Outcome in early cervical cancer following pre-operative low dose rate brachytherapy: a ten-year follow up of 257 patients treated at a single institution.

OBJECTIVE: To report the outcome of preoperative low dose rate uterovaginal brachytherapy (LDR-UVBT) followed by radical surgery in the treatment of early cervical carcinoma. METHODS: 257 patients treated at Institut Curie from 1985 to 2008 for cervical carcinoma less than 4cm (FIGO stages Ib1, IIA and IIB) were studied. Patients received preoperative LDR-UVBT followed by hysterectomy Piver II type, with pelvic lymph nodes dissection (PLND). Predictive factors for pathological response to brachytherapy were analyzed with logistic regression, as well as survival rates. RESULTS: 44% of patients had residual tumor, 4.3% of patients had parametrial invasion and 17.9% of patients had lymph node involvement. Predictive factors for an incomplete pathological response were: initial clinical tumor size 20mm (OR 2.1), pN1 (OR 2.77), glandular carcinoma (OR 2.51) and lymphovascular invasion (OR 4.35). 7.4% and 2.7% of patients had respectively grade 2 and grade 3 post-therapeutic late complications. Median follow up was 122 months [1-282]. Five-year actuarial overall survival and disease free survival were respectively 83% CI [78.3-87.5] and 80.9% CI [76.3-85.7]. In multivariate analysis, factors affecting significantly the overall survival and disease free survival rates were: lymph node involvement (RR 4.53 and 8.96 respectively), parametrial involvement (RR 5.69 and 5.62 respectively), smoking (RR 3.07 and 2.63 respectively). CONCLUSIONS: Preoperative LDR-UVBT results in good disease control with a low complications rate. Its accuracy could be improved by a better selection of patients. Lymph nodes and parametrial evaluation remains a challenging issue that should be achieved with imaging and minimal invasive surgery.

Vacuum-assisted biopsies under MR guidance: results of 72 procedures.

OBJECTIVE: To investigate the clinical accuracy of magnetic resonance imaging-guided breast vacuum-assisted biopsy (MR-VAB). METHODS: Of 97 scheduled MR-VAB for single MRI lesions (negative second-look sonography) categorised as BI-RADS 4 or 5, 4 were cancelled (undetected lesion = 2, technical problems = 2). Twenty-one patients lost to follow-up were excluded. RESULTS: Twenty-three patients (median age 51 years) were at high risk (BRCA1 = 11, BRCA2 = 7, familial risk = 5), 23 had a suspected local recurrence of breast cancer. Seventy-two imaged lesions (focus = 1, mass enhancement = 32, non-mass-like enhancement = 39) were targeted with a 10-gauge VAB probe using MRI guidance, with a median of 18 specimens per lesion (median procedural time 72 min, range 50-131 min) followed by clip placement. In the case of benignity, MRI follow-up was performed (19 patients, median 389 days, range 33-1,592) or mammography (3 patients, median 420 days, range 372-1,354). According to histopathology results, 29 lesions were benign, 10 were high-risk (papillary = 2, radial scar = 1, atypical epithelial hyperplasia = 7) and 33 malignant (ductal carcinoma in situ = 8, invasive cancers = 25). Three false negative results and 3 complications occurred (1 malaise, 1 skin defect, 1 infection). CONCLUSION: MRI-guided VAB represents an accurate tool for the histological diagnosis of lesions visible only at MRI.

Hyperselective intra-arterial preoperative chemotherapy in patients with squamous cell carcinoma of the oral cavity: preliminary results.

