Meta-analysis of microsatellite instability in relation to clinicopathological characteristics and overall survival in gastric cancer.

BACKGROUND: Several associations between microsatellite instability (MSI) and other clinicopathological factors have been reported in gastric cancer, but the results have been ambiguous. This systematic review and meta-analysis investigated the relationship between MSI and overall survival and clinicopathological characteristics of patients with gastric cancer. METHODS: A systematic literature search of the PubMed, Cochrane and Ovid databases until 31 January 2016 was performed in accordance with the PRISMA statement. The articles were screened independently according to PICO (population, intervention, comparator, outcome) eligibility criteria. All eligible articles were evaluated independently by two reviewers for risk of bias according to the Quality In Prognosis Study tool. RESULTS: Overall, 48 studies with a total of 18 612 patients were included. MSI was found in 9·2 per cent of patients (1718 of 18 612), and was associated with female sex (odds ratio (OR) 1·57, 95 per cent c.i. 1·31 to 1·89; P < 0·001), older age (OR 1·58, 2·20 to 1·13; P < 0·001), intestinal Laurén histological type (OR 2·23, 1·94 to 2·57; P < 0·001), mid/lower gastric location (OR 0·38, 0·32 to 0·44; P < 0·001), lack of lymph node metastases (OR 0·70, 0·57 to 0·86, P < 0·001) and TNM stage I-II (OR 1·77, 1·47 to 2·13; P < 0·001). The pooled hazard ratio for overall survival of patients with MSI versus those with non-MSI gastric cancer from 21 studies was 0·69 (95 per cent c.i. 0·56 to 0·86; P < 0·001). CONCLUSION: MSI in gastric cancer was associated with good overall survival, reflected in several favourable clinicopathological tumour characteristics.

Cyberknife® system: a new therapeutic strategy for sinonasal solitary extramedullary plasmacytomae.

Sino-nasal solitary extramedullary plasmacytoma (EMP) is a rare neoplasm with unpredictable progression to multiple myeloma. To improve the precision of irradiation delivery, preserving the healthy surrounding tissue and critical structures we used a CyberKnife® for the treatment of sinonasal solitary extramedullary plasmacytoma. We present the first case of sinonasal-EMP treated with CyberKnife®-stereotactic radiotherapy (SRT) with a complete remission without adverse events. Based on the post-therapeutic results and healthy tissue preservation, we believe that CyberKnife®-SRT represents a good therapeutic option for the treatment of sinonasal-EMP.

The 14bp-deletion allele in the HLA-G gene confers susceptibility to the development of hepatocellular carcinoma in the Brazilian population.

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule involved in tumor escape mechanisms. Considering that the HLA-G 14bp insertion/deletion polymorphism is located at the 3' untranslated region (3'UTR) in exon 8, and since it has been associated with the magnitude of HLA-G production, we studied the association of 14bp insertion/deletion polymorphism with the risk of developing hepatocellular carcinoma (HCC). A total of 109 HCC patients followed at the University Hospital, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil, and 202 healthy controls from the same geographic area were genotyped for the 14bp insertion/deletion polymorphism using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis. Compared to controls, the frequency of the 14bp deletion allele was overrepresented in HCC patients (65% versus 56%, respectively, P = 0.0326). The 14bp deletion conferred an odds ratio (OR) of 1.46 [95% confidence interval (CI): 1.04-2.05]. Similarly, the deletion/deletion genotype was marginally overrepresented in HCC patients (45% versus 35% in controls, P = 0.0871), conferring an OR of 1.54 (95% CI: 0.96-2.48). The frequencies of the deletion/insertion or insertion/insertion genotypes observed in patients were not statistically different from those observed in controls (P > 0.05). Our results suggest that the 14bp-deletion allele in HLA-G gene is associated with HCC susceptibility in a Brazilian population.

Current status and future perspectives in HER2 positive advanced gastric cancer.

Gastric cancer is one of the most common malignancy worldwide with a prognosis less than 1 year in unresectable or metastatic disease. HER2 expression is the main biomarker to lead the addition of trastuzumab to first line systemic chemotherapy improving the overall survival in advanced HER2-positivegastric adenocarcinoma. The inevitable development of resistance to trastuzumab remains a great problem inasmuch several treatment strategies that have proven effective in breast cancer failed to show clinical benefit in advanced gastric cancer. In this review, we summarize the available data on the mechanisms underlying primary and secondary resistance toHER2-targeted therapy and current challenges in the treatment of HER2-positive advanced gastric cancer refractory to trastuzumab. Further, we describe the prognostic value of new non-invasive screening techniques, the current development of novel agents such us HER2 antibody-drug conjugates and bispecific antibodies, and the strategies with antitumor activity on going.

