A Cell-Phone Medication Error eHealth App for Managing Safety in Chronically Ill Young Patients at Home: A Prospective Study.

Introduction: Whereas ample information describes medication errors (MEs) in children or in mixed pediatric and adult populations discharged with acute or chronic diseases from hospital to community settings, little is known about MEs in children and adolescents with chronic diseases discharged home, a major concern. To promote home medication safety, we trained parents of children discharged with chronic diseases to record ME with a tailored cell-phone eHealth app. Methods: In a 1-year prospective study, we used the app to monitor ME in patients with chronic diseases discharged home from a tertiary hospital in Rome, Italy. Univariate and multivariate analyses detected the ME incidence rate ratio (IRR). Results: Of the 310 parents enrolled, 194 used the app. The 41 MEs involved all drug management phases. The ME IRR was 0.46 errors per child. Children <1 year had the highest ME risk (1.69 vs. 0.35, p = 0.002). Children discharged from the cardiology unit had a statistically higher ME IRR than others (3.66, 95% confidence interval: 1.01-13.23%). Conclusions: The highest ME risk at home involves children with chronic diseases <1 year old. A significant ME IRR at home concerns children with heart diseases of any age. Parents find a tailored eHealth app for monitoring and reporting ME at home easy to use. At discharge, clinical teams need to identify age-related and disease-residual risks to target additional actions for monitoring ME, thus increasing medication safety at home.

Analysis of microbiome in gastrointestinal stromal tumors: Looking for different players in tumorigenesis and novel therapeutic options.

Preclinical forms of gastrointestinal stromal tumor (GIST), small asymptomatic lesions, called microGIST, are detected in approximately 30% of the general population. Gastrointestinal stromal tumor driver mutation can be already detected in microGISTs, even if they do not progress into malignant cancer; these mutations are necessary, but insufficient events to foster tumor progression. Here we profiled the tissue microbiota of 60 gastrointestinal specimens in three different patient cohorts-micro, low-risk, and high-risk or metastatic GIST-exploring the compositional structure, predicted function, and microbial networks, with the aim of providing a complete overview of microbial ecology in GIST and its preclinical form. Comparing microGISTs and GISTs, both weighted and unweighted UniFrac and Bray-Curtis dissimilarities showed significant community-level separation between them and a pronounced difference in Proteobacteria, Firmicutes, and Bacteroidota was observed. Through the LEfSe tool, potential microbial biomarkers associated with a specific type of lesion were identified. In particular, GIST samples were significantly enriched in the phylum Proteobacteria compared to microGISTs. Several pathways involved in sugar metabolism were also highlighted in GISTs; this was expected as cancer usually displays high aerobic glycolysis in place of oxidative phosphorylation and rise of glucose flux to promote anabolic request. Our results highlight that specific differences do exist in the tissue microbiome community between GIST and benign lesions and that microbiome restructuration can drive the carcinogenesis process.

Predictive value of NLR, TILs (CD4+/CD8+) and PD-L1 expression for prognosis and response to preoperative chemotherapy in gastric cancer.

The combination of perioperative chemotherapy plus complete surgical resection is currently accounted as the first-choice strategy in patients with locally advanced Gastric Cancer (LAGC). Nevertheless, the partial response rate makes it necessary to search biological parameters useful to select patients who would benefit most from neoadjuvant chemotherapy (NAD-CT). We performed a retrospective analysis on a cohort of 65 LAGC cases, EBV negative and without MMR defect, submitted to perioperative chemotherapy plus surgical resection. We evaluated the neutrophil-lymphocytes ratio (NLR) in peripheral blood, the TILs density (reported as CD4/CD8 tissue ratio) and PD-L1 expression by immunohistochemistry on bioptic tissues before the treatment. Results were correlated with the biological features, histological response (TRG) and clinical outcome (PFS and OS). We found that NLR, TILs and PD-L1 expression showed a significant correlation with TNM stage, lymphovascular invasion and response to NAD-CT (TRG). Correlating the NLR, TILs and PD-L1 expression with PFS and OS, we found that patients with lower NLR levels (< 2.5 ratio), lower TILs (< 0.2 ratio) and higher PD-L1 level (CPS ≥ 1) had a significantly better PFS and OS than those with higher NLR, higher TILs and lower PD-L1 expression (p < 0.0001). Multivariate and multiple regression analyses confirmed the predictive and prognostic role of all three parameters, especially when all three parameters are combined. Our study demonstrated that pre-treatment NLR, TILs and PD-L1 expression are predictive and prognostic parameters in NAD-CT-treated LAGC suggesting a pivotal role of the systemic and tumor microenvironment immunological profile in the response to chemotherapy.

