EORTC 1409 GITCG/ESSO 01 - A prospective colorectal liver metastasis database for borderline or initially unresectable diseases (CLIMB): Lessons learnt from real life. From paradigm to unmet need.

AIM: Multidisciplinary management of metastatic colorectal liver metastases (CRLM) is still challenging. To assess postoperative complications in initially unresectable or borderline resectable CRLM, the prospective EORTC-1409 ESSO 01-CLIMB trial capturing 'real-life data' of European centres specialized in liver surgery was initiated. MATERIAL AND METHODS: A total of 219 patients were registered between May 2015 and January 2019 from 15 centres in nine countries. Eligible patients had borderline or initially unresectable CRLM assessed by pre-operative multidisciplinary team discussion (MDT). Primary endpoints were postoperative complications, 30-day and 90-days mortality post-surgery, and quality indicators. We report the final results of the 151 eligible patients that underwent at least one liver surgery. RESULTS: Perioperative chemotherapy with or without targeted treatment were administered in 100 patients (69.4%). One stage resection (OSR) was performed in 119 patients (78.8%). Two stage resections (TSR, incl. Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy (ALPPS)) were completed in 24 out of 32 patients (75%). Postoperative complications were reported in 55.5% (95% CI: 46.1-64.6%), 64.0% (95% CI: 42.5-82%), and 100% (95% CI: 59-100%) of the patients in OSR, TSR and ALPPS, respectively. Post-hepatectomy liver failure occurred in 6.7%, 20.0%, and 28.6% in OSR, TSR, and ALPPS, respectively. In total, four patients (2.6%) died after surgery. CONCLUSION: Across nine countries, OSR was more often performed than TSR and tended to result in less postoperative complications. Despite many efforts to register patients across Europe, it is still challenging to set up a prospective CRLM database.

The Clinical Benefit of Percutaneous Transhepatic Biliary Drainage for Malignant Biliary Tract Obstruction.

Percutaneous transhepatic biliary drainage (PTBD) is a decompression procedure for malignant proximal biliary obstruction. In this research, over a six-year period, 89 patients underwent PTBD procedure for jaundice caused by malignant disease to restart chemotherapy or for palliative intent. Clinical outcomes after PTBD procedure in the two groups of patients, according to the adequate bilirubin decline (ABD) needed for subsequent chemotherapy, are presented in this paper. Survival and logistic regression were plotted and compared using Kaplan−Meier survival multivariate analysis with a long-range test. Results were processed by MEDCALC software. In the series, 58.4% (52/89) of patients were in good performance status (ECOG 0/1), and PTBD was performed with the intention to (re)start chemotherapy. The normalization of the bilirubin level was seen in 23.0% (12/52), but only 15.4% (8/52) received chemotherapy. The median survival time after PTBD was 9 weeks. In patients with ABD that received chemotherapy, the median survival time was 64 weeks, with 30-day mortality of 27.7%, and 6.4% of death within 7 days. The best outcome was in patients with good performance status (ECOG 0−1), low bilirubin (<120 µmol/L) and LDH (<300 µmol/L) levels and elevated leukocytes at the time of the procedures. PTBD is considered in ABD patients who are candidates for chemotherapy.

Prospective Non-Randomized Study of Intraoperative Assessment of Surgical Resection Margin of Colo-Rectal Liver Metastases.

