miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR.

Regulatory changes occurring early in colorectal cancer development remain poorly investigated. Since the majority of cases develop from polyps in the adenoma-carcinoma transition, a search of early molecular features, such as aberrations in miRNA expression occurring prior to cancer development, would enable identification of potentially causal, rather than consequential, candidates in the progression of polyp to cancer. In the current study, by employing small RNA-seq profiling of colon biopsy samples, we described differentially expressed miRNAs and their isoforms in the adenoma-carcinoma transition. Analysis of healthy-adenoma-carcinoma sequence in an independent validation group enabled us to identify early deregulated miRNAs including hsa-miR-1246 and hsa-miR-215-5p, the expressions of which are, respectively, gradually increasing and decreasing. Loss-of-function experiments revealed that inhibition of hsa-miR-1246 lead to reduced cell viability, colony formation, and migration rate, thereby indicating an oncogenic effect of this miRNA in vitro. Subsequent western blot and luciferase reporter assay provided evidence of hsa-miR-1246 being involved in the regulation of target AXIN2 and CFTR genes' expression. To conclude, the present study revealed possible involvement of hsa-miR-1246 in early colorectal cancer development and regulation of tumor suppressors AXIN2 and CFTR.

The Role of VEGFA, COX2, HUR and CUGBP2 in Predicting the Response to Neoadjuvant Therapy in Rectal Cancer Patients.

Background and objectives: The effectiveness of neoadjuvant therapy, which is commonly used for stage II-III rectal cancer (RC) treatment, is limited. Genes associated with the pathogenesis of RC could determine response to this treatment. Therefore, the aim of this study was to investigate the potential predictive value of VEGFA, COX2, HUR and CUGBP2 genes and the associations between post-treatment changes in gene expression and the efficacy of neoadjuvant therapy. Materials and Methods: Biopsies from RC and healthy rectal tissue of 28 RC patients were collected before neoadjuvant therapy and 6-8 weeks after neoadjuvant therapy. The expression levels of VEGFA, COX2, HUR, CUGBP2 genes were evaluated using a quantitative real-time polymerase chain reaction. Results: The results reveal a significantly higher expression of VEGFA, COX2 and HUR mRNA in RC tissue compared to healthy rectal tissue (p < 0.05), and elevated VEGFA gene expression in pre-treatment tissues was associated with a better response to neoadjuvant therapy based on T-stage downstaging (p < 0.05). The expression of VEGFA, HUR and CUGBP2 genes significantly decreased after neoadjuvant therapy (p < 0.05). Responders to treatment demonstrated a significantly stronger decrease of VEGFA and COX2 expression after neoadjuvant therapy than non-responders (p < 0.05). Conclusions: The findings of this study suggest that the pre-treatment VEGFA gene expression might have predictive value for the response to neoadjuvant therapy, while the post-treatment decrease in VEGFA and COX2 gene expression could indicate the effectiveness of neoadjuvant therapy in RC patients.

Preoperative long-course chemoradiotherapy plus adjuvant chemotherapy versus short-course radiotherapy without adjuvant chemotherapy both with delayed surgery for stage II-III resectable rectal cancer: 5-Year survival data of a randomized controlled trial.

BACKGROUND AND OBJECTIVE: At present, there are common recommendations for treatment for stage II-III resectable rectal cancer patients: preoperative conventional chemoradiotherapy (CRT) with delayed surgery in 6-8 weeks or preoperative short-course radiotherapy (SCRT) followed by immediate surgery. The aim of this study was to compare overall survival (OS) and disease-free survival (DFS) in two treatment groups: preoperative SCRT and CRT both with delayed surgery plus adjuvant chemotherapy in CRT arm. MATERIALS AND METHODS: A total of 150 patients were randomly assigned to two groups: 75 to CRT (preoperative conventional CRT, 50Gy/25 fr with fluorouracil and leucovorin on the 1st and the 5th week of RT followed by TME surgery in 6-8 weeks and 4 cycles of adjuvant fluorouracil/leucovorin every 4 weeks; then follow-up) and 75 to SCRT (preoperative short-course RT, 25Gy/5 fr followed by TME surgery in 6-8 weeks; then follow-up). The data of 140 patients (72 in CRT and 68 in SCRT group) were included in statistical analysis. Primary end points were OS and DFS. RESULTS: Median follow-up was 60.5 (range, 5-108) months. The 5-year DFS was 67% in the CRT group (n=72) and 45% in the SCRT group (n=68) (P=0.013; HR=1.88; 95% CI, 1.13-3.12; P=0.015). The 5-year OS was 79% and 62% in the CRT and SCRT groups, respectively (P=0.015; HR=2.05; 95% CI, 1.13-3.70; P=0.017). The 5-year OS for intent-to-treat (ITT) population (n=150) was 78% in the CRT and 58% in the SCRT group (P=0.003; HR=2.28; 95% CI, 1.30-4.00; P=0.004). CONCLUSIONS: The 5-year DFS and OS were significantly better in the CRT than the SCRT group. For ITT population, OS was also significantly better after CRT versus SCRT.

