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Background The aim of the present study was to investigate the possible correlation between various inflammation-nutritional scores to histological determined Non-Alcoholic Steatohepatitis (NASH) and other liver injury suggestive for Non-Alcoholic Fatty Liver Disease (NAFLD) in a bariatric population. Methods We evaluated consecutively and retrospectively all the patients referred to the department of bariatric surgery in Trieste, Italy. Inflammation-nutritional scores were calculated starting from pre-operative hematologic data. Liver biopsy was performed at the time of bariatric surgery (sleeve gastrectomy or gastric bypass) and pathological assessment was performed using Kleiner-Brunt staging system (NAS score). Results Glasgow Prognostic Score/modified Glasgow Prognostic Score (GPS/ mGPS) and Prognostic Index (PI) were associated to the diagnosis of NASH (p= 0,024 and p=0,03 respectively). The presence of perisinusoidal and/or periportal fibrosis was correlated to Prognostic Nutritional Index (PNI) and Platelet-to-Lymphocyte ratio (PLR) values (p=0,02 and p=0,009 respectively). Conclusions GPS/mGPS and PI are statistically associated to the histological diagnosis of NASH. Further studies on large series are needed to better understand the relationship between these serum markers and liver injury in obese patients.

Objective: Recently, a novel host‐related index, the Host‐index (H‐index), including both inflammatory and nutritional markers, has been described and observed to stratify prognosis in patients with squamous cell carcinoma (SCC) of the oral cavity more accurately than other host‐related indexes This study aimed to investigate the prognostic performance of the H‐index using pretreatment blood tests in patients receiving up‐front surgery for SCC of the larynx. Methods: This retrospective observational study included a multicenter series of consecutive patients with SCC of the larynx diagnosed between 1 January 2009 and 31 July 2018, whose pretreatment blood tests were available and included the parameters necessary for the calculation of neutrophil to lymphocyte ratio (NLR) and the H‐index. Their association with disease‐free survival (DFS) and overall survival (OS) was measured. Results: A total of 231 patients were eligible for the present analysis (median [range] age, 68 [37‐96] years; 191 [82.7%] men). The median follow‐up was 73 months. In multivariable Cox proportional hazards regression models, increasing age (adjusted hazard ratio [aHR], 1.07 per year; 95% CI, 1.04‐1.09), advanced pT stage (aHR = 1.71 95% CI: 1.07‐2.71), and having close or positive surgical margins (aHR = 2.01; 95% CI: 1.21‐3.33) were significantly associated with poor OS. Among blood parameters, a higher neutrophil count was a strong predictor of both worse DFS (aHR for recurrence/death = 2.34; 95% CI: 1.24‐4.40) and OS (aHR for death = 2.67; 95% CI: 1.51‐4.71). Among inflammatory blood indexes, while NLR was not significantly associated with DFS or OS, patients with H‐index ≥8.37 showed a higher aHR for both recurrence/death (2.82; 95% CI: 1.65‐4.79) and death (2.22; 95% CI: 1.26‐3.89). Conclusion: In conclusion, the present study confirms the prognostic value of pretreatment H‐index, an easily measurable inflammatory and nutritional index, in patients with SCC of the larynx. Level of Evidence: III

Background: Poly (ADP-ribose) polymerase-inhibitors (PARPis) showed antitumour activity in BRCA1/2-mutated cancers, with more heterogeneous outcomes in tumours harbouring mutations that impair other genes involved in the DNA homologous recombination repair (HRR) or wild-type (wt). Methods: We conducted a systematic review and meta-analysis to better assess the role of PARPis in the treatment of metastatic solid tumours, with and without BRCA1/2 mutations. The primary end-point was progression-free survival (PFS). The secondary end-points were overall response rate (ORR) and overall survival (OS). A random-effects model was applied. Results: Twenty-nine studies (8,839 patients) were included. PFS was significantly improved (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.51-0.68, p < 0.001), without being affected by BRCA mutational status (p = 0.65). Significant subgroup differences were observed with regard to the tumour site (p = 0.001), line of therapy (p = 0.002), control arm (p < 0.001), type of PARPi (p < 0.001) and trials' phase (p = 0.006). PARPis were associated with ORR (relative risk: 1.35, 95% CI: 1.16-1.56, p < 0.001), with significant subgroup differences observed with regard to treatment line (p = 0.03), control arm (p = 0.04) and PARPis (p < 0.001) and independent of mutational status (p = 0.44), tumour site (p = 0.86) and trials' phase (p = 0.09). OS was significantly improved by PARPis (HR: 0.86, 95% CI: 0.80-0.92, p < 0.001), regardless of mutational status (p = 0.57), tumour site (p = 0.82), treatment line (p = 0.22), control arm (p = 0.21), PARPis (p = 0.30) and trials' phase (p = 0.26). Finally, an exploratory subgroup analysis showed a significant PFS improvement (HR: 0.51, 95% CI: 0.43-0.60, p < 0.001) with PARPis in BRCA-wt/HRR-deficient tumours. Conclusion: Our results confirm the efficacy of already approved PARPi-based treatments in BRCA1/2-mutant solid tumours, support their role also in BRCA-independent HRR-deficient tumours and suggest a potentially broader efficacy in some wt tumours, perhaps with appropriate therapeutic partners. Prospective studies are warranted.

Purpose: Prediction algorithms estimating survival rates for breast cancer (BC) based upon risk factors and treatment could give a help to the clinicians during multidisciplinary meetings. The aim of this study was to evaluate accuracy and clinical utility of three different scores: the Clinical Treatment Score Post-5 Years (CTS5), the PREDICT Score, and the Nottingham Prognostic Index (NPI). Methods: This is a retrospective cohort analysis conducted on prospectively recorded databases of two EUSOMA certified centers (Breast Unit of Trieste Academic Hospital and of Cremona Hospital, Italy). We included patients with Luminal BC undergone to breast surgery between 2010 and 2015, and subsequent endocrine therapy for 5 years for curative intent. Results: A total of 473 patients were enrolled in this study. ROC analysis showed fair accuracy for NPI, good accuracy for PREDICT, and optimal accuracy for CTS5 (AUC 0.7, 0.76, and 0.83, respectively). The three scores seemed strongly correlated in Spearman's rank correlation coefficient analysis. PREDICT partially overestimated OS in patients undergone to mastectomy, and in pT3-4, G3 tumors. Considering DRFS as a surrogate of OS, CTS5 showed women in intermediate and high risk class had shorter OS too (respectively p = 0.001 and p < 0.001). Combining scores does not improve prognostication power. Conclusion: Mathematical models may help clinicians in decision making (adjuvant therapies, CDK4/6i, genomic test's gray zones). CTS5 has the higher prognostic accuracy in predicting recurrence, while score predicting OS did not show substantial advances, proving that pN, G, and pT are still the most important variables in predicting OS.

