Potential Molecular Markers Related to Lymph Node Metastasis and Stalk Resection Margins in Pedunculated T1 Colorectal Cancers Using Digital Spatial Profiling: A Pilot Study with a Small Case Series.

There is a debate regarding the prediction of lymph node metastasis (LNM) in pedunculated T1 colorectal cancer (CRC). In this study with four cases of pedunculated T1 CRCs, we aimed to investigate gene expression variations based on the distance from the Haggitt line (HL) and identify potential molecular risk factors for LNM. By leveraging the Cancer Transcriptome Atlas and digital spatial profiling technology, we meticulously analyzed discrete regions, including the head, HL, proximal stalk region (300-1000 µm from HL), and distal stalk region (1500-2000 µm from HL) to identify spatially sequential molecular changes. Our findings showed significant overall gene expression variations among the head, proximal stalk, and distal stalk regions of pedunculated T1 CRCs compared to the control adenoma. Compared to LNM-negative T1 CRCs, LNM-positive T1 CRC showed that the expression of genes involved in immune-related pathways such as B2M, HLA-B, and HLA-E were significantly downregulated in the distal stalk region compared to the proximal stalk region. In summary, our results may tentatively suggest considering endoscopic resection of the stalk with a minimum 2000 µm margin from the HL, taking into account the gene expression alterations related to immune-related pathways. However, we acknowledge the limitations of this pilot study, notably the small case series, which may restrict the depth of interpretation. Further validation is imperative to substantiate these findings.

Deep learning identifies inflamed fat as a risk factor for lymph node metastasis in early colorectal cancer.

The spread of early-stage (T1 and T2) adenocarcinomas to locoregional lymph nodes is a key event in disease progression of colorectal cancer (CRC). The cellular mechanisms behind this event are not completely understood and existing predictive biomarkers are imperfect. Here, we used an end-to-end deep learning algorithm to identify risk factors for lymph node metastasis (LNM) status in digitized histopathology slides of the primary CRC and its surrounding tissue. In two large population-based cohorts, we show that this system can predict the presence of more than one LNM in pT2 CRC patients with an area under the receiver operating curve (AUROC) of 0.733 (0.67-0.758) and patients with any LNM with an AUROC of 0.711 (0.597-0.797). Similarly, in pT1 CRC patients, the presence of more than one LNM or any LNM was predictable with an AUROC of 0.733 (0.644-0.778) and 0.567 (0.542-0.597), respectively. Based on these findings, we used the deep learning system to guide human pathology experts towards highly predictive regions for LNM in the whole slide images. This hybrid human observer and deep learning approach identified inflamed adipose tissue as the highest predictive feature for LNM presence. Our study is a first proof of concept that artificial intelligence (AI) systems may be able to discover potentially new biological mechanisms in cancer progression. Our deep learning algorithm is publicly available and can be used for biomarker discovery in any disease setting. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Influence of early colorectal cancer component on the positive margins after endoscopic resection: a retrospective study.

BACKGROUND: Endoscopic treatment methods for early colorectal cancer (ECRC) mainly depend on the size and morphology. It is unclear whether different endoscopic resection methods could achieve curative resection for ECRC confined in the mucosa. The study was designed to compare the rate of positive vertical margin (VM) of ECRC with advanced adenomas (AAs) including adenoma > 1 cm, villous adenoma, high-grade intraepithelial neoplasia/dysplasia stratified by different endoscopic resection methods. METHODS: Rate of positive VM for 489 ECRCs including Intramucosal (pTis) and superficial submucosal invasion (pT1) carcinomas were compared with those of 753 AAs stratified by different endoscopic resection methods using Chi-squared test. Multivariate logistic model was performed to investigate the risk factors of positive VM for different endoscopic resection methods. RESULTS: The pTis ECRC exhibited a similar rate of positive VM as that of AAs for en bloc hot snare polypectomy (HSP, 0% Vs. 0.85%, P = 0.617), endoscopic mucosal resection (EMR, 0.81% vs. 0.25%, P = 0.375) and endoscopic submucosal dissection (ESD, 1.82% Vs. 1.02%, P = 0.659). The pTis carcinoma was not found to be a risk factor for positive VM by en bloc EMR (P = 0.349) or ESD (P = 0.368). The en bloc resection achieved for pT1a carcinomas exhibited similar to positive VM achieved through ESD (2.06% Vs. 1.02%, P = 1.000) for AAs. Nonetheless, EMR resulted in higher risk of positive VM (5.41% Vs. 0.25%, P < 0.001) for pT1a carcinomas as compared to AAs. The pT1a invasion was identified as a risk factor for positive VM in polyps with en bloc EMR (odds ratio = 23.90, P = 0.005) but not ESD (OR = 2.96, P = 0.396). CONCLUSION: Collectively, the pTis carcinoma was not found to be a risk factor for positive VM resected by en bloc HSP, EMR or ESD. Additionally, ESD may be preferred over EMR for pT1a carcinomas with lower rate of positive VM.

