MGMT promoter methylation and correlation with protein expression in primary central nervous system lymphoma.

The O (6)-methylguanine-DNA-methyltransferase (MGMT) gene encodes for a DNA repairing enzyme of which silencing by promoter methylation is involved in brain tumorigenesis. MGMT promoter methylation represents a favorable prognostic factor and has been associated with a better response to alkylating agents in glioma and systemic lymphoma. Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal malignant lymphoma. The current standard of care, based on high-dose methotrexate chemotherapy, has improved prognosis but outcome remains poor for a majority of patients. Therapeutic progress in this field is conditioned by limited biological and molecular knowledge about the disease. Temozolomide has recently emerged as an alternative option for PCNSL treatment. We aimed to analyze the MGMT gene methylation status in a series of 24 PCNSLs, to investigate the relationship between methylation status of the gene and immunohistochemical expression of MGMT protein and to evaluate the possible prognostic significance of these biomarkers. Our results confirm that methylation of the MGMT gene and loss of MGMT protein are frequent events in these lymphomas (54 % of our cases) and suggest that they are gender and age related. MGMT methylation showed high correlation with loss of protein expression (concordance correlation coefficient = -0.49; Fisher exact test: p < 0.01), different from what has been observed in other brain tumors. In the subgroup of ten patients who received high dose chemotherapy, the presence of methylated MGMT promoter (n = 4), seems to be associated with a prolonged overall survival (>60 months in three of four patients). The prognostic significance of these molecular markers in PCNSL needs to be further studied in groups of patients treated in a homogeneous way.

Diet composition of Plagioscion squamosissimus (Heckel, 1840), a fish introduced into the Tietê River system.

Plagioscion squamosissimus is a species from the Amazon basin that was introduced into the Tietê River system. The present study aimed to analyse the feeding habits of this species in Bariri Reservoir and to verify the possible occurrence of ontogenetic changes in its diet composition. The samples were gathered in four periods of the year: February, June, September and November 2003. The fish were gathered with different fishing net meshes in three different reservoir portions. The alimentary items found in the stomachs were identified to the lowest possible taxonomic level and had abundance, occurrence frequency, volume and biomass determined. The Alimentary Index (IAi) was calculated for each alimentary item consumed by 'corvina' for each studied period. Comparisons among the diet of different size classes of P. squamosissimus were done using the similarity coefficient of Jaccard and the Cluster Analysis (UPGMA). The Friedman proof was performed to verify if there is a significant ontogenetic variation in the species diet and changes in the consumption of different alimentary categories by P. squamosissimus among the sampled periods. P. squamosissimus presented a piscivorous feeding habit, although other items were also consumed. The biggest values of IAi were obtained for the alimentary item fish in the months of June (0.47) and November (0.39). The item Ephemeroptera (Campsurinae) was the most representative in February (0.30) and June (0.45). Despite the fact that P. squamosissimus consumed an ample spectrum of alimentary items, the ontogenetic changes were evident through the exploration of aquatic insects by the younger classes and by a diet mainly composed of fish in adult individuals. The alimentary plasticity of P. squamosissimus evidenced in this study might have contributed to the success of this species in Bariri Reservoir.

Diet composition of Plagioscion squamosissimus (Heckel, 1840), a fish introduced into the Tietê River system / Composição da dieta de Plagioscion squamosissimus (Heckel, 1840), um peixe introduzido no sistema do Rio Tietê

Plagioscion squamosissimus is a species from the Amazon basin that was introduced into the Tietê River system. The present study aimed to analyse the feeding habits of this species in Bariri Reservoir and to verify the possible occurrence of ontogenetic changes in its diet composition. The samples were gathered in four periods of the year: February, June, September and November 2003. The fish were gathered with different fishing net meshes in three different reservoir portions. The alimentary items found in the stomachs were identified to the lowest possible taxonomic level and had abundance, occurrence frequency, volume and biomass determined. The Alimentary Index (IAi) was calculated for each alimentary item consumed by "corvina" for each studied period. Comparisons among the diet of different size classes of P. squamosissimus were done using the similarity coefficient of Jaccard and the Cluster Analysis (UPGMA). The Friedman proof was performed to verify if there is a significant ontogenetic variation in the species diet and changes in the consumption of different alimentary categories by P. squamosissimus among the sampled periods. P. squamosissimus presented a piscivorous feeding habit, although other items were also consumed. The biggest values of IAi were obtained for the alimentary item fish in the months of June (0.47) and November (0.39). The item Ephemeroptera (Campsurinae) was the most representative in February (0.30) and June (0.45). Despite the fact that P. squamosissimus consumed an ample spectrum of alimentary items, the ontogenetic changes were evident through the exploration of aquatic insects by the younger classes and by a diet mainly composed of fish in adult individuals. The alimentary plasticity of P. squamosissimus evidenced in this study might have contributed to the success of this species in Bariri Reservoir.

