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J C Sabourin

Publications and source records attributed to J C Sabourin.

At least 19 recordsLinked to original sources
PubMed2006

A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with pretreated gastroenteropancreatic well-differentiated endocrine carcinomas.

UNLABELLED: Only a few drugs are active in the treatment of well-differentiated endocrine carcinomas (WDEC). We evaluated the combination of the so-called 'de Gramont schedule' and irinotecan in these tumors in a phase II study. METHODS: 20 patients were enrolled in the study. The combination regimen included irinotecan, 180 mg/m(2) on day 1, followed by 200 mg/m(2) folinic acid in a 2-hour infusion, an intravenous 10-min bolus of 400 mg/m(2) 5-fluorouracil (5FU) and finally 600 mg/m(2) 5FU in a 22-hour infusion. Folinic acid and 5FU were repeated on day 2. Clinical, biological and morphological parameters were assessed by CT every 8 weeks. The site of the primary tumor was the pancreas in 10 cases, the lung in 3 cases and other sites in 7 cases. Sixteen patients had previously received chemotherapy, and 6 of them had had two lines of treatment. Six patients had previously been treated with chemoembolization. RESULTS: The median number of cycles administered was 8. Grade 3-4 neutropenia was observed in 8 patients, and 1 patient experienced febrile neutropenia. There was no toxicity-related death. No complete symptomatic response was observed in 7 evaluable patients; 4 patients had an objective biological response. One patient achieved a morphological objective response, stabilization was observed in 15, but progression occurred in 3 patients. Median survival was 15 months. CONCLUSION: The above-mentioned combination of LV5FU2 + irinotecan does not yield major activity in heavily pretreated unresectable metastatic gastroenteropancreatic WDEC, and significant toxicity was observed.

Adult↗
PubMed2006

Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer.

BACKGROUND: Recent studies have suggested that chemokine receptors are involved in development of organ-specific pattern of metastases. In the present study, we evaluated the association between the chemokine receptors expressed in primary tumor cells and the site of metastatic relapse in patients with breast cancer. METHODS: Primary tumors were obtained from 142 patients with axillary node-positive breast cancer and stained for CX3CR1, CXCR4, CCR6, and CCR7 expression. All statistical analyses were adjusted for systemic post-operative treatment. RESULTS: After a median follow-up of 13 years, none of the chemokine receptors was associated with overall survival or disease free survival. However, expression of chemokine receptors was found to be associated with increased risk of relapse in certain organs. By estimating the Mantel-Haenszel odds ratios (OR), CXCR4 was associated with increased risk of metastasis to the liver (OR = 3.71, P = 0.005), CX3CR1 was associated with metastasis to the brain (OR = 13.18, P = 0.01). Patients with CCR6 positivity were more likely to develop a first metastasis in the pleura (OR = 2.82, P = 0.06). In addition, CCR7 expression was associated with the occurrence of skin metastases (11% versus 0%, P = 0.017). INTERPRETATION: Expression of chemokine receptors in the primary tumor predicts the site of metastatic relapse in patients with axillary node positive breast cancer. This study, in concordance with the data obtained in animal models, suggests that the chemokine receptors family could be the biological support of the 'seed and soil' theory.

Adult↗
PubMed2003

[Is sentinel lymph node mapping relevant for colon cancer?: a feasibility study].

