Impact of diabetes on COVID-19-related in-hospital mortality: a retrospective study from Northern Italy.

PURPOSE: The purpose of this study was to evaluate the impact of pre-existing diabetes on in-hospital mortality in patients admitted for Coronavirus Disease 2019 (COVID-19). METHODS: This is a single center, retrospective study conducted at Policlinico di Monza hospital, located in the Lombardy region, Northern Italy. We reviewed medical records of 373 consecutive adult patients who were hospitalized with COVID-19 between February 22 and May 15, 2020. Data were collected on diabetes status, comorbid conditions and laboratory findings. Multivariable logistic regression was performed to evaluate the effect of diabetes on in-hospital mortality after adjustment for potential confounding variables. RESULTS: Mean age of the patients was 72 ± 14 years (range 17-98), 244 (65.4%) were male and 69 (18.5%) had diabetes. The most common comorbid conditions were hypertension (237 [64.8%]), cardiovascular disease (140 [37.7%]) and malignant neoplasms (50 [13.6%]). In-hospital death occurred in 142 (38.0%) patients. In the multivariable model older age (Relative Risk [RR] 1.06 [1.04-1. 09] per year), diabetes (RR 1.56 [1.05-2.02]), chronic obstructive pulmonary disease (RR 1.82 [1.13-2.35]), higher values of lactic dehydrogenase and C-reactive protein were independently associated with in-hospital mortality. CONCLUSION: In this retrospective single-center study, diabetes was independently associated with a higher in-hospital mortality. More intensive surveillance of patients with this condition is to be warranted.

Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer.

BACKGROUND: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. METHODS: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. RESULTS: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. CONCLUSIONS: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.

Impact of using different biomarkers of liver fibrosis on hepatologic referral of individuals with severe obesity and NAFLD.

PURPOSE: The purpose of this study was to estimate how many individuals with severe obesity and NAFLD should be referred to hepatologists according to the EASL-EASD-EASO guidelines and whether the choice of specific indicators of liver fibrosis would significantly impact the number of referrals. METHODS: This was a single-center retrospective study of 495 individuals with severe obesity screened at our institution between 2012 and 2018 for a bariatric surgery intervention. The guidelines were applied using the NAFLD Liver Fat Score (NLFS) to assess the presence of steatosis and the NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) and Hepamet Fibrosis Score (HFS) to assess the risk of advanced fibrosis. RESULTS: Three hundred and seventy-nine patients (76.6%) had evidence of liver steatosis. The application of the guidelines would lead to referral of 66.3% of patients using NFS, 31.7% using FIB-4 and 34.2% using HFS. When referrals due to abnormal liver function tests were excluded, these percentages dropped to 55.8%, 7.3% and 12.1%, respectively. The strongest inter-biomarker agreement was found between FIB-4 and HFS (κ = 0.86, 95% CI 0.815-0.910). CONCLUSION: Strict application of the guidelines in individuals with severe obesity would probably lead to over-referral, although a great variability exists among the different scores.

Enhanced recovery protocol in esophagectomy, is it really worth it? A cost analysis related to team experience and protocol compliance.

Application of enhanced recovery protocols (ERP) in esophageal surgery seems to lead an advantage in terms of length of hospital staying and outcomes, but only few data exist on its cost effectiveness. Previous literature analyzed pre- and post-ERP groups, finding a cost reduction with the introduction of the pathway. We aimed to study the influence on costs of accumulating experience and compliance in an ERP group. Seventy-one patients have been treated at our institution from January 2014 to June 2017 with our ERP for Ivor-Lewis esophagectomy. Direct costs were divided into subcategories and were analyzed as a function of calendar year and compliance. Factor affecting costs were searched. Univariable analysis highlighted a significant reduction in costs over time. Increase in compliance led to a progressive cost reduction for each ERP item completed (€14 852-€11 045). While age was not found to significantly influence the cost (p = 0.341), complications seemed to nullify the effect of experience: the median was €11 507 in uncomplicated patients, and increased to €13 791 in Clavien-Dindo 3-4 (CD3-4) patients. Compliance and CD3-4 remained significant also in multivariable analysis, accomplished by quantile regression, while year of surgery lost its significance. Our results evidence how accumulating experience in ERP led to a cost reduction over time, which was mainly mediated by an increase in compliance. Indeed, compliance was the main factor in reducing ERP cost while CD3-4 complications were the most important factor in cost increasing, nullifying the benefit of compliance.

