Understanding the influence of surgical parameters on craniofacial surgery outcomes: a computational study.

Sagittal craniosynostosis (SC) is a congenital condition whereby the newborn skull develops abnormally owing to the premature ossification of the sagittal suture. Spring-assisted cranioplasty (SAC) is a minimally invasive surgical technique to treat SC, where metallic distractors are used to reshape the newborn's head. Although safe and effective, SAC outcomes remain uncertain owing to the limited understanding of skull-distractor interaction and the limited information provided by the analysis of single surgical cases. In this work, an SC population-averaged skull model was created and used to simulate spring insertion by means of the finite-element analysis using a previously developed modelling framework. Surgical parameters were varied to assess the effect of osteotomy and spring positioning, as well as distractor combinations, on the final skull dimensions. Simulation trends were compared with retrospective measurements from clinical imaging (X-ray and three-dimensional photogrammetry scans). It was found that the on-table post-implantation head shape change is more sensitive to spring stiffness than to the other surgical parameters. However, the overall end-of-treatment head shape is more sensitive to spring positioning and osteotomy size parameters. The results of this work suggest that SAC surgical planning should be performed in view of long-term results, rather than immediate on-table reshaping outcomes.

Parametrizing the genioplasty: a biomechanical virtual study on soft tissue behavior.

PURPOSE: Sliding genioplasty is used to surgically correct a retruded or misaligned chin: in this procedure, an osteotomy is performed and the bony segment is repositioned. In this study we investigate the effect of surgical parameters (bony segment movement, osteotomy design) on postop soft tissue changes in a patient cohort. METHODS: Seven patients were retrospectively recruited. Cone beam computed tomography data were obtained and soft tissue and bone shape reconstructions were performed. 3D models were created and surgical cuts were replicated according to postop scans. Each model was imported in ANSYS 2019R1 (Ansys Inc, USA) for simulation: the effect of variation in osteotomy plane as well as extent of bony segment movement were assessed by means of design of experiment: surgical parameters were varied in a surgically acceptable range and the soft tissue predictions were evaluated as displacement output of five craniometric landmarks. RESULTS: Simulation results show the overall changes of the lower third of the face are sensitive to changes in horizontal and vertical displacement of the bony segment as well as segment rotation. No significant changes in the soft tissue response were to attribute to the osteotomy design. CONCLUSIONS: Our results are consistent with experimental findings reported in the literature: when planning genioplasty in orthognathic surgery, particular focus on the segment movement (horizontal translation, vertical translation and rotation), rather than on the design of the osteotomy itself, should be considered.

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.

Dermoscopy of genital diseases: a review.

The male and female external genital regions are anatomical areas in which various types of skin disorders may occur. Although most of these conditions can be diagnosed by means of clinical examination and an accurate medical history, in most cases further investigations with time-consuming and/or invasive procedures are needed in order to reach the correct diagnosis. Dermoscopy, as a modern non-invasive tool, is able to better diagnose pigmented and non-pigmented skin tumours along with various inflammatory and infectious skin and appendage disorders. The aim of this paper was to provide a review of the use of dermoscopy in genital disorders based on published data and to include personal experience gained from real life, focusing on any possible gender difference and whether disease mucosal/semimucosal dermoscopy features may differ from those observed on the skin. In conclusion, genital dermoscopy should always be considered during clinical inspection in order to enhance the diagnosis or to rule out those conditions that may look similar but that show a different dermoscopy pattern, thus narrowing down the differential diagnoses and avoiding unnecessary invasive investigations.

Three-dimensional soft tissue prediction in orthognathic surgery: a clinical comparison of Dolphin, ProPlan CMF, and probabilistic finite element modelling.

