Late onset of hepatitis B virus reactivation following hematopoietic stem cell transplantation: successful treatment with combined entecavir plus tenofovir therapy.

Prophylaxis with lamivudine (LAM) is recommended for hepatitis B core antibody-positive allogenic hematopoietic stem cell transplant (HSCT) recipients, but the optimal timing for the institution and duration of the prophylaxis is still unknown. Furthermore, considering the high rate of mortality associated with hepatitis B virus reactivation (HBV-R), the most potent and long-term effective antiviral regimen should be considered. We report here a case of late onset of HBV-R after a long-term prophylaxis with LAM in a patient who underwent HSCT for non-Hodgkin lymphoma and who was successfully treated with a combination antiviral regimen including entecavir and tenofovir disoproxil fumarate.

Melanoma cells and normal melanocytes share antigens recognized by HLA-A2-restricted cytotoxic T cell clones from melanoma patients.

HLA-A2-restricted, CD3+, CD8+, alpha/beta+ cytotoxic T cell (CTL) clones were isolated from peripheral blood (PBL) or tumor infiltrating lymphocytes (TIL) of two HLA-A2+ melanoma patients (9742 and 5810), to evaluate the possible recognition of autologous melanoma and of allogeneic HLA-A2-matched normal melanocytes. These CTL clones lysed not only fresh and cultured autologous melanoma cells, but also allogeneic HLA-A2+, but not HLA-A2-, normal melanocytes. The lysis of autologous neoplastic cells and of melanocytes could be inhibited by an anti-HLA-A2 monoclonal antibody (mAb). Lysis of the normal melanocytes was not dependent on the presence of human or fetal calf serum in the culture medium. HLA-A2-restricted CTL clones recognized not only proliferating melanocytes cultured in complete melanocyte medium, but also melanocytes made quiescent by culture for up to 6 d in a basal medium devoid of exogenous factors such as phorbol ester (O-tetradecanoyl phorbol 13-acetate [TPA]), epidermal growth factor, insulin, and pituitary extracts. Analysis of specificity of four CTL clones (A75, A83, A94, and 119) from patient 9742, performed on a panel of 39 targets, indicated that the three HLA-A2-restricted CTL (A75, A83, and A94) lysed all but one of nine allogeneic melanomas expressing the HLA-A2 molecule with no reactivity on nine HLA-A2- allogeneic melanomas. Only a few instances of borderline reactivity were seen by the same effectors on 21 targets of nonmelanocyte lineage, including 12 carcinomas of different histology, four Epstein-Barr virus-transformed B cells (lymphoblastoid cell lines [LCL]), including the autologous LCL, four lines of normal fibroblasts, and normal kidney cells. Lack of reactivity on allogeneic targets of nonmelanocyte lineage occurred in spite of expression of HLA-A2 on 14 of these targets as determined by conventional tissue typing and cytofluorimetric analysis with four different anti-HLA-A2 mAb. These data indicate that tissue-related antigens can be expressed on normal and neoplastic cells of the melanocyte lineage and can be recognized in association with HLA-A2 by CTL clones from melanoma patients.

T cell receptor (TCR) structure of autologous melanoma-reactive cytotoxic T lymphocyte (CTL) clones: tumor-infiltrating lymphocytes overexpress in vivo the TCR beta chain sequence used by an HLA-A2-restricted and melanocyte-lineage-specific CTL clone.

