Successful treatment of primary cutaneous angiosarcoma of the nose with sequential chemo- and radiotherapy.

•The optimal treatment of primary cutaneous angiosarcoma is considered to be surgical exision.•Concurrent chemo-radiotherapy is efficient in the treatment of primary cutaneous angiosarcoma.•The toxicity profile of this association is acceptable.

A new optical probe for the detection of the sentinel lymph node using patent blue V dye in breast cancer: A preliminary study.

The present study presents a novel near-infrared optical probe for the sentinel lymph node (SLN) detection in breast cancer patients, based on the recording of scattered photons. The aim of this study was to improve the detection of patent blue V (PBV), a dye routinely injected during clinical practice. A combined injection of the dye and radioactive colloid was used in the 24 patients enrolled in the study. The clinical results of the ex vivo detection of 70 dye-marked SLNs are reported, subsequent to the injection of various quantities of PBV (0.25-2 ml). The accuracy and success rate of an isotopic probe for the detection of radioactive colloid tracer, the eye visibility threshold of the surgeon and the use of a new optical probe were examined. The radio-labeled and dye-marked sentinel lymph nodes were all detected by the radio-isotopic probe, as opposed to the 75% detected by the eye visibility threshold of the surgeon. The optical probe detected all of the nodes, regardless of the volume of the dye injected. The relative PBV concentration computed by the probe facing SLNs with infravisible/visually undetectable dye-mark was relatively constant at 5.5±1.4 µmol/l. The optical detection of the sentinel lymph nodes using PBV and the probe presented in this study have the potential to reduce the false negative detection rate. This instrument is likely to provide surgeons with a simple diagnostic tool, without significantly changing their surgical procedures.

[Late outcome of 89 patients with soft-tissue sarcomas treated by surgery and three different radiotherapy schedules]. / Résultats à long terme d'une série de 89 patients suivis pour un sarcome des tissus mous traités par chirurgie conservatrice et trois modalités d'irradiation postopératoire.

PURPOSE: To evaluate the outcome of patients treated for soft tissue sarcoma using three different post-operative radiotherapy schedules. METHODS AND MATERIALS: Between 1990 and 2003, 89 patients (median age 50.8 years) presenting with soft tissue sarcoma (located to the limbs for 66 of them) underwent post-conservative-surgery radiotherapy. Pathology was liposarcoma in 35 cases and 54 others tumors. Tumors grades (FNCLCC classification) were 1, 2, 3 or unknown in 29, 32, 19 and 9 cases, respectively. Surgery was considered as complete in 68 patients. Irradiation was normofractionated (NF) in 62 cases, hyperfractionated (BF) in 19 cases and hypofractionated (HF) in 8 cases. For all the patients, median delivered dose was 61 Gy [34-76 Gy]. RESULTS: Median follow-up of alive patients was 73,8 months [3-184]. Five-year local control (LC) and overall survival (OS) rates were 85.5 and 71.2% respectively. According to multifactorial analysis, favourable prognostic factors were for local control, complete surgery (P=0.0075) and for overall survival, complete surgery (P=0.0267), grade 1 tumor (P=0.012) and absence of distant recurrence (P=0.0488). There was no statistical evidence of difference for the five-year LC and OS rates between the patients who received NF, BF or HF. There were few complications and there were comparable in the three groups. CONCLUSIONS: This retrospective serie showed similar results for all the schedules. There is no evidence to recommend bifractionation. Hypofractionation should be used only in selected patients with poor performans status.

Comparative value of tumour grade, hormonal receptors, Ki-67, HER-2 and topoisomerase II alpha status as predictive markers in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy.

The aim of this study was to evaluate the predictive value of five different biological factors in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy: (1) tumour grade scored according to the Elston-Ellis classification, (2) hormonal receptor (HR) status; (3) tumour cell proliferation evaluated by Ki-67 staining, (4) HER-2 and topoisomerase II alpha (TopoIIalpha) expression evaluated by immunohistochemistry (IHC), (5) HER-2 and TopoIIalpha amplification evaluated by real-time polymerase chain reaction (PCR). 119 patients with operable breast cancer were treated with six cycles of FEC (100 5-fluorouracil (5-FU) 500 mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500 mg/m2). Tumour response was assessed clinically and by computed tomography (CT) scan, then by pathological assessment. The clinical overall response (OR) was 80%, with 19% of complete responders (CR). The radiological OR was 71%, with 16% of CR. A pathological CR was demonstrated in 13% of the patients according to the Sataloff classification. In the multivariate analysis, the absence of HR expression and Ki-67 > or = 20% were predictive for a clinical CR. A high tumour grade was predictive for a pathological CR. Overexpression or amplification of HER2 or Topollcalpha were not predictive of response.

