Search

Background: Incorrect segregation of whole chromosomes or parts of chromosome leads to aneuploidy commonly observed in cancer. The correct centrosome duplication, assuring assembly of a bipolar mitotic spindle, is essential for chromosome segregation fidelity and preventing aneuploidy. Alteration of p53 and pRb functions by expression of HPV16-E6 and E7 oncoproteins has been associated with centrosome amplification. However, these last findings could be the result of targeting cellular proteins in addition to pRb by HPV16-E7 oncoprotein. To get a more detailed picture on the role of pRb in chromosomal instability and centrosome amplification, we analyzed the effects of the acute loss of retinoblastoma gene function in primary conditional Rb deficient mouse embryonic fibroblasts (MEFs). Moreover, since pRb is a transcriptional repressor, microarray analysis was done on pRb-competent and pRb-deficient MEFs to evaluate changes in expression of genes for centrosome homeostasis and for correct mitosis., Results: Acute loss of pRb induces centrosome amplification and aneuploidy in the vast majority of cells analyzed. A time course analysis shows a decrease of cells with amplified centrosomes after 40 days from the adenoviral infection. At this time only 12% of cells still show amplified centrosomes. Interestingly, cells with pRb constitutive loss show a similar percentage of cells with amplified centrosomes. DNA-Chip analyses in MEFs wt (mock infected) and pRb depleted (Ad-Cre infected) cells reveal differential expression of genes controlling both centrosome duplication and mitotic progression., Conclusion: Our findings suggest a direct link between pRb status, centrosome amplification and chromosomal instability, and define specific mitotic genes as targets whose gene expression has to be altered to achieve or maintain aneuploidy.

Purpose: Abdominal rectopexy is the preferred surgical technique for the treatment of total rectal prolapse. In many reported series, its results are impaired by induced constipation. Lateral rectal ligaments preservation could prevent constipation but increase recurrence rates. We report anatomic and functional results of abdominal Orr-Loygue ventral rectopexy with dissection limited to anterior and posterior rectal wall., Methods: Consecutive patients with total rectal prolapse or intra-anal rectal prolapse associated to fecal incontinence or outlet obstruction were treated by abdominal rectopexy. Recurrences, correction of symptoms, and induced constipation were prospectively analyzed., Results: Seventy-three patients were treated between 1993 and 2004. Recurrence was observed in 3 of 73 patients (4.1 percent) after a mean follow-up period of 28.6 (range, 6-84) months. Overall patient satisfaction (correction of prolapse, incontinence, and/or outlet obstruction) after the procedure was classified in three categories: Cured: n = 45 (61.6 percent); Improved: n = 24 (32.9 percent); Failure: n = 4 (5.5 percent). Postoperative constipation appeared in 2 of 36 (5.5 percent) preoperatively nonconstipated patients and worsened in 2 of 37 (5.4 percent) preoperatively constipated patients., Conclusions: Orr-Loygue abdominal ventral rectopexy with limited dissection and preservation of rectal lateral ligaments is a safe and effective procedure for the treatment of complete rectal prolapse, or internal prolapse associated with fecal incontinence or outlet obstruction. Preservation of lateral ligaments seems to prevent postoperative constipation without increasing the risk of prolapse recurrence.

Alterations in the number and/or morphology of centrosomes are frequently observed in human tumours. However, it is still debated if a direct link between supernumerary centrosomes and tumorigenesis exists and if centrosome amplification could directly cause aneuploidy. Here, we report that hydroxyurea treatment induced centrosome amplification in both human fibroblasts expressing the HPV16 -E6-E7 oncoproteins, which act principally by targeting p53 and pRB, respectively, and in conditional pRB deficient mouse fibroblasts. Following hydroxyurea removal both normal and p53 deficient human fibroblasts arrested. On the contrary pRB deficient fibroblasts entered the cell cycle generating aneuploid cells. Also the majority of conditional Rb deficient MEFs showed supernumerary centrosomes and aneuploid cells which increased over time. Finally, our results suggest that pRB dysfunction both in human and murine fibroblasts transiently arrested in G1/S by hydroxyurea allows centrosomes amplification, in the absence of DNA synthesis, that in turn could drive aneuploidy.