Long-term prognosis of curative endoscopic submucosal dissection for early colorectal cancer according to submucosal invasion: a multicenter cohort study.

BACKGROUND: Endoscopic submucosal dissection (ESD) can provide a high en bloc resection rate and has been widely applied as curative treatment for early colorectal cancer (ECC). However, surgical treatment is occasionally required, and reports on the long-term prognosis of ESD are insufficient. This study aimed to investigate the long-term outcomes of ECC removal by ESD, including local recurrence and metastasis. METHODS: This multicenter study was conducted retrospectively on 450 consecutive patients with ECC who were treated with ESD between November 2003 and December 2013. Clinical, pathological, and endoscopic data were collected to determine tumor depth, resection margin, lymphovascular invasion, and recurrence. RESULTS: The median follow-up period was 53.8 (12-138 months). The en bloc resection rate was 85.3% (384) and in intramucosal cancer being 84.1% and in superficial submucosal invasion (SM1) cancer being 89.8% (p = 0.158). The curative resection rate was 76.0% (n = 342), and there was no statistical difference between the two groups (77.3% vs. 71.4%, p = 0.231). The overall recurrence free survival rate (RFS) was 98.7% (444/450). In patients with curative resection, there was no statistically significant difference in RFS according to invasion depth (intramucosal: 99.3% vs. SM1: 97.1%, p = 0.248). CONCLUSIONS: Patients with curatively resected ECC treated with ESD showed favorable long-term outcomes. Curatively resected SM1 cancer has a RFS similar to that of intramucosal cancer.

Local excision of T1 colorectal cancer: good differentiation, absence of lymphovascular invasion, and limited tumor radial infiltration (≤4.25 mm) may allow avoiding radical surgery.

BACKGROUND: Early colorectal cancer (ECC) is defined as T1NXM0 colorectal cancer (CRC). Although a non-negligible number of T1-CRCs presents metastatic lymph-nodes, local excision is increasingly proposed as alternative to radical resection. Several criteria have been suggested to identify low-risk T1-CRC, but recommendations on this topic are still heterogeneous. This study aims to identify criteria associated with N+ T1-CRC, to select patients to undergo (or not) local excision. METHODS: A retrospective analysis of demographic, clinical, and histology criteria of 122 consecutive T1-CRC patients undergoing radical resection at Parma University Hospital between 2000 and 2018 has been performed. RESULTS: Lymph-node metastasis (LNM) was observed in 15/122 patients (12.3%). No LNM was observed among well-differentiated (G1) tumors (0/37), while 10/65 (15.4%) G2 cases as well as 5/20 (25%) G3 patients presented LNM. G1 was associated with absence of LNM (p = 0.013). After excluding G1 patients, the rate of N + T1-CRC was 17.6% (15/85). LNM was observed in 4/8 (50%) patients with lymphovascular invasion (LVI) and in 11/77 (14.2%) without LVI. LVI resulted being associated with LNM (p < 0.042). LNM was reported in 28.3% of cases with a tumor infiltration >4.25 mm (13/46), compared to 5.1% in cases with an infiltration ≤4.25 mm (2/39) (p = 0.012). In Cox regression analysis, the higher hazard ratio (HR) was reported for the LVI + and infiltration >4.25 mm (HR 24.849). CONCLUSIONS: In patients with ECC (pT1NXM0), good differentiation (G1), absence of lymphovascular invasion (LVI-), and tumor radial infiltration ≤4.25 mm may allow performing local resection and avoiding radical surgery.