THUNDER 2: THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI guided radiotherapy.

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC). Since response to radiotherapy (RT) is dose dependent in rectal cancer, dose escalation may lead to higher complete response rates. The possibility to predict patients who will achieve complete response (CR) is fundamental. Recently, an early tumour regression index (ERI) was introduced to predict pathological CR (pCR) after nCRT in LARC patients. The primary endpoints will be the increase of CR rate and the evaluation of feasibility of delta radiomics-based predictive MRI guided Radiotherapy (MRgRT) model. METHODS: Patients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features will be enrolled in the trial. Neoadjuvant CRT will be administered using MRgRT. The initial RT treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45 Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine will be administered continuously. A 0.35 Tesla MRI will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated: if ERI will be inferior than 13.1, the patient will continue the original treatment; if ERI will be higher than 13.1 the treatment plan will be reoptimized, intensifying the dose to the residual tumor at the 11th fraction to reach 60.1 Gy. At the end of nCRT instrumental examinations are to be performed in order to restage patients. In case of stable disease or progression, the patient will undergo surgery. In case of major or complete clinical response, conservative approaches may be chosen. Patients will be followed up to evaluate toxicity and quality of life. The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. DISCUSSION: This clinical trial investigates the impact of RT dose escalation in poor responder LARC patients identified using ERI, with the aim of increasing the probability of CR and consequently an organ preservation benefit in this group of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04815694 (25/03/2021).

Participation of nurses and allied health professionals in research activities: a survey in an academic tertiary pediatric hospital.

BACKGROUND: Involvement in research activities is complex in pediatric nursing and allied health professionals (AHPs). It is important to understand which individual factors are associated with it to inform policy makers in promoting research. METHODS: A cross-sectional observational study was conducted to describe the level of participation in research activities over the last ten years of nurses and AHPs working in a tertiary pediatric hospital. A large sample of nurses and AHPs working in an Italian academic tertiary pediatric hospital completed an online self-report questionnaire between June and December 2018. Three multivariate logistic regression analyses were performed to predict participation in research projects, speaking at conferences, and writing scientific articles. RESULTS: Overall, data from 921 health professionals were analyzed (response rate = 66%), of which about 21% (n = 196) reported participating in a research project, while 33% (n = 297) had attended a scientific conference as a speaker, and 11% (n = 94) had written at least one scientific paper. Having a Master or a Regional Advanced Course, working as an AHP or a ward manager, as well as regularly reading scientific journals and participation in an internal hospital research group or attendance in a specific course about research in the hospital, significantly predicted participation in research projects, speaking at conferences and writing scientific papers. It is important to foster research interest and competencies among health professionals to improve participation in research projects, speaking at conferences, and writing scientific papers. CONCLUSIONS: Overall, we found a good level of attendance at conferences as speakers (33%), a moderate level of participation in research (21%), and low levels for writing scientific papers (11%). Our study highlighted the need to support participation in research activities among nurses and AHPs. Policymakers should identify strategies to promote research among nurses and AHPs, such as protected rewarded time for research, specific education, strengthened collaboration with academics, and financial support. Moreover, hospital managers should promote the development of research culture among health professionals, to improve their research competencies and evidence-based practice.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases: analysis of short- and long-term outcomes.

BACKGROUND: Peritoneal metastases carry the worst prognosis among all sites of colorectal cancer (CRC) metastases. In recent years, the advent of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival for selected patients with limited peritoneal involvement. We report the evolution of CRS and HIPEC for colorectal peritoneal metastases at a tertiary referral center over a 10-year period. METHODS: Patients with colorectal peritoneal metastases undergoing CRS and HIPEC were included and retrospectively analyzed at a tertiary referral center from January 2006 to December 2015. Main outcomes included evaluation of grade III/IV complications, mortality rate, overall and disease-free survival, and prognostic factors influencing survival on a Cox multivariate analysis. RESULTS: Sixty-seven CRSs were performed on 67 patients during this time for colorectal peritoneal metastases. The median patient age was 57 years with 55.2% being female. The median peritoneal carcinomatosis index (PCI) was 7, with complete cytoreduction achieved in 65 (97%) cases. Grade > 2 complications occurred in 6 cases (8.9%) with no mortality. The median overall survival for the entire cohort was 41 months, with a 3-year overall survival of 43%. In case of complete cytoreduction, median overall and disease-free survival were 57 months and 36 months respectively, with a 3-year disease-free survival of 62%. Complete cytoreduction and nonmucinous histology were key factors independently associated with improved overall survival. CONCLUSIONS: CRS and HIPEC for limited peritoneal metastases from CRC are safe and effective, with acceptable morbidity. In selected patients, it offers a highly favorable long-term outcomes.

