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Introduction The corona virus disease 2019 (COVID-19) pandemic forced most of the Italian population into lockdown from 11 March to 18 May 2020. A nationwide survey of Italian Clinical Nutrition and Dietetic Services (Obesity Centers or OCs) was carried out to assess the impact of lockdown restrictions on the physical and mental wellbeing of patients with obesity (PWO) who had follow-up appointments postponed due to lockdown restrictions and to compare determinants of weight gain before and after the pandemic. Methods We designed a structured 77-item questionnaire covering employment status, diet, physical activity and psychological aspects, that was disseminated through follow-up calls and online between 2 May and 25 June 2020. Data were analyzed by multiple correspondence analysis (MCA) and multiple linear regression. Results A total of 1,232 PWO from 26 OCs completed the questionnaires (72% female, mean age 50.2 ± 14.2 years; mean BMI 34.7 ± 7.6 kg/m2; 41% obesity class II to III). During the lockdown, 48.8% gained, 27.1% lost, while the remainder (24.1%) maintained their weight. The mean weight change was +2.3 ± 4.8 kg (in weight gainers: +4.0 ± 2.4 kg; +4.2% ± 5.4%). Approximately 37% of participants experienced increased emotional difficulties, mostly fear and dissatisfaction. Sixty-one percent reduced their physical activity (PA) and 55% experienced a change in sleep quality/quantity. The lack of online contact (37.5%) with the OC during lockdown strongly correlated with weight gain (p < 0.001). Using MCA, two main clusters were identified: those with unchanged or even improved lifestyles during lockdown (Cluster 1) and those with worse lifestyles during the same time (Cluster 2). The latter includes unemployed people experiencing depression, boredom, dissatisfaction and increased food contemplation and weight gain. Within Cluster 2, homemakers reported gaining weight and experiencing anger due to home confinement. Conclusions Among Italian PWO, work status, emotional dysregulation, and lack of online communication with OCs were determinants of weight gain during the lockdown period.

Our aim is the retrospective valuation of results in over 75 year-old patients, with colorectal cancer, treated with laparoscopic and laparotomic surgery, considering how laparoscopic surgery has improved these patients' outcome.We took all over 75 year-old patients, affected by colorectal cancer, treated with colectomy. Patients has been divided into two groups: laparotomy group and laparoscopy group. Data concerning patients, i.e., age, sex, BMI, ASA, comorbidities, were collected with data concerning the operation (surgical time, conversion percentage). Postoperative outcomes - i.e., gas evacuation, bowel movements, solid and liquid feeding, need to ICU, complications, re-surgery, hospitalization and type of discharge, mortality - were evaluated.A total of 145 patients are included: laparotomy 80 and laparoscopy 51. Two groups are homogeneous for age, sex, BMI, ASA, comorbidities. Surgical times are the same. Need to Intesive Care Unit (ICU) is lower in laparoscopy. Gas evacuation and bowel movements are earlier in laparoscopy. Liquid and solid diet is earlier in laparoscopy. Hospitalization was earlier after laparoscopy. Discharge at home is more frequent in laparoscopy. Major and minor complications are lower in laparoscopy. Post-operative mortality is lower in laparoscopy.Laparoscopy improves over 75 year-old patients' outcomes, after elective surgery for colorectal cancer. Surgery trauma, anaesthesia, nutritional and hemodynamic alterations, are factors that break the old patients' fragile physiologic balance. Less traumatic surgery improves old patients' outcomes.

Helicobacter pylori (Hp) may affect the normal balance between gastric epithelial cell proliferation and epithelial cell death, interfering thus with the maintenance of gastric mucosa integrity. The aim of this study was to investigate the effect of Hp infection on cell proliferation index (PI) and apoptotic index (AI) in gastric epithelium of the antrum and corpus.Prospective study in forty-one patients with functional dyspepsia (14 males, 27 females, average age = 54+/-16.1 years). Day one: upper digestive endoscopy with biopsies of the antrum and corpus, and a cytological smear of the antral area for AgNOR (argyrophilic nucleolar organizer region) analysis. Biopsies for the programmed tests were sent in separate labeled containers: to study AI (antibody anti-M30), PI (antibody anti-Ki 67) and histology (Sydney criteria and the detection of Hp). Detection of the AgNORs through the Giménez-Mas et al. technique, using Visilog-Microptic Software. Day two: a blood sample was drawn from each patient for the serologic detection of the status CagA and VacA, and a breath test was carried out with 13C-Urea.SPSS program with the application of Student's t, chi-square and Fisher tests.24 patients were Hp(+) and 17 Hp(-). The PI (Ki 67 and AgNORs) in the antral area was significantly increased in the Hp(+) patients. AI showed no significant difference in the subgroups Hp(+) and Hp(-). Both subgroups showed increased PI in the antrum and increased AI in the gastric corpus. There was significantly higher PI in CagA(+), without an increase in the AI. The AI was significantly higher in CagA(-), when compared with CagA(+). The VacA protein had no influence on PI and AI. Acute and chronic gastritis was more frequent and more severe in Hp(+) patients. This group lacked any correlation between the histological findings and the PI, but the opposite was the case between AI and the degree of cellular infiltration.In patients with functional dyspepsia, Hp infection induces an increase of PI, with significant presence in the antrum area, without the corresponding increase in AI. Cag A(+) promotes the increase of PI, and Cag A(-) promotes the increase of AI. The Vac A status has no influence on the PI or AI. The degree of cellular infiltration interferes with AI.