Malignant potential of colorectal neoplasms in Lynch syndrome: an analysis of 325 lesions endoscopically treated at a single institute.

BACKGROUND: Patients with Lynch syndrome are at an increased risk of developing colorectal cancer, and the adenoma-carcinoma sequence is accelerated in these patients. However, the clinicopathological characteristics of colorectal neoplasms in Lynch syndrome patients are not well-known. METHODS: A total of 325 consecutive colorectal neoplasms were endoscopically removed from 68 patients with Lynch syndrome between June 2005 and May 2018 and retrospectively reviewed. RESULTS: Of the 325 lesions, 94 (29%), 220 (68%) and 11 (3%) were from patients with MLH1, MSH2 and MSH6 mutations, respectively. The median lesion size was 5 mm (range 2-40 mm), with 229 (71%) lesions having a non-polypoid morphology. The frequencies of advanced neoplasms, including high-grade adenomas, intramucosal carcinomas and submucosal invasive carcinomas were 14, 34, 97 and 93% for lesions with diameters of <5, ≥5 and <10, ≥10 and <20, and ≥20 mm, respectively. The frequencies of advanced neoplasms in the proximal colon, distal colon and rectum did not significantly differ (36, 35 and 41%, respectively). CONCLUSIONS: Our results suggest that the malignant transformation interval from low-grade adenomas to advanced neoplasms is similar in all parts of the colon. Furthermore, since one-third of neoplastic lesions with diameters of ≥5 and <10 mm and most of those ≥10 mm were advanced neoplasms, we recommend that in Lynch syndrome patients, careful colonoscopic surveillance should be performed throughout the colon, and all neoplastic lesions, regardless of the size, should be subjected to detailed endoscopic examination, complete resection and detailed pathological examination.

Pedunculated early colorectal cancer with nodal metastasis: a case report.

BACKGROUND: Pedunculated polyps are more likely to be amenable to complete resection than non-pedunculated early colorectal cancers and rarely require additional surgery. We encountered a patient with a pedunculated early colorectal cancer that consisted of poorly differentiated adenocarcinoma with lymphatic invasion. We performed an additional bowel resection and found nodal metastasis. CASE PRESENTATION: A 43-year-old woman underwent colonoscopy after a positive fecal occult blood test. The colonoscopist found a 20-mm pedunculated polyp in the descending colon and performed endoscopic resection. Histopathologic examination revealed non-solid type poorly differentiated adenocarcinoma. The lesion invaded the submucosa (3500 µm from the muscularis mucosa) and demonstrated lymphatic invasion. In spite of the early stage of this cancer, the patient was considered at high risk for nodal metastasis. She was referred to our institution, where she underwent bowel resection. Although there was no residual cancer after her endoscopic resection, a metastatic lesion was found in one regional lymph node. The patient is undergoing postoperative adjuvant chemotherapy, and there has been no evidence of recurrence 3 months after the second surgery. CONCLUSIONS: Additional bowel resection is indicated for patients with pedunculated polyps and multiple risk factors for nodal metastasis, such as poorly differentiated adenocarcinoma and lymphatic invasion. We encountered just such a patient who did have a nodal metastasis; herein, we report her case history with a review of the literature.

Retrospective analysis of LNM risk factors and the effect of chemotherapy in early colorectal cancer: A Chinese multicenter study.