Survival advantage of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer: experience from a Western tertiary referral center.

BACKGROUND: Selection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, Peritoneal Carcinomatosis Index >1) and prophylactic (PCI=0) intent. METHODS: A retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed. RESULTS: A total of 85 patients with AGC were analyzed. Five-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27%, and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04). Five-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05). CONCLUSIONS: Patients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.

Survival advantage of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer: experience from a Western tertiary referral center.

BACKGROUND: Selection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined, and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, peritoneal carcinomatosis index > 1) and prophylactic (PCI = 0) intent. METHODS: A retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed. RESULTS: A total of 85 patients with AGC were analyzed. A 5-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27% and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04). A 5-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05). CONCLUSIONS: Patients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.

Pediatric nurses in pediatricians' offices: a survey for primary care pediatricians.

BACKGROUND: The role played by nurses in caring for children in pediatricians' officies in the community is crucial to ensure integrated care. In Italy, pediatricians are responsible for the health of children aged 0-14 years living in the community. This study aimed to describe Italian primary care pediatricians' opinions about the usefulness of several nursing activities that pediatric nurses could perform in pediatricians' offices. METHODS: An online survey with pediatricians working in primary care in Italy was conducted between April-December 2018. A 40-item questionnaire was used to assess four types of nursing activities: clinical care, healthcare education, disease prevention, and organizational activities. The answers ranged from 1 (not useful at all) to 6 (very useful). Moreover, three open-ended questions completed the questionnaire. RESULTS: Overall, 707 pediatricians completed the online survey. Participants were mainly female (63%), with a mean age of 57.74 (SD = 6.42). The presence of a pediatric nurse within the pediatrician's office was considered very useful, especially for healthcare education (Mean 4.90; SD 1.12) and disease prevention (Mean 4.82; SD 1.11). Multivariate analysis confirmed that pediatricians 'with less working experience', 'having their office in a small town', and 'collaborating with a secretary and other workers in the office' rated the nurse's activities significantly more useful. CONCLUSIONS: A pediatric nurse in the pediatrician's office can significantly contribute to many activities for children and their families in the community. These activities include clinical care, healthcare education, disease prevention, and the organizational processes of the office. Synergic professional activity between pediatricians and pediatric nurses could ensure higher health care standards in the primary care setting.

A detailed analysis of the recurrence timing and pattern after curative surgery in patients undergoing neoadjuvant therapy or upfront surgery for gastric cancer.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine whether the administration of neoadjuvant therapy (NAD) affects the incidence, timing, and pattern of recurrence in patients treated by curative gastrectomy. METHODS: Sixty-nine patients undergoing NAD and R0 gastrectomy were compared with 198 patients undergoing upfront surgery using the propensity score matching (PSM) method. Disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS) analyses were conducted with a log-rank test and Cox regression. Risk factors for recurrence were assessed by logistic regression. RESULTS: Among 69 patients with NAD, 28 (40.6%) experienced recurrence, and signet-ring cell (SRC) carcinoma was the only factor independently associated with recurrence. In the whole sample, NAD did not influence DFS, DSS, rate of recurrence, or PFS. After PSM, the variables associated with DFS were cN1, type of gastrectomy, the presence of SRCs, and the presence of lymphovascular invasion. Variables independently associated with recurrence were cN1, type of gastrectomy, and the presence of SRCs. CONCLUSIONS: NAD had no impact on DFS, DSS, or the pattern of recurrence in any patients with gastric cancer. To define a better treatment strategy, future studies should focus on subtypes that do not respond to the current neoadjuvant regimens.

Impact of COVID-19 pandemic on pediatric patients with epilepsy - The caregiver perspective.