Bile duct injury is a major complication of laparoscopic cholecystectomy (LC). Intraoperative cholangiogram is useful, but faster techniques are available to assist the surgeon, like near-infrared fluorescent cholangiography (NIFC) with indocyanine green (ICG). The aim of our study is to evaluate the usefulness of NIFC during LC. This is a retrospective study conducted on prospectively recorded data of the General Surgery department of Trieste Academic Hospital, Italy. All patients underwent elective LC from January 2016 to January 2020. Patients were randomly divided in 2 groups: in one group, only white light imaging was used (n = 98 patients), in the NIFC group (n = 63) ICG was used. NIFC has been chosen more frequently by residents than consultants ( P = .002). Operative time and length of stay resulted shorter in ICG group ( P = .002 and .006), and this group showed also fewer intraoperative complications ( P = .007). NIFC does not require any learning curve and makes surgery faster and safer.

Objectives Although the reliability of frozen sections for the intraoperative assessment of complete tumour excision has been established, the best location for collection and the impact of the type of sampling are still debated. We retrospectively investigated the reliability of frozen sections when collected from the surgical bed as tissue strips representative of the whole superficial margin and as a bowl of tissue underlying the resection site for deep margin, and the possibility of relying on frozen section negativity to consider resections complete. Materials and methods Frozen section reliability was calculated by comparing histology before and after formalin embedding and then categorised by sampling type, in 182 patients undergoing transoral resection of oral cancer. Results Comparing frozen and permanent histology, sensitivity, specificity and accuracy were 69%, 98% and 96%, respectively; categorisation by sampling type failed to produce statistically significant differences. Based on frozen section negativity after formalin embedding, complete resections were obtained in 91.7% of patients with multiple-strip and bowl frozen sections. Conclusion Frozen sections collected as tissue strips and bowl are as reliable as point sampling in the intraoperative guidance of surgical resections. They effectively provide for margin enlargement, thereby increasing the surgeon's confidence that negative margins are clear.

Context Current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold standard for assessing aortic stiffness, and it predicts cardiovascular morbidity and mortality. Objective Primary outcomes were to investigate if mild pHPT was associated with higher PWV and if parathyroidectomy (PTX) reduced PWV in mild pHPT. Secondary outcome was to investigate blood pressure changes after PTX. Methods Sources were PubMed, Google Scholar, SCOPUS, Web of Science, and the Cochrane Library. Eligible studies included reports of PWV in patients with mild pHPT and controls, or in patients with mild pHPT before and after PTX. Two investigators independently identified eligible studies and extracted data. Pooled mean difference (MD) was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Nine observational studies and one randomized clinical trial were selected, including 433 patients with mild pHPT, 171 of whom underwent PTX, and 407 controls. PWV was significantly higher in mild pHPT than in controls (MD = 1.18, 0.67 to 1.68, P < .0001). Seven studies evaluated the effect of PTX on PWV. PTX significantly reduced PWV (MD = –0.48, –0.88 to –0.07, P = .022). Conclusion Aortic stiffness is increased in patients with mild pHPT, supporting the notion that mild pHPT is also associated with adverse cardiovascular manifestations. PTX significantly reduced arterial stiffness in mild pHPT, indicating that the benefit of PTX over cardiovascular manifestations should not be dismissed but it deserves further studies.

Cancer patients may be at high risk of infection and poor outcomes related to SARS-CoV-2. Analyzing their prognosis, examining the effects of baseline characteristics and systemic anti-cancer active therapy (SACT) are critical to their management through the evolving COVID-19 pandemic. The AIOM-L CORONA was a multicenter, observational, ambispective, cohort study, with the intended participation of 26 centers in the Lombardy region (Italy). A total of 231 cases were included between March and September 2020. The median age was 68 years, 151 patients (62.2%) were receiving SACT, mostly chemotherapy. During a median follow-up of 138 days (range 12–218), 93 events occurred. Age ≥60 years, metastatic dissemination, dyspnea, desaturation, and interstitial pneumonia were all independent mortality predictors. Overall SACT had a neutral effect (Odds Ratio [OR] 0.83, 95%Confidence Interval [95%CI] 0.32–2.15), however, metastatic patients receiving SACT were less likely to die as compared to untreated counterparts, after adjusting for other confounding variables (OR 0.23, 95%CI 0.11–0.51, p &lt, 0.001). Among cancer patients infected by SARS-CoV-2, those with metastases were most at risk of death, especially in the absence of SACT. During the ongoing pandemic, these vulnerable patients should avoid exposure to SARS-CoV-2, while treatment adjustments and prioritizing vaccination are being considered according to international recommendations.

BackgroundResults Biomarkers may play a role as predictive and prognostic factors in colorectal cancer patients. The aims of the study were to verify the prognostic role of pre-operative serum carcinoembryonic antigen (CEA) level in predicting overall survival and risk of recurrence in a cohort of colorectal cancer patients and to evaluate optimal cut-off values.Methods A retrospective cohort analysis was performed on colorectal cancer patients undergoing elective curative surgery between 2004 and 2019 at an Italian Academic Hospital. Main outcomes were overall survival, disease-free survival at 3-years and risk of local, loco-regional and distant recurrence during follow-up. A receiver operating characteristic (ROC) curve analysis was plotted using CEA pre-operative values and follow-up data in order to estimate the optimal cut-off values.A total of 559 patients were considered. The mean CEA value was 12.1 +/- 54.1 ng/mL, and the median 29.3 (0-4995) ng/mL. The ROC curve analysis identified 12.5 ng/mL as the best CEA cut-off value to predict the risk of metastatic development after surgery in stage I-III colorectal cancer patients, and 10 ng/mL as the best CEA cut-off value to predict overall survival and disease-free survival in stage III-IV patients. These data suggest a stratification of colorectal cancer patients in three classes of risk: a low risk class (CEA 12.5 ng/mL).Conclusion In conclusion, pre-operative serum CEA measurements could integrate information to enhance patient risk stratification and tailored therapy.

Background. Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD). This prospective observational study aimed at the evaluation of any correlation between genetic variants associated with IPF susceptibility and high-resolution computed tomography (HRCT) patterns. It also aimed at evidencing any differences in the HRTC pattern between the familial and sporadic form at diagnosis and after two years. Methods. A total of 65 IPF patients (mean age at diagnosis 65 ± 10) were enrolled after having given written informed consent. HRCT and genetic evaluations were performed. Results. A total of 19 familial (mean age 62 ± 15) and 46 sporadic (mean age 70 ± 9) IPF patients were enrolled. A statistically significant difference was evidenced in the HRTC pattern at diagnosis between the two groups. Sporadic IPF patients had a predominantly usual interstitial pneumonia (UIP) pattern compared with those patients with familial IPF (60.0% vs. 21.1%, respectively). Moreover, familial IPF patients had more alternative diagnoses than those with sporadic IPF (31.6% vs. 2.2%, respectively). Furthermore, there was a slight increase in the typical UIP pattern in the familial IPF group at two years from diagnosis. Conclusions. Genetic factors play a pivotal role in the risk of developing IPF. However, further studies are required to clarify how these genetic factors may guide clinical treatment decisions.

