Socioeconomic status and skin cancer incidence: a population-based, cohort study in the province of Ferrara, northern Italy.

To assess the impact of socioeconomic status (SES) on the occurrence of skin cancer in the population living in the province of Ferrara, Italy, a retrospective cohort of patients with squamous cell carcinoma (SCC), basal cell carcinoma (BCC) or malignant melanoma (MM), provided by the local cancer registry, was investigated. The SES was expressed through an ecological-based deprivation index. During the 8-year study period (2006-2013, total person-years 2 859 137), 6051 carcinomas (1535 SCCs, 4365 BCCs) and 459 MMs were diagnosed. Both crude and standardized (on the European population) rates and the standardized incidence ratio showed a direct correlation between BCC and SES. Multivariate analysis confirmed these results for BCC and also for MM, while it showed an excess of SCC incidence in the lowest SES subgroup. This study shows, for the first time, to our knowledge, opposite effects of SES on SCC and BCC occurrence. A role of environmental factors conditioned by SES may be hypothesized.

Hidradenitis suppurativa epidemiology: from the first Italian registry in 2009 to the most recent epidemiology updates - Italian Registry Hidradenitis Suppurativa project 2.

BACKGROUND: The incidence of hidradenitis suppurativa (HS) is still not fully established with only a few studies reporting its estimates. Prevalence estimates range from 5:10 000 to 4:100. These extremely large variations could be explained by a combination of factors, including different selection procedures, different diagnostic criteria, and variations in the sex and age distribution of the examined samples. OBJECTIVES: To analyze variations between two consecutive Italian Registries on HS. METHODS: Data obtained from the second Italian Registry on HS, named 'Italian Registry Hidradenitis Suppurativa (IRHIS) Project 2', are compared to the previous first Italian registry on HS. RESULTS: Data on 944 patients are reported. The more relevant aspects that characterize IRHIS 2 project, in comparison with the previous first Italian Registry on HS, are as follows: (i) the total number of patients, about fourfold higher; (ii) a more uniform national geographic distribution of the patient population; (iii) a larger number of dermatology units involved; (iv) a larger number of items considered in the data collection; (v) 6 years of difference between the onset of the two registries (2009-2013 vs. 2015-2019). Comparing data of the two registries, there are no statistically significant differences in terms of age at the time of the visit, gender, BMI, smoking habits, age at onset and age at first diagnosis by physician. Interestingly, the mean Sartorius score in the IRHIS project 2 (58.8) was significantly lower compared to the first Italian Registry (78.4). CONCLUSIONS: The importance of the registries, at both national and international levels, in collecting useful real-life data is confirmed by these two Italian projects.

Transversal dose distribution optimization for laser-accelerated proton beam medical applications by means of Geant4.

The main purpose of this paper is to quantitatively study the possibility of delivering dose distributions of clinical relevance with laser-driven proton beams. A Monte Carlo application has been developed with the Geant4 toolkit, simulating the ELIMED (MEDical and multidisciplinary application at ELI-Beamlines) transport and dosimetry beam line which is being currently installed at the ELI-Beamlines in Prague (CZ). The beam line will be used to perform irradiations for multidisciplinary studies, with the purpose of demonstrating the possible use of optically accelerated ion beams for therapeutic purposes. The ELIMED Geant4-based application, already validated against reference transport codes, accurately simulates each single element of the beam line, necessary to collect the accelerated beams and to select them in energy. Transversal dose distributions at the irradiation point have been studied and optimized to try to quantitatively answer the question if such kind of beam lines, and specifically the systems developed for ELIMED in Prague, will be actually able to transport ion beams not only for multidisciplinary applications, such as pitcher-catcher nuclear reactions (e.g. neutrons), PIXE analysis for cultural heritage and space radiation, but also for delivering dose patterns of clinical relevance in a future perspective of possible medical applications.

First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness.

Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy's superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + 11B → 3α reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy's ballistic precision with the higher RBE promised by BNCT and 12C-ion therapy is thus demonstrated.

Outcome after laparoscopic and open resections of posterosuperior segments of the liver.

