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Background: Robotic surgery has many clinical advantages but high costs, raising the issue of healthcare sustainability. This study aims to a comparative analysis of the value, in terms of costs and outcomes, of robotic, laparoscopic, and laparotomy surgery for uterine cancer in a University Hospital. Methods: An observational retrospective study was carried out on hospitalizations between 1 Jan 2019 and 31 Oct 2021 for uterine cancer surgery. DRG amount, costs, economic margins and 30-days readmissions percentage (mean values and 95% CIs) were calculated for robotic, laparoscopic and laparotomy surgery. Student’s t and Chi-square tests were used to assess differences and the break-even point was calculated. Results: 1336 hospitalizations were analyzed, 366 with robotic, 591 with laparoscopic, and 379 with laparotomy surgery. Robotic surgery compared to laparoscopic and laparotomy showed a significant difference (p<0,001) for economic margin, which was largely negative (-1069.18 E; 95%CI: -1240.44 - -897.92 E) mainly due to devices cost (3549.37 E; 95%CI: 3459.32 E - 3639.43 E), and a lower 30-days readmissions percentage (1.4%; 95%CI: 0.2% - 2.6%) with a significant difference only versus laparotomy (p = 0.029). Laparoscopic compared to laparotomy surgery showed a significantly (p<0,001) more profitable economic margin (1692.21 E; 95%CI: 1531.75 E - 1852.66 E) without a significant difference for 30-days readmissions. The break-even analysis showed that, on average, for every uterine cancer laparoscopic elective surgery, 1.58 elective robotic surgeries are sustainable for the hospital (95% CI: 1.23 - 2.06). Conclusions: The systematic application of the break-even analysis will allow defining over time the right distribution of robotic, laparoscopic and laparotomy surgeries’ volumes to perform in order to ensure both quality and economic-financial balance and therefore value of uterine oncological surgery in the University Hospital. Key messages: The value-ba

Introduzione La chirurgia robotica per tumore maligno dell’utero presenta molti vantaggi clinici (quali minore perdita di sangue e ridotta probabilità di complicanze), ma costi elevati, ponendo per le strutture sanitarie il problema della sostenibilità economica. L’obiettivo di questo studio è stato effettuare un’analisi comparativa del valore, in termini di costi ed esiti, della chirurgia robotica, laparoscopica e laparotomica per il cancro dell’utero in un ospedale universitario. Materiali e metodi È stato condotto uno studio osservazionale retrospettivo sui ricoveri per chirurgia del cancro dell’utero tra il 1 gennaio 2019 e il 31 ottobre 2021. Sono stati calcolati, per la chirurgia robotica, laparoscopica e laparotomica, importo del DRG, costi, margini economici e percentuale di riammissioni a 30 giorni (valori medi e IC al 95%). L’analisi ha previsto l’applicazione dei test t di Student e del chi-quadrato e il calcolo del breakeven point. Risultati Sono stati analizzati 1336 ricoveri, 366 con chirurgia robotica, 591 con chirurgia laparoscopica e 379 con chirurgia laparotomica. La chirurgia robotica ha mostrato una differenza significativa (p < 0,001) rispetto a quella laparoscopica e laparotomica per il margine economico, ampiamente negativo (-1069,18 €; 95% IC: -1240,44 -≤ -897,92 €) principalmente a causa del costo dei dispositivi (3549,37 €; 95% IC 3459,32-3639,43 €), e una percentuale di riammissioni a 30 giorni inferiore (1,4%; 95% IC: 0,2-2,6%) con una differenza significativa solo rispetto alla laparotomica (p = 0,029). La chirurgia laparoscopica ha mostrato rispetto alla laparotomica un margine economico significativamente (p < 0,001) più redditizio (1692,21 €; 95% IC: 1531,75-1852,66 €) senza una differenza significativa per le riammissioni a 30 giorni. L’analisi di break-even ha mostrato che, in media, per ogni procedura chirurgica elettiva laparoscopica del cancro uterino, sono sostenibili per l’ospedale 1,58

