Restoring bottom-up communication in brain-heart interplay after trauma-focused psychotherapy in breast cancer patients with post-traumatic stress disorder.

BACKGROUND: The psychological impact of breast cancer (BC) is substantial, with a significant number of patients (up to 32 %) experiencing post-traumatic stress disorder (PTSD). Exploring the emotional aspects of PTSD through the functional brain-heart interplay (BHI) offers valuable insights into the condition. BHI examines the functional interactions between cortical and sympathovagal dynamics. This study aims to investigate changes in functional directional BHI after trauma-focused (TF) psychotherapy, specifically Eye Movement Desensitization and Reprocessing (EMDR), in comparison to treatment as usual (TAU) among BC patients with PTSD. To our knowledge, this study represents the first examination of such changes. METHODS: We enrolled thirty BC patients who met the criteria for a PTSD diagnosis, with fourteen receiving EMDR and fifteen receiving TAU over a two- to three-month period. We analyzed changes in the emotional response during a script-driven imagery setting. Quantification of the functional interplay between EEG and sympathovagal dynamics was achieved using the synthetic data generation model (SDG) on electroencephalographic (EEG) and heartbeat series. Our focus was on the difference in the BHI index extracted at baseline and post-treatment. RESULTS: We found statistically significant higher coupling in the heart-to-brain direction in patients treated with EMDR compared to controls. This suggests that the flow of information from the autonomic nervous system to the central nervous system is restored following EMDR-induced recovery from PTSD. Furthermore, we observed a significant correlation between improvements in PTSD symptoms and an increase in functional BHI after EMDR treatment. CONCLUSIONS: TF psychotherapy, particularly EMDR, appears to facilitate the restoration of the bottom-up flow of interoceptive information, which is dysfunctional in patients with PTSD. The application of BHI analysis to the study of PTSD not only aids in identifying biomarkers of the disorder but also enhances our understanding of the changes brought about by TF treatments.

Repression of miR-31 by BCL6 stabilizes the helper function of human follicular helper T cells.

Follicular helper T cells (TFHs) are a key component of adaptive immune responses as they help antibody production by B cells. Differentiation and function of TFH cells are controlled by the master gene BCL6, but it is largely unclear how this transcription repressor specifies the TFH program. Here we asked whether BCL6 controlled helper function through down-regulation of specific microRNAs (miRNAs). We first assessed miRNA expression in TFH cells and defined a TFH-specific miRNA signature. We report that hsa-miR-31-5p (miR-31) is down-regulated in TFH; we showed that BCL6 suppresses miR-31 expression by binding to its promoter; and we demonstrated that miR-31 inhibits the expression of molecules that control T-helper function, such as CD40L and SAP. These findings identify a BCL6-initiated inhibitory circuit that stabilizes the follicular helper T cell program at least in part through the control of miRNA transcription. Although BCL6 controls TFH activity in human and mouse, the role of miR-31 is restricted to human TFH cell differentiation, reflecting a species specificity of the miR-31 action. Our findings highlight miR-31 as a possible target to modulate human T cell dependent antibody responses in the settings of infection, vaccination, or immune dysregulation.

Drug hypersensitivity in clonal mast cell disorders: ENDA/EAACI position paper.

Mastocytosis is a clonal disorder characterized by the proliferation and accumulation of mast cells (MC) in different tissues, with a preferential localization in skin and bone marrow (BM). The excess of MC in mastocytosis as well as the increased releasability of MC may lead to a higher frequency and severity of immediate hypersensitivity reactions. Mastocytosis in adults is associated with a history of anaphylaxis in 22-49%. Fatal anaphylaxis has been described particularly following hymenoptera stings, but also occasionally after the intake of drugs such as nonsteroidal anti-inflammatory drugs, opioids and drugs in the perioperative setting. However, data on the frequency of drug hypersensitivity in mastocytosis and vice versa are scarce and evidence for an association appears to be limited. Nevertheless, clonal MC disorders should be ruled out in cases of severe anaphylaxis: basal serum tryptase determination, physical examination for cutaneous mastocytosis lesions, and clinical characteristics of anaphylactic reaction might be useful for differential diagnosis. In this position paper, the ENDA group performed a literature search on immediate drug hypersensitivity reactions in clonal MC disorders using MEDLINE, EMBASE, and Cochrane Library, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation.