HLA-A2+ melanomas express common melanoma-associated antigens (Ags) recognized in vitro by autologous cytotoxic T lymphocytes (CTL). However, it is not known whether tumor Ags can drive in vivo a selective accumulation/expansion of Ag-specific, tumor-infiltrating T lymphocytes (TIL). Therefore, to evaluate this possibility, 39 CTL clones isolated from several independent mixed lymphocyte tumor cultures (MLTC) of TIL and peripheral blood lymphocytes (PBL) of an HLA-A2+ melanoma patient and selected for T cell receptor (TCR)-dependent, HLA-restricted tumor lysis, were used for analysis of TCR alpha and beta chain structure by the cDNA polymerase chain reaction (PCR) technique with variable gene-specific primers followed by sequencing. Despite absence of oligoclonality in fresh TIL and PBL, as well as in T cells of day 28 MLTC (day of cloning), sequence analysis of TCR alpha and beta chains of TIL clones revealed a dominance of a major category of melanoma-specific, HLA-A2-restricted T cells expressing a V alpha 8.2/J alpha AP511/C alpha and V beta 2.1/D beta 1/J beta 1.1/C beta 1 TCR. The same TCR was also found in 2 out of 14 PBL clones. The other PBL clones employed a V alpha 2.1 gene segment associated with either V beta 13.2, 14, or w22. Clones A81 (V alpha 2.1/J alpha IGRJ alpha 04/C alpha and V beta 14/D beta 1/J beta 1.2/C beta 1) and A21 (V alpha 8.2/J alpha AP511/C alpha and V beta 2.1/D beta 1/J beta 1.1/C beta 1), representative of the two most frequent TCR of PBL and TIL, respectively, expressed different lytic patterns, but both were HLA-A2 restricted and lysed only HLA-A2+ melanomas and normal melanocytes, thus indicating recognition of two distinct HLA-A2-associated and tissue-related Ags. Finally, by the inverse PCR technique, the specific TCR beta chain (V beta 2.1/D beta 1/J beta 1.1/C beta 1) expressed by the dominant TIL clone was found to represent 19 and 18.4% of all V beta 2 sequences expressed in the fresh tumor sample and in the purified TIL, respectively, but < 0.19% of V beta 2+ sequences expressed in PBL. These results are consistent with the hypothesis that a clonal expansion/accumulation of a melanocyte-lineage-specific and HLA-A2-restricted T cell clone occurred in vivo at the site of tumor growth.

Cell retargeting by bispecific monoclonal antibodies. Evidence of bypass of intratumor susceptibility to cell lysis in human melanoma.

Intratumor heterogeneity for susceptibility to cytotoxic T lymphocytes (CTL)-mediated lysis represents a major obstacle to cancer adoptive immunotherapy. To overcome the heterogeneity observed in terms of susceptibility of target cells to cell-mediated lysis, in this study we used two purified bispecific monoclonal antibodies (bsmAbs) that recognize molecules expressed by cytotoxic effector cells (CD3 and IgG Fc receptorial molecules), as well as one high molecular weight melanoma-associated antigen (HMW-MAA). The ability of these reagents to enhance or induce a relevant in vitro cytotoxic activity by a CTL clone (CTL 49) isolated from PBL of a melanoma patient was tested on a large panel of autologous and allogeneic melanoma cell lines and clones. Functional studies revealed that the CTL 49 clone lysed all the HMW-MAA+ tumor lines in the presence of bsmAbs and that these reagents affected the target lysis in a cooperative fashion. The effectiveness of bsmAbs in overcoming the heterogeneous susceptibility of human melanoma cells to cell-mediated lysis may find practical implications in cancer adoptive immunotherapy.

Water load test before and after PPI therapy in patients with gastro-oesophageal reflux disease.

