[Rectal cancer Information dedicated to cancer patients and relatives]. / Comprendre le cancer du rectum Information à l'usage des personnes malades et de leurs proches.

In response to the evolution of the information-seeking behaviour of patients and concerns from health professionals regarding cancer patient information, the French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced, in 1998, an information and education program dedicated to patients and relatives, the SOR SAVOIR PATIENT program. The methodology of this program adheres to established quality criteria regarding the elaboration of patient information. Cancer patient information, developed in this program, is based on clinical practice guidelines produced by the FNCLCC and the twenty French regional cancer centres, the National League against Cancer, The National Cancer Institute, the French Hospital Federation, the National Oncology Federation of Regional and University Hospitals, the French Oncology Federation of General Hospitals, many learned societies, as well as an active participation of patients, former patients and caregivers. The handbook SOR SAVOIR PATIENT Understanding rectal cancer is an adapted version of the clinical practice guidelines (CPG) Standards, Options and Recommendations for rectal cancer. It is meant to provide a basis for the explanation of the disease and treatments and to facilitate discussions with the healthcare team. It is available from the FNCLCC (101, rue de Tolbiac, 75013 Paris, Tel. (0033) 1 44 23 04 68, www.fnclcc.fr). This document has been validated at the end of 2004 and published in 2005. SOR SAVOIR PATIENT guides are systematically updated when new research becomes available. Information leaflets, extracted from the handbook SOR SAVOIR PATIENT Understanding rectal cancer and published in this edition of the Bulletin du cancer, allow patients to better understand colonoscopy and colostomy, which represent an important patient information need. These articles are meant to inform patients and relatives about the disease and its treatments. It also offers health professionals a synthetic evidence-based patient information source which facilitates discussions with the patient.

Treatment of murine hepatocellular carcinoma using genetically modified cells to express interleukin-12.

BACKGROUND AND AIM: The majority of patients cannot benefit from the conventional curative treatments that are currently used for hepatocellular carcinoma (HCC), which remains a world health problem. Interleukin (IL)-12 is one of the most potent anti-tumor cytokines. The aim of the present study was to examine the anti-tumor effect and toxicity of intrahepatic delivery of IL-12 using an ex vivo gene therapy approach in a murine model of HCC. METHODS: Syngenic fibroblasts or MM45T-Li HCC tumor cells were genetically modified in vitro to express IL-12 using a polycistronic TFG murine IL-12 retroviral vector (TFGmIL-12) coding for both p35 and p40 murine IL-12 subunits. Hepatocellular carcinoma was generated using direct intrahepatic inoculation of the tumor cell line into the left liver lobe of BALB/c mice. RESULTS: Direct liver expression of IL-12 by the injected genetically modified tumor cells induced a marked inhibition of tumor growth. This effect was associated with an early infiltration of macrophages, and lymphocytes forming numerous intralobular foci. There was no significant liver toxicity, as shown by normal biochemical liver tests. At a later time, the intralobular foci were rare and consisted mainly of CD4+ T cells, while CD8+ T cells were present in the lobule. Intrahepatic expression of IL-12 did not modify circulating or splenic B lymphocytes or natural killer (NK) cells. The inhibition of tumor growth was maintained in nude mice even when depleted in NK cells. Importantly, in a second model, treatment of established day 7 liver tumors in BALB/c mice using direct intra-tumor injection of syngenic fibroblasts that were genetically modified to express IL-12 significantly reduced tumor size. CONCLUSION: In conclusion, these data provide evidence that experimental HCC can be efficiently and safely treated using ex vivo IL-12 gene therapy, which seems promising for future clinical studies.

[Standards, Options and Recommendations 2004: good practice guidelines for second opinion in anatomic and surgical pathology in oncology (integral report)]. / Standards, Options et Recommandations 2004 pour une bonne pratique de la consultation personnelle et de la relecture en anatomie et cytologie pathologiques en cancérologie (rapport intégral).

CONTEXT: The " Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the French Federation of Cancer Centres (FNCLCC), the 20 French Regional 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 the outcome of cancer patients. OBJECTIVE: To develop good practice guidelines for second opinion in anatomic and surgical pathology in oncology, in collaboration with the French Society for Anatomic and Surgical Pathology. METHOD: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs using the definitions of the Standards, Options and Recommendations project. Once the guideline has been defined, the document is submitted to independent reviewers for review. RESULTS: The working group defined four types of second opinions in anatomic and surgical pathology: personal consultation, inter-institutional consultation, peer review consultation for a scientific survey, intra-departmental consultation in the context of quality control. The main recommendation is that second opinion should respect the patients' rights and the medical ethics code. For each of the four situations defined recommendations have been developed, taking this principle into consideration.

Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01).

PURPOSE: To evaluate the efficacy and toxicity of novel chemotherapy combinations including cisplatin with gemcitabine (GC) or irinotecan (IC) for patients with carcinomas of an unknown primary site. PATIENTS AND METHODS: Eighty patients were randomly assigned to receive GC or IC. In the GC arm, chemotherapy consisted of cycles combining gemcitabine 1,250 mg/m2 intravenously (IV) on days 1 and 8, and cisplatin 100 mg/m2 IV on day 1 at 3-week intervals. Patients in the IC arm originally received 3-week cycles of irinotecan 200 mg/m2 IV on day 1 and cisplatin 80 mg/m2 IV on day 1. After the inclusion of 15 patients in that arm, the toxicity profile required the irinotecan doses to be reduced to 150 mg/m2 per cycle. Independent histologic and radiologic reviews were done. RESULTS: A total of 78 patients were assessable for efficacy and toxicity. The median number of cycles was four in each arm. Objective responses were observed in 21 patients (55%) in the GC arm (95% CI, 34% to 66%) and in 15 patients (38%) in the IC arm (95% CI, 23% to 54%). Treatment had to be stopped because of toxicity in seven patients in the GC arm and in eight patients in the IC arm. With a median follow-up of 22 months, the median survivals were 8 and 6 months in the GC and IC arms, respectively. CONCLUSION: This study demonstrates the activity of both the GC and IC regimens. There was toxicity associated with both regimens. Additional studies of combination chemotherapy regimens are required.

PNL2, a new monoclonal antibody directed against a fixative-resistant melanocyte antigen.

We report the production of a new monoclonal antibody, PNL2, directed against a fixative resistant melanocyte antigen. The analysis of PNL2 immunostaining on a broad range of normal or malignant human tissues and on various melanocytic lesions revealed its high specificity. PNL2 gave a strong cytoplasmic staining of skin and oral mucosae melanocytes, and staining of granulocytes when used at high concentration. PNL2 stained all intra-epidermal nevi irrespective of their histologic type, but common intradermal nevi and the dermal component of compound nevi were largely non-reactive as only scattered nevus cells in the papillary dermis were labeled. PNL2 labeled more than 70% of the neoplastic cells in all primary melanomas irrespective of their histologic type. However, PNL2 did not label desmoplastic melanomas. All metastatic melanomas were also stained but the percentage of labeled cells was occasionally lower than the primary tumor. PNL2, as anti-Melan A and HMB-45 antibodies, stained most of the clear cell sarcoma cells, and a few cells in angiomyolipomas and lymphangioleiomyomatosis. None of the other non-melanocytic lesions tested were labeled. Proteomic approaches showed that the immunoaffinity purified PNL2-binding complexes isolated from melanoma cell lines comprise at least TAP1, Clathrin 17 and prealbumin proteins, but not the gp100 recognized by HMB-45. In conclusion, this new monoclonal antibody, PNL2, is directed against a new fixative resistant melanocyte associated antigen. This antigen is chemically resistant and thus allows immunostaining after melanin bleaching or decalcification. We also demonstrate that it is different from Melan A and from gp100, even if PNL2 and HMB-45 staining patterns are sometimes similar.

Value of cytokeratin 5/6 immunostaining using D5/16 B4 antibody in the spectrum of proliferative intraepithelial lesions of the breast. A comparative study with 34betaE12 antibody.

Previous studies have shown that basal-type cytokeratins (CKs) can distinguish usual ductal hyperplasia (UDH) from the spectrum of atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). Indeed, expression of these CKs is weak or absent in ADH, DCIS and LCIS. However, the diagnostic usefulness of D5/16B4 antibody (anti-CK5/6) has never been compared with that of 34betaE12 antibody (anti-CK1/5/10/14). We performed immunostaining of CK 5/6 and CK1/5/10/14 on 100 breast lesions, including UDH ( n=31), ADH ( n=5), DCIS ( n=54) and LCIS ( n=10). Abundant immunostaining was observed in all UDH using both antibodies. Four of five of the ADH cases showed less than 5% of CK5/6 stained cells, the remaining case showed 30% of labeled cells. With 34betaE12 antibody, three of five of the ADH cases showed less than 5% labeled cells, while two cases showed more than 30% of stained cells. None of the 54 DCIS or the 10 LCIS was labeled by D5/16B4, while a lack of 34betaE12 immunostaining was observed in only 15 of 54 DCIS and 2 of 10 LCIS. We confirmed that D5/16B4 antibody directed against CK5/6 is useful in distinguishing UDH from the spectrum of ADH/DCIS/LCIS. We also demonstrated that D5/16B4 is far a more specific marker than 34betaE12 antibody.

