Early outcome and mid-term survival after open arch repair using selective antegrade cerebral perfusion.

OBJECTIVES: The introduction of selective antegrade cerebral perfusion technique as method of cerebral protection improved the outcome of open arch surgery. The aim of this study was to report early outcomes using this technique. METHODS: Between 1997 and 2017, data were collected retrospectively for all patients who underwent surgical replacement of the aortic arch using selective antegrade cerebral perfusion (n = 938). To confirm the effectiveness of this cerebral protection method, early outcome and results were evaluated. RESULTS: The incidence of postoperative permanent neurological dysfunction was 6.4%. Overall hospital mortality was 11.9% (n = 112). On multivariable analysis, age >75 years, female gender, euroscore at increment of 1 point, chronic renal failure, extension of thoracic aorta replacement and CPB time emerged as independent risk factors for hospital mortality. The mid-term survival at 1, 5, 10 and 15 years was 92%, 78%, 60% and 49%, respectively. The competing risk analysis for permanent neurological dysfunction and aortic reoperations was performed excluding the patients who died during the hospital stay. The cumulative incidence of permanent neurological dysfunction and aortic reoperations was 2% at 3 years, 3% at 5 years, 6% at 10 years, 12% at 3 years, 15% at 5 years and 19% at 10 years, respectively. CONCLUSIONS: From the early 90s to the present day, the selective antegrade cerebral perfusion has confirmed to be a useful and "safe" method of brain protection in aortic arch surgery in terms of postoperative neurological complications.

Prediction of functional loss in emergency surgery is possible with a simple frailty screening tool.

BACKGROUND: Senior adults fear postoperative loss of independence the most, and this might represent an additional burden for families and society. The number of geriatric patients admitted to the emergency room requiring an urgent surgical treatment is rising, and the presence of frailty is the main risk factor for postoperative morbidity and functional decline. Frailty assessment in the busy emergency setting is challenging. The aim of this study is to verify the effectiveness of a very simple five-item frailty screening tool, the Flemish version of the Triage Risk Screening Tool (fTRST), in predicting functional loss after emergency surgery among senior adults who were found to be independent before surgery. METHODS: All consecutive individuals aged 70 years and older who were independent (activity of daily living (ADL) score ≥5) and were admitted to the emergency surgery unit with an urgent need for abdominal surgery between December 2015 and May 2016 were prospectively included in the study. On admission, individuals were screened using the fTRST and additional metrics such as the age-adjusted Charlson Comorbidity Index (CACI) and the ASA score. Thirty- and 90-day complications and postoperative decline in the ADL score where recorded. Regression analysis was performed to identify preoperative predictors of functional loss. RESULTS: Seventy-eight patients entered the study. Thirty-day mortality rate was 12.8% (10/78), and the 90-day overall mortality was 15.4% (12/78). One in every four patients (17/68) experienced a significant functional loss at 30-day follow-up. At 90-day follow-up, only 3/17 patients recovered, 2 patients died, and 12 remained permanently dependent. On the regression analysis, a statistically significant correlation with functional loss was found for fTRST, CACI, and age≥85 years old both at 30 and 90 days after surgery. fTRST≥2 showed the highest effectiveness in predicting functional loss at 90 days with AUC 72 and OR 6.93 (95% CI 1.71-28.05). The institutionalization rate with the need to discharge patients to a healthcare facility was 7.6% (5/66); all of them had a fTRST≥2. CONCLUSION: fTRST is an easy and effective tool to predict the risk of a postoperative functional decline and nursing home admission in the emergency setting.

Comparison of prognostic models in advanced hepatocellular carcinoma patients undergoing Sorafenib: A multicenter study.

BACKGROUND: Sorafenib is the gold standard therapy for the advanced hepatocellular carcinoma (HCC). No scoring/staging is universally accepted to predict the survival of these patients. AIMS: To evaluate the accuracy of the available prognostic models for HCC to predict the survival of advanced HCC patients treated with Sorafenib included in the Italian Liver Cancer (ITA.LI.CA.) multicenter cohort. METHODS: The performance of several prognostic scores was assessed through a Cox regression-model evaluating the C-index and the Akaike Information Criterion (AIC). RESULTS: Data of 1129 patients were analyzed. The mean age of patients was 61.6 years, and 80.8% were male. During a median follow-up period of 13 months, 789 patients died. The median period of Sorafenib administration was 4 months. All the prognostic scores were able to predict the overall survival (p<0.001) at univariate analysis, except the Albumin-Bilirubin score. The Italian Liver Cancer score (CLIP) yielded the highest accuracy (C-index 0.604, AIC 9898), followed by the ITA.LI.CA. prognostic score (C-index 0.599, AIC 9915). CONCLUSIONS: The CLIP score had the highest accuracy in predicting the overall survival of HCC patients treated with Sorafenib, although its performance remained poor. Further studies are needed to refine the current ability to predict the outcome of HCC patients undergoing Sorafenib.