OBJECTIVES: To investigate radiological response and findings after Intra Arterial Chemotherapy (IAC) for patients with Squamous Cell Carcinoma (SCC) of the oral cavity. MATERIALS AND METHODS: Patients received 1-2 cycles of IAC. Radiological assessment was performed on day 7 and day 21 after each cycle using CT scan and MRI. RESULTS: Six patients (median age: 52, ranging 46-60; male/female: 5/1) received 10 cycles (4 patients received 2 cycles). Primary tumors were floor of the mouth (4 patients) and oral tongue (2 patients). TNM classification was T2N0-2b in 3 patients and T4N0-1 in 3 patients. All patients had good locoregional/systemic tolerance and 3 showed clinical objective response (OR). Four patients were evaluable on both CT and MRI, 1 patient on MRI only and 1 patient did not tolerate imaging. Three patients showed OR both on CT and MRI, 1 patient showed stable disease (SD) on CT and OR on MRI and 1 patient showed SD on MRI. Contrast-enhancement of hemiperfused tongue was reported in all evaluable patients. Two patients presented intratumoral necrosis and 5 patients displayed local edema (MRI). One patient had modification of the sternocleidomastoid muscle after IAC. CONCLUSION: Radiological modifications were observed in the infused area and correlated well with clinical response. This study is ongoing.

[Continued complete remission of Merkel cell carcinoma with in-transit metastasis after treatment with isolated limb perfusion regional chemotherapy]. / Rémission complète persistante d'une tumeur de Merkel avec métastases satellites après traitement par chimiothérapie locorégionale de type membre perfusé isolé.

BACKGROUND: Primitive cutaneous neuroendocrine carcinoma or Merkel cell carcinoma is a rare tumor. It may be large since diagnosis is frequently delayed. The usual treatment is extensive surgical removal and radiotherapy. PATIENTS AND METHODS: A 69-year-old woman presented with a large Merkel cell carcinoma of the right leg. MRI showed a tumor invading the deep layers together with several satellite lesions. There was no regional nodal or visceral metastasis. Regional chemotherapy involving isolated limb perfusion with melphalan was performed in order to avoid amputation. Complete response was achieved a few months later and continues 5 and a half years later with minor sequelae comprising cutaneous sclerosis, pigmentation and mild ankle stiffness. DISCUSSION: Only five cases of Merkel cell carcinoma treated with isolated limb perfusion are reported in the literature: four of these involved local relapse and one was a primary tumor with regional lymph node involvement. Only one patient was still in complete remission 18 months after treatment. Isolated limb perfusion chemotherapy could thus be indicated in the treatment of advanced Merkel cell carcinoma of a limb in the absence of bone or regional lymph node involvement.

Correlation between the treated volume, the GTV and the CTV at the time of brachytherapy and the histopathologic findings in 33 patients with operable cervix carcinoma.

BACKGROUND AND PURPOSE: This study correlates the treated volume, the GTV and the CTV at the time of intracavitary brachytherapy (BT) with the histopathological findings obtained by surgery (S) in 33 patients (pts) with cervix carcinoma. PATIENTS AND METHODS: Sixteen pts (group I), FIGO stage IB1 (1), IB2 (4), IIB (10), IIIB (1), received external beam radiotherapy (EBT) with a total dose of 45 Gy in 5 weeks and concomitant CISPLATIN 40 mg/m(2) weekly, followed by BT up to a total dose of 15 Gy. S was performed 6-8 weeks thereafter. Seventeen pts (group II), FIGO IA2 (1), IB1 (14), IIB (2), were treated by BT alone with a total dose of 60 Gy and S after 6-8 weeks. All pts had a MRI examination after BT with a moulded applicator in situ for exact delineation of GTV, CTV and critical organs and a 3D dosimetry directly from MRI data. RESULTS: In group I (EBT + BT + S), the histopathological findings showed complete tumour sterilization (CR) in 56% of pts. Residual disease (RD) was found in 43%. Dosimetric data showed in pts with CR a larger mean treated volume (213 vs. 166 cm(3)) and a better mean coverage of the GTV and the CTV by the reference isodose (99 and 91%) as in pts with RD (85 and 77%). In group II (BT + S), CR was found in 52%, RD in 41%. Dosimetric data showed a larger mean treated volume (154 vs. 109 cm(3)) for pts with RD and a mean coverage of the GTV and the CTV by the reference isodose of 97 and 84% vs. 89 and 80% for pts with CR. CONCLUSIONS: An incomplete coverage of the GTV and/or the CTV by the reference isodose is an important risk factor for RD at the time of surgery. Furthermore, for pts who received BT alone, tumour size seemed to be a limiting factor for an accurate coverage of the CTV by the reference isodose.