Introduction: More than 50% of patients with colorectal cancer (CRC) develop liver metastases during the natural course of disease. Surgical resection is currently the most potentially curative method in the treatment of colorectal liver metastases (CRLM). The goal of surgery is to achieve a negative resection margin (RM) of at least 1 mm, which provides the best prognosis for patients. The RM can be assessed by the pathologist of the resected liver specimen (RLS) and by the surgeon intraoperatively. The aim of this research paper is to determine the degree of agreement on intraoperative assessment of the RM by the surgeon and histopathological RM assessment by the pathologist. Material and methods: This prospective non-randomized double-blind study was approved by the Ethics Committee of the Oncology Institute of Vojvodina and registered on ClinicalTrials.gov #NCT04634526. The study was conducted at the Oncology Institute of Vojvodina, Sremska Kamenica, Serbia. An experienced hepatobiliary surgeon assessed RM for every specimen intra-operatively, immediately after CRLM resection. Resected CRLM lesions were analyzed by two experienced pathologists. These data were compared with pathological RM assessment as a "gold standard". RM of 1 mm or more was rated as negative RM (RM-). Disease-free survival (DFS) and recurrence rate was calculated by RM status defined by surgeon and by pathologist. Results: From 01 January 2015 to 31 August 2019, 98 patients were enrolled in the study. There were 219 RLS with 245 CRLM. The surgeon registered positive RM (RM+) of <1mm in 41 (18.7%) RLS. Taking the result of the histopathological assessment (HPA) as the "gold standard", it was determined that RM was true positive in 32 (14.6%) cases. False positive RM was found in 9 (4.1%) cases. False negative RM was found in 20 (9.1%) cases. True negative RM was found in 158 (72.2%) cases. Sensitivity of surgical assessment (SA) of RM+ was 61.5% (32/52). Specificity of SA of RM+ was 94.6% (158/167). The positive predictive value (PPV) was 78.0% (32/41), while the negative predictive value (NPV) was 88.8% (158/178). The overall accuracy of the RM+ SA was 86.8% (190/219). There was no statistically significant difference in the assessment of RM+ per RLS by surgeon and pathologists (p=0.061), but it was significant when analyses per patients was performed (p=0.017). Recurrence rate for RM+ patients was 48.1% (13/27, p=0.05) for SA and 35.0% (14/40, p=0.17) for HPA. Three year DFS for RM- and RM+ was 66.5% and 27.9% (p=0.04), respectively, by SA, and 64.8% and 42.1% (p=0.106), respectively, by HPA. Conclusion: Intraoperative assessment of RM- by surgeon of RLS is clinically meaningful. There is not a statistically significant difference in the assessment of RM+ by surgeon and pathologists per RLS, but it was statically significant on a per patient basis. RM determined by surgeon has better prognostic impact on recurrence rate and 1- and 3-year DFS than standard histopathological assessment.

Building a collaboration to improve surgical research through EORTC/ESSO 1409-CLIMB study: A prospective liver metastasis database with an integrated quality assurance program.

The challenges of conducting surgical oncology trials have resulted to low quantity and poor quality research [1,2]. Considering the definitive role of surgery to offer cure, immediate response to improve surgical research is needed [3]. The European Organization for Research and Treatment of Cancer (EORTC) and the European Society of Surgical Oncology (ESSO) share the vision to achieve excellent surgical research and care for cancer patients. Building on their complimentary expertise, they embarked on a pilot project to map out challenges and initiate a sustainable collaboration to advance cancer surgery research in Europe. This pilot project is EORTC-ESSO 1409 GITCG/ ESSO-01: A Prospective Colorectal Liver Metastasis Database with an Integrated Quality Assurance Program (CLIMB). This article will describe the challenges, milestones and vision of both organizations in setting up this collaboration.

Both the intratumoral immune and microbial microenvironment are linked to recurrence in human colon cancer: results from a prospective, multicenter nodal ultrastaging trial.

