BACKGROUND AND AIM:Positive margins after endoscopic resection of rectal neuroendocrine tumors (NETs) do not always indicate true residual disease. We aimed to identify risk factors for remnant tumors among patients with incompletely resected rectal NETs. METHODS:We conducted a multicenter retrospective cohort study across 11 tertiary hospitals. Patients who underwent salvage treatment for incompletely resected rectal NETs between January 2010 and December 2023 were retrospectively reviewed. A total of 286 patients were included, and demographic, endoscopic, and pathologic data were analyzed to identify predictors of remnant tumor. RESULTS:The remnant tumor was found in 102 (35.7%) patients. Rates were highest after cold forceps polypectomy (CFP) (63.6%), followed by cold snare polypectomy (32.1%) and conventional endoscopic mucosal resection (EMR) (31.2%). No remnant tumor was observed after modified EMR or endoscopic submucosal dissection (ESD), even in cases with positive or indeterminate margins. On multivariate analysis, CFP (odds ratio [OR], 4.50; 95% confidence interval [CI], 2.33-8.70) and two post-resection scar features-yellowish mucosa (OR, 4.36; 95% CI, 2.26-8.40) and mucosal protrusion (OR, 4.84; 95% CI, 2.17-10.79)-were independent predictors of remnant tumors. The risk rose stepwise with the number of factors: 15.0% (none), 52.6% (one), 78.3% (two), and 87.5% (three) (p for trend < 0.001). CONCLUSIONS:Margin-positive rectal NETs resected by modified EMR or ESD may be managed with surveillance. However, CFP or post-resection scars showing yellowish mucosa or mucosal protrusion indicate high residual risk and warrant prompt salvage resection.

Following a non-curative endoscopic resection of T1 colorectal cancer, current guidelines recommend additional surgery based on high-risk pathological features. However, the actual rates of residual disease, such as residual cancer and lymph node metastasis (LNM), remain unclear and risk factors vary significantly across studies. We aimed to determine the true incidence of residual cancer and LNM and identify independent risk factors to guide surgical decision-making. This multicenter retrospective study included patients who underwent radical surgery after non-curative endoscopic resection of T1 colorectal cancer at four hospitals between 2015 and 2020. Non-curative resection was defined by positive margins, deep submucosal invasion (≥ 1000 μm), poor differentiation, lymphovascular invasion, or high-grade tumor budding in accordance with current guidelines. Among 517 patients, residual cancer was found in 3.7

BACKGROUND/AIM:Malformin A1 (MA1), a fungal-derived cyclic pentapeptide, has been reported to exhibit anti-cancer activity. 5-fluorouracil (5-FU) is a widely used chemotherapeutic agent that inhibits DNA and RNA synthesis and suppresses colorectal cancer (CRC) cell growth. This study aimed to investigate whether MA1 enhances the anticancer effects of 5-FU in CRC cells. MATERIALS AND METHODS:The effects of MA1 and 5-FU on CRC cells were evaluated using the WST-1 cell viability assay, DNA fragmentation analysis, flow cytometry, and western blotting. RESULTS:MA1 treatment demonstrated greater cytotoxic activity in CRC cells compared to 5-FU alone. Combined MA1 treatment enhanced 5-FU-induced apoptosis through activation of PARP, caspase-3, and caspase-9, along with decreased expression of anti-apoptotic proteins Mcl-1 and Survivin, compared with the non-combined treated control. In addition, combined MA1 treatment potentiated 5-FU-induced cell cycle arrest at the sub-G1 phase by increasing p57 protein levels and reducing cyclin D1, CDK6, and Cdc25C protein expression relative to the non-combined treated control. Furthermore, combined MA1 treatment augmented 5-FU-induced inhibition of umbilical vein endothelial cell invasion, tube formation, and the expression of vascular endothelial growth factor (VEGF)-A and -D. The phosphorylation levels of p38 and c-Jun NH2-terminal kinase (JNK) were further upregulated by combined MA1 treatment in CRC cells compared to the non-combined treated control. CONCLUSION:MA1 enhances 5-FU-induced apoptosis, cell cycle arrest, and anti-angiogenic effects in CRC cells through activation of the p38 and JNK signaling pathways. These findings suggest that the combination of MA1 and 5-FU may represent a potential strategy to overcome resistance to 5-FU in CRC cells.

