VEGF-A clinical significance in gastric cancers: immunohistochemical analysis of a wide Italian cohort.

PURPOSE: The clinical significance of VEGF-A expression in gastric cancer (GC) has been reported with contradicting results. We analyzed the expression and clinical significance of VEGF-A in a wide Italian cohort of GC specimens. METHODS: VEGF-A expression was tested by immunohistochemistry in 507 patients with GC of all clinical stages. The impact of VEGF-A on overall survival (OS) was evaluated in conjunction with clinical and pathological parameters. RESULTS: In the Italian cohort we studied VEGF-A was not an independent prognostic factor neither at the univariate nor at multivariate analysis. CONCLUSIONS: Although frequently expressed, in our study VEGF-A was not able to discriminate between groups of patients with different risk.

Advanced thyroid carcinoma: an experience of 385 cases.

AIMS: To report clinical outcomes of a large series of cases with advanced thyroid cancer. STUDY DESIGN: Three hundred and eighty-five patients at the UICC stages III and IV were selected for the study with thyroid cancer. RESULTS: Papillary carcinoma and sclerosing carcinoma have better survival than the Hürthle cell and insular types. Lymphatic metastasis does not appear to worsen the prognosis. All the tumour forms offer the chance of long survival. CONCLUSIONS: Surgical treatment is the primary treatment of thyroid carcinoma. The combined treatments of surgery, metabolic beam therapy, suppressive hormone therapy, radiotherapy and chemotherapy cure a high percentage of patients with the tumour at an advanced stage.

Use of vascularized iliac crest with internal oblique muscle flap for mandible reconstruction.

In the last decade, immediate reconstruction of maxillary bones following extensive trauma, large oncological defects, or late effects of radiation therapy has proved to be a reliable morpho-functional reconstruction technique. Use of the vascularized iliac crest with an internal oblique flap has become our flap of choice for mandible reconstruction when there is no need for overlying facial skin or oral sphincter reconstruction, and for bone segments within 6-15 cm of length. The advantages of this composite bone flap are the large and resizable bone stock available, the quality of bone transferred with an optimal height, depth, and contour of bone to maintain a good facial profile, and the possibility to reconstruct properly the oral lining, with a portion of the internal oblique muscle flap raised with the same pedicle that epithelializes during the healing stages. We present the experience of the Department of Maxillofacial Surgery of "S. Maria della Misericordia" Regional Hospital in Udine, Italy.

Regulation of development and function of memory CD4 subsets.

Immunologic memory refers to the dramatic response to previously encountered antigen (Ag) that is largely controlled by CD4 T cells. Understanding how CD4 memory is regulated is essential for exploiting the immune system to protect against disease and to dampen immunopathology in allergic responses and autoimmunity. Using defined adoptive-transfer models, we are studying parameters that affect differentiation of memory CD4 cells in vivo and have found that a complex interplay of T cell receptor signaling, costimulation, and cytokines can determine the extent of memory development and the balance of Th1 and Th2 memory subsets. On challenge, memory CD4 cells localize in sites of Ag exposure and develop into effectors that regulate memory responses. We are investigating the roles of adhesion molecules, cytokines, and chemokines in the selective recruitment of CD4 memory subsets to address mechanisms by which memory T cells provide long-lasting immunity and, in our recent studies, to determine how memory CD4 cells contribute to the development of autoimmune diabetes.

A notch-independent activity of suppressor of hairless is required for normal mechanoreceptor physiology.

Suppressor of Hairless [Su(H)]/Lag-1/RBP-Jkappa/CBF1 is the only known transducing transcription factor for Notch receptor signaling. Here, we show that Su(H) has three distinct functions in the development of external mechanosensory organs in Drosophila: Notch-dependent transcriptional activation and a novel auto-repression function, both of which direct cell fate decisions, and a novel auto-activation function required for normal socket cell differentiation. This third phase of activity, the first known Notch-independent activation function for Su(H) in development, depends on a cell type-specific autoregulatory enhancer that is active throughout adult life and is required for proper mechanoreception. These results establish a direct link between a broadly deployed cell signaling pathway and an essential physiological function of the nervous system.

Antagonism of notch signaling activity by members of a novel protein family encoded by the bearded and enhancer of split gene complexes.

