Maria Alle Research Articles

Trend of accesses to the Emergency Department of a Teaching Hospital of Tuscany due to bronchiolitis in 2018-2023: new challenges.

Acute bronchiolitis is one of leading causes of lower respiratory tract infection and hospitalisation in children less than one year old worldwide. The aim of our study is investigating the impact of bronchiolitis in children paediatric to the Emergency Department (ED) of Teaching Hospital (AOUS), Santa Maria alle Scotte of Siena, Tuscany (Italy). A retrospective observational study was conducted on the accesses performed at the ED of the AOUS of Siena by children under 18 years of age suffering from bronchiolitis from September 2018 to April 2023. There were 36,031 patients between 0 and 18 years old in the Emergency Department, 383 of which presented bronchiolitis (age 4.8 months C.I.:3.5-6 months.; 54% male). Those who accessed the ED with a higher priority code were more likely to be subsequently admitted (O.R.:2.6; C.I.:1.3-5.1; p < 0.01). Those who accessed the ED with symptoms of bronchiolitis during the weekend were less likely to have been sent from community medicine services or professionals (O.R:0.1; C.I:0.0-0.5; p < 0.001). Children below 1 year old were more likely to access the ED with respiratory distress symptoms (O.R.:2.6; C.I.:1.5-4.3; p < 0.001). Finally, those who accessed the ED with bronchiolitis were more likely to be admitted than those who accessed for other conditions (O.R:24.5; C.I.:19.4-31; p < 0.001). It is necessary to invest protocols integrating hospital services and community medicine in order to achieve a timely diagnosis and to reduce the accesses to the ED of children presenting mild, non-severe form of bronchiolitis in order to avoid the overload of hospital services.

Gallbladder Stones in Pediatric Age: An Emerging Problem: The Risk of Difficult Cholecystectomy and the Importance of a Preoperative Evaluation.

The need for cholecystectomy during pediatric age has significantly increased in the last two decades. As biliary pathology increases, the probability of complicated cholecystectomies increases too. The aim of this article is to analyze our experience with difficult laparoscopic pediatric cholecystectomy, focusing on the importance of an accurate pre-operative imaging study. We retrospectively analyzed all patients affected by cholelithiasis who underwent laparoscopic cholecystectomy at the Pediatric Surgery Department of San Camillo Forlanini hospital of Rome and Santa Maria alle Scotte University Hospital of Siena from 2017 to 2022. Demographic data, body mass index (BMI), recovery data, laboratory tests, imaging exams, surgical findings, post operative management and outcome were taken into account. Overall, 34 pediatric patients, with a mean age of 14.1 years (6-18 years) were included, with a mean BMI of 29. All patients underwent abdominal ultrasonography and a liver MRI with cholangiography (cMRI). We identified five cases as "difficult cholecystectomies". Two subtotal cholecystectomies were performed. Cholecystectomy in pediatric surgery can be difficult. The surgeon must be able to find alternative strategies to total cholecystectomy to avoid the risk of possible bile duct injury (BDI). Pre-operative imaging study trough ultrasound and especially cMRI is crucial to recognize possible difficulties and to plan the surgery.

Vitamin D Deficiency in COVID-19 Patients and Role of Calcifediol Supplementation.

Hypovitaminosis D has been associated with worse outcome in respiratory tract infections, with conflicting opinions regarding its role in Coronavirus-19 disease (COVID-19). Our study aimed to evaluate the possible relationship between 25-OH vitamin D (25OHD) values and the following conditions in patients hospitalized for COVID-19: prognosis, mortality, invasive (IV) and non-invasive (NIV) mechanical ventilation, and orotracheal intubation (OTI). A further objective was the analysis of a possible positive effect of supplementation with calcifediol on COVID-19 severity and prognosis. We analyzed 288 patients hospitalized at the San Giovanni di Dio Hospital in Florence and the Santa Maria alle Scotte Hospital in Siena, from November 2020 to February 2021. The 25OHD levels correlated positively with the partial pressure of oxygen and FiO2 (PaO2/FiO2) ratio (r = 0.17; p < 0.05). Furthermore, when we analyzed the patients according to the type of respiratory support, we found that 25OHD levels were markedly reduced in patients who underwent non-invasive ventilation and orotracheal intubation (OTI). The evaluation of the length of hospitalization in our population evidenced a longer duration of hospitalization in patients with severe 25OHD deficiency (<10 ng/mL). Moreover, we found a statistically significant difference in the mortality rate between patients who had 25OHD levels below 10 ng/mL and those with levels above this threshold in the total population (50.8% vs. 25.5%, p = 0.005), as well as between patients with 25OHD levels below 20 ng/mL and those with levels above that threshold (38.4% vs. 24.6%, p = 0.04). Moreover, COVID-19 patients supplemented with calcifediol presented a significantly reduced length of hospitalization (p < 0.05). Interestingly, when we analyzed the possible effects of calcifediol on mortality rate in patients with COVID-19, we found that the percentage of deaths was significantly higher in patients who did not receive any supplementation than in those who were treated with calcifediol (p < 0.05) In conclusion, we have demonstrated with our study the best prognosis of COVID-19 patients with adequate vitamin D levels and patients treated with calcifediol supplementation.

