Variations in the definition and perceived importance of positive resection margins in patients with colorectal cancer - an EYSAC international survey.

INTRODUCTION: Microscopically positive resection margins (R1) are associated with poorer outcomes in patients with colorectal cancer. However, different definitions of R1 margins exist. It is unclear to what extent the definitions used in everyday clinical practice differ within and between nations. This study sought to investigate variations in the definition of R1 margins in colorectal cancer and the importance of margin status in clinical decision-making. MATERIALS AND METHODS: A 14-point survey was developed by members of The European Society of Surgical Oncology (ESSO) Youngs Surgeons and Alumni Club (EYSAC) Research Academy targeting all members of the multidisciplinary team (MDT) treating patients with colorectal cancer. The survey was distributed on social media, in ESSO's monthly newsletter and via national societies. RESULTS: In total, 137 responses were received. Most respondents were from Europe (89.7%), with the majority from Denmark (56.9%). Less than 2/3 of respondents defined R1 margins as the presence of viable cancer cells ≤1 mm of the margin. Only 60% reported that subdivisions of R1 margins (primary tumour vs tumour deposit vs metastatic lymph node) are routinely available. More than 20% of respondents reported that pathology reports are not routinely reviewed at MDT meetings. Less than half of respondents considered margin status in decision-making for type and duration of adjuvant chemotherapy in Stage III colon cancer. CONCLUSION: The definitions and perceived clinical importance of microscopically positive margins in patients with colorectal cancer appear to vary. Adoption of an international dataset for pathology reporting may help to standardise current practices.

Assisted suicide in patients with cancer.

BACKGROUND: There are limited data on the long-term development and trends of assisted suicide (AS) among cancer patients. PATIENTS AND METHODS: Using data of the Swiss Federal Statistical Office, we analyzed AS trends over an 18-year period (1999-2016; total number of cases = 6553). RESULTS: Among patients who underwent AS, cancer was the most common underlying disease (n = 2704, 41.3% of all AS cases). The most common cancer types were lung (14.0% of cancer-related AS cases), breast (11.0%) and prostate (10.1%). There was a slight preponderance of men compared with women (51.5% versus 48.5%). The proportion of AS cases within cancer types did not change over time. The ratio of cancer-related AS cases in relationship with all cancer-related deaths increased from 0.3% at the beginning of the study period (1999-2003) to 2.1% from 2014 to 2016 (change of age-standardized rates for men: +488%; for women: +417%). At the end of the study period (2014-2016), there were only minor differences between cancer-specific ratios, highest and lowest range: 1.1% (liver cancer) and 2.8% (breast, esophageal and lip/oral cavity/oropharynx cancer). Individuals who underwent AS because of cancer were considerably younger than those who choose AS on account of other diseases (73 years versus 80 years). The median age of people with cancer-related AS was similar to that of all cancer-related deaths (74 years): for women, the median age of cancer-related AS was 72, whereas for men it was 75. The median age at which AS took place increased over time. CONCLUSIONS: During the study period, the proportion of people who chose cancer-related AS has approximately sextupled. However, AS among cancer patients remains rare and represents only ∼2% of all cancer-related deaths.

The impact of age on patient-reported outcomes after oncoplastic versus conventional breast cancer surgery.

PURPOSE: Some studies have indicated age-specific differences in quality of life (QoL) among breast cancer (BC) patients. The aim of this study was to compare patient-reported outcomes after conventional and oncoplastic breast surgery in two distinct age groups. METHODS: Patients who underwent oncoplastic and conventional breast surgery for stage I-III BC, between 6/2011-3/2019, were identified from a prospectively maintained database. QoL was prospectively evaluated using the Breast-Q questionnaire. Comparisons were made between women < 60 and ≥ 60 years. RESULTS: One hundred thirty-three patients were included. Seventy-three of them were ≥ 60 years old. 15 (20.5%) of them received a round-block technique (RB) / oncoplastic breast-conserving surgeries (OBCS), 10 (13.7%) underwent nipple-sparing mastectomies (NSM) with deep inferior epigastric perforator flap (DIEP) reconstruction, 23 (31.5%) underwent conventional breast-conserving surgeries (CBCS), and 25 (34.2%) received total mastectomy (TM). Sixty patients were younger than 60 years, 15 (25%) thereof received RB/OBCS, 22 (36.7%) NSM/DIEP, 17 (28.3%) CBCS, and 6 (10%) TM. Physical well-being chest and psychosocial well-being scores were significantly higher in older women compared to younger patients (88.05 vs 75.10; p < 0.001 and 90.46 vs 80.71; p = 0.002, respectively). In multivariate linear regression, longer time intervals had a significantly positive effect on the scales Physical Well-being Chest (p = 0.014) and Satisfaction with Breasts (p = 0.004). No significant results were found concerning different types of surgery. CONCLUSION: Our findings indicate that age does have a relevant impact on postoperative QoL. Patient counseling should include age-related considerations, however, age itself cannot be regarded as a contraindication for oncoplastic surgery.

