Anticoagulants are a risk factor for delayed bleeding after colorectal endoscopic submucosal dissection: A HASID multicenter study.

INTRODUCTION: Delayed bleeding is an important adverse event following colorectal endoscopic submucosal dissection (ESD). However, whether anticoagulants are risk factors for delayed bleeding after colorectal ESD remains debatable. METHODS: We retrospectively analyzed 1,708 patients who underwent colorectal ESDs between January 2015 and December 2020 at five academic medical centers in South Korea. We aimed to identify the risk factors for delayed bleeding in patients after colorectal ESD and, in particular, to evaluate the effect of anticoagulants. RESULTS: Delayed bleeding occurred in 40 of 1,708 patients (2.3 %). The risk factors for delayed bleeding were antithrombotic agents (odds ratio [OR], 6.155; 95% confidence interval [CI], 3.201-11.825; p < 0.001), antiplatelet agents (OR, 4.609; 95% CI, 2.200-9.658; p < 0.001), anticoagulants (OR, 8.286; 95% CI, 2.934-23.402; p < 0.001), and tumor location in the rectum (OR, 2.055; 95% CI, 1.085-3.897; p = 0.027). In the analysis that excluded patients taking antiplatelet agents, the delayed bleeding rate was higher in patients taking anticoagulants (1.6% no antithrombotic agents vs. 12.5% taking anticoagulants, p < 0.001). There was no difference in the delayed bleeding rate (4.2% direct oral anticoagulants vs. 25.0% warfarin, p = 0.138) or clinical outcomes according to the type of anticoagulant used. CONCLUSIONS: Anticoagulants use was a risk factor for delayed bleeding after colorectal ESD, and there was no difference in the risk of delayed bleeding based on the type of anticoagulant used. Colorectal ESD in patients receiving anticoagulants requires careful observation and management for delayed bleeding.

Differences in clinical outcomes according to the time interval between the bridge to surgery stenting and surgery for left-sided malignant colorectal obstruction.

BACKGROUND: Self-expandable metal stent (SEMS) placement is commonly used as a bridge to surgery (BTS) for left-sided malignant colorectal obstruction (MCO). However, the optimal time interval between BTS stenting and surgery for left-sided MCO is unclear, and the results of previous studies are conflicting. This study aimed to determine the differences in clinical outcomes according to the time interval between BTS stenting and surgery in left-sided MCO. METHODS: Data from 594 patients who underwent SEMS placement for MCO between January 2009 and December 2018 were reviewed. Among them, 148 patients who underwent SEMS placement as BTS treatment and curative surgery were enrolled. The enrolled patients were divided into three groups according to the interval between BTS stenting and surgery: group 1 (interval ≤2 weeks), group 2 (interval 2-3 weeks), and group 3 (interval >3 weeks). RESULTS: Group 2 and 3 patients underwent significantly higher rates of laparoscopic surgery than those in group 1 (83.7, 81.0 vs. 53.2 %, respectively; P=0.003, P=0.003, respectively). Also, rates of stoma formation directly after resection were significantly higher in group 1 compared to groups 2 and 3 (21.3 vs 2.3, 6.9%, respectively; P=0.008, P=0.043, respectively). Bridging interval had no effect on SEMS-related complications, resection-related complications, 90-day mortality, permanent stoma formation, 3-year disease-free survival, and 3-year overall survival. CONCLUSIONS: A bridging interval of > 2 weeks between BTS stenting and surgery for left-sided MCO is preferable for lower stoma formation rates and higher rates of laparoscopic approach operation, with no difference in short-term and long-term outcomes including complication, mortality, and survival.

Clinical outcomes of endoscopic resection for colorectal laterally spreading tumors with advanced histology.