Cell-cell signaling through the Notch receptor is a principal mechanism underlying cell fate specification in a variety of developmental processes in metazoans, such as neurogenesis. In this report we describe our investigation of seven members of a novel gene family in Drosophila with important connections to Notch signaling. These genes all encode small proteins containing predicted basic amphipathic (&agr;)-helical domains in their amino-terminal regions, as described originally for Bearded; accordingly, we refer to them as Bearded family genes. Five members of the Bearded family are located in a newly discovered gene complex, the Bearded Complex; two others reside in the previously identified Enhancer of split Complex. All members of this family contain, in their proximal upstream regions, at least one high-affinity binding site for the Notch-activated transcription factor Suppressor of Hairless, suggesting that all are directly regulated by the Notch pathway. Consistent with this, we show that Bearded family genes are expressed in a variety of territories in imaginal tissue that correspond to sites of active Notch signaling. We demonstrate that overexpression of any family member antagonizes the activity of the Notch pathway in multiple cell fate decisions during adult sensory organ development. These results suggest that Bearded family genes encode a novel class of effectors or modulators of Notch signaling.

[Spigelian hernia: anatomo-clinical considerations]. / L'ernia di Spigelio. Considerazioni anatomo-cliniche.

Two cases of Spigelian hernia are reported. Starting from the analysis of these cases, some observations about the anatomy, the etiology, clinic, diagnostic methods and the best therapeutic choices now available for this uncommon pathology are presented.

Stress and cervical dysplasia.

The aim of the study was to evaluate the relationship between personality, stress and cervical dysplasia. Twenty women with cervical dysplasia were compared to a control group of 23 healthy women. An evaluation of their personality was made by the 16 PF questionnaire; stressing events were investigated with the Paykel scale; hormonal repercussions were studied by using serum and urinary cortisol titers. Significant differences were found in intellectual capability and fancifulness, as well as in cortisol levels. Considering the significant issues that have emerged, we feel that this research is worthy of further investigation and that new evaluation parameters are necessary.

[Ionizing irradiation as a risk factor in thyroid cancer. A case report]. / Le radiazioni ionizzanti come fattore di rischio nel cancro della tiroide. Osservazione di un caso clinico.

The authors report a case of thyroid cancer which developed in a patient with a history of childhood therapeutic irradiation to the head for hemangioma. They confirm the importance of radiation as a risk factor for thyroid cancer and suggest some guidelines for the management and therapy of these particular neoplasms.

[Current trends in the treatment of voluminous eventrations]. / Moderni orientamenti nella terapia delle voluminose eventrazioni.

The authors speak about their experience on the giant incisional hernias. The surgical treatment of these lesions in not always easy, especially when exist some conditions such as the loss of parietal substance and the loss of residence right. In these cases the use of prosthetic meshes and the Goni Moreno's pneumoperitoneum are very helpful. The Authors point out how important is, for a successful treatment, as well as a correct surgical procedure and opportune pre and post operative management.

[Polyps of the gallbladder. Considerations on their real clinical significance]. / I "polipi" della colecisti. Considerazioni sul loro reale significato clinico.

The authors review all the cases of polyps of the gallbladder observed during the period 1964 to 1992 at the Institutes of Pathology and General Surgery at the University of Florence. On the basis of their experience, the authors affirm that these phenomena always cause more or less evident, even if not specific clinical symptoms; moreover, since they are considered high-risk lesions for the onset of malignant tumours, the authors emphasize the need for cholecystectomy in all cases.

[Anatomic and surgical considerations regarding the recurrent laryngeal nerve in thyroidectomy]. / Considerazioni anatomo-chirurgiche sul nervo laringeo ricorrente in corso di tiroidectomia.

The majority of surgeons view the preliminary identification of the recurrent laryngeal nerve (RLN) as an essential stage in thyroidectomy in order to preserve thyroid integrity. This conviction is based on the fact that the anatomical relations of the recurrent nerve during the cervical tract with adjacent structures are highly variable. The preparation of the RLN in a series of 42 thyroidectomies performed by the 1st Department of Pathological Surgery of the University of Florence confirmed this variability above all with regard to relations with the trachea, Berry's ligament and the branches of the lower thyroid artery. As a result, it is justified to consider the identification and preliminary preparation of the RLN on both sides as a fundamental and unavoidable stage in thyroidectomy.

[Combined use of Stoppa's and Rives' techniques in multiple eventration]. / L'applicazione combinata della tecnica di Stoppa e di Rives nelle eventrazioni multiple.

A patient with a complex pathology of the abdominal wall underwent an operation done by the simultaneous combination of Rives' and Stoppa's prosthetic techniques. The absence of complications and perfect staying power of the wall seems to confirm the efficacy of this surgical procedure.

[Diverticular disease of the vermiform appendix. Anatomo-clinical observations]. / La malattia diverticolare dell'appendice vermiforme. Osservazioni anatomo-cliniche.

The authors describe a case of diverticular disease of the appendix. The diagnosis is intraoperative and histological while therapy is based on surgical treatment. The authors seem to be favorable to surgical treatment in case of diverticulosis of the appendix in order to avoid dangerous complications.

[Progressive pneumoperitoneum in the surgical treatment of conspicuous ventral hernias. Importance of the procedure to restore a good respiratory function]. / Il pneumoperitoneo progressivo nella chirurgia delle ernie ventrali di ragguardevoli dimensioni. Importanza del procedimento per ristabilire una buona funzionalità respiratoria.