BACKGROUND: Patients with gastro-oesophageal reflux disease may complain of epigastric pain, bloating, early satiety, epigastric fullness, epigastric burning, nausea and vomiting. AIMS: To evaluate the symptoms in response to gastric distension and its relationship to a therapeutic course in patients with gastro-oesophageal reflux disease using the water load test, compared to healthy controls. METHODS: Thirty gastro-oesophageal reflux disease patients with grade A oesophagitis (studied before and after 4 weeks of therapy with esomeprazole, 40 mg per day) and 15 patients with reflux-related symptoms demonstrated at wireless pH monitoring (non-erosive reflux disease) were compared to 30 healthy volunteers. RESULTS: Patients with grade A oesophagitis and with reflux-related symptoms ingested significantly lower water volumes than did controls, before onset of fullness, without statistically significant difference between erosive or non-erosive gastro-oesophageal reflux disease; this variable improved in patients after treatment. Nausea scores were higher basally in patients, pre- and post-therapy, and improved after therapy. Thirty-minute fullness and bloating scores improved after therapy in all gastro-oesophageal reflux disease patients compared to controls and pre-therapy. In all pre-treatment patients, a significant correlation was found only with epigastric fullness; after treatment, there was no significant relationship between the water load and the symptom scores. CONCLUSIONS: In patients with reflux-related symptoms, with or without grade A oesophagitis, the water load test is frequently abnormal, suggesting an altered gastric function. This could explain the incomplete resolution of symptoms after treatment in some patients, and should lead to additional studies aimed at exploring gastric function in gastro-oesophageal reflux disease patients.

Early reduction of serum TARC levels may predict for success of ABVD as frontline treatment in patients with Hodgkin Lymphoma.

BACKGROUND: Many efforts have been made to predict prognosis of newly diagnosed Hodgkin Lymphoma (HL) patients. Objective of this study was to investigate the association between early reduction of Thymus and Activation-Regulated Chemokine after the first ABVD cycle (TARC-1) and prognosis of HL patients. METHODS: Serum samples of 116 HL patients were collected at baseline, after every ABVD cycle and during follow-up. The 99th centile of TARC distribution in a group of 156 independent healthy subjects (800pg/ml) was considered as cut-off for discriminating between abnormal and normal TARC values. FINDINGS: 101 patients out of 116 had baseline TARC above 800pg/ml (median value 27515pg/ml (IQR, 11001-68139)) and were the object of this analysis. TARC-1 significantly decreased to a median value of 556pg/ml (IQR, 378-977pg/ml). TARC-1 values below 800pg/ml were associated with success of therapy (p=0.0003) and PET-2 negativity (p=0.001). TARC-1≤800pg/ml identified a population with a significantly higher 5-years PFS in the whole cohort (90.1% vs 55.6%; p<0.0001) and in both subgroups of advanced (p=0.003) and early stage patients (p=0.021). At multivariable analysis, TARC-1 was significant independent predictor of PFS (p=0.0035). INTERPRETATION: Early reduction of TARC serum levels can predict success of treatment, being associated with achievement of interim PET-2 negative and favorable long-term outcome in HL patients receiving ABVD as front-line therapy.

Treatment with botulinum toxin of octo-nonagerians with oesophageal achalasia: a two-year follow-up study.

BACKGROUND: Treatment of oesophageal achalasia with intrasphincteric injections of botulinum toxin has proved to be a successful alternative treatment modality. However, little is known about its long-term effects in very old patients. AIM: To evaluate the effects of such treatment in octo-nonagerians during a 2-year follow-up period. PATIENTS AND METHODS: Thirty-three patients with idiopathic oesophageal achalasia (range 81-94 years) entered the study. After basal evaluation and screening procedures, 100 U of botulinum toxin was injected at the lower oesophageal sphincter, and the procedure was repeated 1 month later. Data were collected at baseline and were compared after 1 and 2 years following the procedure. RESULTS: Seventy-eight per cent of patients were considered responders at 1 year and 54% were considered responders at 2 years. The weight gain at the end of the follow-up period was 2 (0-3) kg. No significant relationship was found between baseline lower oesophageal sphincter pressure and symptoms score after 1 and 2 years of follow-up; moreover, no major complications of botulinum toxin therapy were reported. CONCLUSION: Treatment of very old achalasic patients with botulinum toxin is safe, effective and yields good quality of life in a substantial proportion of these subjects.

Classes I and II HLA and melanoma-associated antigen expression and modulation on melanoma cells isolated from primary and metastatic lesions.