The aim of the present study is to investigate the correlation between pregnancies complicated by morphological or chromosomal fetal anomalies and an obstetric history of two or more pregnancy losses, analyzing the association with any maternal risk factor. Study Design: Retrospective analysis of women who had access to the Day Hospital Clinic of Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome from 2012 to 2018 for a pregnancy complicated by fetal malformation and/or abnormal karyotype, and who had an obstetric history of at least one pregnancy loss. Patients were divided into four groups depending on the number of miscarriages and the presence of a genetic anomaly: Group 0 included women with <2 miscarriages and fetal malformations, Group 1 included women with 2 miscarriages and fetal malformations, Group 2 included women with <2 abortion, fetal malformations and the presence of genetic anomalies; Group 3 included women with 2 abortions, fetal malformations and genetic anomalies. Statistical analysis was performed using the SAS v. 9.4 (SAS Institute Inc., Cary, NC, USA). Results: A total of 466 patients were included in the present analysis. Out of these, 379 patients belonged to Group 0; 40 patients entered in Group 1; Group 2 included 42 patients, and 5 patients were part of Group 3. Pregnancies complicated by fetal congenital malformations in patients with two or more pregnancy losses were significantly associated with maternal trombophilic disease and previous birth defects. Recurrent miscarriage and fetal structural anomalies were also significantly correlated with advanced maternal age. Conclusions: An adequate periconceptional counseling regarding the risk of fetal congenital anomalies may be indicated in patients affected by thrombophilic disease, as well as in those of advanced maternal age and with a pregnancy history of fetal malformations. The screening for thrombophilia may be advisable in patients with an obstetric history of conge

Epidermal growth factor receptor (EGFR) content was determined by a radioligand receptor assay in 140 primary laryngeal squamous cell carcinomas (median value of 8.4 fmol mg-1 protein, range 0-169.9 fmol mg-1 protein). Cox univariate regression analysis using EGFR as a continuous variable showed that EGFR levels are directly associated with the risk of death (chi 2 = 14.56, P-value = 0.0001) and relapse (chi 2 = 7.77, P-value = 0.0053). A significant relationship between EGFR status and survival was observed at the different arbitrary cut-off values chosen (8, 16 and 20 fmol mg-1 protein). The cut-off value of 20 fmol mg-1 protein was the best prognostic discriminator. In fact, the 5 year survival was 81% for patients with EGFR- tumours compared with 25% for patients with EGFR+ tumours (P < 0.0001). The 5 year relapse-free survival was 77% for patients with EGFR- tumours compared with 24% for patients with EGFR+ tumours (P < 0.010). When clinicopathological parameters and EGFR status were examined in the multivariate analysis, T classification and EGFR status retained an independent prognostic value. In this study we demonstrated that high EGFR levels single out patients with poor prognosis in laryngeal cancer.

The cyclin D1 (CCND1) gene is amplified, rearranged, and overexpressed frequently in human cancer, including squamous cell carcinoma. The gene dosage of CCND1 was examined in 51 primary laryngeal squamous cell carcinomas, and amplification of the gene was found in 9 (17.6%) cases. CCND1 amplification did not correlate with age, tumor localization and extension, cervical lymph node involvement, histopathological grading, and epidermal growth factor receptor levels. In a univariate analysis, CCND1 amplification, tumor extension, lymph node involvement, poor histological differentiation, and high epidermal growth factor receptor levels were correlated significantly with shorter overall survival. In a median follow-up period of 29 months, the overall survival rate was 71.4% for patients affected with tumors displaying a normal CCND1 dosage and only 25.0% for patients affected with tumors carrying amplified CCND1 (P = 0.0288). In a multivariate analysis, only CCND1 and tumor extension retained statistically significant prognostic values (P = 0.037 and 0.041, respectively). This is the first report in which CCND1 amplification is identified as a significant independent prognostic factor in laryngeal carcinoma. Evaluation of CCND1 amplification could be applicable to the clinical management of laryngeal cancer, allowing identification of patients with poor prognoses.

Sixty-three patients with primary laryngeal squamous-cell carcinoma were followed up for a median of 33 months after surgery. Cathepsin D (Cath D) concentration was assayed using a solid phase 2-site immunoradiometric assay in which the first monoclonal antibody (MAb) was coated on the ELISA solid phase and the second one, MIG8 radiolabeled with 1125-EGF, was used as the tracer. The median value of Cath D (13.8 pM/mg protein) was chosen as cut-off. Cath D > or = median value was closely related to neck lymph node involvement at presentation and to a short metastasis-free survival (MFS) and actual overall survival (OS). The 5-year MFS was 71% for patients with Cath D < median value tumors as compared with 0% for patients with Cath D > or = median value tumors. Lymph node status at presentation was not related to a short MFS and OS. Cox's univariate regression analysis using Cath D as a continuous variable showed that Cath D levels are correlated with neck lymph node metastasis. On multivariate analysis, Cath D status proved to be an independent factor for predicting a short MFS. Cath D assay may prove to be particularly useful in identifying laryngeal cancer patients who, with or without neck lymph node involvement at presentation, are at high risk of metastatic disease and poor outcome.