Plagioscion squamosissimus é uma espécie da Bacia Amazônica que foi introduzida no sistema do Rio Tietê. O presente estudo teve como objetivo analisar o hábito alimentar da espécie no reservatório de Bariri e verificar possível ocorrência de mudanças ontogenéticas na composição da dieta. As amostragens foram realizadas em quatro períodos do ano: fevereiro, junho, setembro e novembro de 2003. Os peixes foram coletados com redes de diferentes malhagens em três porções do reservatório. Os itens alimentares encontrados nos estômagos foram identificados até o menor nível taxonômico possível e tiveram abundância, frequência de ocorrência, volume e biomassa determinados. O Índice de Importância Alimentar (IAi) foi calculado para cada item alimentar consumido pela corvina para cada período estudado. Comparações entre as dietas das diferentes classes de tamanho de P. squamosissimus foram feitas utilizando-se o coeficiente de similaridade de Jaccard e a Análise de Cluster. A Prova de Friedman foi realizada para verificar se há variação ontogenética significante na dieta da espécie e se existem mudanças no consumo das categorias alimentares nos períodos amostrados. P. squamosissimus apresentou um hábito alimentar piscívoro, embora outros itens alimentares também tenham sido consumidos. Os maiores valores do IAi foram obtidos para o item alimentar peixes nos meses de junho (0,47) e novembro (0,39). O item Ephemeroptera foi mais representativo em fevereiro (0,30) e junho (0,45). Apesar do fato de P. squamosissimus consumir um amplo espectro de itens alimentares, as mudanças ontogenéticas ficaram evidentes pela exploração de insetos aquáticos pelas classes mais jovens e por uma dieta principalmente composta por peixe em indivíduos adultos. A plasticidade alimentar de P. squamosissimus evidenciada neste estudo pode ter contribuído para o sucesso da espécie nesse reservatório.

Processing conditions analysis of Eucalyptus globulus plywood bonded with resol-tannin adhesives.

Phenol-formaldehyde resol containing mimosa tannin extract was employed to produce plywood panels with two plies from Eucalyptus globulus veneers. The effect of processing conditions and tannin content on the gelation time of the adhesive in the glue line was evaluated by dynamic-mechanical analysis (DMA). These results were related with shear strength and wood failure of glue line in the final panels. Hazardous petrochemical phenol could be partially substituted in resols in industrial applications by addition of mimosa tannin extracts.

Heparin-induced thrombocytopenia.

BACKGROUND AND OBJECTIVE: There are two types of heparin-induced thrombocytopenia (HIT). HIT I is characterized by a transitory, slight and asymptomatic reduction in platelet count, occurring in the first 1-2 days of therapy, that resolves spontaneously; in contrast, HIT II, which has an immunologic origin, is characterized by a significant thrombocytopenia generally after the fifth day of therapy that usually resolves in 5-15 days only after therapy withdrawal. HIT II is the most frequent and dangerous side-effect of heparin therapy; in fact, in spite of thrombocytopenia, it can be complicated by venous and arterial thrombosis. Therefore, the recognition of HIT II may be difficult due to the underlying thrombotic symptoms for which heparin is administered. The aim of this article is to review the most recent advances in the field and to give critical guidelines for the clinical diagnosis and treatment of HIT II. STATE OF THE ART: The prevalence of HIT II, as confirmed by laboratory tests, seems to be about 2% in patients receiving unfractionated heparin (UH), while it is much lower in those receiving low molecular weight heparin (LMWH). The immunologic etiology of HIT II is largely accepted. Platelet factor 4 (PF4) displaced from endothelial heparan sulphate or directly from the platelets, binds to the heparin molecule to form an immunogenic complex. The anti-heparin/ PF4 IgG immunocomplexes activate platelets and provoke an immunologic endothelial lesion with thrombocytopenia and/or thrombosis. The IgG anti-heparin/PF4 immunocomplex activates platelets mainly through binding with the FcgRIIa (CD32) receptor. The onset of thrombocytopenia is independent of the dosage, schedule and route of administration of heparin. Orthopedic and cardiovascular surgery patients receiving post-surgical prophylaxis or treatment for deep venous thrombosis are at higher risk of HIT II. Besides thrombocytopenia, cutaneous allergic manifestations and skin necrosis may be present. Hemorrhagic events are not frequent, while the major clinical complications in 30% of patients are both arterial and venous thromboses which carry a 20% mortality. The diagnosis of HIT II should be formulated on the basis of clinical criteria and in vitro demonstration of heparin-dependent antibodies. Functional tests, such as platelet aggregation and (14)C-serotonin release assay and immunologic tests, such as the search for anti-PF4/heparin complex antibodies by an ELISA method are available. If HITT II is probable, heparin must be immediately suspended and an alternative anticoagulant therapy should be initiated before resolution of thrombocytopenia and the following treatment with a vitamin K antagonist. The general opinion is to administer low molecular weight heparin (in the absence of in vitro cross-reactivity with the antibodies), heparinoids such as Orgaran or direct thrombin inhibitors such as hirudin. PERSPECTIVES: Further studies are required to elucidate the pathogenesis of HIT II and especially to discover the clinical and immunologic factors that induce the occurrence of thrombotic complications. The best therapeutic strategy remains to be confirmed in larger clinical trials.

