Aerial dispersal of meticillin-resistant Staphylococcus aureus in hospital rooms by infected or colonised patients.

The aim of this study was to assess to what extent patients with meticillin-resistant Staphylococcus aureus (MRSA) at respiratory sites shed viable MRSA into the air of hospital rooms. We also evaluated whether the distance from the patient could influence the level of contamination. Air sampling was performed directly onto MRSA-selective agar in 24 hospital rooms containing patients with MRSA colonization or infection of the respiratory tract. Samplings were performed in duplicate at 0.5, 1 and 2-3 m from the patients' heads. Clinical and environmental isolates were compared using antimicrobial resistance patterns and pulsed-field gel electrophoresis. MRSA strains were isolated from 21 out of 24 rooms, in quantities varying from between 1 and 78 cfu/m3. In each of the 21 rooms, at least one of the environmental isolates was identical to a clinical isolate from the patient in that room. There was no significant difference in MRSA counts between the distance from the patient's head and the sampler. This study demonstrates that most patients with MRSA infection or colonisation of the respiratory tract shed viable MRSA into the air of their room. The results emphasise the need to study MRSA in air in more detail in order to improve infection control recommendations.

[Cushing's syndrome and adrenal adenoma. Two surprising associations]. / Maladie de Cushing et adénome cortico-surrénalien. Deux associations étonnantes.

INTRODUCTION: Cushing's syndrome has a very low incidence (1-10 cases/million/year), and familial cases are even more rare. We report on two situations involving different causes of Cushing's syndrome. CASES: In the first case, we describe the case of a patient with an adrenal adenoma 20 years before the occurrence of Cushing's disease related to the pineal gland. In the second case, two members of the same family were diagnosed almost simultaneously with adrenal cortical adenoma (mother) and Cushing's disease (daughter). DISCUSSION: These cases lead us to consider the known causes of familial Cushing's syndrome, which were not found here.

Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors.

Genetic alterations, such as loss of heterozygosity (LOH) at the 17p13 and 11p15 loci and overexpression of the insulin-like growth factor (IGF)-II gene, are associated with the malignant phenotype in sporadic adrenocortical tumors. A high risk of recurrence after surgery for adrenocortical tumors is predicted in cases with regional invasion or distant metastases. However, patients with localized tumors also have a high risk of recurrence. Reliable prognostic markers are required to identify subjects at high risk of recurrence. The aim of this study was to assess the prognostic value of three molecular markers (17p13 LOH, 11p15 LOH, and overexpression of the IGF-II gene) by assessing disease-free survival in a large series of adult patients with sporadic adrenocortical tumors. Adult patients (114) were prospectively followed up from diagnosis of the disease to June 1999 or to death. Malignancy was initially diagnosed in 18 patients (McFarlane stage III: n = 1 and stage IV: n = 17). The remaining 96 patients with localized adrenal disease at diagnosis (stage I: n = 60 and stage II: n = 36) were at risk of recurrence. Histological grade was assessed according to Weiss criteria, and tumors were classified into two groups (Weiss score or=4). Tumor samples were analyzed for LOH at the 17p13 and 11p15 loci and for IGF-II gene mRNA content. 17p13 LOH was a strong predictor of shorter disease-free survival in univariate analysis (P = 0.001; relative risk, 27), as were histological grade (Weiss score >or=4; P = 0.00001; relative risk, 15), 11p15 LOH (P = 0.004; relative risk, 9), tumor size (size >5 cm; P = 0.006; relative risk, 18), and overexpression of the IGF-II gene (P = 0.01; relative risk, 5). In a Cox proportional hazards regression model, histological grade (P = 0.04; relative risk, 4.2) and 17p13 LOH (P = 0.009; relative risk, 21.5) were independently associated with recurrence. Molecular markers, particularly 17p13 LOH, are predictive of long-term outcome in patients with sporadic adrenocortical tumors. In patients who have undergone curative surgery, routine assessment of these tumor markers is a useful complement to histological scoring for predicting recurrence and guiding decisions for subsequent follow-up and management.