Accepting the therapeutic rational underlying laparoscopic and suprapubic laparotomy access, the same therapeutic goal is achieved through direct inguinal access. In this way, using just one prosthesis, inguinal-crural hernias of the Fruchaud pectineus orifice can be treated. The patented three-dimensional pre-cut Keel Mesh prosthesis made of polypropylene monofilament interwoven in a mesh, is tension-free and endowed with plastic memory. It is applied using a slightly modified Lichtenstein technique and is composed of two assembled elements (A and B-C) of different shapes and sizes. From May 2000 to December 2005, the Keel Mesh prosthesis was used in 358 surgical inguino-crural alloplasty operations according to Lichtenstein-De Pascale in 328 patients. Thirty patients were treated with bilateral allo-plasties. Coexistence of a crural hernia was found in 13 male and 4 female patients (5%). At the present time all the patients who are entering into follow-up at different times show perfect compliance of the prosthesis with no relapses. The theoretical and practical considerations regarding the production of the Keel Mesh prosthesis and its easy application suggest it is an extremely valid, rational device for the initial and combined treatment of inguinal and crural hernia.

The Authors report their experience about 127 ductal carcinoma in situ (DCIS) of the breast. Guidelines for surgical treatment are: radiological or clinical diagnosis, tumor's extension, histological classification, grading and margin status. At the present the Authors prefer breast conserving surgery with tumor margin's study. They report their experience in the last seven years about sentinel node biopsy. Radiotherapy and endocrine therapy are indicated for selected patients; local recurrence after DCIS therapy is 8,1% on a 6,1 years follow-up.

Breast-conserving surgery is the treatment of choice for the breast cancer T < 3 cm. The local recurrence is a problem of diagnosis and consequent treatment. We enrolled, from 1987 to 2004, 1504 breast cancer. In 803 (53.4%) tumor with T < 3 cm we performed conserving surgery. The sentinel lymph node (SN) technique induce to limit the axillary dissection in patients T1a-b to the SN only if non metastatic and located to the first level, the dissection of the 1st level of the axilla in patients T1c-T2 < 3 cm and SN negative, complete axillary dissection in patients with metastatic SN or located to the 2nd level. Our percentage of local recurrence in the follow-up was 3.5% at 5 years and 6% at 10 years.

Objective: To determine whether prolongation of the inflammatory reaction in patients with Behçet's disease (BD) is related to apoptosis resistance and is associated with the up-regulation of antiapoptotic factors., Methods: The percentage of cell death was evaluated by flow cytometry in peripheral blood mononuclear cells from 35 patients with BD and 30 healthy volunteers. The expression levels of antiapoptotic factors and NF-kappaB regulatory proteins were measured using Western blotting and immunohistochemical analyses. To down-regulate NF-kappaB nuclear translocation, BD T lymphocytes were exposed in vitro to thalidomide and subjected to transfection with NF-kappaB small interfering RNA., Results: Although CD95 is highly expressed in BD T cells, the absence of sensitivity to CD95-induced apoptosis observed may be attributable to the inhibitory action of antiapoptotic genes. Immunoblot analysis for major antiapoptotic proteins showed considerable up-regulation of the short form of cellular FLIP (cFLIP) and Bcl-x(L) in BD activated T cells, while levels of Bcl-2, caspase 3, and caspase 8 in activated T cells from patients with BD were comparable with those in activated T cells from normal donors. Moreover, expression of IKK and IkappaB was up-regulated, whereas NF-kappaB translocated to the nucleus in BD T cells, suggesting that NF-kappaB activation may modulate the expression of antiapoptotic genes. Interestingly, thalidomide and NF-kappaB small interfering RNA down-regulated cFLIP and Bcl-x(L) expression levels and sensitized BD activated T cells to CD95-induced apoptosis., Conclusion: Taken together, these results indicate that NF-kappaB contributes to the regulation of the apoptosis-related factors and death receptors leading to apoptosis resistance in BD T cell subsets. Our results suggest that NF-kappaB plays a crucial role in the pathogenesis of BD, and that its pharmacologic control could represent a key strategy in modulating specific immune-mediated disease.