Three-dimensional surgical planning is used widely in orthognathic surgery. Although numerous computer programs exist, the accuracy of soft tissue prediction remains uncertain. The purpose of this study was to compare the prediction accuracy of Dolphin, ProPlan CMF, and a probabilistic finite element method (PFEM). Seven patients (mean age 18years; five female) who had undergone Le Fort I osteotomy with preoperative and 1-year postoperative cone beam computed tomography (CBCT) were included. The three programs were used for soft tissue prediction using planned and postoperative maxillary position, and these were compared to postoperative CBCT. Accurate predictions were obtained with each program, indicated by root mean square distances: RMSDolphin=1.8±0.8mm, RMSProPlan=1.2±0.4mm, and RMSPFEM=1.3±0.4mm. Dolphin utilizes a landmark-based algorithm allowing for patient-specific bone-to-soft tissue ratios, which works well for cephalometric radiographs but has limited three-dimensional accuracy, whilst ProPlan and PFEM provide better three-dimensional predictions with continuous displacements. Patient or population-specific material properties can be defined in PFEM, while no soft tissue parameters are adjustable in ProPlan. Important clinical considerations are the topological differences between predictions due to the three algorithms, the non-negligible influence of the mismatch between planned and postoperative maxillary position, and the learning curve associated with sophisticated programs like PFEM.

Differences in clinicopathological features and distribution of risk factors in Italian melanoma patients.

BACKGROUND: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. OBJECTIVE: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. METHODS: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. RESULTS: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. CONCLUSIONS: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

Malignant melanoma in Ferrara, Northern Italy: epidemiologic survey focusing on tumor thickness.

AIM: Estimates of malignant melanoma (MM) incidence and prognosis vary widely. The present study was performed to analyze epidemiologic and prognostic aspects of primary MM mainly in relation to tumor thickness. METHODS: We conducted a retrospective study on a cohort of 435 patients with diagnosis of primary MM between 1997 and 2011. RESULTS: In the period 2009-2011, among the MM diagnosed 50.00% were thin, 32.43% in situ and 17.57% thicker while in 1997-1999 MM>1 mm accounted for 51.61% of diagnoses. Mean age of patients affected with thin MM was significantly lower than that of patients with MM>1 mm, and mean thickness resulted significantly lower in female patients than in males. Mean thickness of MM located on easily self-evaluable body areas was significantly lower than in those not accessible for skin self-examination. The commonest histogenetic type was superficially spreading melanoma. Mitotic rate, ulceration and vertical growth phase all resulted related to MM thickness. Out of 61 patients with thin MM who underwent SLNB, 3 resulted positive (4.92%): neither thickness >0.75 mm, nor ulceration, mitotic rate or Clark level were found to be associated with SLNB positivity. Five-year survival rate was 98.3% for thin MM patients and 76.4% for thick MM patients. CONCLUSION: Our trend analysis evidences a continuing increase of thinner primary MM throughout the study period, potentially enhancing patient prognosis. Regular skin self-examination could contribute to earlier recognition of MM. Identification of more powerful predictors of thin MM prognosis is necessary.

Characterization of primary and recurrent nodules in liver cirrhosis using contrast-enhanced ultrasound: which vascular criteria should be adopted?

PURPOSE: To assess the impact of different vascular patterns at contrast-enhanced ultrasound (CEUS) on the characterization of small liver nodules (10-30 mm) in cirrhosis and to determine whether primary nodules and recurrent nodules (after a previously treated hepatocellular carcinoma) display variations in enhancement pattern. MATERIALS AND METHODS: A total of 135 cirrhotic patients were evaluated. A diagnosis of hepatocellular carcinoma (HCC) was established according to AASLD Guidelines, based on imaging (computed tomography and/or magnetic resonance) or liver biopsy. All patients underwent CEUS. Different CEUS patterns were evaluated in terms of diagnostic accuracy: HYPER-HYPO: Arterial hyperenhancement followed by washout (hypoechoic appearance compared with surrounding parenchyma) in late phase; HYPER-ISO: Arterial hyperenhancement followed by isoenhancement (isoechoic appearance) in late phase; ISO-ISO: Isoenhancement in all vascular phases. RESULTS: A total of 155 consecutive primary (n = 90) or recurrent (n = 65) nodules were detected. HCC was diagnosed in 127 nodules (71 primary, 56 recurrent). A characteristic HYPER-HYPO CEUS pattern was revealed in 52/127 (40.9%) HCCs (31 primary, 21 recurrent) giving a positive predictive value (PPV) of 98% (97% primary, 100% recurrent) and an accuracy of 51% (54% primary, 46% recurrent). A HYPER-ISO pattern was noted in 46 HCCs (31 primary, 15 recurrent). Assuming this pattern to also be indicative of HCC, the PPV and accuracy were 94% (93% primary, 97% recurrent) and 77% (84% primary, 68% recurrent), respectively. An ISO-ISO pattern was present in 29 HCCs (9 primary, 20 recurrent) and 22 non-HCCs (14 primary, 8 recurrent). CONCLUSION: These data confirm that the HYPER-HYPO pattern at CEUS is definitely diagnostic for HCC in cirrhosis and that the HYPER-ISO pattern has a similar PPV, indicating that this pattern is highly suspicious for HCC. The ISO-ISO pattern was found in > 50% of recurrent nodules and indicates a high risk of HCC.