Altered expression of novH is associated with human adrenocortical tumorigenesis.

NOVH belongs to the CCN (CTGF/CYR61/NOV) family of proteins, some of which have chemotactic, mitogenic, adhesive, and angiogenic properties. Whereas ctgf and cyr61 are growth factor-inducible, immediate-early genes, nov is expressed in growth-arrested or quiescent cells. As nov expression has been shown to be altered in both avian and human nephroblastomas and to be a target of WT1 regulation, NOV may play important roles in normal nephrogenesis and the development of Wilms' tumors. The aim of this study was to determine whether changes in novH expression were associated with tumorigenesis in tissues other than those of the kidney. We showed by Northern blotting and immunohistochemistry that among human adult endocrine tissues, the adrenal gland is a major site of novH expression, and that in adult and fetal adrenal tissue, novH is primarily expressed in the adrenal cortex. Studies with 12 benign and 18 malignant adrenocortical tumors revealed that the levels of novH mRNA and protein decreased significantly (P < 0.004) with progression of adrenocortical tumors from a benign to a malignant state. Although the localization of NOVH did not change, the N-glycosylation profile of benign and malignant tumors differed considerably from that of normal adrenocortical tissue, and these differences may affect the biochemical properties of the molecule. The properties of NOVH here provide the first evidence that this member of the CCN family could be involved in adrenocortical tumor development.

[Adrenocortical tumors with oncocytic cells: benign or malignant?]. / Tumeurs surrénaliennes à cellules oncocytaires: bénignité ou malignité?

Adrenocortical tumor with oncocytic cells are exceptional. They are composed exclusively or almost exclusively of oncocytic cells, which are large cells with eosinophilic granulations, corresponding to numerous mitochondria in electronic microscopic examination. This tumor is usually non-functional and benign, and has to be differentiated from the adrenocortical carcinoma.

[Which adrenal incidentalomas are to be operated?]. / Quels incidentalomes surrénaliens faut-il opérer?

AIM OF THE STUDY: The goal of this retrospective study was to recognize the incidence of adrenal tumors called incidentalomas, that are in fact symptomatic or hormone secreting tumors, to assess if the diagnostic criteria proposed in the literature are reliable for adrenal tumors found incidentally. PATIENTS AND METHOD: The records concerned 147 patients operated between April 1981 and December 2000 for an adrenal mass measuring 3 cm in diameter and larger on CT scan. Clinical and laboratory findings as well as hormone levels and imaging examinations (CT Scan, IRM, scintigraphy) were correlated with operative findings and results of histologic examinations. One hundred and three patients were operated by a traditional approach and forty four by videoendoscopic techniques. RESULTS: In 41 patients (28%), the tumors had to be classified as false incidentalomas (group 1) postoperatively. In 106 patients (72%), the nature of tumor was non definite. In this group 2, there were ten malignant tumors, two pheochromocytomas and 94 benign lesions. Age of patient, size of tumor, increase in size over time and radiological appearance represent criteria that are not reliable to separate malignant from benign tumors. CONCLUSIONS: Tumors of indeterminated and non specific nature only should be classified as incidentalomas. Imaging techniques as well as other criteria of malignancy cannot be relied upon to separate benign from malignant tumors. The risk even small of cancer or pheochromocytoma leads us to recommend excision of tumors > or = 3 cm in radiological diameter. The videoendoscopic approach is a good alternative to open operation in centers with this special expertise.

[Iodine 131 uptake by a bronchogenic cyst in a patient with differentiated carcinoma of the thyroid gland]. / Fixation à l'iode 131 d'un kyste bronchogénique chez une patiente ayant un carcinome différencié thyroïdien.

