Oncological results of oncoplastic breast-conserving surgery: Long term follow-up of a large series at a single institution: A matched-cohort analysis.

PURPOSE: Oncoplastic surgery is a well-established discipline that combines conserving treatment for breast cancer with immediate plastic reconstruction. Although widely practiced, the oncologic outcomes of this combined approach are reported only in small series. The aim of the present paper is to assess the safety of oncoplastic surgery for invasive primary breast cancer. METHODS: We compared 454 consecutive patients who underwent an oncoplastic approach between 2000 and 2008 for primary invasive breast tumors (study group) with twice the number of patients who received conservation alone in the same interval time (control group). Disease free survival and overall survival were estimated using the Kaplan-Meier method. The log-rank test was used to assess differences between groups. RESULTS: The median follow-up was 7.2 years. The overall survival is similar within the two groups, being 91.4% and 91.3% at 10-yr in the study group and in the control group respectively. The disease free survival is slightly lower in the oncoplastic group (69 vs.73.1% at 10-yr). The difference is not statistically significant. DISCUSSION: We have compared a large series of primary breast cancer patients that have undergone oncoplastic surgery (454) with a control group (908) and they were followed for a prolonged period of time. It provides the best available evidence to suggest that oncoplastic surgery is a safe and reliable treatment option for the managing of invasive breast cancer.

Safety of fat grafting in secondary breast reconstruction after cancer.

BACKGROUND: Fat grafting is largely used to correct soft-tissue defects in any region of the human body. This study analysed its safety when the technique is used to correct defects after breast-cancer reconstruction. METHODS: A total of 158 patients who underwent 194 breast fat grafting procedures were analysed. Almost all patients (98%) had a personal history of breast cancer: conservative surgery or mastectomy with breast reconstruction. In all cases, fat grafting was performed according to the Coleman's technique by a single surgeon. RESULTS: Immediate complications included liponecrosis and infection in seven cases (3.6%) that required only daily dressings and oral antibiotics administration. In cases of fat grafting after conservative surgery, only four patients (5.9%) showed minor alterations in the postoperative mammograms, consisting of the appearance of benign images. CONCLUSION: Breast fat grafting can be a good solution to repair defects after breast-cancer treatment and reconstruction, and can reduce the indication for more extensive surgeries such as myocutaneous flaps. Postoperative complication rates are very low and there is little alteration in follow-up mammograms. Two points remain unclear--how much of the fat is absorbed after grafting and the potential risk of local 'dormant' tumour cells being stimulated to induce a local recurrence.

Correlation between administered treatment and patient's living will.

Respecting the wishes of an adequately informed patient should be a priority in any health structure. A patient with advanced or terminal cancer should be allowed to express their will during the most important phases of their illness. Unfortunately, this is seldom the case, and in general instructions regarding an individual's medical care preferences, i.e., their 'living will', expressed when healthy, often change with the onset of a serious illness.At the European Institute of Oncology (IEO), a clinical study is ongoing to verify whether, during clinical practice, the patient is adequately informed to sign an 'informed consent', in a fully aware manner, that will allow the patient and doctor to share in the decisions regarding complex treatment strategies (living will). A further aim of the study is to verify if health workers, both in hospital and at home, respect the patient's will.The observational study 'Respecting the patient's wishes: Correlation between administered treatment and that accepted by the patient in their Living Will' was approved by the IEO Ethical Committee in April 2008.

Surgical 'damage control' treatment of a large retroperitoneal liposarcoma encasing a horseshoe kidney.

Damage control is a surgical strategy for severely compromised trauma patients based on speed control of life-threatening injuries that aims to rapidly resuscitate patients in an intensive care unit (ICU). We report on the use of such therapeutic strategy in a patient affected by a retroperitoneal sarcoma concomitant to a horseshoe kidney, a relatively rare anatomical malformation.

Breast conservative treatment in association with implant augmentation and intraoperative radiotherapy.

