Microscopic Positive Margins in Gastric Adenocarcinoma Following Oncological Resection: Prognostic Factors and Long-Term Survival.

BACKGROUND: In the context of gastric cancer, surgical resection stands as the sole curative treatment. Central to influencing overall survival are the resection margins. This research aims to identify the factors influential in determining microscopically positive resection margins (R1) and to evaluate overall survival. METHODS: Our study encompassed 549 patients diagnosed with adenocarcinoma of the stomach who underwent curative-intent surgery between January 2011 and December 2021 in our Surgery Department. We investigated the incidence of positive margins (R1) and their impact on survival rates, as well as the determinants of R1. The standardization of R1 involved ensuring a margin distance of less than 1 mm from the tumor line to the margin. RESULTS: The incidence of R1 margins was 13.29% (73 patients). Among these, proximal R1 margins were observed in 29 patients (39.72%), while 49 cases (67.12%) presented circumferentially positive margins, with 20 cases (27.39%) exhibiting distally positive margins. Nineteen patients (26.02%) had two R1 margins, and 3 patients had all resection margins microscopically positive (4.10%). Factors such as tumor dimension, invasion of other organs, pT stage, pN stage, pL1 stage, pV1 stage, pPn stage, Lauren type, and tumoral grading demonstrated significance (p < 0.01) in the occurrence of positive R1 margins. CONCLUSION: Tumor dimension, invasion of other organs, pT stage, pN stage, pL1 stage, pV1 stage, pPn stage, Lauren type, and tumoral grading could be regarded as factors for predicting microscopically positive margins. Moreover, positive resection margins have a detrimental impact on overall survival.

Recent Trends in Non-Invasive Methods of Diagnosis and Evaluation of Inflammatory Bowel Disease: A Short Review.

Inflammatory bowel diseases are a conglomerate of disorders causing inflammation of the gastrointestinal tract, which have gained a significant increase in prevalence in the 21st century. As they present a challenge in the terms of diagnosis as well as treatment, IBDs can present an overwhelming impact on the individual and can take a toll on healthcare costs. Thus, a quick and precise diagnosis is required in order to prevent the high number of complications that can arise from a late diagnosis as well as a misdiagnosis. Although endoscopy remains the primary method of evaluation for IBD, recent trends have highlighted various non-invasive methods of diagnosis as well as reevaluating previous ones. This review focused on the current non-invasive methods in the diagnosis of IBD, exploring their possible implementation in the near future, with the goal of achieving earlier, feasible, and cheap methods of diagnosis as well as prognosis in IBD.

Role of Metabolomics in Pathogenesis and Prompt Diagnosis of Gastric Cancer Metastasis-A Systematic Review.

INTRODUCTION: Gastric cancer is the fourth most frequently diagnosed form of cancer and the third leading cause of cancer-related mortality worldwide. The aim of this review is to identify individual metabolic biomarkers and their association with accurate diagnostic values, which can predict gastric cancer metastasis. MATERIALS AND METHODS: After searching the keywords, 83 articles were found over a period of 13 years. One was eliminated because it was not written in English, and two were published outside the selected period. Seven scientific papers were qualified for this investigation after eliminating duplicates, non-related articles, systematic reviews, and restricted access studies. RESULTS: New metabolic biomarkers with predictive value for gastric cancer metastasis and for elucidating metabolic pathways of the metastatic process have been found. The pathogenic processes can be outlined as follows: pro-oxidant capacity, T-cell inactivation, cell cycle arrest, energy production and mitochondrial enzyme impairment, cell viability and pro-apoptotic effect, enhanced degradation of collagen extracellular matrix, migration, invasion, structural protein synthesis, and tumoral angiogenesis. CONCLUSION: Metabolic biomarkers have been recognized as independent risk factors in the molecular process of gastric cancer metastasis, with good diagnostic and prognostic value.

Perineal Hernia Mesh Repair Using Only the Perineal Approach: How We Do It.

Perineal hernia is a rare complication of rectal surgery. Different types of surgical approach have been described, but none of them have proven their superiority. Although there are many methods of closing the defect, we selected two cases to present from a series of five cases, in which the perineal hernia was successfully resolved surgically using only the perineal approach. The reconstruction of the perineal floor and closure of the defect were performed using a synthetic polypropylene mesh. The significance of this Technical Note article lies in the fact that we describe, step by step, a surgical technique for perineal hernia using just a perineal approach.