Osteopontin expression in primary sarcomas of the pulmonary artery.

Primary tumors of the great vessels (aorta, pulmonal artery, and inferior vena cava) are rare and represent in most cases vascular leiomyosarcomas. Furthermore, there also exists a group of sarcomas arising from the intima, known as intimal sarcomas, associated with early metastasis and a very poor prognosis. Osteopontin (OPN) is an extracellular matrix protein that binds to alphav integrins, thereby promoting cell attachment, chemotaxis, and signal transduction. The reported association of OPN with malignancy and metastasis prompted us to examine the expression of this protein in seven sarcomas of the pulmonary artery. Strong OPN-specific staining could be detected in tumor cells and the adjacent extracellular matrix. Using a double labeling procedure, proliferating cells showed a strong positive reaction with antibodies against OPN. In addition, this protein could be demonstrated in the cytoplasm of macrophages. CD44, a putative receptor of OPN, was expressed on the cellular surface of tumor-associated lymphocytes. The expression of OPN in macrophages and tumor cells indicates that this molecule could possibly mediate cellular adhesion of both cell types in pulmonary sarcomas. The detection in the extracellular matrix shows that OPN is actively secreted and may interact with the corresponding receptor, CD44, on the surface of lymphocytes. Although the function of OPN is not yet fully understood, our data indicate that strong expression of this molecule in poorly differentiated sarcomas could play a role in the progression of malignancy and metastasis as described previously for carcinomas.

Expression of drug resistance related proteins in sarcomas of the pulmonary artery and poorly differentiated leiomyosarcomas of other origin.

Sarcomas are known to develop resistance to current chemotherapeutic strategies, displaying a multidrug-resistant phenotype. Mechanisms involved in drug resistance include reduced cellular drug accumulation, drug detoxification as well as alterations in drug target specificity. In seven sarcomas of the pulmonary artery (SPA) and ten leiomyosarcomas of other origin, we studied the immunohistochemical expression of P-glycoprotein (P-gp), multidrug-resistance protein (MRP), lung resistance protein (LRP), metallothionein (MT) and topoisomerase IIalpha. Upregulation was found in tumour cells for P-gp but not for MRP in SPA and other leiomyosarcomas. Topoisomerase IIalpha was expressed at high levels in tissue of primary tumours as well as recurrent tumours. Both P-gp and topoisomerase IIalpha were present in numerous tumour-associated vessels. LRP was expressed at high levels in SPA but to a lesser extent in the other leiomyosarcomas. MT was expressed at low levels but was markedly present at the border of necrosis. The overall survival and the relapse-free survival did not correlate with the expression of these factors. There was no significant relationship between treated and non-treated patients with respect to the expression of the examined molecules. P-gp, but not MRP, may play a role in the development of drug resistance. P-gp, LRP and topoisomerase IIalpha contribute to drug resistance through expression in tumour-associated vessels. Unique high levels of topisomerase IIalpha reflect the high proliferation rate of these tumours. MT seems to serve as a detoxifying agent of metabolites at the border of necrosis. Our findings underline the fact that multiple factors contribute to chemoresistance and that examination of a spectrum of relevant molecules is probably necessary to plan the best therapy.

Degradation of articular cartilage during the progression of antigen-induced arthritis in mice. A scanning and transmission electron microscopic study.