Biomaterials and biophysical stimuli for bone regeneration.

First, we review basic concepts of Tissue Engineering, that is, how the tensegrity is able to modulate the cell behavior. Then, we review our experimental results regarding the bone tissue engineering via biomaterials and bioreactors.

Prevalence and incidence of osteoporotic fractures in patients on long-term glucocorticoid treatment for rheumatic diseases: the Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) study.

Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5) were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide relevant contributions to clinical practice, in particular by highlighting and quantifying in real life the prevalence of GIOP and relative fractures, the frequency of the main risk factors, and the currently sub-optimal prevention. Moreover, these results emphasize the importance of the underlying rheumatic disease on the risk of GIOP associated fractures.

The Standard Model from LHC to future colliders.

This review summarizes the results of the activities which have taken place in 2014 within the Standard Model Working Group of the "What Next" Workshop organized by INFN, Italy. We present a framework, general questions, and some indications of possible answers on the main issue for Standard Model physics in the LHC era and in view of possible future accelerators.

Batf3 deficiency proves the pivotal role of CD8α+ dendritic cells in protection induced by vaccination with attenuated Plasmodium sporozoites.

Increasing evidence indicates that hepatic CD8α+ dendritic cells (DCs) are important antigen cross-presenting cells (APC) involved in the priming of protective CD8+ T-cell responses induced by live-attenuated Plasmodium sporozoites. Experimental proof for a critical role of CD8α+ DCs in protective pre-erythrocytic malaria immunizations has pivotal implications for vaccine development, including improved vectored subunit vaccines. Employing Batf3-/- mice, which lack functional CD8α+ DCs, we demonstrate that deficiency of these particular APCs completely abolishes protection and corresponding signatures of vaccine-induced immunity. We show that in wild-type, but not in Batf3-/- , mice CD8α+ DCs accumulate in the liver after immunization with live irradiation-attenuated P. berghei sporozoites. IFN-γ production by Plasmodium antigen-specific CD8+ T cells is dependent on functional Batf3. In addition, our results demonstrate that the dysfunctional cDC-CD8+ T-cell axis correlates with MHC class II upregulation on splenic CD8α- DCs. Collectively, these findings underscore the essential role of CD8α+ DCs in robust protection induced by experimental live-attenuated malaria vaccines.

Severe polymyositis due to Toxoplasma gondii in an adult immunocompetent patient: a case report and review of the literature.

Toxoplasmosis, a worldwide zoonosis caused by a coccidian parasite Toxoplasma gondii, is more often asymptomatic in immunocompetent patients. We report the case of a 38-year-old immunocompetent male with a polymyositis as the presenting manifestation of T. gondii infection. The patient was hospitalized for a 30-day history of fever (T max 39.5°C), muscle pain, and progressive weakness of the muscles. A diagnosis of polymyositis was made, and he was started on corticosteroid treatment, which caused no reduction of symptoms. After finding a positive polymerase chain reaction (PCR) assay for T. gondii, together with additional clinical findings, a diagnosis of acute toxoplasmosis was made. Specific treatment with pyrimethamine and sulfadiazine was started, with a progressive reduction of symptoms and normalization of laboratory tests.

Energy balance in haemodialysis and peritoneal dialysis patients assessed by a 7-day weighed food diary and a portable armband device.