The modern concept of oncogenesis is based upon the interaction between factors which modulate cellular growth and differentiation, in particular oncogenes and tumor suppressor genes. The molecular events which induce laryngeal carcinogenesis are not yet known. Protoncogenes seem to be the target of the risk factors (cigarette smoking, alcohol abuse, ionizing radiations and, not least HPV-DNA) that are commonly considered related to laryngeal squamous cell carcinoma. New information on the role of alterations of oncogenes and/or their proteic products in laryngeal cancer will be useful in identifying new diagnostic and clinical therapeutical applications. The Authors investigated Epidermal Growth Factor Receptor (EGFR) expression in 103 primary laryngeal squamous cell carcinoma and 42 normal laryngeal tissue specimens in order to assess its clinical significance in primary laryngeal cancer. Significantly higher EGFR levels were found in cancer specimens compared with normal mucosa (p < 0.001). EGFR expression did not correlate with age, tumor localization, T classification, cervicallymphonode involvement or surgery, whereas in G3 tumors it was significantly higher than in G1-G2 (p < 0.05). Follow-up data were available for 74 cases: EGFR levels resulted significantly higher in patients who had a recurrence of the disease than those in recurrence-free patients (p < 0.05). The 24-month disease-free survival (DFS) was 58% for EGFR+ patients and 82% for EGFR-subjects. Multivariate analysis permitted identification of EGFR status and tumor localization as significant independent prognostic factors. Data reported here suggest that EGFR expression probably plays a role not only by regulating the growth of laryngeal cancer, but also by identifying a sub-set of laryngeal cancer patients at a higher degree of relapse risk and with an unfavorable prognosis. Furthermore, in this study p21-ras expression in 43 primary laryngeal cancers and in 7 normal laryngeal mucosa s

Western blotting analysis of the p21 ras oncoprotein was performed in seven normal laryngeal mucosa specimens and 43 primary laryngeal cancers. Varying p21 levels, expressed as optical density (OD), were found in normal mucosa (median 1.94 OD, range 0.90-2.17 OD) and in primary laryngeal tumours (median 1.74 OD, range 0.30-6.37 OD). When p21 expression in laryngeal cancer was compared with the normal counterpart, higher levels were found in neoplastic than in normal laryngeal tissue (median 2.54 OD, range 1.76-6.37 OD, vs median 1.94 OD, range 0.90-2.17 OD) (P = 0.023). Immunohistochemical analysis demonstrated that most of the tumour cells (more than 70%) were immunostained while the stromal component was unreactive. No correlation between p21 expression and tumour location, stage and histopathological grade was observed. The correlation between ras p21 protein expression and epidermal growth factor receptor (EGFR) levels was also investigated. EGFR-positive cases did not show any difference in p21 expression with respect to EGFR-negative cases (median 1.52 OD, range 0.30-6.37 OD, vs median 1.84 OD, range 0.93-3.71 OD). Our findings suggest that overexpression of p21 protein is associated with a malignant phenotype in laryngeal cancer. Further studies should be undertaken to evaluate whether the assessment of p21 protein expression may have clinical significance in laryngeal cancer.

Using an immunoradiometric assay, Cathepsin D (Cath D) levels were measured in the cytosol of 23 normal and 39 neoplastic human laryngeal tissues. Scattered Cath D levels (from 2.2 to 17.8 pM/mg protein; median = 7.6) were found in normal mucosa specimens. Cath D concentrations range from 2.0 to 29.3 pM/mg protein (median = 8.5) in laryngeal tumors. When a comparison between Cath D levels in normal and neoplastic tissue specimens from the same patient was done, Cath D levels were significantly higher in laryngeal cancers than in their normal counterparts (P = 0.03). No correlation with clinico-pathological parameters and steroid hormone and epidermal growth factor receptor status was found. Further studies should investigate whether the production of Cath D by laryngeal tumors could have a clinical relevance for this neoplasia.