NS5A inhibitors impair NS5A-phosphatidylinositol 4-kinase IIIα complex formation and cause a decrease of phosphatidylinositol 4-phosphate and cholesterol levels in hepatitis C virus-associated membranes.

The hepatitis C virus (HCV) nonstructural (NS) protein 5A is a multifunctional protein that plays a central role in viral replication and assembly. Antiviral agents directly targeting NS5A are currently in clinical development. Although the elucidation of the mechanism of action (MOA) of NS5A inhibitors has been the focus of intensive research, a detailed understanding of how these agents exert their antiviral effect is still lacking. In this study, we observed that the downregulation of NS5A hyperphosphorylation is associated with the actions of NS5A inhibitors belonging to different chemotypes. NS5A is known to recruit the lipid kinase phosphatidylinositol 4-kinase IIIα (PI4KIIIα) to the HCV-induced membranous web in order to generate phosphatidylinositol 4-phosphate (PI4P) at the sites of replication. We demonstrate that treatment with NS5A inhibitors leads to an impairment in the NS5A-PI4KIIIα complex formation that is paralleled by a significant reduction in PI4P and cholesterol levels within the endomembrane structures of HCV-replicating cells. A similar decrease in PI4P and cholesterol levels was also obtained upon treatment with a PI4KIIIα-targeting inhibitor. In addition, both the NS5A and PI4KIIIα classes of inhibitors induced similar subcellular relocalization of the NS5A protein, causing the formation of large cytoplasmic NS5A-containing clusters previously reported to be one of the hallmarks of inhibition of the action of PI4KIIIα. Because of the similarities between the effects induced by treatment with PI4KIIIα or NS5A inhibitors and the observation that agents targeting NS5A impair NS5A-PI4KIIIα complex formation, we speculate that NS5A inhibitors act by interfering with the function of the NS5A-PI4KIIIα complex.

The response of the different soybean metallothionein isoforms to cadmium intoxication.

Cadmium is a highly toxic heavy metal for both plants and animals. The presence of Cd in agricultural soils is of major concern regarding its entry into the food chain, since Cd compounds are readily taken up by plants, and accumulated in edible parts due to their high solubility. In this study, we first demonstrate the high capacity for Cd concentration of soybean grains. Consequently, we considered the study and characterization of the molecular determinants of Cd accumulation -such as metallothioneins (MT)- to be of major practical importance. We report here the first characterization of the soybean MT system, with the identification of nine genes (one of which is a truncated pseudogene), belonging to the four plant MT types. The most highly expressed of each type was chosen for further function analysis. All of them are expressed at high levels in soybean tissues: GmMT1, GmMT2 and GmMT3 in roots, shoots and seeds, and GmMT4 only in seeds. The corresponding recombinant soybean MTs, synthesized in Escherichia coli cells cultured in metal supplemented media, exhibit greater cadmium than zinc binding capacity. These results suggest a definite role of GmMTs in Cd(II) accumulation as one of the main responses of soybean to an overload of this metal.

How much specific is the association between hymenoptera venom allergy and mastocytosis?