BACKGROUND: Sentinel lymph node (sln) technique using blue injection is controversial for colon cancer. The aim of this study was to evaluate the feasibility and interest of sentinel node detection to identify the ultrastaging rate detecting occult nodal micrometastases missed on routine H&E examination. METHODS: During surgery blue dye was injected subserously around the tumor in 30 patients operated for a colon cancer. The first lymph nodes to turn blue were noted as sln. For each sln three examination levels were performed; if no tumor was detected by H&E examination, a cytokeratine immunohistochemistry study was performed. RESULTS: For each case, one or more sln were found (100%). The median number of lymph nodes examined and of sln found was, respectively, 23 (range 10-55) and 2 (1-4). There were 21 pN0 tumors, among which we found two cases (9%) with a micrometastasis and one case of isolated tumor cells detected, resulting in a 14% (3/21) ultrastaging for pTxN0. The sln was positive in five patients out of nine with a N+ disease. CONCLUSIONS: Sln detection was a successful technique when there was no evident lymph node involvement, no primary large lesion or no associated liver metastasis. Focused examination of the sln identified 10-20% of additional ultrastaging disease for staged pT1, 2, 3N0M0 tumor. This may have an important implication for follow-up and adjuvant treatment in future protocols.

Adult↗
PubMed2002

[Pulmonary carcinosarcoma with jejunal metastasis: complete response to chemotherapy].

We report a case of pulmonary carcinosarcoma with jejunal metastasis. The lung is an exceptional localization for carcinosarcoma, a tumor with carcinomatous and sarcomatous components. These two components are closely related but well-defined morphologically and immunohistochemically. Risk of metastasis and local recurrence is high. Surgery is the treatment of choice for localized forms. Prognosis depends on the sarcomatous component which is usually sensitive to chemotherapy, with at least doxorubicin and ifosfamide. This rare case illustrates the potential for jejunal metastasis and complete response to chemotherapy, proven histologically at 33 months.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Radio-frequency tissue ablation of the liver: effects of vascular occlusion on lesion diameter and biliary and portal damages in a pig model.

The aim of this study was to assess the effect of vascular occlusion on radio-frequency (RF) lesion size and on potential associated biliary and portal lesions. Radio-frequency lesions using a 1-cm exposed-tip cooled electrode were created in pig liver. Liver perfusion was modified by arterial embolization (n=2), left portal clamping (n=2), and both (n=2). Two pigs were used as controls. Two weeks after, control portography was performed, animals were killed, and ex-vivo cholangiography was carried out. Pathological studies evaluated the lesion surface and associated portal and biliary damages. A mathematical regression model showed that portal occlusion increased by 43 mm2 (+40%) the surface of RF lesions, arterial occlusion by 135 mm2 (+126%), and associated occlusion by 466 mm2 (+435%). Biliary stenoses were found in 4 cases (two arterial occlusions, one portal occlusion, and one associated occlusion). One case of partial portal vein thrombosis was found in one case of portal occlusion and resolved at 2 weeks. Ischemic damages adjacent to RF lesions were found in cases of combined occlusions. The reduction of liver perfusion increases significantly the size of RF lesions but is associated with a risk of biliary, portal, or parenchymal complications.

Animals↗
PubMed2001

Antitumour activity of somatostatin analogues in progressive metastatic neuroendocrine tumours.

A few studies have suggested an antitumour activity of somatostatin analogues in neuroendocrine tumours (NET). The aim of this study was to evaluate the antitumour efficacy of somatostatin analogues in patients with documented progressive tumours. 35 consecutive patients with documented tumour progression were treated with somatostatin analogues. Patients were classified into two groups. In Group 1, tumours were progressing rapidly (an increase of 50% or more in the lesion surface area in 3 months) and in Group 2, tumours were progressing more slowly (an increase of less than 50% in the lesion surface area in 3 months but greater than 25% in 6 months). Treatment consisted of subcutaneous (s.c.) octreotide, 100 microg thrice daily for 17 patients, intramuscular lanreotide, 30 mg/every 14 days for 11 patients and for 7 patients both somatostatin analogues were used successively during the follow-up. Primary tumour sites were the small intestine (n=12), pancreas (n=13), lungs (n=5), and other sites (n=5). 18 patients had the carcinoid syndrome with flushing and/or diarrhoea. The median duration of treatment was 7 months. Treatment was discontinued in 3 patients due to side-effects. One patient (3%) achieved a partial response and the disease was stabilised in 20 patients (57%) for a median duration of 11 months (6-48 months). Stabilisation of patients in Group 1 was significantly less frequent at 6 months than that of patients in Group 2 (4/12 and 13/17 respectively, P<0.02). Somatostatin analogue treatment resulted in one partial response (3%) and 20 cases of stabilisation (57%) in 35 patients with progressive NET. A slow tumour growth rate before treatment is predictive of a good response to somatostatin analogues which could be considered an option for first-line treatment.