Breast cancer in patients with Lynch syndrome: A single institution retrospective analysis.

e22549 Background: Lynch syndrome (LS) is associated with an increased risk of several malignancies including gastrointestinal, genitourinary, gynecologic, skin, and brain cancers. However, whether patients with LS have higher risk of developing breast cancer (BC) or not is still controversial and a relevant clinical question. Methods: From the Santa Maria alle Scotte Hospital registry, we retrospectively identified consecutive patients with LS diagnosed by detecting a germline heterozygous pathogenic or likely-pathogenic variant in MLH1, MSH2, MSH6 or PMS2 on molecular genetic testing within April 2016-January 2022. We compared our sample size to Surveillance, Epidemiology, and End Results Program (SEER) of 2017 National Cancer Institute database. Results: Overall, 43 patients with LS were identified. Of those, 11 (25.6%; 95% CI 1.58-26.72%; p &lt; 0.0001) had histologically confirmed BC, 10 (91%) of whom were hormone receptor positive tumors and BC is the only diagnosis of cancer to date. In this 11 patients median age at diagnosis was 54.5 years. 45% of 11 BC LS patients has germinal MSH2 mutation , 45% of 11% are MSH6 mutaded and has a more aggressive breast cancer. Median follow-up was 3 years and 8 months. All patients are still alive and under treatment. Conclusions: Within the limitations of a small sample size and retrospective design, our analysis suggests a significant association between patients with LS and the diagnosis of primary BC. Validation of such findings through prospective clinical studies with larger samples is warranted and would lead to fundamental modifications to LS screening and follow-up international recommendations.

To Keep or Not to Keep? The Hamletic Umbilical Dilemma: Preservation versus Reconstruction of the Umbilicus in Vertical Abdominoplasty.

(1) Background: The role of the umbilical scar and its repositioning remains one of the most important surgical steps in the execution of any type of abdominoplasty, including those involving "inverted-t" or "fleur de lys" incisions. A consequence of this is a surgeon's Hamletic dilemma: to keep or not to keep the original umbilical scar? (2) Methods: A retrospective observational study was conducted on all patients undergoing "T-inverted" abdominoplasty at the Department of Plastic Surgery of the Santa Maria alle Scotte University Hospital, Siena, between January 2018 and December 2020. Twelve months after the surgery we submitted to all patients the U-score questionnaire about their feelings about their umbilicus's appearance. Patients could assign a score from 1 (very dissatisfied) to 4 (very satisfied) to each of the five items of the score. (3) Results: The average of the scores attributed by the nine patients in whom the navel was preserved is 13 (Range 10-17), while in patients on whom a navel reconstruction was performed, the mean score is 16.8 (Range 12-20). The mean score of patients with a reconstructed umbilicus is, therefore, statistically higher than that of the other group of patients (t-value = 3.88, p = 0.000374) with an average increase of 3.8 points. (4) Conclusions: We can state that the reconstruction of a new navel is the right answer to the Hamletic dilemma in patients having undergone vertical or anchor abdominoplasty.

The prognostic value of CD3+ tumor-infiltrating lymphocytes for stage II colon cancer according to use of adjuvant chemotherapy: A large single-institution cohort study

BackgroundHigh tumor infiltrating lymphocytes (TILs) density was previously shown to be associated with favorable prognosis for patients with colon cancer (CC). However, the impact of TILs on overall survival (OS) of stage II CC patients who received adjuvant chemotherapy (ADJ) or not (no-ADJ) is unknown. We assessed the prognostic value of CD3+ TILs in stage II CC patients according to whether they had ADJ or not. MethodsPatients treated with curative surgery for stage II CC (2002–2013) were selected from the Santa Maria alle Scotte Hospital registry. TILs at the invasive front, center of tumor, and stroma were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as >20%. Patients were categorized as high or low TILs (L-TILs) and ADJ or no-ADJ. ResultsOf the 678 patients included, 137 (20%) received ADJ and 541 (80%) did not. The distribution of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ patients showed a significantly increased OS (P<.01) regardless of the TILs rate whereas L-TILs/no-ADJ had significantly decreased OS and higher risk of death (HR=1.41; 95% CI, 1.06–1.88; P<.0001). On multivariable analysis, the unfavorable prognostic value of L-TILs (vs. H-TILs) for no-ADJ patients was confirmed (HR=1.36; 95% CI 1.02, 1.82; P=.0373). ConclusionLow CD3+ TILs rate was associated with shorter OS in those with stage II colon cancer who did not receive adjuvant therapy. Low CD3+ TILs could be considered an additional risk factor for still ADJ-untreated stage II CC patients, which could facilitate clinical decision making.