Dry Eye Disease and Tear Cytokine Levels-A Meta-Analysis.

Background-It is recognized that inflammation is an underlying cause of dry eye disease (DED), with cytokine release involved. We systematically reviewed literature with meta-analyses to quantitatively summarize the levels of tear cytokines in DED. Methods-The PubMed, Embase, Web of Science, Ovid, Cochrane, and Scopus databases were reviewed until September 2019, and original articles investigating tear cytokines in DED patients were included. Differences of cytokines levels of DED patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed by applying Newcastle-Ottawa-Scale and the GRADE quality score. Methods of analytical procedures were included as covariate. Results-Thirteen articles investigating 342 DED patients and 205 healthy controls were included in the meta-analysis. The overall methodological quality of these studies was moderate. Systematic review of the selected articles revealed that DED patients had higher tear levels of interleukin (IL)-1ß, IL-6, chemokine IL-8, IL-10, interferon-γ, IFN-γ, and tumor necrosis factor-α, TNF-α as compared to controls. Evidence was less strong for IL-2 and IL-17A. Conclusions-Data show that levels of tear cytokines in DED and control display a great variability, and further studies of higher quality enrolling a higher number of subjects are needed, to define a cut-off value.

Impact of coronary bypass or stenting on mortality and myocardial infarction in stable coronary artery disease.

BACKGROUND: To assess whether coronary bypass (CABG) or stenting reduce the risk of mortality and myocardial infarction (MI) compared with optimal medical therapy (OMT) in stable coronary artery disease (CAD). METHODS: We performed a systematic review and network meta-analysis of contemporary randomized controlled trials comparing OMT, CABG and different stent types in stable CAD. All-comer trials were included if the rate of patients with acute myocardial infarction (AMI) was≤20%. Endpoints were all-cause mortality and MI. RESULTS: Ninety-seven trials including 75,754 patients were analyzed at a weighted mean follow up of 42.5 months. Compared to OMT, CABG was associated with a lower risk of death (OR = 0.84; 95%CI:0.71-0.97). After exclusion of trials in left main and/or multivessel disease(LM/MVD) this benefit was not statistically significant (OR = 0.89; 95%CI:0.74-1.06). CABG was associated with a lower risk of MI (OR = 0.67;95%CI: 0.49-0.91) showing, however, a certain degree of inconsistency (p=0.10). None of the stent types included was associated with a lower risk of death. However, durable-polymer-CoCr-everolimus-eluting stent, by mixed evidence, after exclusion of either LM/MVD (OR = 0.73;95%CI: 0.54-0.98) or all-comer/post-MI trials (OR = 0.62;95%CI:0.39-0.98) was associated with a lower risk of MI than OMT. Similar findings, by indirect evidence, were confirmed for bio-absorbable-polymer-CoCr-sirolimus eluting stent (LMV/MVD trials excluded OR = 0.46; 95%CI = 0.29-0.74, all-comer/post-MI trials excluded: OR = 0.41;95%CI:0.22-0.79). CONCLUSIONS: In stable CAD, CABG reduces the risk of mortality and MI compared to OMT, especially in patients with higher extent of CAD. Our study suggests that some of second and latest-generation drug-eluting stents may reduce the risk of MI. Future research should confirm these latter findings.

Does the Site of Origin of the Microcarcinoma with Respect to the Thyroid Surface Matter? A Multicenter Pathologic and Clinical Study for Risk Stratification.