Since the large multicenter DIG trial has shown no effects of digitalis on the all-cause mortality of patients with chronic heart failure (HF), the broad prescription of this drug in patients with HF appears to be at the very least, questionable. The aims of this study were: to analyze prescription patterns of digitalis, from 1995 to 2000, in a large group of outpatients with HF; to analyze the independent predictors of digitalis prescription and to evaluate the impact of the results of the DIG trial on the prescription rate of this drug.From 1995 to 2000, 11 070 HF outpatients (mean age 64 +/- 12 years, ejection fraction 35 +/- 12%) were enrolled in a large Italian database.Out of 11 070 patients, 7198 (65%) were treated with digitalis. At multivariate analysis, the following variables were independently associated with digitalis prescription; atrial fibrillation (odds ratio [OR] 3.3, 95% confidence interval [CI] 2.9-3.8), ejection fraction30% (OR 1.7, 95% CI 1.5-1.9), NYHA class III-IV vs II-III (OR 1.3, 95% CI 1.2-1.5), admission for HF during the previous year (OR 1.4, 95% CI 1.2-1.5). After the publication of the DIG trial, there was a significant reduction in the rate of digitalis prescription: the percentage of patients taking digitalis fell from 68% in 1996-1997 to 61% in 1998-1999 (p0.001).Over 60% of Italian outpatients with HF were treated with digitalis; as expected, patients with a low ejection fraction, atrial fibrillation and in a more advanced stage of HF are more likely to receive this drug. Finally, after the publication of the DIG trial, the rate of digitalis prescription significantly decreased.

Familial Adenomatous Polyposis in an autosomal dominant disease in which the large bowel is carpeted by polyps of various dimensions appearing during the second or third decade of life. Several extracolonic manifestations complete the clinical spectrum of Familial Adenomatous Polyposis. If untreated, the disease leads invariably to colorectal cancer. The gene responsible for the disease, adenomatous Polyposis Coli, has been localized at chromosome 5q21.To describe the clinical features of 156 Familial Adenomatous Polyposis patients (from 41 families) and to analyze possible correlations between genotype and phenotype.Familial Adenomatous Polyposis was defined as the presence of 100 or more polyps in the large bowel. In 17 families (41%), the proband was the only affected individual (single cases). Adenomatous Polyposis Coli gene mutations were studied on DNA extracted from peripheral white blood cells and evaluated by polymerase chain reaction single strand conformation polymorphism, followed by direct sequencing of samples showing abnormal banding at single strand conformation polymorphism.The large majority of Familial Adenomatous Polyposis patients underwent surgery; colectomy with ileorectal anastomosis was the most frequent approach, however, cancer of the rectal stump developed in 11.6% of patients submitted to colectomy and ileorectal anastomosis. Adenomas were rare in the stomach (8.8%), but their frequency increased in the duodenum (33.8%) and jejunum (55.0%, chi 2 for trend 23.7, p0.001). Desmoid tumours were diagnosed in 17 patients (10.9% of the total) and in 6 families. Mutations of the Adenomatous Polyposis Coli gene were studied in 20 out of 25 families (80%) and on a total of 75 individuals. The most frequent alterations were 1 to 5 bp deletions leading to stop codons and truncated proteins. Desmoid tumours, presence of duodenal or jejunal adenomas were associated with an ample range of mutations, from codon 215 to codon 1464. In contrast, particularly severe polyposis (mean age at appearance of polyps 11-16 years, and of cancer development 27-32 years) was associated with a "hotspot" mutation site at codons 1303-1309.In patients with Familial Adenomatous Polyposis, subtotal colectomy with ileorectal anastomosis is still the treatment of choice. Adenomatous lesions seem to show a "gradient" distribution from the stomach to the large bowel. Desmoid tumours are relatively common, though their incidence is limited to some of the families. Constitutional mutations can be detected in 80% of the investigated families. Genotype-phenotype correlations showed a hot-spot at codons 1303-1309, frequently associated with severe polyposis.

Genetic instability related to defective DNA mismatch repair genes may be involved in the pathogenesis of carcinoma in Hereditary Non-Polyposis Colorectal Cancer (HNPCC). To test that the targets of genetic instability could include critical transforming genes involved in colon tumor progression, we examined 23 colorectal carcinomas in patients with HNPCC in order to detect somatic mutations in K-ras and p53 genes. Using single strand conformation polymorphism followed by direct DNA sequencing, we detected 4 mutations in K-ras gene (17%) and 3 in p53 gene (13%) which change the amino acid sequence of the protein p53. This is significantly lower than in sporadic cancer. Our data suggest that colon cancer in HNPCC might partly involve a distinct pathogenetic mechanism that involves other genes than those altered in sporadic tumors.

Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) is characterized by the early onset of colorectal neoplasms, frequently localized in the right colon, increased occurrence of multiple primaries, vertical transmission and aggregation of tumours in families in accordance to a Mendelian dominant type of inheritance. The syndrome accounts for approximately 5% of all colorectal cancers. The purpose of the present study was to describe the tumour spectrum and the most relevant clinical features of 28 kindreds with HNPCC, classified according to the guidelines of the International Collaborative Study Group, and of 61 "suspected" HNPCC. These families were observed during a 6-year registration of colorectal neoplasms in a health-care district of Northern Italy. Colorectal cancer was by far the most frequent malignancy; gastric cancer was the second. Uterine carcinoma was only slightly more frequent than expected. Lung- and breast-tumour rates were lower than expected. Cancer distribution in the large bowel showed that about two fifths of the tumours developed in the right colon. The occurrence of cancer before the age of 50 to 60 was much more frequent in HNPCC. Multiple tumours developed in 25 patients with HNPCC and in 32 with "suspected" HNPCC. Pancolonoscopy remains the procedure of choice for surveillance; other examinations, such as gastroscopy, gynaecological investigations, urography and cholangiography, are suggested only to selected families. One of the main features of the study was the inclusion of 61 "suspected" HNPCC, a heterogeneous group of families which nonetheless deserves careful follow-up.