Direct Versus Indirect Corneal Neurotization for the Treatment of Neurotrophic Keratopathy: A Multicenter Prospective Comparative Study

To analyze the comparative safety and efficacy of two techniques of corneal neurotization (CN) (direct corneal neurotization [DCN] vs indirect corneal neurotization [ICN]) for the treatment of neurotrophic keratopathy (NK). Multicenter interventional prospective comparative case series. This study took place at ASST Santi Paolo e Carlo University Hospital, Milan; S.Orsola-Malpighi University Hospital, Bologna; and Santa Maria alle Scotte University Hospital, Siena, Italy. The study population consisted of consecutive patients with NK who underwent CN between November 2014 and October 2019. The intervention procedures included DCN, which was was performed by transferring contralateral supraorbital and supratrochlear nerves. ICN was performed using a sural nerve graft. The main outcome measures included NK healing, corneal sensitivity, corneal nerve fiber length (CNFL) measured by invivo confocal microscopy (IVCM), and complication rates. A total of 26 eyes in 25 patients were included: 16 eyes were treated with DCN and 10 with ICN. After surgery, NK was healed in all patients after a mean period of 3.9months without differences between DCN and ICN. Mean corneal sensitivity improved significantly 1 year after surgery (from 3.07 to 22.11mm; P < .001) without differences between the 2 groups. The corneal sub-basal nerve plexus that was absent before surgery in all patients, except 4, become detectable in all cases (mean CNFL: 14.67 ± 7.92mm/mm2 1 year postoperatively). No major complications were recorded in both groups. CN allowed the healing of NK in all patients as well as improvement of corneal sensitivity in most of them thanks to nerve regeneration documented by IVCM. One year postoperatively, DCN and ICN showed comparable outcomes.

CD3+ tumor-infiltrating lymphocytes (TILs) as prognostic in patients (pts) with stage II colon cancer (CC) not treated with adjuvant chemotherapy (ADJ).

167 Background: Previous studies have reported high TILs are a favorable prognostic factor in stage II CC. However, whether the impact of TILs on overall survival (OS) differs among pts who did or did not receive ADJ is still to be determined. We assessed the prognostic value of CD3+ TILs in pts with stage II CC according to whether they received ADJ or not (no-ADJ). Methods: Pts treated with curative surgery for stage II CC (2002-2013) were identified through the Santa Maria alle Scotte Hospital database. CD3+ TILs at the invasive front, center of tumor, and stroma, were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as &gt; 20%. Pts were classified as high or low TILs (L-TILs) and ADJ or no-ADJ. Cox models were used to assess OS with hazard ratio estimates (95% CI). Results: Of the 678 pts included (356 deaths), 137 (20%) received ADJ while 541 (80%) did not. ADJ comprised fluoropyrimidine +/- oxaliplatin. Median follow-up was 8.5 years. The distributions of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ pts had a significantly longer OS (P &lt; .0001) regardless of the TILS rate while L-TILs/no ADJ had significantly shorter OS and higher risk of death (HR = 1.41; 95% CI, 1.06-1.88; P &lt; .0001) [See table]. On multivariable analysis, adjusting for perforation, obstruction, T-stage, grade, &lt; 12 lymph nodes resected, lymphovascular and perineural invasion, the adverse prognostic impact of L-TILs (vs H-TILs) in no-ADJ pts was confirmed (HR = 1.36; 95% CI 1.02, 1.82; P = .0373). Conclusions: Low CD3+ TILs rate was independently associated with shorter OS in stage II CC pts who did not receive ADJ, but was not prognostic among pts who had ADJ. These data suggest a potentially different impact of TILs in chemo-treated vs -untreated stage II CC which could affect clinical decision making. [Table: see text]

Intraoperatory radiotherapy (IORT) during breast cancer surgery: Acute cardiac safety tested by troponin

Intraoperatory radiotherapy (IORT) during breast cancer surgery: Acute cardiac safety tested by troponin

Health Services OutPatient Experience questionnaire: factorial validity and reliability of a patient-centered outcome measure for outpatient settings in Italy.