It is unclear whether the site of origin of papillary thyroid microcarcinoma (mPTC) with respect to the thyroid surface has an influence on clinicopathologic parameters. The objectives of the study were to: (i) Accurately measure the mPTC distance from the thyroid surface; (ii) analyze whether this distance correlates with relevant clinicopathologic parameters; and (iii) investigate the impact of the site of origin of the mPTC on risk stratification. Clinicopathologic features and BRAF mutational status were analyzed and correlated with the site of origin of the mPTC in a multicenter cohort of 298 mPTCs from six Italian medical institutions. Tumors arise at a median distance of 3.5 mm below the surface of the thyroid gland. Statistical analysis identified four distinct clusters. Group A, mPTC: size ≥ 5 mm and distance of the edge of the tumor from the thyroid capsule = 0 mm; group B, mPTC: size ≥ 5 mm and distance of the edge of the tumor from the thyroid capsule > 0 mm; group C, mPTC: size < 5 mm and distance of the edge of the tumor from the thyroid capsule = 0 mm; and group D, mPTC: size < 5 mm and distance of the edge of the tumor from the thyroid capsule > 0 mm. Univariate analysis demonstrates significant differences between the groups: Group A shows the most aggressive features, and group D the most indolent ones. By multivariate analysis, group A tumors are characterized by tall cell histotype, BRAF V600E mutation, tumor fibrosis, aggressive growth with invasive features, vascular invasion, lymph node metastases, and intermediate ATA risk. The mPTC clinicopathologic features vary according to the tumor size and distance from the thyroid surface. A four-group model may be useful for risk stratification and to refine the selection of nodules to be targeted for fine needle aspiration.

Factors affecting the number of lymph nodes retrieved after colo-rectal cancer surgery: A prospective single-centre study.

BACKGROUND: The number of harvested lymph nodes (LNs) in colorectal cancer surgery relates to oncologic radicality and accuracy of staging. In addition, it affects the choice of adjuvant therapy, as well as prognosis. The American Joint Committee on Cancer defines at least 12 LNs harvested as adequate in colorectal cancer resections. Despite the importance of the topic, even in high-volume colorectal centres the rate of adequacy never reaches 100%. The aim of this study was to identify factors that affect the number of harvested LNs in oncologic colorectal surgery. MATERIALS AND METHODS: We prospectively collected all consecutive patients who underwent colorectal cancer resection from January 1st 2013 to December 31st 2017 at Emergency Surgery Unit St Orsola University Hospital of Bologna. RESULTS: Six hundred and forty-three consecutive patients (382 elective, 261 emergency) met the study inclusion criteria. Emergency surgery and laparoscopic approach did not have a significant influence on the number of harvested LNs. The adequacy of lymphadenectomy was negatively affected by age >80 (OR 3.47, p < 0.001), ASA score ≥3 (OR 3.48, p < 0.001), Hartmann's or rectal resection (OR 3.6, p < 0.001) and R1-R2 resection margins (OR 3.9, p = 0.006), while it was positively affected by T-status ≥3 (OR 0.33 p < 0.001). CONCLUSION: Both the surgical technique and procedure regimen did not affect the number of lymphnodes retrieved. Age >80 and ASA score ≥3 and Hartmann's procedure or rectal resection showed to be risk factors related to inadequate lymphadenectomy in colorectal cancer surgery.

Predictors of survival in malignant aortic tumors.

OBJECTIVE: Malignant aortic tumors (MATs) are exceedingly rare, and a comprehensive review of clinical and therapeutic aspects is lacking in the literature. The aim of this study was to analyze all known cases of MATs and to identify predictors of patients' survival. METHODS: All patients diagnosed with an aortic tumor treated in a single center along with all case reports and reviews available in the literature through a specific PubMed search using keywords such as "malignant" and "aorta" or "aortic," "tumor," or "sarcoma" or "angiosarcoma" were analyzed. The tumor's primary location, clinical presentation, histologic subtype, and treatment choice were examined. Survival at 1 year, 3 years, and 5 years and the possible preoperative and operative outcome predictors were evaluated using Kaplan-Meier analysis with a log-rank test and by Cox regression for multivariate analysis. RESULTS: In addition to the 5 cases treated in our center, 218 other cases of MAT were reported in the literature from 1873 to 2017. The mean age of the patients was 60.1 ± 11.9 years, and the male to female ratio was 1.59:1. The median overall survival from diagnosis was 8 (7-9) months; 1-, 3-, and 5-year survival rates were 26%, 7.6%, and 3.5%, respectively. Chronic hypertension (P = .03), fever (P = .03), back pain (P = .01), asthenia (P = .04), and signs of peripheral embolization (P = .007) were significant predictors of a poor result. Histologic subtypes had a different impact on survival, with no statistical significance. Compared with other treatment strategies, combined surgical-medical therapy had the best impact on the median survival rate (surgical-medical, 12 [8-24] months; medical, 8 [5-10] months; surgical 7 [2-16] months; no treatment, 2 [0.5-15] months; P = .001). Analyzing exclusively medical approaches, chemotherapy and radiotherapy had the best impact on median survival rate compared with untreated patients (chemotherapy-radiotherapy, 18 [10-26] months; radiotherapy, 16 [8-20] months; chemotherapy, 10 [7-24] months; no medical treatment, 6 [2-16] months; P = .005); these data were not sustained by multivariate analysis. CONCLUSIONS: Aortic tumors are a malignant pathologic condition with a short survival rate after initial diagnosis. Survival is further diminished in the presence of clinical factors such as hypertension, fever, back pain, asthenia, and signs of peripheral embolization. Combined surgical and medical treatment, particularly with chemotherapy and radiotherapy, has shown the highest survival rate.