The recent COVID-19 pandemic has disrupted care systems around the world. We assessed how the COVID-19 pandemic affected children with epilepsy in Italy, where lockdown measures were applied from March 8 to May 4, 2020. We compiled an Italian-language online survey on changes to healthcare and views on telehealth. Invitations were sent to 6631 contacts of all patients diagnosed with epilepsy within the last 5 years at the BambinoGesù Children's Hospital in Rome. Of the 3321 responses received, 55.6% of patients were seizure-free for at least 1 year before the COVID-19-related lockdown, 74.4% used anti-seizure medications (ASMs), and 59.7% had intellectual disability. Only 10 patients (0.4%) became infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Seizure frequency remained stable for most patients during the lockdown period (increased in 13.2%; decreased in 20.3%), and seizure duration, use of rescue medications, and adherence to treatment were unchanged. Comorbidities were more affected (behavioral problems worsened in 35.8%; sleep disorder worsened in 17.0%). Visits were canceled/postponed for 41.0%, but 25.1% had remote consultation during the lockdown period (93.9% were satisfied). Most responders (67.2%) considered continued remote consultations advantageous. Our responses support that patients/caregivers are willing to embrace telemedicine for some scenarios.

Telocytes are the physiological counterpart of inflammatory fibroid polyps and PDGFRA-mutant GISTs.

PDGFRA mutations in the gastrointestinal (GI) tract can cause GI stromal tumour (GIST) and inflammatory fibroid polyp (IFP). Hitherto no cell type has been identified as a physiological counterpart of the latter, while interstitial Cajal cells (ICC) are considered the precursor of the former. However, ICC hyperplasia (ICCH), which strongly supports the ICC role in GIST pathogenesis, has been identified in germline KIT-mutant settings but not in PDGFRA-mutant ones, challenging the precursor role of ICC for PDGFRA-driven GISTs. Telocytes are a recently described interstitial cell type, CD34+/PDGFRA+. Formerly considered fibroblasts, they are found in many organs, including the GI tract where they are thought to be involved in neurotransmission. Alongside IFPs and gastric GISTs, GI wall "fibrosis" has been reported in germline PDGFRA-mutants. Taking the opportunity offered by its presence in a germline PDGFRA-mutant individual, we demonstrate that this lesion is sustained by hyperplastic telocytes, constituting the PDGFRA-mutant counterpart of germline KIT mutation-associated ICCH. Moreover, our findings support a pathogenetic relationship between telocyte hyperplasia and both IFPs and PDGFRA-mutant GISTs. We propose the term "telocytoma" for defining IFP, as it conveys both the pathogenetic (neoplastic) and histotypic ("telocytary") essence of this tumour, unlike IFP, which rather evokes an inflammatory-hyperplastic lesion.

Early Gastric Cancer: Clinical Behavior and Treatment Options. Results of an Italian Multicenter Study on Behalf of the Italian Gastric Cancer Research Group (GIRCG).

BACKGROUND: Early gastric cancer (EGC) generally has a good prognosis. However, the current definition of EGC includes various subgroups of patients with different pathological characteristics and different prognoses, some of whom have aggressive disease with a biological behavior similar to that of advanced carcinoma. MATERIALS AND METHODS: We retrospectively evaluated 1,074 patients with EGC who had undergone surgery between 1982 and 2009. The cumulative incidence function of cancer-specific mortality and competing mortality were estimated using the Fine and Gray method. RESULTS: The median follow-up period was 193 months (range 1-324). Five hundred and sixty-two (52.3%) patients died, 96 (8.9%) from EGC. The 5-, 10-, and 15-year cumulative incidence rates for mortality of all causes were 20.5% (95% confidence interval [CI] 18.0-22.9), 37.1% (95% CI 34.7-40.7), and 52.6% (95% CI 49.1-56.0), respectively; for cancer-specific mortality, 6.0% (95% CI 4.5-7.6), 9.9% (95% CI 7.9-11.9), and 11.1% (95% CI 8.8-13.3), respectively; and for mortality of other causes, 14.4% (95% CI 12.1-16.6), 27.2% (95% CI 24.2-30.2), and 41.5% (95% CI 38.1-43.3), respectively. A significant increase in the risk of cancer-specific mortality was observed for lesions >2 cm (adjusted hazard ratio [HR] = 1.44, 95% CI 1.07-1.94), Pen A-type disease (adjusted HR = 1.73, 95% CI 1.15-2.61), and node-positive cancers (adjusted HR = 2.28, 95% CI 1.61-3.21). CONCLUSION: Patients with EGC with tumors >2 cm, Pen A-type disease according to Kodama, or lymph node metastases show a poorer prognosis and an increased risk of cancer-specific mortality. IMPLICATIONS FOR PRACTICE: Early gastric cancer generally has a good prognosis, and some patients can be treated radically by endoscopic resection. However, the current definition of early gastric cancer includes subgroups of patients with an aggressive disease. In particular, patients with lymph node metastases and Pen A-type tumors according to Kodama's classification need a more invasive treatment, such as subtotal or total gastrectomy with an extended D2 lymphadenectomy, plus eventual adjuvant chemotherapy.