BACKGROUND: Estimating the risk of lymph node metastasis (LNM) is crucial for determining subsequent treatments following curative resection of early colorectal cancer (ECC). This multicenter study analyzed the risk factors of LNM and the effectiveness of postoperative chemotherapy in patients with ECC. METHODS: We retrospectively analyzed the data of 473 patients with ECC who underwent general surgery in five hospitals between January 2007 and October 2018. The correlations between LNM and sex, age, tumor size, tumor location, endoscopic morphology, pathology, depth of invasion and tumor budding (TB) were directly estimated based on postoperative pathological analysis. We also observed the overall survival (OS) and recurrence in ECC patients with and without LNM after matching according to baseline measures. RESULTS: In total, 473 ECC patients were observed, 288 patients were enrolled, and 17 patients had LNM (5.90%). The univariate analysis revealed that tumor size, pathology, and lymphovascular invasion were associated with LNM in ECC (P = 0.026, 0.000, and 0.000, respectively), and the multivariate logistic regression confirmed that tumor size, pathology, and lymphovascular invasion were risk factors for LNM (P = 0.021, 0.023, and 0.001, respectively). There were no significant differences in OS and recurrence between the ECC patients with and without LNM after matching based on baseline measures (P = 0.158 and 0.346, respectively), and no significant difference was observed between chemotherapy and no chemotherapy in ECC patients without LNM after surgery (P = 0.729 and 0.052). CONCLUSION: Tumor size, pathology, and lymphovascular invasion are risk factors for predicting LNM in ECC patients. Adjuvant chemotherapy could improve OS and recurrence in patients with LNM but not always in ECC patients without LNM.

A real world analysis of recurrence risk factors for early colorectal cancer T1 treated with standard endoscopic resection.

BACKGROUND AND STUDY AIM: Currently, endoscopic resection of early colorectal cancer defined as carcinoma with limited invasion of the mucosa (Tis) and submucosa (T1) is possible. However, lymph node spreading increases to 16.2% of cases when tumor invades the submucosa. We analyzed the previously identified factors for lymph node dissemination and recurrence, in our population. PATIENTS AND METHODS: We analyzed retrospectively all patients with T1 tumors, treated at our center with endoscopic resection and some with additional surgery between January 2006 and January 2018. Statistical analysis was performed using IBM SPSS Statistics 25.0. RESULTS: One hundred fifty-nine patients were treated with endoscopic resection, 56.6% with additional surgery. The mean age was 68.74 years and 69. 9% were male. All patients who underwent additional surgery presented negative margins and 8.8% presented positive lymph nodes. In a mean follow-up of 23.36 months, 13 patients had relapsed. The risk of relapse did not differ between patients treated with additional surgery from those who only underwent endoscopic resection (p = 0.506). On the other hand, lymph node dissemination (p = 0.007) and a positive endoscopic margin (p = 0.01) were independent risk factors for relapse. There was a positive association between lymph node dissemination and lymphatic (p = 0.07), vascular (p = 0.007), and perineural (p = 0.001) invasion and also with degree of histological differentiation (p = 0.001). CONCLUSION: In our study, lymphatic, vascular, and perineural invasion and also the degree of histological differentiation were associated with lymph node dissemination. However, the only independent risk factors for long-term recurrence were a positive margin and lymph node dissemination.

Significant polyp and early colorectal cancer - SPECC: The role of the Colorectal Cancer Clinical Nurse Specialist (CNS): promoting patient-centred care.

AIMS: The colorectal Clinical Nurse Specialist (CNS) makes an important contribution to the care of individuals diagnosed with a significant polyp and early colorectal cancer (SPECC). METHODS: This paper offers an expert opinion on the role of the CNS in SPECC, informed by relevant literature. RESULTS: A CNS can support the patient through the diagnostic and treatment pathway acting as the patient's advocate as a core member of the multidisciplinary team. They will offer support and information to help patients understand their diagnosis, make choices about their available treatment options and help them to feel prepared for any treatment undertaken. CONCLUSION: By providing care that is respectful of, and responsive to, individual patient preferences, needs and values, the CNS can play an important role in promoting patient-centred care.