BackgroundRadiofrequency ablation (RFA) has gained ground as an effective and well-tolerated technique to treat benign thyroid nodules. Most of the available studies have described the short-term outcomes of RFA, whereas there is a limited number of studies evaluating long-term issues, such as regrowth and the likelihood of retreatments. In addition, risk markers of regrowth and retreatment remain to be defined. The initial ablation ratio (IAR) is an index that measures the amount of ablation after RFA, which has been associated with technique efficacy (i.e. volume reduction >50% after 1 year from the procedure). This study aimed at evaluating i) IAR reproducibility and ii) IAR predictive value for RFA 5-year outcomes.Materials and MethodsThis is a retrospective single center study on patients with benign thyroid nodules treated with RFA and followed for 5 years after initial treatment. IAR interobserver reproducibility was evaluated with Bland-Altman method and Lin’s concordance correlation coefficient (ρc). IAR predictive value for RFA 5-year outcomes was evaluated with linear and logistic regression models, as well as with Cox models, while receiver operating characteristic (ROC) analyses were used for cut-offs.ResultsWe selected 78 patients with 82 benign thyroid nodules. The procedure significantly reduced nodule volume and this reduction was generally maintained over time. Technique efficacy was achieved in 92% of patients, while 23% of nodules regrew and 12% of nodules were retreated. Median IAR was 83%. Lin’s concordance and Pearson’s correlation coefficients suggested a good interobserver reproducibility of this index, consistent with the limits of agreement of the Bland-Altman plot. IAR was significantly associated with technique efficacy, 1- and 5-year volume reduction ratio, and with the likelihood of a retreatment, but not with nodule regrowth. ROC analyses showed that IAR cut-off was 49% for technique efficacy and 73% for retreatment.ConclusionsOur results show for the first time that IAR is reproducible and that it predicts the volume reduction and the likelihood of a retreatment after 5 years from RFA.

Background Adult patients with both inflammatory bowel disease (IBD) and celiac disease (CeD) have peculiar phenotypic features. This study aimed at describing the characteristics and natural history of children with both IBD and CeD. Methods This was a case-control study based on a national registry. Cases included children diagnosed with both IBD and CeD. Two matched IBD controls without CeD, and 2 matched CeD controls were selected for each case. Inflammatory bowel disease phenotype and natural history, comprising growth and pubertal development, were compared between groups. Results Forty-nine (1.75%) patients with IBD and CeD were identified out of 2800 patients with IBD. Compared with patients with IBD alone, patients with IBD and CeD presented more frequently with autoimmune diseases (odds ratio, 2.81; 95% CI, 0.97–8.37; P = 0.04). Ileocolonic localization (46.1% vs 73.1%), treatment with azathioprine (46.2% vs 71.2%), and anti-TNF biologics (46.2% vs 69.2%) were less common in patients with Crohn’s disease and CeD than in patients with Crohn’s disease alone. Patients with ulcerative colitis and CeD had an increased risk of colectomy despite similar medical treatments compared with patients with ulcerative colitis alone (13.0% vs 0%). Pubertal delay was more common in patients with IBD and CeD compared with patients with IBD alone (14.9% vs 3.2%; odds artio, 5.24; 95% CI, 1.13–33.0; P = 0.02) and CeD alone (14.9% vs 1.1%; P = 0.002). Conclusions Children with IBD and CeD may have peculiar features with a higher risk for autoimmune diseases, colectomy, and pubertal delay compared with IBD alone.

Background and objectives: Cryoablation is emerging as a safe and effective therapeutic option for treating renal cell carcinoma. This study analyzed the safety and long-term oncological outcomes of cryoablation in our center. Materials and methods: Patients who underwent computed tomography (CT)-guided percutaneous cryoablation between February 2011 and June 2020 for one or more clinically localized renal tumors were identified. Technical success and treatment efficacy were assessed. Post-procedural complications were classified according to the Clavien-Dindo system. Recurrence–free survival was determined for biopsy-proven malignant renal tumors. Results: A total of 174 renal tumors, 78 of which were biopsy-proven malignant carcinomas, were treated in 138 patients (97 males and 41 females, mean age: 73 years, range: 43–89 years). Mean tumor size was 2.25 cm and 54.6% of the lesions required a complex approach. Technical success was achieved in 171 out of 174 tumors (98.3%). Primary treatment efficacy was 95.3% and increased to 98.2% when retreats were taken into account. The overall complication rate was 29.8%. No complications of Clavien-Dindo grade III or more were encountered. Median follow-up was 21.92 months (range: 0.02–99.87). Recurrence-free survival was 100% at 1 year, 95.3% (95% CI: 82.1%–98.8%) at 3 years, and 88.6% (95% CI: 71.8%–95.7%) at 5 years. Conclusions: Cryoablation is a safe and effective technique for the treatment of small renal lesions, with no major complications when performed by expert interventional radiologists. The multidisciplinary discussion is essential, especially considering the high number of histologically undetermined lesions. Our long-term oncological outcomes are encouraging and in line with the literature.

The aim of this study was to investigate the correlation between psychological distress and taste and sense of smell dysfunctions on healthcare workers (HCW) who contracted the COVID-19 infection in the midst of the disease outbreak. Reports of sudden loss of taste and smell which persist even after recovery from COVID-19 infection are increasingly recognized as critical symptoms for COVID-19 infections. Therefore, we conducted a cross-sectional study on COVID-19 HCW (N = 104) who adhered to respond to a phone semistructured interview addressing the virus symptoms and associated psychological distress. Data were collected from June to September 2020. Findings confirm the association between experienced taste/olfactory loss and emotional distress and suggest that dysfunctions of taste and smell correlate positively with anxiety and depression. Furthermore, their psychological impact tends to persist even after the recovery from the disease, suggesting the need for appropriate psychological interventions to prevent people from developing more serious or long-lasting psychological disorders and, as far as HCW, to reduce the risk of work-related distress.