[Standards, options and recommendations: practice guidelines for difficult diagnosis in surgical pathology or cytopathology in cancer patients]. / Standards, options et recommandations: conduite a tenir devant une lésion de diagnostic anatomo-cyto-pathologique difficile en cancérologie.

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).

Loss of MDM2 expression in human head and neck squamous cell carcinomas and clinical significance.

The transforming potential of the MDM2 oncogene has been attributed to the overproduction of the protein. In order to investigate regulation of MDM2 expression in head and neck squamous cell carcinomas, we analysed MDM2 gene amplification, and mRNA and protein expression in tumour specimens from 62 patients, in cell lines, and in normal epithelium adjacent to tumours or obtained from healthy patients. Additionally, TP53-induced MDM2-P2 transcription was evaluated and compared with TP53 status. MDM2 gene amplification and mRNA over-expression is infrequent, 7 and 9%, respectively. The predominant transcript codes for full-length MDM2 protein (90kD) and the level of alternatively spliced forms is not significant. We show that only 47% of tumours exhibit MDM2 immunostaining in more than one third of the neoplastic cells, and thus more than half of the tumours display no or low levels of MDM2 protein. In contrast, MDM2 protein is always detectable in basal and parabasal cells of morphologically normal epithelium outside the invasively growing tumour, as well as in a normal uvula sample. Similarly, the total amount of MDM2 transcripts analysed by reverse transcriptase-polymerase chain reaction is reduced in tumour samples compared to normal tissues, essentially due to a decrease in P2 transcript levels. The relationship between mutated p53 status and low levels of MDM2 found in cell lines is also observed to a certain extent in primary tumour samples. Overall, there is a high frequency of TP53 mutation and under-expression of MDM2 in the head and neck tumours. Moreover, a significant association of decreased MDM2 expression is observed with advanced tumour stage and 3 years survival.

Chemotherapy response of breast cancer depends on HER-2 status and anthracycline dose intensity in the neoadjuvant setting.

We evaluated the predictive value of a tumor's HER-2 status for chemotherapy response in the neoadjuvant setting and the effect of anthracycline dose intensity on this predictive value. HER-2 status was evaluated by immunochemistry on microbiopsy before neoadjuvant chemotherapy (monoclonal antibody CB-11; Novocastra) in 39 patients (group A) treated with FEC50 (500 mg/m(2) 5-fluorouracil, 50 mg/m(2) epirubicin, and 500 mg/m(2) cyclophosphamide) and 40 patients (group B) treated with FEC100 (500 mg/m(2) 5-fluorouracil, 100 mg/m(2) epirubicin, and 500 mg/m(2) cyclophosphamide). All tumors were stage II or noninflammatory stage III adenocarcinoma. Overall response rate (OR) was evaluated through ultrasound and mammographic measurements. Pathological complete response was evaluated by tumor excision and axillary node resection after six cycles of chemotherapy. Patient and tumor characteristics (age, tumor size, clinical nodal status, SBR grade, hormonal receptor status, and HER-2 expression) were similar in the two groups. In univariate analyses, anthracycline dose was the only factor predictive of response (OR = 61.5% with FEC50; OR = 82.5% with FEC100; P = 0.038). When anthracycline dose was correlated with HER-2 status, an OR of 73.9% was demonstrated in HER-2- tumors (tumors without HER-2 overexpression), and an OR of 12.5% was demonstrated in HER-2+ tumors (tumors with HER-2 with overexpression) in group A. In group B, an OR of 69.5% was demonstrated in HER-2- tumors, and an OR of 100% was demonstrated in HER-2+ tumors. There was no difference in OR for HER-2- tumors treated with FEC50 or FEC100 (P = 0.74). On the other hand, erbB-2+ tumors treated with FEC100 had a significantly better OR than HER-2+ tumors treated with FEC50 (P = 0.0003). In a multivariate analysis, the most powerful predictive factor of OR was a conditional variable associating anthracycline dose with HER-2 status. Low-dose anthracycline and HER-2+ predicted a poor OR, low- or high-dose anthracycline and HER-2- predicted an intermediate OR, and high-dose anthracycline and HER-2+ predicted a high OR. Our results merit additional studies, given the possibility for choosing anthracycline dose according to a tumor's HER-2 status.