[Clinical practice guidelines: Standards, Options and Recommendations for the diagnosis of carcinomas of unknown primary site]. / Recommandations pour la pratique clinique: Standards, Options et Recommandations 2002 pour le diagnostic des carcinomes de site primitif inconnu.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, 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 the outcome of cancer patients. OBJECTIVES: To define Clinical Practice Guidelines (CPG) for the diagnosis of carcinomas of unknown primary site. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers. RESULTS: The main recommendations for the diagnosis of carcinomas of unknown primary site are: 1) Diagnostic strategy should aim to identify anatomoclinical entities of carcinomas of unknown primary site for which there is a specific treatment. For other anatomoclinical entities, identification of the primary tumour has no impact on the prognostic or therapeutic consequences, thus a systematic complete assessment is unnecessary. 2) An immunohistochemical investigation for the diagnosis should be performed using an appropriate panel of specific antibodies. This should enable the diagnosis of lymphoma, melanoma, germ cell tumour and sarcoma to be eliminated and the diagnosis of prostate, breast, ovary, thyroid or neuroendocrine tumours to be positively identified. 3) A sample can be frozen to enable typing, cytogenetic and, particularly, molecular biological studies to be performed later. 4) The clinician and pathologist should compare their opinions before and after the pathological diagnosis.

[Standards, Options and Recommendations for the management of patient with carcinoma of unknown primary site]. / Standards, Options et Recommandations 2002 pur la prise en charge des patients atteints de carcinomes de site primitif inconnu (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Cancer Centers, 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 the outcome of cancer patients. The methodology is based on a 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 for carcinoma of unknown primary site (CUPS) patients according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 81 independent reviewers. RESULTS: The main recommendations for the management of patients CUPS are presented below: 1) An adapted immunochemistry test using a specific antibody battery should be performed for the anatomopathologic diagnosis. 2) The aim of the diagnosis is to identify specific anatomoclinical forms that can be treated by a specific treatment (standard, level of evidence B2). Except these forms, searching for the primary tumor site have no prognosis or therapeutic interest that can justify a systematic diagnosis assessment (standard, level of evidence B2). 3) The management of poorly differentiated neuroendocrine carcinoma consists of platin/etoposide based chemotherapy. There is no standard treatment for the differentiated forms. 4) Surgical node excision and adjuvant radiotherapy should be performed in case of epidermoid carcinoma with cervical node metastases. In the event of a non operable tumor, an irradiation should be performed. 5) The management of axillary node metastases in women with adenocarcinoma should be the same as the management of patients with lymph node metastases in breast cancer. If mammary MRI is negative, surgical treatment and mammary irradiation are not recommended and an axillary node excision should be performed. 6) The standard treatment for women with primary papillary serous carcinoma of the peritoneum is a surgical resection followed by chemotherapy, as recommended for ovarian cancer. 7) CUPS not belonging to any specific anatomoclinical forms can be treated by chemotherapy, symptomatic treatment alone or treatment based on biphosphonates in presence bone metastases.

[Standards, Options and Recommendations: good practice for the management and shipment of histological and cytopathological cancer specimens]. / Standards, Options et Recommandations: bonne pratique de l'acheminement et de la prise en charge initiale d'un prélèvement en anatomie et cytologie pathologiques en cancérologie.

CONTEXT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical specialty societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery. OBJECTIVES: Produce clinical practice guidelines for the management and shipment of histological and cytopathological cancer specimens using the methodology developed by the Standards, Options and Recommendations project. METHODS: The FNCLCC designated the group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers. RESULTS: The main recommendations are: 1) high-quality transmission of information between professionals is essential to the management of cancer specimens in order to assure high-quality diagnosis and evaluation of prognostic factors; 2) written procedures concerning sample shipment, handling, storage, registration, tracking and fixation exist; these procedures, as well as the necessary shipping material, will be sent to all clinical services involved; 3) when possible, fresh, unfractionated, oriented surgical samples will be submitted to the same histological and cytopathological laboratory; 4) samples collected for extemporaneous examination, freezing or cell culture must be shipped immediately under appropriate storage conditions; 5) Once frozen, samples can be stored in a deep freezer at temperatures of 80 C or below, or kept in liquid nitrogen; 6) fixing tissues shortly after sample collection is essential to prevent cell lysis; 7) computerised systems will be used to assure correct specimen registration and tracking in histological and cytopathological laboratories.