Patients undergoing colon resection are often concerned about their functional outcomes after surgery. The primary aim of this prospective, multicentric study was to assess the intestinal activity and health-related quality-of-life (HRQL) after ileocecal valve removal. The secondary aim was to evaluate any vitamin B12 deficiency. The study included patients undergoing right colectomy, extended right colectomy and ileocecal resection for either neoplastic or benign disease. Selected items of GIQLI and EORTC QLQ-CR29 questionnaires were used to investigate intestinal activity and HRQL before and after surgery. Blood samples for vitamin B12 level were collected before and during the follow-up period. The empirical rule effect size (ERES) method was used to explain the clinical effect of statistical results. Linear mixed effect (LME) model for longitudinal data was applied to detect the most important parameters affecting the total score. A total of 158 patients were considered. Applying the ERES method, the analysis of both questionnaires showed clinically and statistically significant improvement of HRQL at the end of the follow-up period. Applying the LME model, worsening of HRQL was correlated with female gender and ileum length when using GIQLI questionnaire, and with female gender, open approach, and advanced cancer stage when using the EORTC QLQ-CR29 questionnaire. No significant deficiency in vitamin B12 levels was observed regardless of the length of surgical specimen. In our series, no deterioration of HRQL and no vitamin B12 deficiency were found during the follow-up period. Nevertheless, warning patients about potential changes in bowel habits is mandatory. In our series, no deterioration of HRQL and no vitamin B12 deficiency were found during the follow-up period. Nevertheless, warning patients about potential changes in bowel habits is mandatory.

Simple Summary Hormone receptor-positive (HR+)/HER2-negative is the most frequent subgroup of metastatic breast cancer (MBC). Important therapeutic advances in the treatment of this tumor type have been observed in the last 20 years, with the approval of numerous endocrine therapies (ET) with or without target therapies (TT). To improve our current knowledge and support clinical decision-making, we conducted a systematic literature and meta-analysis focused on the most relevant/promising first-/second-line ET ± TT of the last 20 years. We observed that CDK4/6-inhibitors(i) + ET were the most effective regimens. At the same time, mTORi-based combinations proved to be a valid therapeutic option in endocrine-resistant tumors, as well as PI3Ki + ET in PIK3CA-mutant patients. Single agent ET might still be a valuable upfront treatment in endocrine sensitive and non-visceral disease. Abstract A precise assessment of the efficacy of first-/second-line endocrine therapies (ET) ± target therapies (TT) in clinically-relevant subgroups of hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC) has not yet been conducted. To improve our current knowledge and support clinical decision-making, we thus conducted a systematic literature search to identify all first-/second-line phase II/III randomized clinical trials (RCT) of currently approved or most promising ET ± TT. Then, we performed a meta-analysis to assess progression-free (PFS) and/or overall survival (OS) benefit in several clinically-relevant prespecified subgroups. Thirty-five RCT were included (17,595 patients). Pooled results show significant reductions in the risk of relapse or death of 26–41% and 12–27%, respectively, depending on the clinical subgroup. Combination strategies proved to be more effective than single-agent ET (PFS hazard ratio (HR) range for combinations: 0.60–0.65 vs. HR range for single agent ET: 0.59–1.37; OS HR range for combinations: 0.74–0.87 vs. HR range for single agent ET: 0.68–0.98), with CDK4/6-inhibitors(i) + ET being the most effective regimen. Single agent ET showed comparable efficacy with ET+TT combinations in non-visceral (p = 0.63) and endocrine sensitive disease (p = 0.79), while mTORi-based combinations proved to be a valid therapeutic option in endocrine-resistant tumors, as well as PI3Ki + ET in PIK3CA-mutant tumors. These results strengthen international treatment guidelines and can aid therapeutic decision-making.

Background Breast intraoperative electron radiation therapy (B-IOERT) can be used in clinical practice both as elective irradiation (partial breast irradiation – APBI) in low risk breast cancer patients, and as an anticipated boost. The procedure generally includes the use of a shielding disk between the residual breast and the pectoralis fascia for the protection of the tissues underneath the target volume. The aim of the study was to evaluate the role of intraoperative ultrasound (IOUS) in improving the quality of B-IOERT. Patients and methods B-IOERT was introduced in Trieste in 2012 and its technique was improved in 2014 with IOUS. Both, needle and IOUS were used to measure target thickness and the latter was used even to check the correct position of the shielding disk. The primary endpoint of the study was the evaluation of the effectiveness of IOUS in reducing the risk of a disk misalignment related to B-IOERT and the secondary endpoint was the analysis of acute and late toxicity, by comparing two groups of patients treated with IOERT as a boost, either measured with IOUS and needle (Group 1) or with needle alone (Group 2). Acute and late toxicity were evaluated by validated scoring systems. Results From the institutional patients who were treated between June 2012 and October 2019, 109 were eligible for this study (corresponding to 110 cases, as one patients underwent bilateral conservative surgery and bilateral B-IOERT). Of these, 38 were allocated to group 1 and 72 to group 2. The target thickness measured with the IOUS probe and with the needle were similar (mean difference of 0.1 mm, p = 0.38). The percentage of patients in which the shield was perfectly aligned after IOUS introduction increased from 23% to more than 70%. Moreover, patients treated after IOUS guidance had less acute toxicity (36.8% vs. 48.6%, p = 0.33) from radiation therapy, which reached no statistical significance. Late toxicity turned out to be similar regardless of the use of IOUS guidance: 39.5% vs. 37.5% (p = 0.99). Conclusions IOUS showed to be accurate in measuring the target depth and decrease the misalignment between collimator and disk. Furthermore there was an absolute decrease in acute toxicity, even though not statistically significant, in the group of women who underwent B-IOERT with IOUS guidance.

Anastomotic leakage (AL) represents one of the most relevant complications of colorectal cancer surgery. The aim of this study was to evaluate the utility of intraoperative indocyanine green (ICG) fluorescence imaging in the prevention of AL during laparoscopic colorectal surgery. Methods. We retrospectively analyzed 272 patients who underwent rectal and left colon surgery, consecutively enrolled between 2015 and 2019. Due to the heterogeneity of our groups, a propensity score matching (PSM) was performed with a 1:1 PSM cohort. Results. AL occurred in 36 (13.2%) patients. One hundred seventy-seven (65%) of them underwent an intraoperatory ICG test (ICG-group), whereas 95 patients (35%) did not receive the intraoperatory ICG test (no-ICG group). AL occurred in 10.8% of ICG group patients and in 17.8% of no-ICG group patients ( P = 0.07). The ICG group registered significantly less type B and type C fistulas than the no-ICG group (57.9 vs 88.2%; P = .043). After PSM, the overall AL rate was less in the ICG group than the no-ICG group (9.3% vs 16%; P = 0.058), while type B and type C fistulas occurred in 5.48% in the ICG group vs 13.70% in the no-ICG group ( P = 0.09). Univariate analysis demonstrated a protective effect of intraoperative ICG imaging against AL occurrence (odds ratio (OR: 0.66)). Conclusions. Hypoperfusion is a well-recognized cause of AL. The ICG assessment of colic vascularization is a simple, inexpensive, and side effects free method, which can sensibly reduce both overall AL and type B and type C fistulas when routinely used.