Colon cancer (CC) is the third most common cancer diagnosed in the United States and the incidence has been rising among young adults. We and others have shown a relationship between the immune infiltrate and prognosis, with improved disease-free survival (DFS) being associated with a higher expression of CD8+ T cells. We hypothesized that a microbial signature might be associated with intratumoral immune cells as well as DFS. We found that the relative abundance of one Operational Taxonomic Unit (OTU), OTU_104, was significantly associated with recurrence even after applying false discovery correction (HR 1.21, CI 1.08 to 1.36). The final multivariable model showed that DFS was influenced by three parameters: N-stage, CD8+ labeling, as well as this OTU_104 belonging to the order Clostridiales. Not only were CD8+ labeling and OTU_104 significant contributors in the final DFS model, but they were also inversely correlated to each other (p=0.022). Interestingly, CD8+ was also significantly associated with the microbiota composition in the tumor: CD8+ T cells was inversely correlated with alpha diversity (p=0.027) and significantly associated with the beta diversity. This study is the first to demonstrate an association among the intratumoral microbiome, CD8+ T cells, and recurrence in CC. An increased relative abundance of a specific OTU_104 was inversely associated with CD8+ T cells and directly associated with CC recurrence. The link between this microbe, CD8+ T cells, and DFS has not been previously shown.

The Negative Impact of Body Mass Index on the Tumor Microenvironment in Colon Cancer: Results of a Prospective Trial.

BACKGROUND: The association between tumor mismatch repair status and obesity in colon cancer is not well understood. The authors of this study hypothesized that mismatch repair deficiency in colon cancer may be associated with a lower Body Mass Index (BMI) and improved patient outcome due to an enhanced tumor immune microenvironment. METHODS: For this study, 70 patients were randomly selected from a prospective trial evaluating nodal ultrastaging for colon cancer. The mismatch repair status of tumors and immunomarker expression were correlated with clinicopathologic characteristics and evaluated for disease-free survival. RESULTS: Patients with mismatch repair-deficient tumors (n = 11) had a lower mean BMI than those with mismatch repair-proficient tumors (n = 59) (22.16 vs. 26.30 kg/m2, respectively; p = 0.029).The findings showed that CD3+ T cells were inversely associated with mismatch repair proficiency (p = 0.048). Mismatch repair-proficient tumors in nonobese patients (BMI < 30 kg/m2) versus obese patients had a higher density of CD8+ (p = 0.008) and FOXP3+ (p = 0.005) T cells. Multivariable analysis linked CD4+ (hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.35-0.76), CD8+ (HR 0.67; 95% CI 0.50-0.89), and number of tumor-positive lymph nodes (HR 1.19; 95% CI 1.03-1.36) to disease-free survival for patients with mismatch repair-proficient tumors. CONCLUSIONS: Tumor mismatch repair status and obesity are correlated in patients with colon cancer. Increased intratumoral T cells in nonobese patients suggests an unexplored link between tumor mismatch repair and immunoprofile.

Sex-Specific Differences in Colon Cancer when Quality Measures Are Adhered to: Results from International, Prospective, Multicenter Clinical Trials.

BACKGROUND: There is no consensus on the relationship between patient sex and the location, stage, and oncologic outcome of colon cancer (CC). We hypothesized that there is a sex-specific difference in the biology and management of CC. STUDY DESIGN: Our cohort was drawn from a database of patients enrolled in international trials of nodal ultrastaging for nonmetastatic CC. These trials required strict adherence to surgical and pathologic quality measures. Postoperative follow-up included colonoscopy at 1 and 4 years and annual CT scans. Sex-specific differences in tumor biology, location, stage, and recurrence were evaluated by chi-square, Fischer's exact, and independent t-tests. RESULTS: The cohort included 435 males (median age 69 years) and 423 females (median age 70 years). Females had more right-sided (p = 0.03) and earlier T stage (p = 0.05) tumors, but there was no sex-based difference in pathologic grade, total lymph nodes retrieved, nodal positivity (p = 0.47) or lymphovascular invasion (p = 0.45). The overall 4-year disease-free survival (DFS) was comparable in females and males (77.9% and 77.5%, respectively). By multivariate analysis, only nodal positivity and cancer recurrence affected overall survival (OS) (p = 0.008). Neither sex nor primary tumor affected DFS or OS. CONCLUSIONS: This is the first prospective study to demonstrate sex-specific differences in location and T stage of CC when surgical and pathologic management adhered to strict quality standards. The predominance of right-sided CC in females suggests that flexible sigmoidoscopy may be inadequate for screening and surveillance. Interestingly, earlier stage and right-sided location did not confer a DFS or OS advantage for women. Additional studies are needed to determine why females have a higher propensity for right-sided lesions and a potential difference in CC biology.