How I do it: Flexible 3-D endoscope for endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is technically challenging as a result of a lack of depth perception. The present article investigated the 3-D endoscope for carrying out ESD and translated the technique from bench to clinical use. In a preclinical porcine experiment, ESD using a 3-D endoscope was compared between an experienced and a novice endoscopist. All ESD were completed without perforation. Median operative time per surface area was significantly lower for the experienced endoscopist than for the novice (197.9 s/cm2 vs 434.7 s/cm2 ; P = 0.05). The second part was a prospective clinical experience to evaluate use of the 3-D endoscope for carrying out ESD. Ten patients received ESD using the 3-D endoscope. Four patients had gastric ESD, two had duodenal ESD and four had sigmoid and rectal ESD. There were no complications, whereas ESD failed in one patient who had gastric neoplasia at anastomosis. Mean operative time was 99.4 min, and operative time per surface area resection was 391 s/cm2 . The operating endoscopist did not complain of motion sickness, whereas the assistants had some dizziness upon prolonged ESD procedure. This study showed that carrying out ESD was safe and effective using a 3-D endoscope with an excellent 3-D view enhancing depth perception. Future study should be conducted to compare 3-D against 2-D endoscopes for ESD.

Estimation of invasion depth of early colorectal cancer using EUS and NBI-ME: a meta-analysis.

BACKGROUND: Endoscopic ultrasonography (EUS) and narrow band imaging-magnifying endoscopy (NBI-ME) are often used as diagnostic tools to estimate the depth of invasion in early colorectal cancer (CRC). The aim of this study was to compare NBI-ME with EUS in distinguishing between slight submucosal invasion (invasion depth < 1000 µm) and massive submucosal invasion in patients with early CRC, since slight submucosal invasion is currently considered as an indication for endoscopic resection. METHODS: For this meta-analysis, relevant studies were identified from PubMed, Embase, Web of Science, Scopus and the Cochrane Library databases between January 1997 and September 2016. Data on the yield of tumors were extracted, pooled, and analyzed by stata12.0 software. The sensitivity, specificity, positive likelihood ratio and negative likelihood ratio in differentiating slight submucosal invasion from massive submucosal invasion were calculated for both diagnostic modalities. RESULTS: Sixteen studies involving 2197 lesions were included: nine were studies on EUS and 7 were studies on NBI-ME. The pooled sensitivity of EUS was 0.902 (95% CI 0.863-0.930), the specificity was 0.877 (95% CI 0.810-0.922), the positive likelihood ratio was 7.314 (95% CI 4.551-11.755) and the negative likelihood ratio was 0.112 (95% CI 0.076-0.164). The pooled sensitivity and specificity of NBI-ME were 0.981 (95% CI 0.949-0.993) and 0.651 (95% CI 0.600-0.699), respectively, the positive likelihood ratio was 2.815 (95% CI 2.432-3.258) and the negative likelihood ratio was 0.029 (95% CI 0.010-0.080). CONCLUSIONS: The sensitivity tended to be higher in ME-NBI than EUS for early CRC with slight submucosal invasion, whereas the specificity was significantly lower in NBI-ME than in EUS.

Implementation of mentor-assisted colorectal endoscopic submucosal dissection in Sweden; learning curve and clinical outcomes.

OBJECTIVE: It's still challenging to introduce colorectal (CR) ESD in Western countries. We assessed the feasibility of introducing and implementing CR-ESD in Sweden with hiring Japanese expert as a supervisor. METHODS: We analyzed 71 consecutive CR-ESD cases performed by two endoscopists who had no (endoscopist A (E-A)) or 20 cases (endoscopist B (E-B)) of experience in ESD. E-A performed rectal lesions while E-B performed lesions in any locations. Factors associated with failure in en bloc resection and in self-accomplishment were analyzed. RESULTS: Overall en bloc and R0 resection rates were 80.3% and 70.4%. Adverse event occurred in 7.0% including two perforations, two post-operative hemorrhage and one delayed perforation. Only case with delayed perforation underwent surgical treatment. Total self-accomplishment rate was 50% (10/20) for E-A, and 37.3% (19/51) for E-B. Dividing each performer's cases into three learning phases, self-accomplishment rates increased from 42.9% to 83.3% for E-A, and from 29.4% to 70.6% for E-B, as well as en bloc resection rates from 71.4% to 100% for E-A, and from 52.9% to 94.1% for E-B. Multivariate analysis revealed that location upper than rectum, lesions with formerly taken biopsy and lesions larger than 30mm were significantly associated with en bloc resection failure. CONCLUSIONS: Implementation of CR-ESD with hiring Japanese supervisor for certain period was safe for patients and effective for good learning curve.