A recent clinical report regarding a patient with a voluminous laparocele treated using progressive pneumoperitoneum justifies this short paper on the use of this method as a preparatory act to reparative surgery. The paper emphasises the undoubted advantages deriving from the use of this technique, especially in the case of those subjects with a particularly poor respiratory function secondary to hernia.

[Therapeutic approach in ventral hernia]. / La tattica nella terapia dei laparoceli.

Laparoceles are diseases of the abdominal wall and their repair does not usually involve technical problems which are difficult to resolve. The use of classic surgical methods, such as direct suture and plastic surgery, enables the parietal defect to be easily repaired in most case. However, cases do occur in which the surgeon is faced with considerable technical and tactical difficulties largely due to anatomopathological causes: the "loss of the right of domicile" of herniated viscera and the loss of musculo-aponeurotic substance. In the former case it is necessary to prepare the peritoneal cavity using pneumoperitoneum. In the event of the extensive destruction of the muscular component, or when the parietal breech is located next to bone or cartilagenous structures, it is essential to use a prosthesis. The paper goes on to describe the indications for the use of various techniques and their respective methods of use under different anatomo-clinical conditions.

[Pneumoperitoneum in preparation for surgery of large ventral hernia]. / Il pneumo-peritoneo nella preparazione agli interventi dei grandi laparoceli.

Reparative surgery of ventral hernia may be relatively simple or, on the other hand, the surgeon may be confronted with a number of tactical and technical problems. Many of these are caused by the "loss of the right of domicile". In order to avoid this particular condition it is useful to resort to preoperative pneumoperitoneum. This method entails the gradual and progressive introduction of air into the peritoneal cavity. In this way abdominal capacity is increased and it is therefore possible to re-insert all the viscera into their natural cavities avoiding all the harmful consequences for respiratory and cardio-circulatory organs following forced replacement. Preoperative pneumo-peritoneum is a relatively well consolidated surgical technique in large scale eventration. The methods is simple to perform and has a low incidence of complications.

Expression of homeobox-containing genes in primary and metastatic colorectal cancer.

Homeobox genes are a network of genes encoding nuclear proteins functioning as transcriptional regulators. Human and murine homeobox genes of the HOX family are organised in four clusters on different chromosomes. Gene order within each cluster is highly conserved, perhaps in direct relation to their expression. Homeobox genes have recently been involved in normal development and oncogenesis. We have analysed HOX gene expression in normal human colon and in primary and metastatic colorectal carcinomas. The majority of HOX genes are active in normal adult colon and their overall expression pattern is characteristic of this organ. Furthermore, the expression of some HOX genes is identical in normal and neoplastic colon indicating that these genes may exert an organ-specific function. In contrast, other HOX genes exhibit altered expression in primary colon cancers and their hepatic metastases which may suggest an association with colon cancer progression.

HOX gene expression in normal and neoplastic human kidney.

As a consequence of transformation, cancer cells generally lose some of their differentiative properties. Thus, alterations interfering with the genetic mechanisms required to maintain embryonic determination could lead to tumorigenesis. Homeobox genes are a network of genes encoding nuclear proteins containing DNA-binding homeodomains that are highly conserved throughout evolution. They are expressed in a stage-related fashion in the developing embryo and, in adult life, in normal tissues. In mice and humans, homeobox genes of the HOX family are organized in 4 clusters on different chromosomes which have presumably evolved by duplication of a primordial gene cluster. Strikingly, the order of genes within each cluster is also highly conserved throughout evolution, suggesting that the physical organization of HOX genes might be essential for their expression. Recent reports indicate that homeobox mutant mice display morphological abnormalities or show neoplastic alterations, and that growth factors can turn on homeobox genes. We have studied the expression of the Antennapedia-like HOX genes in normal human kidney and in renal carcinomas. The great majority of the HOX genes analyzed are expressed in a peculiar manner in normal kidney: blocks of genes, even entire HOX loci, are coordinately regulated. Alterations in HOX gene expression in renal carcinoma can be observed in 2 genes of the HOX-2 locus, HOX-2A and HOX-2E, which are actively expressed in normal kidney and silent in cancer biopsies. The HOX-3H gene is not expressed in normal kidney whereas the HOX-3H transcripts are present in renal carcinomas. Homeobox genes within the 4 HOX loci can be aligned on the basis of the maximal sequence homology of their homeodomains: this alignment defines 13 paralogous gene groups. In renal carcinomas, genes of group 10 (HOX-1D, 2F, 3E, 4B) display a marked difference in their transcript classes when compared to those of normal kidney. Our findings suggest an association between altered HOX gene expression and kidney cancer.