BACKGROUND: Colorectal laterally spreading tumors (LSTs) are large, flat neoplasms that are usually treated using different endoscopic techniques based on their morphology, size, and histology. The aim of this study was to evaluate the clinical outcomes of LSTs with advanced histology treated by endoscopic resection. METHODS: A total of 246 LSTs with advanced histology [i.e., high-grade dysplasia (HGD) and adenocarcinoma (AC)] treated by endoscopic resection [i.e., endoscopic mucosal resection (EMR), EMR-precutting (EMR-P), and endoscopic submucosal dissection (ESD)] were enrolled. Clinicopathological characteristics were collected by review of patient's medical records. RESULTS: The en bloc resection and R0 resection rates were 75.6% and 85.0%, respectively. The bleeding and perforation rates were 10.2% and 2.4%, respectively. The frequency of cancerous pit pattern and bleeding was significantly higher in LSTs with AC than in LSTs with HGD. The R0 resection rate in LSTs with HGD was significantly higher than that in LSTs with AC. The frequency of cancerous pit patterns in LST cases with submucosal AC was significantly higher than those with intramucosal AC. The mean size of the LSTs was significantly larger in ESD group than in EMR or EMR-P groups. The frequencies of nodular mixed subtype, cancerous pit patterns, and en bloc resection rates were significantly higher in the ESD group than in the EMR or EMR-P groups. However, the frequency of perforation was significantly higher in EMR-P group than in EMR or ESD groups. CONCLUSIONS: These results indicate that ESD is a more acceptable treatment approach for resection of colorectal LSTs of larger size, with nodular mixed subtype, having a cancerous pit pattern or AC, using either en bloc or curative resection methods, compared to EMR or EMR-P procedures.

Livin is associated with the invasive and oncogenic phenotypes of human hepatocellular carcinoma cells.

AIM: Livin, a member of the inhibitors of apoptosis proteins, is expressed in variable cancers, and its expression is considered a poor prognostic marker. The aims of this study were to observe the effect of Livin on the behaviors of hepatocellular carcinoma (HCC) cells and to evaluate its expression in HCC tissues and its relation to prognosis. METHODS: The biological effects of Livin on tumor cell behavior were investigated using siRNA in HepG2 and Chang cells. Migration, invasion and proliferation assays were performed. Flow cytometric analyses and western blotting were used to evaluate the impact of Livin on apoptosis and the cell cycle. In addition, western blotting and immunohistochemistry were used to investigate Livin expression in HCC tissues. RESULTS: Livin knockdown suppressed tumor cell migration, invasion and proliferation in HCC cells, and increased the proportion of apoptotic cells as compared with scrambled siRNA-transfected HCC cells. Furthermore, Livin knockdown resulted in the activation of caspases and increased apoptosis. In addition, Livin knockdown modulated cell cycle regulatory protein levels such as decrease of cyclins and cyclin-dependent kinase (CDK) level, and increase of CDK inhibitor (CDKI) level in HCC cells. The Livin protein level was significantly elevated in HCC tissues as compared with normal hepatic tissues. However, Livin expression was not found to be associated with clinicopathological parameters, which included patient survival. CONCLUSION: These results suggest that Livin is associated with invasive and oncogenic phenotypes of human HCC cells.

Outcomes of Colorectal Endoscopic Submucosal Dissection According to the Size of Colorectal Neoplasm: A HASID Multicenter Study.

BACKGROUND/AIM: Endoscopic submucosal dissection (ESD) is a valuable technique for treating colorectal neoplasms. However, there are insufficient data concerning the treatment outcomes in relation to the size of colorectal neoplasms. PATIENTS AND METHODS: The data on ESD for colorectal epithelial neoplasms between January 2015 and December 2020 were retrospectively collected from five tertiary medical centers. Colorectal neoplasms were stratified into groups based on their longitudinal diameter: <20 mm as Group 1, 20-39 mm as Group 2, 40-59 mm as Group 3, and 60 mm or more as Group 4. RESULTS: Of the 1,446 patients, 132 patients were in Group 1 (<20 mm), 1,022 in Group 2 (20-39 mm), 249 in Group 3 (40-59 mm), and 43 in Group 4 (≥60 mm). There was an observed trend of increasing age from Group 1 to Group 4, accompanied by a corresponding increase in the Charlson Comorbidity Index. Procedure time also exhibited a gradual increase from Group 1 to Group 4. Similarly, the length of hospital stay tended to increase from Group 1 to Group 4. The predictive model, using restricted cubic spline curves, revealed that as the size of lesion exceeded 30 mm, complete resection steadily decreased, and major complications notably increased. CONCLUSION: As the size of colorectal neoplasms increases, the rate of complete resection decreases and the rate of complications increases.

