Follow-up of thyroid cancer patients with "poor prognosis".

High-risk differentiated thyroid carcinoma is the most frequent thyroid tumor of "poor prognosis": this mainly includes patients with extra-thyroidal invasion, or distant metastases, younger patients (<16 years old), and older patients (>45 years old). Among them, metastatic patients with multiple organ involvement at the time of initial diagnosis have the higher risk of cancer death. Additionally, certain histological subtypes are classically more aggressive, and bilateral cervical lymph-nodes metastases or mediastinal involvement may also impart a poorer overall prognosis. More aggressive therapy to produce undetectable thyrotropin levels is usually recommended, although the benefit of such therapy and how long to maintain thyrotropin suppression has not been definitively established. As about two-thirds of the recurrences occur within the first decade after initial treatment, this first decade seems particularly critical, even if follow-up is necessary throughout the patient's life as recurrences may also occur over several decades. Coupled thyroglobulin (Tg) and Tg antibody (TgAb) assay is the first-line tool in their follow-up. Tg measurement obtained either after LThyroxine withdrawal or rhTSH stimulation may permit the selection of patients for scanning with a high dose of 131-I. When either basal Tg level is high or TgAb increases, it appears preferable to schedule patients directly for 131-I therapy followed by a post-therapy WBS. Therefore, the discovery of foci of 131-I uptake is possible in 60 to 80% of such patients. 131-I therapy is proposed as long as metastases trap 131-I without any limit to the cumulative dose of 131-I, although the risk of leukemia rises slightly above a 500 mCi (18,500 MBq) cumulative dose. But when 131-I post therapeutic WBS is negative, any further administration of 131-I is not justified. Alternative imaging procedure is thus required to detect metastases that have lost their capacity to concentrate 131-I. Conventional imaging with ultrasonography of the neck, a CT scan or an MRI of the neck and the chest and bone imaging, and even non-conventional imaging with other isotope procedures, such as 18-FDG whole-body scanning, are nowadays indicated. The goal is to localize those metastases in order to propose the more adequate therapeutic options.     

The site of platelet destruction in thrombocytopenic purpura as a predictive index of the efficacy of splenectomy

The significance of the site of platelet sequestration in determining the indication for splenectomy in idiopathic thrombocytopenic purpura (ITP) is a controversial subject. However, most of the negative conclusions are based on 51chromium labelling of homologous platelets. We report here the results of an analysis of 222 cases in which the kinetic study of 111indium-oxinate-labelled autologous platelets was performed under homogeneous technical conditions. 103 of these patients subsequently underwent splenectomy. This study demonstrates that the site of platelet sequestration in active ITP constitutes a variable independent of the patient's age, history of the disease and its severity (platelet count, lifespan). The sequestration site is a good predictive element of the short-term efficacy of splenectomy (71/76 cases with splenic sequestration obtained a platelet count exceeding 100 x 10(9)/l versus 7/13 cases with mixed sequestration and 1/14 cases with hepatic sequestration), and the long-term results (6 months to 5 years after splenectomy) do confirm the clinical value of this study.     

Prevalence of monoclonal gammopathy in patients with primary hyperparathyroidism: a prospective study

BACKGROUND: The association between primary hyperparathyroidism (PHPT) and monoclonal gammopathy has been reported, but whether it is fortuitous remains unsettled. We conducted a prospective study to determine the prevalence of monoclonal gammopathies in patients with surgically proved PHPT. METHODS: In 101 consecutive patients with PHPT, serum immunoglobulins were systematically studied using agarose gel electrophoresis and immunofixation before and, when appropriate, after parathyroid surgery. The PHPT population was compared with a control series of patients with other diseases requiring surgery and with a group of patients with benign disease of the thyroid gland matched for age and sex to the PHPT population. RESULTS: Monoclonal immunoglobulin was detected in 10 (10%) of 101 patients with PHPT (including 2 with multiple myeloma) compared with 2 (2%) of 127 patients who underwent other surgery (P =.005) and 3 (3%) of 101 patients with benign thyroid diseases (P =.04). CONCLUSIONS: The prevalence of monoclonal gammopathies is high in patients with PHPT. At minimum, sensitive serum protein electrophoresis should be performed routinely in all patients with PHPT. Conversely, in patients with monoclonal gammopathy who have hypercalcemia but no other symptoms of progressive disease, clinicians must seek PHPT.     

A new HLA-B*27 allele (B*2719) identified in a Lebanese patient affected with ankylosing spondylitis

Eighteen different HLA-B*27 alleles (B*2701-B2718) have so far been recognized by the WHO Nomenclature Committee for Factors of the HLA System. Frequency and disease association of these alleles with spondyloarthropathies differ among ethnic groups. We describe here a novel HLA-B*27 subtype identified in a Lebanese patient suffering from ankylosing spondylitis (AS). This new variant differs from the common HLA-B*2705 DNA sequence at five different nucleotide positions. These nucleotide changes lead to three amino acid differences in the alpha2 domain; Thr to Ile at position 94, Leu to Ile at position 95 and Asn to Arg at position 97. Since this novel allele is encountered in an AS patient, the associated sequence changes are not expected to affect significantly neither the presentation of a putative arthritogenic peptide nor the conformation-dependent recognition by effector cells.     

Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T cell clonal expansions found in autoimmune inflammatory processes

We recently evidenced a dramatic enrichment for T cells reactive against Epstein-Barr virus (EBV) within inflamed joints of two rheumatoid arthritis patients. To assess the generality of this phenomenon and its relevance to autoimmunity, we studied the responses of CD8 T cells from patients with either acute or chronic inflammatory diseases (rheumatoid arthritis: n = 18, ankylosing spondylitis: n = 5, psoriatic arthritis: n = 4, Reiter's syndrome: n = 3, arthrosis: n = 2, uveitis: n = 2, multiple sclerosis: n = 2, encephalitis: n = 1) against viral proteins derived from EBV and another common herpes virus, human cytomegalovirus (CMV). T cell responses against EBV and/or CMV epitopes were frequently observed within CD8 T cells derived from chronic inflammatory lesions, irrespective of their location (knee, eye, brain) and autoimmune features. In most cases, CD8 T cells derived from affected organs yielded stronger anti-viral T cell responses than CD8 T cells derived from patients' PBL, even in chronic inflammatory diseases devoid of autoimmune features or induced by defined bacterial agents. Taken together, these results suggest that the presence of virus-specific T cells within inflamed lesions of patients suffering from autoimmune diseases is a general phenomenon associated with chronic inflammation rather than the initiating cause of the autoimmune process. Since this phenomenon was sometimes associated with long-term T repertoire biases within inflamed lesions, the physiopathological significance of T cell clonal expansions found in a recurrent fashion within chronically inflamed autoimmune lesions should be interpreted with caution.     

CD4+NKG2D+ T cells in Crohn's disease mediate inflammatory and cytotoxic responses through MICA interactions

BACKGROUND & AIMS: Crohn's disease (CD) is an inflammatory bowel disease characterized by uncontrolled immune responses to bacterial flora, with excessive activation of T lymphocytes. MICA is a stress-induced major histocompatibility complex-related molecule expressed on normal intestinal epithelial cells (IECs) and recognized by the NKG2D-activating receptor on CD8(+) T cells, gammadelta T cells, and natural killer cells. We examined the role of MICA-NKG2D interactions in the activation of T lymphocytes in CD. METHODS: MICA expression was analyzed by flow cytometry on IECs isolated from patients with active inflammatory bowel disease and controls. NKG2D expression and function were analyzed on lamina propria and peripheral blood lymphocytes. RESULTS: MICA expression was significantly increased on IECs in CD, with higher expression in macroscopically involved areas. A subset of CD4(+) T cells expressing NKG2D was increased in the lamina propria from patients with CD compared with controls and patients with ulcerative colitis. CD4(+)NKG2D(+) T cells with a Th1 cytokine profile and expressing perforin were increased in the periphery and in the mucosa in CD. CD4(+)NKG2D(+) T-cell clones were functionally active through MICA-NKG2D interactions, producing interferon-gamma and killing targets expressing MICA. IECs from patients with CD had the ability to expand this subset in vitro. CD4(+)NKG2D(+) lamina propria lymphocytes from patients with CD highly expressed interleukin-15R alpha, and interleukin-15 increased NKG2D and DAP10 expression in CD4(+)NKG2D(+) T-cell clones. CONCLUSIONS: These findings highlight the role of MICA-NKG2D in the activation of a unique subset of CD4(+) T cells with inflammatory and cytotoxic properties in CD.     

Effect of (18)F-FDG PET/CT imaging in patients with clinical Stage II and III breast cancer

PURPOSE: To investigate the potential effect of using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial assessment of patients with clinical Stage II or III breast cancer. METHODS AND MATERIALS: During 14 consecutive months, 39 patients (40 tumors) who presented with Stage II or III breast cancer on the basis of a routine extension assessment were prospectively included in this study. PET/CT was performed in addition to the initial assessment. RESULTS: In 3 cases, PET/CT showed extra-axillary lymph node involvement that had not been demonstrated with conventional techniques. Two of these patients had hypermetabolic lymph nodes in the subpectoral and infraclavicular regions, and the third had a hypermetabolic internal mammary node. PET/CT showed distant uptake in 4 women. Of these 4 women, 1 had pleural involvement and 3 had bone metastasis. Overall, of the 39 women, the PET/CT results modified the initial stage in 7 (18%). The modified staging altered the treatment plan for 5 patients (13%). It led to radiotherapy in 4 patients (bone metastasis, pleural lesion, subpectoral lymph nodes, and internal mammary nodes) and excision of, and radiotherapy to, the infraclavicular lymph nodes in 1 patient. CONCLUSIONS: PET/CT can provide information on extra-axillary lymph node involvement and can uncover occult distant metastases in a significant percentage of patients. Therefore, initial PET/CT could enable better treatment planning for patients with Stage II and III breast cancer.