Long-term outcomes in ypT0 rectal cancers: An international multi-centric investigation on behalf of Italian Society of Surgical Oncology Young Board (YSICO).

AIM: To investigate the outcome and pattern of survivals of rectal cancer patients presenting a complete or nearly complete tumor response after neo-adjuvant treatment. METHODS: Young surgeons <40 years old affiliated to the Italian Society of Surgical Oncology (YSICO) from 13 referral centers for colorectal cancer treatment, were invited to participate a retrospective study. Records from patients treated from 2005 to 2015 with a pathological diagnosis of ypT0/ypTis were retrieved and pooled in a common data-base for statistical purposes. All clinical and pathological variables were reviewed. Univariate and multivariate analyses were conducted with the end-point of survivals. RESULTS: Two hundreds and sixty-one patients were analyzed including 237 ypT0 and 24 ypTis. Nodal positive patients were 8.7%. More than sixty-six percent of the patients did not perform adjuvant chemotherapy, with a statistical difference comparing N0 versus N+ patients (66.8% vs 40.9%, p 0.02). Mean follow-up was of 47.6 months. Twenty-two relapses were observed, 91.6% at a distant site. The mean time to recurrence was of 35.3 months. On univariate analysis, the use of adjuvant chemotherapy correlated with better OS exclusively in ypT0N + patients and not in ypT0N0. Univariate and multivariate analyses documented nodal positivity as the only prognostic factor correlated with a worse OS. CONCLUSION: Recurrences were mostly diagnosed at a distant site and within the third year of follow-up. Nodal positivity was the only variable independently correlated with a worse OS. Univariate analysis documented a benefit for the use of adjuvant chemotherapy treatment exclusively in ypT0N + rectal cancers.

Surgical management of advanced gastric cancer: An evolving issue.

Worldwide, gastric cancer represents the fifth most common cancer and the third leading cause of cancer deaths. Although the overall 5-year survival for resectable disease was more than 70% in Japan due to the implementation of screening programs resulting in detection of disease at earlier stages, in Western countries more than two thirds of gastric cancers are usually diagnosed in advanced stages reporting a 5-year survival rate of only 25.7%. Anyway surgical resection with extended lymph node dissection remains the only curative therapy for non-metastatic advanced gastric cancer, while neoadjuvant and adjuvant chemotherapies can improve the outcomes aimed at the reduction of recurrence and extension of survival. High-quality research and advances in technologies have contributed to well define the oncological outcomes and have stimulated many clinical studies testing multimodality managements in the advanced disease setting. This review article aims to outline and discuss open issues in current surgical management of advanced gastric cancer.

Duodenal gastrointestinal stromal tumor: From clinicopathological features to surgical outcomes.

Duodenal gastrointestinal tumors represent an extremely rare subset of stromal tumors arising from interstitial cells of Cajal. In the last 30 years the comprehension of the pathophysiology and natural history of this previously misunderstood clinical entity, in association with developments in endoscopy, imaging technology, and immunohistochemistry has resulted in novel diagnostic and treatment approaches. This is a comprehensive review of the current data of the literature on the various aspects of the diagnosis and treatment of these tumors. The duodenum is the less commonly involved site for these tumors in the digestive tract. Endoscopy and computed tomography can usually establish the diagnosis, confirmed by immunohistochemical staining and occasionally molecular genetic analysis. Endoscopic ultrasound with fine needle aspiration has been recently found to be the gold diagnostic standard with high sensitivity and specificity rates, diagnosing GIST in up to 80% of patients. Due to the complex anatomy of the pancreatico-duodenal region optimal therapeutic strategy of duodenal GISTs are challenging. Nevertheless surgical resection with microscopically clear resection margins seems to be the only potentially curative treatment for non-metastatic primary GISTs of the duodenum. Imatinib mesylate plays a key role in the management of GISTs both as neoadjuvant therapy and in patients with recurrent and metastatic disease. Meanwhile, the advances in the comprehension of the pathophysiology and natural history of this previously misunderstood clinical entity as well as the treatment of these tumors may render feasible, in the near future, the advent of newer and more effective treatment options.

Effects of glibenclamide on ventricular fibrillation in non-insulin-dependent diabetics with acute myocardial infarction.