Outcomes of Colorectal Endoscopic Submucosal Dissection for Elderly Patients: A Multicenter Study by the Honam Association for the Study of Intestinal Disease (HASID).

BACKGROUND/AIM: The aging population has been growing gradually; therefore, the proportion of elderly patients undergoing colorectal endoscopic submucosal dissection (ESD) has also been increasing. However, there is a lack of large-scale studies on the efficacy and safety of colorectal ESD in elderly patients. PATIENTS AND METHODS: This retrospective analysis evaluated colorectal ESDs performed at five tertiary medical institutions between January 2015 and December 2020. Patients were categorized into the following four age groups: Middle-aged (<65 years), young-elderly (≥65 to <75 years), mid-elderly (≥75 to <85 years), and very elderly (≥85 years). Of the 1,446 patients included, 668 (46.2%), 466 (32.2%), 293 (20.3%), and 19 (1.3%) were in the middle-aged, young-elderly, mid-elderly, and very-elderly groups, respectively. RESULTS: Compared to younger patients, more older patients used aspirin, clopidogrel, and anti-thrombotic agents. Additionally, the Charlson comorbidity index increased significantly with increasing age. However, no significant differences were observed in the complete resection rates nor the rates of complications, such as perforation, bleeding, and post-ESD coagulation syndrome, among the different age groups. A restricted cubic spline curve was used to construct predictive models for complete resection and major complications based on age and showed that the need for complete resection did not decrease with increasing age. Furthermore, major complications did not significantly differ with age progression. CONCLUSION: Colorectal ESD should be actively considered as a relatively safe and effective treatment method for elderly patients.

Successful Transcatheter Arterial Embolization of Abdominal Wall Hematoma from the Left Deep Circumflex Iliac Artery after Abdominal Paracentesis in a Patient with Liver Cirrhosis: Case Report and Literature Review.

The occurrence of an abdominal wall hematoma caused by abdominal paracentesis in patients with liver cirrhosis is rare. This paper presents a case of an abdominal wall hematoma caused by abdominal paracentesis in a 67-year-old woman with liver cirrhosis with a review of the relevant literature. Two days prior, the patient underwent abdominal paracentesis for symptom relief for refractory ascites at a local clinic. Upon admission, a physical examination revealed purpuric patches with swelling and mild tenderness in the left lower quadrant of the abdominal wall. Abdominal computed tomography revealed advanced liver cirrhosis with splenomegaly, tortuous dilatation of the para-umbilical vein, a large volume of ascites, and a large acute hematoma at the left lower quadrant of the abdominal wall. An external iliac artery angiogram showed the extravasation of contrast media from the left deep circumflex iliac artery. Embolization of the target arterial branches using N-butyl-2-cyanoacrylate was then performed, and the bleeding was stopped. The final diagnosis was an abdominal wall hematoma from the left deep circumflex iliac artery after abdominal paracentesis in a patient with liver cirrhosis.