The Influence of Intravenous Lidocaine Infusion on Postoperative Outcome and Neutrophil-to-Lymphocyte Ratio in Colorectal Cancer Patients. A Pilot Study.

BACKGROUND AND AIMS: In the last years increasing scientific evidence drew attention on the potential effects of anesthetic drugs on postoperative outcome in cancer patients. Local anesthetics, especially lidocaine, have been intensively studied in relation with postoperative outcome in colorectal cancer patients. Our study objectives were to investigate the effects of perioperative intravenous lidocaine infusion on neutrophil-to-lymphocyte ratio and short-term postoperative outcome. Additionally, we also looked at 1 year outcome after intended radical colorectal cancer surgery. METHODS: 150 patients scheduled for colorectal cancer surgery were randomized to receive sevoflurane anaesthesia with or without 48 hours lidocaine infusion. RESULTS: 73 patients were included in the group A (sevoflurane) and 77 in the group B (sevoflurane with lidocaine). Lidocaine infusion did not modify neutrophil-to-lymphocyte ratio at 24 hours after surgery (p=0.58). Patients receiving intravenous lidocaine had significantly lower morphine consumption (p=0.04), faster mobilization time (p=0.001) and fewer days spent in the hospital (p=0.04). Moreover, at 1 year follow- up, patients in group B had a significant decreased rate of recurrences (p=0.03). There was no significant difference in 1 year survival (p=0.22). CONCLUSIONS: In our study, intravenous lidocaine infusion hastened the postoperative recovery of patients in terms of mobilization, hospital discharge and opioid consumption and reduced 1 year recurrence rate. Further studies on larger groups of patients are needed.

Surgical management of hydatid cyst disease of the liver: An improvement from our previous experience?

BACKGROUND: Hydatid liver disease remains an important issue in endemic areas, which may require immediate surgery. Although laparoscopic surgery is on the rise, the presence of certain complications may require conversion to the open approach. AIM: To compare the results of laparoscopic treatment and the open approach in the context of a 12-year single institution experience, and to perform a further comparison between results from the current study and those from a previous study. METHODS: Between January 2009 and December 2020, 247 patients underwent surgery for hydatic disease of the liver in our department. Of the 247 patients, 70 underwent laparoscopic treatment. A retrospective analysis between the two groups was performed, as well as a comparison between current and previous laparoscopic experience (1999-2008). RESULTS: There were statistically significant differences between the laparoscopic and open approaches regarding the cyst dimension, location, and presence of cystobiliary fistula. There were no intraoperative complications in the laparoscopic group. The cutoff value for the cyst size regarding the presence of cystobiliary fistula was 6.85 cm (P = 0.001). CONCLUSION: Laparoscopic surgery still plays an important role in the treatment of hydatid disease of the liver, with an increase in its usage over the course of years that has shown benefits regarding the postoperative recovery with a decreased rate of intraoperative complications. Although experienced surgeons can perform laparoscopic surgery in the most difficult conditions, there are some selection criteria that need to be maintained for higher quality results.

A novel step-by-step training program for transanal endoscopic surgery.

BACKGROUND: The objective of our study is to develop an effective training platform for transanal endoscopic surgery and to validate a step-by-step training program for learning the basic skills necessary for this approach. METHODS: We have designed a two-part study: an experimental study (with the aim to design the training platform and the training exercises - on synthetic and biological material) and a prospective analytical study, in order to validate the training program by enrolling as participants general surgery residents and specialists, without previous experience in transanal endoscopic interventions. The performance of the participants was assessed based on the time of completion, as well as the quality of the execution. RESULTS: We have developed three different diameter platforms (5 cm, 7.5 and 10 cm), that can be used with both the TEO and TAMIS platforms; specific exercises were developed to train different surgical skills like manipulation of tissue, cutting, dissection and suturing. Forty participants were enrolled for the validation of the proposed training program (12 young residents, 16 senior residents and 12 specialist surgeons). A statistically significant improvement of the performance time, from round to round, was observed for all participants in all exercises. The time of completion for the exercises, considering the correct technical execution, was the shortest for more experienced surgeons: specialist surgeons, followed by senior residents and young residents. The biological material exercises, that closely recreate intraoperative conditions and had more strict technical requirements, were difficult to be performed by young residents; better completion rates were seen in senior residents, while all the participants in the specialist surgeons group have completed these exercises. CONCLUSIONS: Our training program is an effective simulation based educational model for recreating intraoperative conditions particular to transanal endoscopic surgery. The proposed step-by-step training program has demonstrated to be useful in developing the important basic skills needed for transanal endoscopic surgery and assured the progress of all the participants, regardless of their surgical experience.