BACKGROUND: Laparoscopic resection of posterosuperior (PS) segments of the liver is hindered by limited visualization and curvilinear resection planes. The aim of this study was to compare outcomes after open and laparoscopic liver resections of PS segments. METHODS: Patients who underwent minor open liver resection (OLR) and laparoscopic liver resection (LLR) between 2006 and 2014 were identified from the institutional databases of seven tertiary referral European hepatobiliary surgical units. Propensity score-matched analysis was used to match groups for known confounders. Perioperative outcomes including complications were assessed using the Dindo-Clavien classification, and the comprehensive complication index was calculated. Survival was analysed with the Kaplan-Meier method. RESULTS: Some 170 patients underwent OLR and 148 had LLR. After propensity score-matched analysis, 86 patients remained in both groups. Overall postoperative complication rates were significantly higher after OLR compared with LLR: 28 versus 14 per cent respectively (P = 0·039). The mean(s.d.) comprehensive complication index was higher in the OLR group, although the difference was not statistically significant (26·7(16·6) versus 18·3(8·0) in the LLR group; P = 0·108). The mean(s.d.) duration of required analgesia and the median (range) duration of postoperative hospital stay were significantly shorter in the LLR group: 3·0(1·1) days versus 1·6(0·8) days in the OLR group (P < 0·001), and 6 (3-44) versus 4 (1-11) days (P < 0·001), respectively. The 3-year recurrence-free survival rates for patients with hepatocellular carcinoma (37 per cent for OLR versus 30 per cent for LLR; P = 0·534) and those with colorectal liver metastases (36 versus 36 per cent respectively; P = 0·440) were not significantly different between the groups. CONCLUSION: LLR of tumours in PS segments is feasible in selected patients. LLR is associated with fewer complications and does not compromise survival compared with OLR.

Simultaneous Parenchyma-Preserving Liver Resection, Cytoreductive Surgery and Intraperitoneal Chemotherapy for Stage IV Colorectal Cancer.

BACKGROUND: The outcome of stage IV colorectal cancer (CRC) has improved with modern systemic therapy. However, the concomitant presence of liver metastases (LM) and peritoneal carcinomatosis (PC) remains associated with a dismal prognosis and surgery in this context remains exceptional. METHODS: Stage IV CRC patients with LM and PC undergoing simultaneous cytoreductive surgery, intraperitoneal chemotherapy (IPC) and liver resection/ablation were identified from prospectively collected databases. We assessed response to neoadjuvant chemotherapy (NACT), postoperative complications, progression free survival (PFS), and overall survival (OS). RESULTS: Twenty-one patients with resectable disease were treated between 2007 and 2014. In 16 patients (76%), NACT was administered and tumour response defined their selection. The remaining 5 (24%) were selected according to the pattern of recurrence. Median peritoneal cancer index was 5 (range: 3-10.5). Liver surgery included 34 wedge resections, 5 ablations and one bisectionectomy to treat a total of 45 hepatic lesions with a median of 2 per patient (range: 1-2) and a median size of 1.35 cm (range: 0.8-2). Tumour regression grade 4 (fibrosis but residual cancer cells predominate) was seen in 50% of the resected metastases after NACT. Median hospital stay was 17 days (range: 14-24); severe morbidity (Clavien-Dindo grade 3-4) occurred in 24% and no perioperative mortality (0-90 days) was recorded. The median OS was 44 months (range: 31-57) while the median PFS was 10 months (range: 8-12). CONCLUSIONS: Combined parenchyma-preserving liver resection, cytoreductive surgery and IPC in patients with LM and PC from CRC can be performed safely and results in promising mid-term overall survival.

Indocyanine green near-infrared fluorescence in pure laparoscopic living donor hepatectomy: a reliable road map for intra-hepatic ducts?

Indocyanine green (ICG) near-infrared (NIR) fluorescence cholangiography (FC) has shown its usefulness to visualize the biliary ducts in open living donor hepatectomy (LDH) to check the intraoperative biliary anatomy. The fully laparoscopic LDH approach has been recently described. However, this procedure is very demanding for a possible misperception of right parenchymal transection line and the cut point of the lobar biliary ducts (BD). To explore the potential of ICG-NIR-FC method we report our experience in 11 fully laparoscopic left LDH using 5 different protocols. Protocol-A, consisted on intravenous (i.v.) ICG injection of 2.5 mg with immediate cut of the BD; -B, same dose and late cut; -C, 1 mg i.v. and late cut; -D, intra-cystic duct injection of 2.5 mg and immediate cut; -E, intra-cystic injection of 5 mg and immediate cut. Protocol-A showed fast fluorescence in the lobar artery and portal vein followed by the BD sheet ; -B showed intraductal excretion with a high parenchymal signal; -C showed a very week signal; -D failed to visualize the ducts; -E showed a good signal without parenchymal fluorescence. ICG-NIR-FC is an additional method to visualize the lobar ducts in fully laparoscopy LDH, but still insufficient for the segmental ducts.

Indocyanine Green Near-Infrared Fluorescence in Pure Laparoscopic Living Donor Hepatectomy: a Reliable Road Map for Intra-Hepatic Ducts ?