Aim: New models of care are proposed to reduce the costs of traditional hospitalization and to improve the utilization of resources in surgery. Day surgery is widely employed in breast surgery. In this study we report the conversion rate and causes in ordinary hospitalization and we identify some contraindications related to breast surgery in day surgery., Methods: A cohort study was performed on 306 patients operated on between July 1999 and December 2001 for breast lesions with uncertain interpretation at the clinical and/or instrumental examination. Those patients who lived at a distance of less than 50 km from the hospital, had a telephone, a suitable house, direct family support and, if necessary, could benefit from home health care in addition to hospitalization, were considered as eligible to day surgery. The kind of anesthesia and hospital admission were established after clinical, psycho-emotional, and socio-familiar evaluation of the patients by the surgeon and the anesthetist., Results: A total of 250 excisional biopsies and 56 biopsies with a Mammotome were performed. Surgery was performed under local anesthesia in 278 patients and general anesthesia in 28 subjects. Observation exceeding 24 hours was only necessary in 10 patients reporting hypotension syndrome and anxiety. The conversion rate in ordinary hospitalization was 0.3%. Postoperative morbidity was 1%., Conclusion: Day surgery is an effective model of care in breast surgery for diagnostic and therapeutic purposes without axillary dissection. A good selection of patients, perfect interdisciplinary collaboration, and an efficient structural organization are necessary to control the complication and conversion rates of traditional hospitalization.

Large teratomas with gastric mucosa are rare. We report a case of mature cystic teratoma in an ovary of a young woman. Tumor growth was large and rapid enough to displace abdominal organs. The cyst was aspirated (removing 101 of mucinoid liquid) and excised by medial hypogastric laparotomy. The histological examination revealed differentiated gastric fundal mucosa with no other tissue involvement.

Study Aim: The aim of this prospective multicentric non-randomised trial was to report the complications of the central venous catheter insertion with different techniques and to assess the advantages of the low lateral approach to the internal jugular vein, according to the technique originally described by Jernigan et al, with our own modifications., Patients and Method: From January 1993 to August 1997, 2,290 CVC (2,286 by percutaneous puncture and 4 by surgical approach) were placed. The following complications were analysed prospectively: pneumothorax, accidental arterial puncture, more than two punctures of the same vein, necessity to shift to another venous approach, complete failure, malposition of catheter., Results: The veins the most frequently used were internal jugular vein (48.7%), femoral vein (27%) and subclavian vein (24.2%). Internal jugular vein was punctured especially by low lateral approach (75%) and subclavian vein by infraclavicular approach (92%). With these two placements, the rate of pneumothorax was 0% and 3.1% respectively (p < 0.001), the rate of accidental arterial puncture was 1% and 2.7% respectively (p < 0.03) and the rate of more than two consecutive punctures was 3.1% and 6.3% respectively (p < 0.008)., Conclusion: On our experience, we advocate the low lateral approach to the internal jugular vein as first choice technique for venipuncture in both adults and children for both short and long-term central venous approach, because it is associated to high rate of outcome and to low rate of complications in comparison with other techniques.

The concept of sentinel node biopsy, initially introduced for melanoma, has also been used for breast cancer since the 90's, in that, with the increasingly, widespread use of mammographic screening and of other minimally invasive diagnostic procedures, smaller and smaller cancers are now being diagnosed. For these cancers axillary dissection often constitutes overtreatment. For cancers at an initial stage with a low risk of axillary metastases investigation of sentinel lymph nodes enables us the surgeon to assess the axillary lymph-node status and avoid axillary dissection which is responsible for a certain amount of morbidity. Sentinel nodes can be sought using colorimetric or radioisotope methods. To date there is no common consensus of opinion as to which is the better procedure and the respective indications. Both methods allow detection of sentinel nodes in roughly 90% of cases and the combination of the two yields 100% detection rates. It is widely accepted that sentinel node biopsy should be reserved for unifocal tumours which have not been treated previously and which measure less than 15 mm in diameter. The advantages of the procedure are substantial provided it is performed correctly by surgeons properly trained in its use. The learning curve is relatively brief and is based on no more than 30-40 cases.

To clarify the possible role of persistent thrombocytosis after splenectomy as being a predisposing factor causing thromboembolism. Blood coagulation profiles were studied in 35 patients (20 M and 15 F, mean age 42 +/- 17.5) suffering from thrombocytosis (> 500,000/dl) who underwent splenectomy for non-malignant and non-traumatic diseases. Seventy healthy subjects acted as a control group. Tests were performed 6 months after the operation and for both groups (patients and controls) blood samples were collected for: platelets, fibrinogen, PT, APTT, AT III, plasminogen, F1 + 2, t-PA and DNA analysis for F V, F II and MTHFR. After one year all subjects were controlled for thrombocytosis, genomic abnormalities and venous thrombosis. All the analyses were performed according to the Statistical Package for Social Science. The significance of the differences in means was evaluated by non-parametric tests, differences with a P value < 0.05 being considered significant. Increased plasma levels of fibrinogen, D-dimer, F1 + 2 and PAI-1 were found in the patients compared with the control group. TPA was significantly lower in the patients than in the controls. At the one year follow-up, two patients with genetic polymorphism had suffered deep venous thrombosis. Our findings indicate that splenectomy contributes to abnormal platelet aggregation and endothelial cell activation with hypercoagulability.