PurposeThe patient-centered approach to health care does not seem to be sufficiently developed in the Italian context, and is still characterized by the biomedical model. In addition, there is a lack of validated outcome measures to assess outpatient experience as an aspect common to a variety of settings. The current study aimed to evaluate the factorial validity, reliability, and invariance across sex of the Health Services OutPatient Experience (HSOPE) questionnaire, a short ten-item measure of patient-centeredness for Italian adult outpatients. The rationale for unidimensionality of the measure was that it could cover global patient experience as a process common to patients with a variety of diseases and irrespective of the phase of treatment course.Patients and methodsThe HSOPE was compiled by 1,532 adult outpatients (51% females, mean age 59.22 years, standard deviation 16.26) receiving care in ten facilities at the Santa Maria alle Scotte University Hospital of Siena, Italy. The sample represented all the age cohorts. Twelve percent were young adults, 57% were adults, and 32% were older adults. Exploratory and confirmatory factor analyses were conducted to evaluate factor structure. Reliability was evaluated as internal consistency using Cronbach’s α. Factor invariance was assessed through multigroup analyses.ResultsBoth exploratory and confirmatory analyses suggested a clearly defined unidimensional structure of the measure, with all the ten items having salient loadings on a single factor. Internal consistency was excellent (α=0.95). Indices of model fit supported a single-factor structure for both male and female outpatient groups. Young adult outpatients had significantly lower scores on perceived patient-centeredness relative to older adults. No significant difference emerged on patient-centeredness between male and female outpatients.ConclusionThe HSOPE questionnaire seemed to be a tool with high acceptability and excellent psychometric properties to measure patient-centeredness as a unidimensional construct. Limitations and implications for future research are discussed.

LONG TERM NEURODEVELOPMENTAL OUTCOME IN A COHORT OF PRETERM INFANTS BORN AT GESTATIONAL AGE

Advances in perinatal care have led to an increase in survival of preterm children but have also increased the risk of long-term sequelae, like neurodevelopmental impairment and behavioral or emotional disturbance. To investigate neurodevelopmental patterns of preterm infants born at S. Maria alle Scotte Hospital, Siena, Italy. 128 babies with gestational age (GA) ≤32 weeks were admitted in 2006-2008 to Siena Hospital; 105 infants survived and were followed until three years of age, corrected for prematurity. Neurodevelopmental follow up was performed using Bayley scale of Infant and Toddler Development IIIed that consisted of five scales: Cognitive (CS), Language (LS), Motor (MS), Social-Emotional (SES) and Adaptive Behavior Scale (ABS). Intraventricular haemorrhage (IVH) was associated with lower motor score (P<0,001). Babies with retinopathy of prematurity (ROP) showed a lower score in CS, LS, MS and SES Bayley’s items (respectively p≤0,01; p≤0,05; p≤0,01; p≤0,05). Multiple regression analysis indicated as predictors of neurological outcome: gestational age (GA) for poor cognitive (p=0,016), language (p=0,004) and social-emotional development (p<0,0001), IVH for poor motor (p<0,0001) and adaptive behavior development (p<0,0001), twinship for better language (p=0,001) and social-emotional development (p=0,003). Bronchopulmoanry dyspasia (BPD) and patent ductus arteriosus (PDA) had a negative effect on respectively cognitive development (p=0,049) and social-emotional development (p=0,023). ROP, BPD, IVH, PDA, and GA significantly contributes to poor neurological outcome in preterm infants. BPD and IVH are the best predictors being associated with the lowest scores at Bayley scales. Surprisingly, twinship appeared to be a protective factor.