The institution of a colorectal Cancer Register in a health care district of Northern Italy gave the authors the opportunity to evaluate the prognostic relevance of several morphologic and clinical variables by univariate and multivariate analyses. Of the 134 patients registered in 1984, 132 were followed up until the end of 1989. Overall 5-year survival was 37%, but the figure increased to 43% when only colorectal cancer-related deaths were considered. Univariate analysis for clinical variables showed that TNM staging and age at diagnosis were significantly related to prognosis, whereas none of the other parameters were indicative of the clinical outcome. With a similar analysis, among the various morphologic variables, pattern of growth (infiltrating versus expanding) and extent of fibrosis (extensive versus little or absent) appeared to be indicators of prognosis. When the variables that were significant (stage, age, pattern of growth, and fibrosis) in the univariate analysis were entered into the Cox model of multivariate analysis, TNM staging was the only parameter that maintained an independent prognostic importance. The authors state that their results confirm the importance of stage in predicting survival for cancer of the large bowel and suggest that the possible prognostic value of clinical and morphologic variables should be investigated within each of the major TNM or Dukes' classes.

OBJECTIVES: This study describes up-to-date cancer incidence and survival in Italian paediatric and adolescent patients, based on data collected by the network of Italian cancer registries (AIRTUM). It updates the monograph published on the same topic in 2008. The main objective of this monograph is to present the statistics according to standard rigorous epidemiological methods and disseminate them to a wide range of readers, including the lay public. Given the deep impact of the 2008 monograph on the general public, in this update we complement descriptive statistics with additional data and commentaries on issues of importance for public health, in order to provide unambiguous criteria on how to interpret the statistics. The study is the result of the collaboration between AIRTUM and AIEOP (Italian Association of Paediatric Haematology and Oncology) with contributions from interested parties, including representatives of parent associations. The monograph is divided into three parts. The first part presents incidence rates, survival probabilities, and time trends, by sex, age, geographical area, and cancer site or type, by means of tables and graphs as in the previous monograph, to facilitate direct comparisons. Four articles summarize and comment the results. The second part uses data from AIRTUM and AIEOP to outline patient management and health care issues; it includes estimates of the number of new cases in the next decade and of young adults living after a paediatric cancer diagnosis. Health organizational aspects of treatment services for paediatric patients, based on the AIEOP database, are also discussed, along with long-term complications in cured patients. The third section describes the changes in mortality trends due to improving therapies and healthcare services, and discusses risk factors and prevention of childhood cancer, late adverse events in cured patients, and other related issues. MATERIAL AND METHODS: Data herein presented were provided by AIRTUM population-based cancer registries, covering 47%of the Italian population below age 20 years, in the period 2003-2008. Quality of cancer registration in Italy is elevated, with high proportions of microscopically verified diagnoses (91%in the 0-14 years age group and 96% between 15 and 19 years of age) and a very small proportion of cases collected through death certificate only (0.1%).The proportion of cases in diagnostic groups XI (other malignant epithelial neoplasms) and XII (other and unspecified neoplasms) of the International Classification for Childhood Cancer (ICCC), based on the third revision of the International Classification of Diseases for Oncology (ICD-O-3), were 7.0% in the 0-14 years age group and 26.0%in the 15-19 years age group.The ratio between mortality and incidence was 17.7% in both children and adolescents. Detailed results are presented in 24 fact sheets for the 12 major ICCC-3 diagnostic groups and 10 sub-groups of special interest; the series is completed by a sheet on all malignant tumours and one on all tumours including non-malignant neoplasms of the central nervous system. All sheets include results for three age groups (0-14, 15-19, and 0-19 years) and are followed by two commentaries on incidence in the recent period, one on trends and the other on survival. Incidence rates were age-standardized on the European population and presented per million children. Incidence rates are also presented by age group, sex, and geographical area. Incidence trends were evaluated for two periods, 1988-2008 and 1998-2008, using estimated annual percent changes, and survival estimates were calculated by age and period. Indicators and corresponding 95% confidence intervals are shown in forms of graphics and tables at the end of the monograph and online at http://www.registri-tumori.it. Geographical analyses were conducted rearranging cancer registries into four macroareas (North-West, North-East, Centre, and South and Islands). Age groups were the same used in descriptive studies on children worldwide (0, 1-4, 5-9, 10- 14 years for paediatric tumours and 15-19 years for adolescents). Incidence trend analyses included cancer registries with three or more years of registration in the 5-year period, using Poisson regression models. Observed survival was computed according to the Kaplan-Meier method. The estimate of expected cases in the next decade was based on observed incidence rates in the most recent period, extended to the Italian estimated population of children and adolescents in the periods 2011-2015 and 2016-2020. The AIEOP database (Modello 1.01) allowed us to compare the number of patients treated and followed-up in specialized centres with expected cases based on AIRTUM estimates. The AIEOP database also provided information regarding health care migration throughout Italian regions and the number of foreign (immigrated) children treated in Italian AIEOP centres. RESULTS: In the period 2003-2008, 31 cancer registries reported 4,473 incident malignant neoplasms, 2,855 in children and 1,618 in adolescents. Cancer incidence rates were 164 cases per million in children aged 14 years or below and 269 cases per million in patients aged 15-19 years. Limited geographical variations emerged. In children (0-14 years) a significant increase in malignant cancer incidence was observed until 1997 (APC: +3.2%), followed by a plateau (APC: -1.1%not statistically significant).Until the late Nineties, a statistically significant increase was also observed in the incidence of all leukaemias in males (APC: +5.7%), lymphoid leukaemias (APC: +5.6%), representing 80% of all leukaemias, Hodgkin and non- Hodgkin lymphomas (APC: +6.3%). A significant decrease emerged for lymphoid leukaemia starting in 1995 (APC: -1.9%), while no substantial change in cancer incidence rates was observed in the last decade of observation for all malignant neoplasms and lymphomas. In addition, no variation emerged for malignant (according to the most recent classification) central nervous system (CNS) neoplasms, while an annual increase of 1.8% (significant) was observed in the period 1988-2008, when non-malignant tumours were included. Increases in cancer incidence were observed throughout the study period for neuroblastoma (APC: +1.9%) and epithelial tumours or melanoma (APC: +4.1%). In the period 1998-2008, in addition to lymphoid leukaemias, a significant decrease was observed for all malignant neoplasms, lymphomas in girls, CNS tumours (males and females), and renal tumours in girls, while no increases were observed in this age group. In adolescents (15-19 years) between 1988 and 2008, a significant increase in incidence rates was observed (APC: +2.0%) for all malignant neoplasms, all lymphomas (APC: +2.9%; in particular Hodgkin lymphoma, APC: +3.6%), thyroid cancer (APC: +6.1%), and melanoma (APC: +8.1%). Conversely, lymphoid leukaemia is the only neoplasm showing a long-term decrease in adolescents. Recent trends (1998-2008) confirm the long-term increases only for all malignant neoplasms in girls and thyroid cancer (APC: +7.9%, boys and girls), while a decrease in bone tumour incidence emerged in girls, albeit based only on 46 cases. Cancer mortality in children showed a persistent decrease for all neoplasms and even for more frequent cancer sites or types, and mortality rates for cancer were three-fold higher in the early Seventies than in 2008. In addition, five-year survival after cancer diagnosis increased in the last three decades and was still increasing in the period 2003- 2008, reaching 82% in children and 86% in adolescents. In the period 2008-2010, 4,488 children (0-14 years) were treated in one of the AIEOP clinical centres and we estimate, based on the above-presented incidence rates, that they represented 92% of all cancer cases in Italy. However, in adolescents, the proportion of patients treated in AIEOP centres was only 25%. A migration of patients living in the South of Italy to Central and Northern Italy emerged from AIEOP information. The expected number of cancer cases in children aged between 0 and 14 years of age is approximately 7,000 in the period 2016- 2020, while the corresponding figure for adolescents between 15 and 19 years of age is 4,000, with no relevant variation in comparison with the previous five-year period. COMMENTS: The present findings update descriptive cancer epidemiology in children and adolescents in Italy based on data provided by an extensive network of general and specialized population-based cancer registries. Data obtained from cancer registries are supplemented by additional information collected by specialized clinical AIEOP centres and mortality reports collected by the National Institute of Statistics (ISTAT). Incidence rates reported in Italy were slightly higher in comparison to other developed Countries, but relatively consistent between different Italian areas. Our results also showed that the significant increase in cancer incidence observed until the end of Nineties has halted, with the exception solely of thyroid cancer in adolescents. Efficacy of therapeutic protocols has improved constantly since the Seventies, and recent findings confirm this trend in all age groups and, in particular, for rarer tumours and cancer types that have very poor prognosis. Findings derived from cross-analysis with AIEOP data suggest that it is possible to further improve the efficiency of our healthcare system, in particular for adolescents; migration can be reduced with a more rational use of hospitals throughout Italy.