[Computerized tomography of the meniscus with a stress device]. / Studio con Tomografia Computerizzata dei menischi con apparecchio distrattore.

PURPOSE: We investigated the usefulness of a mechanical stress device to increase widening of the articular rima in CT studies of the meniscus on forced varus and valgus. MATERIAL AND METHODS: September 1997 to October 1998, we examined 284 patients with symptoms and clinical signs of meniscal injury. CT was performed during forced varus and valgus, depending on the site of the suspected damage, in 70 of 284 patients. We used an FOV of 18 cm, with a potential difference of 140 kVp and power of 170 mA. The reconstruction matrix was 512 x 512 and acquisition time was 3 s. A set of 8-10 partially overlapping scans were acquired craniocaudally, with slice thickness of 1.5 mm and gap of 1 mm. The mechanical strainer was locked in the correct position and a second set of 4-5 images acquired at the meniscus. Then the patients were submitted to arthroscopy to check the radiological findings. RESULTS: CT performed in forced varus and valgus had 96.8% specificity, 97.3% sensitivity and 97.1% diagnostic accuracy. Sensitivity was 100%, specificity 96% and diagnostic accuracy 98% in the medial meniscus, while we had 88.9%, 100% and 94.7% respectively in the external meniscus. CONCLUSIONS: CT with a mechanical stress device was extremely useful in defining the meniscal loose edge. It also showed the exact shape and complexity of meniscal injury, even in the cases with narrow articular rima or those where conventional CT had performed poorly.

Uneven distribution and size of rabbit lens capsule proteoglycans.

To document the ultrastructural distribution of lens capsule proteoglycans, rabbit lens capsules were fixed and stained overnight in 50 mM sodium acetate, pH 5.6, containing 2.5% glutaraldehyde, 0.2% Cuprolinic Blue and 0.2 M MgCl2. They were rinsed, stained with 1% aqueous sodium tungstate, embedded in Epon, sectioned (60 nm), and examined with an electron microscope at 60 kV. Proteoglycan-Cuprolinic Blue complexes mainly appeared as networks of small electron-dense filaments throughout the posterior and anterior capsules. The posterior capsule was a single layer with a network of small proteoglycan filaments gradually decreasing in size from the humoral side (90 x 10 nm) to the lenticular side (30 x 8 nm). The humoral side of the anterior capsule had a thin lamina (400 nm) containing large (180 x 40 nm), very electron-dense proteoglycan-Cuprolinic Blue complexes plus small proteoglycans. Below this lamina, the complexes were only seen as filaments slightly smaller than those in the corresponding area of the posterior capsule. Cuprolinic Blue binding of the anterior and posterior lens capsules revealed differences in the size and distribution of their sulphated proteoglycans which do not correspond to the patterns of their immunoreactivity with anti-heparan sulphate proteoglycan. The humoral lamina in the anterior capsules, with large proteoglycan structures, might be a distinct structural and functional compartment.

Antithrombotic drugs in the primary medical management of intermittent claudication: a meta-analysis.