BACKGROUND: Glibenclamide, a hypoglycemic sulfonylurea, has shown antiarrhythmic effects in acutely ischemic myocardium. The aim of the present study was to evaluate the effectiveness of the drug in preventing ventricular fibrillation in diabetic patients with acute myocardial infarction. METHODS: We studied 232 patients with non-insulin-dependent diabetes mellitus (106 on glibenclamide, group A1; 126 treated with another hypoglycemic drug or with diet only, group A2) and 830 non-diabetic people. All the patients were admitted to our coronary care unit with their first myocardial infarction. RESULTS: Ventricular fibrillation occurred in 1.9% of group A1, 7.9% of group A2, and 9.9% of the non-diabetic (A1 versus A2, P < 0.05; A2 versus the non-diabetic group, NS; A1 versus the non-diabetic group, P < 0.01). Sustained ventricular tachycardia was not significantly different among the groups. CONCLUSIONS: The antiarrhythmic effectiveness of glibenclamide might be related to its blocking action on the ATP-dependent potassium channel, with consequent attenuation of the efflux of potassium induced by ischemia. We also observed a higher mortality rate resulting from heart failure in group A2 than in group A1 or the non-diabetic group. Since glibenclamide has never shown significant effects on myocardial contractility, this finding remains to be elucidated. Glibenclamide therefore appears to have an antifibrillatory effect in acute myocardial infarction; with respect to acute coronary events, the drug might be able to prevent ventricular fibrillation, which is most often fatal when it occurs before hospitalization.

Effects of infusion of glucose-insulin-potassium on myocardial function after a recent myocardial infarction.

UNLABELLED: We studied the effects of glucose, insulin, and KCl infusion (GIK), on regional myocardial perfusion and function by 99m-Tc-tetrofosmin-gated SPECT. METHODS: We studied 21 male patients with their first uncomplicated acute myocardial infarction (AMI). All patients underwent a rest and submaximal stress before and after 24-hour infusion of GIK-solution (group A) or saline solution (group B). RESULTS: Group A showed better stress tolerance and ischaemic threshold improvement after GIK infusion whilst no statistical differences were found between basal and post-infusion test in group B. At first the stress test in group A, of the 192 segments analysed, 52 (27%) showed reversible perfusion defect. In group B, of 144 segments analysed, 31 (21%) showed reversible perfusion defect. A post-infusion analysis in group A showed a post-GIK end-diastolic significant count improvement in 21 segments, and a post-GIK end-systolic count improvement in 22 segments. In group B, perfusion increase was observed only in 4 segments, whilst systolic thickening increase was observed only in 1 segment. CONCLUSION: These data demonstrate the efficacy of GIK infusion to improve regional myocardial perfusion and function mainly in segments adjacent to the recently infarcted area.

A new method to make vascular and bronchial casts of voluminous organs.

Vascular and bronchial endocasts represent a useful instrument to study the ramification pattern of these structures. Casts have been made from different materials, such as waxes in ancient times and, more recently, silicon-like compounds or resins (see e.g. Mercox) to study the finest details. These techniques are valuable for small specimens, whereas they are inadequate for very large organs, where technical difficulties require the development of specific instrumentation. In this study we present a new simple injection technique, based on expanded polyurethane, which allows preparing vascular and bronchial trees for macroscopic and microscopic studies. The new injection technique is very easy to carry out, since the propulsion is provided by compressed air, and it does not require special instrumentation. To this aim, endocasts of the entire tracheal-bronchial tree and casts of vascular kidney from different animals were prepared. The specimens have a very low weight, show the finest ramifications, and are very stable and resistant to mechanical stress. To examine microscopically the details of the casts, specimens from the kidney cast were also analyzed by scanning electron microscopy, revealing good preservation of microcirculatory structures, functional sphincters and endothelial cell impressions. Therefore, the technique may be useful for macroscopic studies of large specimens, retaining sufficiently fine details.

[Detection and assessment of myocardial stunning with perfusion tomographic scintigraphy using gated SPECT]. / Rivelazione e valutazione di stordimento miocardico mediante tomoscintigrafia di perfusione con metodica gated-SPECT.