BACKGROUND: After thyroidectomy for differentiated thyroid carcinoma, extracervical uptake of iodine 131 is suggestive of metastasic dissemination. False positives can however occur. CASE REPORT: Differentiated thyroid carcinoma was found in a female patient with a non-functional nodule. Two years after subtotal thyroidectomy and an ablative dose of iodine 131, the whole body scan showed abdominal mediastinal uptake with low serum thyroglobulin level. Considering the possibility of tumor recurrence or lymph node metastasis, the mass was excised. The histology diagnosis was mediastinal bronchogenic cyst. DISCUSSION: To date, iodine uptake in a bronchogenic cyst has not been reported among other false-positives previously described. The pathophysiology of this iodine 131 uptake in a bronchogenic cyst is still unknown: the presence of NIS symporter or a protein which can organify iodine in the mucus cells of the cyst remains to be proven.

Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation: a report of three cases.

BACKGROUND/AIMS: Post-transplant lymphoproliferative disorders (PT-LPD) are a well-known complication of organ transplantation. Their incidence after liver transplantation in adults ranges from 1.8 to 4%. Reduction of immunosuppression led to remission in a few cases. Other treatments include chemotherapy, interferon alpha therapy and/or intravenous-immunoglobulins, or antiviral drugs. However, monoclonal antibodies directed against B-cell specific antigens have rarely been used in those patients. Our aim was to study the feasibility and efficacy of Rituximab, a new, promising human chimeric antibody that recognizes the CD20 antigen, for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation. METHODS: Rituximab (IDEC-C2HB8; Roche Laboratories, Neuilly-sur-Seine, France) was administered at a 375 mg/m2 dose on days 1, 8, 15, and 22, in an outpatient setting, in three patients with PT-LPD. The tumor was classified as polymorphic PT-LPD in two cases and PT-LPD with features of large cell lymphoma in one case. All the tumors expressed the CD20 antigen and were EBV-related, and the clonality was confirmed in all three cases. The 4 injections of the anti-CD20 monoclonal antibody were associated with reduced immunosuppression in the three patient. RESULTS: The treatment with Rituximab was well tolerated without any side effects. The two patients with polymorphic PT-LPDs underwent rapid complete remission, whereas the treatment modalities were ineffective in the patient with the large-cell non-Hodgkin-lymphoma. CONCLUSION: These results must be confirmed in a larger cohort of liver transplant recipients suffering from lymphoproliferation. However, they indicate rapid efficiency of Rituximab in association with reduced immunosuppression in these disorders.

Relation between cytogenetic characteristics of two human colonic adenocarcinoma cell lines and their ability to grow locally or metastasize or both: an experimental study in the nude mouse.

This study was aimed at elucidating the relation between the cytogenetic characteristics and the invasive ability of two human colonic adenocarcinoma cells lines, HT29 and CaCO2. These two cell lines have very different tumorigenic and metastatic capacities after intrasplenic injection into nude mice: high for HT29 and relatively weak for CaCO2. At the time of injection, cytogenetic studies of the two cell lines revealed shared abnormalities: paratriploidy with seven common extra chromosomes or chromosome regions and specific particularities. In HT29 cells, we observed a large marker of unknown origin, an isochromosome i(11)(q10) and 5, 12, 13, 15, 19, and (19q+) supernumerary chromosomes, and, finally, the absence of one chromosome 16. In CaCO2 cells, we observed a chromosome 1-derived marker with q24-31 duplication, 12q and 16 supernumerary chromosomes, and a der(16) marker. The most striking difference between the karyotypes of these two cell lines concerned chromosome 16 (under- and overexpressed in HT29 and CaCO2 cells, respectively), overexpression of chromosomes 13, 15, and 19 in HT29 cells, and the relative loss of 12p in CaCO2 cells. Although some differences may be due to the intrinsic characteristics of the stem line, the establishment of specific cytogenetic abnormalities points out the role of many regions of the genome in tumorigenic and metastatic capacities of malignant cells.

Increased expression of interleukin-4 during liver allograft rejection.