BACKGROUND: Energy balance (EB) is important when assessing nutritional status. EB has never been assessed in haemodialysis (HD) and peritoneal dialysis (PD) patients. The present study aimed to assess weekly EB in these patients. METHODS: This clinical cross-sectional study was conducted for 7 days in eight HD and eight PD patients. Nutritional status was assessed by anthropometry, bioelectrical impedance analysis and biochemical markers. Energy intake (EI per day) and total energy expenditure (TEE per day) were determined by a 7-day weighed food diary and a portable armband device, respectively. RESULTS: No significant differences in age, body mass index, fat free mass (FFM), parathyroid hormone were found between the two groups. EB was calculated by subtracting TEE per day from EI per day. EB was negative in HD {-1347 (1276) kJ day(-1) [-322 (305) kcal day(-1) ]}, as well as in PD patients {-427 (5338) kJ day(-1) [-102 (395) kcal day(-1) ]}. TEE per day was positively correlated with EI per day, prealbumin, FFM. EI per day was positively correlated with prealbumin. C-reactive protein was negatively correlated with TEE and FFM (P < 0.05). EB showed a positive correlation with EI per day (P = 0.012) and a negative trend with TEE. CONCLUSIONS: HD and PD patients have a negative EB and are at risk of malnutrition. Inflammatory status determines a lower EI per day and a reduction in TEE per day. The most important parameter in determining EB in HD and PD patients is EI per day. This topic deserves further investigation to better understand the mechanisms of impaired EB with respect to preserving patients' nutritional status.

Upper gastrointestinal symptoms in patients with advanced cancer: relationship to nutritional and performance status.

GOALS OF WORK: The goals of the study were to determine the relationship of upper gastrointestinal symptoms with nutritional status and to assess their association with performance status in patients with advanced cancer. MATERIALS AND METHODS: We studied 143 patients (50 F, 93 M, mean age 68 +/- 11 years, mean body mass index 22.39 +/- 4.3 kg/m(2)). Assessed symptoms were the following: anorexia, nausea, vomiting, dysphagia for solids, dysphagia for liquids, xerostomia, hypogeusia, dysgeusia, hiccup and chewing disturbances. We determined anthropometric parameters, daily energy intake and serum albumin, prealbumin and transferrin. MAIN RESULTS: The most common upper gastrointestinal symptoms were xerostomia (73%), anorexia (49%) and chewing disturbances (40%). Fifty-four percent of patients had weight loss greater than 10%. Seventy-three patients (51%) had daily energy intake lower than their resting energy expenditure. Mean serum prealbumin, albumin and transferrin were below normal range. Mean Eastern Cooperative Oncology Group performance status scale was 3.1 +/- 0.49. Symptoms were often strongly correlated, and usually, patients experienced at least three upper gastrointestinal symptoms at the same time. Anorexia, nausea and vomiting were the symptoms mostly correlated with other symptoms. A correlation was found between vomiting and hiccup. Energy intake (EI) was the nutritional parameter mostly affected by upper gastrointestinal symptoms; moreover, EI is the most predictive factor of upper gastrointestinal symptoms, particularly xerostomia, anorexia and dysphagia for solids. CONCLUSIONS: Upper gastrointestinal symptoms are linked to nutritional parameters: In particular, energy intake represents the most predictive variable of symptom occurrence. The performance status is not affected by upper gastrointestinal symptoms. A rigorous nutritional assessment and the managing of upper gastrointestinal symptoms are crucial in patients with advanced cancer.

RPGRIP1L mutations are mainly associated with the cerebello-renal phenotype of Joubert syndrome-related disorders.

Joubert syndrome-related disorders (JSRDs) are autosomal recessive pleiotropic conditions sharing a peculiar cerebellar and brainstem malformation known as the 'molar tooth sign' (MTS). Recently, mutations in a novel ciliary gene, RPGRIP1L, have been shown to cause both JSRDs and Meckel-Gruber syndrome. We searched for RPGRIP1L mutations in 120 patients with proven MTS and phenotypes representative of all JSRD clinical subgroups. Two homozygous mutations, the previously reported p.T615P in exon 15 and the novel c.2268_2269delA in exon 16, were detected in 2 of 16 families with cerebello-renal presentation ( approximately 12%). Conversely, no pathogenic changes were found in patients with other JSRD phenotypes, suggesting that RPGRIP1L mutations are largely confined to the cerebello-renal subgroup, while they overall represent a rare cause of JSRD (<2%).

Trace element levels in adult patients with proteinuria.