Laparoscopic approach for treatment of colorectal lesion is gaining acceptance gradually. Evidence from numerous randomised controlled trials has shown the short-term benefits of laparoscopic colon resection over open surgery, and its long-term outcomes also does not differ considerably from those of open surgery. This study aims at a retrospective analysis of operative and short term outcomes of patients.All laparoscopic colon and rectal resections performed between September 2004 and September 2011 were included. The clinical parameters, operative parameters and short-term outcome details of laparoscopic colorectal surgery patients were collected from the retrospectively reviewed database.A total of 347 patients, median age 71 years (range 32 to 96), underwent laparoscopic resection of the colon and rectum. The median Body Mass Index (BMI) was 26.5. The majority of the procedures were performed for malignant disease (97,1%) and the most common procedure was right colectomy (41%). The median duration of surgery was 202,3 minutes, with conversion to open surgery in 40 patients (11.5%). Complications occurred in 23 patients (6.6%). The median length of hospital stay was 8.9 days. In patients with malignant disease, the median number of lymph nodes removed was 14.9.Our results show that laparoscopic approach for colon-rectal lesions is safe, feasible and produces favourable results. The most important aspect of surgery for malignant disease is the ability to remove radically the disease. However all data are still related to the experience of the operator.

To evaluate current colorectal cancer (CRC) screening practices in Saskatchewan and identify barriers to screening with the goal of improving current practice.Survey of family physicians.Saskatchewan.A total of 773 family physicians were surveyed.Demographic characteristics, individual screening practices, and perceived barriers to screening.The response rate to the survey was 44.5%. When asked what method they used for fecal occult blood testing, almost 40% of respondents were either unsure or did not answer the question. Of those who did respond, 35.8% employed hemoccult testing following digital rectal examination, a practice not recommended for CRC screening. Screening guidelines for average-risk patients were generally well adhered to, with 79.9% of respondents recommending screening beginning at age 50. For screening patients at increased risk of CRC owing to family history, only 64.2% of respondents began screening 10 years before the age of the index patient at diagnosis. Physicians who were more likely to follow guidelines were female, in practice fewer than 10 years, trained in Canada, and practising in urban areas. More than 90% of family physicians agreed that a standard provincewide screening program would be beneficial.We have identified considerable knowledge gaps with regard to CRC screening. There is confusion about which fecal occult blood tests are recommended for screening. Also, screening guidelines for patients with a family history of CRC are poorly understood. These findings suggest that better physician education about CRC screening is required. Introduction of a provincewide screening program should improve overall screening success.