BACKGROUND: Gated-SPECT using 99mTc-labeled flow tracers provides the simultaneous assessment of global and regional myocardial perfusion and function. The aim of this study was to identify patients with stress-induced postischemic stunning, among those with reversible stress perfusion defects, and patients with artifactual defects among those with fixed defects, in order to assess the value of the functional data provided by gated acquisition of perfusion imaging in the characterization of ischemia. METHODS: We studied 221 consecutive patients who underwent conventional diagnostic dual day stress/rest gated-SPECT following injection of 925 MBq of 99mTc-tetrofosmin using a dual head SPECT camera, 115 of whom (52%) showed reversible perfusion defects, and 66 (30%) fixed defects. Perfusion was analyzed on ungated images using 20 segments scored on a 5-point scale (0 = normal, 4 = no uptake), while wall thickening was assessed visually on stress/rest end-systolic images using a 4-point score (0 = normal, 3 = absence of wall thickening). Left ventricular ejection fraction and volumes were calculated using an automatic algorithm (quantitative gated-SPECT). Fifty-two out of 221 (23.5%) patients underwent coronary angiography. RESULTS: In 40/115 (35%) patients with reversible perfusion defects, post-stress left ventricular ejection fraction was > 5% lower than that at rest (Group A: stunned), whereas in the remaining 75 patients, post-stress left ventricular ejection fraction was either +/- 5% or greater than that at rest (Group B: non-stunned). Peak exercise angina and ischemic electrocardiographic response to exercise were present in 79 and 58% respectively of Group A patients and in 33 and 39% of Group B patients. The number of patients with multivessel disease was significantly higher in Group A compared to Group B (58 vs 41%, p < 0.05). The total stress and rest perfusion scores were significantly higher in Group A than in Group B (p < 0.01); even the total stress wall thickening score was significantly higher in Group A (p < 0.001). As for global parameters, post-stress end-systolic volume was significantly higher in the stunned group (p < 0.05). In 40 out of 66 (60.5%) patients without reversible ischemia fixed defects were judged to be ischemic (Group C), while in 26/66 (39.5%) they were attributed to attenuation artifacts (Group D). Eighty percent of Group C patients had a previous myocardial infarction against none of Group D. Stress/rest perfusion and wall thickening scores were significantly higher in Group C than in Group D. CONCLUSIONS: Gated-SPECT myocardial perfusion evaluation allowed us to identify a subgroup of post-stress stunned coronary artery diseased patients. The post-stress left ventricular ejection fraction reduction in this population seems to be due to the increase in end-systolic volume. The stunned patients showed more severe perfusion defects and wall thickening abnormalities.

[Religious diversity in hospitals: an aspect to be considered?]. / La diversità religiosa in ospedale: un aspetto da considerare?

A study was undertaken among 132 nurses in two religions and two public hospitals on religious needs among patients from oriental countries. Aim of the research was to investigate the religious needs, among patients generally and particularly, among oriental religions and how nurses and hospital administrations are considering those needs. From the results it was evidenced that nurses in religious hospital paid more attention, to patients needs, than those in public hospital. Both groups of nurses seemed to pay little attention concerning liturgy, during hospitalization and especially when caring for a patient that is dying. A recommendation is therefore to adapt nursing care plan including "religion" and besides to prepare information supports with details on practices and living conditions regarding major oriental religions existing in Italy.

Alleles and genotypes of polymorphisms of IL-18, TNF-α and IFN-γ are associated with a higher risk and severity of hepatocellular carcinoma (HCC) in Brazil.

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver. We evaluated the association of alleles and genotypes of polymorphisms of IL-18 (-607C/A and -137G/C), IFN-γ (+874T/A) and TNF-α (-238G/A and -308G/A) with the risk and severity of HCC. One-hundred-and-twelve patients with HCC and 202 healthy controls were studied. Single nucleotide polymorphisms (SNPs) were amplified by PCR with specific primers and the products were submitted to polyacrylamide gel electrophoresis and stained with silver. We evaluated tumor presentation, tumor size and presence of metastasis. Significant higher risk of HCC was associated with: alleles IL-18 -607(*)A (P=0.0235; OR=1.48; 95%CI=1.06-2.08); TNF-α -238(*)A (P=0.0025; OR=2.12; 95%CI=1.32-3.40) and TNF-α -308(*)A (P=0.0351; OR=1.82; 95%CI=1.07-3.08); and genotypes IL-18-607AA (P=0.0048; OR=3.03; 95%CI=1.40-6.55); TNF-α -238GA (P=0.0011; OR=2.44; 95%CI=1.45-4.12); and TNF-α -308GA (P=0.0031; OR=2.51; 95%CI=1.39-4.51). Significant association was found between multinodular HCC and IL-18 -607(*)C allele (P=0.029; OR=2.40, 95%CI: 1.09-5.28), and IL-18 -607CC genotype (P=0.028; OR=3.5, 95%CI: 1.24-9.86). Diffuse HCC was significantly associated with IFN-γ +874TA genotype (P=0.044; OR=3.6, 95%CI: 1.03-12.47). The IL-18 -137(∗)C allele showed a significant association with the presence of metastasis. Thus, IL-18 -607(*)A and TNF-α (-238(*)A and -308(*)A) alleles may confer susceptibility to HCC, while IL-18 -607(*)C and -137(*)C alleles more severe disease.