Ultrastructural changes of knee articular cartilage in C57B1/6 mice were studied in the course of antigen-induced arthritis by means of scanning and transmission electron microscopy. First damages of the cartilage surface were seen one hour after arthritis induction. The earliest signs were the loss of the superficial electron-dense layer as well as a progressive loss of proteoglycans in the cartilaginous matrix on the surface. Breaks of collagen fibres were already detected at the first day of arthritis. The chondrocytes of the superficial cartilage layer showed an increase of the intracellular membraneous system in the early phase of arthritis. Thereafter chondrocytes on the surface became more and more necrotic. On the 7th day of arthritis acute alterations of cartilage had developed completely. Many lacunae of chondrocytes were opened and the cartilage surface showed deep structural defects with adhering cells, probably lymphocytes and macrophages. In the following time these destructive processes were demonstrated along with cellular proliferation as a sign of repair attempts in hyaline cartilage.

Synovial giant cells in rheumatoid arthritis: expression of cystatin C, but not of cathepsin B.

This study was designed to investigate the expression of the matrix degrading proteinase cathepsin B and its endogenous inhibitor cystatin C in rheumatoid arthritis (RA) with special regard to multinucleated synovial giant cells (SGC). We applied an immunohistochemical double-labeling technique. SGC strongly expressed cystatin C and CD68, but were negative for cathepsin B. This staining pattern occurred in osteoclasts as well. Our findings support the idea that in RA matrix destruction by cathepsin B is not mediated by SGC or osteoclasts, but by mononuclear synoviocytes.

Expression of LFA-1 (CD11a/CD18) and ICAM-1 (CD54) in an animal model of renal interstitial fibrosis induced by unilateral ureteral obstruction.

Unilateral ureteral obstruction (UUO) has been used as an experimental model to induce tubulointerstitial damage and interstitial fibrosis. UUO is characterized by cellular proliferation, accumulation of inflammatory cells, and subsequent replacement of renal parenchyma by fibrous tissue. The influx of inflammatory cells into the renal interstitium is mediated by adhesion molecules. In this study, the development of fibrosis in the UUO model of the rat was examined and its relation to the time course of LFA-1 and ICAM-1 expression was assessed by immunohistochemistry. An increase in interstitial connective tissue was detected on day 10 after UUO, with a maximum on day 35. After unilateral ureteral obstruction, LFA-1 was prominently expressed in interstitial infiltrates, and to a lesser degree in glomerular areas. An initial increase in LFA-1-positive cells was noted already on day 10, with a maximum on day 20 and a decline on day 25. During the time course of 35 days after UUO, we observed an increase in ICAM-1 expression in the vascular endothelium, in tubular epithelium and in interstitial areas. This study shows that LFA-1 expression and ICAM-1 expression are concordant and that this process is associated with increasing interstitial fibrosis. ICAM-1 interstitial tissue may facilitate the homing and persistence of an interstitial infiltrate by ICAM-1/LFA-1 interactions, thereby preceding the development of renal interstitial fibrosis.

[An integrated medical image network of patient records: experience of the Picture Archiving and Communication System (PACS) of the Gustave-Roussy Institute]. / Un réseau d'images médicales intégrées au dossier du patient: expérience du Picture Archiving and Communication System (PACS) de l'Institut Gustave-Roussy.

The PACS (Picture Archiving and Communication System) is a central radiologic image archiving system coupled with an information system which allows rapid access to these images. It permits rapid access of the entire file of radiologic images of a patient for radiologists and clinicians. After installation of an MRI and CT scan unit at the IGR, a PACS system was installed in July, 2000. The preparation phase and characteristics of the PACS system at the IGR are described here. The data in the literature and the short experience of the PACS system at the IGR show benefits of this system at several levels: improved efficiency (for technicians, radiologists, and secretaries), improved image quality and interpretation, improved clinical management of patients resulting from more timely image interpretation and execution of clinical decisions, increased ease of image transfer for tele-imagery, and improved teaching and publication possibilities. The PACS significantly modifies work habits since the interpretation and consultation of images is done exclusively at the console and progressively obviates the need for actual films.