In hereditary nonpolyposis colorectal cancer (HNPCC, or Lynch syndrome) a close surveillance is usually proposed to high-risk family members with the ultimate goal of reducing cancer incidence and mortality. Through a specialized registry, between 1984 and 1996, we identified 31 families with clinical features of HNPCC. A total of 390 first-degree relatives of affected patients were considered at high risk for colorectal cancer. The main purposes of this study were: (a) to assess overall compliance; and (b) to evaluate the frequency and morphological features of tumors detected at endoscopy. Two hundred twenty-three subjects could be directly interviewed and colonoscopy strongly recommended. Each of the 86 individuals who underwent colonoscopy was matched to a control of the same age (+/-3 years) and sex (control subjects were seeking endoscopy for constipation, rectal bleeding or abdominal discomfort). Of the 390 individuals traced as "at risk," 223 (57.2%) could be contacted, and, of these, 86 (38.6%, or 22.0% of the total) underwent colonoscopy. One or more colorectal lesions were found in 35 of 86 (40.7%) HNPCC asymptomatic family members and in 15 (17.4%; P0.001) controls. In the former group, 29 adenomas were detected in 20 individuals as opposed to 11 adenomas in 9 subjects among controls (P0.03). Moreover, adenomas in family members were significantly larger [9.1 +/- 5.9 mm (mean +/- SD) versus 5.8 +/- 3.7 mm; P0.02] and more frequently showed a tubulovillous histological type and a high degree of dysplasia. Five colorectal carcinomas (in four patients) were detected among cases (four of which were located between the cecum and the hepatic flexure); only one was detected among controls. Surveillance of high-risk subjects in HNPCC families can be carried out only in a fraction of them, because the majority cannot be reached or refuse to collaborate. On the other hand, the frequency of newly detected lesions among family members and the possible aggressive behavior of the lesions render pancolonoscopy necessary at regular intervals of time.

Despite considerable progress achieved in the management of head and neck carcinomas (HNC) in the last decade, the prognosis of patients with advanced squamous cell HNC is still dismal. On the basis of the reported good activity of a new vinca alkaloid derivative, i.e., vinorelbine (VNR), we tested the combination of cisplatin and VNR in a series of patients with recurrent or previously untreated unresectable squamous cell HNC. Thirty-five patients with recurrent or previously untreated unresectable squamous cell HNC were treated with a combination of cisplatin 80 mg/m2 on day 1, plus vinorelbine 25 mg/m2 i.v. push on days 1 and 8. This cycle was repeated every 3 weeks. Analysis of response rates was carried out separately for previously untreated patients, and those with recurrent disease after surgery and/or radiotherapy. In the group of 20 patients with recurrent disease the overall response rate was 55% (95% CL 44-66%), with 3 patients (15%) showing a complete response with a mean duration of 6.2+ months and 8 patients showing a partial response with a mean duration of 8.6+ months. In the group of patients with previously untreated unresectable disease, 13 patients (87%, 95% CL 78-96%) had a major objective response with a complete response rate of 27%. This regimen was quite well tolerated, with meyelosuppression and vomiting being the most frequent toxicities. The occurrence of an acute pain syndrome following vinorelbine administration in 4 patients is noteworthy. In conclusion, this combination is active in advanced squamous cell head and neck carcinoma. However, although it may be recommended in recurrent carcinoma, the complete response rate achieved in previously untreated patients is lower than that reported with other more intensive regimens.

Purpose Only a few studies are available on dose-related effects of sacubitril/valsartan (angiotensin receptor neprilysin inhibition (ARNI)) in real-life patients with heart failure and reduced ejection fraction (HFrEF). We sought to investigate clinical and functional effects in real-life HFrEF patients receiving ARNI at a different cumulative dose. Methods This was an observational study in consecutive outpatients admitted for HFrEF from October 2017 to June 2019. The PARADIGM criteria were needed for enrolment. ARNI was uptitrated according to blood pressure, drug tolerability, renal function and kaliemia. At least 10-month follow-up was required in each patient. Clinical assessment, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-min walk test and strain echocardiography were performed in each patient on a regular basis during the observational period. At the end of the study, patients were divided into two groups based on the median yearly dose of the ARNI medication. Results A total of 90 patients, 64 ± 11 years, 82% males, were enrolled. The cut-off dose was established in 75 mg BID, and the study population was divided into group A (≤ 75 mg), 52 patients (58%), and group B (> 75 mg), 38 patients (42%). The follow-up duration was 12 months (range 11–13). NYHA class, KCCQ score and 6MWT performance ameliorated in both groups, with a quicker time to benefit in group B. The proportion of patients walking > 350 m increased from 21 to 58% in group A (p

The expansion of coronavirus disease 2019 (COVID-19) prompted measures of disease containment by the Italian government with a national lockdown on March 9, 2020. The purpose of this study is to evaluate the rate of hospitalization and mode of in-hospital treatment of patients with chronic limb-threatening ischemia (CLTI) before and during lockdown in the Campania region of Italy. The study population includes all patients with CLTI hospitalized in Campania over a 10-week period: 5 weeks before and 5 weeks during lockdown ( n = 453). Patients were treated medically and/or underwent urgent revascularization and/or major amputation of the lower extremities. Mean age was 69.2 ± 10.6 years and 27.6% of the patients were women. During hospitalization, 21.9% of patients were treated medically, 78.1% underwent revascularization, and 17.4% required amputations. In the weeks during the lockdown, a reduced rate of hospitalization for CLTI was observed compared with the weeks before lockdown (25 vs 74/100,000 inhabitants/year; incidence rate ratio: 0.34, 95% CI 0.32–0.37). This effect persisted to the end of the study period. An increased amputation rate in the weeks during lockdown was observed (29.3% vs 13.4%; p < 0.001). This study reports a reduced rate of CLTI-related hospitalization and an increased in-hospital amputation rate during lockdown in Campania. Ensuring appropriate treatment for patients with CLTI should be prioritized, even during disease containment measures due to the COVID-19 pandemic or other similar conditions.