Preoperative conventional chemoradiotherapy versus short-course radiotherapy with delayed surgery for rectal cancer: results of a randomized controlled trial.

BACKGROUND: There still is no evidence which neoadjuvant therapy regimen for stage II-III rectal cancer is superior. The aim of this study was to compare results achieved after long-course chemoradiotherapy (CRT) with short-term radiotherapy (RT) followed by delayed surgery. METHODS: A randomized trial was carried out between 2007-2013. One hundred fifty patients diagnosed with stage II-III rectal cancer were randomized into one of two neoadjuvant treatment arms: conventional chemoradiotherapy (CRT) and short-term radiotherapy (RT) followed by surgery after 6-8 weeks. Primary endpoints of this trial were downstaging and pathological complete response rate. Secondary endpoints were local recurrence rate and overall survival. RESULTS: The pathological complete response was found in 3 (4.4%) cases after RT and 8 (11.1%) after CRT (P = 0.112). Downstaging (stage 0 and I) was observed in 21 (30.9%) cases in RT group vs. 27 (37.5%) cases in CRT group (P = 0.409). Median follow-up time was 39.7 (range 4.9-79.7) months. 3-years overall survival (OS) was 78% in RT group vs. 82.4% in CRT group (P = 0.145), while disease-free survival (DFS) differed significantly - 59% in RT group vs. 75.1% in CRT group (P = 0,022). Hazard ratio of cancer progression for RT patients was 1.93 (95% CI: 1.08-3.43) compared to CRT patients. CONCLUSION: Three-years disease-free survival was better in CRT group comparing with RT group with no difference in overall survival. TRIAL REGISTRATION: http://clinicaltrials.gov identifier NCT00597311. January 2008.

Surgical treatment of pilonidal disease - Short-term follow up results of minimally invasive pit-picking surgery versus radical excision without suturing: A prospective randomised trial.

Background: In this study we compared the potential benefits of surgical treatments for chronic symptomatic pilonidal disease (PD) - minimally invasive pit-picking surgery and radical excision without wound suturing. Materials and methods: A total of 100 adult patients with chronic symptomatic PD were enrolled in this study at the Kaunas Hospital of the Lithuanian University of Health Sciences. They were randomly divided into two groups: pit-picking surgery (n = 50) and radical excision with open healing (n = 50). Recurrent PD patients were not excluded. The comparison of the techniques was based on pain within the first postoperative week, failed surgery rates, and wound healing time. Additionally, pain levels at different time intervals following the treatment, analgesic consumption, and time off work, were assessed and compared. Results: A total of 89 patients (89 %) were available for follow-up after 6 months. Pain levels the first postoperative week were significantly lower in the pit-picking group compared to the radical excision group, with median scores of 10.0 and 20.0, respectively (p = 0.002). The complete wound healing time was longer in the radical excision group (60 days) versus the pit-picking group (17 days), with a significant difference noted (p = 0.00). No significant difference was observed between the type of surgery and the rate of failed surgery, with 5 (11.9 %) cases in the pit-picking group and 4 (8.5 %) in the radical excision group. Conclusion: Based on our short-term findings, minimally invasive pit-picking surgery is a better option regarding pain, wound healing time and failed surgery rate. In cases where this approach is not suitable, other alternatives should be contemplated, as radical surgery without wound suturing should not be employed as a treatment method for PD. Additionally, the relationship between PD and recurrence rates should be investigated further.