Human melanoma cells freshly isolated from 20 patients with primary and 73 patients with metastatic melanomas were analyzed by indirect immunofluorescence staining with monoclonal antibodies (MoAb) to class I (HLA-A, -B, and -C) and class II (HLA-DR and -DQ) antigens and to melanoma associated antigen (MAA). The latter included the GD3-MAA and the high molecular weight MAA. HLA class I antigens were present in 91 and 93% of primary and metastatic tumors, respectively. GD3-MAA was detected in 100% of primary and 80% of metastatic tumors. Whereas the high molecular weight MAA was expressed in 75% of tumors. Sixty % of primary and 50% of metastatic melanomas were stained by anti-HLA-DR MoAb, whereas 38 and 21% of cases, respectively, were stained by anti-HLA-DQ MoAb. Marked phenotypic heterogeneity was evident among primary and metastatic tumors, including different metastases from the same patient. Moreover, in vitro culture of melanoma cells isolated from metastases was associated with an increase from 50 to 75% of tumors stained by anti-HLA-DR MoAb but not of tumors positive for HLA class I antigens and MAA. In vitro incubation with partially purified or recombinant human gamma-interferon enhanced the expression of HLA-DR antigens on all short-term cultured melanoma cells tested but induced and/or augmented the expression of HLA-DQ antigens only in 5 of the 8 cases examined. The average increase in antigenic expression was higher for HLA-DQ than for HLA-DR antigens. Flow cytometric measurement of DNA content of melanoma cells treated with gamma-interferon revealed that the increase of HLA-DR and -DQ expression induced by gamma-interferon was independent from the cell cycle of the tumor cells.

Human heat shock protein 70 peptide complexes specifically activate antimelanoma T cells.

Members of the heat shock protein 70 (HSP70) family display a broad cellular localization and thus bind a repertoire of chaperoned peptides potentially derived from proteins of different cellular compartments. In this report, we show that HSP70 purified from human melanoma can activate T cells recognizing melanoma differentiation antigens in an antigen- and HLA class I-dependent fashion. HLA class I-restricted anti-melanoma T cells were susceptible to MHC-restricted, HSP70-dependent stimulation, indicating that HSP70 complexed peptides were able to gain access to the class I HLA presentation pathway. In addition, MHC matching between the melanoma cells used as a source of HSP and the responding T cells were not required, indicating that HSP70 activation may occur across MHC barriers. Besides the MHC-restricted and peptide-dependent activation pathway, HSP70 with no endogenous complexed peptides or HSP70 purified from antigen-negative cells was also able to induce IFN-gamma release by antimelanoma T cells by a MHC-independent mechanism. In this case, however, higher doses of HSP70 were required. The capacity to activate class I-restricted, antitumor T cells as well as antigen-presenting cells, together with the finding that the HSP70 chaperoned peptide repertoire includes melanoma-shared epitopes, holds promise for a HSP70-based cancer vaccine.

A superagonist variant of peptide MART1/Melan A27-35 elicits anti-melanoma CD8+ T cells with enhanced functional characteristics: implication for more effective immunotherapy.

In the present study, we show that a singly substituted peptide derived from the epitope MART1(27-35) and containing a Leu in position 1 (LAGIGILTV; 1L) behaves as a superagonist by in vitro inducing specific T cells with enhanced immunological functions. 1L-specific CTLs can be raised from peripheral blood of HLA-A2+ melanoma patients more efficiently than T cells specific for the cognate peptide. These T cells show a greater sensitivity to native MART1(27-35) when compared with CTL variable raised to parental peptide from the same patients. More importantly, anti-1L but not anti-native T cells display high levels of interferon gamma production at early time points, and readily secreted interleukin-2 in response to native epitope endogenously presented by melanoma cells. Additionally, anti-1L T cells are insensitive to the inhibitory effects of MART1(27-35) natural analogues that antagonize the lytic response of CTLs raised to the cognate peptide. Analysis of T-cell receptor variable beta usage suggests that the native and 1L peptides stimulate different components of the MART1(27-35)-reactive T cell population. These data provide rationale to the use of superagonist analogues of tumor antigens for inducing in vivo immunization potentially able to overcome tumor immune escape and mediate a more significant control of tumor growth.