BACKGROUND/AIMS: To investigate the respective roles of interleukin-2 (IL-2) and IL-4 during rejection, we evaluated the expression of IL-2, IL-2 receptor and IL-4 in human liver allografts. METHODS: Immunohistochemistry and RT-PCR were performed in liver biopsies. To determine the effects of immunosuppression and cholestasis in IL-4 production, in vitro experiments were also designed. RESULTS: IL-2 protein and its mRNA were absent in the liver, with minimal expression of IL-2 receptor, during rejection. In contrast, IL-4 protein and its mRNA were highly expressed during acute and chronic rejection, whereas this expression was absent in stable liver transplant recipients. In vitro, cyclosporine potently inhibited IL-2 and IL-2 receptor expression of activated mononuclear blood cells, but poorly inhibited IL-4 expression. Chenodeoxycholic acid decreased IL-2 and IL-2 receptor expression, but increased IL-4 expression. CONCLUSIONS: During liver allograft rejection, IL-2 pathway is down-regulated, while IL-4 expression is increased by cholestasis and poorly inhibited by cyclosporine. These data suggest that IL-4 is involved in the mechanisms of liver allograft rejection in patients treated with cyclosporine.

Is acute rejection deleterious to long-term liver allograft function?

BACKGROUND/AIMS: The decreasing incidence of chronic rejection after liver transplantation emphasizes the need for an alternative end-point to assess the long-term consequences of acute rejection. The purpose of this study was to determine the effects of resolved episodes of acute rejection on late liver allograft function. METHODS: Parameters of hepatic function (liver biochemistry, indocyanine green and sulfobromophthalein clearances, histology) were analyzed in 170 consecutive adult recipients, who were followed prospectively on the basis of repeat annual work-up. Mean follow-up was 3.7+/-0.2 years. RESULTS: The rates of acute and chronic rejection were 51% and 4.1%, respectively. At the last follow-up, there was no significant difference in graft function between patients with a single episode of acute rejection (n=56) and those without rejection (n=84). Among patients treated for a single episode of acute rejection, late hepatic function was not influenced by the severity of acute rejection and the response to corticosteroids. In contrast, patients with recurrent acute rejection (n=30) had significant impairment of liver function tests (aspartate aminotransferase, p<0.05; alanine aminotransferase, p<0.01; alkaline phosphatase, p<0.01; gamma-glutamyl transpeptidase, p<0.001), lower dye clearances (indocyanine green, p<0.01; sulfobromophthalein, p<0.01) and more severe histologic damage (p<0.001). CONCLUSIONS: Single episodes of acute rejection do not impair the long-term hepatic function, whereas recurrent episodes leave sequellar damage to the liver allograft. These results provide a rationale for converting patients with rejection to a heavier immunosuppressive regimen, while leaving nearly half the recipients on a lifelong light immunosuppressive regimen.

[Possibilities and limits of surgical treatment of malignant adrenal cortex carcinomas. Apropos of a series of 74 cases]. / Possibilités et limites du traitement chirurgical des cortico-surrénalomes malins. A propos d'une série de 74 cas.

The aim of this study was to report our experience of 74 patients operated on for adrenocortical carcinomas in the last 15 years with particular reference to survival rate and prognostic factors. The tumors were secreting in 78% of the cases and non secreting in 22% of the cases, encompassing stade I: 7%, stade II: 43%, stade III: 21%, stade IV: 29%, according to the MacFarlane classification. All patients were operated on whatever the stade. Adrenalectomy with regional lymphadectomy was performed in 50% of the cases. Other procedures included extended adrenalectomy with nephrectomy (n = 27), hepatectomy (n = 7), and desobstruction or resection of inferior vena cava (n = 13). The resection was curative for 66% of the patients and palliative in 34% of the patients. Local recurrences were operated on in 13 patients. Operative mortality was 4%. Stade I and II had significantly the best actuarial survival rates (78 and 62% at 5 years, respectively), when compared to stade III (27%). Extension to the vena cava was not considered as a contra indication even in cases of massive extension. The survival rate of patients with local recurrences was the same as patients wich stade III: 32% at 5 years. Stade IV tumors had the poorer prognosis with a survival rate of 5% at 3 years. In this group, some patients may have benefited from mitotane. Further studies are mandatory to appreciate the benefit of adjuvant therapy with mitotane and palliative chemotherapy.