Rectal prolapse and rectal intussuception correspond to two stages of the same disease. Rectal prolapse is unusual but requires surgical treatment. Abdominal rectopexy is the most effective procedure but increases the risk of postoperative constipation. This risk decreases when the lateral sides are not touched during rectal dissection. The Delorme procedure is associated with a higher rate of recurrence and must be reserved for patients presenting a high risk of postoperative complications. Rectal intussuception is more frequent and is pathological only when arising in the anal sphincter. Rectal intussuception may lead to solitary rectal ulcer and has in this case to be treated by rectopexy. Rectal intussuception involvement in terminal constipation is not yet proved. Internal mucosectomy seems to be the best treatment for terminal constipation.

The value of radio-surgical protocols in the treatment of advanced rectal cancer has been studied retrospectively. 21 patients operated between 1986 and 1990 fulfilling some criteria were considered for this study. They were 9 men and 12 women with rectal cancer Duke's stage B2-C; 16 were treated with preoperative radiotherapy (30-35 Gy), 5 were treated with postoperative radiotherapy (40-60 Gy). The operative procedures were 12 anterior resections and 9 Miles operations. The 5 years results were: a) cancer free survival 52%; 2 patients alive with relapse; 2 patients with non cancer related death (DIC, radiation enteritis); d) cancer related deaths 28%; e) local recurrence was observed (3 pts) only in association with metastatic disease; f) no isolated local recurrence was observed. Preoperative radiotherapy with 30-35 Gy is judged the preferred protocol for decreasing the rate of isolated local recurrence and for increasing the survival rate. Omental flap transposition plays an important role in the radio-surgical treatment of advanced rectal cancer.

A recent case of pleural plaques fibrosis in a worker exposed since 20 years to asbestos induced us to report our experience. A 52-year-old man was seen because of chest multiple opaques of soft tissue density without any symptoms. The CT-scan of thorax with i.v. contrast showed multiple lesions of diameter 0.5-4 cm on the posterolateral pleura bilaterally. FNAB of one lesion CT guided was not diagnostic. The pleural biopsy obtained at surgical exploration showed hyaline tissue, avascular, almost acellular, with calcifications and inflammation of low grade. The pleural plaques are generally multifocal and bilateral. They usually affect the parietal pleura. The connection between asbestos and plaques is firmly established. The pathogenesis is not well known. The pleural plaques fibrosis is a benign disease and a very common manifestation of asbestos exposure; it is not related to mesothelioma and it does not need any treatment. Because of the lack of symptoms it must be searched for in high risk subjects.

Intraoperative radioimmunodetection is a new staging technique for epithelial neoplasms. After intravenous injection, a radioimmunoconjugate compound (monoclonal antibody and isotope) attaches itself to the antigens expressed on the surface of neoplastic cells, causing them to emit gamma rays. Radioactivity is detected at the presurgical stage by immunoscintigraphy and intraoperatively with a gamma-detecting probe (GDP). In our experience, intraoperative tumor-to-normal-tissue (T/NT) GDP ratio counts > or =3:1 were considered positive radioimmunoguided surgery (RIGS) findings. We studied 52 colorectal cancer patients, 48 with primary lesions and 7 with relapses. Positive RIGS findings were obtained in 33 patients whose lymph node assessments were characterised by eight false positive identifications. In 10 patients, RIGS data yielded a more accurate staging of the disease. Unreliable RIGS findings were recorded in 15 patients: four injected with monoclonal antibody (MAb) B72.3 labeled with Iodine-125; five with MAb anti-carcinoembryonic antigen (CEA) labeled with 99mTechnetium (Tc); two with MAb B72.3 labeled with Indium-111; and three with MAb B72.3 labeled with Iodine-131 plus interferon-beta. In analysis, our experience did not permit definitive evaluation of the method's diagnostic and staging accuracy.