NAFLD/NASH in patients with type 2 diabetes and related treatment options.

Type 2 diabetes may reduce life expectancy and patients' quality of life due to its micro- and macro-vascular complications and to the higher risk of several types of cancer. An emerging important factor is represented by the hepatic involvement; it is recognized that excessive hepatic fat accumulation represents a typical feature of diabetic patients and that it also plays an important pathogenic role. It is now evident that non-alcoholic fatty liver disease (NAFLD), generally perceived as a benign condition, may have on the contrary an important deleterious impact for diabetic patients increasing the risk to develop cardiovascular complications but also serious hepatic diseases, in particular non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Lifestyle intervention, bariatric surgery and several drug therapies have now accumulated evidence of efficacy in treating NASH. On the other hand, their durability and safety in the long-term is yet to be proven and their use may be sometimes associated with side effects or higher risk of adverse events limiting the regular administration or contraindicating it. Professional health care providers, building awareness about the importance of these hepatic complications, should put more efforts in primary prevention using a behavioral therapy needing a multidisciplinary approach, in secondary prevention applying on a regular basis in the clinical setting available predictive algorithms to identify the patients at higher cardiovascular and hepatologic risk, and in tertiary prevention treating, when not contraindicated, the diabetic patients preferentially with drugs with proven benefit on NAFLD/NASH.

Establishment of an Italian chronic migraine database: a multicenter pilot study.

To optimize chronic migraine (CM) ascertainment and phenotype definition, provide adequate clinical management and health care procedures, and rationalize economic resources allocation, we performed an exploratory multicenter pilot study aimed at establishing a CM database, the first step for developing a future Italian CM registry. We enrolled 63 consecutive CM patients in four tertiary headache centers screened with face-to-face interviews using an ad hoc dedicated semi-structured questionnaire gathering detailed information on life-style, behavioral and socio-demographic factors, comorbidities, and migraine features before and after chronicization and healthcare resource use. Our pilot study provided useful insights revealing that CM patients (1) presented in most cases symptoms of peripheral trigeminal sensitization, a relatively unexpected feature which could be useful to unravel different CM endophenotypes and to predict trigeminal-targeted treatments' responsiveness; (2) had been frequently admitted to emergency departments; (3) had undergone, sometime repeatedly, unnecessary or inappropriate investigations; (4) got rarely illness benefit exemption or disability allowance only. We deem that the expansion of the database-shortly including many other Italian headache centers-will contribute to more precisely outline CM endophenotypes, hence improving management, treatment, and economic resource allocation, ultimately reducing CM burden on both patients and health system.

Genetic prediction of long-term survival after neoadjuvant chemoradiation in locally advanced esophageal cancer.

Candidate genes involved in DNA repair, 5-fluorouracil metabolism and drug detoxification were genotyped in 124 patients receiving neoadjuvant chemoradiation treatment for locally advanced esophageal cancer and their predictive role for long-term relapse-free survival (RFS) and cancer-specific survival (CSS) were evaluated. A panel including MTHFR 677TT, MDR1 2677GT, GSTP1 114CC, XPC 499CC and XPC 939AC+CC, defined as high-risk genotypes, discriminated subgroups with significantly different outcomes. When the panel was combined with histology, patients split into two subsets with 5-year RFS and CSS rates of 65% vs 27% (hazard ratio (HR) 3.0, P<0.0001) and 69% vs 31% (HR 2.9, P<0.0001), respectively. Combining the 5-single-nucleotide polymorphism (5-SNP) panel with pathological response defined two major informative risk classes with 5-year PFS and CSS rates of 79.4% vs 17.7% (HR 6.71, P<0.0001) and 79.3% vs 26.3% (HR 6.25, P<0.0001), respectively. This classification achieved a sensitivity of 79%, a specificity of 85.4% and an accuracy of 81.8%.