LONG TERM NEURODEVELOPMENTAL OUTCOME IN A COHORT OF PRETERM INFANTS BORN AT GESTATIONAL AGE &lt;32 WEEKS

Advances in perinatal care have led to an increase in survival of preterm children but have also increased the risk of long-term sequelae, like neurodevelopmental impairment and behavioral or emotional disturbance. To investigate neurodevelopmental patterns of preterm infants born at S. Maria alle Scotte Hospital, Siena, Italy. 128 babies with gestational age (GA) ≤32 weeks were admitted in 2006-2008 to Siena Hospital; 105 infants survived and were followed until three years of age, corrected for prematurity. Neurodevelopmental follow up was performed using Bayley scale of Infant and Toddler Development IIIed that consisted of five scales: Cognitive (CS), Language (LS), Motor (MS), Social-Emotional (SES) and Adaptive Behavior Scale (ABS). Intraventricular haemorrhage (IVH) was associated with lower motor score (P&lt;0,001). Babies with retinopathy of prematurity (ROP) showed a lower score in CS, LS, MS and SES Bayley’s items (respectively p≤0,01; p≤0,05; p≤0,01; p≤0,05). Multiple regression analysis indicated as predictors of neurological outcome: gestational age (GA) for poor cognitive (p=0,016), language (p=0,004) and social-emotional development (p&lt;0,0001), IVH for poor motor (p&lt;0,0001) and adaptive behavior development (p&lt;0,0001), twinship for better language (p=0,001) and social-emotional development (p=0,003). Bronchopulmoanry dyspasia (BPD) and patent ductus arteriosus (PDA) had a negative effect on respectively cognitive development (p=0,049) and social-emotional development (p=0,023). ROP, BPD, IVH, PDA, and GA significantly contributes to poor neurological outcome in preterm infants. BPD and IVH are the best predictors being associated with the lowest scores at Bayley scales. Surprisingly, twinship appeared to be a protective factor.

Photophobia and bilateral pulvinar involvement in non-alcoholic Wernicke’s encephalopathy

Photophobia is a subjective discomfort to light, varying from mild to intolerable pain, which can be associated with disorders of the anterior eye segment, or intracranial diseases [1]. Although the exact pathophysiology remains obscure, an interaction between the trigeminal nociceptive pathway and the visual system at various brain and ocular levels is accepted [1, 2]. A possible involvement of pulvinar has been recently considered, since it receives both second-order trigeminal neurons projections [3] and direct retinal fibers belonging to the non-visual forming pathway (NVFP) [4, 5]. Wernicke’s encephalopathy (WE) is an acute neurological disorder due to thiamine deficiency, usually involving specific brain areas, such as thalamus and periaqueductal region, also accounted in the pathway of photophobia. Photophobia, however, has never been reported as presenting symptom in WE. Here we report two patients with photophobia as manifesting symptom of non-alcoholic WE, who, beside the involvement of the nociceptive brainstem structures, presented a clear involvement of the pulvinar at brain MRI. The two subjects, respectively, of 70 and 63 years of age, have been described in a review reporting the clinical and MRI findings of ten patients who developed WE after gastrointestinal surgery for cancer [6]. The study was performed according to the Declaration of Helsinki and was approved by the local Ethics Committee. The older patient underwent a surgical procedure of pancolectomy for a colon cancer. One month later, he suddenly became confused, with deterioration of shortterm memory, and asleep. Neurological examination showed horizontal and vertical gaze restriction, mild cerebellar signs as dysarthria and dysmetria, and photophobia. Pupillary diameter was 3 mm they were poor reactive to light and near. Spot light exposure was associated with painful photophobia. Brain MRI evidenced areas of signal alterations in periaqueductal gray, mammillary bodies, medial thalami, both pulvinars, frontal and parietal cortex confirming the diagnosis of WE (Fig. 1a, b). A substitutive therapy with thiamine 300 mg/daily was administrated 2 days after the onset of neurological symptoms. Although the neurological conditions significantly improved with therapy, the patient died for pulmonary complications. The younger subject was diagnosed with a rectal tumor. Ten days after the surgical removal of cancer, he presented with agitation and mental confusion. Neurological examination pointed out cerebellar signs, such as mild dysarthria, dysmetria and gaze-evoked nystagmus, and vertical gaze restriction. Short-term memory was affected. Pupillary diameter was 3.5 mm with poor reactivity and intense F. Rosini E. Pretegiani G. Lucii P. Federighi A. Rufa (&) Eye Tracking and Visual Applications Lab (EVA Lab), Department of Medical, Surgical and Neurological Sciences, University of Siena, Policlinico ‘‘Santa Maria alle Scotte’’, viale Bracci 2, Siena, Italy e-mail: rufa@unisi.it

A 72-year-old patient with neuromyelitis optica (NMO) spectrum disorder: A case report

R. Buccoliero *, N. Hickley , K. Sansam , A. Gough , D. Scullion , S. Hasan , A. Cerase e Department of Neurology, Harrogate District Foundation Trust, Harrogate HG2 7SX, UK Department of Rheumatology, Harrogate District Foundation Trust, Harrogate, UK Department of Radiology, Harrogate District Foundation Trust, Harrogate, UK Department of Neuroscience, York Teaching Hospital, York, UK Unit NINT Neuroimaging and Neurointervention, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Universitaria Senese, ‘‘Santa Maria alle Scotte’’ General Hospital, Viale Mario Bracci 16, 53100 Siena, Italy Available online at