The complex interplay among atherosclerosis, inflammation, and degeneration in ascending thoracic aortic aneurysms.

OBJECTIVE: To assess the histopathological findings of a large series of ascending thoracic aortic aneurysm (TAA) surgical specimens applying the updated classification on noninflammatory degenerative and inflammatory aortic diseases proposed by the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology clinicopathological correlations. METHODS: A total of 255 patients surgically treated for ascending TAA were enrolled. Surgical ascending aorta specimens were examined. RESULTS: The histopathological substrate of ascending TAAs was mainly degenerative (67.5%), but with a remarkable prevalence of atherosclerotic lesions (18.8%) and aortitis (13.7%). Degenerative patients more frequently had bicuspid aortic valve (37.2%; P = .002). Patients in the atherosclerotic group were older (median age, 69 years; P < .001), more often with a history of hypertension (87.5%; P = .059), hypercholesterolemia (75%; P = .019), diabetes (16.6%; P = .054), current smoking (22.9%; P = .066), and a history of coronary artery disease (18.7%; P = .063). Patients with aortitis represented the older group (median age, 75 years, P < .001), were mostly females (68.6%; P < .001), and had a larger ascending aorta diameter (median, 56 mm; P < .001). Both patients with atherosclerosis and aortitis presented a higher incidence of concomitant abdominal aortic aneurysm (20.8% and 22.8%, respectively; P < .001). CONCLUSIONS: Although degenerative histopathology is the most frequent substrate in ascending TAA, atherosclerosis and inflammation significantly contribute to the development of chronic aortic thoracic disease.

Interleukin 28 Polymorphisms and Hepatocellular Carcinoma Development after Direct Acting Antiviral Therapy for Chronic Hepatitis C.

BACKGROUND AND AIMS: Cirrhotic patients with hepatitis C virus (HCV) infection remain at risk of developing hepatocellular carcinoma (HCC) even after the sustained virologic response (SVR). We aimed to evaluate whether the IL28 (rs12979860) single nucleotide polymorphism (SNP) may constitute a predisposing genetic factor and to identify the SVR patients at risk of HCC. METHODS: Two hundred patients undergoing DAAs treatment for chronic hepatitis C with advanced fibrosis (F3- F4) were consecutively enrolled. Besides normal routine laboratory testing for HCV, patients' sera were evaluated also for retinol, retinol-binding protein 4 and the following SNPs: PNPLA3 (rs738409), TM6SF2 (rs58542926), MBOAT7 (rs641738), IL28B (rs12979860), TIMP-1 (rs4898), TIMP-2 (rs8179090), NF-kB promoter (rs28362491). Statistical analyses were conducted using Stata/SE 14.2 statistical software (Stata Corp, College Station, TX). RESULTS: Almost all patients (197/200) obtained SVR24. Seventeen patients had a previous history of treated HCC before DAAs. Six patients developed HCC recurrence and five patients developed de novo HCC after a mean period of 18 months since EOT. All these patients had SVR. A significant association between IL28B - TT genotype and HCC development after DAAs therapy was observed (OR 4.728, CI 95% 1.222 - 18.297, p=0.024). CONCLUSION: IL28B rs12979860 polymorphism was significantly associated with HCC development after DAAs. Assessment of this SNP may better identify patients at risk of developing HCC after treatment. Further prospective studies are required to confirm these hypotheses.

Real-life comparison of pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis: A 24-month assessment.

