ᅟObstruction and perforation due to colorectal cancer represent challenging matters in terms of diagnosis, life-saving strategies, obstruction resolution and oncologic challenge. The aims of the current paper are to update the previous WSES guidelines for the management of large bowel perforation and obstructive left colon carcinoma (OLCC) and to develop new guidelines on obstructive right colon carcinoma (ORCC).MethodsThe literature was extensively queried for focused publication until December 2017. Precise analysis and grading of the literature has been performed by a working group formed by a pool of experts: the statements and literature review were presented, discussed and voted at the Consensus Conference of the 4th Congress of the World Society of Emergency Surgery (WSES) held in Campinas in May 2017.ResultsCT scan is the best imaging technique to evaluate large bowel obstruction and perforation. For OLCC, self-expandable metallic stent (SEMS), when available, offers interesting advantages as compared to emergency surgery; however, the positioning of SEMS for surgically treatable causes carries some long-term oncologic disadvantages, which are still under analysis. In the context of emergency surgery, resection and primary anastomosis (RPA) is preferable to Hartmann’s procedure, whenever the characteristics of the patient and the surgeon are permissive. Right-sided loop colostomy is preferable in rectal cancer, when preoperative therapies are predicted.With regards to the treatment of ORCC, right colectomy represents the procedure of choice; alternatives, such as internal bypass and loop ileostomy, are of limited value.Clinical scenarios in the case of perforation might be dramatic, especially in case of free faecal peritonitis. The importance of an appropriate balance between life-saving surgical procedures and respect of oncologic caveats must be stressed. In selected cases, a damage control approach may be required.Medical treatments including appropriate fluid resuscitation, early antibiotic treatment and management of co-existing medical conditions according to international guidelines must be delivered to all patients at presentation.ConclusionsThe current guidelines offer an extensive overview of available evidence and a qualitative consensus regarding management of large bowel obstruction and perforation due to colorectal cancer.

CPR after CMT for rectal cancer is associated with improved local and distal control as well as better OS and DFS.

AimSARS-CoV-2 infection is a world-wide public health problem. Several aspects of its pathogenesis and the related clinical consequences still need elucidation. In Italy, Sardinia has had very low numbers of infections. Taking advantage of the low genetic polymorphism in the Sardinian population, we analyzed clinical, genetic and immunogenetic factors, with particular attention to HLA class I and II molecules, to evaluate their influence on susceptibility to SARS-CoV-2 infection and the clinical outcome.Method and MaterialsWe recruited 619 healthy Sardinian controls and 182 SARS-CoV-2 patients. Thirty-nine patients required hospital care and 143 were without symptoms, pauci-symptomatic or with mild disease. For all participants, we collected demographic and clinical data and analyzed the HLA allele and haplotype frequencies.ResultsMale sex and older age were more frequent in hospitalized patients, none of whom had been vaccinated during the previous seasonal flu vaccination campaignes. Compared to the group of asymptomatic or pauci-symptomatic patients, hospitalized patients also had a higher frequency of autoimmune diseases and glucose-6-phosphate-dehydrogenase (G6PDH) deficiency. None of these patients carried the beta-thalassemia trait, a relatively common finding in the Sardinian population. The extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 [OR 0.1 (95% CI 0–0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C*04:01 allele and the three-loci haplotype HLA-A*30:02, B*14:02, C*08:02 [OR 3.8 (95% CI 1.8–8.1), Pc = 0.025] were more frequently represented in patients than controls. In a comparison between in-patients and home care patients, the HLA-DRB1*08:01 allele was exclusively present in the hospitalized patients [OR > 2.5 (95% CI 2.7–220.6), Pc = 0.024].ConclusionThe data emerging from our study suggest that the extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 has a protective effect against SARS-CoV-2 infection in the Sardinian population. Genetic factors that resulted to have a negative influence on the disease course were presence of the HLA-DRB1*08:01 allele and G6PDH deficiency, but not the beta-thalassemic trait. Absence of influenza vaccination could be a predisposing factor for more severe disease.