Aim: To investigate the role of endothelial PV-1 in patients with untreated celiac disease (CD)-associated liver injury. Materials & methods: PV-1 and PV-1 mRNA were measured in intestinal biopsies from untreated CD patients with elevated or normal alanine transaminase levels, controls, patients with inflammatory bowel disease and patients with toxic liver injury. Circulating PV-1 levels were also evaluated. Results: Circulating PV-1 levels were significantly increased in the serum of patients with CD-associated liver injury and reverted to normal following a gluten-free diet. Mucosal PV-1 and PV-1 mRNA were no different in patients with CD-associated liver injury. Conclusion: Serum but not mucosal PV-1 represents a marker of gluten-dependent liver injury and response to a gluten-free diet in patients with untreated CD.

Background: Intestinal coeliac auto-antibodies are the marker of coeliac disease (CD). Since the determination of these antibodies is still not widely available, we used immunoassays to identify the most suitable technology for revealing intestinal auto-antibodies in the wide clinical spectrum of CD. Methods: Intestinal auto-antibodies have been prospectively investigated in CD suspected children using two immunoassays: intestinal-deposits of IgA anti-tissue transglutaminase antibodies (anti-tTG) and biopsy-culture IgA anti-endomysium (AEA). Intestinal IgM antibodies have been determined in IgA-deficient subjects. Findings: Two-hundred and twenty-one suspected CD patients were enrolled. Intestinal antibodies were tested positive for both assays in classical CD patients (n = 178) with villous atrophy and positive serum-CD antibodies, potential CD patients (n = 16) with normal intestinal mucosa and positive serum-CD antibodies, and pre-potential CD patients (n = 14) with normal intestinal mucosa and negative serum-CD antibodies. In 13/221 with normal intestinal mucosa, negative CD-serum antibodies and negative intestinal antibodies CD has been excluded. All classical, 14/16 potential and 11/14 pre-potential CD patients on gluten-free diet (GFD) improved their symptoms. In 9/11 pre-potential patients intestinal antibodies disappeared on GFD. Both assays were negative in 69/71 control subjects. The two assays showed high diagnostic sensitivity (100%) and specificity (99%). Interpretation: Intestinal CD-antibodies make prompt diagnosis in the wide clinical spectrum of CD reducing the delay in diagnosis and treatment, especially in pre-potential CD patients. The easy handling biopsy culture assay is an effective diagnostic tool which should be carried out by any gastroenterology unit to recognize all CD clinical manifestations. Funding: Interreg Central-Europe, IRCCS “Burlo Garofolo”. Keywords: Biopsy culture, Coeliac disease, Diagnosis, Gluten-free diet, Intestinal deposits

Purpose mTOR inhibitor everolimus is used for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (mBC). No reliable predictive biomarker of response is available. Following evidences from other solid tumors, we aimed to assess the association between treatment-associated immune system features and everolimus activity. Methods We retrospectively explored a correlation with the therapeutic activity of everolimus and tumor-associated immune pathways with ingenuity pathway analysis (IPA), neutrophil-to-lymphocyte ratio (NLR), circulating lymphocytes, and endothelial cells (CECs) in 3 different HR+ mBC studies, including the BALLET phase IIIb study. Results The circulating levels of CD3+/CD8+, CD3+/CD4+, and overall T lymphocytes were higher in responders versus non-responders at baseline (p = 0.017, p p = 0.034) and after treatment (p = 0.01, p = 0.003, p = 0.023). Reduced CECs, a tumor neoangiogenesis marker, were observed in responders after treatment (p 4.4) (p = 0.01). IPA showed that the majority of immunity-related genes were found upregulated in responders compared to non-responders before treatment, but not after. Conclusions Lymphocytes subpopulations, CECs and NLR could be interesting biomarkers predictive of response to everolimus-based regimens, potentially useful in daily clinical practice to select/monitor everolimus-based treatment in mBC. Further studies to confirm such hypotheses are warranted.

Anastomotic leak (AL) is one of the worst complications of rectal anterior resection (RAR) and its incidence varies according to the anatomical site, increasing in lower anastomoses. Many etiological factors have been evaluated and most of these are related to bowel perfusion. Indocyanine green-enhanced fluorangiography (ICGf) has been proposed to help surgeons assess colonic perfusion with higher reliability than subjective clinical judgment. The aim of the study was to evaluate the efficacy of this tool in patients subjected to elective laparoscopic RAR for extraperitoneal rectal cancer. All the patients subjected to elective laparoscopic RAR for extraperitoneal rectal cancer between May 2015 and January 2017 were considered. In all of them, ICGf was performed to evaluate bowel perfusion. The control group included an equal number of patients subjected to the same procedure from January 2014 to April 2015, before the start of routine use of this tool at our institution. The endpoint of the study was to compare the incidence of AL between the two groups. A total of 33 patients were included in both groups. Relying on fluorescence intensity in the indocyanine green (ICG) group, we changed the level of resection in 6/33 patients (18.2%). An AL developed in 2/33 patients (6%) in the ICG group versus in 7/33 patients (21.2%) in the control group. The routine use of this technique may help surgeons in selecting the best level of proximal bowel resection during RAR.

Comfortable walking speed and energy cost of walking are physiological markers of metabolic activity during gait. People with multiple sclerosis are characterized by altered gait biomechanics and energetics, related to the degree of disability and spasticity, which lead to an increased energy cost of walking. Several studies concerning the energy cost of walking in multiple sclerosis have been published. Nevertheless, differences in protocols and characteristics of the sample have led to different outcomes. The aim of the present meta-analysis is to summarize results from studies with specific inclusion characteristics, and to present data about the comfortable walking speed and the energy cost of walking at that speed. Moreover, a detailed discussion of the potential mechanisms involved in the altered metabolic activity during exercise was included. A total of 19 studies were considered, 12 of which were also part of the quantitative analysis. Despite the strict selection process, high between-group heterogeneity was found for both outcomes. Nevertheless, the overall results suggest a pooled mean comfortable walking speed of 1.12 m/s (95% CI 1.05–1.18) and energy cost of 0.19 mLO2/kg/m (95% CI 0.17–0.21). These findings support the results of previous studies suggesting that energy cost of walking may be increased by 2–3 times compared to healthy controls (HC), and encourage the use of this marker in association with other parameters of the disease.

Radiofrequency and laser ablation (RFA and LA) are effective treatments for benign thyroid nodules. Due to their relatively recent introduction into clinical practice, there are limited long-term follow-up studies. This study aimed to evaluate technique efficacy, rate of regrowth and retreatment over 5 years following RFA or LA and to identify predictive factors of outcome.