Association between use of enhanced recovery after surgery protocols and postoperative complications in colorectal surgery in Europe: The EuroPOWER international observational study.

STUDY OBJECTIVE: Assess the relationship between the Enhanced Recovery After Surgery (ERAS®) pathway and routine care and 30-day postoperative outcomes. DESIGN: Prospective cohort study. SETTING: European centers (185 hospitals) across 21 countries. PATIENTS: A total of 2841 adult patients undergoing elective colorectal surgery. Each hospital had a 1-month recruitment period between October 2019 and September 2020. INTERVENTIONS: Routine perioperative care. MEASUREMENTS: Twenty-four components of the ERAS pathway were assessed in all patients regardless of whether they were treated in a formal ERAS pathway. A multivariable and multilevel logistic regression model was used to adjust for baseline risk factors, ERAS elements and country-based differences. RESULTS: A total of 1835 patients (65%) received perioperative care at a self-declared ERAS center, 474 (16.7%) developed moderate-to-severe postoperative complications, and 63 patients died (2.2%). There was no difference in the primary outcome between patients who were or were not treated in self-declared ERAS centers (17.1% vs. 16%; OR 1.00; 95%CI, 0.79-1.27; P = 0.986). Hospital stay was shorter among patients treated in self-declared ERAS centers (6 [5-9] vs. 8 [6-10] days; OR 0.82; 95%CI, 0.78-0.87; P < 0.001). Median adherence to 24 ERAS elements was 57% [48%-65%]. Adherence to ERAS-pathway quartiles (≥65% vs. <48%) suggested that patients with the highest adherence rates experienced a lower risk of moderate-to-severe complications (15.9% vs. 17.8%; OR 0.71; 95%CI, 0.53-0.96; P = 0.027), lower risk of death (0.3% vs. 2.9%; OR 0.10; 95%CI, 0.02-0.42; P = 0.002) and shorter hospital stay (6 [4-8] vs. 7 [5-10] days; OR 0.74; 95%CI, 0.69-0.79; P < 0.001). CONCLUSIONS: Treatment in a self-declared ERAS center does not improve outcome after colorectal surgery. Increased adherence to the ERAS pathway is associated with a significant reduction in overall postoperative complications, lower risk of moderate-to-severe complications, shorter length of hospital stay and lower 30-day mortality.

Lymph node retrieval after resection of rectal cancer following preoperative chemoradiotherapy.

BACKGROUND: According to the current guidelines of proper TNM staging, 12 lymph nodes per specimen are crucial. This study assessed the role of preoperative radiochemotherapy on the number of lymph nodes detected in the tumor-bearing specimen. MATERIAL AND METHODS: Retrospective data of 138 patients who underwent surgery for stage II and III rectal cancer without preoperative radiochemotherapy during the period of 2004-2006 (control group) were compared with prospective data of 38 patients who received preoperative radiochemotherapy during the period of 2007-2008 (study group). The number of patients with metastatic lymph nodes, number of lymph nodes per specimen, number of metastatic lymph nodes per specimen, and the size of the tumor between the groups were compared. RESULTS: Positive lymph nodes were detected in 88 (64%) patients in the control group as compared with 9 (21%) patients in the study group (P<0.05). The mean number of lymph nodes per specimen in the control group was 13.5, while in the study group, the mean number of lymph nodes per specimen was 6.29 (P<0.05). There was a significant difference in the mean number of metastatic lymph nodes per specimen between the groups (5.12 in the control group versus 2.11 in the study group; P<0.05). The mean size of the tumor was 4.37 cm in the control group and 2.45 cm in the study group (P<0.01). CONCLUSIONS: Preoperative radiochemotherapy for advanced rectal cancer significantly decreased the number of lymph nodes detected in the tumor-bearing specimen. This also resulted in a significant decrease in the number of metastatic lymph nodes detected in the specimen, and fewer patients with stage III (N+) cancer were diagnosed. Preoperative radiochemotherapy could induce a significant downsizing and downstaging of advanced rectal cancer, but great care in operative and pathologic examination techniques must be taken to ensure appropriate staging.

Colonic intussusception caused by colonic lipoma: a case report.