Predictive factors associated with technical difficulty in colorectal endoscopic submucosal dissection: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

Colorectal endoscopic submucosal dissection (ESD) is a promising but challenging procedure. It is not widely performed due to its technical difficulty. We aimed to find the predictive factors associated with technical difficulty in colorectal ESD before the procedure. Clinical data from patients who underwent ESD for colorectal tumors in 5 hospitals in Honam province of South Korea between 2015 and 2020 were reviewed retrospectively. Technically difficult colorectal ESD procedure was defined in 3 points. Long procedure time (longer than 60 minutes), occurrence of perforation, and failure of en bloc resection. Factors associated with technically difficult ESD were included as main outcome measure. 1446 patients were identified and their data were analyzed. Median procedure time was 30.0 minutes and median long axis of the tumor was 20.1 mm. Technically difficult procedures including long procedure time were 231 cases (16.0%), perforation occurred in 34 cases (2.3%), and en bloc resection was done in 1292 cases (89.3%). Tumor size larger than 35 mm (odd ratio [OR]: 1.474, P = .047), central depression or ulceration in the lesion (OR: 1.474, P = .013), previous endoscopic mucosal resection (EMR) or polypectomy procedure (OR: 2.428, P = .020) were associated with technically difficult ESD. Descending colon-located tumor (OR: 5.355, P < .001), and use of IT knife (OR: 4.157, P = .003) were associated with perforation. Recognizing factors associated with technically difficult ESD can help in planning the ESD procedure beforehand.

Clinical outcomes of colorectal neoplasm with positive resection margin after endoscopic submucosal dissection.

A positive resection margin after colorectal endoscopic submucosal dissection (ESD) is associated with an increased risk of recurrence. We aimed to identify the clinical significance of positive resection margins in colorectal neoplasms after ESD. We reviewed 632 patients who had en bloc colorectal ESD at two hospitals between 2015 and 2020. The recurrence rates and presence of residual tumor after surgery were evaluated. The rate of additional surgery after ESD and recurrence rate were significantly higher in patients with incomplete resection (n = 75) compared to patients with complete resection (n = 557). When focusing solely on non-invasive lesions, no significant differences in recurrence rates were observed between the groups with complete and incomplete resection (0.2% vs. 1.9%, p = 0.057). Among 84 patients with submucosal invasive carcinoma, 39 patients underwent additional surgery due to non-curative resection. Positive vertical margin and lymphovascular invasion were associated with residual tumor. Lymphovascular invasion was associated with lymph node metastasis. However, no residual tumor nor lymph node metastases were found in patients with only one unfavorable histological factor. In conclusion, a positive resection margin in non-invasive colorectal lesions, did not significantly impact the recurrence rate. Also, in T1 colorectal cancer with a positive vertical resection margin, salvage surgery can be considered in selected patients with additional risk factors.

A disintegrin and metalloprotease 12 contributes to colorectal cancer metastasis by regulating epithelial­mesenchymal transition.

A disintegrin and metalloprotease 12 (ADAM12) and epithelial­mesenchymal transition (EMT) are linked in the metastasis of various types of cancer. The present study aimed to assess the ability of ADAM12 to induce EMT and its potential as a therapeutic target for colorectal cancer (CRC). ADAM12 expression in CRC cell lines, CRC tissues and a mouse model of peritoneal metastasis was assessed. The effect of ADAM12 on CRC EMT and metastasis was investigated using ADAM12­pcDNA6­myc and ADAM12­pGFP­C­shLenti constructs. ADAM12 overexpression enhanced the proliferation, migration, invasion and EMT of CRC cells. The phosphorylation levels of factors associated with the PI3K/Akt pathway were also increased by ADAM12 overexpression. The knockdown of ADAM12 reversed these effects. ADAM12 expression and the loss of E­cadherin expression were significantly associated with poorer survival compared with other expression statuses of both proteins. In a mouse model of peritoneal metastasis, overexpression of ADAM12 induced increased tumor weight and peritoneal carcinomatosis index compared with that in the negative control group. Conversely, knockdown of ADAM12 reversed these effects. Furthermore, E­cadherin expression was significantly decreased by overexpression of ADAM12 compared with in the negative control group. By contrast, E­cadherin expression was increased by knockdown of ADAM12 compared with in the negative control group. ADAM12 overexpression contributed to CRC metastasis by regulating EMT. In addition, in the mouse model of peritoneal metastasis, ADAM12 knockdown exhibited strong anti­metastatic action. Consequently, ADAM12 may be considered a therapeutic target for CRC metastasis.