Background and Aims: Anti-tissue transglutaminase antibodies (anti-tTG) have simplified celiac disease (CD) diagnosis. However, in atypical forms of CD, intestinal biopsy sampling is still required. This prospective study investigates whether histologic analysis of the duodenal bulb combined with intestinal IgA anti-tTG deposit immunoassay makes CD diagnosis possible in at-risk children with low concentrations of serum anti-tTG. Methods: Histologic and intestinal IgA anti-tTG deposit immunoassays were used. Results: Two hundred forty-five symptomatic children positive for serum anti-tTG (>7 U/mL) were enrolled and divided into 3 groups: extensive duodenal atrophy (n Z 209), with IgA anti-tTG deposits throughout the duodenum and high serum anti-tTG concentrations (157 178 U/mL); bulb duodenal atrophy (n Z 22), with widespread IgA anti-tTG deposits in 9 and in the bulb alone in 13 and low serum anti-tTG concentrations (13.9 8.7 U/mL); and normal duodenum (n Z 14), with widespread IgA anti-tTG deposits in 8 and in the bulb alone in 6 and low serum anti-tTG concentrations (10.6 6.2 U/mL). All patients in the first 2 groups were diagnosed with CD and 8 from the third group. All improved after 1 year of gluten-free diet. Bulb duodenal analysis led to a 12% (30/245) increase in CD diagnosis. No CD-related lesions were observed in the 30 control subjects. Conclusions: In children at risk for CD, bulb duodenum biopsy sampling is essential to identify villous atrophy and detect IgA anti-tTG deposits even in absence of intestinal lesions. These mucosal autoantibodies could well represent a new standard for diagnosing CD. (Gastrointest Endosc 2018;-:1-6.)

PURPOSE: Surgical site infection (SSI) is the most common complication of colorectal surgery, resulting in significant burden in terms of morbidity and length of hospital stay. The aims of this study were to establish the incidence of SSI in patients undergoing colorectal surgeries and to identify potentially modifiable risk factors to reduce overall SSI rates. METHODS: This retrospective study analyzed patients who underwent colorectal resection at our Department. Patients were identified using a prospective SSI database. Univariate and multivariate analyses were used to identify risk factors. RESULTS: A total of 687 patients were enrolled in the study and the overall SSI rate was 19.9% (137 patients). Superficial incisional surgical site infections (SSSIs) developed in 52 (7.6%) patients, deep incisional surgical site infections (DSSIs) developed in 15 (2.2%), and organ/space infections (OSIs) developed in 70 (10.1%). Univariate and multivariate analyses confirmed that age, diabetes, emergency surgery, and a high infection risk index are risk factors for SSI. CONCLUSIONS: There are some modifiable and non-modifiable risk factors for SSI. IRI and age are non-modifiable, whereas the timing of surgery and diabetes can be modulated by trying to defer some emergency procedures to elective ones and normalizing the glycemia of diabetic patients.

In the medical literature, the role of breastfeeding and reproductive factors in the risk of breast carcinoma is still an open debate in premenopausal women. We highlight the role of breastfeeding and reproductive factors in luminal A and luminal B, the most frequent breast cancers. This case-control study analyzes a White premenopausal population of 286 breast cancer patients, divided into molecular subtypes, and 578 controls matched by age. Multivariate logistic regression models were used to assess the relationships of breastfeeding and other reproductive factors (age at menarche, parity, age at first pregnancy, number of children) with the risk of breast cancers. Among the variables examined, reproductive factors did not alter the risk of cancer, whereas breastfeeding up to 12 months was a significant protective factor against luminal B breast cancer (multivariate odds ratio: 0.22, 95% confidence interval: 0.09-0.59, P=0.002). In contrast, luminal A cases did not significantly correlate with breastfeeding or other reproductive factors. Breastfeeding up to 12 months is strongly protective against the more aggressive luminal B, but not against the less aggressive luminal A breast cancer in premenopausal White women.

BackgroundWe investigated the correlation between pancreatic ductal adenocarcinoma patient prognosis and the presence of tumour infiltrating lymphocytes and expression of 521 immune system genes.MethodsIntratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochemistry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenectomy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA).ResultsTwenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like receptor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell development); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NFκB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37.DiscussionTumour infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumour infiltrating lymphocyte levels and expression level of the immune system genes listed above influence pancreatic ductal adenocarcinoma prognosis. This information could be used to improve selection of best responders to immune inhibitors.

Objectives Optimal laryngeal exposure during transoral laryngeal surgery is fundamental. We aimed to evaluate the reliability of a recently proposed score (Laryngoscore) in predicting difficult laryngeal exposure (DLE) in an independent cohort of patients undergoing elective microlaryngoscopy. We also verified the relation between DLE, surgeon's expertise, and difficult intubation, and investigated possible areas for score improvement. Study design Prospective validation study. Methods A total of 136 patients were preoperatively evaluated using the Laryngoscore. Patients were divided into three classes according to patient position, type of laryngoscope, and need for external counterpressure to expose the anterior commissure. Based on their mean scores, two groups were identified: good laryngeal exposure (GLE) and DLE. A receiver operating characteristic curve with the Youden index was used to calculate the optimal cutoff value. The χ2 and Fisher exact test were used to correlate GLE and DLE to the surgeon's expertise and difficult intubation. The intraoperative anatomical parameters underlying DLE were also recorded. Results The optimal cutoff value for differentiating GLE and DLE was 4, which identified 80.6% of DLE cases. No statistically significant difference in GLE and DLE distribution was found between surgeons (P = 0.43). The correlation between difficult intubation and DLE was statistically significant (P = 0.03). The intraoperative parameters determining DLE were epiglottis characteristics (floppy, tight, or short), bulky abdomen and chest, bulky tongue base, mobile teeth, and a narrow laryngeal aditus. Conclusion The Laryngoscore is reliable for detecting DLE preoperatively. The inclusion of additional parameters may allow a more complete assessment and maximize its diagnostic accuracy. Level of evidence 2b Laryngoscope, 129:1438-1443, 2019.

Introduction: Minimally invasive nonsurgical techniques are gaining ground as alternatives to surgery for the treatment of benign thyroid nodules. Here, we aimed at comparing patient satisfaction after radiofrequency ablation (RFA) to that after surgery. Methods: In this cross-sectional study, we recruited 126 patients treated with RFA and 84 treated with surgery for a single benign thyroid nodule. All patients were contacted by phone call and were asked the following questions: Are you satisfied with the symptom resolution?; Are you satisfied with the cosmetic results?; Are you satisfied overall with the procedure?; Are you taking any medication for your thyroid? Patients’ general characteristics were collected from our database. Results: In the surgery group, there was a higher percentage of patients fully satisfied with the resolution of nodule-related symptoms (p = .02). In the RFA group, there was a higher percentage of patients fully satisfied with the cosmetic results (p = .001). In terms of overall satisfaction, there were no differences between the groups (p = .26). Nevertheless, RFA led to differing results based on thyroid nodule function. In patients with nonfunctioning thyroid nodules, RFA was as effective as surgery in terms of satisfaction with symptom resolution, while it was not in patients with autonomously functioning thyroid nodules (AFTN). Conclusion: Our data on postoperative patient satisfaction support the notion that both RFA and surgery are valid therapeutic options for nonfunctioning thyroid nodules, while surgery should be still preferred for AFTN.