RATIONALE:In patients receiving immune checkpoint inhibitors, subclinical inflammatory bowel disease can be unmasked, leading to severe colitis. Ulcerative colitis, in particular, may remain undetected when initial symptoms are mild. This report describes a patient with metastatic melanoma whose previously unrecognized ulcerative colitis flared severely after initiating nivolumab. PATIENT CONCERNS:A 35-year-old man presented with chronic mild diarrhea, persisting for several months, which was initially overlooked. Three months after starting nivolumab therapy, he developed frequent diarrhea and hematochezia that required hospitalization. DIAGNOSES:Sigmoidoscopy demonstrated ulcerations with bleeding in the rectosigmoid junction and rectum. Histopathology revealed crypt architectural distortion and inflammatory infiltrates, consistent with ulcerative colitis. Infectious etiologies were excluded. INTERVENTIONS:High-dose intravenous corticosteroids were administered, followed by an oral steroid taper and 5-aminosalicylic acid. Nivolumab was briefly held during acute exacerbations but was ultimately resumed to continue melanoma management. OUTCOMES:Two months after resuming nivolumab, the patient experienced a diffuse ulcerative colitis flare, now involving the entire colon. A second course of high-dose pulse steroid therapy was initiated, and a further hold on nivolumab is currently under consideration. LESSONS:Mild ulcerative colitis can be unmasked and exacerbated by immune checkpoint inhibitors such as nivolumab, emphasizing the importance of early evaluation for inflammatory bowel disease in patients with persistent diarrhea.

BACKGROUND AND AIMS:Colonic stenting using self-expandable metallic stents (SEMS) as a bridge to surgery offers an effective alternative to emergency surgery for the management of malignant colorectal obstruction. However, the optimal timing of elective surgery after stenting remains controversial. METHODS:This retrospective multicenter cohort study analyzed 380 patients with obstructive colorectal cancer who were treated with SEMS as a bridge to surgery. Patients were categorized into four groups based on the time from stent insertion to surgery: within 7 days, 8-14 days, 15-21 days, and 22 days or more. RESULTS:The study cohort had a slight male predominance (55.8%), with an average age of 65.8 years. Most surgeries (74.2%) were laparoscopically performed. No significant differences were observed in stoma formation rates or postoperative complications between the different timing groups. Similarly, recurrence-free survival, overall survival, locoregional recurrence, and distant metastasis rates showed no significant variations with the timing of post-stenting surgery. A restricted cubic spline curve indicated that surgery within the 15-21-day period post-SEMS insertion resulted in the lowest incidence of stoma formation. CONCLUSIONS:Delaying elective surgery for up to 3 weeks post-SEMS placement for obstructive colorectal cancer is recommended, particularly within the 15-21-day period, to minimize stoma formation rates without compromising on long-term outcomes.

Purpose:The selection of primary tumor resection (PTR) vs. self-expanding metallic stents (SEMS) in obstructive unresectable stage IV colorectal cancer (CRC) is critical, profoundly impacting patient outcome. This study evaluates the influence of PTR and SEMS on overall survival (OS) in conjunction with chemotherapy. Methods:The analysis included 137 patients with obstructive, unresectable stage IV CRC who underwent PTR or attempted SEMS placement. The primary objective was to assess the OS of patients, specifically examining how PTR and SEMS interventions influence these survival outcomes. Results:In a cohort of 137 patients with obstructive, unresectable stage IV CRC, 30 initially opted for PTR, while stent placement was attempted in 107 cases. Following 14 stent failures, which resulted in 8 diversions and 6 additional PTR interventions, exclusions due to elective surgeries led to a final analysis of 36 PTR and 72 SEMS cases. Cox regression analysis identified no significant survival advantage between PTR and SEMS interventions (hazard ratio [HR], 0.848; 95% confidence interval [CI], 0.555-1.298; P = 0.449). Critical findings highlighted that the absence of chemotherapy markedly reduced survival prospects (HR, 1.963; 95% CI, 1.200-3.211; P = 0.007). These insights were substantiated through propensity score matching. Conclusion:The comparative analysis reveals that neither PTR nor SEMS offers a definitive survival advantage in managing obstructive, unresectable stage IV CRC. However, the necessity for subsequent invasive interventions is notably lower in the PTR group.