Prospective randomized controlled trial comparing standard analgesia with combined intra-operative cystic plate and port-site local anesthesia for post-operative pain management in elective laparoscopic cholecystectomy.

BACKGROUND: Various mechanisms, including somatic and visceral nociceptive stimulation, have been suggested as a cause for pain after laparoscopic cholecystectomy (LC). We therefore conducted a prospective randomized controlled trial (PRCT) to evaluate whether somatovisceral pain blockade reduces pain after LC. HYPOTHESIS: Analgesic efficacy of multimodal analgesia is superior to standard analgesia for patients undergoing elective LC for symptomatic cholelithiasis. Specifically, topical cystic plate and port-site injection with 0.25 % bupivacaine significantly reduces pain after LC. DESIGN: This study was designed as single-blinded PRCT. SETTING: This study was conducted in an academic medical center. PATIENTS AND METHODS: Between February and May 2010 we randomly assigned 63 patients with symptomatic cholelithiasis in a 1:1 ratio to non-opioid/opioid analgesic combinations (Control Group, n = 32) and non-opioid/opioid analgesic combinations plus topical 0.25 % bupivacaine onto the cystic plate and local 0.25 % bupivacaine port-site injection, post-LC (Study Group, n = 31). Primary endpoint was patient-reported pain 1, 4, 6, 12, 24 h and 1 week post-LC using the Visual Analog Scale (VAS 0-10). RESULTS: Study groups were comparable clinicopathologically. There were no adverse events. A statistically significant reduction in mean pain score was apparent in Study Group patients in comparison with Control Group (mean VAS 4.83 ± 2.33 vs. 6.80 ± 1.87; p < 0.001) at all early (1-6 h) post-operative time points following LC. CONCLUSION: This PRCT shows significantly improved pain control with somatovisceral pain blockade over non-opioid/opioid analgesic combinations following LC for symptomatic cholelithiasis. For centers not utilizing adjunctive local anesthetic for LC, this topical use of bupivacaine may improve patient comfort during recovery. This trial was registered on www.ClinicalTrials.gov NCT# 01972620.

Postoperative complications and overall survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

INTRODUCTION: Pancreaticoduodenectomy (PD) performed for pancreatic ductal adenocarcinoma (PDA) has a postoperative morbidity of 40-50%. In this study, we analyzed the impact of high grade complications after PD for PDA on overall survival. METHODS: A total of 596 patients that underwent PD for PDA between 2001 and 2009 were identified from a prospective database. Complications were defined and graded (1-5) as per our Institutional Surgical Secondary Events Program. High grade complications were defined as ≥grade 3. Postoperative mortality (≤90 days) was excluded. Univariate and multivariate analyses were performed to identify factors associated with overall survival. RESULTS: Median survival was 24 months. Overall complication rate was 51% (301/596). Low grade complications were recorded in 266 patients (45%) and high grade complications in 22% (n = 129). Our 90 day mortality was 3.7% (n = 22). Anastomotic fistula/leak/abscess rate was 14% (n = 82). Multivariate Cox-Regression analysis identified node positivity, estimated blood loss (EBL) >600 ml, length of stay (LOS) >10 days, margin positivity, and vascular procedures as predictors of decreased overall survival (P < 0.05). High grade complications were not associated with overall survival (P = 0.948). CONCLUSION: In this study, the occurrence of high grade postoperative complications was not associated with overall survival.

Prognostic Effect of Ultra-Staging Node-Negative Colon Cancer Without Adjuvant Chemotherapy: A Prospective National Cancer Institute-Sponsored Clinical Trial.