AIM: Trace elements are involved in many metabolic processes. They circulate prevalently bound to protein. In literature few studies deal with metal metabolism in adult patients with proteinuria, so we decided to further investigate metal metabolism in proteinuric patients. METHODS: We studied 27 patients (14 male, 13 female), mean age 61.6+/-17 years with different degrees of renal function, serum albumin and proteinuria. Metal concentrations of copper (Cu), zinc (Zn) and aluminum (Al) were measured in serum and urine. No patient had environmental exposure to these metals. RESULTS: The serum Zn level was below the normal range in 11 patients. The serum Cu level was reduced in 5 patients. The Al serum level was elevated in 4 patients. Six patients had reduced and 6 patients had elevated Zn excretion. The urinary Cu excretion was elevated in 6 patients. The urinary Al excretion was elevated in 1 patient. Trace metal concentrations were related neither to renal function nor to total serum protein or albumin levels. Serum zinc was directly correlated with proteinuria and urinary zinc and negatively correlated with testosterone levels in both sexes. CONCLUSION: Adult patients with proteinuria have several modification of trace metal concentration in serum and urine. Serum concentration of metals did not depend on renal function or serum protein levels. Urinary Zn excretion was directly related to proteinuria and serum Zn levels. A negative correlation between serum Zn levels and testosterone was found in both sexes. Renal failure reduced urinary excretion of Cu and Al.

Twelve-month azathioprine as maintenance therapy in early diffuse systemic sclerosis patients treated for 1-year with low dose cyclophosphamide pulse therapy.

OBJECTIVE: To investigate the role of azathioprine in maintaining improvement after 1-year low-dose IV pulse CYC therapy in patients with early diffuse Systemic Sclerosis (dcSSc). METHODS: Thirteen patients with early dcSSc who had completed a year of treatment with low-dose IV pulse CYC underwent AZA treatment (100 mg/day) in a prospective 1-year study. Modified Rodnan skin score (mRss), Health Assessment Questionnaire-Disability Index (HAQ-DI), forced vital capacity (FVC), and diffusing lung capacity for CO (DLCO) were assessed as outcome measures. In addition, the nine organ/system Medsger et al. severity scores and the European Scleroderma Study Group (ESSG) activity index were evaluated. RESULTS: The improvement from a year of CYC therapy was maintained by AZA treatment. No outcome measures deteriorated (mRss 8.23 +/- 2.9 vs. 6.38 +/- 3.4; HAQ-DI 0.38 +/- 0.4 vs. 0.32 +/- 0.3; FVC 89.5 +/- 13.2 vs. 89.4 +/- 15.9; DLCO 73.6 +/- 14.4 vs. 75.0 +/- 19.5), nor were there any increases in any organ/system severity scores or ESSG activity index detected. CONCLUSION: This study suggests a role of AZA in maintaining the improvement induced by low dose pulse CYC in early dcSSc, making it possible a short duration of treatment at a low cumulative dose of the drug. These results, however, await confirmation in controlled studies.

Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients.

OBJECTIVE: Fibromyalgia (FMS) is a chronic syndrome characterized by widespread pain, troubled sleep, disturbed mood, and fatigue. Several analgesic strategies have been evaluated but the results are moderate and inconsistent. Antidepressant agents are now considered the treatment of choice in most patients. It has been recently suggested that FMS may be associated with metabolic alterations including a deficit of carnitine. In this multicenter randomized clinical trial we evaluated the efficacy of acetyl L-carnitine (LAC) in patients with overt FMS. METHODS: One hundred and two patients meeting the American College of Rheumatology criteria for FMS were randomized into the study. The treatment consisted of 2 capsules/day of 500 mg LAC or placebo plus one intramuscular (i.m.) injection of either 500 mg LAC or placebo for 2 weeks. During the following 8 weeks the patients took 3 capsules daily containing either 500 mg LAC or placebo. The patients were seen during treatment after 2 (visit 3), 6 (visit 4) and 10 weeks (visit 5). The patients were also visited 4 weeks after treatment discontinuation (follow-up visit). Outcome measures included the number of positive tender points, the sum of pain threshold (kg/cm2 or "total myalgic score"), the Short Form 36 (SF36), a 100 mm visual analog scale (VAS) for self-perceived stiffness, fatigue, tiredness on awakening, sleep, work status, depression, and muscular-skeletal pain, and the Hamilton depression scale. RESULTS: The "total myalgic score" and the number of positive tender points declined significantly and equally in both groups until the 6th week of treatment. At the 10th week both parameters remained unchanged in the placebo group but they continued to improve in the LAC group with a statistically significant between-group difference. Most VAS scores significantly improved in both groups. A statistically significant between-group difference was observed for depression and musculo-skeletal pain. Significantly larger improvements in SF36 questionnaire were observed in LAC than in placebo group for most parameters. Treatment was well-tolerated. CONCLUSION: Although this experience deserves further studies, these results indicate that LAC may be of benefit in patients with FMS, providing improvement in pain as well as the general and mental health of these patients.