After conservative treatment for small breast cancer the use of breast implants is controversial due to the negative effects of external conventional radiotherapy on soft tissues and the risk of capsular contracture. The literature reports several cases of unsuccessful breast augmentation due to implant displacement, a high percentage of capsular contracture and postoperative complications. We report the case of a 47-year-old woman with a small tumour between the inner quadrants of the left breast. She underwent quadrantectomy and sentinel node biopsy and intraoperative radiotherapy (IORT) of the target zone. Simultaneously, she received a bilateral augmentation mammaplasty. One year later we observed no evidence of local recurrence, no local fibrosis and radiodistrophy. Cosmetic results are excellent and the patient is very satisfied. The surgical technique and the possible advantage of such a procedure are also discussed.

Clinical presentation and outcome of pituitary adenomas in teenagers.

OBJECTIVE: Pituitary adenomas rarely occur in childhood and adolescence, but their mass effect and endocrine abnormalities can compromise both quality and length of life. In this study we evaluated the symptoms at onset and the long-term consequences induced in teenagers by functioning or nonfunctioning pituitary adenomas. DESIGN AND PATIENTS: Clinical, biochemical and neuroradiological data of 44 young patients (12 males and 32 females, aged 16.3 +/- 1.9 years at diagnosis) with pituitary adenomas were evaluated retrospectively at baseline and after therapy. Patients underwent surgery, radiotherapy and/or medical treatment depending on clinical history and endocrine secretion of the tumour. Follow-up ranged from 8 to 252 months (median 55 months). MEASUREMENTS: Baseline and dynamic pituitary function were evaluated in all cases at diagnosis and after treatments. Magnetic resonance imaging (MRI) or computed tomography (CT) scan were performed before therapy and during follow-up. Hormone levels were measured using commercial radioimmunologic or immunoradiometric methods. RESULTS: Pituitary macroadenomas (group 1) or microadenomas (group 2) were found in 61% and 39% of cases, respectively. Overall, 68% were PRL-secreting, 7% GH-secreting, 5% ACTH-secreting and 20% nonfunctioning. The most frequent symptoms at onset were oligoamenorrhoea (62%) and galactorrhoea (59%) in the girls, and headache (58%) in the boys. Pubertal development was delayed in 12/27 (44%) cases with macroadenoma. Growth failure was observed in 4/44 (9%) patients (3 in group 1 and 1 in group 2). At diagnosis, hypopituitarism was detected in 10/27 (37%) patients with macroadenoma. Surgery alone cured 4/18 (22%) and 4/9 (44%) patients in group 1 and group 2, respectively. Adjuvant therapies (second surgery and/or radiotherapy and/or medical treatment) cured the disease in 2/13 (15%) patients with macroadenoma and allowed a persistent normalization in other 4/13 (31%) and 2/4 (50%) cases in group 1 and group 2, respectively. Medical treatment alone cured 2/9 (22%) patients with PRL-secreting macroadenoma and normalized PRL levels in another six (66%) with macroprolactinoma and in 2/7 (28%) patients with microprolactinoma. CONCLUSION: Delay of growth was rarely observed in teenagers with pituitary adenomas. At the onset of the disease, many girls complained of oligoamenorrhoea and galactorrhoea, while headache and delay of pubertal development were the symptoms more frequently referred by boys. Surgery alone was effective in a minority of patients and adjuvant therapies were helpful to obtain the remission of the disease in many cases. In patients with PRL-secreting pituitary adenoma, medical treatment, both as first choice or as adjuvant therapy, normalizes serum PRL levels in 14/27 (52%) cases.

Learning curve for translaryngeal tracheotomy in head and neck surgery.