The prognostic implications of primary tumor location on recurrence in early-stage colorectal cancer with no associated risk factors.

PURPOSE: Recently, several reports have suggested that tumor location serves as a prognostic biomarker in advanced colorectal cancer. However, the prognostic implication of tumor location in patients with early-stage colorectal cancer remains unclear. This study was aimed to examine the prognostic implication of tumor location in patients with early-stage colorectal cancer. METHODS: Patients with stage I and low-risk stage II colorectal cancer, treated with radical surgery in a hospital setting between May 2003 and September 2014, were retrospectively reviewed. Patients who underwent (neo) adjuvant chemotherapy and/or radiotherapy and whose microsatellite instability (MSI) status was lacked were excluded. Distal colon cancer was defined as tumors located from the splenic flexure colon to the sigmoid colon. RESULTS: A total of 712 patients were included in this study. Of these patients, 23 (3.2%) had a recurrence at a median follow-up time of 46 months. The tumor recurrence rate was significantly low in patients with proximal colon cancer. In the multivariate analysis, tumors located in the distal colon or rectum (distal colon, hazard ratio [HR] 9.213, P = 0.035; rectum, HR 15.366, P = 0.009) and T3 tumors (HR 4.590, P = 0.017) were related to tumor recurrence. A higher prevalence of tumor recurrence was found in patients with two recurrence factors than those who had only one factor or none (P < 0.001). CONCLUSIONS: Tumor location, as well as T stage, had prognostic implication in patients with early-stage colorectal cancer. Validation of our results is needed in a large cohort with genetic characterization.

Variations in the management of significant polyps and early colorectal cancer: results from a multicentre observational study of 383 patients.

AIM: The concept of significant polyps and early colorectal cancer (SPECC) encompasses complex polyps not amenable to routine snare polypectomy or where malignancy cannot be excluded. Surgical resection (SR) offers definitive treatment, but is overtreatment for the majority which are benign and amenable to less invasive endoscopic resection (ER). The aim of this study was to investigate variations in the management and outcomes of significant colorectal polyps. METHOD: This was a retrospective observational study of significant colorectal polyps, defined as nonpedunculated lesions of ≥ 20 mm size, diagnosed across nine UK hospitals in 2014. Inclusion criteria were endoscopically or histologically benign polyps at biopsy. RESULTS: A total of 383 patients were treated by primary ER (87.2%) or SR (12.8%). Overall, 108/383 (28%) polyps were detected in the Bowel Cancer Screening Programme (BCSP). Primary SR was associated with a significantly longer length of stay and major complications (P < 0.01). Of the ER polyps, 290/334 (86.8%) patients were treated without undergoing surgery. The commonest indication for secondary surgery was unexpected polyp cancer, and of these cases 60% had no residual cancer in the specimen. Incidence of unexpected cancer was 10.7% (n = 41) and was similar between ER and SR groups (P = 0.11). On multivariate analysis, a polyp size of > 30 mm and non-BCSP status were independent risk factors for primary SR [OR 2.51 (95% CI 1.08-5.82), P = 0.03]. CONCLUSION: ER is safe and feasible for treating significant colorectal polyps. Robust accreditation within the BCSP has led to improvements in management, with lower rates of SR compared with non-BCSP patients. Standardization, training in polyp assessment and treatment within a multidisciplinary team may help to select appropriate treatment strategies and improve outcomes.

Estimation of perioperative invasiveness of colorectal endoscopic submucosal dissection evaluated by energy metabolism.