[Pregnancy in chronic dialysis. A case report and a review of the literature]. / La gravidanza in dialisi cronica: esperienza personale e revisione della letteratura.

A case report of a pregnancy in a patient with end-stage renal disease on chronic dialysis is presented. The epidemiological data regarding this rare event and the factors influencing and limiting fertility in uremic women are discussed. The outcomes of pregnancy in dialysis as reported in national registries and literature series are analyzed. For the management of pregnancy in dialysis several practical problems have to be dealt with: the type of dialysis, sterilization of dialysis materials, dialysis dose, dialysis bath composition, extracorporeal circuit anticoagulation, and the diet of the pregnant woman. All these issues are discussed, with special attention to solutions facilitating the best outcome of pregnancy. Finally, the main complications of both normal and uremic pregnancies, anemia and hypertension, are discussed together with the solutions proposed in this particular condition.

Leflunomide in psoriatic arthritis: a retrospective study of discontinuation rate in daily clinical practice compared with methotrexate.

OBJECTIVE: To assess the safety profile of leflunomide (LEF) in a two-year retrospective analysis of psoriatic arthritis (PsA) patients (pts) treated in daily clinical practice compared with methotrexate (MTX). PATIENTS: Fourty-two PsA patients with polyarticular involvement or asymmetrical oligoarticular arthritis, satisfying ESSG criteria for the spondyloarthropathies, treated with LEF monotherapy (10-20mg/die without loading dose) between September, 2004 and August, 2006 were reviewed. They were compared with MTX (7.5-15mg/week) users (44 cases). The adverse events (AEs) and the causes of withdrawal were evaluated. RESULTS: At 24 months, cumulative survival rate of pts remaining on drugs was 54.9% in LEF users and 57.0% in MTX users (p > 0.05). The discontinuation rate (DR) for toxicity was higher in LEF group (29.2%) than in MTX group (10.8%) (p = 0.07). The occurrence of AEs was more frequently registered in the first year in both groups. LEF monotherapy showed a significant higher crude incidence for any AEs (38.7 events x100 person-years) compared to MTX (14.3 events x100 person-years) (p < 0.001). The cumulative DR for inefficacy was greater but not statistically significant in MTX group than LEF (28.6% vs. 12.6% respectively; p = 0.056). Finally, DR for other causes accounted for 8.7% vs. 11.0% respectively (p > 0.05). CONCLUSIONS: Our data showed, in a setting of clinical practice, that the rate of PsA pts remaining on drug was comparable between LEF and MTX, and a manageable LEF safety profile during a 24 months of follow-up, even if a greater incidence of DR for AEs was registered than in MTX users.

[Metabolic syndrome in inflammatory rheumatic diseases]. / La sindrome metabolica nelle malattie reumatiche infiammatorie.

Toward the end of the last century a better knowledge of cardiovascular (CV) risk factors and their associations led investigators to propose the existence of a unique pathophysiological condition called "metabolic" or "insulin resistance syndrome". Among all, insulin-resistance and compensatory hyperinsulinemia are considered its most important treatment targets. Different definitions have been provided by World Health Organization (WHO) and by The Third Report of The National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP III). In particular, abdominal obesity, hypertension, low HDL cholesterol and hyperglicemia are the most common items used for its definition. The presence of MetS is effective in predicting the future risk of diabetes and coronaropathies. The evidence of a higher CV risk rate among different rheumatic inflammatory diseases has recently been associated with high prevalence of MetS in some cases. Rheumatoid or psoriatic arthritis have the large series among arthritis, whereas systemic lupus erythematosus among connective tissue disorders. This review analyses all most important studies about the evidence of MetS in rheumatic patients and the main clinical and prognostic significance of this relation.