Lymphatic mapping and sentinel node biopsy of operable breast cancer.

The aim of this study was to evaluate the reliability and accuracy of sentinel node biopsy for invasive breast cancer and the predictability of axillary node status. Between January 1996 and June 1997 a total of 73 patients underwent patent blue dye lymphatic mapping and sentinel node biopsy followed by standard (level I and II) axillary node dissection (one bilateral procedure). The sentinel node was identified in 82.4% (61/74) of the cases and was predictive of axillary status in 96.7% (59/61). The false-negative rate of the procedure was 8.0% (2/25). The sentinel node was involved in 37.7% (23/61) and was the only one invaded in 30.4% (7/23). The sensitivity of the procedure was 92% (CI95% 74-99%) and its specificity 100%. It is currently considered to be an attractive new procedure undergoing evaluation in prospective controlled trials. This study confirmed the reliability and reproducibility of intraoperative lymphatic mapping and sentinel node biopsy. This is the first step toward a new era of minimally invasive axillary surgery for breast cancer.

Antitumour activity of heparin on metastatic colon cancer.

We present the case history of a 47-year-old patient with metastatic colon cancer, whose anticoagulant treatment led to a prolonged disease-free survival.

Sarcoma after radiation therapy: retrospective multiinstitutional study of 80 histologically confirmed cases. Radiation Therapist and Pathologist Groups of the Fédération Nationale des Centres de Lutte Contre le Cancer.

PURPOSE: To evaluate the best strategy for treatment of sarcoma that occurs after radiation therapy. MATERIALS AND METHODS: Records were retrospectively reviewed for 80 patients with a confirmed histologic diagnosis of sarcoma that occurred after radiation therapy performed during 1975-1995. The patients were treated for breast cancer (n = 33, 42%), non-Hodgkin lymphoma (n = 9, 11%), cervical cancer (n = 9, 11%), benign lesions (n = 4, 5%), or other tumors (n = 25, 31%). Sarcoma occurred after a mean latency of 12 years (range, 3-64 years), with most (70%) developing in the soft tissue. Treatment included surgery (28 patients), surgery and chemotherapy (18 patients), chemotherapy only (15 patients), and radiation therapy (14 patients). RESULTS: By the end of the study, 51 patients were dead, including 46 due to sarcoma. Median survival was 23 months. Overall survival rates at 2 and 5 years, respectively, were 69% and 39% for patients treated with surgery, 10% and 0% for those treated with chemotherapy, and 52% and 35% for those treated with surgery and chemotherapy (P =.001). The 2- and 5-year rates for survival without recurrence were 54% and 32%, respectively. CONCLUSION: The results confirm the beneficial effect of surgery. Further study is needed to explore the roles of combined treatments.

Sentinel node biopsy in vulvar malignancies: a preliminary feasibility study.

Sentinel lymph node biopsies (SLNB) were investigated in 8 cases (6 squamous cell carcinomas, 2 melanomas) of vulvar malignancy. The sentinel node was detected by patent blue dye injection (1 case), pre operative lymphoscintigraphy with intra-operative gamma hand-held probe (2 cases), and combined techniques (5 cases). The procedure was successful in all cases but one (1 invasive squamous cell carcinoma) in which there was medial groin recurrence at 6 months. Nodal invasion was observed in only one case and was confined to the sentinel node. No specific morbidity related to the SLNB procedure occurred. SLNB appears to be a feasible and promising technique, however, requiring further evaluation before being considered as a reliable method to spare inguinofemoral lymphadenectomy in early-stage patients free of sentinel node metastasis, or to be substituted in screening elderly clinically node-negative females.

[Identification of axillary sentinel node by lymphotropic dye in breast cancer. Feasibility study apropos of 128 cases]. / Individualisation du ganglion axillaire sentinelle par colorant lymphotrope dans les cancers du sein. Etude de faisabilité à propos de 128 cas.

