Lipid Handling Protein Gene Expression in Colorectal Cancer: CD36 and Targeting miRNAs.

The reprogramming of lipid metabolism has been highlighted in colorectal cancer (CRC) studies, suggesting a critical role for the scavenger receptor CD36 and fatty acid synthase (FASN) in this malignancy. In this study, we analyzed the gene expression levels of CD36, FASN, the cell surface glypican 4 (GPC4), and the two transporters SLC27A3 and SLC27A4 in 39 paired tumoral and peritumoral tissues from patients with CRC compared with 18 normal colonic mucosae. Moreover, the levels of seven miRNAs targeting CD36 and most of the analyzed genes were evaluated. We found a significant impairment of the expression of all the analyzed genes except GPC4 as well as the differential expression of miR-16-5p, miR-26b-5p, miR-107, miR-195-5p, and miR-27a-3p in the colonic mucosa of CRC patients. Interestingly, CD36 and miR-27a-3p were downregulated and upregulated, respectively, in tumoral tissues compared to peritumoral and control tissues, with a significant negative correlation in the group of patients developing lymph node metastasis. Our results sustain the relationship between CRC and fatty acid metabolism and emphasize the importance of related miRNAs in developing new therapeutic strategies.

Molecular profile of the NF-κB signalling pathway in human colorectal cancer.

The development and progression of colorectal cancer (CRC) have been associated with inflammation processes that involve the overactivation of the NF-κB signalling pathway. The characterization of the NF-κB expression profile in CRC is an important topic since the suppression of NF-κB represents a potential therapeutic approach. In this study, we assessed the expression levels of 84 NF-κB-related genes in paired tumoral (T) and peritumoral (PT) tissues from 18 CRC patients and 18 normal colonic mucosae, and the expression levels of three miRNAs targeting the most dysregulated genes revealed by the case-control analysis. Comparing the gene expression profile of T and controls, 60 genes were dysregulated. The comparison of T and PT revealed 17 dysregulated genes in the tumoral tissues, with IL1B, CXCL8, IL1A, and CSF2 being the most upregulated. Notably, through a bioinformatics analysis, the differential gene expression of 11 out of the 17 genes was validated on a larger cohort of 308 CRC patients compared with 41 controls. Moreover, a decrease in the levels of RELA, NOD1, CASP8, BCL2L1, ELK1, and IKBKB was identified in poorly differentiated tumours compared to moderately differentiated tumours. The analysis of the three miRNAs targeting IL1B, CXCL8, IL1A, and CSF2 showed that miR-182-5p was upregulated in T compared with PT, whereas miR-10b-5p was downregulated in T compared with PT and control tissues. Our results may contribute to the design of new experimental therapeutic strategies based on endogenous molecules, such as miRNAs, to target the genetic key players of the NF- κB pathway.

Let-7 microRNAs Are Possibly Associated with Perineural Invasion in Colorectal Cancer by Targeting IGF Axis.

Increased insulin-like growth factor (IGF) axis activity is associated with the development and progression of different types of malignancies, including colorectal cancer (CRC). MicroRNAs (miRNAs) belonging to the let-7 family have been reported to target genes involved in this axis and are known as tumor suppressors. In this study, in silico bioinformatic analysis was performed to assess miRNA-mRNA interactions between eight miRNAs belonging to the let-7 family and genes involved in the IGF signaling pathway, coding for receptors and substrates. miRNAs' expression analysis revealed that hsa-let-7a-5p, hsa-let-7b-5p, hsa-let-7c-5p, hsa-let- 97 7d-5p, hsa-let-7e-5p, hsa-let-7f-5p, and hsa-let-7g-5p were significantly down-regulated in 25 CRC tumoral tissues (T) compared to the corresponding adjacent peritumoral tissues (PT). Moreover, our results showed an upregulation of miR-let-7e-5p in CRC tissues with mutations in KRAS codon 12 or 13, and, for the first time, found a specific dysregulation of let-7a-5p, let-7b-5p, let-7c-5p, let-7d-5p, and let-7i-5p in CRC with perineural invasion. Our results sustain the relationship between the IGF axis, let-7 miRNAs, and CRC and suggest an association between the expression of these miRNAs and perineural invasion.

TNF-alpha releasing capacity of the whole blood drops after open total splenectomy, but increases after partial/subtotal or minimally invasive splenectomy.

BACKGROUND: The mechanisms that induce immunodeficiency after splenectomy remain unknown. The aim of this study was to measure the cytokine releasing capacity of the whole blood as an expression of the innate immunity after total (TS) and subtotal/partial splenectomy (S/PS) in order to assess the impact of splenectomy on the individual cytokine reactivity. METHODS: We prospectively collected blood before (D0) and at multiple time points after splenectomy (7 days - D7, 30 days - D30, 90 days - D90, 180 days - D180, and 360 days - D360) and measured the cytokines releasing capacity of IL-6, TNF-alpha and IL-10 from whole blood under LPS stimulation which we normalized to the monocytes number. RESULTS: When analyzing all splenectomies at D0, D7 and D30, normalized ΔTNF-alpha significantly dropped after splenectomy (p = .0038) and normalized ΔIL-6 and ΔIL-10 did not significantly change. More specifically, normalized ΔTNF-alpha dropped after TS (p = .0568) and significantly increased after S/PS (p = .0388). Open surgery induced a decrease in normalized ΔTNF-alpha (p = .0970), whereas minimally invasive (MI) surgery significantly increased the normalized ΔTNF-alpha releasing capacity (p = .0178). The cytokine levels were heterogenous between pathologies at D0, and ΔIL-6 dropped mainly in cirrhotic patients after splenectomy (all underwent TS), ΔTNF-alpha dropped in immune thrombocytopenic purpura patients (all underwent TS), but increased in spherocytosis (91% underwent S/PS) after splenectomy. CONCLUSIONS: Splenectomy induces a decrease of the pro-inflammatory cytokine TNF-alpha and if splenic parenchyma is spared and the surgery is performed MI, this change is hindered.

