Room for improvement in the treatment of pancreatic cancer: Novel opportunities from gene targeted therapy.

Pancreatic cancer is one of the highest and in fact, unchanged mortality-associated tumor, with an exceptionally low survival rate due to its challenging diagnostic approach. So far, its treatment is based on a combination of approaches (such as surgical resection with or rarely without chemotherapeutic agents), but with finite limits. Thus, looking for additional space to improve pancreatic tumorigenesis therapeutic approach, research has focused on gene therapy with unexpectedly growing horizons not only for the treatment of inoperable pancreatic disease, but also for its early stages. In vivo gene delivery viral vectors, despite few disadvantages (possible immunogenicity, toxicity, mutagenicity, or high cost), could be one of the most efficient cancer gene therapeutic strategies for clinical application due to their superiority compared with other systems (ex vivo delivery strategies). Their dominance consists of simple preparation, easy operation and a wide range of functions. Adenoviruses are one of the most common used vectors, inducing strong immune as well as inflammatory reactions. Oncolytic virotherapy, using the above mentioned in vivo viral vectors, is one of the most promising non-pathogenic, highly-selective cytotoxic anti-cancer therapy using anti-cancer agents with high anti-tumor potency and strong oncolytic effect. There have been a variety of targeted therapeutic and pre-clinical strategies tested for gene therapy in pancreatic cancer such as gene-editing systems (e.g., clustered regularly interspaced palindromic repeats-Cas9), RNA interference technology (e.g., microRNAs, short hairpin RNA or small interfering RNA), adoptive immunotherapy and vaccination (e.g., chimeric antigen receptor T-cell therapy) with encouraging results.

Laboratory manifestations and pathophysiological aspects of coronavirus disease 2019 pandemic: focusing on the digestive system.

Since December 2019, the severe acute respiratory syndrome coronavirus 2 has constituted a serious threat to global health. So far, there is little published evidence on the laboratory features of coronavirus disease 2019 (COVID-19). We have reviewed laboratory findings from multiple studies, mostly relating to the digestive system, since the virus outbreak. Laboratory data from older coronaviruses endemics, as well as other RNA viruses, were also reported. Although the main route of transmission is considered to be respiratory droplets, the distribution of ACE2 receptors in the gastrointestinal tract in combination with the detection of the virus in feces may imply a potential fecal-oral transmission route, and thus, emphasis should be given to patients with gastrointestinal symptoms. Interestingly, there is evidence that severe acute respiratory syndrome coronavirus 2 displays similar laboratory and clinical findings with older members of the coronavirus family, and so, comparable diagnostic and therapeutic approaches may be used. Regarding laboratory abnormalities, lymphopenia appears to be the most common finding, together with coagulation disorders and inflammatory markers elevation, reflecting a sustained systemic response. Abnormal liver and, occasionally, pancreatic tests are also common and even more severe in patients with gastrointestinal symptoms or diseases. Thus, the aim of this study is to focus on the laboratory and pathophysiologic side of this novel disease in order to strengthen current knowledge and urge further research. Detailed investigation of numerous studies may suggest a common laboratory pattern between COVID-19 patients. It is important for clinicians not to underestimate patients with gastrointestinal comorbidities, as they have been associated with severe COVID-19 disease.

COVID-19 pandemic: Pathophysiology and manifestations from the gastrointestinal tract.

The pandemic of coronavirus disease 2019 (COVID-19), caused by a newly identified ß-coronavirus (SARS-CoV-2) has emerged as a dire health problem, causing a massive crisis for global health. Primary method of transmission was firstly thought to be animal to human transmission. However, it has been observed that the virus is transmitted from human to human via respiratory droplets. Interestingly, SARS-CoV-2 ribonucleic acid (RNA) has been isolated from patient stools, suggesting a possible gastrointestinal (GI) involvement. Most commonly reported clinical manifestations are fever, fatigue and dry cough. Interestingly, a small percentage of patients experience GI symptoms with the most common being anorexia, diarrhea, nausea and vomiting. The presence of viral RNA in stools is also common and fecal tests can be positive even after negative respiratory samples. The exact incidence of digestive symptoms is a matter of debate. The distribution of Angiotensin converting enzyme type 2 receptors in multiple organs in the body provides a possible explanation for the digestive symptoms' mechanism. Cases with solely GI symptoms have been reported in both adults and children. Viral RNA has also been detected in stool and blood samples, indicating the possibility of liver damage, which has been reported in COVID-19 patients. The presence of chronic liver disease appears to be a risk factor for severe complications and a poorer prognosis, however data from these cases is lacking. The aim of this review is firstly, to briefly update what is known about the origin and the transmission of SARS-CoV-2, but mainly to focus on the manifestations of the GI tract and their pathophysiological background, so that physicians on the one hand, not to underestimate or disregard digestive symptoms due to the small number of patients exhibiting exclusively this symptomatology and on the other, to have SARS-CoV-2 on their mind when the "gastroenteritis" type symptoms predominate.

Screening and surveillance methods for dysplasia in inflammatory bowel disease patients: Where do we stand?

Patients with long-standing ulcerative colitis (UC) and extensive Crohn's colitis (CC) are at increased risk for dysplasia and colorectal cancer (CRC). Several studies have shown that UC extending proximal to the rectum, CC involving at least 1/3 of the colon, co-existence of primary sclerosing cholangitis, undetermined or unclassified colitis, family history of CRC and young age at diagnosis appear to be independent risk factors for inflammatory bowel disease (IBD) - related CRC. Therefore, screening and surveillance for CRC in IBD patients is highly recommended by international and national guidelines, whilst colonoscopy remains the unequivocal tool in order to detect potentially resectable dysplastic lesions or CRC at an early stage. Although the importance of screening and surveillance is widely proven, there is a controversy regarding the time of the first colonoscopy and the criteria of who should undergo surveillance. In addition, there are different recommendations among scientific societies concerning which endoscopic method is more efficient to detect dysplasia early, as well as the terminology for reporting visible lesions and the management of those lesions. This article concisely presents the main endoscopic methods and techniques performed for detecting dysplasia and CRC surveillance in patients with IBD focusing on their evidence-based accuracy and efficiency, as well as their cost-effectiveness. Finally, newer methods are mentioned, highlighting their applicability in daily endoscopic practice.

Secondary metastatic lesions to colon and rectum.

Metastatic lesions of the colon are a rare clinical entity that may present difficulties in management. The incidence of these metastases appears to be increasing, as a result of physicians' greater awareness during follow-up investigations of a primary neoplasm. Furthermore, the presence of a greater proportion of these abnormalities at autopsy should be a triggering factor for further investigation for doctors dealing with colorectal oncology. Their clinical presentation may vary from asymptomatic to signs similar to those of colorectal cancer. However, immunohistological analysis is considered the cornerstone for differentiating metastases to the colon, originating from other primaries, from primary colorectal neoplasms. Survival reports and treatment options vary. This article concisely presents the main characteristics of the secondary lesions to the colon from neoplasms that metastasize to the large intestine (namely, lung, ovary, breast, prostate, kidney, and melanoma) focusing on their incidence, their clinical presentation and the workup investigation. Physicians aware of this uncommon entity are much better prepared to apply an efficient diagnosis and workup, as well as an appropriate treatment strategy.