BACKGROUND: We recently reported, in a prospective randomized trial, that ultra-staging of patients with colon cancer is associated with significantly improved disease-free survival (DFS) compared with conventional staging. That trial did not control for lymph node (LN) number or adjuvant chemotherapy use. STUDY DESIGN: The current international prospective multicenter cooperative group trial (ClinicalTrials.gov identifier NCT00949312; "Ultra-staging in Early Colon Cancer") evaluates the 12-LN quality measure and nodal ultra-staging impact on DFS in patients not receiving adjuvant chemotherapy. Eligibility criteria included biopsy-proven colon adenocarcinoma; absence of metastatic disease; >12 LNs staged pathologically; pan-cytokeratin immunohistochemistry (IHC) of hematoxylin and eosin (H&E)-negative LNs; and no adjuvant chemotherapy. RESULTS: Of 445 patients screened, 203 patients were eligible. The majority of patients had intermediate grade (57.7%) and T3 tumors (64.9%). At a mean follow-up of 36.8 ± 22.1 months (range 0 to 97 months), 94.3% remain disease free. Recurrence was least likely in patients with ≥12 LNs, H&E-negative LNs, and IHC-negative LNs (pN0i-): 2.6% vs 16.7% in the pN0i+ group (p < 0.0001). CONCLUSIONS: This is the first prospective report to demonstrate that patients with optimally staged node-negative colon cancer (≥12 LNs, pN0i-) are unlikely to benefit from adjuvant chemotherapy; 97% remain disease free after primary tumor resection. Both surgical and pathologic quality measures are imperative in planning clinical trials in nonmetastatic colon cancer.

Value of primary tumor gene signatures in colon cancer when national quality standards are adhered to: preliminary results of an international prospective multicenter trial.

BACKGROUND: The purpose of this study was to determine if gene signatures are informative in colon cancer (CC) when National Quality Standards (NQS) are adhered to. Several studies have demonstrated the prognostic potential of gene signatures in primary CC. This has never been evaluated prospectively with adherence to NQS. METHODS: This was a prospective, international, multicenter trial. Eligibility criteria were: no distant metastasis, ≥12 lymph nodes (LNs), and no adjuvant chemotherapy for LN-negative CC. RNA from frozen tumor samples was considered reliable if RNA Integrity Number >9. Using an Agilent whole human genome array, 44,000 genes were analyzed in primary tumors for differential gene expression (DGE). ANOVA applied at 2-fold expression level was performed in at least 8 experiments to obtain the DGEs. RESULTS: Molecular analysis was completed in 113 of 128 patients. With median follow-up of 27 months, 11.5 % recurred within 3 years after surgery. Significant DGE was identified in recurrent tumors reflected by upregulation (UR) in cellular proliferation and by downregulation (DR) in prodifferentiating panel of 9 genes, independent of T or N classification. By multivariate analysis 3-year disease-free survival was 12.5 % in the UR/DR group versus 93.4 % in the non-UR/DR group (p < .0001; HR = 24.2; 95 % CI 4.8-120.4). CONCLUSIONS: This is the first prospective trial to evaluate gene signatures in CC with adherence to a 12-node minimum quality standard. Certain molecular pathways may be prognostically relevant if both surgery and pathology are standardized, regardless of T or N classification. Careful consideration should be made to include surgical quality measures when planning clinical trials to evaluate the true effect of molecular markers in CC.

Time-dependent estimates of recurrence and survival in colon cancer: clinical decision support system tool development for adjuvant therapy and oncological outcome assessment.