Pancreatic tumors: comparison of dual-phase helical CT and endoscopic sonography.

OBJECTIVE: The purpose of this study was to compare dual-phase helical CT and endosonography for the diagnosis and staging of pancreatic tumors. SUBJECTS AND METHODS: Thirty patients with suspected pancreatic tumors underwent endosonography and dual-phase helical CT. A pathologic diagnosis was obtained in all cases with surgery (n = 23) or biopsy (n = 7), resulting in 27 neoplasms. Dual-phase helical CT and endosonographic findings were correlated with surgical and pathologic findings to determine diagnosis and resectability of pancreatic tumors. RESULTS: Overall diagnostic sensitivity was 92% for dual-phase helical CT and 100% for endosonography (p = .45). Overall accuracy for staging of pancreatic tumors was 93% for both dual-phase helical CT and endosonography. Overall accuracy for predicting resectability was 90% for both dual-phase helical CT and endosonography. Accuracy of predicting unresectability was 100% for dual-phase helical CT and 86% for endosonography (p > .80). Differences were not considered statistically significant. CONCLUSION: Dual-phase helical CT and endoscopic sonography do not differ significantly for diagnosis and assessment of resectability of pancreatic tumors.

Structural and functional abnormalities at 11p15 are associated with the malignant phenotype in sporadic adrenocortical tumors: study on a series of 82 tumors.

Abnormalities of the 11p15 region with overexpression of the normally imprinted insulin-like growth factor II (IGF-II) gene have been implicated in the pathogenesis of adrenocortical tumors. We evaluated the frequency and distribution of 11p15 loss of heterozygosity (LOH) and IGF-II gene overexpression in a series of 82 sporadic adrenocortical tumors, screened for pathological functional imprinting of the 11p15 region in tumors not exhibiting LOH and evaluated the expression of H19 gene in these tumors. Abnormalities of the 11p15 region as LOH (loss of the maternal allele and duplication of the paternal allele) and/or IGF-II gene overexpression are frequent features of the malignant state and were found in 27 of 29 (93.1%) of the malignant tumors and in only 3 of 35 (8.6%) of the benign tumors. Tumors without abnormality of the 11p15 region (mainly benign tumors) did not exhibit pathological functional imprinting. In tumors with mosaicism for 11p15 LOH, biallelic expression of the IGF-II gene was constant in the tumor cell contingent not undergoing LOH. Abrogation of H19 expression correlated with the loss of the maternal allele (LOH or pathological imprinting), but did not always correlate with overexpression of the IGF-II gene. These data indicate the involvement of dysregulation of the 11p15 region in late steps of adrenocortical tumorigenesis and provide us with new molecular markers for a better diagnostic and prognostic evaluation of adrenocortical tumors.

[Hepatic distomatosis of tumor form after prolonged treatment with corticoids]. / Distomatose hépatique à forme tumorale après traitement prolongé par les corticoïdes.

A 49-year woman, living in Cameroun and treated by steroids for connective tissue disease, was admitted for a liver mass and epigastric pain. An increase in blood count of eosinophils (1,590.10(9)/L) was observed. Imaging examination showed the presence of a voluminous, multilocular, and heterogeneous hepatic lesion. Pathological examination of the liver showed no evidence of tumor but revealed a rounded cuticle remnant, compatible with bilharziosis eggs or loase transversal section, and Charcot-Leyden's crystals. Due to the uncertainty of diagnosis, a right hepatectomy was performed. Pathological and parasitological examination of the surgical specimen confirmed the diagnosis of hepatic distomatosis, with typical eggs of Fasciola hepatica within necrotic tissue, surrounded by eosinophilic inflammatory infiltrates. Specific serology was positive. The presence of intraparenchymatous eggs was unusual and reflected the ectopic migration of a mature fluke into the hepatic parenchyma, even though the worm was not found in the surgical specimen. Serology for fascioliasis should be performed in any patient suffering from hepatic lesions with eosinophilia.