Superselective ophthalmic artery infusion of melphalan for intraocular retinoblastoma: preliminary results from 140 treatments

To report our experience in superselective ophthalmic artery infusion of melphalan (SOAIM) for intraocular retinoblastoma. From June 2008 to October 2010, 38 patients (18 women, 20 men; age range at first treatment, 7 months to 22 years) with 41 eyes with retinoblastoma were scheduled for SOAIM, for 17 newly diagnosed retinoblastomas Tumour, Node and Metastasis (TNM) 7th Edition 1a (n = 1), 1b (n = 1), 2a (n = 7), 2b (n = 4) and 3a (n = 4) and 24 retinoblastomas with partial remission/relapse TNM 7th Edition 1b (n = 13), 2a (n = 1) and 2b (n = 10). Eight patients (ten eyes) have been treated by SOAIM alone. Follow-up was 6-27 months in 28 patients (30 eyes). Ophthalmic artery cannulation failed in two patients. Thirty-six patients underwent 140 treatments by internal (n = 112) or external (n = 28) carotid arteries. No major procedural complications occurred. Two patients have been lost to follow-up. Remaining 34 patients (37 eyes) had no metastatic disease. Four patients suffered permanent ocular complications: chorioretinal dystrophy (n = 2), ptosis (n = 1) and strabismus/exotropia (n = 1). Eight (22%) eyes in eight (24%) patients underwent enucleation: 7/16 (43%) newly diagnosed retinoblastomas and 1/22 (4.5%) retinoblastomas undergoing partial remission/relapse. For all treated eyes, Kaplan-Meier eye enucleation-free rates (K-M) were 85.4% (95% CI, 73.3-97.5%), 74.4% (95% CI, 57-91.8%) and still stable at 6, 12 months and 2 years, respectively. For eyes with partial remission/relapse, and eyes at presentation, K-M at 2 years were 95.5% (95% CI, 86.9-100%) and 45.6% (95% CI, 16.6-74.6%), respectively. Superselective ophthalmic artery infusion of melphalan was safe and powerful, especially following other therapies. Superselective ophthalmic artery infusion of melphalan should be added to focal therapies spectrum. In selected cases, melphalan should be combined with other chemotherapeutic agents.

6140 POSTER Cetuximab-mediated Immune-enhancing Effects in Vitro and in Metastatic Colorectal Cancer (mCRC) Patients

6140 POSTER Cetuximab-mediated Immune-enhancing Effects in Vitro and in Metastatic Colorectal Cancer (mCRC) Patients P. Correale1, C. Botta1, M.G. Cusi2, E. Bestoso1, S. Apollinari1, M. Caraglia3, M.T. Del Vecchio4, A. Abbruzzese3, A. Aquino5, P. Tagliaferri6. 1“S. Maria alle Scotte” Siena University Hospital, Department of Oncology, Siena, Italy; 2“S. Maria alle Scotte” Siena University Hospital, Department of Molecular Biology Microbiology Section, Siena, Italy; 3II University of Naples, Department of Biochemistry and Biophysics, Naples, Italy; 4“S. Maria alle Scotte” University Hospital of Siena, Section of Pathological Anatomy Department of Human Pathology and Oncology, Siena, Italy; 5“Tor Vergata” University, Department of Neurosciences Pharmacology Section, Rome, Italy; 6Magna Graecia University and Tommaso Campanella Cancer Center Catanzaro, Medical Oncology, Catanzaro, Italy Introduction: Cetuximab is a chimeric human-murine monoclonal IgG1 to the Epidermal-growth-factor-Receptor, approved for colorectal cancer treatment with chemotherapy. Its human constant fragment (Fc), throughout receptor binding, trigger additional immune-mediated effects, which may offer significant contribute to the final therapeutic effect. We investigated cetuximab ability in vitro to promote colon cancer cell phagocytosis and antigen-cross-priming by dendritic cells (DCs) to tumour-specific cytotoxic- T-cell (CTL) precursors. We also carried-out an immunological study in 26 mCRC patients enrolled in an on-going phase 2 trial, receiving an experimental biochemotherapy (GILFICet) regimen combining gemcitabine, irinotecan, fluoruracil, levofolinate, cetuximab, and metronomic sc. aldesleukine. Material and Methods: Transmission-electron-microscopy (TEM) and Flow cytometry were used to evaluate the susceptibility of multiple colon cancer cell lines to DC-mediated phagocytosis. Human DCs loaded with cetuximab-coated colon cancer cells, exposed or not to a combination of anti-cancer drugs, were used to in vitro sensitize human PBMCs from normal donors and cancer patients collected at baseline and after 3 GILFICet courses. T-cell cultures were characterized for immunephenotype and tumour-antigen specific CTL activity by Flow cytometry, LDH release and IFNg-ELISPOT. Results: ILF (irinotecan+ folinate+5-flurouracil) and GILF (gemcitabine+ ILF) poly-chemotherapies confirmed their ability to induce antigen remodelling and danger signals in colon cancer cells. After exposure to poly-chemotherapy and cetuximab these cells became highly susceptible to Fc-receptor-mediated phagocytosis/trogocytosis by human DCs, promoted their activation, and increased their ability to elicit a highly efficient CTL response on human PBMCs in vitro. Our study on the PBMCs of colon cancer patients enrolled in the GILFICet trial, revealed a significant treatment-related increase in na¨ive and central-memory-Tcells, activated-CTLs, NK/NKTs, mature-activated DCs and IFNg-releasing cells. Substantial differences were observed in T-cell lines generated from patients’ PBMCs taken before and after biochemotherapy. In the latter group there was in fact, a remarkable increase in proliferating CD8+Ki67+CTLs and tumour-antigen specific CTLs’ precursors. Discussion: These results suggest that cetuximab may exert immuneenhancing effects with potential antitumour activity