Vaccination of melanoma patients with interleukin 4 gene-transduced allogeneic melanoma cells.

A human melanoma line genetically modified to release interleukin 4 (IL-4) was utilized to immunize advanced melanoma patients in order to elicit or increase a specific anti-melanoma immune response, which may affect distant lesions. Twelve metastatic melanoma patients were injected subcutaneously at least three times with 5 x 10(7) IL-4 gene-transduced and irradiated allogeneic melanoma cells per dose. Both systemic and local toxicities were mild, consisting of transient fever and erythema, swelling, and induration at the vaccination site. Two mixed but not complete or partial clinical responses were recorded. To assess the immune response of vaccinated patients, both serological and cell-mediated activities were evaluated. Antibodies to alloantigens could be detected in 2 of 11 patients tested. Mixed tumor-lymphocyte cultures were performed, utilizing autologous and allogeneic HLA-A2-matched melanoma lines as simulators and targets. A significant increase in IFN-gamma release was detected in 7 of 11 cases when postvaccination lymphocytes were stimulated by the untransduced allomelanoma cells. However, induction of a specific recognition of autologous melanoma cells by PBLs was obtained after vaccination in only one of six cases studied. This response involved the melanoma peptide Melan-A/MART-1(27-35) that was recognized in an HLA-A2-restricted fashion. These results indicate that vaccination with allogeneic melanoma cells releasing IL-4 locally can expand a T cell response against antigen(s) of autologous, untransduced tumor, although in a minority of patients.

Expansion of major histocompatibility complex-restricted antimelanoma cytotoxic T-cell lymphocyte clones with identical T-cell receptor from tumor-infiltrating lymphocytes.

Tumor-infiltrating lymphocytes (TILs) were isolated from a subcutaneous metastasis of melanoma and cytotoxic T-cell lymphocyte (CTL) lines were obtained by sensitizing in vitro four separate aliquots of TILs with autologous tumor cells and recombinant interleukin-2. All CTL lines were predominantly WT31+, CD3+, and CD8+ and displayed a preferential cytotoxic activity against the autologous tumor. T-cell receptor (TCR) composition was analyzed by using the polymerase chain reaction with 5' variable region (V alpha or V beta)-specific primers and 3' constant (C alpha or C beta) primers. The entire repertoire of the V alpha and V beta gene families tested was present in fresh TILs and in the CTL lines, although, in the latter, consistent quantitative variations in transcripts of several V alpha and V beta occurred. CTL clones that exhibited CD3-dependent and major histocompatibility complex-restricted killing of the autologous melanoma were isolated from the four TIL cultures. TCR analysis indicated that, independently from the culture of origin, only two combinations of V alpha and V beta gene families were present in the majority of these CTL clones. These V alpha and V beta gene families were not found in a panel of CTL clones that did not lyse the autologous tumor. This study indicates that recognition of melanoma antigens can strongly select for certain types of TCR-bearing T-lymphocytes.

An autologous T cell clone overcomes intra-melanoma heterogeneity for susceptibility to cell-mediated lysis by using multiple lytic mechanisms: in vitro and in vivo analysis.