Comparison of high intensity focused ultrasound and radioiodine for treating toxic thyroid nodules.

PURPOSE: We compared the effectiveness of high intensity focused ultrasound (HIFU) and radioiodine (RAI) to treat patients carrying toxic thyroid nodule (TTN). Normalization of serum thyrotropin (TSH) 1 year after treatment was the primary end-point; concurrent changes in nodules' volume and scintigraphic pattern were also evaluated as secondary end-points. MATERIALS AND METHODS: Among patients ≥18 years old with TTN observed at our centre between January 1st, 2016 and December 31th, 2016 we prospectively enrolled 17 and 15 age and sex-matched patients treated with RAI and HIFU, respectively. Biochemical thyroid tests and nodules' volume were assessed before and 3, 6 and 12 months after treatments. A thyroid scintigraphy was performed before and 1 year after treatment, respectively. RESULTS: The final series included 17 patients treated with RAI and 15 patients treated with HIFU, respectively. Neither demographic nor clinical differences were found at baseline. One year after treatment 14 of 17 RAI-treated and 4 of 15 HIFU-treated patients fulfilled criteria for response to treatment (P = .0008). Indeed, the median TSH value was 1.5 IU/mL and 0.2 IU/mL in HIFU and RAI groups, respectively (P < .0001). Finally, despite a similar decrease in nodules' volume in both groups, a scintigraphic response was achieved in 16 of 17 (94%) RAI-treated compared to 8 of 15 (53%) HIFU-treated patients (P = .024), respectively. CONCLUSIONS: In our series, RAI clearly outperforms HIFU in treating patients carrying TTN and remains the first-line noninvasive treatment in such cases.

SOCS3 Immunohistochemical Expression Seems to Support the 2005 and 2014 International Society of Urological Pathology (ISUP) Modified Gleason Grading System.