There is limited evidence on characterization and natural history of supraventricular tachycardia (SVT)-induced left ventricular (LV) dysfunction. The aim of this work was to characterize clinical features and long-term evolution of SVT-induced LV dysfunction. Patients consecutively admitted with sustained SVT and heart rate >100 bpm as the only known cause of a new onset LV systolic dysfunction (i.e., LV ejection fraction [EF]

The echocardiographic estimation of right atrial pressure (RAP) is based on the size and inspiratory collapse of the inferior vena cava (IVC). However, this method has proven to have limits of reliability. The aim of this study is to assess feasibility and accuracy of a new semi-automated approach to estimate RAP. Standard acquired echocardiographic images were processed with a semi-automated technique. Indexes related to the collapsibility of the vessel during inspiration (Caval Index, CI) and new indexes of pulsatility, obtained considering only the stimulation due to either respiration (Respiratory Caval Index, RCI) or heartbeats (Cardiac Caval Index, CCI) were derived. Binary Tree Models (BTM) were then developed to estimate either 3 or 5 RAP classes (BTM3 and BTM5) using indexes estimated by the semi-automated technique. These BTMs were compared with two standard estimation (SE) echocardiographic methods, indicated as A and B, distinguishing among 3 and 5 RAP classes, respectively. Direct RAP measurements obtained during a right heart catheterization (RHC) were used as reference. 62 consecutive ‘all-comers’ patients that had a RHC were enrolled; 13 patients were excluded for technical reasons. Therefore 49 patients were included in this study (mean age 62.2 ± 15.2 years, 75.5% pulmonary hypertension, 34.7% severe left ventricular dysfunction and 51% right ventricular dysfunction). The SE methods showed poor accuracy for RAP estimation (method A: misclassification error, ME = 51%, R2 = 0.22; method B: ME = 69%, R2 = 0.26). Instead, the new semi-automated methods BTM3 and BTM5 have higher accuracy (ME = 14%, R2 = 0.47 and ME = 22%, R2 = 0.61, respectively). In conclusion, a multi-parametric approach using IVC indexes extracted by the semi-automated approach is a promising tool for a more accurate estimation of RAP.

Objective The objective of this study was to assess early and midterm results after endovascular aortic arch repair using a double inner branch stent graft (DIBSG) in patients with aortic arch aneurysm or dissection unfit for open surgery. Methods Between 2012 and 2018, there were 24 patients with aortic arch disease who were treated with a single model of a DIBSG (Terumo Aortic, Glasgow, United Kingdom) in nine Italian cardiovascular centers. We investigated technical success, mortality, occurrence of major complications, and need for reintervention in a multicenter, nonrandomized, retrospective fashion. Results The in-hospital mortality rate was 16.7%. Cerebrovascular events occurred in 25% of patients and major strokes in 12.5%. Two patients experienced a retrograde dissection (8.3%), whereas none reported any type I or type III endoleak. During a mean follow-up of 18 months (range, 1-60 months), one patient died of a nonaortic cause and one reported a nonarch-related major stroke. No late secondary intervention was needed during the follow-up. Excluding from the analysis the first six patients treated until 2014 as part of the learning curve, in-hospital mortality, major stroke, and retrograde dissection rates were 11.1%, 11.1%, and 5.6%, respectively. Conclusions Endovascular aortic arch repair using this model of DIBSG is feasible, and results are acceptable for a new technique in a high-risk subset of patients. Operative mortality suffers the effect of a learning curve, whereas midterm aorta-related survival is promising. Endovascular repair of aortic arch disease with a DIBSG should always be considered to give high-risk patients a chance of repair. Large-scale studies are needed to assess the long-term durability of this technique.

Objectives Left dorsolateral prefrontal cortex anodal transcranial direct current stimulation (tDCS) was applied in a group of patients with disorders of consciousness to determine the effects of modulation of spontaneous oscillatory brain activity. Methods 12 patients in an unresponsive wakefulness syndrome (UWS) and 12 in a minimally conscious state (MCS) underwent 2-weeks active and 2-weeks sham tDCS. Neurophysiological assessment was performed with EEG power spectra and coherence analysis directly before and after each session. Results An increase of power and coherence of the frontal and parietal alpha and beta frequency bands and significant clinical improvements were seen after the active tDCS in MCS patients. In contrast, UWS patients showed some local frontal changes in the slow frequencies. No treatment effect was observed after sham. Conclusions tDCS could induce changes in cortical EEG oscillations, modulating the travel of alpha and beta waves between anterior and posterior brain areas when some cognitive functions were preserved. This plays an important role in consciousness by integrating cognitive-emotional processing with the state of arousal. In unresponsive people, brain integration seems to be lost. Significance Our results further support the critical role of long-range fronto-parietal connections in consciousness and show the potential therapeutic utility of tDCS.

