[Liquid biopsy as indication of tumour progression in lung cancer: a potential intervention in tertiary prevention]. / La biopsia liquida quale segnale di progressione tumorale nel carcinoma polmonare: potenziale di intervento in prevenzione terziaria.

In the era of personalised therapies, liquid biopsy is considered an important diagnostic tool in the clinical management of cancer patients. Tissue specimen represents the gold standard for molecular evaluation of specific gene targets alterations that lead cancer patients to benefit of a "tailed therapy" based on molecular features of the tumour. This innovative source of nucleic acids was introduced in clinical setting only for non-small-cell lung cancer (NSCLC) patients to test epidermal grow factor receptor (EGFR) mutations when tissue is not available for a number of reasons (difficult access to the lesion, the presence of other disabling pathologies, especially in elderly patients, rejection by the patient, etcetera) or to monitor acquired resistance mutation after a first line of treatment. The present study aimed at assessing the diagnostic potential of liquid biopsy in balanced tertiary screening modelling. The cases relating to 5 years of activity regarding to molecular diagnostics performed on liquid biopsy specimens in the Predictive diagnostic laboratory of the University hospital "Federico II" of Naples (Campania Region, Southern Italy) were reviewed. Laboratory data were collected through the software SPSS. Non-parametric analysis was performed in order to test the differences between "wild type" patients or not. A multivariate logistic model was performed in order to assess the effect of mutation, age, and gender on the tumour progression. The results of the revision concern 515 total cases (almost of all plasma or peripheral blood), which allowed to evaluate the liquid biopsies for women and men. The average age of the patients is 66.3 years, and the 25° percentile is 59 years. The cases are: 221 basal and 294 by progression. The cases with mutation, as expected, have an odds ratio of 4,15, compared to the basal, to have a tumour progression (95%IC 2,7-6,3), regardless of gender and age. The detected mutations were 131 from different types of pulmonary carcinomas. Working on case data, specifying the characteristics of the patients with mutations will drive a further estimate in tertiary prevention screening designs.

[Network references for rare diseases: state of the art for the paroxysmal nocturnal hemoglobinuria]. / I network di riferimento per le malattie rare: lo stato dell'arte per l'emoglobinuria parossistica notturna.

BACKGROUND: recently, healthcare network models have been proposed to improve general awareness of rare diseases for patients and specific knowledge about diagnosis, treatment, and management for healthcare services. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare haematological disease that still has no framing in an official network. OBJECTIVES: to describe the use of network models in diagnosis, treatment, and management of PNH patients both in Italy and abroad and its impact on patients and healthcare service. DISEGN: literature search was performed using the keywords "Hemoglobinuria", "Network", "PHN", and "Screening" in both MedLine and EMBASE. Search was restricted to the articles published in the last 5 years and written in English, French or Italian language. RESULTS: from the total 251 articles of the initial search, only 21 were finally included in our review. None of the included study explicitly described a network model. In general, we were able to identify two different kind of networks implicitly described in the studies: laboratory networks for diagnostic harmonization or screening of the population at risk of PNH (10/21 studies) and PNH registry as network of clinical information to be use for better understanding of the natural history of the disease and to assess therapeutic effectiveness (11/21 studies). CONCLUSIONS: few network approaches in PNH diagnosis, treatment, and management are described in literature. Despite the scarce application of the networks, our review highlights the positive impact that networks have in both patients and healthcare services.

[Organ donation and transplantation: the "friendly access initiative" in the Federico II Hospital (Naples), between nudging and narrative medicine]. / Donazione e trapianto d'organi: l'esperienza dello "sportello amico" dell'AOU Federico II (Napoli), tra nudging e medicina narrativa.

In Italy, to show the willingness to donate one's organs, there is the principle of the explicit consensus (or disagreement) (Law n. 91 of the 01.04.1999, Art. 23; Decree of the Italian Health Ministry of the 08.04.2000). According to data of the Italian Association for the donation of organs, tissues and cells (AIDO), in 2017 in Campania Region (Southern Italy) an average of 12.5 people x1,000,000 donated their organs vs. a national average of 23.7. This negative discrepancy between national and regional data highlights that it is imperative to promote awareness-raising measures to address to the population of Campania Region in order to improve the following of a practice which is still object of preconceptions and scarce knowledge. This paper describes a pilot project started in 2017 by the "Sportello amico trapianti" (friendly access to transplantation) to promote the donation of organs within the university-hospital "Federico II" (Naples, Campania Region). The first phase of this project was based on the nudge theory, that is the "little push" to direct decisional processes of groups and individuals. This phase took place during the "Atelier della salute" (a health workshop), organized by the Medicine and Surgery school of the university-hospital "Federico II": here, a questionnaire was administered to 60 people. The questionnaire consisted in 12 questions, answered by volunteers, which aim was to test the general knowledge about organ donation and transplantation. Analysing the answers, a panel of 7 experts (2 epidemiologists, 1 social worker, 2 experts in public and institutional communication, 1 biologist expert in donation of haematopoietic progenitor cell, 1 transplant surgeon), responsible for the coordination and monitoring of the activities, identified the critical elements to bring attention to in order to raise awareness in the population. The second phase consisted in a literary workshop which aim was to identify nudge cases. The text used was Never let me go by Kazuo Ishiguro, a novel focused on organ donation in a dystopic context where the protagonists are clones created to facilitate the donation of organs. Six students participated in this workshop: all six considered the dystopic scenario as a potential nudge to humanize the approach to organ donation and transplant. In conclusion, we believe that the nudge methodology may be used in order to improve awareness and adherence to donation of organs.