BACKGROUND: In the 2014, The International Society of Urological Pathology (ISUP) consensus conference update the grading of prostate, last revised in 2005. In this study we evaluate the SOCS3 immunohistochemical protein expression in different Gleason prostatic adenocarcinoma: classical Gleason grade 3, classical Gleason grade 3 upgraded to Gleason grade 4 according to the ISUP modifications and classical and modified Gleason grade 4. The major conclusions were: (i) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (ii) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (iii) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than all as pattern 4; and (iv) Intraductal carcinoma of the prostate without invasive carcinoma should not assigned Gleason grade and a comment about aggressive carcinoma probably associated should be made. In a recent report we analyzed the methylathion status of cytokine signaling (SOCS) proteins 3 (SOCS3) gene and the consequences of promoter hypermethylation on mRNA and protein expression in a collection of prostate cancer and benign prostate hyperplasia (BPH) and for the first time we demonstrated that a hypermethylation of SOCS3 with a significant reduction of its mRNA and protein expression identifies a subgroup of prostate cancer with a more aggressive behavior. Moreover we demonstrated that the immunohystochemical analysis of SOCS3 protein expression in prostatic cancer biopsies may provide a useful and easier method than SOCS3 methylation analysis to individuate in cancer with intermediate-high grade Gleason score a subgroup of prostate cancer with a more aggressive behavior. METHODS: A total of 148 radical prostatectomy with diagnosis of prostatic acinar adenocarcinoma were stratified into three different categories on the basis of Gleason grade: (i) Twenty-six prostatic adenocarcinoma with classical and modified Gleason grade 3; (ii) Fifty seven prostatic adenocarcinoma with classical Gleason grade 3 upgraded to Gleason grade 4 by 2005 and 2014 ISUP Consensus Conference; and (iii) Sixty five prostatic adenocarcinoma with classical and modified Gleason grade 4. Immunohistochemical analysis for SOCS3 was performed and SOCS3 staining intensity were evaluated by two pathologists in three different ways on the basis of the intensity of cytoplasmatic staining: positive (intense cytoplasmatic staining in more than 50% of neoplastic cells) (+), negative (absence of cytoplasmatic staining in more than 50% of neoplastic cells) (-), weakly positive (weak cytoplasmatic staining in more than 50% of neoplastic cells (+/-). RESULTS: In the group of prostatic adenocarcinoma Gleason grade 3 we found that SOCS3 positivity (+) were observed in 19 out of 26 cases (73.1%); in 5 out of 26 prostatic adenocarcinoma the neoplastic glands showed weak intensity SOCS3 staining (+/-) (19.2%), while in only two cases we found SOCS-3 negativity (-) (7.7%); in the group of cases with prostatic adenocarcinoma with Gleason grade 4, 16 out 65 cases (24.6%) showed SOCS3 positivity (+); 18 out 65 cases (27.7%) SOCS3 weakly positive (+/-), and in 31 cases (47.7%) SOCS3 negative staining (-) were observed. Interestingly, the group of prostatic adenocarcinoma with histological Gleason 3 pattern upgraded to Gleason 4 pattern according to the 2005 and 2014 ISUP modified grading system, showed SOCS3 positivity (+) in 16 out of 57 cases (28%), in 16 out 57 cases (28%) a weakly positive for SOCS3 (+/-) were observed, while 25 cases (44%) showed negative SOCS3 staining (-). CONCLUSIONS: In this study we demonstrated a significant association of SOCS3 positivity (+) with prostatic carcinoma classical Gleason pattern 3 (P < 0.0001), while SOCS3 negative pattern (-) or SOCS3 weakly positive pattern (+/-) were associated to prostatic carcinomas with Gleason pattern 3 upgraded to Gleason pattern 4 (P = 0.0002) and with classical Gleason pattern 4. The significant difference of SOCS3 immunohistochemical expression between classical Gleason grade 3 and Gleason grade 4 upgraded to grade 4 seems to support the definitions and the modifications of Gleason grade 4 of the 2005 and the 2014 International Society of Urological Pathology (ISUP). The hypoexpression of SOCS3 protein in glomeruloid glands could support the hypothesis that from molecular point of view this growth pattern could be different from classical Gleason pattern 3 and biologically more closely to Gleason pattern 4, confirming the conclusions of the 2014 ISUP Conference assigning a Gleason pattern 4 to glomeruloid glands regardless of morphology. Prostate 77: 597-603, 2017. © 2017 Wiley Periodicals, Inc.

The Italian Research Group for Gastric Cancer (GIRCG) guidelines for gastric cancer staging and treatment: 2015.

This article reports the guidelines for gastric cancer staging and treatment developed by the GIRCG, and contains comprehensive indications for clinical management, including radiological, endoscopic, surgical, pathological, and oncological paths.

Syndromic gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of gastrointestinal tract. They feature heterogeneous triggering mechanisms, implying relevant clinical differences. The vast majority of GISTs are sporadic tumors. Rarely, however, GIST-prone syndromes occur, mostly depending on heritable GIST predisposing molecular defects involving the entire organism. These conditions need to be properly identified in order to plan appropriate diagnostic, prognostic and therapeutic procedures. Clinically, GIST-prone syndromes must be thought of whenever GISTs are multiple and/or associated with accompanying signs peculiar to the background tumorigenic trigger, either in single individuals or in kindreds. Moreover, syndromic GISTs, individually considered, tend to show distinctive features depending on the underlying condition. When applicable, genotyping is usually confirmatory. In GIST-prone conditions, the prognostic features of each GIST, defined according to the criteria routinely applied to sporadic GISTs, combine with the characters proper to the background syndromes, defining peculiar clinical settings which challenge physicians to undertake complex decisions. The latter concern preventive therapy and single tumor therapy, implying possible surgical and molecularly targeted options. In the absence of specific comprehensive guidelines, this review will highlight the traits characteristic of GIST-predisposing syndromes, with particular emphasis on diagnostic, prognostic and therapeutic implications, which can help the clinical management of these rare diseases.

PDGFRA-mutant syndrome.