Unanswered questions remain in determining which high-risk node-negative colon cancer (CC) cohorts benefit from adjuvant therapy and how it may differ in an equal access population. Machine-learned Bayesian Belief Networks (ml-BBNs) accurately estimate outcomes in CC, providing clinicians with Clinical Decision Support System (CDSS) tools to facilitate treatment planning. We evaluated ml-BBNs ability to estimate survival and recurrence in CC. We performed a retrospective analysis of registry data of patients with CC to train-test-crossvalidate ml-BBNs using the Department of Defense Automated Central Tumor Registry (January 1993 to December 2004). Cases with events or follow-up that passed quality control were stratified into 1-, 2-, 3-, and 5-year survival cohorts. ml-BBNs were trained using machine-learning algorithms and k-fold crossvalidation and receiver operating characteristic curve analysis used for validation. BBNs were comprised of 5301 patients and areas under the curve ranged from 0.85 to 0.90. Positive predictive values for recurrence and mortality ranged from 78 to 84 per cent and negative predictive values from 74 to 90 per cent by survival cohort. In the 12-month model alone, 1,132,462,080 unique rule sets allow physicians to predict individual recurrence/mortality estimates. Patients with Stage II (N0M0) CC benefit from chemotherapy at different rates. At one year, all patients older than 73 years of age with T2-4 tumors and abnormal carcinoembryonic antigen levels benefited, whereas at five years, all had relative reduction in mortality with the largest benefit amongst elderly, highest T-stage patients. ml-BBN can readily predict which high-risk patients benefit from adjuvant therapy. CDSS tools yield individualized, clinically relevant estimates of outcomes to assist clinicians in treatment planning.

Dysfunctional ectopic thyroid gland: a case report.

INTRODUCTION: Lingual thyroid gland is a rare anomaly of thyroid gland development, occurring more frequently in females. If it causes local symptomatology such as dysphagia, dysphonia or dyspnea it is diagnosed in childhood, however, if it is asymptomatic it is usually diagnosed in adulthood. CASE OUTLINE: We present a 23-year-old female patient in whom we diagnosed lingual thyroid gland coincidentally during diagnostic procedures of a concomitant disease. The application of 131I scintigraphy showed an oval field of intensive accumulation of radio markers in the zone of medial face line, around tongue base, with the absence of thyroid gland in its physiological position. Functional testing proved primary hypothyroidism and we started the application of substitution therapy. The application of levothyroxine resulted in reaching euthyroid state and the reduction of thyroid gland size. CONCLUSION: We present a very rare anomaly of the thyroid gland, and so far there have been no clear attitudes about further treatment. The general condition of the patient, age, the size of ectopic thyroid gland and the existence of local symptomatology or complications represent the factors that have influence on the choice of treatment method.

Evidence-based Guidelines for Precision Risk Stratification-Based Screening (PRSBS) for Colorectal Cancer: Lessons learned from the US Armed Forces: Consensus and Future Directions.

Colorectal cancer (CRC) is the third most common cause of cancer-related death in the United States (U.S.), with estimates of 143,460 new cases and 51,690 deaths for the year 2012. Numerous organizations have published guidelines for CRC screening; however, these numerical estimates of incidence and disease-specific mortality have remained stable from years prior. Technological, genetic profiling, molecular and surgical advances in our modern era should allow us to improve risk stratification of patients with CRC and identify those who may benefit from preventive measures, early aggressive treatment, alternative treatment strategies, and/or frequent surveillance for the early detection of disease recurrence. To better negotiate future economic constraints and enhance patient outcomes, ultimately, we propose to apply the principals of personalized and precise cancer care to risk-stratify patients for CRC screening (Precision Risk Stratification-Based Screening, PRSBS). We believe that genetic, molecular, ethnic and socioeconomic disparities impact oncological outcomes in general, those related to CRC, in particular. This document highlights evidence-based screening recommendations and risk stratification methods in response to our CRC working group private-public consensus meeting held in March 2012. Our aim was to address how we could improve CRC risk stratification-based screening, and to provide a vision for the future to achieving superior survival rates for patients diagnosed with CRC.

Serum-based DNA methylation biomarkers in colorectal cancer: potential for screening and early detection.