Aim Her2 protein is the key marker determining the choice of Herceptin therapy after a diagnosis of breast cancer. Its evaluation is made in most laboratories by immunohistochemistry, and interpreted by a pathologist using an optical microscope, a process subject to inter-observer variability, particularly for samples scored as equivocal (2+). Software analysis products have been introduced, seeking to reduce this variability. In this study, we compared the results of both traditional evaluation and a specific software package (VISIA Imaging) to those from fluorescent in situ hybridization (FISH). Materials and methods We selected 176 cases of invasive breast cancer sampled during 2012–2014 that were classified as equivocal after evaluation of Her2 immunohistochemistry, and that were also evaluated by FISH. Each tissue slide was scanned with a digital D-Sight Fluo 2.0 microscope and analysed with VISIA Imaging S.r.l. software. The final results were categorised as follows: negative (0–1+), equivocal (2+), or positive (3+). Then each result was compared to that obtained by FISH. Result The digital method confirmed 85 samples (48.3%) as equivocal (2+), while 23 (15.1%) were reclassified as negative (1+) and 44 (28.9%) as positive (3+). Of the 176 cases, 24 (13.6%) were not suitable for digital analysis (inadequate). Of 67 reclassified cases (1+ or 3+), 62 were in agreement with FISH results (concordance rate 92.5%). The sensitivity and specificity of the digital method were 100% and 82%, respectively. Conclusion The application of this analysis software led to an improvement in the interpretation of cases classified as equivocal, decreasing the need for FISH and increasing diagnostic certainty.

An intragastric balloon is a non-surgical device enhancing a sensation of early satiety and reducing food intake. The aim of this study is to analyze the results in terms of weight loss and patient satisfaction undergoing intragastric balloon implantation. Air-filled and water-filled devices were used. All patients were participated in strict follow-up programs. Weight, body mass index (BMI), total body weight loss (TWL), percentage of excess weight loss (EWL), and satisfaction degree were taken into account. Eighty-one patients completed a 6-month period with a device in place; 72 of them were then contacted for a follow-up at 12.3 ± 2.4 months post-removal. During treatment period, in 76 cases (93.8 %), a statistically significant reduction in weight was observed. A statistically meaningful linear correlation between a 3-month EWL (or TWL) and a 6-month EWL (or TWL) was found. At the end of endoscopic treatment, a significant link between baseline BMI and EWL >20 % was found. Sixty-three percent of the patients were not satisfied with the procedure, did not deem useful to change their diet, and refused to perform it again. In our study, at device removal and 1 year thereafter, a statistically significant reduction in weight was observed. Most of the patients were found to have a weight loss more than the cut-off of 20 %. The weight reached at the third month appears to be predictive of the effectiveness of endoscopic treatment. Data showed an overall dissatisfaction with procedure.

Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, metastatic breast cancer has a poor prognosis. In an era of personalized medicine, there is an urgent need for better knowledge of the biology leading to the disease, which can lead to the design of increasingly accurate drugs against patients’ specific molecular aberrations. Among one of the actionable targets is the fibroblast growth factor receptor (FGFR) pathway, triggered by specific ligands. The Fibroblast Growth Factor Receptors/Fibroblast Growth Factors (FGFRs/FGFs) axis offers interesting molecular targets to be pursued in clinical development. This mini-review will focus on the current knowledge of FGFR mutations, which lead to tumor formation and summarizes the state-of-the-art therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC.

PURPOSE In a previous pilot study we observed that intra-operative narrow-band imaging (NBI) helps achieve clear superficial resection margins. The aim of this study was to verify if the use of intra-operative NBI can help to obtain tailored resections and if it is influenced by the lesion site, aspects not investigated in our previous study. MATERIALS AND METHODS The resection margins of 39 oral and 22 oropharyngeal squamous cell carcinomas were first set at 1.5cm from the macroscopic lesion boundary (white light, WL, tattoo). Then, the superficial tumor extension was more precisely defined with NBI, giving rise to three possible situations: NBI tattoo larger than the WL tattoo, NBI tattoo coinciding with the WL tattoo, or NBI tattoo smaller than the WL tattoo. For each of these situations the space comprised between the NBI and WL tattoos was defined "NBI positive", "NBI null", and "NBI negative", respectively. Resections were performed following the outer tattoo. The number of clear superficial resection margins, and the pathological response on the "NBI-positive" and the "NBI-negative" areas were recorded. RESULTS We obtained 80.3% negative superficial resection margins. NBI provided a more precise definition of superficial tumor extension in 43 patients. Sensitivity, specificity, positive and negative predictive values were 94.4%, 64%, 79.1% and 88.9%, respectively; a test of proportions demonstrated they were not influenced by tumor site. CONCLUSIONS NBI could allow for real-time definition of superficial tumor extension with possible tailored resections and fewer positive superficial resection margins; it is not influenced by tumor site.

According to many Societies' guidelines, patients presenting with clinical T4 colorectal cancer should conventionally be approached by a laparotomy. Results of emerging series are questioning this attitude. METHODS: We retrospectively analysed the oncologic outcomes of 147 patients operated on between June 2008 and September 2015 for histologically proven pT4 colon cancers. All patients were treated with curative intent, either by a laparoscopic or open "en bloc" resection. RESULTS: Median operative time, blood loss and hospital length of stay were significantly reduced in the laparoscopic group. Postoperative surgical complication rate and 30-day mortality did not significantly differ between the two groups ( p = 0.09 and p = 0.99, respectively). R1 resection rate and lymph nodes harvest, as well, did not remarkably differ when comparing the two groups. In the laparoscopic group, conversion rate was 19%. Long-term outcomes were not affected in patients who had undergone conversion. Five-year overall survival and disease-free survival did not significantly differ between the two groups (44.6% and 40.3% vs. 39.4% and 38.9%). Locally advanced stages (IIIB-IIIC) and R1 resections were detected as independent prognostic factors for overall survival. CONCLUSION: Laparoscopic approach might be safe and acceptable for locally advanced colon cancer and does not jeopardize the oncologic results. Conversion to open surgery should be a part of a strategy as it does not seem to adversely affect perioperative and long-term outcomes. We consider laparoscopy, in expert hands, the last diagnostic tool and the first therapeutic approach for well-selected locally advanced colon cancers. Larger prospective studies are needed to widely assess this issue.