[Brachytherapy in cervix cancers: development of techniques and concepts]. / Curiethérapie dans les cancers du col utérin: évolution des techniques et des concepts.

Brachytherapy plays an important role in the treatment of patients with cervical carcinoma. Technical modalities have evolved during the last years and have benefited from imaging modalities development, specially MRI. Imaging modalities contribute to a better knowledge of tumoral extension and critical organs. Ultrasound during brachytherapy has led to the almost complete eradication of uterine perforation. In the future, a more systematic use of systems allowing optimization may induce a better dose distribution in the tumor as well as in the critical organs. Recent data provided information in favor of a better analysis in the relative role of dose-rate, total dose and treated volume and their influence on the local control and complication incidence. Concomitant radiochemotherapy represents a standard in the treatment of patients with tumoral size exceeding 4 cm. Some questions still remain: is concomitant chemotherapy of benefit during brachytherapy? Is there any place for complementary surgery, specially in patients with complete response after external irradiation with concomitant chemotherapy and brachytherapy? In order to answer the former question, a phase III randomized trial is going to start, with the Fédération Nationale des Centres de Lutte Contre le Cancer as a promoter.

[Endometrial surveillance of women on tamoxifen]. / Surveillance de l'endomètre des femmes sous tamoxifène.

Tamoxifen estrogenic action in the uterus induces several uterine diseases, benign and/or malignant ones. The risk of endometrial adenocarcinoma is multiplied by two to three in post-menopausal women. It is mainly linked with the doses and the length of the treatment. However, the global benefit of that drug is not questioned anymore. What matters now though is to find the best way to follow patients on tamoxifen. As a matter of fact, there is no such thing as a consensus that would include specific tests, nor a surveillance protocol in women on tamoxifen. Most teams do not propose any special follow-up. Some patients already show uterine anomalies prior to the beginning of tamoxifen treatment. A yearly gynecologic examination, together with a cervico-vaginal smear, is enough when there are no specific endometrial adenocarcinoma risk factors, nor anomalies detected during the pre-therapeutical evaluation, nor clinical symptomatology. In case of risk factors, or cervical stenosis, or again initial abnormalities though, a yearly transvaginal sonography may be proposed. There is no need for other exploratory examinations if the results are satisfying. In case of symptoms, anomalies in the cervico-vaginal smears, intra-uterine liquid retention with a stenosed cervix, or suspicious endometrial thickness, then an endometrial sampling must be carried out. MRI could be of interest in asymptomatic patients with unclear ultrasonography images. Follow-up must be continued after interruption of tamoxifen. It is important to inform patients about the additional risks of developing an endometrial cancer because of tamoxifen, while still being reassuring. Besides, it is absolutely necessary to recommend them to take quickly medical advice in case of gynecologic symptoms.

[Swallowing study with kinetic MRI using a single shot fast spin echo sequence in healthy volunteers and patients treated for head and neck cancer]. / Etude de la déglutition par ciné-IRM utilisant la séquence single shot fast spin écho (SSFSE) chez des volontaires sains et des patients traités pour un cancer ORL.

PURPOSE: To evaluate the single shot fast spin echo sequence (SSFSE) rapid MRI sequence for swallowing study, to describe the swallowing phases analyzable by kinetic MR Imaging and to show the advantages and the limits of the method in patients treated for head and neck cancer. METHODS AND MATERIALS: A preliminary study was conducted in 8 healthy volunteers and 11 patients treated for a head and neck cancer between June 1999 and April 2001. Examinations were obtained on a 1.5 T machine using a multi-slice SSFSE sequence with an acquisition time of 1 second/slice. The different phases of swallowing were analyzed. Examinations were done with and without water ingestion. RESULTS: Kinetic MRI allows to clearly analyze the anatomy and the dynamic of the tongue, the soft palate, the hyoid bone, the larynx and the posterior pharyngeal wall. The hypopharyngeal and esophageal phases were suboptimally assessed. CONCLUSION: Kinetic MRI allows to clearly analyze the oral and early pharyngeal phases of swallowing, which can be correlated with normal and surgically reconstructed areas in spite of the low temporal resolution and the non-physiologic position. It is simple and rapid to perform and may be useful in treated patients with head and neck cancer.