OBJECTIVES: Translaryngeal tracheotomy (TLT) is a widely accepted procedure in intensive-care units for its simplicity of execution, low morbidity, rapid wound closure after cannula removal, good esthetic results, and lack of long-term sequelae. The aim of this study was to evaluate the feasibility and use of adopting TLT in patients with cancer undergoing major head and neck surgery. STUDY DESIGN: Prospective analysis of learning curve and incidence of complications in 41 patients with cancer who underwent TLT at the Division of Head and Neck Surgery of the European Institute of Oncology from November 1997 to June 1999. METHODS: Patient characteristics, pathology, anatomic characteristics of the neck, and surgical short-term and long-term complications were noted. The patients were divided into consecutive groups of six or seven patients, and time trends in occurrence of complications and time to execute the procedure were assessed. RESULTS: TLT performance time decreased from 50 minutes in the first seven patients to 24 minutes in the last group. The technique was easy to perform and safe, with only two minor complications during surgery. However, minor complications occurred in three and major complications in 17 patients in the days immediately following surgery, almost entirely attributable to lack of counter-cannula and stylet. CONCLUSIONS: In view of the high proportion of major complications, TLT using the presently available kit is unsuitable for major head and neck surgery. However, the considerable advantages of the technique would recommend it as a valid alternative to surgical tracheotomy if the kit included a counter-cannula and stylet.

Actin cytoskeleton organization in response to integrin-mediated adhesion.

Cell matrix adhesion regulates actin cytoskeleton organization through distinct steps, from formation of filopodia and lamellipodia in the early phases of cell adhesion to organization of focal adhesions and stress fibers in fully adherent cells. In this review, we follow the events induced by integrin-mediated adhesion, such as activation of GTPases Cdc42 and Rac and their effectors and their role in actin polymerization leading to formation of lamellipodia and filopodia and cell spreading. We also show that actin stress fiber and focal adhesion formation following adhesion requires cooperation between integrin-mediated signaling and additional stimuli, including activation of PKC, Rho GTPases, and PTKs such as p125Fak and Src.

Integrin-mediated adhesion of endothelial cells induces JAK2 and STAT5A activation: role in the control of c-fos gene expression.

Integrin-mediated adhesion induces several signaling pathways leading to regulation of gene transcription, control of cell cycle entry and survival from apoptosis. Here we investigate the involvement of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway in integrin-mediated signaling. Plating primary human endothelial cells from umbilical cord and the human endothelial cell line ECV304 on matrix proteins or on antibody to beta1- or alphav-integrin subunits induces transient tyrosine phosphorylation of JAK2 and STAT5A. Consistent with a role for the JAK/STAT pathway in regulation of gene transcription, adhesion to matrix proteins leads to the formation of STAT5A-containing complexes with the serum-inducible element of c-fos promoter. Stable expression of a dominant negative form of STAT5A in NIH3T3 cells reduces fibronectin-induced c-fos mRNA expression, indicating the involvement of STAT5A in integrin-mediated c-fos transcription. Thus these data present a new integrin-dependent signaling mechanism involving the JAK/STAT pathway in response to cell-matrix interaction.

Integrins induce activation of EGF receptor: role in MAP kinase induction and adhesion-dependent cell survival.

Adhesion of human primary skin fibroblasts and ECV304 endothelial cells to immobilized matrix proteins, beta1 or alphav integrin antibodies stimulates tyrosine phosphorylation of the epidermal growth factor (EGF) receptor. This tyrosine phosphorylation is transiently induced, reaching maximal levels 30 min after adhesion, and it occurs in the absence of receptor ligands. Similar results were observed with EGF receptor-transfected NIH-3T3 cells. Use of a kinase-negative EGF receptor mutant demonstrates that the integrin-stimulated tyrosine phosphorylation is due to activation of the receptor's intrinsic kinase activity. Integrin-mediated EGF receptor activation leads to Erk-1/MAP kinase induction, as shown by treatment with the specific inhibitor tyrphostin AG1478 and by expression of a dominant-negative EGF receptor mutant. EGF receptor and Erk-1/MAP kinase activation by integrins does not lead per se to cell proliferation, but is important for entry into S phase in response to EGF or serum. EGF receptor activation is also required for extracellular matrix-mediated cell survival. Adhesion-dependent MAP kinase activation and survival are regulated through EGF receptor activation in cells expressing this molecule above a threshold level (5x10(3) receptors per cell). These results demonstrate that integrin-dependent EGF receptor activation is a novel signaling mechanism involved in cell survival and proliferation in response to extracellular matrix.