Training Models in Pediatric Minimally Invasive Surgery: Rabbit Model Versus Porcine Model: A Comparative Study.

AIM: The porcine model is the most widely used animal model for laparoscopic training. However, in pediatric surgery, an experimental setting with smaller animals could improve the training conditions. We compared the efficiency of a rabbit model versus the porcine model for training in pediatric minimally invasive surgery (MIS). MATERIALS AND METHODS: At the training center of Cardarelli Hospital in Naples, Italy, 10 young pediatric surgeons underwent training sessions on rabbit and porcine models under the supervision of five experienced tutors. The results of four laparoscopic techniques (inguinal hernia repair, varicocelectomy [basic procedures], nephrectomy, and fundoplication [advanced procedures]) were evaluated in regard to mean operative time, intraoperative complications, and surgical performances. Results were analyzed using Fisher's exact test and Student's t test. RESULTS: Practitioners were significantly more confident in the rabbit model compared with the pig model, especially for advanced procedures (P = .03). The overall surgical performance score (ranging from 0 [unacceptable] to 10 [excellent]) was significantly higher in the rabbit model compared with the pig model (8.1 versus 6.0; P = .01). The most significant scoring differences between the surgical performances of the trainees in the two models were reported in regard to dissection, suturing and knot-tying, tissue handling, and handling of instruments. In addition, the length of surgery for advanced procedures was statistically shorter in the rabbit model compared with the pig model (P = .01). We found that only the performances of those who started on the pig had a significantly higher improvement when transitioning to the rabbit compared with those who started on the rabbit (P = .01). Of the trainees, 90% preferred the rabbit model to the pig model. CONCLUSIONS: On the basis of our preliminary results, rabbits are preferred over pigs as the training model in pediatric MIS. In the rabbit model it is possible to perform more procedures and perform them more easily compared with the porcine model. The rabbit model provides a comfortable approach to technical training in basic and advanced laparoscopic procedures.

Season of birth and Parkinson's disease: possible relationship?

The amount of sun exposure in early life and consequent vitamin D3 level may influence the risk of developing Parkinson's disease (PD). Yet few studies have previously investigated birth trends in PD related to a possible seasonality and sun exposure. The aim of this study was to investigate a possible relationship between PD risk and sun exposure looking at seasonal birth variation of PD subjects in the homogenous geographic area of Naples, Italy. We selected 898 PD subjects and matched with 1796 controls. McNemar's test with Bonferroni correction and autocorrelation were used to test seasonality in birth trends. No difference was found for the month and season of birth between PD subjects and controls. We found a 3.3 % increase of PD female subjects born in September (3.3 %) and 4.1 % increase of PD male subjects born in spring comparing to controls but were not significant after Bonferroni correction. This study evaluated for the first time the seasonal birth trends in relation to PD risk in a Southern European population. We found no association between seasonal birth variations and risk of PD.

Technical standardization of laparoscopic lymphatic sparing varicocelectomy in children using isosulfan blue.

PURPOSE: The lymphatic preservation to prevent hydrocele formation after laparoscopic varicocelectomy is essential. Lymphatic sparing procedures using scrotal injection give a rate of mapping failures of 20%-30%. The aim of the present study is to standardize the technique of injection to perform a lymphatic sparing procedure in case of laparoscopic varicocelectomy. METHODS: We retrospectively evaluated 50 patients who underwent laparoscopic varicocelectomy from July 2010 to July 2013. Patients were divided into two groups: G1 (25 patients) those who underwent a classical isosulfan blue scrotal intra-dartos injection and G2 (25 patients) those who underwent the new standardized isosulfan blue scrotal intra-dartos/intra-testicular injection. RESULTS: In G1 lymphatic vessels were identified as blue coloured in 19/25 of cases (76%), in G2 in 25/25 of cases (100%). The results were analyzed using test χ(2) with Yates' correction and there was a statistically significant difference (χ(2)=0.05,1) between G2 and G1. Postoperative hydrocele was noted in 2/6 patients of G1 in whom the lymphatic vessels were not identified. CONCLUSIONS: Laparoscopic lymphatic sparing varicocelectomy is an effective procedure to adopt in children with varicocele. The intra-dartos/intra-testicular injection of isosulfan blue is significantly better than the previously described intra-dartos injection, permitting to identify lymphatic vessels in 100% of cases in our series. No allergy to isosulfan blue was reported in both groups.

Long-term results of laparoscopic treatment of esophageal achalasia in children: a multicentric survey.