BACKGROUND: Real-life data on the use of pirfenidone and nintedanib to treat patients with idiopathic pulmonary fibrosis (IPF) are still scarce. METHODS: We compared the efficacy of either pirfenidone (n = 78) or nintedanib (n = 28) delivered over a 24-month period in patients with IPF, followed at two regional clinic centers in Italy, with a group of patients who refused the treatment (n = 36), and who were considered to be controls. All patients completed regular visits at 1- to 3-month intervals, where primary [forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)] and secondary outcomes (side effects, treatment compliance, and mortality) were recorded. RESULTS: Over time, the decline in FVC and DLCO was significantly higher (p = 0.0053 and p = 0.037, respectively) in controls when compared with the combined treated group, with no significant difference between the two treated groups. Compared to patients with less advanced disease (GAP (Gender, Age, Physiology) stage I), those in GAP stages II and III showed a significantly higher decline in both FVC and DLCO irrespective of the drug taken. Side effects were similarly reported in patients receiving pirfenidone and nintedanib (5% and 7%, respectively), whereas mortality did not differ among the three groups. CONCLUSION: This real-life study demonstrated that both pirfenidone and nintedanib were equally effective in reducing the decline of FVC and DLCO versus non-treated patients after 24 months of treatment; however, patients with more advanced disease were likely to show a more rapid decline in respiratory function.

Open distal anastomosis in the frozen elephant trunk technique: initial experiences and preliminary results of arch zone 2 versus arch zone 3†.

OBJECTIVES: We compared the results of 2 groups of patients who underwent aortic arch replacement with the frozen elephant trunk technique. In the first group, the distal anastomosis was performed in arch zone 2; in the second control group, the distal anastomosis was performed in arch zone 3. METHODS: Between January 2007 and April 2018, the frozen elephant trunk technique was used in 282 patients. The median age was 62 years (range 18-83 years), and 233 patients were men (82.6%). Two different frozen elephant trunk prostheses were used: the Jotec E-vita open prosthesis in 167 patients (59.2%) and the Vascutek Thoraflex hybrid prosthesis in 115 patients (40.8%). Patients were divided into 2 groups according to the distal anastomosis site: zone 2 group (69 patients) and zone 3 group (213 patients). The main indications were chronic aortic dissection (n = 164, 58.2%), degenerative aneurysm (n = 72, 25.5%) and acute aortic dissections (n = 45, 16%). RESULTS: The overall in-hospital mortality rate was 17%: 20% for the zone 2 group and 16% for the zone 3 group, without significant differences, also in terms of cardiopulmonary bypass and myocardial ischaemia times. However, the visceral ischaemia time was significantly shorter for the zone 2 group, whereas the antegrade selective cerebral perfusion time was significantly longer for the same group. Recurrent laryngeal nerve injury rate was lower in the zone 2 group. The overall postoperative paraplegia rate was 3.5%, whereas the occurrence of permanent neurological dysfunction and dialysis was 9% and 19%, respectively, with no significant differences between the groups. CONCLUSIONS: 'Proximalization' of the distal anastomosis can be used for arch reconstruction, especially in complex cases such as reoperations or acute aortic dissections. Furthermore, with the aid of branched hybrid grafts, a reduction of the visceral ischaemia time is achieved.

A Simple Screening Tool to Predict Outcomes in Older Adults Undergoing Emergency General Surgery.

OBJECTIVES: To determine whether the Flemish version of the Triage Risk Screening Tool (fTRST) can be used to accurately assess frailty in an emergency setting. DESIGN: Prospective observational study. SETTING: of a tertiary referral hospital. PATIENTS: All individuals aged 70 and older consecutively admitted to the emergency surgery unit with an urgent need for abdominal surgery between December 2015 and May 2016 who met inclusion criteria (N=110). MEASUREMENTS: Individuals were screened with the fTRST and additional metrics such as the age-adjusted Charlson Comorbidity Index and American Society of Anesthesiology score. Thirty- and 90-day postoperative complications where recorded. Regression analyses were performed to identify possible preoperative predictors of adverse outcomes. RESULTS: Thirty-day major complications (Clavien-Dindo Classification 3-5) occurred in 28.2% of participants (n=31). fTRST had the highest correlation with major complications (odds ratio (OR) = 7.42). All participants who died within 30 days of surgery has a fTRST score of 2 or greater (area under the receiver operating curve (AUC)=71.3). When risk factors for overall 90-day mortality were analyzed, a fTRST score of 2 or greater had sensitivity of 96% (95% confidence interval CI=79.6-99.9%), specificity of 43.5% (95% CI=32.8-54.7%) (AUC=69.8%; OR=18.50, 95% CI=2.39-143.11, p = .005). The average length of hospital stay was more than twice as long in the group with a fTRST score of 2 or greater (15.2 days) than in those with a score less than 2 (6.6 days) (p = .005). CONCLUSION: The fTRST is an effective tool to predict mortality, morbidity, and length of stay after emergency surgery and can therefore be used to anticipate postoperative course, determine care goals, and plan for involvement of a dedicated geriatric care team. J Am Geriatr Soc 67:309-316, 2019.