The aim of this study was to assess the perioperative invasiveness of endoscopic submucosal dissection for colorectal cancer quantitatively by using energy metabolism. In fifty-three patients who underwent endoscopic submucosal dissection for colorectal cancer, resting energy expenditure using an indirect calorimeter, body weight and basal energy expenditure using the Harris-Benedict equation before and after endoscopic submucosal dissection. Resting energy expenditure/body weight and resting energy expenditure/basal energy expenditure were 19.7 ± 2.5 kcal/kg/day and 0.96 ± 0.12 on the day of endoscopic submucosal dissection, whereas one day after the endoscopic submucosal dissection they increased to 21.0 ± 2.9 kcal/kg/day and 1.00 ± 0.13 (p<0.001 and p<0.05, respectively). The stress factor on the postoperative day 1 was computed as 1.06. The increase was lower comparing with that experienced for surgery, suggesting that the perioperative invasiveness of colorectal endoscopic submucosal dissection is lower in comparison to that during surgery. Furthermore, in spite of technical difficulty, stress factor of colorectal endoscopic submucosal dissection was approximately equal to that of gastric endoscopic submucosal dissection. (The study of the resting energy metabolism and stress factor using an indirect calorimeter in the perioperative period of endoscopic operation: UMIN000027135).

Short-term Prospective Questionnaire Study of Early Postoperative Quality of Life After Colorectal Endoscopic Submucosal Dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) has become popular as an alternative to laparoscopy-assisted colectomy (LAC) for early colorectal cancer. AIM: To validate postoperative quality of life (QOL) based on subjective symptoms of patients from questionnaire survey. METHODS: We prospectively enrolled patients planned to undergo ESD for adenoma or Tis/T1a cancer at our institution between December 2011 and January 2013. Controls were prospectively enrolled LAC patients diagnosed with T1b cancer. Patients answered questionnaire survey on QOL on postoperative day (POD) 1 and POD14. Questions were scored using visual analog scale (0 points = worst condition, 100 points = best condition) and were classified into six categories: health status, mental status (MeS), motor status (MoS), bodily painless, passage and anorectal function (PAF), and stress for the treatment. Total score was also calculated. We compared the median scores among categories using the Wilcoxon rank-sum test. RESULTS: A total of 82 ESDs and 41 LACs were included. Median score for the factors in questionnaire (POD1/POD14) in ESDs versus LACs for colonic lesion (rectal lesion) was as follows: MeS, 74/83 versus 54/73 (72/85 vs. 42/62); MoS, 98/96 versus 51/75 (95/90 vs. 66/67); PAF, 90/96 versus 80/80 (90/95 vs. 70/53); total score, 83/91 versus 58/75 (81/87 vs. 51/66). These items showed statistical significant differences between ESDs and LACs. CONCLUSIONS: Postoperative QOL and symptoms are significantly better on POD1 and POD14 following ESD compared with LAC.

Investigating intra-tumor heterogeneity and expression gradients of miR-21, miR-92a and miR-200c and their potential of predicting lymph node metastases in early colorectal cancer.

INTRODUCTION: miR-21, miR-92a and miR-200c are regulators of pathways involved in migration, intravasation and metastasis, and their tumor expression levels have been proposed as potential prognostic markers in colorectal cancer (CRC). In two parallel cohorts we examine intra-tumor expression levels in early stage CRC tissue in order to determine intra-tumor heterogeneity, potential systematic intra-tumor expression gradients of the miRNAs and to investigate the association to metastatic disease in early stage CRC. MATERIAL AND METHODS: Two parallel studies on archived formalin-fixed paraffin-embedded (FFPE) CRC tissue. Intra-tumor and inter-patient variances were analyzed in 9 early metastatic CRCs by measuring expression levels by qRT-PCR on isolated tissue samples from luminal, central and invasive border zones. Associations between miRNA expression levels and early metastasizing tumors was investigated in FFPE tissue from invasive border and central tumor zones from 47 early metastatic CRCs matched with 47 non-metastatic CRCs. Intra-tumor expression gradients were analyzed on both cohorts. RESULTS: Mean intra-tumor coefficient of variation in the heterogeneity cohort was 38.5% (range: 33.1-49.0%) only slightly less than variation between patients (45.1%, range 37.0-49.5%). We demonstrated systematic expression gradients between tumor zones equal to a 3.23 (p=0.003) and 1.36 (p=0.014) fold lower expression in invasive areas for miR-200c, 1.52 (p<0.001) and 1.27 (p=0.021) fold lower expression in invasive areas for miR-92a. For miR-21 we found a 1.75 (p<0.001) and 1.21 (p=0.064) fold higher expression in invasive areas compared to luminal and central zones, respectively. No significant difference in expression levels between metastatic and non-metastatic tumors was demonstrated, nor a difference in intra-tumor gradients between metastatic and non-metastatic tumors. CONCLUSION: This study provides evidence for moderate intra-tumor and inter-patient heterogeneities of three well-described potential prognostic markers in CRC. We demonstrate intra-tumor expression gradients indicating a differentiated expression of the target miRNAs between functional tumor zones, but the potential role as markers of early metastatic disease is still not fully clarified.