BACKGROUND: There is no consensus on the efficacy of the antithrombotic drugs available for patients with intermittent claudication. METHODS: A Medline and manual search was used to identify relevant publications. Uncontrolled or retrospective studies, double reports or trials without clinical outcomes were excluded. Included studies were graded as level 1 (randomised and double- or assessor-blind), level 2 (open randomised), or level 3 (non-randomised comparative). Mortality, cerebro- or cardiovascular events, amputations, arterial occlusions or number of revascularization procedures performed in the lower limbs, pain-free and total walking distance, ankle brachial index and calf blood flow, were the main outcomes considered. When feasible, end of treatment results, either continuous or binary, were combined with appropriate statistical methods. RESULTS: Mortality was significantly decreased by ticlopidine compared to placebo (common odds ratio 0.68, 95% C.I., 0.49 - 0.95); clopidogrel decreased vascular events in comparison to aspirin (odds ratio 0.76, 95% C.I., 0.63 - 0.92) in level 1 studies. Arterial occlusions and the number of revascularization procedures performed were statistically significantly decreased by aspirin and ticlopidine, respectively. A small but statistically significant improvement in pain-free walking distance was determined by picotamide, indobufen, low molecular weight heparins, sulodexide and defibrotide, in small studies. CONCLUSIONS: Clopidogrel and ticlopidine do reduce clinically important events in patients with intermittent claudication and could be added to the primary medical treatment of these patients. The use of aspirin in these patients cannot be based on direct evidence, but only on analogy with coronary and cerebral atherosclerosis, where it has documented efficacy. Other antithrombotic drugs were not properly evaluated in patients with intermittent claudication.

Clinical and laboratoristic remission after cryosupernatant plasma exchange in thrombotic thrombocytopenic purpura.

We describe a case of thrombotic thrombocytopenic purpura (TTP) resistant to conventional therapy with fresh-frozen plasma (FFP)-plasma exchange (PEX) as well as to steroids, immunoglobulins, vincristine, dipyridamole, dextran and iloprost, achieving complete remission with cryosupernatant-plasma exchange. Our case shows the effectiveness of cryosupernatant PEX, when FFP-PEX and alternative therapies have failed.

Prevalence and patterns of symptomatic thromboembolism in oncohematology.

BACKGROUND AND OBJECTIVE: Approximately 15% of patients with cancer will experience a thrombotic episode at some time. Some patients are at particularly high risk depending on the histology of the malignant disease. The aim of the study was to determine the actual prevalence of thrombotic episodes in oncohematologic patients. DESIGN AND METHODS: We conducted a retrospective cohort analysis on a total of 515 patients that were admitted to the out-patients clinic (Institute of Medical Semeiotics) from January 1, 1986 to January 31, 1996. Two main groups were selected for this study: 133 patients suffering from a myeloproliferative disorder and 382 patients affected by a lymphoproliferative disorder. Follow-up lasted a median of 33 months in both groups (range 3-144 months). The difference between the observed events for each group was estimated by the odds ratio and chi square. Age and sex distribution were estimated by the Mann-Whitney test. Distribution of overall survival was estimated by the Kaplan-Meier method and compared between groups (DVT patients and non DVT patients) by the log-rank test. RESULTS: Twenty-three patients experienced a venous thrombotic disorder. The prevalence of deep vein thrombosis (DVT) in myeloproliferative and lymphoproliferative disorders was 8.27% (n = 11) and 3.14% (n = 12) respectively (odds ratio = 0.36; 95% CI = 0.14-0.90; chi-square = 4.94 p = 0.028). DVT was apparently idiopathic in 17 cases. In 4 patients another cancer was present; in the remaining 2 patients the thrombotic episode was associated with other predisposing factors. Although 7 of the 23 patients with DVT died, we cannot find any difference in the overall survival compared to oncohematologic patients who did not experience DVT. INTERPRETATION AND CONCLUSIONS: The prevalence of symptomatic DVT in the oncohematological patients is lower than reported for solid tumor. Patients affected by myeloproliferative disease have a higher risk of developing thrombosis. DVT if well-treated does not influence the survival of oncohematological patients.

Primary breast lymphoma.

