Genetic Features of Metachronous Esophageal Cancer Developed in Hodgkin's Lymphoma or Breast Cancer Long-Term Survivors: An Exploratory Study.

Background Development of novel therapeutic drugs and regimens for cancer treatment has led to improvements in patient long-term survival. This success has, however, been accompanied by the increased occurrence of second primary cancers. Indeed, patients who received regional radiotherapy for Hodgkin's Lymphoma (HL) or breast cancer may develop, many years later, a solid metachronous tumor in the irradiated field. Despite extensive epidemiological studies, little information is available on the genetic changes involved in the pathogenesis of these solid therapy-related neoplasms. Methods Using microsatellite markers located in 7 chromosomal regions frequently deleted in sporadic esophageal cancer, we investigated loss of heterozygosity (LOH) and microsatellite instability (MSI) in 46 paired (normal and tumor) samples. Twenty samples were of esophageal carcinoma developed in HL or breast cancer long-term survivors: 14 squamous cell carcinomas (ESCC) and 6 adenocarcinomas (EADC), while 26 samples, used as control, were of sporadic esophageal cancer (15 ESCC and 11 EADC). Results We found that, though the overall LOH frequency at the studied chromosomal regions was similar among metachronous and sporadic tumors, the latter exhibited a statistically different higher LOH frequency at 17q21.31 (p = 0.018). By stratifying for tumor histotype we observed that LOH at 3p24.1, 5q11.2 and 9p21.3 were more frequent in ESCC than in EADC suggesting a different role of the genetic determinants located nearby these regions in the development of the two esophageal cancer histotypes. Conclusions Altogether, our results strengthen the genetic diversity among ESCC and EADC whether they occurred spontaneously or after therapeutic treatments. The presence of histotype-specific alterations in esophageal carcinoma arisen in HL or breast cancer long-term survivors suggests that their transformation process, though the putative different etiological origin, may retrace sporadic ESCC and EADC carcinogenesis

Immunonutrition before esophagectomy: Impact on immune surveillance mechanisms

Preoperative oral immunonutrition was demonstrated to improve immune response and to decrease the infection rate in patients with cancer. This study aimed to assess how immunonutrition could influence the immune cell response in the mucosal microenvironment of esophageal adenocarcinoma. Therefore, A prospective cohort of consecutive patients undergoing esophagectomy for esophageal adenocarcinoma was enrolled. A subgroup of them was given preoperative oral immunonutrition with Oral Impact and was compared to those who received no preoperative supplementation. Mucosal samples from healthy esophagus were obtained at esophagectomy. Histology, immunohistochemistry, gene expression analysis, and cytofluorimetry were performed. Markers of activation of antigen-presenting cells (CD80, CD86, and HLA-I), innate immunity (TLR4 and MyD88), and cytotoxic lymphocyte infiltration and activation (CD8, CD38, CD69, and CD107) were measured. In all, 50 patients received preoperative Oral Impact and 129 patients received no nutritional support. CD80, CD86, MyD88, and CD69 messenger RNA expression was significantly increased in patients receiving immunonutrition compared to controls. In the subgroup of patients with stages I-II cancer, the rate of epithelial cells expressing CD80 and HLA-ABC was significantly higher in those receiving immunonutrition compared to controls as well as CD8+ CD28+ cell rate. Immunonutrition administration before surgery was significantly associated to increased degranulating CD8 and natural killer cells (CD107+) infiltrating the healthy esophageal mucosa. All the comparisons were adjusted for cancer stage and preoperative therapy. In conclusion, in healthy esophageal mucosa of patients undergoing esophagectomy, a 5-day course of immunonutrition enhances expression of antigen-presenting cells activity and increased CD8+ T cell activation and degranulating activity. Further studies are warranted to understand the clinical implication in terms of cancer recurrence

A framework for assessing the impact of health research from a broad population perspective