International audience; PURPOSE:To compare the outcomes of PN to those of RN in very elderly patients treated for clinically localized renal tumor.PATIENTS AND METHODS:A purpose-built multi-institutional international database (RESURGE project) was used for this retrospective analysis. Patients over 75 years old and surgically treated for a suspicious of localized renal with either PN or RN were included in this database. Surgical, renal function and oncological outcomes were analyzed. Propensity scores for the predicted probability to receive PN in each patient were estimated by logistic regression models. Cox proportional hazard models were estimated to determine the relative change in hazard associated with PN vs RN on overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM).RESULTS:A total of 613 patients who underwent RN were successfully matched with 613 controls who underwent PN. Higher overall complication rate was recorded in the PN group (33% vs 25%; p = 0.01). Median follow-up for the entire cohort was 35 months (interquartile range [IQR] 13-63 months). There was a significant difference between RN and PN in median decline of eGFR (39% vs 17%; p

AIMS: The study aimed at evaluating the reliability and reproducibility of various noninvasive echocardiographic techniques for the estimation of the main hemodynamic parameters in clinical practice. METHODS: A total of 84 patients with a generic indication of right heart catheterization (RHC) executed a transthoracic echocardiography shortly before or after the RHC. All the parameters necessary for a noninvasive hemodynamic evaluation of right atrial pressure, pulmonary artery pressure (PAP), pulmonary capillary wedge pressure, pulmonary vascular resistance and cardiac output were acquired and the agreement with the invasive measures was evaluated by a Bland-Altman analysis. RESULTS: Noninvasive evaluation of right atrial pressure showed a moderate and low correlation with RHC using inferior vena cava parameters (r = 0.517) and tricuspid E/E' ratio (sensitivity 0.23, specificity 0.72), respectively. PAPs estimation from the tricuspid regurgitation peak velocity had a good correlation (r = 0.836) and feasibility (82.1%), as well as PAPm from tricuspid regurgitation mean gradient (r = 0.78, applicability 72.6%) and from pulmonary acceleration time (sensitivity 0.85, specificity 0.5, applicability 92.9%). Pulmonary capillary wedge pressure multiparametric evaluation, as suggested by the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations, showed a good correlation (sensitivity 0.96, specificity 0.59). The noninvasive evaluation of pulmonary vascular resistance and cardiac output did not prove to be clinically accurate. CONCLUSION: Various hemodynamic parameters can be adequately estimated with noninvasive methods. In particular, a multiparametric approach for the evaluation of left ventricle filling pressures is advisable and the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations are reliable even in a heterogeneous population with a significant quota of precapillary pulmonary hypertension.

Background: Earlobe deflation caused by fat atrophy is normally treated with lipofilling, mostly in the context of facelift surgery. In this report, we aim at reporting on Hyaluronic Acid injections to treat earlobe deflation. Materials and Methods: 16 Mowlavi Grade I and II patients were treated with HA injections, followed by molding to shape the lobule. Results: Effective correction, lasting 14months on average, is achieved. Five patients needed a touch-up procedure after 4-6months to improve the result. Conclusions: Earlobe augmentation with HA is an ideal option for correction of earlobe atrophy in cases of Mowlavi Grades I and II ptosis. Long-lasting (about 14months) correction is achieved with no downtime.

Sir: We have read the article by Mowlds and Lambros1 with great interest and enthusiasm. The findings of their study show that the nasolabial fold does not improve after cheek injection. By analyzing three-dimensional images of the face before and immediately after cheek injection of high- G′ hyaluronic acid, they demonstrate that the perceived nasolabial fold improvement, reported after cheek injections,2,3 is attributable to overall improvement in facial appearance rather than to actual nasolabial fold improvement. As a consequence, it might be ruled out that the nasolabial fold is a consequence of cheek deflating and it is likely attributable predominantly to change in the corner of the mouth and to muscular traction.4 This finding is of paramount importance because cheek overvolumization is frequently performed in an attempt to achieve something that will not occur: correction of the nasolabial folds. This practice is responsible for the bloated, overfilled appearance of the cheeks. Cheek overfilling gives a bulging, unnatural result, especially on animation. Increasing cheek volume and enhancing malar projection, by injecting the deep medial cheek fat compartment, is part of the treatment because lost volumes should be replaced.5 It is overfilling in an attempt to improve nasolabial and nasojugal folds that causes unnatural results. In fact, we see more and more patients asking to avoid that overfilled appearance. We also strongly agree with the authors’ statement that “young faces benefit from filling prominences and older faces benefit from filling hollows.” We would like to emphasize how important it is to fill the nasolabial fold and nasojugal crease directly in the subdermal plane as they become hollow with age. The benefit of treating these areas is clearly shown by the case presented (Figs. 1 and 2). The result is obtained progressively (in two sessions separated by 10 days) using LP–nonanimal stabilized hyaluronic acid gel (Restylane Perlane, now Lyft, Restylane; Q-Med, Uppsala, Sweden). The result is long lasting and can be maintained by yearly repeated injections (Fig. 2). Treating the nasolabial and nasojugal creases directly allows not only elimination of the crease but also maintenance of a natural result by avoiding overfilling of the cheek. We aim at supporting the breakthrough findings of Mowlds and Lambros that volumizing the cheek does not improve the nasolabial fold. Filling of the cheek must be performed judiciously to reshape the cheek, and any attempt at treating the nasolabial fold by volumizing the cheek will fail. To flatten the nasolabial fold, it should be directly injected.

Corticosteroid injection–related tissue atrophy might cause permanent skin and soft tissue deformities1 due to several factors, most importantly fibroblast inhibition and decreased Type I collagen synthesis. Correction of these deformities is challenging and is mostly based on volume replacement with lipofilling or other methods. Clinical observations and research have shown that injection of stabilized hyaluronic acid (HA) induces collagen synthesis, partially restoring dermal matrix components, and eventually producing a permanent effect.2–5 Based on these data, we hypothesize that HA injections might successfully treat atrophic tissue changes caused by corticosteroid injection. We describe a case of persistent buttock corticosteroid injection–related skin and soft tissue atrophy treated successfully with repeated HA injections.