Impact of gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance on the non-invasive diagnosis of small hepatocellular carcinoma: a prospective study.

BACKGROUND: Gadoxetic acid (Gd-EOB-DTPA) is a 'hepatocyte-specific' contrast agent for magnetic resonance (MR) in both the vascular and the hepatobiliary phases. AIM: To evaluate the contribution of the hepatobiliary phase of Gd-EOB-DTPA MR in the diagnosis of small hepatocellular carcinoma (HCC) in cirrhotic patients under surveillance. METHODS: Between 2008 and 2011, 48 consecutive small (10-30 mm) liver nodules were detected in 33 patients, who prospectively underwent contrast-enhanced ultrasound (CEUS), Gd-EOB-DTPA-enhanced MR and helical-computed tomography (CT) in a blind study. The diagnosis of HCC was established according to AASLD 2005 criteria. RESULTS: Of the 48 nodules, 38 (79%) were diagnosed as HCC, 24 (63%) of them based on AASLD non-invasive criteria, 11 diagnosed at histology and 3 during follow-up. The typical vascular pattern (arterial hypervascularisation and venous/late washout) was detected in 30 (79%) HCC nodules by MR, in 22 (58%) by CT and in 17 (45%) by CEUS. Hypointensity during the MR hepatobiliary phase was observed in all HCC nodules and in 3 nonmalignant nodules (sensitivity 100%, specificity 70%, positive predictive value 93%, negative predictive value 100%, positive likelihood ratio 3.33, negative likelihood ratio 0). Eight (21%) of the 38 HCC nodules, 7 of which lacked the typical vascular features at any of the imaging modalities, showed washout in the portal/venous phase and hypointensity in the hepatobiliary phase at MRI, while this pattern was not detected in any nonmalignant lesion. CONCLUSIONS: Gadoxetic acid magnetic resonance may enhance the sensitivity of the non-invasive diagnosis of small hepatocellular carcinoma nodules in cirrhotic patients under surveillance. Double hypointensity in the portal/venous and hepatobiliary phases could be considered a new magnetic resonance pattern, highly suggestive of hypovascular hepatocellular carcinoma.

Accuracy of VirtualTouch Acoustic Radiation Force Impulse (ARFI) imaging for the diagnosis of cirrhosis during liver ultrasonography.

PURPOSE: VirtualTouch is a new technique recently proposed to evaluate liver stiffness during B-mode ultrasonography. The goal of the present study was to analyze the diagnostic accuracy of VirtualTouch in the diagnosis of cirrhosis and its correlation with transient elastography (Fibroscan). MATERIALS AND METHODS: A total of 133 patients with chronic liver disease were enrolled. 90 of 133 underwent VirtualTouch and transient elastography and 70 patients assessed with VirtualTouch were submitted to liver biopsy. Stiffness was assessed by both techniques in the right liver lobe. The diagnostic accuracy for cirrhosis was first assessed in the 90 patients submitted to transient elastography with > 13 kPa (47 % of patients) as diagnostic for cirrhosis values. The best cut-off for cirrhosis with VirtualTouch was then tested in the 70 patients with biopsy (cirrhosis in 38 % of patients). 41 patients were assessed by VirtualTouch by two different operators. RESULTS: The VirtualTouch values in controls, chronic hepatitis and cirrhosis were respectively 113, 147 and 255 cm/sec. The AUROC of liver VirtualTouch for the diagnosis of cirrhosis (reference Fibroscan) was 0.941 with 175 cm/sec as the best cut-off (sensitivity 93.0 %; specificity 85.1 %). VirtualTouch confirmed good performance also in patients with bioptic diagnosis of cirrhosis (AUROC 0.908, sensitivity 81.5 %, specificity 88.4 %,). The correlation of VirtualTouch with transient elastography was strict (r = 0.891) and the correlation in VirtualTouch measurements between two operators was also good (r = 0.874). CONCLUSION: VirtualTouch is able to identify the presence of cirrhosis with good accuracy, shows good interobserver reproducibility and the correlation of its values with those obtained by transient elastography with Fibroscan is good.