Role of liver and spleen stiffness in predicting the recurrence of hepatocellular carcinoma after resection.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a frequent complication of liver disease. When feasible, hepatic resection is the first-choice therapy. However, tumor recurrence complicates at least 2/3 hepatic resections at 5 years. Early recurrences are mainly tumor or treatment-related, but predictors of late recurrences are undefined. We aimed to evaluate the factors related to HCC recurrence after curative resection, with liver and spleen stiffness measurement (LSM and SSM) as markers of severity and duration of the underlying liver disease. METHODS: We enrolled patients with chronic liver disease and primary HCC suitable for hepatic resection. We followed up patients for at least 30 months or until HCC recurrence. We performed uni- and multivariate analyses to evaluate the predictive role of tumor characteristics, laboratory data, LSM and SSM for both early and late recurrence of HCC. RESULTS: We prospectively enrolled 175 patients. Early HCC recurrence at multivariate analysis was associated with viral etiology, HCC grading (3 or 4), resection margins <1 cm and being beyond the Milan criteria. HCC late recurrence at univariate analysis was associated with esophageal varices (hazard ratio [HR] 3.321, 95% CI 1.564-7.053), spleen length (HR 3.123, 95% CI 1.377-7.081), platelet/spleen length ratio if <909 (HR 2.170, 95% CI 1.026-4.587), LSM (HR 1.036, 95% CI 1.005-1.067), SSM (HR 1.046, 95% CI 1.020-1.073). HCC late recurrence at multivariate analysis was independently associated only with SSM (HR 1.046, CI 1.020-1.073). Late HCC recurrence-free survival was significantly different according to the SSM cut-off of 70 kPa (p = 0.0002). CONCLUSIONS: SSM seems to be the only predictor of late HCC recurrence, since it is directly correlated with the degree of liver disease and portal hypertension, both of which are involved in carcinogenesis. LAY SUMMARY: The main result of this study is that spleen stiffness measurement, evaluated by transient elastography, seems to be the only predictor of the late recurrence of hepatocellular carcinoma, defined as recurrence after 24 months from liver resection. Indeed, spleen stiffness measurement is directly correlated with the degree of liver disease and portal hypertension, which are both involved in carcinogenesis.

Hepatocellular carcinoma risk assessment by the measurement of liver stiffness variations in HCV cirrhotics treated with direct acting antivirals.

BACKGROUND: Direct-acting antivirals (DAA) are an effective treatment for hepatitis C virus infection. However, sustained virologic response (SVR) after DAA treatment does not seem to reduce the risk of hepatocellular carcinoma (HCC) development in these patients. Liver stiffness measurement (LSM) may predict the risk of developing HCC in liver cirrhosis patients. AIMS: The aim of our study was to evaluate the role of LSM variation as predictor of HCC development in patients treated with DAA. METHODS: In 139 HCV-related cirrhotic patients, LSM and laboratory tests were carried out at baseline (BL) and at the end of DAA treatment (EOT). Patients were followed for at least 6 months after the EOT. LSM reduction was expressed as Delta LS (∆LS). Cox regression analysis was used to identify prognostic factors for HCC development after DAA. RESULTS: Median LSM values were significantly reduced from BL to EOT (from 18.6 to 13.8 kPa; p < 0.001). The median ∆LS was -26.7% (IQR: -38.4% -13.6%). During a median follow-up of 15 months after DAA treatment, 20 (14.4%) patients developed HCC. Significant LSM reduction was observed both in patients who developed HCC and in those who did not, but this was significantly lower in the patients who developed HCC (-18.0% vs -28.9% p = 0.005). At multivariate analysis, ∆LS lower than -30%, Child-Turcotte-Pugh-B and history of HCC were independently associated with HCC development. CONCLUSION: Our results indicate that ∆LS is a useful non-invasive marker for predicting HCC development after DAA treatment.