BACKGROUND: The preferential association of mastocytosis with hymenoptera sting reactions is well known, but there is no data on the prevalence of clonal mast cell disorders in subjects with severe systemic reactions due to foods or drugs. METHODS: Patients with food- or drug-induced severe systemic reactions, including anaphylaxis, and increased serum tryptase were studied for the presence of mastocytosis, and compared with a population of patients with hymenoptera allergy. The aetiological role of foods or drugs was assessed according to current recommendations. Systemic reactions were graded in severity according to the procedure described by Mueller. Serum tryptase was considered increased if the level was >11.4 ng/ml. Subjects with increased tryptase had dermatological evaluation and Bone marrow(BM) aspirate-biopsy, which included histology/cytology, flow cytometry and detection of KIT mutations. RESULTS: A total of 137 subjects (57 male, mean age 42 years) were studied. Of them, 86 proved positive for drugs and 51 for foods. Overall, out of 137 patients, only nine (6.6%) had a basal tryptase >11.4 ng/ml, and only two (1.5%) were diagnosed with mastocytosis. This was clearly different from patients with hymenoptera allergy, where 13.9% had elevated tryptase and 11.1% had a clonal mast cell disorder. CONCLUSION: The association of clonal mast cell disorders with hymenoptera allergy seems to be more specific than that with food- or drug-induced systemic reactions.

Standardization of skin tests for diagnosis and prevention of hypersensitivity reactions to oxaliplatin.

BACKGROUND: Platinum salts can cause allergic sensitization. Recently, hypersensitivity reactions to oxaliplatin, the most recent platinum coordination complex introduced into clinical practice, have been reported. OBJECTIVE: To validate and standardize skin tests to diagnose and possibly prevent hypersensitivity reactions to oxaliplatin. The secondary aims were to confirm IgE-mediated pathogenesis of the clinical manifestations and to evaluate skin tests to predict patients at risk of hypersensitivity reactions to oxaliplatin. METHODS: We performed skin tests at increasing concentrations of oxaliplatin on 15 patients never exposed to platinum salts, on 10 patients treated with oxaliplatin without any adverse reactions, and on 4 patients who had shown hypersensitivity reactions to the drug. Moreover we performed skin tests on 8 additional patients starting before the 5th dose and following a course of chemotherapy. RESULTS: A positive skin reaction to the prick test at a concentration of 1 mg/ml was seen in 1 patient with hypersensitivity reactions. The intradermal test was positive in all the patients with hypersensitivity reactions at a concentration of 0.1 mg/ml. It was negative in the 15 nonexposed subjects, and in the 10 patients who had been exposed to oxaliplatin without hypersensitivity reactions. The skin test administered to patients before chemotherapy was positive in one case. CONCLUSION: A skin prick test at a concentration of 1 mg/ml and, in the case of a negative response, an intradermal test at the optimal concentration of 0.1 mg/ml should be used, starting from the 5th course of therapy, to diagnose and prevent hypersensitivity reactions to oxaliplatin.

Disruption of iron homeostasis in Saccharomyces cerevisiae by high zinc levels: a genome-wide study.

Zinc is an essential metal that, when in excess, can be deleterious to the cell. Therefore, homeostatic mechanisms for this cation must be finely tuned. To better understand the response of yeast in front of an excess of zinc, we screened a systematic deletion mutant library for altered growth in the presence of 6 mM zinc. Eighty-nine mutants exhibited increased zinc sensitivity, including many genes involved in vacuolar assembling and biogenesis. Interestingly, a mutant lacking the Aft1 transcription factor, required for the transcriptional response to iron starvation, was found to be highly sensitive to zinc. Genome-wide transcriptional profiling revealed that exposure to 5 mM ZnCl(2) results in rapid increase in the expression of numerous chaperones required for proper protein folding or targeting to vacuole and mitochondria, as well as genes involved in stress response (mainly oxidative), sulphur metabolism and some components of the iron regulon. The effect of the lack of Aft1 both in the absence and in the presence of zinc overload was also investigated. Exposure to high zinc generated reactive oxygen species and markedly decreased glutathione content. Interestingly, zinc excess results in decreased intracellular iron content and aconitase and cytochrome c activities in stationary-phase cultures. These findings suggest that high zinc levels may alter the assembly and/or function of iron-sulphur-containing proteins, as well as the biosynthesis of haem groups, thus establishing a link between zinc, iron and sulphur metabolism.

Barrett's esophagus: combined treatment using argon plasma coagulation and laparoscopic antireflux surgery.