High levels of 18F-FDG uptake in aortic aneurysm wall are associated with high wall stress.

BACKGROUND: Functional imaging using positron emission tomography (PET) showed increased metabolic activities in the aneurysm wall prior to rupture, whereas separate studies using finite element analysis techniques found the presence of high wall stresses in aneurysms that subsequently ruptured. This case series aimed to evaluate the association between wall stress and levels of metabolic activities in aneurysms of the descending thoracic and abdominal aorta. METHODS: Five patients with aneurysms in the descending thoracic aorta or abdominal aorta were examined using positron emission tomography-computed tomography (PET-CT). Patient-specific models of the aortic aneurysms were reconstructed from CT scans, and wall tensile stresses at peak blood pressure were calculated using the finite element method. Predicted wall stresses were qualitatively compared with measured levels of 18F-fluoro-2-deoxy-glucose (18F-FDG) uptakes in the aneurysm wall. RESULTS: The distribution of wall stress in the aneurysm wall was highly non-uniform depending on the individual geometry. Predicted high wall stress regions co-localised with areas of positive 18F-FDG uptake in all five patients examined. In the two ruptured cases, the locations of rupture corresponded well with regions of elevated metabolic activity and high wall stress. CONCLUSIONS: These preliminary observations point to a potential link between high wall stress and accelerated metabolism in aortic aneurysm wall and warrant further large population-based studies.

CagA and VacA Helicobacter pylori antibodies in gastric cancer.

BACKGROUND: Infection with different genotypes of virulent Helicobacter pylori strains (cytotoxin-associated gene A [CagA]- and/or vacuolating cytotoxin A [VacA]-positive) can play a role in the development of atrophic gastritis, duodenal ulcer (DU) and gastric cancer (GC). OBJECTIVE: To determine whether patients with GC and H pylori-negative histological staining had previously been infected with H pylori CagA- and/or VacA-positive virulent strains. METHODS: Twenty-three GC patients with a mean (+/- SD) age of 68.14+/-9.8 years who tested H pylori-negative on histological staining took part in the study. Three control groups were included. The first group comprised 19 patients with past H pylori infection and DUs eradicated 10 years earlier, with a mean age of 58+/-18.2 years. H pylori-negative status for this group was determined every year with Giemsa staining, and follow-up testing occured 120+/-32 months (mean +/- SD) after therapy. The subsequent control groups included 20 asymptomatic children, with a mean age of 7+/-4.47 years, and with H pylori-negative fecal tests; the final group contained 30 patients without clinical symptoms of H pylori infection, with a mean age of 68+/-11.6 years, who tested H pylori-negative by histological staining. RESULTS: Prevalence of CagA and VacA seropositivity, respectively was 82.6% and 73.91% in GC patients; 84.2% and 84.2% in H pylori-negative DU patients; 25% and 5% in H pylori-negative children; and 36.6% and 16.6% in the patients without clinical symptoms on histological staining. CagA and VacA antibody positivity was not significantly different between GC patients and patients with DUs that had been eradicated 10 years earlier. Significant positivity was found between the children's group and the H pylori-negative (with past DUs) group (P<0.001). A statistically significant difference was found in age between groups (P<0.03). CONCLUSIONS: Patients with GC, even when H pylori-negative at the time of the present study, may have been infected by H pylori before the onset of the disease, as confirmed by CagA and VacA seropositivity. These data reinforce the hypothesis that H pylori may be a direct carcinogenic agent of GC.

Low prevalence of twisted hair in anorexia nervosa.