Abdominoperineal Resection for Rectal Cancer: Open, Laparoscopic or Robotic Approach.

OBJECTIVES: The present study compares abdominoperineal resection (APR) performed by minimally invasive and open approach, regarding preoperative selection criteria, intraoperative and early postoperative aspects, in choosing the suitable technique performed by surgical teams with experience in both open and minimally invasive surgery (MIS). Methods: This is a retrospective study, conducted between 2008-2020. Two hundred thirty-three patients with APR performed for low rectal or anal cancer were included. The cohort was divided into two groups, depending on the surgical approach used: Minimally Invasive Surgery (laparoscopic and robotic procedures) and Open Surgery (OS). The perioperative characteristics were analyzed in order to identify the optimal approach and a possible selection criteria. Results: We identified a high percentage of patients with a history of abdominal surgery in the open group (p = .0002). Intraoperative blood loss was significantly higher in the open group (p= .02), with an increased number of simultaneous resections (p = .041). The early postoperative outcome was marked by significantly lower morbidity in the MIS group (p = .005), with mortality recorded only in the open group (3 cases), in patients that associated severe comorbidities. The hystopathological results identified a significant number of patients with stage T2 in the MIS group (p= .037). Conclusions: Minimally invasive surgery provides a major advantage to APR, by avoiding an additional incision, the specimen being extracted through the perineal wound. The success of MIS APR seems to be assured by a good preoperative selection of the patients, alongside with experienced surgical teams in both open and minimally invasive rectal resections. The lack of conversion identified in robotic APR confirm the technical superiority over laparoscopic approach.

D2 Lymphadenectomy for Gastric Adenocarcinoma: Long-term Results and the Impact of Surgeon Experience on the Survival Rates.

Background: Surgery is the main component of the multimodality treatment of gastric cancer (GC). The present study aims to comparatively assess the early and long-term outcomes after D1 and D2 lymph node dissection. Furthermore, the impact of surgeon case-load on the long-term survival after D2 gastrectomies is also explored. Methods: A number of 773 patients with curative-intent surgery for GC adenocarcinoma (1997 - 2010: 325 patients with D1 lymphadenectomy, 448 patients with D2 lymphadenectomy) were included. Results: No statistically significant differences of overall morbidity rates were observed between the D1 and D2 groups of patients (16.3%for D1 group vs. 18.8% for D2 group, p = 0.39). However, statistically significant higher rates of post operative pancreatic fistulae rates were observed in the D2 group of patients (3.2% for D1 group vs. 7.9% for D2 group, p 0.001). Interestingly, statistically significant higher rates of mortality were observed for the D1 group of patients (8.9% for D1 group vs. 2.9% for D2 group, p 0.001). The 5-year survival rate was statistically significant higher in the D2 group of patients (median overall survival time of 18 months for D1 group vs. 60 months for D2 group, p 0.001). A statistically significant correlation (p=0.005, r=0.571) was observed between the overall survival time and the number of D2 lymphadenectomies performed by each surgeon. Conclusions: D2 lymph node dissection is associated with statistically significant improved longterm survivals at the expense of higher postoperative pancreatic fistulae rates, compared to D1 surgery. However, no increased mortality rates were observed in the D2 group of patients. D2 radical gastrectomies should be performed in high-volume centers by high case-load surgeons.

Hereditary Spherocytosis - Diagnosis, Surgical Treatment and Outcomes. A Literature Review.

Hereditary spherocytosis (HS) is a disease affecting the red blood cells membrane and belongs to the congenital hemolytic anemias. The clinical spectrum ranges from asymptomatic patients to severe forms requiring transfusions in early childhood. The diagnosis can be based on the physical examination, complete red blood cell count, reticulocytes count, medical history and specific tests, preferentially the EMA test (eosin-5-maleimide binding) test and AGLT (Acidified Glycerol Lysis Time). Splenectomy is considered the standard surgical treatment in moderate and severe forms of hereditary spherocytosis. Total splenectomy exposes the patient to a life - long risk of potentially lethal infections and thus, its usage was reconsidered. Because of this reason, a feasible alternative is the partial splenectomy. The use of partial splenectomy aims to retain splenic immunologic function, while at the same time to decrease the rate of hemolysis. The long - term outcomes of patients with total or subtotal splenectomy for congenital hemolytic anemia, still remain unclear, but the majority of the studies showed a qualitative resolution of anemia and reduction of transfusion rate. Despite the well known advantages of conservative surgery, the optimal choice of treatment and outcomes should be confirmed with the patient.