Sperm protein antigen 17 and Sperm flagellar 1 cancer testis antigens are expressed in a rare case of ciliated foregut cyst of the common hepatic duct.

INTRODUCTION: Ciliated foregut cysts (CFCs) are frequently described in liver, pancreas and gallbladder and generally considered benign although one case of squamous cell metaplasia and five cases of squamous cell carcinoma arising from a ciliated hepatic foregut cyst have been reported. Here we explore two cancer-testis antigens (CTAs), Sperm protein antigen 17 (SPA17) and Sperm flagellar 1 (SPEF1) expression in a rare case of CFC of the common hepatic duct MATERIALS AND METHODS: 3 µm-thick CFC sections were immunohistochemically treated with antibodies raised against human SPA17 or SPEF1. In silico Protein-Protein Interaction (PPI) network and differential protein expression were also investigated RESULTS: Immunohistochemistry revealed SPA17 and SPEF1 in the cytoplasm of ciliated epithelium. SPA17, but not SPEF1, was also detected in cilia. The PPI networks demonstrated that other CTAs are significantly predicted functional partners with SPA17 and SPEF1. The differential protein expression demonstrated that SPA17 was higher in breast cancer, cholangiocarcinoma, liver hepatocellular carcinoma, uterine corpus endometrial carcinoma, gastric adenocarcinoma, cervical squamous cell carcinoma, bladder urothelial carcinoma. SPEF1 expression was higher in breast cancer, cholangiocarcinoma, uterine corpus endometrial carcinoma and kidney renal papillary cell carcinoma CONCLUSIONS: Our study suggests that further characterization of SPA17 and SPEF1 in patients with CFCs might provide significant insights to understand the mechanisms underlying their potential to malignant transformation.

The Multifaceted Role and Regulation of Nlrp3 Inflammasome in Colitis-Associated Colo-Rectal Cancer: A Systematic Review.

Colitis-associated colo-rectal cancer remains the leading cause of mortality in inflammatory bowel diseases, with inflammation remaining one of the bridging points between the two pathologies. The NLRP3 inflammasome complex plays an important role in innate immunity; however, its misregulation can be responsible for the apparition of various pathologies such as ulcerative colitis. Our review focuses on the potential pathways of upregulation or downregulation of the NLRP3 complex, in addition to evaluating its role in the current clinical setting. Eighteen studies highlighted the potential pathways of NLRP3 complex regulation as well as its role in the metastatic process in colo-rectal cancer, with promising results. Further research is, however, needed in order to validate the results in a clinical setting.

A Group of Tumor-Suppressive micro-RNAs Changes Expression Coordinately in Colon Cancer.

MicroRNAs (miRNAs) are molecules with a role in the post-transcriptional regulation of messenger RNA, being involved in a wide range of biological and pathological processes. In the present study, we aim to characterize the behavior of a few miRNAs with roles in the cell cycle and differentiation of colon cancer (CC) cells. The present work considers miRNAs as reflections of the complex cellular processes in which they are generated, their observed variations being used to characterize the molecular networks in which they are part and through which cell proliferation is achieved. Tumoral and adjacent normal tissue samples were obtained from 40 CC patients, and the expression of miR-29a, miR-146a, miR-215 and miR-449 were determined by qRT-PCR analysis. Subsequent bioinformatic analysis was performed to highlight the transcription factors (TFs) network that regulate the miRNAs and functionally characterizes this network. There was a significant decrease in the expression of all miRNAs in tumor tissue. All miRNAs were positively correlated with each other. The analysis of the TF network showed tightly connected functional modules related to the cell cycle and associated processes. The four miRNAs are downregulated in CC; they are strongly correlated, showing coherence within the cellular network that regulates them and highlighting possible approach strategies.

Residents Can Do It! A Training Program in Laparoscopic Liver Surgery for General Surgery Residents.