In a series of 30 patients affected by severe anorexia nervosa (AN) we examined hair samples to detect the prevalence of acquired pili torti (APT). True APT were not detected but in two cases (6.6%) twisted hair was observed. The first case was a 24-year-old woman with secondary amenorrhoea for 9 years, whose body mass index (BMI) was 12.2 kg/m2. She also had severe skin xerosis and hypertrichosis. The second case was a 24-year-old woman with secondary amenorrhoea for 1 year, whose BMI was 11.3 kg/m2. She also had severe skin and lip xerosis, severe effluvium, cystic acne, acrocyanosis, perimylolysis (severe erosion of the dentition) and scars due to cigarette burns on her forearms. Reviewing the literature we noticed that the largest series of pili torti--congenital and acquired--were published by authors from countries such as Israel and Egypt. We therefore hypothesize that, under the same conditions, a genetic factor may predispose to this hair shaft defect.

Cutaneous infection caused by Salmonella typhi.

Salmonella typhi is a flagellated, gram-negative bacillus belonging to the family Enterobacteriaceae responsible for typhoid fever, which is a prolonged bacteraemic, systemic illness with minimal, at least initially, diarrhoea. Localized infection is a not uncommon complication of salmonella septicaemia, particularly occurring in immunocompromised patients. However, salmonella localization to the skin presenting as cutaneous ulceration is regarded as a rare event. We report a unique case of such a presentation as the sole clinical manifestation of infection with S. typhi and highlight the possible salmonella aetiology for unusual cutaneous lesions in individuals coming from endemic areas.

Fontan conversion to total cavopulmonary connection and arrhythmia ablation: clinical and functional results.

OBJECTIVES: To assess the early results of conversion from atriopulmonary to total cavopulmonary connection in patients with failing Fontan operation. DESIGN: Early clinical and instrumental evaluation of patients undergoing conversion from atriopulmonary to total cavopulmonary connection from April 1999 to November 2000. SETTING: Tertiary referral centre for congenital heart disease. PATIENTS: 11 Fontan patients (mean (SD) age 20.9 (6.7) years) with refractory arrhythmias or ventricular dysfunction. INTERVENTIONS: Total cavopulmonary connection, intraoperative ablation, and AAIR pacemaker implantation. MAIN OUTCOME MEASURES: Holter monitoring, transoesophageal atrial stimulation, ergometric test, and myocardial scintigraphy at a mean (SD) follow up of 16.8 (5.6) months. RESULTS: One early postoperative death occurred. During follow up three patients had relapse of atrial tachycardia, controlled by medical treatment, and two were pacemaker dependent. Transoesophageal stimulation did not induce atrial tachycardia in any patient. Ergometric test showed a diminished exercise tolerance in all but one patient. Mean minute ventilation and maximum oxygen consumption were 62% and 40% of their respective predicted values. Myocardial scintigraphy showed reversal of rest or exercise dysfunction in five patients and improved systemic ventricular function in seven. Mean basal ejection fraction increased from 39.4% (95% confidence interval (CI) 32% to 46%) to 46.5% (95% CI 41.7% to 51.2%) and ejection fraction on effort from 42.3% (95% CI 33.9% to 50.7%) to 50.2% (95% CI 44.5% to 55.9%). CONCLUSIONS: Our data show that total cavopulmonary connection associated with intraoperative ablation and pacemaker implantation allows for better control of arrhythmias and improves ventricular function in the majority of patients with failing Fontan.

Regression of pulmonary fistulas in congenital heart disease after redirection of hepatic venous flow to the lungs.

Although the etiology of pulmonary fistulas in congenital heart disease remains unknown, several hemodynamic factors are thought to play a role. Recently it was postulated that hepatic venous effluent might protect the pulmonary bed from development of pulmonary fistulas. However, there are no experimental data supporting this hypothesis. Here, we present the cases of 2 patients in whom pulmonary fistulas developed after unintentional surgical exclusion of the hepatic venous flow from the pulmonary circulation. In both patients, symptoms resolved after rerouting of the hepatic venous blood to the lungs.

A rare form of interrupted aortic arch.

We report the case of a newborn with DiGeorge syndrome and aortic atresia associated with a complex anomaly of the aortic arch, interpreted as interrupted aortic arch type C, a persistent right ventral aorta and an aberrant right innominate artery. At 8 months the child underwent Norwood palliation with interposition of an 8 mm PTFE tube between the pulmonary trunk and the descending aorta and of a 3.5 mm shunt between the junction of the right ventral aorta to the left carotid artery and the right pulmonary artery. At 11 months he had substitution of the PTFE tube and bidirectional cavopulmonary anastomosis; he is now waiting for biventricular correction.