Adult↗
PubMed2001

[Standards, options and recommendations: practice guidelines for difficult diagnosis in surgical pathology or cytopathology in cancer patients].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993 is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for difficult diagnoses in surgical pathology or cytopathology in cancer patients. METHODS: Data were identified by searching Medline and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 71 independent reviewers. RESULTS: The main recommendations to prevent and reduce the number of difficult diagnoses in surgical pathology or cytopathology are: 1) The development of quality insurance programs with use of written procedures in each pathology laboratory (standard). 2) The knowledge of clinical data in order to explain surgical pathology or cytopathology results (standard). 3) The availability of complementary patient informations (radiologic data . . .) can be useful to explain surgical pathology or cytopathology results (option). The main recommendations to detect lesions associated with difficult diagnosis in surgical pathology or cytopathology are: 1) Tumor types known as potential difficult diagnosis in surgical pathology or cytopathology should be reviewed by a second pathologist. 2) The systematic second reviewing for every case is expensive but has to be done when the difficulty is know (sarcoma, lymphoma . . .) by experienced pathologists. The main recommendations to solve difficult diagnosis in surgical pathology or cytopathology are: 1) Block recuts, use of special techniques (immunocytohistochemistry and molecular biology), additional data from clinicians, second opinion by a local pathologist, or new specimen can be required for establishing the diagnosis (options). 2) Outside second opinion by expert pathologist has to be considered once the other steps did not allow to establish surgical or cytopathology diagnosis (recommendations, expert agreement).

Humans↗
PubMed2001

[Role of the pathologist in management of familial cancers].

Pathologists have long been in charge of the morphological analysis of human cancers, and have been used to be at the end of a chain in the diagnostic procedure. With the search for somatic mutations and new prognostic markers, the pathologists have become key-members in oncogenetics. New modalities for tissue fixation, microdissection of tumors, and forwarding of specimens to the molecular biologists are therefore requested. Two examples are presented to illustrate the need for tumor DNA, with the diagnostic utility of a microsatellite testing as a prescreening test in HNPCC tumors, and the search for new prognostic markers in some inherited predispositions to breast cancers.

Acetic Acid↗
PubMed2000

Anti-Müllerian hormone is a specific marker of sertoli- and granulosa-cell origin in gonadal tumors.

Sex cord stromal tumors are gonadal neoplasms containing Sertoli, granulosa, Leydig, or thecal cells, which originate from cells derived from either the sex cords (Sertoli and granulosa cell tumors) or the specific mesenchymal stroma (Leydig and thecal cell tumors) of the embryonic gonad. Only granulosa and Sertoli cells produce anti-Müllerian hormone (AMH). Our purpose was to investigate whether AMH can be used as a specific marker of human granulosa or Sertoli cell origin in gonadal tumors, to distinguish them from other primary or metastatic neoplasms, using immunohistochemistry. We studied 7 juvenile and 6 adult-type granulosa cell tumors of ovarian localization and 3 extraovarian metastases, 20 other ovarian tumors, 6 testicular Sertoli cell tumors, 2 gonadoblastomas, and 13 extragonadal tumors. Granulosa cell tumors, both juvenile- and adult-type of either ovarian or metastatic localization, showed an heterogeneous pattern of AMH immunoreactivity: Areas containing intensely or weakly AMH-positive cells were intermingled with AMH-negative areas. Although in most cases AMH-positive areas represented a minor proportion of tumor cells, we found a positive reaction in all the cases examined. In testes, although normal prepubertal Sertoli cells were intensely positive, testicular Sertoli cell tumors showed large areas of negative reaction, with few positive cells scattered throughout the tumor. AMH was also reactive in most of the cells of sex-cord origin in gonadoblastomas. No AMH immunoreaction was observed in other gonadal and extragonadal tumors. We conclude that AMH expression is conserved in only a small proportion of tumor cells of granulosa or Sertoli cell origin; however, a positive reaction in a few cells helps to distinguish between granulosa or Sertoli cell tumors or gonadoblastomas and other gonadal tumors of different origin.