Abstract   Background: research in the health sector is an activity associated with an uncertain return on investment. This study aims to outline a multidimensional framework for assessing the imact of research funded by public (or mixed public and private) sponsors.  Methods: a focus group representing different stakeholders was created to develop a sense of purpose that would be shared by the intended beneficiaries of the research assessment process, and others with a direct or indirect interest in a program’s implementation.  Results: a framework was designed that takes a holistic approach to the impact of research in which not only technical, but also economic, social and political dimensions are interrelated with the results achieved for the population and health services.  Conclusions: the framework reflected the views of different stakeholders, favoring the development of the positive, proactive relationships essential to orienting the process of transforming the evidence emerging from research into action for health.&nbsp

Let-7c down-regulation in Helicobacter pylori-related gastric carcinogenesis

open12siAberrant let-7c microRNA (miRNA) expression has been observed in Helicobacter pylori-related gastric cancer (GC) but fragmentary information is available on the let-7c dysregulation occurring with each phenotypic change involved in gastric carcinogenesis. Let-7c expression was assessed (qRT-PCR) in a series of 175 gastric biopsy samples representative of the whole spectrum of phenotypic changes involved in H. pylori-related gastric oncogenesis including: i) normal gastric mucosa, as obtained from dyspeptic controls (40 biopsy samples); ii) non-atrophic gastritis (40 samples); iii) atrophic-metaplastic gastritis (35 samples); iv) intra-epithelial neoplasia (30 samples); v) GC (30 samples). Let-7c expression was also tested in 20 biopsy samples obtained from 10 patients before and after H. pylori eradication therapy (median follow-up: 10 weeks; range: 7-14). The results obtained were further validated by in situ hybridization on multiple tissue specimens obtained from 5 surgically treated H. pylori-related GCs. The study also included 40 oxyntic biopsy samples obtained from serologically/histologically confirmed autoimmune gastritis (AIG: 20 corpus-restricted, non-atrophic; 20 corpus-restricted, atrophic-metaplastic). Let-7c expression dropped from non-atrophic gastritis to atrophic-metaplastic gastritis, intra-epithelial neoplasia, and invasive GC (p<0.001). It rose again significantly following H. pylori eradication (p=0.009). As in the H. pylori model, AIG also featured a significant let-7c down-regulation (p<0.001). The earliest phases of the two pathways to gastric oncogenesis (H. pylori-environmental and autoimmune host-related) are characterized by similar let-7c dysregulations. In H. pylori infection, let-7c down-regulation regresses after the bacterium's eradication, while it progresses significantly with the increasing severity of the histological lesions.openFassan, Matteo; Saraggi, Deborah; Balsamo, Laura; Cascione, Luciano; Castoro, Carlo; Coati, Irene; DE BERNARD, Marina; Farinati, Fabio; Guzzardo, Vincenza; Valeri, Nicola; Zambon, CARLO-FEDERICO; Rugge, MassimoFassan, Matteo; Saraggi, Deborah; Balsamo, Laura; Cascione, Luciano; Castoro, Carlo; Coati, Irene; DE BERNARD, Marina; Farinati, Fabio; Guzzardo, Vincenza; Valeri, Nicola; Zambon, CARLO-FEDERICO; Rugge, Massim

CDX2 hox gene product in a rat model of esophageal cancer

<p>Abstract</p> <p>Background</p> <p>Barrett's mucosa is the precursor of esophageal adenocarcinoma. The molecular mechanisms behind Barrett's carcinogenesis are largely unknown. Experimental models of longstanding esophageal reflux of duodenal-gastric contents may provide important information on the biological sequence of the Barrett's oncogenesis.</p> <p>Methods</p> <p>The expression of <it>CDX2 </it>hox-gene product was assessed in a rat model of Barrett's carcinogenesis. Seventy-four rats underwent esophago-jejunostomy with gastric preservation. Excluding perisurgical deaths, the animals were sacrificed at various times after the surgical treatment (Group A: <10 weeks; Group B: 10–30 weeks; Group C: >30 weeks).</p> <p>Results</p> <p>No Cdx2 expression was detected in either squamous epithelia of the proximal esophagus or squamous cell carcinomas. <it>De novo </it>Cdx2 expression was consistently documented in the proliferative zone of the squamous epithelium close to reflux ulcers (Group A: 68%; Group B: 64%; Group C: 80%), multilayered epithelium and intestinal metaplasia (Group A: 9%; Group B: 41%; Group C: 60%), and esophageal adenocarcinomas (Group B: 36%; Group C: 35%). A trend for increasing overall Cdx2 expression was documented during the course of the experiment (<it>p </it>= 0.001).</p> <p>Conclusion</p> <p><it>De novo </it>expression of Cdx2 is an early event in the spectrum of the lesions induced by experimental gastro-esophageal reflux and should be considered as a key step in the morphogenesis of esophageal adenocarcinoma.</p