Validation of two prognostic models for recurrence and survival after radical gastrectomy for gastric cancer.

BACKGROUND: Prognostic models from Korea and Italy have been developed that predict overall survival and cancer recurrence respectively after radical gastrectomy for gastric cancer. The aim of this study was to validate the two models in independent patient cohorts, and to evaluate which factors may explain differences in prognosis between Korean and Italian patients with gastric cancer. METHODS: Patients who underwent radical gastrectomy for gastric cancer between January 2000 and December 2004 at Seoul National University Hospital and at eight centres in Italy were included. Discrimination of the models was tested with receiver operating characteristic (ROC) curves and calculation of area under the curve (AUC). Calibration was evaluated by plotting actual survival probability against predicted survival probability for the Korean nomogram, and actual against predicted risk of recurrence for the Italian score. RESULTS: Some 2867 and 940 patients from Korea and Italy respectively were included. The Korean nomogram achieved good discrimination in the Italian cohort (AUC 0·80, 95 per cent c.i. 0·77 to 0·83), and the Italian model performed well in the Korean cohort (AUC 0·87, 0·85 to 0·89). The Korean nomogram also achieved good calibration, but this was not seen for the Italian model. Multivariable analyses confirmed that Italian ethnicity was an independent risk factor for cancer recurrence (odds ratio (OR) 1·72, 1·31 to 2·25; P < 0·001), but not for overall survival (OR 1·20, 0·95 to 1·53; P = 0·130). CONCLUSION: Both prognostic models performed fairly well in independent patient cohorts. Differences in recurrence rates of gastric cancer may be partially explained by ethnicity.

Meditation training for people with amyotrophic lateral sclerosis: a randomized clinical trial.

BACKGROUND AND PURPOSE: Studies investigating psychological interventions for the promotion of well-being in people with amyotrophic lateral sclerosis (ALS) are lacking. The purpose of the current study was to examine the use of an ALS-specific mindfulness-based intervention for improving quality of life in this population. METHODS: A randomized, open-label and controlled clinical trial was conducted on the efficacy of an ALS-specific meditation programme in promoting quality of life. Adults who received a diagnosis of ALS within 18 months were randomly assigned either to usual care or to an 8-week meditation training based on the original mindfulness-based stress reduction programme and tailored for people with ALS. Quality of life, assessed with the ALS-Specific Quality of Life Revised scale, represented the primary outcome, whilst secondary outcomes included anxiety and depression, assessed with the Hospital Anxiety and Depression Scale, and specific quality of life domains. Participants were assessed at recruitment and after 2, 6 and 12 months. The efficacy of the treatment was assessed on an intention-to-treat basis of a linear mixed model. RESULTS: A hundred participants were recruited between November 2012 and December 2014. Over time, there was a significant difference between the two groups in terms of quality of life (ß = 0.24, P = 0.015, d = 0.89). Significant differences between groups over time were also found for anxiety, depression, negative emotions, and interaction with people and the environment. CONCLUSIONS: An ALS-specific meditation programme is beneficial for the quality of life and psychological well-being of people with ALS.

New minimally invasive technique for cystoscopic laser treatment of fetal ureterocele.

Prenatal ultrasound detection of fetal ureterocele with bilateral hydroureteronephrosis, obstruction of the bladder outlet and progressive amniotic fluid reduction have been associated with a significant risk of end-stage chronic renal disease after birth. Fetal cystoscopic laser incision of the ureterocele, using standard 3.5-mm fetoscopic access to the amniotic cavity and the fetal bladder with the aim of relieving the bladder outflow obstruction to preserve renal function, has been reported previously in a case with a favorable outcome. We report on two additional cases of fetal ureterocele treated by cystoscopic laser decompression. In the first case, a standard 3.3-mm uterine entry was used. In the second case, a new approach was adopted using an 'all-seeing needle' 1.6-mm endoscope. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Enhanced recovery after surgery protocol in patients undergoing esophagectomy for cancer: a single center experience.