Primary Duodenal Mucosa-associated Lymphoid Tissue Lymphoma Treated with Radiation Therapy Alone.

Primary mucosa-associated with a lymphoid tissue (MALT) lymphoma is a rare distinct subtype of non-Hodgkin's lymphoma that occurs in approximately 8% of all non-Hodgkin lymphomas. Primary gastrointestinal MALT lymphoma usually occurs in the stomach, but duodenal involvement is extremely rare. Therefore, the clinical manifestations, treatment, and prognosis of primary duodenal MALT lymphoma have not yet been validated because of its rarity. This paper reports a case of a 40-year-old male with primary duodenal MALT lymphoma who was treated successfully with radiation therapy alone. A 40-year-old male visited for a medical check-up. Esophagogastroduodenoscopy revealed whitish multi-nodular mucosal lesions in the second and third portions of the duodenum. Biopsy specimens from mucosal lesions in the duodenum were reported to be suspicious for MALT lymphoma of the duodenum. He received a total dose of 3,000 cGy in 15 fractions with external beam radiation therapy for three weeks. Three months after radiation therapy, an endoscopic examination revealed complete resolution of the duodenal lesions. The follow-up 12 months after radiation therapy showed no evidence of tumor recurrence.

Expression of Apurinic/Apyrimidinic Endonuclease 1 in Colorectal Cancer and its Relation to Tumor Progression and Prognosis.

BACKGROUND/AIM: Over-expression of apurinic/apyrimidinic endonuclease 1 (APE1) has been demonstrated to be associated with cancer progression, chemo- and radioresistance in various cancers. This study examined the expression of APE1 and its relation to tumor progression and prognosis in patients with colorectal cancer (CRC). MATERIALS AND METHODS: We investigated 193 patients with CRC who received curative surgery for whom formalin-fixed and paraffin-embedded blocks were available, and long-term tumor-specific survival rate analysis was possible. The expression of APE1 was investigated by reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry in CRC and lymph node tissues. The apoptosis, proliferation, and angiogenesis of CRC cells were determined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and immunohistochemical staining for Ki-67 and CD34 antibodies. RESULTS: APE1 was over-expressed in CRC and metastatic lymph node tissues compared with normal colorectal mucosa and non-metastatic lymph node tissues. Over-expression of APE1 was significantly associated with advanced stage, lymphovascular invasion, perineural invasion, deeper tumor invasion, lymph node metastasis, distant metastasis, and poor survival. Multivariate analysis demonstrated that APE1, perineural invasion, and lymph node metastasis were the independent prognostic factors associated with overall survival. The mean Ki-67 labeling index value of APE1-positive tumors was significantly higher than that of APE1-negative tumors. However, there was no significant association between APE1 expression and the apoptotic index or microvessel density. CONCLUSION: Over-expression of APE1 is significantly associated with tumor progression and poor survival in patients with CRC. Therefore, APE1 may be a novel biomarker and present a potential prognostic factor for CRC.

Effectiveness and Safety of Endoscopic Submucosal Dissection for Colorectal Neoplasm in Patients with High Charlson Comorbidity Index Score: A HASID Multicenter Study.

Endoscopic submucosal dissection (ESD) is an effective method for removing early colorectal lesions. However, research on the safety and efficacy of ESD in patients with various underlying conditions remains limited. This study retrospectively examined ESD outcomes in colorectal neoplasm patients from five tertiary medical centers. The Charlson Comorbidity Index (CCI) and age-adjusted CCI (ACCI) were analyzed, and the differences in complete resection and complication rates were analyzed. The CCI, ACCI, and complication rates tended to gradually increase proportionally, and the complication resection rate increased from CCI 2 to ACCI 4 as the starting point, followed by a decreasing trend. Of these, 140 patients (9.7%) had a CCI score of 3 or higher. The high CCI group was older (70.6% vs. 64.7%, p < 0.01) and had a higher proportion of men (70.7% vs. 58.7%, p < 0.01) than the low CCI group. The high CCI group had a higher incidence of cancer than the low CCI group (77.9% vs. 65.2%, p < 0.01). The en bloc resection rate (90.0% vs. 89.3%, p = 0.79) and complete resection rate (75.7% vs. 81.2%, p = 0.12) were not significantly different between the two groups. Colorectal ESD can be safely and effectively performed in patients with various underlying medical conditions.