[Differentiated thyroid carcinomas manifesting as toxic adenoma]. / Carcinomes thyroïdiens différenciés se manifestant comme un adénome toxique.

BACKGROUND: Hot thyroid nodules are generally benign. We report two exceptional cases of thyroid carcinomas mimicking toxic adenomas. CASE REPORTS: A 35-year-old man and a 55-year-old woman had thyroid carcinoma behaving as an autonomously hyperfunctioning nodule. DISCUSSION: Only twenty similar cases have been reported in the literature. While a hot nodule on radio-iodine scan is unlikely to be malignant, the possibility of carcinoma should not be overlooked. Surgery should therefore be the preferred treatment of toxic adenoma.

Immunohistochemical study of 100 pancreatic tumors in 28 patients with multiple endocrine neoplasia, type I.

One hundred pancreatic tumors ranging in size from 0.3 to 7 cm were studied in 28 patients (17 male and 11 female patients; mean age 35 years) with multiple endocrine neoplasia, type I. An immunohistochemical study was performed on deparaffinized sections using the following antibodies: neuron-specific enolase, chromogranin A or synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP), gastrin, adrenocorticotropic hormone, alpha-subunit of human chorionic gonadotropin, gonadotropin-releasing factor, serotonin, and calcitonin. Among the 100 tumors (all multiple), seven were unclassified, 10 were plurihormonal, and 83 produced a predominant hormonal secretion (with 50-90% of the same cell type), including 37 "A-cell tumors" (glucagon), 27 "B-cell tumors" (insulin), 11 PP-cell tumors, one G-cell tumor (gastrin) and one vasoactive intestinal peptide (VIP)-cell tumor. These multiple tumors had a different predominant hormonal secretion in the same patient in 23 of the 28 cases. There was a preferential association of A-cell tumor and B-cell tumor. Hyperplasia of the islets of Langerhans was not detected in adjacent pancreas. Nesidioblastosis was observed in 30% of cases.

Multifocal stenosing ulcerations of the small intestine revealing vasculitis associated with C2 deficiency.

A patient with cryptogenic multifocal ulcerous stenosing enteritis characterized by repeated bouts of intestinal obstruction, ulcerative stenosis of the small bowel relapsing after surgical resection, and steroid sensitivity is described. Fourteen strictures of the jejunum were found at laparotomy. Despite resection, abdominal pain persisted. Steroid therapy was effective but led to dependence. In our patient, cryptogenic multifocal ulcerous stenosing enteritis was associated with fever, asthma, Raynaud's phenomenon, sicca syndrome, heterozygous type I C2 deficiency (28-base pair gene deletion), stenosis, and aneurysms in selective mesenteric angiography. It is hypothesized that cryptogenic multifocal ulcerous stenosing enteritis might be related to a particular form of polyarteritis nodosa with mainly intestinal expression or to a yet unclassified independent vasculitis.

[Riedel's thyroiditis and lymphoma. Diagnostic difficulties]. / Thyroïdite de Riedel et lymphome. Difficultés diagnostiques.

Two cases of Riedel's thyroiditis demonstrated the difficulties encountered in diagnosis. In the first case, subtotal thyroidectomy was performed due to compressive goiter. The intraoperative macroscopic aspect suggested Riedel's thyroiditis. The pathology report also discussed the diagnosis, despite a major lymphoid component, as dense fibrosis had multilated the thyroid parenchyma. Subsequent clinical course led to the diagnosis of lymphoma. The clinical presentation in the second case was classical with rapid increase in size of a hard thyroid gland. Histology was however atypical showing calcifications and liquid cysts within the fibrous thyroid tissue. The initial signs of Riedel's thyroiditis, a very rare disease, usually suggest neoplasia: ligneous compressive goiter with deep adherences. Histologically, there is invasive fibrous thyroiditis with highly suggestive occlusive phlebitis in certain cases. The origin of the disease remains obscure. The differential diagnosis between a sclerosing form and lymphoma is particularly important for therapeutic management.