AIM OF THE STUDY: The goal of this study was to evaluate the technical feasibility of sentinel node biopsy in breast cancer and its predictivity of axillary node status. PATIENTS AND METHODS: Between January 1996 and June 1997, 128 patients with invasive breast carcinomas, referred to the Cancer Center of Strasbourg and Lyon (France), underwent lymphatic mapping (Patent Blue dye) and sentinel node biopsy followed by axillary clearance (Berg's level I to II). RESULTS: Sentinel node was identified in 76.5% of cases and was predictive of axillary status in 94.9% of cases. The false negative rate of the procedure was 5.1%. Sentinel lymph node was involved in 43.9% of cases and it was the only one involved in 30.2% of cases. The sensitivity of the procedure was 94% (CI: 95% = [88%-98%]) and its specificity 100%. CONCLUSION: Actually considered as new attractive procedure under ongoing evaluation in prospective controlled trials, this study confirms the feasibility and reproductibility of lymphatic mapping and sentinel node biopsy, first stage before entering a new era of minimally invasive axillary surgery in breast cancer.

[Oncocytic cancers of the thyroid. Hürthle cell cancers]. / Les cancers oncocytaires de la thyroïde. Cancers à cellules de Hürthle.

Hürthle cell cancers of the thyroid have been a subject of debate for many years because it is difficult to differentiate between benign and malignant tumours. Diverse therapeutic strategies have thus ensued. Recent work describing the morphologic and biologic criteria for a more precise diagnosis have led to better therapeutic strategies. We report a series of 85 tumours of the thyroid with Hürthle cells including 19 Hürthle cell tumours (22%) operated between 1976 and 1994. Hürthle cell tumour represented 6.7% of 282 thyroid cancers operated during the same period. The mean age of the patients was 56.6 years (range 23 to 78 years) and 63% of the tumours were large > or = 4 cm (classed T3T4). Treatment was total thyroidectomy in 79% of the cases. 5-year survival was 58.3% and 25% of the cases had metastatic extension at the time of initial treatment. Hürthle cell cancer have now been recognized as a particular anatomic and clinical entity. They were formerly confounded with vesicular cell cancers but now have been separated into a single entity due to a poor prognosis, lack of response to radioactive iodine and high incidence of metastasis. The current histological criteria make diagnosis more precise and allow more logical treatment with total thyroidectomy. A few familial cases have been reported. Although less frequent than in medullary cancer, this form would suggest that a genetic survey should be conducted for this particular type of thyroid cancer.

[Stromal tumors of the digestive tract. Prognostic evaluation of a series of 36 cases]. / Les tumeurs stromales du tube digestif. Evaluation pronostique d'une série de 36 cas.

Clinical outcome of gut's stromal tumors is difficult to predict by morphological data. The prognostic significance of a set of morphological criterias and immunostaining for proliferating cell nuclear antigen (PCNA) was studied. Thirty six tumours were classified benign (group A) or malignant (group B) according to ten year follow-up. Patient's sex and age, site of origin, tumour size, mitotic count and cytonuclear atypia were considered. Growth kinetic was studied by immunohistochemical analysis of PCNA (PC 10, DakoR). In univariate analysis, mitotic count, PCNA index, tumor size and cytonuclear atypia were associated with patient outcome. However, in multivariate analysis, only mitotic count and tumour size were independent prognosis factors. Thus, mitotic count remains the best prognostic indicator for these tumours since a cut off value of 2 mitosis/high power field allows an accurate prognosis in 33/36 tumors.

[Cystic dystrophy on an aberrant duodenal pancreas. Apropos of a case]. / Dystrophie kystique sur pancréas aberrant duodénal. A propos d'une observation.

Cystic dystrophy of the aberrant pancreas is a rare poorly understood condition which is difficult to diagnose and treat. The primary clinical signs are epigastralgia associated with poor general health and complications due to stenosis of the duodenum. Endoscopy gives the most information on tissue lesions and cystic formations in the duodenal mucosa. Although the condition is benign, and due to the lack of sufficient history in endoscopically treated cases, cystic dystrophy of the aberrant duodenal pancreas appears to require duodenopancreatectomy.

[Hepatosplenic silicosis]. / Silicose hépatosplénique.

A case of hepatosplenic silicosis complicating a pulmonary silicosis is reported. Numerous calcified splenic nodules seen with conventional radiology, ultrasound or computed tomography, hepatic microcalcifications and "egg shell" abdominal lymph nodes best seen with computed tomography represent the radiologic signs. However, hepatosplenic silicosis can only be confirmed by pathological examination of liver biopsies showing birefringent particles within hyalinized nodules.