Cytochrome P450 Family 46 Subfamily A Member 1 Promotes the Progression of Colorectal Cancer by Inducing Tumor Cell Proliferation and Angiogenesis.

BACKGROUND/AIM: Cytochrome P450 family 46 subfamily A member 1 (CYP46A1) has been implicated in the development and progression of various cancers. This study aimed to analyze the expression of CYP46A1, examining its relationship with oncogenic behaviors, and determining its prognostic implications in colorectal cancer (CRC). MATERIALS AND METHODS: A total of 225 patients with CRC who underwent curative surgical resection were examined using paraffin-embedded tissue blocks and subjected to tumor-specific survival analysis. The expression of CYP46A1 was assessed in CRC tissues through reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. The CRC cells' apoptosis, proliferation, angiogenesis, and lymphangiogenesis were analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays, alongside immunohistochemical staining for Ki-67, CD34, and D2-40 antibodies. RESULTS: CYP46A1 expression was found to be up-regulated in CRC tissues compared to normal colorectal mucosa. Such expression was significantly associated with advanced stage, deeper tumor invasion, lymph node metastasis, distant metastasis, and decreased survival. Furthermore, the mean Ki-67 labeling index and microvessel density values in CYP46A1-positive tumors were significantly elevated compared to CYP46A1-negative tumors. However, there was no discernible correlation between CYP46A1 expression and either the apoptotic index or lymphatic vessel density value. CONCLUSION: CYP46A1 promotes CRC progression, specifically through the induction of tumor cell proliferation and angiogenesis. The insights provided may hold potential implications for future therapeutic interventions targeting CYP46A1.

Primary Esophageal Malignant Melanoma in Korea: Clinical features, Management and Prognosis.

Primary esophageal melanoma is a rare disease with a poor prognosis. To date, 18 cases have been reported in Korea. Four patients visited the Chonnam National University Hwasun Hospital with dysphagia, followed by epigastric pain and discomfort, odynophagia, and weight loss. Esophagogastroduodenoscopy revealed a black pigmented polypoid mass, protruding mass, or black-pigmented flat lesions. Two patients had distant metastases and lymphadenopathies in imaging studies. Two patients underwent esophagectomy and intrathoracic esophagogastrostomy. One patient was treated with chemotherapy and interferon-alpha. The other patient declined further treatment. The routine histology using H&E revealed brown-colored atypical melanocytes. Immunohistochemical staining exhibited strong reactivity for Melan-A, S-100, and HMB-45 proteins. The biopsy specimens were interpreted to be malignant melanoma. One patient had multiple distant metastases 13 months after surgery. The other patient had no recurrence for 33 months after surgery. The patient treated with chemotherapy and interferon-alpha showed disease progression in the follow-up examination. Primary esophageal melanoma in Korea is a rare disease characterized by aggressive behavior, early metastasis, and poor prognosis.

Clinical Outcome and Risk Factors of Chronic Radiation Proctitis Following Pelvic Radiation Therapy.