The treatment of Barrett's esophagus is still controversial. Actually, the only method to prevent the development to cancer is endoscopic surveillance, which ensures good results in terms of long-term survival. An ideal treatment capable of destroying columnar metaplasia, followed by squamous epithelium regeneration could potentially result in a decrease of the incidence of adenocarcinoma. Recently most ablative techniques were used, such as photodynamic therapy, ablation therapy with Nd-YAG laser or argon plasma coagulation and endoscopic mucosal resection. We started a prospective study in January 1998, enrolling 94 patients affected by Barrett's esophagus and candidates for antireflux repair in order to assess the effectiveness and the results of endoscopic coagulation with argon plasma combined with surgery in the treatment of uncomplicated Barrett's esophagus. All patients underwent endoscopic treatment with argon plasma; we observed complete response in 68 patients (72.34%), 27 of them (39.7%) underwent antireflux surgery and the other 41 continued medical therapy. Post-operatively 19 patients (70%) underwent regular surveillance endoscopies and in two cases metaplasia recurred. The final objective of these combined treatments should be the complete eradication of metaplastic mucosa. Our experience was that argon plasma coagulation combined with antireflux surgery or proton pump inhibitor therapy gave satisfactory results, even if follow-up is too short to evaluate the potential evolution of metaplasia to cancer. For this reason, we recommend that this technique should be done only in specialized centres and that these patients continue their endoscopic surveillance program.

Alterations of rCBF and mitochondrial dysfunction in major depressive disorder: a case report.

OBJECTIVE: A mitochondrial disease might be considered when depressive disorder is associated with diabetes mellitus or other symptoms commonly found in mitochondrial disease. Scattered regional cerebral blood flow (rCBF) decreases and increases have been reported in depressive and mitochondrial disorders. A 61-year-old male patient with early adult onset of depressive disorder and a slowly developing multiorgan syndrome including diabetes mellitus was investigated. METHOD: 99mTc-HMPAO rCBF SPECT and muscle biopsy to assess mitochondrial functions were performed in the patient. RESULTS: Alterations of rCBF were found in the patient, with the most pronounced decreases in the left dorsolateral frontal and inferior parietal lobes, and the most pronounced increases in the bilateral superior parietal lobes. Muscle biopsy revealed myopathy and decrease of mitochondrial adenosine triphosphate production rates (MAPRs). CONCLUSION: The MAPRs decreases support the suspicion of mitochondrial dysfunction in the patient. A subgroup of depressed patients may have mitochondrial dysfunctions.

Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability.

Histone H3 lysine 9 methylation has been proposed to provide a major "switch" for the functional organization of chromosomal subdomains. Here, we show that the murine Suv39h histone methyltransferases (HMTases) govern H3-K9 methylation at pericentric heterochromatin and induce a specialized histone methylation pattern that differs from the broad H3-K9 methylation present at other chromosomal regions. Suv39h-deficient mice display severely impaired viability and chromosomal instabilities that are associated with an increased tumor risk and perturbed chromosome interactions during male meiosis. These in vivo data assign a crucial role for pericentric H3-K9 methylation in protecting genome stability, and define the Suv39h HMTases as important epigenetic regulators for mammalian development.

Epirubicin, cisplatin and continuous infusion 5-fluorouracil (ECF) in locally advanced or metastatic gastric cancer: a single institution experience.