Breast involvement by non-Hodgkin lymphoma is uncommon. Differences between primary and secondary breast lymphoma have been well-defined. However, histopathological features, therapeutic approach and outcome are still debated. We report the clinical and pathological features of 5 cases of malignant lymphoma primarily involving the breast. The literature is extensively reviewed paying particular attention to pathological features, therapeutic approach and survival analysis. All patients were women; the median age was 63.2 yr. The clinical course was indistinguishable from that of breast carcinoma. High-grade lymphoma was found in 4 cases; T cell lineage antigens were expressed in one case. All patients were in stage I or II. Treatment consisted of chemotherapy and/or radiotherapy. The follow-up period ranged from 20 to 54 months (mean, 33.2). All patients are still in complete clinical remission. Analysis of the literature showed that about 80% of cases are high grade lymphoma. In this group, stage I at presentation statistically gives the best survival rate; surgery does not appear to have a role in high-grade lymphoma treatment.

Remission in hairy cell leukemia-variant following splenic radiotherapy alone.

The therapeutic approach to hairy cell leukemia (HCL) is in some instances still debated. A variant form of HCL (HCL-V) characterized by high white cell count, splenomegaly, hypercellular and aspirable bone marrow has been described; differential diagnosis often arises with some other B-cell disorders which also show circulating hairy or villous lymphocytes. Conventional treatment for HCL is often less effective in HCL-V. In this report we describe a case with features consistent with HCL-variant treated with splenic radiotherapy. We not only obtained an hematological response but also the near total disappearance of bone marrow infiltration, compatible with a clinical complete remission. Clinical and biological implications of this phenomenon are discussed on the basis of this unexpected therapeutic result, obtained with splenic radiotherapy alone.

Idiopathic myelofibrosis with neutrophil myeloperoxidase deficiency: a case report.

We describe a case of idiopathic myelofibrosis with total neutrophil myeloperoxidase deficiency. The combination of this enzymatic defect with myelofibrotic changes in the nuclear shape of neutrophils confers a peculiar appearance on leukograms produced by a Technicon H*1. The clinical course of the disease was shortened by recurrent infections that may be ascribed, at least in part, to reduced leukocyte microbicidal ability.

Hypertriglyceridemia during long-term interferon-alpha therapy in a series of hematologic patients.

Adverse reactions to interferon-alpha (IFN-alpha) therapy include flu-like syndrome, bone marrow suppression, neurotoxic effects, and autoimmunity. A slight increase in triglyceride levels has been described less frequently during IFN-alpha administration. The incidence of IFN-alpha-induced hypertriglyceridemia seems variable, and there are no clear data on how to treat it. We report the effect of long-term (more than 12 months) IFN-alpha treatment on triglyceride levels in 43 patients suffering from hairy cell leukemia (18), multiple myeloma (10), chronic myelogenous leukemia (6), cryoglobulinemia (5), non-Hodgkin's lymphoma (3), and Sezary syndrome (1). Hypertriglyceridemia was found in 6 patients (15%). In 3 patients, gemfibrozil restored normal triglyceride values. This study suggests that hypertriglyceridemia is a minor side effect of long-term IFN-alpha therapy and that gemfibrozil might be considered the treatment of choice.

[High-resolution ultrasonography in the study of carpal tunnel syndrome]. / L'ecografia con alta risoluzione nello studio della sindrome del tunnel carpale.

We investigated the reliability of some US signs in the diagnosis of the carpal tunnel syndrome. We carried out a single-blind study with 13-MHz high resolution probes and electromyography on 132 patients with clinical evidence of the carpal tunnel syndrome; a control group of 20 asymptomatic patients was also submitted to US. Eighty-six of 107 patients with US signs of the carpal tunnel syndrome were then submitted to surgical decompression (resection of the transverse carpal ligament), while the extant 21 patients underwent conservative treatment and clinical follow-up. To diagnose the carpal tunnel syndrome, we considered the following US patterns: median nerve changes (swelling before its entrance into the carpal tunnel and flattening in the tunnel itself), palmar bowing of the flexor retinaculum, thickening of the transverse carpal ligament and increased depth of the carpal tunnel, as measured from the apex of the transverse carpal ligament convexity to the underlying carpal bone. Median nerve changes were unreliable signs and were missing in many cases: only 45 of 107 patients exhibited median nerve swelling before and/or its flattening in the carpal tunnel (42%). Such indirect signs as the thickening of the transverse carpal ligament in chronic cases were demonstrated in 94 of 107 patients with the carpal tunnel syndrome (88%) and canal deepening in all unilateral carpal tunnel syndromes was shown in 92 of 107 patients (87%); both these signs proved to be much more reliable. The palmar bowing of the flexor retinaculum was also difficult to demonstrate in surgical patients or in those with connective tissue fibrosis within the tunnel: this sign was demonstrated in 80 of 107 patients with the carpal tunnel syndrome confirmed with electromyography (75%). Tanzer and Rietze reported median nerve changes observed at surgery in 43% and 66% of their patients, respectively. Recent MR findings in asymptomatic wrists have demonstrated that the normal median nerve has an elliptical shape inside the carpal tunnel. To conclude, high resolution US exhibited 96% sensitivity, 95% specificity and 93% diagnostic accuracy and proved to play a major role in the diagnosis of the carpal tunnel syndrome.