Adrenal Cortex Neoplasms↗
PubMed2000

Extensive molecular screening for hereditary non-polyposis colorectal cancer.

The genetic abnormalities underlying hereditary non-polyposis colorectal cancer (HNPCC) are germline mutations in one of five DNA mismatch repair genes or in the TGFbetaRII gene. The aim of our study was to evaluate the significance of simple tests performed on tumours to select appropriate candidates for germline mutational analysis. We studied three groups of patients, HNPCC kindreds fulfilling the International Collaborative Group (ICG) criteria (n = 10), families in which at least one of the criteria was not satisfied (n = 7) and sporadic colorectal cancer (CRC) diagnosed before the age of 50 (n = 17). We searched for microsatellite instability (MSI), presence of hMSH2 and hMLH1 germline mutations, expression of hMSH2, hMLH1 and p53 proteins in tumoural tissue samples by immunostaining. Fifteen out of 17 (88%) of HNPCC and incomplete HNPCC cases were MSI and eight pathogenic germline mutations in hMSH2 or hMLH1 were detected in these two groups (53%). All the 17 early-onset sporadic cases were MSS and no germline mutations were detected among the seven investigated cases. Thirteen out of 15 (81%) familial cases were MSI and p53 protein-negative, whereas 13/14 (93%) sporadic cases were MSS and strongly p53 protein-positive. This extensive molecular investigation shows that simple tests such as MS study combined with hMSH2 and hMLH1 protein immunostaining performed on tumoural tissues may provide valuable information to distinguish between familial, and probably hereditary, and sporadic CRC cases.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Immunohistochemical expression of WT1 by desmoplastic small round cell tumor: a comparative study with other small round cell tumors.

Desmoplastic small round cell tumors (DSRCTs) present a reciprocal chromosomal translocation, t(11;22)(p13;q12), that results in fusion of Ewing's sarcoma and Wilms' tumor (WT1) genes. The authors evaluated 15 DSRCTs and 71 other tumors often considered in the differential diagnosis for immunoreactivity using a polyclonal antibody directed against the WT1 part of the chimeric protein resulting from this translocation. WT1 immunostaining was performed on paraffin material using the WT(C-19) antibody after heat-antigen retrieval. All the DSRCTs (15 of 15, 100%) demonstrated strong WT1 nuclear immunoreactivity. Ten of 14 nephroblastomas (71%) disclosed WT1-positive nuclei in accordance with the staining reported by others, and rare and focal nuclear positivity was detected in two of 17 rhabdomyosarcomas. WT1 immunoreactivity was not observed in Ewing's sarcoma/primitive neuroectodermal tumors (zero of 21, 0%), neuroblastomas (zero of 17, 0%), or rhabdoid tumors of the kidney (zero of two, 0%). In nephroblastoma, differential diagnosis with DSRCT was not difficult: Clinical and morphologic data are not similar for these two entities. The current study validates WT1 immunoreactivity as a useful marker to separate DSRCT from other small round cell tumors.

Abdominal Neoplasms↗
PubMed2000

Isolated para-aortic node involvement in stage IB/II cervical carcinoma.