This Report intends to estimate the total number of people still alive in 2010 after cancer diagnosis in Italy, regardless of the time since diagnosis, and to project these estimates to 2015. This study is also aimed to estimate the number of already cured cancer patients, whose mortality rates have become undistinguishable from that of the general population of the same age and sex.The study took advantage of the information from the AIRTUM database, which included 29 Cancer Registries (covering 21 million people, 35% of the Italian population). A total of 1,624,533 cancer cases diagnosed between 1976 and 2009 contributed to the study. For each registry, the observed prevalence was calculated. Prevalence for lengths of time exceeding the maximum duration of the registration and of the complete prevalence were derived by applying an estimated correction factor, the completeness index. This index was estimated by means of statistical regression models using cancer incidence and survival data available in registries with 18 years of observation or more. For 50 types or combinations of neoplasms, complete prevalence was estimated at 1.1.2010 as an absolute number and as a proportion per 100,000 inhabitants by sex, age group, area of residence, and years since diagnosis. Projections of complete prevalence for 1.1.2015 were computed under the assumption of a linear trend of the complete prevalence observed until 2010. Validated mixture cure models were used to estimate: the cure fraction, that is the proportion of patients who, starting from the time of diagnosis, are expected to reach the same mortality rate of the general population; the conditional relative survival (CRS), that is the cumulative probability of surviving some additional years, given that patients already survived a certain number of years; the time to cure, that is the number of years necessary so that conditional survival in the following five years (5-year CRS) exceeds the conventional threshold of 95% (i.e., mortality rates in cancer patients become undistinguishable compared to those of the general population); the proportion of patients already cured, i.e., people alive since a number of years exceeding time to cure.As of 1.1.2010, it was estimated that 2,587,347 people were alive after a cancer diagnosis, corresponding to 4.4% of the Italian population. A relevant geographical heterogeneity emerged, with a prevalence above 5% in northern registries and below 4% in southern areas. Men were 45% of the total (1,154,289) and women 55% (1,433,058). In the population aged 75 years or more, the proportions of prevalent cases were 20% in males and 13% in females, 11% between 60 and 74 years of age in both sexes. Nearly 600,000 Italian women were alive after a breast cancer diagnosis (41% of all women with this neoplasm), followed by women with cancers of the colon rectum (12%), corpus uteri (7%), and thyroid (6%). In men, 26% of prevalent cases (295,624) were patients with prostate cancer, 16% with either bladder or colon rectum cancer. The projections for 1.1.2015 are of three million (3,036,741) people alive after a cancer diagnosis, 4.9% of the Italian population; with a 20% increase for males and 15% for females, compared to 2010. The cure fractions were heterogeneous according to cancer type and age. Estimates obtained as the sum of cure fractions for all cancer types showed that more than 60% of patients diagnosed below the age of 45 years will reach the same mortality rate of the general population. This proportion decreased with increasing age and it was30% for cancer diagnosed after the age of 74 years. It was observed that 60% of all prevalent cases (1,543,531 people or 2.6% of overall Italian population) had been diagnosed5 years earlier (long-term survivors). Time to cure (5-year CRS95%) was reached in10 years by patients with cancers of the stomach, colon rectum, pancreas, corpus and cervix uteri, brain, and Hodgkin lymphoma. Mortality rates similar to the ones reported by the general population were reached after approximately 20 years for breast and prostate cancer patients. Five-year CRS remained95% for25 years after cancer diagnosis in patients with liver and larynx cancers, non-Hodgkin lymphoma, myeloma, and leukaemia. Time to cure was reached by 27% (20% in men and 33% in women) of all people living after a cancer diagnosis, defined as already cured.The study showed a steady increase over time (nearly +3% per year) of prevalent cases in Italy. A quarter of Italian cancer patients alive in 2010 can be considered as already cured. The AIRTUM Report 2014 describes characteristics of cancer patients and former-patients for 50 cancer types or combinations by sex and age. This detailed information promotes the conduction of studies aimed at expanding the current knowledge on the quality of life of these patients during and after the active phase of treatments (prevalence according to health status), on the long-term effects of treatments (in particular for paediatric patients), on the cost profile of cancer patients, and on rare tumours. All these observations have a high potential impact on health planning, clinical practice, and, most of all, patients' perspective.

Stage I colorectal carcinomas display a highly variable behavior which is not accurately predicted by the available prognostic markers. CD133 is considered a useful marker to identify the so-called cancer stem cells in colorectal cancers (CRCs) and its expression has been shown to have prognostic significance in CRC patients. This study aimed to verify whether immunohistochemical evaluation of CD133 might correlate with the progression risk of stage I CRC patients.Expression levels of the CD133 molecule were analyzed and compared in two series of stage I surgically resected CRC patients showing disease progression and death for the disease and patients with no evidence of disease progression after at least 6 years after surgery.A positive staining for CD133 was detected in 52% of the cases with poor prognosis and only in 9% of the group with good prognosis, and this difference was highly significant (p0.001). A significant correlation was detected between CD133 expression and histological parameters, such as tumor budding, vascular invasion, and presence of lymph node micrometastases but not tumor grading, gender, and age. Disease-free survival and cancer-specific survival of CD133 negative tumors were significantly longer compared to positive cases. In multivariate analyses, CD133 staining confirmed to be a predictor of shorter survival independent from vascular invasion but not from lymph nodes micrometastases.These findings demonstrate that CD133 immunostaining is a useful predictor of high risk progression in stage I CRC patients and might help to identify patients eligible for adjuvant chemotherapy.