AIMS AND BACKGROUND: The role of chemotherapy in locally advanced or metastatic gastric cancer has been controversial, but chemotherapy has recently been shown to relieve tumor-related symptoms, improve quality of life and prolong survival when compared with best supportive care. Furthermore, palliative chemotherapy is also cost-effective. "Second-generation" combination chemotherapy regimens were developed in the 1980s with high activity in advanced or metastatic gastric cancer (EAP, FAMTX, PELF, ECF). In randomized studies, EAP demonstrated no difference in activity but a significantly higher overall toxicity and toxic death rate than FAMTX, and the ECF (epirubicin, cisplatin, 5-fluorouracil) regimen gave a survival and response advantage, tolerable toxicity, better quality of life and was more cost-effective than FAMTX. METHODS: Sixty patients with locally advanced or metastatic gastric cancer were treated with the ECF regimen (21 weeks of 5-fluorouracil given by continuous infusion through a central line at 200 mg/m2 for 24-hr combined with cisplatin at 60 mg/M2 iv and epirubicin at 50 mg/M2 iv beginning on day 1 and repeated every 3 weeks for 8 courses). There were 42 males and 18 females, with a median age of 64 years (range, 40-74). The median performance status was 1. The histologic type was adenocarcinoma in 44 patients and undifferentiated carcinoma in 16 (27%). Three patients had locally advanced disease (5%) and 57 had metastatic disease (95%). Seven patients (12%) had received prior chemotherapy for advanced disease. RESULTS: All patients were assessable for toxicity and 55 for response (5 had insufficient treatment). Toxicity was mild or moderate, and there was no toxic death. Incidence of WHO toxicity > or = 2 was nausea and vomiting in 3%, mucositis in 3%, leukopenia in 7%, anemia in 3%, and thrombocytopenia in 2%. Port-a-Cath toxicity was thrombosis in 4, dislocation in 2 and infection in 3 patients. Seven complete responses and 13 partial responses (overall response rate, 36%) were achieved, with a response rate of 39% in untreated and 17% in pretreated patients. Nine patients (16%) had stable disease and 26 (47%) progressive disease. Most patients felt symptomatically improved on ECF. CONCLUSIONS: Our study confirms that the ECF regimen has a favorable pattern of toxicity and is feasible on an outpatient basis. However, it did not confirm the high response rate reported in other phase II trials.

Solitary breast metastases from a renal cell carcinoma.

A case of solitary and metachronous breast metastases from a renal cell carcinoma is described nine years after surgery. The review of the literature proves that the breast is an unusual site for metastatic disease.

Current status of surgery for carcinoma of the hypopharynx and cervical esophagus.

Hypopharynx and cervical esophagus represent a critical location for a squamous cell carcinoma, a neoplasm that usually requires extensive surgery. Although morbidity and mortality of resection have markedly decreased over the past decade, the major issue in these patients remains quality of life owing to the need for combination with a laryngectomy to provide radical treatment. Chemoradiation therapy has the potential to downstage and even cure the disease without altering quality of life dramatically. Today, in the absence of randomized trials, the choice between surgery and definitive chemoradiotherapy should be based on clear information and the patient's preference. Salvage surgery is feasible and effective in selected patients.

Slow-release lanreotide in the treatment of acromegaly: a study in 66 patients.