Engraftment of HLA-matched sibling hematopoietic stem cells after immunosuppressive conditioning regimen in patients with hematologic neoplasias.

BACKGROUND AND OBJECTIVE: The main objective of this pilot study was to assess the possibility of achieving engraftment of HLA-matched sibling donor mobilized hematopoietic stem cells after immunosuppressive non-myeloablative therapy. The second objective was to verify whether high-dose therapy with autologous stem cells rescue followed by allografting conditioned by only an immunosuppressive regimen, can be combined in order to achieve the reduction of tumor burden after autografting and the control of residual disease with immune-mediated effects after allografting. DESIGN AND METHODS: To enter the pilot study the patients had to fulfil the following criteria: advanced resistant disease, presence of an HLA matched sibling donor, no general contraindications to stem cell transplantation. Our data refers to 9 patients: Hodgkin's disease (n = 4), non-Hodgkin's lymphoma (n = 2), advanced chronic myelogenous leukemia (n = 2) (one patient with accelerated phase Ph-negative but p190 BCR-ABL gene positive by RT-PCR and one with Ph-positive blastic phase), refractory anemia with excess of blasts t(1;3) (p36;q21) (n = 1). All patients but one received the combined approach. At a median of 40 days (range 30-96), after high-dose therapy and autologous stem cell engraftment, the patients were treated with immunosuppressive therapy consisting of fludarabine and cyclophosphamide (Flu-Cy protocol) and then HLA matched donor mobilized stem cells were infused into the patients. GvHD prophylaxis consisted of cyclosporin and methotrexate. RESULTS: To date, with a median observation period of 4 months (range, 2-10), complete chimerism (100% donor cells) has been achieved in 6 patients. Three patients did not achieve complete chimerism: one patient died of progressive Hodgkin's disease when he reached 55% of donor cells, another patient is now in increasing phase of donor cell engraftment and the last patient (blastic phase-CML) was the only case who appears to have had autologous recovery. Two of the Hodgkin's disease patients, who were in partial remission after autografting, achieved complete remission after allografting and both are disease free 2 and 6 months after. Another Hodgkin's disease patient is alive at 10 months but she has progressive disease. One of the two patients with non-Hodgkin's lymphoma, who achieved partial remission after autografting, obtained complete remission and he is disease free 2 months after allografting. The other patient maintains partial remission obtained after autografting. The accelerated phase-CML patient obtained hematologic and molecular remission; the RAEB patient achieved hematologic and cytogenetic remission. In two patients severe aGVHD (grade II-III) was the single major complication but neither patient died of it. Mild aGVHD was seen in another patient. In only one patient did the ANC decrease to below 1 x 10(9)/L and in no case did platelets decrease below 20 x 10(9)/L. No patients required a sterile room or any red cell or platelet transfusions. INTERPRETATION AND CONCLUSIONS: Immunosuppressive therapy with a Flu-Cy protocol allowed engraftment of HLA-matched sibling donor stem cells without procedure-related deaths; moreover, we have demonstrated that this combined procedure can be pursued in safety in a serious ill population and some of these patients achieved a complete remission. This procedure is not likely to be curative, but a fascinating step along the path to curing these diseases. Of course, the follow-up is too short to document the incidence of cGvHD.

Combined lung volume reduction surgery and thoracic aortic aneurysm resection.

Postoperative improvement of respiratory function has been reported with lung volume reduction surgery (LVRS) in patients with severe emphysema. Since smoking is an established risk factor for lung cancer, vascular diseases and emphysema, it is not infrequent to find these diseases associated in the same patient. Combined treatment of lung cancer and emphysema has already been reported. Surgical treatment of vascular diseases in emphysematous patients could also benefit from the application of LVRS techniques. We report resection of an aortic aneurysm combined with LVRS in a patient with concomitant thoracic aortic aneurysm and severe emphysema. Respiratory function improved in the postoperative period.