This article is about an emerging issue in esophageal surgery: enhanced recovery after surgery (ERAS) Few data are published in literature and its safety and feasibility is still debated. The focus of our paper is on the feasibility of an ERAS protocol for esophagectomy (including both the Ivor-Lewis and McKeown procedure) in a high volume center comparing to a standard perioperative protocol. We introduced a novelty item on this type of surgery: resume of oral feeding in the first postoperative day. We analyzed the dropout rate for each item and the postoperative morbidity. We studied 39 patients operated in the Upper GI division of Verona University Hospital between January 2013 and August 2014; 22 patients (ERAS group) were studied in a perspective way while 17 patients (standard group) were studied retrospectively. The enhanced recovery protocol included intraoperative fluid management, time of extubation after surgery, intensive care unit discharge, drains and nasogastric tube management, mobilization of the patient, oral food intake. We compared the results between the two groups in term of hospital stay, postoperative morbidity and mortality. We also calculated the percentage completion of the protocol, evaluating patient drop-out rates for each of the items. Patients showed an improvement in the ERAS group in terms of earlier extubation, earlier intensive care unit discharge (p < 0.01), earlier thoracic drain, urinary catheter (p < 0.01) and nasogastric tube removal (p = 0.02), earlier mobilization (p < 0.01), and resume of oral feeding (p < 0.01). Median length of hospital stays in the ERAS group was 9 days while in the standard group was 10 days (p = 0.23). Postoperative morbidity and mortality were comparable between the two groups. This study shows the feasibility and safety of an ERAS protocol for esophageal surgery in a high-volume center. These data strengthen the literature results on this argument calling for larger sample size studies.

Evidence for a Strong Topological Insulator Phase in ZrTe_{5}.

The complex electronic properties of ZrTe_{5} have recently stimulated in-depth investigations that assigned this material to either a topological insulator or a 3D Dirac semimetal phase. Here we report a comprehensive experimental and theoretical study of both electronic and structural properties of ZrTe_{5}, revealing that the bulk material is a strong topological insulator (STI). By means of angle-resolved photoelectron spectroscopy, we identify at the top of the valence band both a surface and a bulk state. The dispersion of these bands is well captured by ab initio calculations for the STI case, for the specific interlayer distance measured in our x-ray diffraction study. Furthermore, these findings are supported by scanning tunneling spectroscopy revealing the metallic character of the sample surface, thus confirming the strong topological nature of ZrTe_{5}.

Ultrafast dynamics in unaligned MWCNTs decorated with metal nanoparticles.

The relaxation dynamics of unaligned multi-walled carbon nanotubes decorated with metallic nanoparticles have been studied by using transient optical measurements. The fast dynamics due to the short-lived free-charge carriers excited by the pump are not affected by the presence of nanoparticles. Conversely, a second long dynamics, absent in bare carbon nanotubes, appears only in the decorated samples. A combination of experiment and theory allows us to ascribe this long dynamics to relaxation channels involving electronic states localized at the tube-nanoparticle interface.

TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients.

BACKGROUND: About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor ß activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma. METHODS: TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT-PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma. RESULTS: In vitro, (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard's tumour regression grade classifications, respectively). CONCLUSIONS: The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy.

Ultrafast Optical Control of the Electronic Properties of ZrTe5.