Purpose: MET, the tyrosine kinase receptor for hepatocyte growth factor, is frequently overexpressed in colon cancers with high metastatic tendency. We aimed to evaluate the role of its negative regulators, miR-1 and miR-199a à , and its transcriptional activator, the metastasis-associated in colon cancer 1 (MACC1), in controlling MET expression in human colon cancer samples.Experimental Design: The expression of MET, miR-1, miR-199a à , and MACC1 was evaluated by realtime PCR in 52 matched pairs of colorectal cancers and nontumoral surrounding tissues. The biological role of miR-1 in controlling MET expression and biological activity was assessed in colon cancer cells either by its forced expression or by AntagomiR-mediated inhibition.Results: MiR-1 was downregulated in 84.6% of the tumors and its decrease significantly correlated with MET overexpression, particularly in metastatic tumors. We found that concurrent MACC1 upregulation and miR-1 downregulation are required to elicit the highest increase of MET expression. Consistent with a suppressive role of miR-1, its forced in vitro expression in colon cancer cells reduced MET levels and impaired MET-induced invasive growth. Finally, we identified a feedback loop between miR-1 and MET, resulting in their mutual regulation.Conclusions: This study identifies an oncosuppressive role of miR-1 in colorectal cancer in which it acts by controlling MET expression through a feedback loop. Concomitant downregulation of miR-1 and increase of MACC1 can thus contribute to MET overexpression and to the metastatic behavior of colon cancer cells.

A review concerning some embryogenetic aspects of the cardiac outflow tract is presented. Two main topics are discussed: the truncal septation and the secondary heart field. In the context of the septation of the truncus arteriosus, the development of the arterial valves is largely discussed, particularly in reference to the sinuses of Valsalva. Emphasis is also given to the fate of the external myocardial wall of the truncus arteriosus, as this primordial myocardial surface disappears later in the development. Molecular genetics data concerning Sox4 and NF-Atc transcription factors are correlated in the present review with rare forms of truncus malformations encountered in human pathology. The roles exerted by the secondary heart field and the neural crest on the development and growth of the conotruncal musculature are largely discussed. Reported experimental ablations of both secondary heart field and neural crest, showed conotruncal defects such as persistent truncus arteriosus, tetralogy of Fallot, and double-outlet right ventricle, which were considered as the result of a short outflow tract causing, ultimately, a lack of conotruncal rotation. In this regard, some morphologic correlations are carried out, in the present review, between these experimental animal models and human malformations, and it is thought that this sort of conotruncal defects cannot be explained always in terms of conotruncal hypoplasia. Finally, influence of Pitx2c, a left-right laterality signaling gene, on the modulation of the conotruncal rotation, as most recently reported, is emphasized in terms of very likely multifactorial contributions in the embryogenesis of the conotruncal region of the heart. Anat Rec Part A, 288A: 936-943, 2006

Colorectal cancer (CRC) develops through the accumulation of both genetic and epigenetic alterations. However, while the former are already used as prognostic and predictive biomarkers, the latter are less well characterized. Here, performing global methylation analysis on both CRCs and adenomas by Illumina Infinium HumanMethylation450 Bead Chips, we identified a panel of 74 altered CpG islands, demonstrating that the earliest methylation alterations affect genes coding for proteins involved in the crosstalk between cell and surrounding environment. The panel discriminates CRCs and adenomas from peritumoral and normal mucosa with very high specificity (100%) and sensitivity (99.9%). Interestingly, over 70% of the hypermethylated islands resulted in downregulation of gene expression. To establish the possible usefulness of these non-invasive markers for detection of colon cancer, we selected three biomarkers and identified the presence of altered methylation in stool DNA and plasma cell-free circulating DNA from CRC patients.

Very low tumors with a high serum CEA are very unlikely to reach a CPR. The predictive value of these easily available clinical factors should not be underestimated, and better therapeutic strategies for these tumors are needed.

This protocol is the first prospective trial that investigates the role of both local excision and watch and wait approaches in patients treated with neoadjuvant therapy for rectal cancer. The trial is registered at clinicaltrials.gov (NCT02710812).