An HLA-A2-specific cytotoxic T lymphocyte (CTL) clone (CTL49), capable of killing the HLA-A2-negative autologous melanoma (Me665/2) in a T cell receptor and MHC-independent fashion, lysed six of 16 Me665/2 tumour clones in short-term (4 and 18 hour) 51Cr-release assays. In long-term (96 hour) lytic assays, CTL49 could lyse all the 16 tumour clones. The lysis observed in the 96 hour assay could be enhanced by stimulating CTL49 with anti-CD3 monoclonal antibodies (MAb) and interleukin-2 (IL-2). Supernatants of anti-CD3- or antigen-stimulated CTL49, known to contain tumour necrosis factor (TNF) alpha and interferon (IFN)gamma, were also able to lyse all but one (665/2/51) of the tumour clones in 96 hour assays. Absence of lysis of tumour clone 2/51 by supernatants correlated with resistance of the same tumour clone to lysis by recombinant IFN-gamma plus TNF-alpha. Antibodies to TNF-alpha and, to a lesser extent, to IFN-gamma, reduced significantly the 96 hour lysis of Me2/9 and Me2/10, two of the tumour clones killed in long term but not in short term assays. Winn assays in nude mice revealed that CTL49, stimulated with anti-CD3-MAb plus IL-2, could abolish tumour cell growth when injected together with clones 2/9 or 2/10. These results indicate that intra-tumour heterogeneity for susceptibility to lysis can be overcome even by a single CTL clone providing that appropriate signals (i.e. anti-CD3-MAb and IL-2) are supplied to an effector able to mediate tumour cell lysis by multiple mechanisms.

Two autologous melanoma-specific and MHC-restricted human T cell clones with identical intra-tumour reactivity do not share the same TCR V alpha and V beta gene families.

Among tumour infiltrating lymphocytes (TIL) of a melanoma patient, A CD8+, WT31+ CTL clone (8B3) had been previously isolated which exhibited specific and MHC-restricted lytic activity against the autologous tumour. To molecularly characterize T cell receptor (TCR) alpha and beta transcripts of clone 8B3, sequence analysis of several cDNA isolates was carried out. Such analysis indicated that the functional alpha and beta chain of 8B3 are composed of V alpha 2.1/J alpha/C alpha and V beta 8.2/D beta/J beta 1.2/C beta 1 gene segments. Eleven additional melanoma-reactive T cell clones from the same patient (one MHC-restricted and 10 MHC-unrestricted) were analysed for usage of the 8B3 V alpha 2 and V beta 8 gene segments by Northern blot hybridization. Neither the V alpha 2 nor the V beta 8 segments were used by 8D9, the second MHC-restricted melanoma-specific TIL clone that displayed intra-tumour reactivity identical to that of 8B3 recognizing only 4 out of 25 melanoma clones isolated from the same metastases. No V beta 8 expression was found among the MHC-unrestricted T cell clones and all but two (found in duplicate as 4C4 and 4A6) were also negative for V alpha 2 expression. Southern blot analysis revealed different TCR beta chain rearrangements in most MHC-unrestricted T cell clones providing evidence of their independent derivation. Taken together these findings show that TCR of clone 8B3 is unique in composition and not shared by MHC-unrestricted melanoma-reactive T cell clones. The different set of V alpha and V beta families used by clone 8D9 further indicates that the TCR usage in the specific and MHC-restricted response to melanoma can be polyclonal.

Evaluation on serum 2'-5'oligoadenylate synthetase (2'-5'oligoAS) and beta 2 microglobulin (B2M) in patients with nodal metastases from cutaneous malignant melanoma treated with rIFN-alpha 2A.

UNLABELLED: IFN-alpha is a promising adjuvant agent in patients with regional melanomatous metastases (stage IIIB). The aim of this study was to verify whether serum evaluation of the interferon induced proteins 2'-5'oligoAS and B2M can predict the clinical response to rIFN-alpha 2A therapy. PATIENTS AND METHODS: Forty-two patients who had undergone radical dissection of nodal metastases were evaluated. All patients received adjuvant rIFN-alpha 2A (3 million units s.c. three times weekly) for 3 years or until progression. The patients were followed for a medium period of 43 months (range 19-46). During follow-up 22 of the 42 patients had disease progression. In all patients blood samples were obtained before starting adjuvant therapy and after 1 and 6 months of therapy with rIFN-alpha 2A. 2'-5' oligoAS and B2M were measured by radioimmunoassay. RESULT: During the first month of adjuvant therapy with rIFN-alpha 2A the serum levels of 2'- 5' oligoAS increased 10-fold, and this trend was maintained in the following 6 months. Similar results were obtained for B2M serum levels. However, we did not find any significant difference in AS and B2M serum levels between responders and non-responders. CONCLUSION: Our results, therefore, indicate that AS and B2M are markers of the biological activity of administered IFN but that they have little efficacy in predicting the clinical outcome of the treated patients.