INTRODUCTION: Laparoscopic liver resections (LLRs) constitute an area of surgery that has been kept away from residents in their hands-on training. The aim of our study is to assess the feasibility and the value of a didactic "step-by-step" program for LLR performed by residents using the swine training model. METHODS: From May 2018 to November 2019, three hands-on workshops were held. The protocol involved the performance of cholecystectomy, liver mobilization, minor and major hepatectomies. The participants' performance results in terms of operative time, blood loss, conversion, trainers' intervention, and intraoperative mortality, were recorded. The first workshop was comprised of 30 residents who previously participated in laparoscopic surgery workshops. In the second workshop, after six residents dropped out due to residency completion, the findings for the remaining 24 residents were compared to those for 24 junior-attending surgeons who did not follow the protocol and had not performed LLR previously, and to another 24 residents in a third workshop, who had not taken the training program before but followed the protocol. RESULTS: All residents fully completed the surgical procedures. Trained residents achieved better operative times and less blood loss compared to junior-attending surgeons (p < 0.017), however, the remaining parameters were comparable. When compared to non-trained residents, those who underwent training achieved significantly better results only in operative times (p < 0.001). CONCLUSION: A continuous LLR "step-by-step" training program on swine for residents is feasible and the "step-by-step" protocol is a valuable tool for a proper surgical education.

Trends in Minimally Invasive Approaches for Liver Resections-A Systematic Review.

BACKGROUND: SILS (single incision laparoscopic surgery) and NOTES (natural orifice transluminal endoscopic surgery) are considered breakthroughs in minimally invasive surgery, the first consisting in the surgeon working via a single entrance site and the second via a natural orifice (e.g., oral cavity). METHODS: Since 2000 until 2022, the original articles published in the online databases were analyzed. Eligible studies included information about the current therapy of patients with liver surgical pathology and how the two new techniques improve the surgical approach. RESULTS: A total of 798 studies were identified. By applying the exclusion criteria, nine studies remained to be included in the review. Two out of nine studies examined the NOTES approach in liver surgery, whereas the other seven focused on the SILS technique. The age of the patients ranged between 24 and 83 years. Liver resections for hepatocellular carcinoma or colorectal metastases were undertaken and biliary or hydatid cysts were removed. The mean procedure time was 95 to 205 min and the average diameter of the lesions was 5 cm. CONCLUSIONS: When practiced by multidisciplinary teams, transvaginal liver resection is feasible and safe. The goals of SILS and NOTES are to be less intrusive, more easily tolerated and aesthetic.

Impact of the COVID-19 pandemic on the training of general surgery residents: Surgical training and the COVID-19 pandemic.

Background: The educational process of young doctors should be a topic of high interest, since it is central to preparing the new generations of healthcare providers. The COVID-19 pandemic has affected the medical system on multiple levels, including medical education. Methods: We conducted a descriptive survey study, designed to reflect the impact of the pandemic on the training of general surgery residents. Two questionnaires were delivered to general surgery residents at two different periods: one in the pre-COVID-19 era (December 2019) and one in the COVID-19 era (December 2020). Data were gathered on participants' characteristics, current clinical practice and knowledge, extracurricular activities, and involvement in the management of COVID-19 cases. Results: We registered 33 responses in the pre-COVID-19 era and 45 responses in the COVID-19 era. Most participants felt that the pandemic significantly affected their training in classic and laparoscopic surgery. The number of days per week that the residents were active in the operating room and the possibility of training in laparoscopic surgery outside the hospital decreased significantly in the COVID-19 era. Most participants consider they have not gained sufficient knowledge to practice laparoscopic surgery or to assure their employment in another hospital after finishing their residency program. Conclusion: The pandemic reduced the hands-on activities of general surgery residents, while training in laparoscopy was deficient both before and during the pandemic. New training methods should be sought and used in order to adapt the educational system to the current context.

Perioperative Management of Patients with Pancreatic Cancer - the ERAS Protocols.

Background: Pancreatic cancer represents the fifth leading cause of death in industrialized countries. The prognosis is reserved, surgical resection being the only curative treatment, but the complications associated bear important impact on the patients survival, prognosis, and quality of life. The ERAS protocols come to meet these shortcomings for enhanced recovery after major pancreatic resections. Material and method: A systematic review was performed following the guidelines outlined by The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Original articles published in the online databases Pubmed (Medline), Embase and Cochrane since 2017 until 2022 were screened after using specific keywords. Results: A total of 252 studies was obtained by searching through online databases. Following the exclusion criteria, we included 7 studies in the systematic review. Conclusions: The ERAS protocols are safe to be applied in the common practice. They are efficient in the perioperative management of patients undergoing pancreatic resections. They can further decrease hospitalization stay, promote better recovery of gastrointestinal function, and speed up postoperative recovery.

A role for serum cytokines and cell adhesion molecules in the non-invasive diagnosis of colorectal cancer.