Matricellular proteins and survival in patients with pancreatic cancer: A systematic review.

Extracellular matrix (ECM) plays a fundamental role in tissue architecture and homeostasis and modulates cell functions through a complex interaction between cell surface receptors, hormones, several bioeffector molecules, and structural proteins like collagen. These components are secreted into ECM and all together contribute to regulate several cellular activities including differentiation, apoptosis, proliferation, and migration. The so-called "matricellular" proteins (MPs) have recently emerged as important regulators of ECM functions. The aim of our review is to consider all different types of MPs family assessing the potential relationship between MPs and survival in patients with pancreatic ductal adenocarcinoma (PDAC). A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement issued in 2009 was conducted through Ovid interface, and literature review was performed in May 2017. The search text words were identified by means of controlled vocabulary, such as the National Library of Medicine's MESH (Medical Subject Headings) and Keywords. Collected data showed an important role of MPs in carcinogenesis and in PDAC prognosis even though the underlying mechanisms are still largely unknown and data are not univocal. Therefore, a better understanding of MPs role in regulation of ECM homeostasis and remodeling of specific organ niches may suggest potential novel extracellular targets for the development of efficacious therapeutic strategies.

Long-term survivors of pancreatic adenocarcinoma show low rates of genetic alterations in KRAS, TP53 and SMAD4.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection. OBJECTIVE: The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery. METHODS: Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 was tested using immunohistochemistry. MGMT promoter methylation was investigated. RESULTS: Tumors from "LS" have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation. CONCLUSIONS: Our data indicate that absence of KRAS, TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome.

Baseline factors associated with response to ruxolitinib: an independent study on 408 patients with myelofibrosis.

In patients with Myelofibrosis (MF) treated with ruxolitinib (RUX), the response is unpredictable at therapy start. We retrospectively evaluated the impact of clinical/laboratory factors on responses in 408 patients treated with RUX according to prescribing obligations in 18 Italian Hematology Centers. At 6 months, 114 out of 327 (34.9%) evaluable patients achieved a spleen response. By multivariable Cox proportional hazard regression model, pre-treatment factors negatively correlating with spleen response were: high/intermediate-2 IPSS risk (p=0.024), large splenomegaly (p=0.017), transfusion dependency (p=0.022), platelet count <200×109/l (p=0.028), and a time-interval between MF diagnosis and RUX start >2 years (p=0.048). Also, patients treated with higher (≥10 mg BID) average RUX doses in the first 12 weeks achieved higher response rates (p=0.019). After adjustment for IPSS risk, patients in spleen response at 6 months showed only a trend for better survival compared to non-responders. At 6 months, symptoms response was achieved by 85.5% of 344 evaluable patients; only a higher (>20) Total Symptom Score significantly correlated with lower probability of response (p<0.001). Increased disease severity, a delay in RUX start and titrated doses <10 mg BID were associated with patients achievinglower response rates. An early treatment and higher RUX doses may achieve better therapeutic results.

A new CT-score as index of hemodynamic changes in patients with chronic thromboembolic pulmonary hypertension.

PURPOSE: The aim of this study was to retrospectively assess the relationship between radiological and hemodynamic parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We introduced a new CT-score to evaluate hemodynamic changes, only employing CT-pulmonary angiography (CTPA). MATERIALS AND METHODS: 145 patients affected by CTEPH underwent hemodynamic and CTPA evaluation. Among these 145 patients, 69 underwent pulmonary endarterectomy (PEA) and performed a CTPA evaluation even after surgery. Hemodynamic assessment considered the values of mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR), obtained through right heart catheterization (RHC). Radiological evaluation included CTPA signs of pulmonary hypertension. RESULTS: A highly significant statistical correlation was observed between the new CT-score and both mPAP and PVR (p < 0.000) in the whole sample and also in the subgroup who underwent PEA. In addition, mPAP and PVR showed an important association with the severity of mosaic perfusion (p < 0.000). mPAP also correlated with main pulmonary artery diameter (p < 0.01); a significant association was found in both between PVR and tricuspid regurgitation(p < 0.000) and with PVR and presence of unilateral or bilateral pulmonary thromboembolic occlusion (p < 0.05). CONCLUSION: Our results confirm the diagnostic role of CTPA in evaluating patients with CTEPH and in addition open a new horizon in assessing hemodynamic changes in patients with CTEPH, only employing a CTPA, especially when RHC is contraindicated or not possible.