Idebenone treatment in Friedreich patients: one-year-long randomized placebo-controlled trial.

The authors carried out a 1-year, randomized, placebo-controlled trial of idebenone in 29 patients with Friedreich ataxia. They found significant reductions of interventricular septal thickness and left ventricular mass in the idebenone group vs the placebo group, with no improvement in other heart ultrasound measures or neurologic condition. The absolute cardiac changes were modest, but the findings suggest that larger trials should assess whether idebenone reduces ventricular hypertrophy in patients with Friedreich ataxia.

[A comparison between attenuation-corrected and -uncorrected transmission-emission SPECT images obtained with Tl-201 in CAD patients]. / Confronto tra immagini SPECT trasmissive-emissive corrette per attenuazione e non corrette, ottenute con Tl-201 in coronaropatici.

BACKGROUND: The aim of this study was to evaluate the impact of attenuation correction (AC) on the diagnostic accuracy of conventional stress/red thallium SPECT studies. METHODS: We studied 60 consecutive patients (36 males) who underwent conventional diagnostic stress/red study with and without AC (NAC) using a dual-head SPECT camera (Vertex ADAC) with a 153Gd source. The mean age of these patients was 60 years (30-80) and 29 of the subjects had a history of MI. Reconstructed images were visually analyzed using 20 segments scored on a 5-point scale (0 = normal, 4 = no uptake). Diagnostic accuracy was evaluated in 24 consecutive patients who underwent coronary angiography. Polar plots from each of the four reconstructed data sets per patient were normalized on the maximum and quantified using a nine segment model. RESULTS: The comparison between the segmental stress score obtained with and without AC showed agreement in 1057 out of 1200 (88%) segments analyzed, K statistic value = 0.67. The number of fixed defects was significantly lower after AC. The diagnostic accuracy, evaluated in 24 patients (480 segs), was not significantly different between AC and NAC analysis (80 vs 84% respectively). CONCLUSIONS: AC seems to reduce the number of fixed defects due to attenuation artefacts without improving diagnostic accuracy, probably because of the low number of subjects submitted to angiography and of the interpreting bias due to the expertise of the operators. In fact, in the rather small group of patients evaluated, no improvement in diagnostic accuracy was observed, probably because several attenuation defects were not considered pathological due to operator expertise.

[Myocardial scintigraphy by the gated SPECT method in coronary disease patients with postischemic stunning]. / Scintigrafia miocardica con metodica gated SPECT in coronaropatici con stordimento post-ischemico.

UNLABELLED: Gated SPECT using Tc-99m-labeled flow tracers provides simultaneous assessment of global and regional myocardial perfusion and function. The aim of this study was to evaluate whether regional wall thickening (WT) obtained after stress and at rest makes it possible to identify and analyze a subgroup of post-ischemic stunned patients. METHODS: We studied 20 patients (18 males) who underwent conventional diagnostic dual-day stress/rest Gated SPECT following injection of 925 MBq of 99mTc-tetrofosmin using a dual-head SPECT camera (Vertex ADAC). The mean age of these patients was 59 years (38-71) and 10 of them had a history of previous acute myocardial infarction (AMI). Perfusion was analyzed on ungated images using 20 segments scored on a 5-point scale (0 = normal, 4 = no uptake), while WT and motion were assessed visually on stress/rest end-systolic images using a 4-point score (0 = normal, 3 = absence of WT/motion). Left ventricular ejection fraction (LVEF) and volumes were calculated. All patients underwent coronary angiography. RESULTS: All patients showed at least one reversible defect with post-stress WT reduction and normal rest WT. The stunned group showed a significant post-stress reduction of LVEF and a statistically non-significant increase of end systolic volume (ESV). A good correlation was observed between global perfusion and WT score both at stress and rest conditions; LVEF showed a significant inverse correlation with global post-stress and rest perfusion and WT score. ESV and the global perfusion stress/rest score showed a good correlation, while end-diastolic volume did not correlate. In 44% of the segments with fixed defects, there was a normal WT and normal coronary-related vessel (false positives); 28% of reversible segments showed a post-stress pathological WT and five of them a rest pathological WT. CONCLUSIONS: The gated SPECT myocardial perfusion evaluation allowed us to analyze a subgroup of post-stress stunned coronary artery disease patients. The post-stress LVEF reduction in this population seems to be due to the increase of end-systolic volume caused by endocardial ischemia. The stunned segments showed severe perfusion defects.