Comprehensive Roles and Future Perspectives of Exosomes in Peritoneal Metastasis of Gastric Cancer

Gastric cancer (GC) is one of the most prevalent digestive malignancies. A great number of patients at first visit or post curative resections are diagnosed with widespread metastasis within the peritoneal cavity. Overwhelming evidence has demonstrated that exosomes, a variety of biologically functional extracellular vesicles comprising active factors, mediate the progression and metastasis of GC. Although the regulatory mechanisms of exosomes remain fairly elusive, they are responsible for intercellular communication between tumor cells and normal stroma, cancer-related fibroblasts, immune cells within the primary tumor and metastatic niche. In this review, we provide new insight into the molecular signatures of GC-associated exosomes in reprogramming the tumor microenvironment and the subsequent promotion of peritoneal metastasis—including infiltration of the gastric wall, implantation of tumor cells onto the pre-metastatic peritoneum, and remodeling of the pre-metastatic niche. Based on this review, we hope to draw a more general conclusion for the functions of exosomes in the progression and peritoneal metastasis of GC and highlight the future perspective on strategies targeting exosomes in prognostic biomarkers and therapy for peritoneal metastasis.

Manifestaciones gastrointestinales en neurofibromatosis tipo 1. Reporte de un caso

Neurofibromatosis type 1, also known as von Recklinghausen disease, is an inherited neurocutaneous disorder with gastrointestinal involvement in 5-25% of the patients, which develops following cutaneous manifestations. Only 5% have symptoms such as abdominal pain, diarrhea, palpable mass, bleeding, obstruction or intestinal perforation. There is an increased risk of developing digestive malignancies, frequently in the small bowel. The following report presents the case of a patient with neurofibromatosis type 1, with the diagnosis of a jejunal gastrointestinal stromal tumor and a fibroid inflammatory polyp in the context of gastrointestinal bleeding.

TNF Inhibitors and Risk of Malignancy in Patients with Inflammatory Bowel Diseases: A Systematic Review

Background and Aims The association between tumour necrosis factor inhibitors [TNFi] and malignancy in patients with inflammatory bowel disease [IBD] is not well understood. Our aim was to systematically evaluate the impact of TNFi use on risk of malignancy in IBD patients in daily clinical practice. Methods We searched Pubmed, Embase and Scopus until March 1, 2020 for observational cohort studies on adult IBD patients reporting malignancy occurrence and TNFi use. Results Twenty-eight studies [20 retrospective and eight prospective] were included, involving 298 717 IBD patients. Mean age at inclusion ranged from 28 to >65 years. Mean follow-up varied from 7 to 80 months. Infliximab was the most frequently used TNFi [13/28 studies, 46.4%], followed by adalimumab [3/28, 10.7%], while both infliximab and adalimumab were evaluated in five studies [17.8%]. In total, 692 malignancies were diagnosed in IBD patients treated with TNFi, accounting for an overall occurrence of 1.0%. The most frequent malignancies were non-melanoma skin cancers [123/692, 17.8%], digestive malignancies [120/692, 17.3%] and haematological malignancies [106/692, 15.3%]. The association between TNFi and malignancy was evaluated in 11 studies [39.3%]: no significant association was found in ten studies, while an increased risk of lymphoma in patients exposed to TNFi was reported in one study. Conclusion TNFi treatment is not associated with an increased risk of malignancy in IBD patients in real-life settings. Further large studies are needed to assess the prognosis of patients exposed to TNFi and risk of recurrence or new cancers in subjects with personal malignancy history.