Objectives Early diagnosis of upper gastrointestinal (UGI) amyloidosis and the establishment of appropriate treatment and follow-up strategies remains challenging. This study aimed to elucidate the endoscopic characteristics and clinical courses of patients with isolated UGI amyloidosis. Methods We retrospectively reviewed 11 patients diagnosed with isolated UGI amyloidosis at Chonnam National University Hospital and Chonnam National University Hwasun Hospital. None of the patients exhibited systemic involvement or multiple myeloma. Clinical data, including endoscopic features, presenting symptoms, and outcomes such as disease progression and mortality, were analyzed. Results The cohort included seven males (63.6%) and four females (36.4%), with a median age of 72 (37–82) years. Isolated gastric amyloidosis was identified in four patients, and five patients had disease confined to the duodenum. Two patients (18.2%) presented with gastric or duodenal involvement. Endoscopic findings were heterogeneous, with diffuse yellowish linear lesions being the most frequently observed in four patients (36.4%). Histopathological analysis revealed AA amyloidosis in three patients, whereas five patients exhibited only amorphous deposits without amyloid A, amyloid P, or light chains. Six patients (54.5%) were asymptomatic at diagnosis, whereas gastrointestinal bleeding was observed in two patients (18.2%). Only one patient (9.1%) experienced disease progression that necessitated systemic chemotherapy. The mean follow-up duration was 20 months, and the 3-year mortality rate was 9.1%. Conclusions Isolated UGI amyloidosis is a heterogeneous condition that can be easily misdiagnosed. Familiarity with the characteristic endoscopic features and natural disease course is essential for appropriate management.

BACKGROUND/AIM:Oxysterol-binding protein-like 3 (OSBPL3) is a member of the intracellular lipid receptor and transporter protein family involved in regulating lipid metabolism. Altered OSBPL3 expression has been observed in various cancers, where it has been associated with both oncogenic and tumor-suppressive roles. However, its precise functions and underlying mechanisms in colorectal cancer (CRC) remain unclear. This study aimed to investigate the role of OSBPL3 in CRC cells and evaluate its prognostic significance. MATERIALS AND METHODS:A small interfering RNA vector targeting OSBPL3 was employed to silence its expression in CRC cell lines. OSBPL3 levels in CRC tissues were assessed using reverse transcription-polymerase chain reaction and immunohistochemistry. Tumor cell apoptosis, proliferation, and angiogenesis were evaluated via a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and immunohistochemical staining for Ki-67 and CD34. RESULTS:OSBPL3 silencing inhibited tumor cell migration and invasion in CRC. OSBPL3 knockdown reduced proliferation and induced apoptosis through caspase activation and cell cycle arrest mediated by the regulation of cyclins, cyclin dependent kinases (CDKs), and CDK inhibitors. OSBPL3 suppression impaired the invasion and tube formation of human umbilical vein endothelial cells by down-regulating angiogenic factors and up-regulating angiostatic factors. OSBPL3 expression correlated significantly with tumor size, tumor stage, invasion depth, lymph node involvement, distant metastasis, and reduced survival. The apoptotic index was lower and microvessel density was higher in OSBPL3-positive tumors than in OSBPL3-negative tumors. CONCLUSION:OSBPL3 contributes to CRC progression by regulating tumor cell apoptosis and angiogenesis.

