular genetic analysis. After 11 years of follow up, this MALT lymphoma remained indolent, without local progression or blastic transformation, and the H pylori infection was still persistent, even though the density of bacteria had decreased drastically. Interestingly, two different clonal immunoglobulin (Ig) gene rearrangements were found in two series of biopsies performed with an interval of 11 years. This case report supports the following notions: (1) H pylori associated gastritis is a risk factor for gastric MALT lymphoma, but might not be sufficient by itself for the progression of the disease, and (2) in the evolution of MALT lymphomas, different cell clones characterised by different Ig rearrangements may emerge.

Aged↗
PubMed2001

Intratumor genetic heterogeneity in advanced human colorectal adenocarcinoma.

Colorectal carcinogenesis is widely accepted as one of the best-characterized examples of stepwise progression. The existing colorectal carcinogenesis model assumes genetic homogeneity of individual tumors for the main known genetic alterations: K-ras and p53 genes point mutations and loss of heterozygosity (LOH) of chromosome 5q and 18q. The object of the present study was to demonstrate the existence of an intratumor genetic heterogeneity in advanced sporadic colorectal carcinoma for these genetic alterations. Using improved tissue microdissection and DNA extraction, for each tumor, amplifiable DNA was obtained from 15 to 20 areas, of which 1 to 2 concerned lymph node metastases (LNM). This study revealed that 10 of 15 (67%) analyzed tumors were heterogeneous for at least 1 genetic alteration, with between 2 and 6 genotypically different clones detected per tumor. No correlation was observed between the genotype of these subclones and histological differentiation or invasive propensity. Intratumor heterogeneity was more frequently observed for LOH than for point mutations, 67% and 58% for LOH at APC and DCC locus, and 20% for mutation of either the K-ras or p53 gene. In 5 of the 9 (56%) heterogeneous cases with available LNM, the genotype observed in the LNM was different from that of the main clone in the primary tumor, and moreover, 2 of the LNM displayed a genotype undetected in the primary tumor. In conclusion, intratumor genetic heterogeneity was demonstrated in advanced sporadic colorectal carcinoma and was represented as topographically distinct genotypic subclones. Taking into account such a significant genetic heterogeneity of colorectal tumors, the use of genetic markers for prognosis management should be reconsidered.

Adenocarcinoma↗
PubMed2001

Expression of telomerase genes correlates with telomerase activity in human colorectal carcinogenesis.

The human telomerase enzyme is composed of two essential components, hTR, which acts as a template for reverse transcription, and hTERT, which is the putative catalytic subunit for the enzyme. Recent studies have demonstrated a good correlation between hTERT expression and telomerase activation, whereas RT-PCR results seemed to reveal that hTR is ubiquitously expressed in all cells. These observations left unclear the role of hTR, and to a lesser extent hTERT, in the regulation of telomerase activation. In the present study, the correlation of telomerase activity and the expression of these genes was examined in a total of 70 colorectal tissues (25 adenocarcinomas, 30 adenomas, and 15 samples of normal colorectal mucosa). Total RNA for RT-PCR analysis and cell extracts for TRAP assay were obtained from consecutive sections and histological control was simultaneously performed. To avoid false-positive results, due to the fact that hTR cDNA and genomic hTR DNA are identical (the gene has no introns), extensive DNase digestion was performed before cDNA synthesis. RT-PCR analysis revealed that hTERT mRNA was expressed in all cancers and in 13 of 14 telomerase-positive adenomas, but never in telomerase-negative colorectal tissues. hTR transcripts were observed in all telomerase-positive samples but also in three telomerase-negative samples, two adenomas, and one normal colonic mucosa. It is concluded that hTERT and hTR expression is strongly correlated with telomerase activity. hTR transcripts, however, also occur in some telomerase-negative tissues and these results are in keeping with the concept that hTERT expression is a major regulator of telomerase activity.

Adenocarcinoma↗
PubMed2001

Dukes B colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location.

PURPOSE: The aim of this study was to determine whether tumor location proximal or distal to the splenic flexure is associated with distinct molecular patterns and can predict clinical outcome in a homogeneous group of patients with Dukes B (T3-T4, N0, M0) colorectal cancer. It has been hypothesized that proximal and distal colorectal cancer may arise through different pathogenetic mechanisms. Although p53 and Ki-ras gene mutations occur frequently in distal tumors, another form of genomic instability associated with defective DNA mismatch repair has been predominantly identified in the proximal colon. To date, however, the clinical usefulness of these molecular characteristics remains unproven. METHODS: A total of 126 patients with a lymph node-negative sporadic colon or rectum adenocarcinoma were prospectively assessed with the endpoint of death by cancer. No patient received either radiotherapy or chemotherapy. p53 protein was studied by immunohistochemistry using DO-7 monoclonal antibody, and p53 and Ki-ras gene mutations were detected by single strand conformation polymorphism assay. RESULTS: During a mean follow-up of 67 months, the overall five-year survival was 70 percent. Nuclear p53 staining was found in 57 tumors (47 percent), and was more frequent in distal than in proximal tumors (55 vs. 21 percent; chi-squared test, P < 0.001). For the whole group, p53 protein expression correlated with poor survival in univariate and multivariate analysis (log-rank test, P = 0.01; hazard ratio = 2.16; 95 percent confidence interval = 1.12-4.11, P = 0.02). Distal colon tumors and rectal tumors exhibited similar molecular patterns and showed no difference in clinical outcome. In comparison with distal colorectal cancer, proximal tumors were found to be statistically significantly different on the following factors: mucinous content (P = 0.008), degree of histologic differentiation (P = 0.012), p53 protein expression, and gene mutation (P = 0.001 and 0.01 respectively). Finally, patients with proximal tumors had a marginally better survival than those with distal colon or rectal cancers (log-rank test, P = 0.045). CONCLUSION: In this series of Dukes B colorectal cancers, p53 protein expression was an independent factor for survival, which also correlated with tumor location. Eighty-six percent of p53-positive tumors were located in the distal colon and rectum. Distal colon and rectum tumors had similar molecular and clinical characteristics. In contrast, proximal neoplasms seem to represent a distinct entity, with specific histopathologic characteristics, molecular patterns, and clinical outcome. Location of the neoplasm in reference to the splenic flexure should be considered before group stratification in future trials of adjuvant chemotherapy in patients with Dukes B tumors.