BACKGROUND/AIM: Pelvic radiation therapy (RT) is a common treatment for malignancies, including gynecological, genitourinary, and lower gastrointestinal tract cancers. However, chronic radiation proctitis (RP) is an unavoidable side effect, and its clinical presentation varies from asymptomatic to potentially life-threatening. This study evaluated the clinical characteristics and risk factors of chronic RP. PATIENTS AND METHODS: Patients with chronic RP (212) following RT for various pelvic cancers between January 2015 and December 2021 were enrolled. Clinical characteristics of RP were analyzed retrospectively. Severity was graded according to the Radiation Therapy Oncology Group (RTOG) modified rectal toxicity score and Vienna rectoscopy score (VRS), and risk factors were statistically analyzed. RESULTS: The most common pelvic cancer observed was cervical cancer. The patients received three-dimensional conformal RT (3D-CRT), intensity-modulated RT, or a combination of 3D-CRT and intracavitary RT (ICR). Rectal bleeding occurred in 70 (33.0%) patients. Previous abdominopelvic surgery and total radiation dose significantly correlated with the RTOG score and VRS. Previous abdominopelvic surgery, ICR, and total radiation dose were associated with chronic hemorrhagic RP. All patients with chronic hemorrhagic RP were treated with argon plasma coagulation (APC). 91.4% of cases required 1-3 APC sessions to resolve the bleeding, with a mean of 1.7 sessions. CONCLUSION: Our results showed that previous abdominopelvic surgery and total radiation dose were significant risk factors related to chronic RP, while total radiation dose was related to chronic hemorrhagic RP. We also showed that APC was effective and safe for chronic hemorrhagic RP.

CD47 mediates the progression of colorectal cancer by inducing tumor cell apoptosis and angiogenesis.

CD47 is an immunoregulatory protein that is found on the cell surface and plays significant roles in cellular functions such as proliferation, apoptosis, migration, and immune homeostasis. CD47 is overexpressed in various human cancers and is associated with tumor development, progression, and poor prognosis. In this study, we analyzed the expression of CD47 to determine whether it affected the oncogenic behavior of colorectal cancer (CRC) and investigated the prognostic value of CD47 expression in patients with CRC. We investigated 468 patients with CRC who underwent curative surgery and examined the expression of CD47 in tumor and lymph node tissues by performing RT-PCR and immunohistochemistry. Apoptosis, proliferation, angiogenesis, and lymphangiogenesis were determined via a TUNEL assay and immunohistochemical staining for Ki-67, CD34, and D2-40. CD47 expression was increased in human CRC tumors and metastatic lymph nodes compared with normal colorectal mucosa and non-metastatic lymph node tissues. CD47 expression was significantly associated with perineural invasion, lymphovascular invasion, cell differentiation, cancer stage, depth of invasion, lymph node metastasis, distant metastasis, and poor survival. The mean apoptotic index and microvessel density value of CD47-positive tumors were significantly higher than those of CD47-negative tumors. However, no significant difference was observed between CD47 expression and Ki-67 labeling index or lymphatic vessel density. These results indicate that CD47 mediated the progression of CRC by inducing tumor cell apoptosis and angiogenesis.

Clinical outcomes of palliative self-expandable metal stent placement in right- and left-sided malignant colon obstruction: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

Self-expandable metal stent (SEMS) placement is commonly used for palliation of left-sided malignant colorectal obstruction (MCO). However, right-sided MCO is usually treated surgically. Recent studies that compared palliative SEMS insertion and emergency surgery in right-sided MCOs have reported conflicting results. This study aimed to compare the effectiveness of palliative SEMS placement in left-sided MCOs and right-sided MCOs and to investigate the predictive factors for clinical success and risk factors for complications. Data from 469 patients who underwent palliative SEMS placement for MCO at 6 hospitals in the Honam province of South Korea between 2009 and 2018 were reviewed. Among them, 69 patients with right-sided MCO and 400 patients with left-sided MCO who underwent SEMS placement for palliative purposes were enrolled. Clinical success, overall survival, complications, and predictive factors for clinical success and risk factors for complications were included as the main outcome measures. The clinical success rates were 97.1% (65/67) in right-sided MCO patients and 88.2% (353/400) in left-sided MCO patients. Complications including stent migration, tumor ingrowth, outgrowth, perforation, bacteremia/fever, and bleeding occurred in 10.1% (7/69) of right-sided MCO patients and 19.9% (79/400) of left-sided MCO patients. The mean overall survival of right-sided MCO was 28.02 months and 18.23 months for left-sided MCO. In multivariate logistic regression analysis, T3 stage tumors and the use of uncovered stents were significant factors for the clinical success of SEMS. The use of covered stents and performance status score of 0 to 2 were independent significant risk factors for complications. Palliative SEMS placement in right-sided MCO showed better clinical success rates than left-sided MCO. The use of uncovered stents is recommended for higher clinical success rates and lower complication rates.