BACKGROUND: This report describes three Italian centers' experience in the treatment of children with esophageal achalasia. PATIENTS AND METHODS: Between June 2000 and June 2012, 31 children (13 girls and 18 boys, with a median age of 8.4 years) affected by esophageal achalasia were treated in three different institutions with an esophagomyotomy according to Heller's procedure via laparoscopy associated with a Dor antireflux procedure. Between 2000 and 2005 (for 14 patients) we used mono- or bipolar coagulation to perform myotomy; after 2005 (for 17 patients) we used the new hemostatic devices to perform it. RESULTS: Median length of surgery was 120 minutes. Median hospital stay was 4 days. We recorded eight complications in our series: 3 patients (9.6%) had a mucosal perforation, and 5 children (16.1%) presented dysphagia after surgery. When comparing the data before and after 2005, it seems that the new hemostatic devices statistically shortened the length of surgery (P<.01, Student's t test). CONCLUSIONS: On the basis of our experience, laparoscopic Heller's myotomy associated with an antireflux procedure is a safe and effective method for the treatment of achalasia in the pediatric population. Intraoperative complications were <10%, and they occurred mostly at the beginning of our experience. Residual dysphagia occurred in about 16% of cases. The use of the new hemostatic devices seems to reduce the length of surgery and intraoperative bleeding. Considering the rarity of this pathology, we believe that patients with achalasia have to be treated only at centers with a strong experience in the treatment of this pathology.

Work-related upper limb musculoskeletal disorders in paediatric laparoscopic surgery. A multicenter survey.

BACKGROUND: Surgeons are at risk for developing work-related musculoskeletal symptoms (WMS). The present study aims to examine the physical factors and their association with WMS among pediatric laparoscopic surgeons. METHODS: A questionnaire consisting of 21 questions was created and mailed to 25 pediatric laparoscopic surgeons (LG). 23/25 surgeons (92%) completed the survey. The questionnaire was analyzed and then split into 2 groups. Group 1 (LG1) included surgeons with greater laparoscopic experience, and group 2 (LG2) included surgeons with less important laparoscopic experience. In addition, we constructed and sent to the same surgeons a similar questionnaire focused on WMS after an open procedure (OG) with the aim to compare results of LG with OG. RESULTS: The prevalence rate of WMS with shoulder symptoms was 78.2% in surgeons that performed laparoscopy for more than 10 years, with 60.8% also reporting other pain. In 66.6% this pain is evident only after a long-lasting procedure. Forty-four percent of these surgeons require painkillers at least twice a week. Fifty percent of these surgeons also suffer at home. Fifty-five and one half percent of surgeons indicate that this pain is related to their laparoscopic activity. Forty-three and a half percent think that laparoscopy is beneficial only for the patient but has a bad ergonomic effect for surgeons. Sixty-five and two-tenths percent think that robotic surgery can be helpful to improve ergonomics. Comparing the groups, WMS occur more frequently in LG (78.2%) than in OG (56.5%), but this difference was not statistically significant (χ(2)=0.05). In addition, WMS occur more frequently in LG1 (84.6%) than in LG2 (70%), but this difference was not statistically significant (χ(2)=0.05). CONCLUSIONS: These results confirmed a strong association between WMS and the number of laparoscopic procedures performed. Skilled laparoscopic surgeons have more pain than less skilled laparoscopic surgeons. WMS in the same group of surgeons are more frequent after laparoscopy than after open procedures. The majority of surgeons refer to shoulder symptoms.

Blue patent lymphography prevents hydrocele after laparoscopic varicocelectomy: 10 years of experience.

PURPOSE: Laparoscopic varicocelectomy according to the Palomo technique is the most common procedure adopted in children with testicular varicocele. This procedure involves the ligation of the internal spermatic cord and is associated with a 3%-5% incidence of recurrence and up to 30% incidence of hydroceles. We sought to determine the impact of lymphatic preservation on hydrocele formation and the success of varicocelectomy. PATIENTS AND METHODS: We retrospectively evaluated 396 patients with a mean age of 13.2 years who underwent laparoscopic varicocelectomy. Patients were divided into two groups: those who underwent a lymphatic-sparing (LS) procedure using isosulfan blue scrotal intra-dartoic injection and those who underwent a non-LS (NLS) technique. The incidences of recurrence/persistence and postoperative hydrocele formation requiring surgery or aspiration were analyzed statistically using the chi-squared test. RESULTS: Of 396 patients, 244 received a laparoscopic LS procedure, and 152 received an NLS operation. The LS patients in whom the lymphatic vessels were not identified (26/244 [10.6%]) were considered NLS repairs. The follow-up was at least 12 months. LS surgery (218 patients) was associated with a decreased incidence of postoperative hydrocele (0/218 [0%] versus 18/178 [10.1%]; chi-squared test=25.84, difference statistically significant). There was no significant difference in incidence of persistent or recurrent varicocele requiring reoperation following the initial procedure (5/218 [2.2%] versus 5/178 [2.8%]; chi-squared test=0.41, difference statistically not significant). CONCLUSIONS: Laparoscopic LS varicocelectomy using isosulfan blue is preferable to laparoscopic Palomo repair that does not preserve the lymphatics. It has a significantly lower incidence of postoperative hydroceles and still maintains a low incidence of persistence/recurrence.