[Role of Doppler color in the differential diagnosis of benign and malignant adenopathies]. / Ruolo del color Doppler nella diagnosi differenziale delle adenopatie benigne e maligne.

The diagnosis of enlarged lymph nodes is of the utmost importance especially in the treatment planning of cancer patients. US yields such morphological findings as node size, longitudinal/transverse diameter ratio, hilum visibility and cortical thickness, which however do not permit the differential diagnosis of benign from malignant forms. Some authors tried to distinguish inflammatory enlargement from metastatic forms on the basis of color Doppler findings, with conflicting and questionable results. We investigated the potentials of color Doppler US in the differential diagnosis of benign and malignant lymph node enlargement using morphological data and flow measurements in lymphatic hilum vessels. The palpable superficial lymph nodes of 70 patients were studied with color Doppler with a linear probe (7.5-10 MHz) equipped for Doppler flow measurements. The largest lymph node was studied in multiple enlargement. The final diagnosis was made with US-guided cytology and/or excisional biopsy. The venous hilar vessels were depicted with color Doppler US in 44/45 patients with lymphadenitis and only in 1/17 patients with metastatic enlargement. Spectral Doppler exams of the hilar arteries showed flows with a wide telediastolic component in lymphadenitis (relative RI:0.58), while flow was rapid and with poor telediastolic component (relative RI:0.84) in metastatic enlargement. Average RI was 0.62 in Hodgkin's lymphomas and 0.71 in all the other lesions. We conclude that the distortion and compression of the main hilar vessels in metastatic lymph node enlargement often prevents color Doppler depiction of venous vessels. Moreover, the compression and distortion of the intranodal capillary network (the "mass" effect) often results in increased RI, as detected with power Doppler in the lymphatic hilum. Even though color Doppler US studies of the hemodynamic changes in the hilar vessels need further validation in larger series of cases, our preliminary results suggest interesting potentials in distinguishing inflammatory from metastatic enlargement, which differentiation remains nevertheless difficult especially in Hodgkin's lymphoma.

Migration of metallic clips used during laparoscopic cholecystectomy and formation of gallstones around them: surgical implications from a prospective study.

Two groups of patients, with laparoscopic cholecystectomy (LC) were prospectively studied. All patients had serial plain abdominal X-ray examinations at various intervals after operation, to record the position of clips placed during LC. Seventy-one patients had less cystic duct (CD) dissection and > or =4 clips placed during the procedure. One hundred and fifteen patients had a larger CD dissection and only 4 clips placed (2 on the cystic artery and 2 on the CD, without additional clips on smaller vessels). In the former group, 7 patients had clip migration within 1 month and 11 within 1 year vs 1 either at 1 month or 1 year in the latter group (p = 0.01 and <0.001, respectively). During the follow-up, a 72-year-old man belonging to the former group had a recurrent common duct brown pigment stone containing a metallic clip 26 months after operation. He was treated successfully by endoscopic sphincterotomy. Factors predisposing to clip migration were short cystic stump, inadvertent clip dislodgment or incorrect placement, cystic duct ischemic necrosis, and local suppurative complications. Data from 29 patients with GS formed around suture material or phytobezoars observed during a prospective study and from the physicochemical and structural analysis of a cumulative series of 64 GS containing foreign bodies are also presented and discussed. It is suggested that metallic clips can migrate from their initial sites at various intervals within the peritoneal cavity or into the common duct and serve as a nidus for GS formation. Metallic clip migration in most cases is due to technical factors and can usually be prevented. However, it is not possible to prevent either clip migration or GS formation in every case, since even well-placed clips can migrate due to suppurative complications or local ischemic damage, and, once that penetration within the bile tract has occurred, GS are usually going to form, irrespective of the nature and the shape of the foreign body.