Colorectal cancer (CRC) is the third most common cause of cancer-related death in the United States. Early identification and treatment of pre-cancerous colorectal lesions, or node-negative CRC are highly effective interventions that substantially reduce disease-specific mortality. Colonoscopy remains a highly effective primary screening tool based on its excellent diagnostic accuracy, and its ability to remove pre-cancerous lesions. However, the nature of the procedure limits compliance with colonoscopy intended for population-based CRC screening. A significant advance in the screening and care of these patients could be realized by blood-based biomarkers, which could accurately identify patients at-risk for CRC development whom might benefit from early and/or more frequent surveillance for disease. We reviewed and herein discuss the potential for serum based DNA methylation biomarkers for screening and early detection of CRC.

Significance of infectious agents in colorectal cancer development.

Colorectal cancer (CRC) is a major burden to healthcare systems worldwide accounting for approximately one million of new cancer cases worldwide. Even though, CRC mortality has decreased over the last 20 years, it remains the third most common cause of cancer-related mortality, accounting for approximately 600,000 deaths in 2008 worldwide. A multitude of risk factors have been linked to CRC, including hereditary factors, environmental factors and inflammatory syndromes affecting the gastrointestinal tract. Recently, various pathogens were added to the growing list of risk factors for a number of common epithelial cancers, but despite the multitude of correlative studies, only suggestions remain about the possible relationship between selected viruses and bacteria of interest and the CRC risk. United States military service members are exposed to various risk factors impacting the incidence of cancer development. These exposures are often different from that of many sectors of the civilian population. Thereby, cancer risk identification, screening and early detection are imperative for both the military health care beneficiaries and the population as a whole. In this review, we will focus on several pathogens and their potential roles in development of CRC, highlighting the clinical trials evaluating this correlation and provide our personal opinion about the importance of risk reduction, health promotion and disease prevention for military health care beneficiaries.

The Diagnostic and Prognostic Role of microRNA in Colorectal Cancer - a Comprehensive review.

The discovery of microRNA, a group of regulatory short RNA fragments, has added a new dimension to the diagnosis and management of neoplastic diseases. Differential expression of microRNA in a unique pattern in a wide range of tumor types enables researches to develop a microRNA-based assay for source identification of metastatic disease of unknown origin. This is just one example of many microRNA-based cancer diagnostic and prognostic assays in various phases of clinical research.Since colorectal cancer (CRC) is a phenotypic expression of multiple molecular pathways including chromosomal instability (CIN), micro-satellite instability (MIS) and CpG islands promoter hypermethylation (CIMP), there is no one-unique pattern of microRNA expression expected in this disease and indeed, there are multiple reports published, describing different patterns of microRNA expression in CRC.The scope of this manuscript is to provide a comprehensive review of the scientific literature describing the dysregulation of and the potential role for microRNA in the management of CRC. A Pubmed search was conducted using the following MeSH terms, "microRNA" and "colorectal cancer". Of the 493 publications screened, there were 57 papers describing dysregulation of microRNA in CRC.

Tumor-infiltrating immune cells promoting tumor invasion and metastasis: existing theories.

It is a commonly held belief that infiltration of immune cells into tumor tissues and direct physical contact between tumor cells and infiltrated immune cells is associated with physical destructions of the tumor cells, reduction of the tumor burden, and improved clinical prognosis. An increasing number of studies, however, have suggested that aberrant infiltration of immune cells into tumor or normal tissues may promote tumor progression, invasion, and metastasis. Neither the primary reason for these contradictory observations, nor the mechanism for the reported diverse impact of tumor-infiltrating immune cells has been elucidated, making it difficult to judge the clinical implications of infiltration of immune cells within tumor tissues. This mini-review presents several existing hypotheses and models that favor the promoting impact of tumor-infiltrating immune cells on tumor invasion and metastasis, and also analyzes their strength and weakness.