[Significance of sentinel lymph node biopsy in Merkel cell carcinoma. Analysis of 11 cases]. / Intérêt du ganglion sentinelle dans le carcinome de Merkel. Analyse de 11 cas.

BACKGROUND: Merkel cell carcinoma is an aggressive cutaneous neoplasm with a high propensity for nodal metastases. Regional lymph node involvement develops in 45 to 65 p. 100 of patients. We evaluated in Merkel cell carcinoma the use of sentinel lymph node biopsy which allows the identification of occult nodal metastases. PATIENTS AND METHODS: Eleven patients diagnosed with Merkel cell carcinoma without clinical nodal involvement underwent pre-operative lymphoscintigraphy followed by sentinel lymphadenectomy with histologic analysis. Identification of microscopic nodal metastases led to complete lymph node dissection and adjuvant radiation therapy to the lymph node basin. RESULTS: The sentinel lymph node was successfully identified in 9 patients. Two patients demonstrated metastatic disease in their sentinel lymph nodes. At subsequent complete node dissection, one of two patients had an additional metastatic lymph node. None of the eleven patients experienced recurrent disease at a follow-up varying from 1 to 42 months. One patient with a negative sentinel lymph node experienced lymphoedema. COMMENTS: Our results are consistent with the 14 published studies which totalled 93 patients with Merkel cell carcinoma and identified 29 patients (30 p. 100) with nodal involvement. Metastatic disease was identified only after immunohistochemical analysis in 20 p. 100 of these patients (n=6). Lymph node involvement appears to be a bad prognostic factor with 29.6 p. 100 of disease recurrence, as opposed to 3 p. 100 in patients with an uninvolved sentinel lymph node. Although the prognostic significance of this technique seems interesting, there is no optimal therapeutic approach to sentinel lymph node involvement.

[Preoperative concomitant radiochemotherapy in bulky carcinoma of the cervix: Institut Curie experience]. / Chimioradiothérapie concomitante préopératoire dans les carcinomes du col utérin de stades IB2 à IIB : expérience de l'institut Curie.

PURPOSE: To evaluate the treatment results of patients (pts) with Figo stage IB2, IIA, IIB cervical carcinoma (CC) treated with preoperative radiochemotherapy, followed by extended radical hysterectomy. PATIENTS AND METHODS: Retrospective study of 148 women treated at the Institut Curie for operable Figo Stage IB2 to IIB, biopsy proved CC. Among them, 70 pts, median age 46 years, were treated using the same regimen associating primary radiocisplatinum based chemotherapy, intracavitary LDR brachytherapy, followed by extended radical hysterectomy. Kaplan-Meier estimates were used to draw survival curves. Comparisons of survival distribution were assessed by the log-rank test. RESULTS: Complete histological local-regional response was obtained in 56% of the pts (n=39). Residual macroscopic or microscopic disease in the cervix was observed in 28 pts (40%). All but one had in situ microscopic residual CC. Lateral residual disease in the parametria was also present in nine pts, all with residual CC. Pelvic lymph nodes were free from microscopic disease in 56 pts (80%). Eight of 55 (11%) radiological N0 patients had microscopic nodal involvement, as compared to 6/15 (40%) radiological N1 (p=0.03). Seventeen pts (25%) had residual cervix disease but negative nodes. After median follow-up of 40 months (range, 8-141), 38/70 patients (54.1%) are still alive and free of disease, six (8.6%) alive with disease, and 11 (15.8%) patients were lost for follow-up but free of disease. CONCLUSION: The treatment of locally advanced CC needs a new multidisciplinary diagnostic and treatment approach using new therapeutic arms to improve the survival and treatment tolerance among women presenting this disease.