Indocyanine green (ICG) near-infrared (NIR) fluorescence cholangiography (FC) has shown its usefulness to visualize the biliary ducts in open living donor hepatectomy (LDH) to check the intraoperative biliary anatomy. The fully laparoscopic LDH approach has been recently described. However, this procedure is very demanding for a possible misperception of right parenchymal transection line and the cut point of the lobar biliary ducts (BD). To explore the potential of ICG-NIR-FC method we report our experience in 11 fully laparoscopic left LDH using 5 different protocols. Protocol-A, consisted on intravenous (i.v.) ICG injection of 2.5 mg with immediate cut of the BD; -B, same dose and late cut; -C, 1 mg i.v. and late cut; -D, intra-cystic duct injection of 2.5 mg and immediate cut; -E, intra-cystic injection of 5 mg and immediate cut. Protocol-A showed fast fluorescence in the lobar artery and portal vein followed by the BD sheet; -B showed intraductal excretion with a high parenchymal signal; -C showed a very week signal; -D failed to visualize the ducts; -E showed a good signal without parenchymal fluorescence. ICG-NIR-FC is an additional method to visualize the lobar ducts in fully laparoscopy LDH, but still insufficient for the segmental ducts.

Nuclear reaction measurements on tissue-equivalent materials and GEANT4 Monte Carlo simulations for hadrontherapy.

When a carbon beam interacts with human tissues, many secondary fragments are produced into the tumor region and the surrounding healthy tissues. Therefore, in hadrontherapy precise dose calculations require Monte Carlo tools equipped with complex nuclear reaction models. To get realistic predictions, however, simulation codes must be validated against experimental results; the wider the dataset is, the more the models are finely tuned.Since no fragmentation data for tissue-equivalent materials at Fermi energies are available in literature, we measured secondary fragments produced by the interaction of a 55.6 MeV u(-1) (12)C beam with thick muscle and cortical bone targets. Three reaction models used by the Geant4 Monte Carlo code, the Binary Light Ions Cascade, the Quantum Molecular Dynamic and the Liege Intranuclear Cascade, have been benchmarked against the collected data. In this work we present the experimental results and we discuss the predictive power of the above mentioned models.

Carbon fragmentation measurements and validation of the Geant4 nuclear reaction models for hadrontherapy.

Nuclear fragmentation measurements are necessary when using heavy-ion beams in hadrontherapy to predict the effects of the ion nuclear interactions within the human body. Moreover, they are also fundamental to validate and improve the Monte Carlo codes for their use in planning tumor treatments. Nowadays, a very limited set of carbon fragmentation cross sections are being measured, and in particular, to our knowledge, no double-differential fragmentation cross sections at intermediate energies are available in the literature. In this work, we have measured the double-differential cross sections and the angular distributions of the secondary fragments produced in the (12)C fragmentation at 62 A MeV on a thin carbon target. The experimental data have been used to benchmark the prediction capability of the Geant4 Monte Carlo code at intermediate energies, where it was never tested before. In particular, we have compared the experimental data with the predictions of two Geant4 nuclear reaction models: the Binary Light Ions Cascade and the Quantum Molecular Dynamic. From the comparison, it has been observed that the Binary Light Ions Cascade approximates the angular distributions of the fragment production cross sections better than the Quantum Molecular Dynamic model. However, the discrepancies observed between the experimental data and the Monte Carlo simulations lead to the conclusion that the prediction capability of both models needs to be improved at intermediate energies.

Hepatitis B prophylaxis in hepatitis B-negative recipients transplanted with donor grafts positive for hepatitis B core antibodies.

BACKGROUND AND AIMS: Use of grafts from hepatitis B (HBV) core antibody (HBcAb(+)) individuals is a routine transplant practice. Herein, we have reported the results of 20 HBV-negative patients transplanted with a HBcAb-positive liver grafts in order to access the efficacy of HBV prophylaxis using immunoglobulin (IE) and antiviral drugs. METHODS: From January 2004 to December 2009, we performed 168 liver transplantations including 38 HBcAb-positive grafts (22.6%) in 18 cases of HBV-positive recipients and 20 HBV-negative recipients. Histological data obtained from these last 20 grafts during retrieval showed an Ishak 1 score in three and no fibrosis in the other cases. HBV prophylaxis included infusion of 10,000 UI IG during the anhepatic phase and every 24 hours for the first 7 days irrespective of the antibody titer as well as lamivudin (100 mg) administered daily. Once discharged, outpatient management provided modulated IG infusions according to when the antibody titer was lower than 400 UI. RESULTS: No patient displayed an HBV infection. The overall survival was 80%. Two patients died within the first month after transplantation due to septic complications; one patient succumbed at 24 months after transplantation because of a lymphoproliferative malignancy and another died due to an aggressive hepatitis C virus recurrence at 6 months post transplant. CONCLUSION: By using appropriate anti-HBV prophylaxis, HBcAb-positive grafts can be used safely for HBcAb-negative recipients.