Engulfment and Cell Motility 1 (ELMO1) Regulates Tumor Cell Behavior and Predicts Prognosis in Colorectal Cancer.

BACKGROUND/AIM: Engulfment and cell motility 1 (ELMO1) plays a crucial role in the process of migration, chemotaxis, and metastasis of tumor cells. ELMO1 has been implicated in the pathogenesis of various cancers. However, the distinct function of ELMO1 in colorectal cancer (CRC) is unclear. We determined whether ELMO1 affects the oncogenic behavior of CRC cells and investigated its prognostic value in CRC patients. MATERIALS AND METHODS: We investigated the impact of ELMO1 on tumor cell behavior using small interference RNA (siRNA) in CRC cell lines, including SW480 and DLD1. The expression of ELMO1 was investigated by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) in cancer tissues and sera obtained from CRC patients. RESULTS: ELMO1 knockdown suppressed tumor cell proliferation in SW480 and DLD1 cells. ELMO1 knockdown-induced apoptosis through up-regulation of caspase-3, -7, and PARP activities and down-regulation of the anti-apoptotic Mcl-1 protein. ELMO1 knockdown-induced cell-cycle arrest by decreasing cyclin D1, cyclin-dependent kinase 2, 4 and 6, and the 25C cell division cycle (CDC25C). ELMO1 knockdown suppressed tumor cell invasion and migration. The expression of E-cadherin was increased, while that of Vimentin and Claudin 1 decreased following ELMO1 knockdown. The phosphorylation levels of PDK1, Akt, and GSK-3ß and were down-regulated after ELMO1 knockdown. The expression of ELMO1 was found up-regulated in cancer tissues and sera taken from CRC patients. ELMO1 expression was significantly associated with tumor stage, lymph node metastasis, distant metastases, and poor survival. CONCLUSION: ELMO1 mediates tumor progression by increasing tumor cell motility and inhibiting apoptosis in human CRC.

Rectal inflammatory myofibroblastic tumor: Case report and literature review.

RATIONALE: Rectal inflammatory myofibroblastic tumor (IMT) is an extremely rare mesenchymal tumor characterized by a mixture of spindle-shaped myofibroblasts or fibroblasts and inflammatory infiltration of lymphocytes and plasma cells. To date, only 8 cases of rectal IMT have been reported. Herein, we report an additional case of rectal IMT in a 28-year-old woman. PATIENT CONCERNS: A 28-year-old woman presented with abdominal pain and hematochezia. DIAGNOSES: Colonoscopy showed a 3.0-cm subepithelial tumor with central ulceration, covered by white exudate in the rectum. Rectal magnetic resonance imaging revealed a 4.0 × 3.0-cm-sized well-defined subepithelial tumor in the right wall of the rectum, with suspicious right perirectal fat infiltration. INTERVENTIONS: Laparoscopic anterior resection was performed. Microscopic examination of the surgical specimen revealed bland-looking spindle cells intermingled with lymphoplasma cells. Immunohistochemistry and fluorescence in situ hybridization showed anaplastic lymphoma kinase positivity and anaplastic lymphoma kinase positivity rearrangement. Rectal IMT was confirmed based on histological, immunohistochemical, and fluorescence in situ hybridization findings. The patient was doing well without evidence of tumor recurrence 1 year after the surgery. LESSONS: Rectal IMT, despite its rarity, should be considered in the differential diagnosis of rectal cancer. Second, an accurate histopathologic diagnosis and complete surgical resection can be the most important approaches to offer a chance for the cure of rectal IMT.