Germline PDGFRA mutations cause multiple heterogeneous gastrointestinal mesenchymal tumors. In its familial form this disease, which was formerly termed intestinal neurofibromatosis/neurofibromatosis 3b (INF/NF3b), has been included among familial gastrointestinal stromal tumors (GISTs) because of its genotype, described when GIST was the only known PDGFRA-mutant gastrointestinal tumor. Shortly afterwards, however, inflammatory fibroid polyps also revealed PDGFRA mutations. Subsequently, gastrointestinal CD34+ 'fibrous tumors' of uncertain classification were described in a germline PDGFRA-mutant context. Our aim was to characterize the syndrome produced by germline PDGFRA mutations and establish diagnostic criteria and management strategies for this hitherto puzzling disease. We studied a kindred displaying multiple gastrointestinal mesenchymal tumors, comparing it with published families/individuals with possible analogous conditions. We identified a novel inherited PDGFRA mutation (P653L), constituting the third reported example of familial PDGFRA mutation. In adult mutants we detected inflammatory fibroid polyps, gastric GISTs and gastrointestinal fibrous tumors of uncertain nosology. We demonstrate that the syndrome formerly defined as INF/NF3b (exemplified by the family reported herein) is simplistically considered a form of familial GIST, because inflammatory fibroid polyps often prevail. Fibrous tumors appear variants of inflammatory fibroid polyps. 'INF/NF3b' and 'familial GIST' are misleading terms which we propose changing to 'PDGFRA-mutant syndrome'. In this condition, unlike KIT-dependent familial GIST syndromes, if present, GISTs are stomach-restricted and diffuse Cajal cell hyperplasia is not observed. This restriction of GISTs to the stomach in PDGFRA-mutant syndrome: (i) focuses oncological concern on gastric masses, as inflammatory fibroid polyps are benign; (ii) supports a selective role of gastric environment for PDGFRA mutations to elicit GISTs, justifying the known predilection for stomach of sporadic PDGFRA-mutant GISTs. An awareness that inflammatory fibroid polyps, relatively common among gastrointestinal mesenchymal tumors, may be the prevailing tumor in PDGFRA-mutant syndrome could eventually reveal an unsuspected prevalence of this condition.

Interobserver agreement and accuracy of preoperative endoscopic ultrasound-guided biopsy for histological grading of pancreatic cancer.

BACKGROUND AND STUDY AIM: Poorly differentiated/high grade pancreatic ductal adenocarcinoma (PDAC) is associated with an early unfavorable outcome, and patients with these tumors may be candidates for neo-adjuvant treatment. Endoscopic ultrasound-guided pancreatic fine-needle biopsy (EUS-FNB) may, in theory, allow preoperative assessment of PDAC histological grading. The aim of the current study was to assess the interobserver agreement and accuracy of preoperative PDAC grading from EUS-FNB specimens. METHODS: Data from 42 postsurgical PDAC patients who had undergone preoperative EUS-FNB were retrieved. Four experienced pathologists independently reviewed the EUS-FNB slides and reported tumor grading (well, moderately, or poorly differentiated). Agreement among pathologists for grading of preoperative EUS-FNB samples was expressed by using Cohen's or Fleiss' kappa statistic, as appropriate. Postsurgical PDAC grading was used as the gold standard to assess the cumulative accuracy of EUS-FNB for the preoperative prediction of PDAC grading. RESULTS: The kappa values for PDAC grading on EUS-FNB specimens ranged from 0.09 to 0.41. The total agreement among the four pathologists was only fair (κ = 0.27; 95 % confidence interval [CI] 0.14 - 0.38). When tumor grades were grouped as well or moderately differentiated vs. poorly differentiated, kappa values ranged from 0.19 to 0.50, with only a fair overall agreement (κ = 0.27; 95 %CI 0.21 - 0.49). The accuracy of preoperative grading from EUS-FNB was 56 % (75/134 readings; 95 %CI 40 % - 65 %), with mean sensitivity and specificity to detect a high grade, poorly differentiated tumor of 41 % (95 %CI 19 % - 54 %) and 78 % (53/68 readings; 95 %CI 60 % - 99 %), respectively. CONCLUSIONS: Preoperative EUS-FNB-based histological grading of PDAC is unreliable, and current results do not support the use of this information in clinical practice. This appears to be due to suboptimal interobserver agreement among pathologists and an overall low accuracy in predicting postsurgical grading.