[The effectiveness of enoximone in patients with serious left ventricular dysfunction submitted for aorto-coronary bypass]. / Efficacia dell'enoximone in pazienti con grave disfunzione ventricolare sinistra sottoposti a bypass aorto-coronarico.

BACKGROUND: The purpose of this study was to investigate whether the combined positive inotropic and vasodilating properties of enoximone have a short-term benefit when used in patients who underwent open heart surgery. METHODS: From 7/1994 to 1/1995 twenty-six patients with severe myocardial dysfunction (ejection fraction < 35%) were enrolled into a prospective trial before undergoing coronary artery bypass graft. They were randomly selected into two study groups: the first treated with enoximone (group E) and the other one with dopamine (group D). Anaesthesia was the same for both groups using high-dose fentanyl. Buckberg cardioplegia was used. All patients were followed by: conventional monitoring, Swan-Ganz catheter and transesophageal echocardiography. measurements (hemodynamic parameters, end-systolic and diastolic area and left ventricular wall motion) were recorded: after induction of anesthesia, after loading-dose and an intensive care unit. Enoximone- and dopamine infusions were started during weaning from cardiopulmonary bypass and tailored to hemodynamic parameters (cardiac index > 2.8 l/min, wedge pressure < 16 mmHg, mixed venous blood saturation > 65%). Major events were defined as: endotracheal intubation > 36 h, using intraortic balloon pump or centrifugal pump, intensive care timer > 48 h, in hospital cardiac death. Prices, were established by DRG-tables (diagnosis related groups). Statistical analysis were performed by X and "t" Student tests. RESULTS: Cardiac index increased more significantly in group E (CI 1.9-->3.9 vs 2.3-->3.3; p 0.05) thanks to a higher reduction of vascular systemic (SVRI 2889-->1447 vs 2536 -->1565; p 0.005) and pulmonary resistances (PVRI 271-->193 vs 288-->218; p 0.05). Fewer major cumulative events and intensive care costs were observed in group E rather than group D. CONCLUSIONS: Enoximone administer immediately after open heart surgery had more beneficial hemodynamic and clinical effects than dopamine in patients with severe left ventricular dysfunction.

Cerebral ischemia after venous air embolism in the absence of intracardiac defects.

Cerebral air embolism occurred in a patient undergoing posterior fossa surgery performed in the sitting position for acoustic neuroma removal. The patient experienced two episodes of venous air embolism, as evidenced by precordial Doppler, end-tidal carbon dioxide reduction, and oxygen desaturation. In both cases, air was aspirated from the central venous catheter; during the second episode there was arterial hypotension and electrocardiogram changes, and air bubbles were visualized in the cerebellar arteries. The patient did not regain consciousness after surgery and developed early tonic-clonic convulsions and electroencephalogram status epilepticus, which was treated with barbiturate coma. Intracardiac septal defects were not detected by transesophageal echocardiography, and computerized tomography of the brain demonstrated multifocal discrete ischemic areas in the cerebral hemispheres. The patient died 6 days after surgery without having regained consciousness. This case appears to represent the occurrence of transpulmonary passage of venous air embolism.

[Prognostic factors in chronic lymphatic leukemia]. / Fattori prognostici nella leucemia linfatica cronica.