BACKGROUND The beneficial effects of bariatric surgery on diabetes and obesity have been widely demonstrated in the literature. The aim of our study was to evaluate the rate of failure of laparoscopic gastric bypass both in terms of weight loss and metabolic remission after one follow-up year. METHODS A longitudinal, multicenter prospective study was carried out on 771 patients affected by pathological obesity. The following parameters were recorded for each patient before surgery: anthropometric, metabolic, social, smoking habits and previous failure of other bariatric procedures. After 1 follow-up year, final weight, final Body Mass Index (BMI), final percentage of lost excess body weight and percentage of lost BMI were evaluated. RESULTS Statistical analysis showed a correlation between BMI>50 kg/m2, presence of metabolic syndrome, presence of diabetes, gastric pouch volume greater than 60 mL and failure of weight loss outcome. Statistical analysis of metabolic failure has recognized a high preoperative glycated hemoglobin percentage (HbA1c%) value as a statistically significant negative predictive factor. CONCLUSIONS Bariatric Surgery is the most effective treatment for weight loss and metabolic improvement. However, in our study, surgery did not achieve the expected outcome in patients with specific metabolic, anthropometric and surgical characteristics (BMI>50 kg/m2, presence of metabolic syndrome, presence of T2DM with high preoperative HbA1c% level and gastric pouch volume greater than 60 mL).

Interval breast cancers (IBC) have been of great concern since breast mammogram screening programs were introduced. We compared IBC to screen-detected cancers (SDC). IBC accounted for one-fifth of all breast cancers diagnosed in women who followed the regional screening program. IBC appeared to be more aggressive than SDC in terms of tumor invasiveness, size, and St Gallen molecular subtype, leading to worse overall and disease-free survival. Background: The introduction of breast screening programs has raised the problem of interval breast cancers (IBC). The aims of this study were to analyze the impact of IBC on the screening program, to compare IBC and screendetected cancers (SDC), and to identify possible predictors of mortality. Patients and Methods: Patients with breast cancer diagnosed during the regional breast screening program between January 2008 and December 2013 at a single center in Italy were included. Demographic, preoperative, and postoperative data were prospectively collected and retrospectively analyzed. Results: Five hundred thirty-four patients were enrolled; 106 women (19.9%) had IBC and 428 women (80.1%) SDC. IBC presented more aggressive features compared to SDC, such as tumor invasiveness (95% vs. 85%; P ¼ .005), tumor size ( pT2 37% vs. 21%; P ¼ .001), grade (G3 39% vs. 17%; P < .001), and St Gallen molecular subtype (triple negative 22% vs. 7%; P < .001), resulting in higher distant recurrence rate (8% vs. 2%; P ¼ .009) and worse overall and disease-free survival (P ¼ .03 and P ¼ .001, respectively). Cox multivariate regression analysis identified St Gallen molecular subtype as the only predictor of mortality in patients with breast cancer (P ¼ .03). Conclusion: IBC accounted for one-fifth of all breast cancers diagnosed in women who followed the regional screening program. Furthermore, IBC appeared to have more aggressive features compared to SDC, leading to worse survival. These worse survivals depended on St Gallen molecular subtype.

Background. Gallstone disease affects 15–20% of the general population and up to 20% of these patients present common bile duct stones. Aim. This observational study reports our experience on routine cysticotomy and flushing of the cystic duct in patients with low risk of common duct stones. Materials and Methods. We analyzed 731 patients who underwent laparoscopic cholecystectomy between September 2013 and September 2015. Results. Patients were preoperatively stratified on the clinical risk; those presenting with low preoperative risk of common bile duct stones were referred to undergo laparoscopic cholecystectomy and routine cysticotomy with bile duct flushing. Patients presenting thick bile sludge, solid debrides, and/or increased tension of bile outflow underwent unplanned cholangiography. No intraoperative complications or conversion to open technique occurred. Average follow-up time was 22,8 months (range 12 to 37). Rate of retained ductal stones accounted for 0,3%. Conclusions. Routine cysticotomy and bile flushing in our experience is a valid, simple, and not time consuming manoeuvre that can help decompressing and flushing CBD. Moreover, it is a valid tool for extending selective IOC approach in a focused manner. Further evaluations have to be conducted to evaluate risks and effectiveness of this manoeuvre.

Radiofrequency ablation has been advocated as an alternative to radioiodine and/or surgery for the treatment of autonomously functioning benign thyroid nodules. However, only a few studies have measured radiofrequency ablation efficacy on autonomously functioning benign thyroid nodules. The aim of this work was to evaluate the 12-month efficacy of a single session of radiofrequency ablation (performed with the moving shot technique) on solitary autonomously functioning benign thyroid nodules.Thirty patients with a single, benign autonomously functioning benign thyroid nodules, who were either unwilling or ineligible to undergo surgery and radioiodine, were treated with radiofrequency ablation between April 2012 and May 2015. All the patients underwent a single radiofrequency ablation, performed with the 18-gauge needle and the moving shot technique. Clinical, laboratory, and ultrasound evaluations were scheduled at baseline, and after 1, 3, 6, and 12 months from the procedure.A single radiofrequency ablation reduced thyroid nodule volume by 51, 63, 69, and 75 % after 1, 3, 6, and 12 months, respectively. This was associated with a significant improvement of local cervical discomfort and cosmetic score. As for thyroid function, 33 % of the patients went into remission after 3 months, 43 % after 6 months, and 50 % after 12 months from the procedure. This study demonstrates that a single radiofrequency ablation allowed us to withdraw anti-thyroid medication in 50 % of the patients, who remained euthyroid afterwards.This study shows that a single radiofrequency ablation was effective in 50 % of patients with autonomously functioning benign thyroid nodules. Patients responded gradually to the treatment. It is possible that longer follow-up studies might show greater response rates.

Results: The meanDose to the PTVbreast-boost was significantly lower in Tech2 than in Tech1 (53,45 Gy vs 51 Gy) whereas D98% and D95% were comparable in the 2 techniques. The D2% and D5% were also lower of about 10% in Tech2 (p

Aims: To understand how coupled plasma filtration and adsorption (CPFA) could influence the time course of the advanced stages of sepsis, mean arterial pressure (MAP) and norepinephrine dosage. Methods: Patients with severe sepsis and septic shock with ≥2 organ failures not responding to volume resuscitation and vasopressor infusion were treated with CPFA within 8 h of admission to the intensive care unit. Results: Thirty-nine patients were treated (median age: 63 years, median SAPS II score: 45) and 28 survived advanced sepsis. In the latter, the median MAP increased and the norepinephrine dosage decreased significantly after CPFA, whereas in the nonsurvivors these values did not change significantly. The volume of treated plasma was significantly higher in survivors than nonsurvivors. Conclusion: These results suggest a possible existence of a dose-response effect for CPFA. Future studies are therefore recommended to evaluate the efficacy of this treatment and to determine its best timing and intensity.