The aim of this report was to describe exceptional cases of patients treated for stage Ib and II cervical carcinoma with isolated para-aortic node involvement and to deduce therapeutic implications. Between 1985 and 1998, 491 women with stage IB or II cervical carcinoma underwent radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy. Five patients had para-aortic metastatic nodes but no external iliac, obturator or common iliac node involvement. These five patients had a tumor size >3 cm. According to these cases, in patients with bulky cervical carcinoma systematic complete lymphadenectomy should be performed in order to avoid misdiagnosis of para-aortic node involvement.

Adult↗
PubMed2000

Krukenberg tumor: a clinico-pathological study of 15 cases.

Krukenberg tumor clinically mimics primary ovarian cancer. We report a series of 15 cases of Krukenberg tumor. The patients' age range from 13 to 71 years. Most ovarian tumors (14/15) were bilateral. A primary digestive tumor was diagnosed pre-operatively in 3 cases, per-operatively in 3 cases and post-operatively in 4 cases. No primary tumor was identified in the 5 other cases. Histological diagnosis of Krukenberg tumor is usually easy either on paraffin or frozen sections. Mucin stains are helpful. Two main histological types were found in our series : the classic form with sarcoma-like storiform tumoral stroma and an alternative cellular-acellular pattern. Mucinous carcinoid was microscopically challenged in two cases. Most patients died within 2 years (median survival 14 months). Nor surgery, neither chemotherapy is efficient but bilateral oophorectomy should be proposed in post-menopausal women with gastric linitis removed surgically.

Adolescent↗
PubMed2000

[Response of metastatic colorectal cancers to treatment with CPT11 (irinotecan): implications of the mismatched base repair system].

AIMS: The aim of our study was to assess the potential relationships between tumor responsiveness to CPT11, an analogue of camptothecin, which selectively inhibits DNA topoisomerase I, and the microsatellite instability, a feature of tumors with DNA mismatch repair defect. METHODS: We designed a retrospective clinical study including 35 patients with metastatic colorectal cancer treated with CPT11, for which we analyzed the expression of hMLH1 and hMSH2 in the tumor and determined microsatellite status of repeated mononucleotide tracts present in the coding region of RII-TGFB, BAX, hMSH3 and hMSH6 genes. RESULTS: A partial or minor response was observed in 9 patients, disease stabilization in 14 patients and progression in 12 patients. Staining of hMLH1 was undetectable in 2 of the 35 tumors, while only 1 tumor lacked hMSH2 expression. Four of the 31 tumors analyzed displayed intragenic microsatellite instability. We found a good correlation between inactivation of TGFB-RII, BAX or hMSH3 genes and tumor response to CPT-11 (P =0.002). CONCLUSION: Our preliminary data suggest that intragenic microsatellite instability may influence tumor response to CPT-11 in patients with colorectal cancer.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Deletion mapping of the tumor suppressor locus involved in colorectal cancer on chromosome band 8p21.

Several somatic genetic alterations have been described in colorectal carcinoma (CRC). Recurrent chromosomal deletions have suggested the presence of tumor suppressor genes (TSG) specifically involved in colorectal carcinogenesis. For one of them, two non-overlapping regions have been proposed on the short arm of chromosome 8, encompassing the LPL and NEFL genes. The short arm of chromosome 8 has been extensively studied in colorectal cancer and in other cancer types. Both regions have been reported as candidate loci for a TSG. In order to delineate a reliable region of deletional overlap on chromosome arm 8p in CRC, a series of 365 CRC samples was selected for the absence of microsatellite instability (RER, replication error); tumor and normal matched DNAs were studied for 54 microsatellite polymorphisms distributed on 8p using multiplex-PCR amplification. After purification of tumor nuclei by flow cytometry based on either the abnormal DNA index or the presence of a high expression of cytokeratin, complete allelic losses on 8p were observed in 48% of cases. Measurement of the DNA index showed that 88% of RER tumors were hyperploid. Complete allelic losses of only part of the short arm were observed on 26 occasions. These data allowed us to define a 1 cM interval of common deletion, flanked by the loci D8S1771 and NEFL, where a putative TSG may be localized.

Animals↗