OBJECTIVE: Slow-release (SR) lanreotide is a long-acting somatostatin analog that has been developed in order to overcome the inconvenience of multiple daily subcutaneous injections of octreotide, required for metabolic control in acromegaly. Lanreotide SR has been found to be well tolerated and effective in reducing GH and IGF-I levels but clinical data are still limited compared with those with subcutaneous octreotide treatment. DESIGN: Sixty-six unselected patients with active acromegaly were therefore evaluated in a multi-center, prospective, open label study. Lanreotide SR was given at a dose of 30mg intramuscular every 7-14 days. METHODS: At baseline and after 2, 4, 8, 12, 24, 36 and 48 weeks patients underwent a clinical examination with assessment of acromegaly related symptoms, and blood was sampled for serum GH, IGF-I, prolactin, glycosylated hemoglobin, fasting glucose, hematology, kidney function and liver function tests. Biliary ultrasonography and pituitary magnetic resonance imaging were performed at baseline and after one year. RESULTS: Treatment resulted in a significant improvement in the symptom score from 2.69+/-0.27 to 1.06+/-0.17 (P<0.0001). Serum IGF-I levels fell from 699+/-38microg/l at baseline to 399+/-26microg/l (P<0.0001, n=60) after one month, after which levels remained stable: 480+/-37microg/l after 6 months (n=54) and 363+/-32microg/l after one year (n=46). GH levels dropped from 13.8+/-3.2microg/l to 4.3+/-0.7microg/l after one month (P<0.0001, n=60) and remained stable thereafter: 3.9+/-0.4microg/l (n=54) after 6 months and 3.5+/-1.1microg/l after one year (n=46). Twenty-nine out of 66 patients (44%) attained a normal age-corrected IGF-I level and 30 patients (45%) attained a GH level below 2.5microg/l. Pituitary adenoma shrinkage of at least 25% was found in 5 of 14 patients (36%) after one year. Side effects were mainly transient gastrointestinal symptoms and pain at the injection site, resulting in drug discontinuation in only 6 patients (9%). Two patients developed new gall stones. No difference was found between subcutaneous octreotide and lanreotide SR in efficacy and almost all patients preferred the easier dose administration of lanreotide SR. CONCLUSIONS: Long-term treatment of acromegaly with SR-lanreotide is effective in controlling GH and IGF-I levels and symptoms and is well tolerated in the majority of patients. Compared with subcutaneous octreotide, lanreotide SR considerably improves patient's acceptance of therapy while having the same overall efficacy.

Biological versus prosthetic ring in mitral-valve repair: enhancement of mitral annulus dynamics and left-ventricular function with pericardial annuloplasty at long term.

OBJECTIVE: The effects of different annuloplasty rings on mitral annulus dynamics and left-ventricular (LV) function after mitral-valve repair (MVR) are still controversial. This study sought to compare biological versus prosthetic rigid rings for annular remodelling in MVR at long term. METHODS: Forty-four consecutive patients were retrospectively enrolled. All patients had isolated posterior-leaflet prolapse and underwent identical surgical mitral-valve reconstruction (quadrangular resection of the posterior leaflet associated with annuloplasty). Twenty-three patients underwent mitral annuloplasty with an autologous pericardial ring (group I), whereas 21 patients had MVR with a Carpentier-Edwards rigid ring (group II). No differences existed between the groups in terms of pre-operative patient profile. Post-operative LV systolic indices have been assessed by two-dimensional echocardiography at rest and during supine bicycle exercise. Mitral annular motion has been examined by means of the extent of mitral annulus systolic excursion (MASE), as measured in four longitudinal LV segments (anterior, inferior, septal and lateral). Mean and peak trans-mitral flow velocities (TMFV) have been also evaluated by continuous-wave Doppler. RESULTS: The mean follow-up did not differ between the groups, those being 41+/-12 months in group I (range17-65 months) and 46+/-15 months in group II (range 23-83 months), respectively. Post-operative echocardiographic study did not show significant mitral regurgitation at rest or at peak exercise in any patient. ANOVA analysis for repeated measures showed a significant interaction in peak TMFV (F((1,42))=5.23; P=0.03), and in left-ventricular ejection fraction (LVEF; F((1,42))=7.61, P=0.01). The analysis of contrasts showed a significant increase in TMFV in both groups (group I from 1.22+/-0.22 to 1.79+/-0.32 m/s, t=-8.8, P<0.0001; and group II from 1.19+/-0.17 to 1.96+/-0.33 m/s, t=-12.8, P<0.0001). Recruitment of LVEF reserve during exercise was observed only in group I (from 59.5+/-6 to 65.8+/-6%, t=-3.95, P<0.005), whereas no substantial change occurred in LV performance in group II. A trend towards better MASE at all the studied longitudinal segments at rest and during exercise was observed in group I. No minor or major calcifications have been observed on pericardial rings. CONCLUSIONS: The autologous pericardium seems to be superior to rigid prosthetic rings for annuloplasty in MVR since it provides more favourable mitral annulus dynamics and preserves LV function during stress conditions. Effective and durable annular remodelling with the autologous pericardium is achieved up to 6 years from surgery, with no echocardiographic sign of degeneration in the long term. Further studies are required to compare biological versus flexible prosthetic rings in MVR.