Adenocarcinoma↗
PubMed2001

Malacoplakia simulating organ invasion in a rectosigmoid adenocarcinoma: report of a case.

Malacoplakia is a histiocytic inflammatory response that may be associated with colorectal tumors. We report the case of a 65-year-old male taking steroids for a severe pulmonary disease. He presented with a rectosigmoid tumor that seemed to infiltrate the urinary bladder and the sacrum on the preoperative CT scan and echography and at laparotomy. A low anterior resection en bloc with a partial cystectomy was performed. The pathologic analysis showed a pT3pN0 adenocarcinoma with an extensive malacoplakia infiltrating the bladder and the pericolic and perirectal tissues. This case report emphasizes the overstaging that malacoplakia may induce and underlines a situation the surgeon may possibly confront. Our observation confirms the association of malacoplakia, colorectal carcinoma, and steroid treatment.

Abdominal Pain↗
PubMed2001

Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer.

The INK4a-ARF locus encodes two tumor suppressor proteins involved in cell-cycle regulation, p16INK4a and p14ARF, whose functions are inactivated in many human cancers. The aim of this study was to evaluate p14ARF and p16INK4a gene inactivation and its association with some clinocopathological parameters in colon cancer. The mutational and methylation status of the p14ARF and p16INK4a genes was analyzed in 60 primary colon carcinomas and 8 colon cancer cell lines. We have identified the first two reported mutations affecting exon 1beta of p14ARF in the HCT116 cell line and in one of the primary colon carcinomas. Both mutations occur within the N-terminal region of p14ARF, documented as important for nucleolar localization and interaction with Mdm2. Tumor-specific methylation of the p14ARF and p16INK4a genes was found in 33% and 32% of primary colon carcinomas, respectively. Methylation of the p14ARF was inversely correlated with p53 overexpression (p = 0.02). p14ARF and p16INK4a gene methylation was significantly more frequent in right-sided than in left-sided tumors (p = 0.02). Methylation of the p14ARF gene occurred more frequently in well-differentiated adenocarcinomas (p = 0.005), whereas the p16INK4a gene was more often methylated in poorly differentiated adenocarcinomas (p = 0.002). The present results underline the role of p14ARF and p16INK4a gene inactivation in the development of colon carcinoma. They suggest that the methylation profile of specific genes, in particular p14ARF and p16INK4a, might be related to biologically distinct subsets of colon carcinomas and possibly to different tumorigenic pathways.

Adaptor Proteins, Signal Transducing↗
PubMed2000

p53 and Ki-ras as prognostic factors for Dukes' stage B colorectal cancer.

Mutations of the TP53 and Ki-ras genes have been reported to be of prognostic importance in colorectal carcinomas. An increased intracellular concentration of the p53 protein, although not identical to, is sometimes seen in tumours with TP53 mutation and has been correlated with poor prognosis in some tumour types. Previous colorectal cancer studies, addressing the prognostic importance of Ki-ras mutation and TP53 aberrations, yielded contradictory results. The aim of this study was to determine in a clinically and therapeutically homogeneous group of 122 sporadic Dukes' B colorectal carcinomas with a median follow-up of 67 months (3-144 months) whether or not p53 protein expression, TP53 mutation and K-ras mutation correlated with prognosis. p53 staining was performed by immunohistochemistry, using the monoclonal antibody DO7 on paraffin-embedded tissue. Mutations in exons 5-8 of the TP53 gene and in codons 12 and 13 of the K-ras gene were assayed in paraffin-embedded tissue by the single-strand conformation polymorphism (SSCP) assay. Nuclear p53 staining was found in 57 (47%) tumours. Aberrant migration patterns indicating mutation of the TP53 gene were found in 39 (32%) tumours. Forty-six carcinomas (38%) showed a mutation of the Ki-ras codons 12 or 13. In a univariate analysis, patients with wild-type TP53 status showed a trend towards better survival, compared with those with mutated TP53 (log-rank test, P = 0.051). Likewise, tumours immunohistochemically positive for p53 showed a worse prognosis than p53-negative tumours (P = 0.010). The presence or absence of mutations in Ki-ras did not correlate with prognosis (P = 0.703). In multivariate analysis, only p53 immunoreactivity emerged as an independent marker for prognosis hazard ratio (HR) = 2.16, 95% confidence interval (CI) 1.12-4.11, P = 0.02). Assessment of p53 protein expression is more discriminative than TP53 mutation to predict the outcome of Dukes' stage B tumours and could be a useful tool to identify patients who might benefit from adjuvant therapy.

Adenocarcinoma↗