We report on the temperature dependence of the ZrTe(5) electronic properties, studied at equilibrium and out of equilibrium, by means of time and angle resolved photoelectron spectroscopy. Our results unveil the dependence of the electronic band structure across the Fermi energy on the sample temperature. This finding is regarded as the dominant mechanism responsible for the anomalous resistivity observed at T*∼160 K along with the change of the charge carrier character from holelike to electronlike. Having addressed these long-lasting questions, we prove the possibility to control, at the ultrashort time scale, both the binding energy and the quasiparticle lifetime of the valence band. These experimental evidences pave the way for optically controlling the thermoelectric and magnetoelectric transport properties of ZrTe(5).

Chronic headaches: a clinician's experience of ICHD-3 beta.

The International Classification of Headache Disorders, 3rd edition (beta version) has significantly improved the categorization of chronic headaches. From a clinical standpoint, however, it still has a few limitations, both general and specific. Among the former is the fact that international headache classifications are aimed less at defining the disease than at characterizing the features of attacks, meaning that their structure is ill suited to dealing with chronic headaches where the patient must be the focus of the discussion. Among the latter is the fact that the diagnostic criteria for chronic migraine do not distinguish between cases differing widely in severity and that the issue of whether medication overuse headache can be considered an autonomous entity is still unsolved. We propose that changes be made in the systematizations of chronic migraine and medication overuse headache to make them more consistent with clinical practice.

The PACE study: past-year prevalence of tension-type headache and its subtypes in Parma's adult general population.

The mean global prevalence of tension-type headache (TTH) in adult is 42 %. To date, there have been no Italian studies on TTH prevalence in the adult general population. Therefore, we conducted a cross-sectional study, called PACE, aimed at detecting the prevalence of primary headaches in the city of Parma's adult general population. 904 subjects representative of Parma's adult general population were interviewed face to face by a physician of our Headache Centre. Crude past-year prevalence for definite TTH was 19.4 % (95 % CI 16.8-21.9; 18.4 %, 95 % CI 14.6-22.3 in men, and 20.1 %, 95 % CI 16.6-23.6 in women), namely, 9.0 % (95 % CI 7.1-10.8) for infrequent TTH, 9.8 % (95 % CI 7.9-11.8) for frequent TTH, and 0.6 % (95 % CI 0.1-1) for chronic TTH. Crude prevalence for probable TTH was 2.3 % (95 % CI 1.3-3.3; 2 %, 95 % CI 0.6-3.4 in men, and 2.6 %, 95 % CI 1.2-3.9 in women). Our results indicate a TTH prevalence (19.4 %) at the lower limit of data ranges for Western countries, and prevalence rates for infrequent forms (9 %) do not appear different from those of frequent forms (9.8 %).

Concurrent comparison of the measurement properties of generic and disease-specific questionnaires in obese inpatients.

BACKGROUND: The concurrent comparison of questionnaires assessing health-related quality of life in the same population is necessary for better appreciating their performance and to select the best instrument for a given purpose (e.g. clinical trials and observational studies). AIM: The aim of this study was to compare the measurement properties of two disease-specific and generic questionnaires: the Obesity-related Well-Being (ORWELL97), the Obesity-Related Disability test (TSD-OC), the EuroQoL, and the World Health Organization Quality of Life questionnaire. MATERIALS/SUBJECTS: Two-hundreds and forty-nine obese inpatients [age 47 (standard deviation, SD 15) years, body mass index 44.4 (SD 5.2) kg/m(2), 69 % female] completed the four questionnaires before and after a 3-week multidisciplinary weight reduction program. Standard measurement properties were calculated and compared. RESULTS: Intra-class correlation coefficient ranged from 0.73 to 0.90 for most of the instruments and subscales. The standard error of measurement ranged from 9 to 21 % for the generic instruments, and from 9 to 44 % for the specific questionnaires. Missing data and ceiling effects were found for TSD-OC. Responsiveness was similar for all the instruments. The correlations between the change scores of the instruments were small (<0.37). CONCLUSIONS: It was not possible to identify a "best" instrument, but overall the ORWELL97 seems to show better measurement properties. The two specific instruments measured different constructs and they did not show a clear superior performance compared to the generic questionnaires.