Colorectal cancer (CRC) remains a major cause of cancer-related mortality. Consequently, new diagnostic and therapeutic approaches are being investigated including the serum levels of cytokines and other molecules, although the results are often inconclusive. Thus, the present study aimed to determine whether serum level of cytokines, cell adhesion molecules or matrix metalloproteinases (MMPs), alone or in combination, may contribute to the non-invasive diagnosis of CRC. The serum levels of nine cytokines [ILs; IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-17, IL-22 and IL-33, and interferon (IFN)-γ], two cell adhesion molecules (intercellular adhesion molecule-1 and P-selectin) and an MMP-7 were measured by ELISA in 33 patients with CRC and 35 healthy controls. Combined capacity of all molecules to detect the presence of CRC was assessed by logistic regression. Molecules and molecule combinations were tested for all stages and tumor grades. A significant increase was identified for IL-8 in patients compared with healthy controls; IL-10 was found to be significantly decreased. The biomarker potential of each significantly modified molecule was tested: IL-8 had a sensitivity of 0.865, a specificity of 0.600 and an area under the curve (AUC) of 0.777; for IL-10, sensitivity was 0.65, specificity was 0.69, with an AUC of 0.689. Logistic regression determined the best discriminative potential between patients and control groups for the combination IL-4 + IL-6 + IL-8 + IFN-γ, with 0.97 sensitivity and 0.58 specificity. For the early stages of CRC, the combination IL-6 + IL-8 + IL-22 showed good performance. It was concluded that increased IL-8 had potential as single biomarker in CRC. Cytokine combinations are superior to single cytokine analysis in showing the presence of CRC.

CT-Based Radiomic Analysis May Predict Bacteriological Features of Infected Intraperitoneal Fluid Collections after Gastric Cancer Surgery.

The ability of texture analysis (TA) features to discriminate between different types of infected fluid collections, as seen on computed tomography (CT) images, has never been investigated. The study comprised forty patients who had pathological post-operative fluid collections following gastric cancer surgery and underwent CT scans. Patients were separated into six groups based on advanced microbiological analysis of the fluid: mono bacterial (n = 16)/multiple-bacterial (n = 24)/fungal (n = 14)/non-fungal (n = 26) infection and drug susceptibility tests into: multiple drug-resistance bacteria (n = 23) and non-resistant bacteria (n = 17). Dedicated software was used to extract the collections' TA parameters. The parameters obtained were used to compare fungal and non-fungal infections, mono-bacterial and multiple-bacterial infections, and multiresistant and non-resistant infections. Univariate and receiver operating characteristic analyses and the calculation of sensitivity (Se) and specificity (Sp) were used to identify the best-suited parameters for distinguishing between the selected groups. TA parameters were able to differentiate between fungal and non-fungal collections (ATeta3, p = 0.02; 55% Se, 100% Sp), mono and multiple-bacterial (CN2D6AngScMom, p = 0.03); 80% Se, 64.29% Sp) and between multiresistant and non-multiresistant collections (CN2D6Contrast, p = 0.04; 100% Se, 50% Sp). CT-based TA can statistically differentiate between different types of infected fluid collections. However, it is unclear which of the fluids' micro or macroscopic features are reflected by the texture parameters. In addition, this cohort is used as a training cohort for the imaging algorithm, with further validation cohorts being required to confirm the changes detected by the algorithm.

The Role of IL-22 in Wound Healing. Potential Implications in Clinical Practice.

Wound healing is a complex process that is mediated and influenced by several cytokines, chemokines, and growth factors. Interleukin-22 (IL-22) is a cytokine that plays a critical role in tissue regeneration. Our study is a systematic review that addressed the implications of IL-22 in the healing of wounds caused by external factors. Thirteen studies were included in our review, most of them being experimental studies. Three clinical studies underlined the potential role of IL-22 in day-to-day clinical practice. IL-22 plays a central role in wound healing, stimulating the proliferation, migration, and differentiation of the cells involved in tissue repair. However, overexpression of IL-22 can cause negative effects, such as keloid scars or peritoneal adhesions. The results of the presented studies are promising, but further research that validates the roles of IL-22 in clinical practice and analyzes its potential implication in surgical healing is welcomed.

Analysis of the MLH1, MLH2, MLH6, PMS2 genes and their correlations with clinical data in rectal mucinous adenocarcinoma.