Carbon Dioxide: Maybe Not the Only One but an Efficient and Secure Gas for Treating Local Adiposities

Currently, carbon dioxide therapy represents an evidencebased and mini-invasive method for treating local adiposities. Many studies [1–3] performed on both women and men have already demonstrated its effectiveness in decreasing local fat in several anatomical areas. Recently, Balik et al. [4] compared the effects of both CO2 and breathable air injection on subcutaneous tissue in a sample of 28 experimental rats. They concluded that the mechanical effects are the same for both gas injections and the changes in microcirculation documented on laser Doppler flow examination are not statistically significant. With respect their article, we would like to make a few comments. We evaluated in a cohort of 48 [5] and 42 patients [6] the effects of CO2 therapy from a histological (through biopsies of tissues performed after the therapy) and a biochemical point of view by showing changes in the laser Doppler signal in association with the assessment of the concentration of transcutaneous oxygen tension (tcPO2). Both these methods are mandatory to evaluate CO2 effects on the microvascular network [3, 7]. Lee [8] confirmed our findings with a study protocol evaluating some anthropometrical parameters on 101 patients (divided per age) after treatment with CO2 injected in several body areas. Furthermore, the gas injection mode of Balik’s study is not comparable to the described protocols for the treatment of local adiposities by CO2 therapy. Medical CO2 injection treatments in previous clinical studies were administered through certified equipment that guarantees both constant gas delivery and electronic flow control. The paraphysiological hyperoxia that underlies the metabolic CO2 effects needs to be evaluated by following a particular treatment timing. This was not done in Balik’s study and therefore the inefficacy of these methods is not clear in the discussion. The data related to tissue oxygenation certainly need further biochemical studies. Moreover, microvascular effects were not completely and correctly evaluated and not demonstrated by using the previously cited association of laser Doppler flow and tcPO2. In addition, it is important to point out that in our studies, tcPO2 data are constant and highly significant (P \ 0.01), whereas laser Doppler flow evaluations are significant (P \ 0.01) but not constant [5]. These results depend on some technical situation (i.e., patient immobility, constant temperature) not easily reproducible in animal models. The histological data presented by Balik et al. showed direct lipoclasic effects of the studied gas. We also found these effects in our studies but they could not be assessed in humans. It is clear that before demonstrating the effectiveness of an alternative gas (e.g., ambient air) in reducing local adiposities, it is necessary to test its security and absence of toxicity. Because of the proven safety and daily use in laparoscopic surgery [9, 10], CO2 has been injected on voluntary patients after informed consent and the approval of the local ethics committee. The aim of our study was to evaluate both the effectiveness and safety of CO2 injection treatments. In our opinion, CO2 therapy combines the characteristics previously cited (Fig. 1). C. Brandi M. Campana (&) F. Russo A. Brafa G. Nisi L. Grimaldi C. D’Aniello Department of General and Specialistic Surgery, Plastic and Reconstructive Surgery Unit, ‘‘Santa Maria alle Scotte’’ Hospital, University of Siena, Viale Bracci 1, 53100 Siena, SI, Italy e-mail: matteocamp@gmail.com