Hepatoma-Derived Growth Factor: An Overview and Its Role as a Potential Therapeutic Target Molecule for Digestive Malignancies

Hepatoma-derived growth factor (HDGF) was identified in research seeking to find a novel growth factor for hepatoma cells. Subsequently, four HDGF-related proteins were identified, and these proteins are considered to be members of a new gene family. HDGF has a growth-stimulating role, an angiogenesis-inducing role, and a probable anti-apoptotic role. HDGF is ubiquitously expressed in non-cancerous tissues, and participates in organ development and in the healing of damaged tissues. In addition, the high expression of HDGF was reported to be closely associated with unfavorable clinical outcomes in several malignant diseases. Thus, HDGF is considered to contribute to the development and progression of malignant disease. We herein provide a brief overview of the factor and its functions in relation to benign and malignant cells. We also describe its possible role as a target molecule for digestive malignancies.

Multivisceral Resection of Advanced Sigmoid Colon Cancer

Introduction: Colorectal cancer is one of the most common digestive malignancies, with a high mortality and morbidity rate, with nonspecific symptoms in the early stages and with a diagnosis in the advanced stage most often. In a significant percentage there are cases in which tumors with invasion in the border organs and multiorgan resections are required. In women, the invasion frequently occurs in the vagina, uterus and bladder. Case report: We report the case of a 52-year-old woman, who presented in the Department of Surgery with the following complaints: fecaluria, pneumaturia, constipation and moderate abdominal pain, with onset of 4 months, in wich the patient neglected her symptoms. Following the investigations, a large tumor formation of sigmoid colon was diagnosed, with invasion in the uterus and bladder, with which it communicates through a 16mm fistula. The result of the biopsy was of low / moderate grade adenocarcinoma differentiated G2. Cystoscopy revealed bladder trigone invasion without being able to identify ureteral orifices, biopsy and urine cytology was also positive for cancer. The surgery was performed by a multidisciplinary team and a multivisceral resection was performed. Conclusions: Multiorgan resections require trained, experienced teams, and oncological pathology raises special issues when it comes to radical visa. The management of invasive colonic tumors in the border organs must be established preoperatively, in agreement with the patient, because it involves problems related to the quality of life and the potential for survival.

Percutaneous transhepatic biliary drainage (PTBD) in patients (pts) with advanced solid malignancies: Clinical outcomes and prognostic factors.

315 Background: Obstructive jaundice (OJ) is a cumbersome complication in pts with advanced digestive malignancies, and PTBD is often used to relieve symptoms and allow chemotherapy (CT) administration. Methods: From July 2008 to August 2011, a total of 71 pts with OJ due to advanced solid malignancies underwent PTBD in our institution. Baseline characteristics, procedure complications and outcome were retrospectively collected. The primary goal was to estimate overall survival (OS) after PTBD. Results: Patients’ median age was 60 years old, 52% were male, 72% had an ECOG performance status (PS) of 1-2 and 10% were in supportive care (SC). Most had metastatic disease at diagnosis (59.2%) and primary gastrointestinal tumors (biliary tract 42.3%, gastric 18.3%, colorectal 11.3%, pancreas 16.9% and 11.3% other sites). Mean hospital stay was 16.6 days (2-90), with bilirubin value decreased (BVD) in 80% of pts. The rate of cholangitis following PTBD was 66.2% and 60.6% of pts had readmissions related to procedure complications. Only 51.6% of pts not in SC were eligible for CT after PTBD. Median OS was 2.9 months (95% CI: 0.62-5.2). Prognostic factors on univariate analysis were ECOG ≤2 (13 versus 0.72 months p<0.0001); BVD (6.7 versus 0.33 months p<0.0001); CT after PTBD (13.7 versus 1.2 months p<0.0001). SC was a negative prognostic factor (0.8 versus 4.5 months p<0.0001). On the multivariate analysis, palliative CT after procedure was related to better OS (HR 0,16 CI: 0.05-0.48 p<0.001). Conclusions: Malignant OJ is a late, and often final event in cancer pts. Thorough evaluation is needed before determining pts eligibility to PTBD, due to its high complication and hospitalization rates. In the current analysis, pts with PS >2 and who are not candidates for further CT had a dismal prognosis, and should probably not be offered PTBD.