Osteoprotegerin reduces the loss of periarticular bone mass in primary and secondary spongiosa but does not influence inflammation in rat antigen-induced arthritis.

OBJECTIVE: To assess the effect of osteoprotegerin (OPG) on joint swelling, synovial inflammation and cartilage destruction, periarticular and axial bone volume, and bone turnover in rat antigen-induced arthritis (AIA). DESIGN: Rats were treated with OPG (3 mg/kg/day) at regular intervals from day 1 to day 20 of AIA. Disease activity was evaluated by measurement of joint swelling as well as, joint inflammation and destruction by histology. Bone volume and cellular turnover parameters of secondary spongiosa of the right tibia head and the third lumbar vertebra were evaluated by histomorphometry. Periarticular bone volume of the primary spongiosa at the right tibia head was measured by linear scanning. The findings were compared with those of PBS-treated AIA and healthy animals. RESULT: OPG treatment did not reduce joint swelling or histological signs of inflammation. Cartilage destruction was reduced. However, this effect did not reach statistical significance . In the secondary spongiosa OPG treatment reduced the loss of periarticular bone volume. However, the latter did not reach the level of healthy controls. OPG treatment significantly reduced parameters of bone formation and bone resorption. In the primary spongiosa, OPG-treatment led to a higher amount of mineralized tissue and a greater number of trabeculae compared to PBS-treated animals with AIA or healthy controls. In the axial skeleton, OPG treatment reduced bone formation and bone resorption parameters compared to healthy animals. This treatment had no influence on bone volume. CONCLUSIONS: In periarticular bone of AIA rats, OPG treatment reduced the loss of bone volume and decreased the bone turnover, thus preventing periarticular bone destruction. OPG treatment had no influence on inflammatory process or on cartilage destruction.

Microcystic adnexal carcinoma: report of seven cases including one with lung metastasis.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a rare cutaneous neoplasm, with a high rate of local recurrences. OBJECTIVE: A series of MAC was analyzed and compared to previously published cases. METHODS: Seven cases of MAC were identified in the register of the institution. Medical and pathological records were reviewed. RESULTS: The primary MAC were located on the face in all patients, and 85% were initially misdiagnosed. The mean follow-up duration was 108 months. The recurrence rate was high: 4 patients developed recurrences. In 3 patients, the course of the disease was severe: one of them developed pathologically proven lung metastasis. CONCLUSION: The present study and review of the literature confirm the clinically aggressive evolution of MAC and its rare ability to give rise to metastasis. Long-term clinical follow-ups with imaging investigations are mandatory.

Adoptive transfer of susceptibility to antigen-induced arthritis into severe combined immunodeficient (SCID) mice: role of CD4+ and CD8+ T cells.

Antigen-induced arthritis (AIA) in mice occurs after immunization and a subsequent intra-articular injection with methylated bovine serum albumin (mBSA). The role of T lymphocytes in the adoptive transfer of susceptibility to AIA into SCID mice was investigated. Pooled spleen and lymph node cells from immunized syngeneic or allogeneic donor mice, isolated either before or after the induction of arthritis, could transfer the capacity both to develop arthritis and to produce antibodies to mBSA, collagen type II and cartilage proteoglycans into SCID mice. The intra-articular injection of mBSA in responder animals, immediately after the cell transfer, resulted in a chronic arthritis in the induced joint. The histologic examination revealed synovial hyperplasia, mononuclear infiltration of the synovial membrane, exudation of polymorphonuclear leucocytes into the joint space, and chondrocyte death. The depletion of CD4+ T cells before transfer prevented the manifestation of arthritis in SCID mice, with a concomitant decrease in antibody levels to mBSA, collagen type II and cartilage proteoglycans. In contrast, removal of CD8+ T cells did not significantly affect the transfer of arthritis into SCID mice. The results demonstrate an essential role of CD4+ T cells in the pathogenesis of AIA, whereas CD8+ T cells do not seem to be required for the induction and perpetuation of this disease.