A Simple Atraumatic Way to Remove Breast Implants

Sir: The removal of a breast implant is a relatively frequent operation in both plastic surgery and reconstructive surgery. As for the implant also, the removal occurs through rather small skin incisions with respect to the dimensions of the prosthesis. In general, the implant to remove is eliminated from its pocket manually by the operator who, to be able to proceed in such an operation, is forced to pinch the implant with his or her fingers to ensure optimal take, and to put it in traction with a force directly proportional to the dimensions of the prosthesis and inversely proportional to the dimensions of the skin incision. This solution exposes the prosthesis and in particular its external coating to two forces: one of compression (because of the initial pinching) and one of traction (the amount of which greatly increases the possibility of rupture of the prosthesis). Despite the high frequency of this action during surgical procedures with the use of prostheses in mammary areas, only a few solutions have been proposed.1,2 To reduce the mechanical stress on the prosthesis as much as possible, in our clinic practice, we developed a simple system based on the use of negative pressure applied on a unique surface reduced by the coating of the implant, allowing simple removal, by avoiding manual contact of the operator and reducing the possibility of rupture of the implant. In particular, a syringe of 60 ml is used, without the plunger, which is connected with the beak of the flask to the aspiration system (Fig. 1).Fig. 1.: A 60-ml syringe, without the plunger, connected with the beak of the flask to the aspiration system.The back part of the syringe is then made to adhere to the implant's surface, creating a vacuum system that allows the implant to be removed through a soft traction toward the outside. The advantages of such a system are many and represented (1) by the absence of the pressure and back-pressure exercised by the digital pinching with mechanical stress limited to a sole surface of the shell (Fig. 2), allowing safer removal, especially in case of a ruptured silicone gel implant; and (2) by greater control of the force of traction exercised by the operator through the comfortable grip offered by the length of the syringe cylinder.Fig. 2.: The back part of the syringe is made to adhere to the implant's surface, creating a vacuum system that allows the implant to be removed through soft traction toward the outside.Giuseppe Nisi, M.D. Matteo Campana, M.D. Massimiliano Calabrò, M.D. Anna Brafa, M.D., Ph.D. Carlo D'Aniello, M.D. Department of General and Specialistic Surgery Plastic and Reconstructive Surgery Unit “S. Maria alle Scotte” Hospital University of Siena Siena, Italy

Clinical and microbiological features of acute bacterial conjunctivitis at the primary eye care unit in a hospital of central Italy

Purpose Aim of this study is to identify bacteria causing conjunctivitis in a central Italian area and to analyze their chemosusceptibility. Methods From 2005 to 2006, 91 conjunctival swabs were collected from acute conjunctivitis cases who were examined in the primary eye care unit at the "S. Maria alle Scotte" Hospital in Siena. All swabs collected were screened for common bacteria and fungi. Susceptibility tests were performed on isolates. Results Isolated bacteria were Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae for an amount of 86.2%. Overall, 100% of strains were susceptible to chloramphenicol and 96.6% to quinolones. Conversely, 20.7% of isolates were tetracycline-resistant and, even if all Gram negative isolates were susceptible to gentamicin, more frequently isolated pneumococci are constitutively resistant. Conclusion Acute “red eye” is one of the commonest reasons for consultation with primary eye care physicians; in the majority of cases an acute bacterial conjunctivitis is diagnosed, the pathogens most frequently responsible are Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. Guidelines on the management of conjunctivitis recommend antibiotic routine use where bacterial infection is suspected. This study provides a support in rational choice of empiric therapy with distinct regional preferences in the topical agent to be used.

Clinical and microbiological features of acute bacterial conjunctivitis at the primary eye care unit in a hospital of central Italy

Abstract Purpose Aim of this study is to identify bacteria causing conjunctivitis in a central Italian area and to analyze their chemosusceptibility. Methods From 2005 to 2006, 91 conjunctival swabs were collected from acute conjunctivitis cases who were examined in the primary eye care unit at the "S. Maria alle Scotte" Hospital in Siena. All swabs collected were screened for common bacteria and fungi. Susceptibility tests were performed on isolates. Results Isolated bacteria were Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae for an amount of 86.2%. Overall, 100% of strains were susceptible to chloramphenicol and 96.6% to quinolones. Conversely, 20.7% of isolates were tetracycline‐resistant and, even if all Gram negative isolates were susceptible to gentamicin, more frequently isolated pneumococci are constitutively resistant. Conclusion Acute “red eye” is one of the commonest reasons for consultation with primary eye care physicians; in the majority of cases an acute bacterial conjunctivitis is diagnosed, the pathogens most frequently responsible are Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. Guidelines on the management of conjunctivitis recommend antibiotic routine use where bacterial infection is suspected. This study provides a support in rational choice of empiric therapy with distinct regional preferences in the topical agent to be used.