Survival of hereditary non-polyposis colorectal cancer patients compared with sporadic colorectal cancer patients

<p>Abstract</p> <p>Background</p> <p>Patients with hereditary non-poliposys colorectal cancer (HNPCC) have better prognosis than sporadic colorectal cancer (CRC). Aim of our retrospective study was to compare the overall survival between sporadic CRC and HNPCC patients.</p> <p>Methods</p> <p>We analyzed a cohort of 40 (25 males and 15 females) HNPCC cases with a hospital consecutive series of 573 (312 males and 261 females) sporadic CRC observed during the period 1970–1993. In 15 HNPCC patients we performed mutational analysis for microsatellite instability. Survival rates were calculated by Kaplan-Meier method and compared with log rank test.</p> <p>Results</p> <p>The median age at diagnosis of the primary CRC was 46.8 years in the HNPCC series versus 61 years in sporadic CRC group. In HNPCC group 85% had a right cancer location, vs. 57% in the sporadic cancer group. In the sporadic cancer group 61.6% were early-stages cancer (Dukes' A and B) vs. 70% in the HNPCC group (p = ns). The crude 5-years cumulative survival after the primary CRC was 94.2% in HNPCC patients vs. 75.3% in sporadic cancer patients (p < 0.0001).</p> <p>Conclusion</p> <p>Our results show that overall survival of colorectal cancer in patients with HNPCC is better than sporadic CRC patients. The different outcome probably relates to the specific tumorigenesis involving DNA mismatch repair dysfunction.</p

Desmoid Tumors Characteristics, Clinical Management, Active Surveillance, and Description of Our FAP Case Series

(1) Background: desmoid tumors (DTs) are common in patients with familial adenomatous polyposis (FAP). An active surveillance approach has been recently proposed as a valuable alternative to immediate treatment in some patients. However, no clear indication exists on which patients are suitable for active surveillance, how to establish the cut-off for an active treatment, and which imaging technique or predictive factors should be used during the surveillance period. (2) Results: we retrospectively analyzed 13 FAP patients with DTs. A surveillance protocol consisting of scheduled follow-up evaluations depending on tumor location and tissue thickening, abdominal computed tomography (CT) scan/Magnetic resonance imaging (MRI) allowed prompt intervention in 3/11 aggressive intra-abdominal DTs, while sparing further interventions in the remaining cases, despite worrisome features detected in three patients. Moreover, we identified a possible predictive marker of tumor aggressiveness, i.e., the &ldquo;average monthly growth rate&rdquo; (AMGR), which could distinguish patients with very aggressive/life-threatening tumor behavior (AMGR &gt; 0.5) who need immediate active treatment, from those with stable DTs (AMGR &lt; 0.1) in whom follow-up assessments could be delayed. (3) Conclusion: surveillance protocols may be a useful approach for DTs. Further studies on larger series are needed to confirm the usefulness of periodic CT scan/MRI and the value of AMGR as a prognostic tool to guide treatment strategies

Two Cases, Too Little, Too Late: Surveillance for Gastric Cancer in Patients with FAP

Familial adenomatous polyposis is an autosomal dominant disease due to a mutation in the adenomatous polyposis coli (APC) gene. The disease, characterized by the development of adenomas throughout the colon and rectum, is also associated with extracolonic manifestations including gastric fundic polyps and cancer. In this report, we describe two patients with FAP with advanced gastric adenocarcinoma who received systemic chemotherapy. We reviewed the literature published over the past two decades on gastric cancer in FAP patients to assess the clinical course of this disease. Due to its recent increased incidence in Western countries, close endoscopic surveillance to detect early gastric neoplastic lesions is recommended

Type and frequency of MUTYH variants in Italian patients with suspected MAP: A retrospective multicenter study

To determine prevalence, spectrum and genotype-phenotype correlations of MUTYH variants in Italian patients with suspected MAP (MUTYH-associated polyposis), a retrospective analysis was conducted to identify patients who had undergone MUTYH genetic testing from September 2002 to February 2014. Results of genetic testing and patient clinical characteristics were collected (gender, number of polyps, age at polyp diagnosis, presence of colorectal cancer (CRC) and/or other cancers, family data). The presence of large rearrangements of the MUTYH gene was evaluated by Multiplex Ligation-dependent Probe Amplification analysis. In all, 299 patients with colorectal neoplasia were evaluated: 61.2% were males, the median age at polyps or cancer diagnosis was 50 years (16-80 years), 65.2% had <100 polyps and 51.8% had CRC. A total of 36 different MUTYH variants were identified: 13 (36.1%) were classified as pathogenetic, whereas 23 (63.9%) were variants of unknown significance (VUS). Two pathogenetic variants were observed in 78 patients (26.1%). A large homozygous deletion of exon 15 was found in one patient (<1.0%). MAP patients were younger than those with negative MUTYH testing at polyps diagnosis (P<0.0001) and at first cancer diagnosis (P=0.007). MAP patients carrying the p.Glu480del variant presented with a younger age at polyp diagnosis as compared to patients carrying p.Gly396Asp and p.Tyr179Cys variants. A high heterogeneity of MUTYH variants and a high rate of VUS were identified in a cohort of Italian patients with suspected MAP. Genotype-phenotype analysis suggests that the p.Glu480del variant is associated with a severe phenotype