The analysis of our case histories aims at verifying if the immunological phenotype of the leukaemic lymphocyte B, essential diagnostic element, can have prognostic meaning and integrate the known methods of staging. We tested peripheral blood and samples of bone marrow at the cytofluorimeter with techniques of immunofluorescence. We considered the density of the sIg, lymphocytic doubling time (LDT), clusters of designation 23 (CD23), as immunological marker of activation, we also documented a relationship between these indicators and the classic clinical stage. We observed that the chronic lymphocytic leukaemia (CLL) in the stage B and C have generally sIg at high density, correlated to a short time of lymphocytic doubling, and that in the group with a low risk (stage A) the low density of sIg is correlated with a long time of doubling, index of the growth of tumoral bulk. The activation marker (CD23) shows a positive prognostic meaning, as it is more expressed in CLL at a low density of sIg and present in larger quantity in the initial clinical stage. We defined a classic immunophenotypic pattern for the CLL-B with positivity of CD5, sIg at a low density, Ag of activation highly positive related to a history of favourable disease; while an immunologic structure with CD5 negativity, less activated and more differentiated phenotype (CD23 low expression, high density sIg) seems to define a more severe prognosis.

Endometrial cells of the "lower uterine segment" (LUS) in cervical smears obtained by endocervical brushings: a source of potential diagnostic pitfall.

The use of endocervical brushes has led to a generous sampling of both endocervical and "lower uterine segment" (LUS) cells. To an unfamiliar eye, the large fragments of endometrial tissue from the LUS may lead to misinterpretation as endometriosis or glandular malignancy, as happened in our institution when the use of endocervical brush and recognition of LUS cells in cervical smears were limited. Eight cases, cytologically interpreted as such, were proven to be benign following cervical biopsy or endometrial curettage. The nature of LUS cells was recognized only on retrospective review of this cytologic material. However, in recent years, routine use of the endocervical brush resulted in an influx of similar cases referred by the cytotechnologists to the pathologist as glandular atypia. Thus, to get familiarized with the cytomorphology of LUS cells and its diagnostic pitfalls, a prospective study was undertaken. This entailed a review of 62,187 consecutive cervicovaginal smears (women of post-hysterectomy status were excluded) received within a 12-mo period (July 1, 1992-June 30, 1993). A total of 344 smears (0.55%) showed large tissue fragments of branching tubular endometrial glands with and without surrounding stroma. Patients ranged from 14-82 yr of age. History of cervical cone biopsy was noted in nine patients (2.6%). Repeat cervical smear or concurrent endometrial or endocervical biopsy available in 84 patients (24.4%) were negative. LUS cells may be mistaken for endometriosis, epithelial glandular atypia, as well as carcinoma of both endocervical and endometrial origin. In addition to glandular abnormality, LUS cells may also be misinterpreted as that of squamous intraepithelial lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous intra-arterial blood gas monitoring. A clinical experience.

Miniaturized sensors, based upon the principles of optical fluorescence, can measure in vivo the pH, pCO2 value and pO2 value of blood. In this report we studied continuous intra-arterial blood gas monitoring in 27 patients undergoing cardiac surgery (no. 16 coronary artery by-pass grafting, no. 2 valvular surgery) and major vascular surgery (no. 9 abdominal aortic aneurysms). Total duration of continuous intra-arterial blood gas monitoring was 677 hours, with a ratio of 25.0 +/- 14.8 hours/patient (range 4-96 hours). The in vitro values of pH, pCO2 and pO2 were compared to simultaneous records from the fiberoptic sensor for each of the 283 arterial blood gas samples obtained, by means of linear regression and Bland-Altman method, in order to test the correlation and the agreement between the two methods of measuring. For pH average bias was -0.023 and intersensor precision was 0.028, with a strong correlation (R = 0.92; p < 0.001) and agreement. For pCO2 the average bias was 0.91 and the inter-sensor precision was 2.65, with a slight decrease in correlation (R = 0.89; p < 0.001) and agreement. For pO2 average bias was -2.69 and the intersensor precision was 12.16, with a strong correlation (R = 0.97; p < 0.001) and agreement. In addition, we tested the reliability of the system for values of pO2 above 100 mmHg and we found a strong correlation (R = 0.96; p20.001) and agreement even for these clinical conditions, largely out of physiologic parameters. This study demonstrates the feasibility and reliability of continuous intra-arterial three-component PB 3300 (Puritan Bennett) blood gas monitoring.