Intussusception is a pediatric condition that rarely presents in adults. Colonic lipomas 4 cm and more in diameter can cause colonic intussusception leading to emergency operation. Surgical resection of the involved segment must be the procedure of choice. We report a case of colonic intussusception caused by colonic lipoma in an adult. The patient underwent operation, and histopathological examination of the specimen confirmed the diagnosis of colonic submucosal lipoma.

[Laparoscopic surgery for malignancies of the colon, rectum, and anus in Lithuania in 2008]. / Laparoskopines storosios zarnos ir isanges piktybiniu naviku operacijos Lietuvoje 2008 m.

UNLABELLED: THE OBJECTIVE OF THIS STUDY: was to analyze data on laparoscopic surgery for malignant diseases of the colon, rectum, and anus in Lithuania during the period of January 1, 2005, to February 15, 2008. MATERIAL AND METHODS: During the above-mentioned period in Lithuania, 130 laparoscopic surgeries for malignancies of colon, rectum, and anus were performed in seven different hospitals. There were 73 males and 57 females with a mean age of 68 years (range, 35-85 years). Laparoscopic procedures were attempted in 140 cases. Out of them, 130 were completed laparoscopically; 10 operations were converted to open, and conversion rate was 7.1%. Twenty-seven (20.8%) patients had stage I, 45 (34.6%) stage II, 45 (34.6%) stage III, and 13 (10%) stage IV disease. Ninety-two (70.8%) patients underwent straight laparoscopic surgery and 38 (29.2%) - hand-assisted laparoscopic surgery. Time in surgery was from 50 to 365 min, with a mean of 183 min. During 130 operations, in 11 (8.5%) cases, blood vessels were ligated through specimen retrieval site. Out of 104 operations, where anastomosis was performed (23 abdominoperineal resections and 3 Hartmann's procedures), in 68 (65.4%) cases it was done laparoscopically and in 36 (34.6%) cases using conventional extracorporal suturing. RESULTS: Hospital stay ranged from 7 to 59 days, with a mean of 12 days. One (0.8%) patient died. Postoperative complications occurred in 27 (20.8%) cases. Reoperation rate was 4.6% (6 cases). Complications were as follows: suture insufficiency (3 cases), eventration (3 cases), wound infection (7 cases), intraperitoneal abscess (1 case), abdominal wall phlegmon (1 case), intra-abdominal infiltrate (1 case), perineal hematoma (1 case), proctovaginal fistula (2 case), intraoperative bleeding from uterus (1 case), urinary retention (4 cases), cystitis (1 case), pneumonia (1 case), acute cardiovascular insufficiently (1 case). In histological specimens, 10 lymph nodes were found on the average (range, 2 to 27). CONCLUSIONS: Laparoscopic surgery for malignant diseases of the colon, rectum, and anus is dominating among laparoscopic surgeries for colorectum. Complication rate is similar to other authors. To evaluate disease relapse and outcomes, observation time is not sufficient yet.

The impact of age on post-operative outcomes of colorectal cancer patients undergoing surgical treatment.

BACKGROUND: the purpose of study was to evaluate the impact of age on outcomes in colorectal cancer surgery. METHODS: patients on hospital database treated for colorectal cancer during the period 1995 - 2002 were divided into two groups: Group 1--patients of 75 years or older (n = 154), and Group 2--those younger than 75 years (n = 532). RESULTS: In Group 1, for colon cancers, proximal tumors were significantly more common (23% vs. 13.5%, p < 0.05), complicated cases were more frequent (46 % vs. 33%, p = 0.002), bowel obstruction more common at presentation (40% vs. 26.5%, p = 0.001), and more frequent emergency surgery required (24% vs. 14%, p = 0.003). Postoperative overall morbidity was higher in the elderly group, but with no differences in surgical complications rate. Overall 5 year survival was 39% vs. 55% (p = 0.0006) and cancer related 5 year survival was 44% vs. 62% (p = 0.0006). Multivariate Cox analysis showed that age was not an independent risk factor for postoperative mortality. CONCLUSION: Preoperative complications and co-morbidities, more advanced disease, and higher postoperative nonsurgical complication rates adversely affect postoperative outcomes after surgery for colorectal cancer in the elderly.