Cementoplasty in the management of painful extraspinal bone metastases: our experience.

PURPOSE: The aim of this study was to demonstrate the effectiveness of interventional techniques in the palliative management of painful extraspinal bone metastases. MATERIALS AND METHODS: Cementoplasty alone or in combination with radiofrequency (RF) ablation was performed in 14 skeletal extravertebral segments in 13 patients with ages ranging from 50 to 74 (average 67) years. The primary tumours were myeloma (n=5), renal carcinoma (n=5), hepatocellular carcinoma (n=2) and bladder carcinoma (n=2). Metastases were located at the acetabulum (n=4), femur (n=5), humerus (n=1), scapula (n=2) and iliac bone (n=2). The clinical indication was a pain intensity score >4 on the visual analogue scale (VAS) partially or totally refractory to analgesic medication. Clinical evaluation was based on clinical and neurological conditions before and immediately after the procedure and during the follow-up. RESULTS: Technical success was achieved in all cases. Ten patients were treated by cementoplasty alone and four cases by cementoplasty combined with RF ablation. After treatment, all patients experienced improved symptoms, as demonstrated by the VAS score, which remained constant during follow-up. All patients were followed for between 2 and 14 (average 6.1) months. We had one major complication in a patient who developed an abscess, which was treated by percutaneous drainage. CONCLUSIONS: In our experience, cementoplasty alone for small lesions or combined with RF ablation in larger lesions is an effective and safe therapy in the palliative management of painful extraspinal bone metastases.

[Role of the subfascial endoscopic perforating veins surgery in the treatment of venous ulceration: physiopathology and diagnosis]. / Ruolo della interruzione sottofasciale delle vene perforanti per via endoscopica nella terapia delle ulcere flebostatiche: fisiopatologia e diagnostica.

Chronic venous insufficiency is a recurrent pathology, but affected patients often undergo clinical observation at a most severe and clearly symptomatic stage of the disease. In this late stage, therapy can only relieve symptoms of the disease which often lead to disability. In the clinical course of chronic venous insufficiency, phlebostatic ulceration constitutes a recurrent finding and it is responsible of compromising patients quality of life. The role of perforating veins, made refluxive by various pathogenic noxa, in the genesis of ulcerative lesions has been known since long time. For many years the interest in perforating veins surgery has been limited because of the several negative consequences of the operations. The possibility of modifying the hemodynamics of perforating veins compartment without causing post-operation complications by video-supported surgery, led to the debate on the role of these vessels in the chronic venous insufficiency. The phlebostasis non-invasive diagnosis uses imaging techniques consisting in tests which mostly are cheap, simple and easy to perform, thus representing the best early approach to the patient. It is widely thought that even though complex examinations are available, most precious information can be obtained by only two examinations: color-Doppler ultrasonography and, limitedly, plethysmography. By these diagnostic directions it is possible to better identify the site and the hemodynamic origin of the venous insufficiency.

[Role of the subfascial endoscopic perforator vein surgery in the treatment of venous ulcers]. / Ruolo della interuzione sottofasciale delle vene perforanti per via endoscopica nella terapia delle ulcere flebostatiche.

BACKGROUND: Limbs phlebostatic ulcers are in many cases associated with perforator reflux veins often caused by post-thromboflebitis syndrome. The origin operation consisting in perforating vein interruption, described by Linton in 1938, allowed high quality exposition of these vessels and gave successful therapeutic results only affected by complications which prolonged hospitalisation. The most unfavorable prognostic factor was the need of performing an incision in skin sites affected by dermo-hypodermic degeneration induced by phlebopathy which inhibits post-surgery cicatrization. The therapeutic importance of reflux perforator vein interruption induced vascular surgeons to improve various procedures not affected by post-surgery complications and able to excise as much incontinent vessels as possible. METHODS: By video-surgery and new surgery tools nowadays available, the Subfascial Endoscopic Perforating Veins Surgery (SEPS) was established as a feasible and valuable method. At present, there are many surgical techniques differing from each other for the tools and the subneurotic compartement from which the perforating veins start. The results obtained from 45 SEPS procedures performed on 45 patients presenting lymphodermatosclerosis or venous ulcers caused by chronic venous insufficiency have been retrospectively evaluated. RESULTS: Thirty-six patients reached ulcer healing within 4 weeks after the operation; 7 ulcers healed over a 2 month time, while for 2 patients no clinical improvement has been recorded yet. CONCLUSIONS: SEPS is a valid alternative to the Linton procedure and provides remarkable advantages both in economic and clinical terms since it yields a more rapid lesions healing of small incisions which makes it one of the most minimally invasive surgical technique.