Correction to: Effects of immune suppression for transplantation on inflammatory colorectal cancer progression (Oncogenesis, (2018), 7, 6, (46), 10.1038/s41389-018-0055-5)

At the time of publication, the html version of this paper contained an error; the authors Imerio Angriman and Lucrezia Furian were not tagged as equally contributing authors. This has now been fixed in the html version of the paper, the PDF was correct at the time of publication. Erratum for Effects of immune suppression for transplantation on inflammatory colorectal cancer progression. [Oncogenesis. 2018

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Inflammatory myofibroblastic tumor as adverse outcome of eosinophilic esophagitis.

An emergency esophagogastroduodenoscopy performed in a dyspeptic 19-yearold girl with hematemesis, abdominal pain, and anemia (l" Fig. 1) revealed a polypoid esophageal mass with distal erosion. A subsequent CT scan confirmed the bulky lesion (14 \u94 4 \u94 3.5 cm) extending from the carina to the cardia level. Both extraesophageal extension and nodal and extranodal metastases were excluded. The extent and location of the mass ruled out any endoscopic resection and a total esophagectomy with gastric pull-up was performed. Both histology and immunophenotyping (positive for vimentin, MNF116, and smooth muscle actin; negative for S100 and CD117) were consistent with the \u201cclassical variant\u201d of inflammatory myofibroblastic tumor (IMT). A prominent eosinophilic infiltrate (l" Fig. 2a \u2013c) was also present, spreading from the lesional to the extralesional area, where the squamous epithelium featured rich eosinophic infiltrate, fully consistent with eosinophilic esophagitis (l" Fig. 2d). Within the upper gastrointestinal tract, IMTs are rare [1], polymorphic clinicopathological entities that have been associated with gastric ulcers [2], ischemic disease, and gastroesophageal reflux [3]. In accordance with these clinical settings, the hypothesis of IMT as an \u201cexaggerated reparative response\u201d has been established. In eosinophilic esophagitis, the promoting role for eosinophils in the onset of subepithelial fibrosis is supported by the high transcript levels of both interleukin- 5 and TGF-b detected in tissue samples from lesions [3\u20135]. Most recently, this hypothesis has been validated in murine models of eosinophilic esophagitis, where eosinophilia leads to collagen accumulation, finally resulting in esophageal wall remodeling [5]. A causative role for eosinophilic esophagitis is further sustained by the clinical finding that more than 50% of cases of eosinophilic esophagitis coexist with fibrotic esophageal strictures (e. g., Schatzki rings and esophageal webs), which might be seen as part of the same \u201ctumorigenic field\u201d in which IMT may develop. The clinical observation of a young patient with concomitant eosinophilic esophagitis and IMT, supported by recent experimental and molecular evidence, suggests that IMTs can definitely be considered among the unfavorable outcomes of (long-standing) eosinophilic esophagitis

Hepatic spleen nodules (HSN)

Hepatic splenosis is a nodular implant of normal spleen tissue in the liver. This innocent liver nodule is frequently misinterpreted as a malignancy. Almost all hepatic splenoses have been associated with a clinical history of splenic trauma or prior surgery. This report describes two cases of hepatic splenosis. In both patients, the nodular lesions were initially thought to be liver malignancies and they were ultimately assessed by histology. The clinico-pathological findings of all published cases of liver splenosis underwent critical review. Although they are rare, hepatic spleen nodules should always be included in the diagnostic spectrum of nodular liver lesions because of their impact on treatment decisions