Application of carbon nanoparticles to mark locations for re-inspection after colonic polypectomy.

BACKGROUND: Endoscopic surgery has been a novel treatment for colon polyps or even early colorectal cancer. However, the exact re-inspection after colonic polypectomy to detect the scar from polyp removal was difficult to be performed. In our previous study, colon cancer tattooed with carbon nanoparticles was easily found during surgery. We speculated that carbon nanoparticles could be used in exact re-inspection after colonic polypectomy. OBJECTIVE: To evaluate the efficiency of carbon nanoparticles for re-inspection after colonic polypectomy. METHODS: Twenty-four patients with precancerous lesion or early colorectal cancer that underwent colonoscopic polypectomy between October 2012 and December 2013 were enrolled in the study. Participants were divided into two groups. Group A patients were injected with carbon nanoparticles beneath the lesion sites 3 cm. Group B patients were not treated with nanoparticles. All patients underwent quarterly colonoscopies. Once the colonoscope was withdrawn from the site last time record, the time spent searching for lesions was recorded. RESULTS: There were no significant differences between general conditions or lesion pathology between the groups. The time spent searching for lesions in Group B was much longer than that in Group A (13.67 ± 8.07 vs. 1.21 ± 0.39 min, P < 0.001). Carbon nanoparticles marked lesions for 12 months in some patients, and no adverse reactions were reported. LIMITATIONS: It was a small sample study. CONCLUSIONS: Tattooing lesions using carbon nanoparticles suspensions is safe. The durability of dye enables lesions to be re-checked by colonoscopy or laparoscopy for up to 1 year.

Endoscopic submucosal dissection versus local excision for early rectal cancer: a systematic review and meta-analysis.

Endoscopic submucosal dissection (ESD) and local excision (LE) are minimally invasive procedures that can be used to treat early rectal cancer. There are no current guidelines or consensus on the optimal treatment strategy for these lesions. A systematic review was conducted to compare the efficacy and safety of ESD and LE. A meta-analysis was conducted following all aspects of the Cochrane Handbook for systematic reviews and preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. To perform the statistical analysis, the odds ratio (OR) was used for categorical variables and the weighted mean difference (WMD) for continuous variables. Four studies, involving a total of 307 patients, were identified. The length of hospital stay was longer in the group of patients undergoing LE [weighted mean difference (WMD) -1.94; 95% CI -2.85 to -1.02; p < 0.0001]. The combined results of the individual studies showed no significant differences as regards en-bloc resection rate (OR 0.82; 95% CI 0.25-2.70; p = 0.74), R0 resection rate (OR 1.53; 95% CI 0.62-3.73; p = 0.35), overall complication rate (OR 0.67; 95% CI 0.26-1.69; p = 0.40), and tumor size (WMD 0.57; 95% CI -3.64 to 4.78; p = 0.79) between ESD and LE. When adopting the fixed effect model which takes into account the study size, ESD was associated with a lower recurrence rate than LE (OR 0.15; 95% CI 0.03-0.87; p = 0.03), while with the random-effect model the difference was not significant (OR 0.18; 95% CI 0.02-2.04; p = 0.17). Over the last decade improvements in technology have improved the technical feasibility of rectal ESD. In specialized centers with highly experienced endoscopists, ESD can provide high-quality en-bloc excision of rectal neoplasms equivalent to traditional local excision.