[Systemic mastocytosis. A review of current diagnostic and therapeutic approaches]. / La mastocitosi sistemica. Revisione degli attuali approcci diagnostico-terapeutici.

Mastocytosis is a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells in skin, bone marrow, bone, gastrointestinal tract, liver, spleen and lymph nodes. Today, regarding its biological features, mastocytosis (with or without myeloid accompanying disorders) is considered to be a hematologic disease. The classification proposed by Metcalfe in 1991 is the most useful in caring for patients with mastocytosis. In this classification 4 groups are described: 1) indolent mastocytosis with or without extracutaneous involvement; 2) systemic mastocytosis with an associated hematologic disorder; 3) aggressive mastocytosis; 4) mast-cell leukemia. Cutaneous mastocytosis typically presents as urticaria pigmentosa or diffuse cutaneous mastocytosis and these patients usually have a benign course. On the contrary, systemic mastocytosis is a disease with an increased risk to develop an aggressive hematologic disorder. In these patients a second hematologic process, such as myeloproliferative or myelodysplastic syndrome or acute leukemia, may occur. These patients often present without skin involvement and they have a very poor prognosis. Mast cell is a medium-sized granulated cell releasing chemical mediators (histamine, heparin, protease and cytokines). Mast cells originate from pluripotent hemopoietic progenitor cells that express the CD34 antigen. Mast cells are present in the bone marrow and are distributed throughout the connective tissues. Recently a mast-cell growth factor (MGF) has been identified. Clinical symptoms occur from the release of chemical mediators and the pathologic infiltration of cells. Although no effective therapy for patients with Mastocytosis is known, some patients may benefit from corticosteroid and interferon alpha treatment. The present article gives an overview of current knowledge about the biology, heterogeneity and treatment of human mastocytosis.

Complications of subcutaneous infusion port in the general oncology population.

Subcutaneous infusion ports (SIPs) represent a valid method for long-term chemotherapy. The SIPs have several advantages over other methods of venous access: they are easy to implant under local anaesthesia, have less discomfort for the patients, allow low costs, can be implanted in day hospital, and can be managed ambulatorily. However, SIPs have delayed complications, frequently related to clinical conditions of the neoplastic patients, and immediate complications, often due to the placement technique. From March 1992 to March 1997 we placed, under local anaesthesia and under fluoroscopic control, 102 SIPs in 99 general oncology patients for long-term chemotherapy (88% solid, 12% haematological tumours). The percutaneous venous access devices were in the subclavian vein in 96% of the cases and in the internal jugular vein in 4% of them. Immediate complications were: 1 haemopneumothorax, which required thoracic aspirations and two blood transfusions, 1 loop of the tunneled part of the catheter without alterations in SIP function, and 1 left jugular thrombosis in a patient with subclavian veins already thrombosed. The venous access was in the subclavian vein in the first 2 cases, and it was not necessary to suspend the therapeutic program. In the third instance, implanted in jugular vein, it was necessary to remove the SIP. Delayed complications were: 1 necrosis of the skin over the port, 1 infection of subcutaneous pocket, 2 infections of the system, 1 catheter deconnection, and 3 catheter ruptures with embolization of the catheter tip. The SIPs were removed in all cases but 1 in whom infection was successfully treated by appropriate antibiotic therapy. Embolization of the catheter required removal from the pulmonary artery under fluoroscopic guidance in the cardiac catheterization laboratory. In conclusion, infection and thrombosis are the two major complications of SIP in general oncology patients. In these cases it is not necessary to remove systematically the system, but a correct therapy (antibiotic, fibrinolytic agents) can be utilized with good results. The catheter rupture is often due to the wear over the costoclavicular angle. The interventional radiology is the method of choice in the treatment of the catheter embolization by rupture or dislocation. The experience of the surgical and nursing staff is probably the most important factor in decreasing the total rate of complications.