A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal Cancer

8-Oxoguanine, a common mutagenic DNA lesion, generates G:C>T:A transversions via mispairing with adenine during DNA replication. When operating normally, the MUTYH DNA glycosylase prevents 8-oxoguanine-related mutagenesis by excising the incorporated adenine. Biallelic MUTYH mutations impair this enzymatic function and are associated with colorectal cancer (CRC) in MUTYH-Associated Polyposis (MAP) syndrome. Here, we perform whole-exome sequencing that reveals a modest mutator phenotype in MAP CRCs compared to sporadic CRC stem cell lines or bulk tumours. The excess G:C>T:A transversion mutations in MAP CRCs exhibits a novel mutational signature, termed Signature 36, with a strong sequence dependence. The MUTYH mutational signature reflecting persistent 8-oxoG:A mismatches occurs frequently in the APC, KRAS, PIK3CA, FAT4, TP53, FAT1, AMER1, KDM6A, SMAD4 and SMAD2 genes that are associated with CRC. The occurrence of Signature 36 in other types of human cancer indicates that DNA 8-oxoguanine-relatedmutations might contribute to the development of cancer in other organs. (C) 2017 The Authors. Published by Elsevier B.V

Association of Polygenic Risk Score and Bacterial Toxins at Screening Colonoscopy with Colorectal Cancer Progression: A Multicenter Case-Control Study

Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and its incidence is correlated with infections, chronic inflammation, diet, and genetic factors. An emerging aspect is that microbial dysbiosis and chronic infections triggered by certain bacteria can be risk factors for tumor progression. Recent data suggest that certain bacterial toxins implicated in DNA attack or in proliferation, replication, and death can be risk factors for insurgence and progression of CRC. In this study, we recruited more than 300 biopsy specimens from people undergoing colonoscopy, and we analyzed to determine whether a correlation exists between the presence of bacterial genes coding for toxins possibly involved in CRC onset and progression and the different stages of CRC. We also analyzed to determine whether CRC-predisposing genetic factors could contribute to bacterial toxins response. Our results showed that CIF toxin is associated with polyps or adenomas, whereas pks+ seems to be a predisposing factor for CRC. Toxins from Escherichia coli as a whole have a higher incidence rate in adenocarcinoma patients compared to controls, whereas Bacteroides fragilis toxin does not seem to be associated with pre-cancerous nor with cancerous lesions. These results have been obtained irrespectively of the presence of CRC-risk loci

Multicentric, observational, longitudinal study for the evaluation of nutritional management implications in newly diagnosed Italian cancer patients: the Italian Registry of Malnutrition in Oncology (IRMO)

Background Malnutrition is a frequent problem in oncology and is associated with reduced response to cancer treatments, increased drug-related toxicity, higher rates of clinical complications, reduced quality of life (QoL) and worse prognosis. Guidelines on clinical nutrition in oncology emphasise the usefulness of early assessment of nutritional status for a prompt identification of malnutrition and the implementation of effective interventions, but no real-world clinical data are available on the adequate management of nutritional support in patients with cancer in Italy.Methods and analysis This is an observational, longitudinal, multicentre registry of patients with a new diagnosis of cancer or metastatic disease, candidates for active treatment. They will be identified in at least 15 Italian oncological centres, members of the Alliance Against Cancer Working Group ‘Survivorship Care and Nutritional Support’. At least 1500 patients with cancer are expected to be enrolled each year. Detailed clinical and nutritional data will be collected by oncologists and clinical nutritionists during the visits foreseen in the clinical practice, through an ad hoc developed digital platform (e-Nutracare). The effects of malnutrition and nutritional support—at diagnosis and during follow-up—on overall survival and progression-free survival, as well as on patients’ symptoms and QoL, will be investigated.Ethics and dissemination The study protocol was approved by the Ethics Committee of the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy and from the Ethics Committees of all other participating centres. An informed consent will be obtained from each patient enrolled in the study. Study findings will be disseminated through peer-reviewed journals, conferences and patients with cancer or professional associations. The registry will allow a better monitoring of the nutritional status of patients with cancer, promoting adequate and sustainable nutritional support, with the ultimate goal of improving the care and prognosis of these patients