BACKGROUND: Microsatellites are short repeated DNA sequences normally found in the human genome. Following specific mutations, microsatellites can vary in the number of repeats thus making the DNA unstable. Microsatellite instability (MSI) is responsible for approximately 20% of rectal cancers, while the remaining 80% are caused by chromosomal instability. One of the following genes, MLH1, MLH2, MLH 6, and PMS2, is inactivated, leading to MSI colorectal cancers. AIM: This study aimed to analyze the expression of some MMR system genes presenting mutations in mucinous rectal cancer and their correlations with clinical data. METHODS: A retrospective study was performed on patients with rectal mucinous adenocarcinoma who underwent surgery between January 2000 and January 2017. We collected a total of 42 patients and analyzed the demographic data, histopathological results and MMR system genes mentioned above. RESULTS: Almost 93% of the cases analyzed had MSI-H and only 7% were MSI-L. For MLH1, 50% of stage T2 and 50% of stage T4 had weak expression, while in stage T3, 42.50% had moderate expression. Regarding the N stage, we found that 66.67% of the patients with moderate gene expression (2+) were N2, while 42% of the patients with weak expression were N0. For MSH2, the majority of patients with strong gene expression were in stage T3 (27%). Weak expression was found in 50% of the patients in stage T2, 35% of the patients in stage T3, and 33.3% in T4. In 44.44% of the weak expression was N2, while for strong expression, there was an equivalent percentage of 33.33% in stages N1 and N2. Describing the MSH6 gene, we found that the most heterogeneous results were in stage T3. Weak expression was observed in 38.46% of the patients, while moderate and strong expression was observed in 30.77% and 11.54% respectively. Analysis of PMS2 revealed that 66.67% of the patients in stage T4 had a weak expression of the gene, while the same expression was found in 38.46% of the patients in stage T3. A total of 23.08% of patients in stage T3 had strong gene expression. We also analyzed the overall gene expression. Thus, we found that three patients (7.14%) had only 1, three genes were expressed, nine (21.42%) had two genes and the remaining 27 patients had all 4. The 1-year survival rate in the analyzed lot was 75%, decreasing to 60% in the second year and 35% in the 3rd. There were no statistically significant differences in survival data between the stages or gene expression. CONCLUSIONS: Our study showed no statistical difference regarding the survival on different gene expression or staging, consistent with studies that found that mucin expression does not have a significant impact on local recurrence, nor does it affect nodal down staging. KEY WORDS: Mucinous adenocarcinoma, Microsatelites instability.

Extramedullary Hematopoiesis of the Liver and Spleen.

Hematopoiesis is the formation of blood cellular components and, consequently, immune cells. In a more complete definition, this process refers to the formation, growth, maturation, and specialization of blood cells, from the hematopoietic stem cell, through the hematopoietic progenitor cells, to the s pecialized blood cells. This process is tightly regulated by several elements of the bone marrow microenvironment, such as growth factors, transcription factors, and cytokines. During embryonic and fetal development, hematopoiesis takes place in different organs: the yolk sac, the aorta-gonad mesonephros region, the lymph nodes, and not lastly, the fetal liver and the spleen. In the current review, we describe extramedullary hematopoiesis of the spleen and liver, with an emphasis on myeloproliferative conditions.

Circulating microRNA-194 and microRNA-1228 Could Predict Colon Cancer Proliferation via Phospho S6 Modulation.

BACKGROUND AND AIMS: Although colon cancer has a decreasing incidence trend in Europe, because of its still high frequency and not fully understood pathogenesis, this malignancy still remains a subject of intense research. The aim of this study was to investigate the role of microRNA-194 and microRNA-1228 in colon cancer proliferation. METHODS: RNA was extracted from patients with colon cancer with or without advanced disease and microRNA expression levels were determined through qRT-PCR. Assays were performed on HCT116 cell line and included qRT-PCR, western blotting and cell counting. RESULTS: We observed that both microRNAs 194 and 1228 were altered in patients with colon cancer compared with healthy individuals. We observed a lower expression of both microRNA-194 and microRNA-1228 in patients with advanced colon cancer. To validate their pathogenetic role we performed viability and invasion assays on HCT116 cell line transfected with mimics or inhibitors of the mentioned microRNAs, with observable changes in viability and invasion. Furthermore, to determine the altered signaling induced by these microRNAs, we performed western blotting for phospho S6 on HCT116 cells transfected with mimic and inhibitor of the above-mentioned microRNAs with observable differences. CONCLUSION: In the current study we have shown that both microRNA-194 and microRNA-1228 alteration was correlated with the presence of advanced colon cancer, a fact that was further validated in vitro through an invasion assay. Moreover, we have also shown that their effect might be mediated through phospho S6 expression.