Gene therapy in melanoma.

The identification of genes involved in different biologic functions and in the pathogenesis of diseases has paved the way to the possibility of either interfering with the role of such genes or replacing them in somatic cells in case of loss, which may occur in some genetic diseases or cancer. Such progress has been accomplished thanks to advances in molecular biology and applied technology that allow the transport and insertion of genes into recipient cells by viral or physical vectors as well as the inhibition of gene transcription by antisense oligonucleotides. Methods have also been devised to transfer genes not only in vitro but also in vivo, although this latter approach is still limited owing to poor selectivity and targeting of most vectors when given systemically. Viral and physical vectors have been employed; each of these vectors has distinct advantages and disadvantages, and, therefore, the appropriate vector should be selected according to the therapeutic system involved (1). Retro viral vectors have been used largely for their ability to selectively transfect proliferating cells, a feature that can be advantageous in case one wishes to target only proliferating tumor cells. Owing to the heterogeneous proliferation rate in different parts of a tumor, however, it could be desirable, under some circumstances, to be able to target even the fraction of nonproliferating tumor cells. This can now be obtained by the use of lentivirus (2) or by switching to the use of adenoviruses that can target both dividing and quiescent cells but also induce unwanted inflammmatory reactions from the host.

Effectiveness of a dental preventive program on plaque index results in 8-year-old children of Bergamo, Italy.

The study presents the results of a preventive program based on a children's book and carried out in the elementary schools of Bergamo, Italy. The book was published to improve 8-year-old schoolchildren's knowledge of primary dentition, dental plaque, nutrition, oral hygiene, fluoride and regular dental visits. The study was experimental. A total of 440 schoolchildren were selected to test the effectiveness of the book. They were divided into four groups: two groups underwent the training program and the other two were control groups. Measurements were made using the Quigley-Hein index before and after the program. A significant difference reduction of the plaque index of -0.6 was observed (P < 0.005).

Kasabach-Merritt syndrome associated to angiosarcoma of the breast. A case report and review of the literature.

INTRODUCTION: Kasabach-Merritt syndrome is characterized by the association of a consumptive thrombohemorrhagic disorder and angioma occurring usually in children. In the present study, a case of Kasabach-Merritt syndrome associated to an angiosarcoma of the breast is reported. CLINICAL HISTORY: The tumor together with the thrombohemorrhagic disorder manifested in a 28-year-old woman. The patient underwent mastectomy. The tumor recurred in the same site 2 years later. The patient died of severe anemia 8 years after the first appearance of the angiosarcoma. MATERIAL AND METHODS: Tissues were formalin fixed and paraffin embedded; in addition, selected sections were immunohistochemically stained. RESULTS AND CONCLUSIONS: A well-differentiated angiosarcoma was visible throughout the removed organ. A review of the literature showed that only 6 cases of Kasabach-Merritt syndrome associated to malignant vascular tumors have been previously reported. All these 6 cases occurred in adult patients. On the contrary, Kasabach-Merritt syndrome associated to benign vascular tumors affects children. This is the first case occurring in the breast.

[The surgical contribution to the etiopathogenic picture of temporomandibular ankylosis]. / Apporto del tempo chirurgico nell'inquadramento etio-patogenetico dell'anchilosi temporo-mandibolare.

On the basis of 3 cases of mouth opening reduction, the Authors assess the etiopathogenic theories compared with the anamnestic and radiographical data. Sometimes only surgical procedures can clarify symptoms and clinical data.

[Bone remodelling after condylar fractures in children]. / Rimodellamento osseo in seguito a fratture condilari nei bambini.

The results of functional treatment of condylar fractures in children are reported. Ten patients were subjected to a radiographic study. Long-term follow-up shows a very good osseus remodelling of fractured condyles.