Surgical and functional outcomes of Dorsal Inlay Graft urethroplasty in revision vs primary hypospadias repair in the pediatric age.

INTRODUCTION: Over the years, Dorsal Inlay Graft (DIG) urethroplasty has gained worldwide acceptance for primary hypospadias repair. However, its safety and effectiveness for revision surgery are yet to be proven. OBJECTIVE: The aim of the study is to assess and compare complication rates and functional outcomes of DIG surgery in revision versus primary hypospadias repair. MATERIAL AND METHODS: We carried out a retrospective analysis of data collected from 53 consecutive DIG urethroplasties performed by a single surgeon at our institution. Patients were stratified in two groups - primary repair and redo-urethroplasty. For each group, we recorded standard pre-operative characteristics, surgical technicalities, complication rates and uroflowmetry parameters. RESULTS: Out of 53 DIG urethroplasties, 21 (39.6 %) where primary and 32 (60.4 %) were re-do. As expected, the two groups differed for median age at surgery: 20 months for primary and 68.5 months for revision surgery (p < 0.001). Additionally, all 21 (100 %) primary interventions were performed with a preputial graft, whereas among revision DIG urethroplasties only 2 (6.3 %) where preputial and 30 (93.8 %) were buccal (p < 0.001). Catheterization time (7 vs 8 days, p = 0.155) and postoperative complication rates (14.3 % vs 9.4 %, p = 0.581) were comparable between the primary and revision surgery group, respectively (all p > .05). Forty-two of the 53 patients underwent uroflowmetry during follow-up. Of these, 19 (63 %) patients presented with abnormal uroflowmetry and 11 (37 %) had equivocal parameters with no difference between the two groups. DISCUSSION: Dorsal Inlay Graft urethroplasty has long been known to be safe and effective for primary hypospadias repair. On the other hand, data on dorsal inlay graft urethroplasty as a salvage surgery after primary hypospadias repair failure is scarce. Surprisingly, according to our findings, surgical outcomes and complication rates are comparable between primary and revision hypospadias cases. Additionally, our results in the redo group are absolutely encouraging if compared to those reported in the literature for the same subset of patients. CONCLUSIONS: According to our findings, DIG urethroplasty is a safe and effective option to treat revision hypospadias repair.

A clinical-biological risk stratification model for resected gastric cancer: prognostic impact of Her2, Fhit, and APC expression status.

BACKGROUND: To obtain a prognostic stratification model for resected gastric cancer patients. PATIENTS AND METHODS: Clinicopathological and molecular data (expression of Cdx2, Apc, ß-catenin, E-cadherin, Fhit, p53, and human epidermal growth factor receptor-2 (Her2); HER2 and TOPO2A gene copy number; PIK3CA mutations; microsatellite instability) were correlated to cancer-specific/overall survival (CSS/OS) using a Cox model. Individual patient probability (IPP) was estimated by logistic equation. A continuous score to identify risk-classes was derived according to the model ratios. RESULTS: Two-hundred eight patients were studied (median follow-up 20 months). At multivariate analysis, sex, stage, margins, location, nodes, Apc, and Fhit were independent predictors for CSS; the same factors (and age and Her2, except Fhit) predicted OS. Multivariate model predicted IPP with high prognostic accuracy (0.90 for CSS; 0.91 for OS). A two-class model significantly separated low- and high-risk patients for CSS (23.4% and 85.6%, P < 0.0001) and OS (21.4% and 82.0%, P < 0.0001). A three-class model differentiated low-, intermediate-, and high-risk patients for CSS (6.3%, 35.3%, and 88.0%, P < 0.0001) and OS (6.1%, 34.6%, and 86.5%, P < 0.0001). CONCLUSIONS: A risk classification system comprising the immunohistochemical expression of three proteins (Apc, Fhit, and Her2) and five clinicopathological parameters (stage, resected nodes, margins, location, and sex) accurately separates the resected gastric cancer patients into three classes of risk.