Self-expandable metal stents (SEMS) are effective in alleviating malignant colorectal obstruction. However, bowel perforation following SEMS placement remains a significant concern, as it can adversely affect oncological outcomes. This study aimed to evaluate the recurrence and overall survival rates associated with SEMS-related bowel perforations. This multicenter, retrospective analysis included patients with obstructive colorectal cancer who underwent SEMS placement as a bridge to surgery. The data collection period spanned from January 2008 to May 2019, with patient matching in a 1:5 ratio based on age, sex, tumor location, pathological stage, and achievement of curative resection. Among the 412 patients who received SEMS placement, 25 (6.1

BACKGROUND:SRY-related high-mobility-group box gene 4 (SOX4) is overexpressed in various cancers and has been studied as a therapeutic target in multiple malignancies. Therefore, this study aims to investigate the role of SOX4 in cancer progression and chemoradioresistance in head and neck squamous cell carcinoma (HNSCC). METHODS:Utilizing in vitro silencing techniques and an orthotopic mouse xenograft model that simulates HNSCC biological characteristics, the effect of SOX4 modulation on cell proliferation, invasion, migration, and apoptosis was assessed. RESULTS:The results showed that SOX4 knockdown led to significant inhibition of cell proliferation, reduced invasion and migration capabilities, and increased apoptosis in human HNSCC cells. Furthermore, SOX4 knockdown enhanced chemoradiosensitivity, as evidenced by increased apoptosis levels following treatment with cisplatin and irradiation. Conversely, SOX4 overexpression in an orthotopic mouse model of HNSCC significantly promotes tumor invasion, metastasis, and chemoresistance to cisplatin. CONCLUSIONS:These findings highlight the essential role of SOX4 in HNSCC progression and treatment resistance, suggesting SOX4 is a predictive biomarker and potential therapeutic target for improving treatment outcomes in patients with HNSCC.

A tailgut cyst is a rare tumor arising from the persistent embryonic remnants of the postanal gut. The cyst is usually located in the retrorectal space, lying anterior to the sacrum and posterior to the rectum. In rarer cases, it is occasionally found at the perirenal, perianal, subcutaneous, and intradural sites. A 60-year-old woman visited the authors' clinic for a routine health screening examination. Colonoscopy revealed a subepithelial tumor, measuring 5 mm in diameter and located in the lower rectum near the anal sphincter, which may be a neuroendocrine tumor. An endoscopic mucosal resection (EMR) was performed for an accurate histologic diagnosis and treatment, and the rectal lesion was completely removed en bloc and then diagnosed as a tailgut cyst. This paper reports a case of a rectal tailgut cyst treated with EMR in a 60-year-old woman. The 12-month follow-up showed no evidence of recurrence. To the best of the authors' knowledge, this is the second reported case worldwide of a rectal tailgut cyst successfully treated with an EMR, and the first such case reported in Korea.

BACKGROUND Traditional serrated adenoma (TSA) is a rare and precancerous lesion of colorectal cancer. The clinical and endoscopic differentiations between TSAs without dysplasia or adenocarcinoma (TSAOs) and TSAs with dysplasia or adenocarcinoma (TSADs) remain unclear. AIM To evaluate the characteristics of colorectal TSAs and compare the characteristics of TSAOs with those of TSADs. METHODS This retrospective study included 193 patients who underwent endoscopic resection and received a pathologic diagnosis of TSA. We reviewed the medical, endoscopic, and histopathologic records of patients who underwent endoscopic resection of TSAs between January 2010 and December 2023. RESULTS TSAs were more frequently located in the rectosigmoid colon. Most TSAs had 0-Ip, 0-Isp, or 0-Is morphologies. The TSAD lesions were larger than TSAO lesions. TSAD lesions more commonly had a red color and an irregular border than TSAO lesions. TSAOs were usually treated using conventional endoscopic mucosal resection, whereas TSADs were treated using conventional endoscopic mucosal resection, endoscopic submucosal dissection, and surgery. Post-polypectomy bleeding was more common with TSADs than with TSAOs. Univariate analysis showed that gastrointestinal bleeding, red color, 0-IIa, irregular border, and lobular mucosal surface were significantly associated with TSADs. Multivariate analysis showed that gastrointestinal bleeding, an irregular border, and a lobular mucosal surface were significantly associated with TSADs. CONCLUSION TSAs with gastrointestinal bleeding, an irregular border, and a lobular mucosal surface are associated with an increased risk of dysplasia or adenocarcinoma.

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.

Background/Aim: Transcriptional factor prospero homeobox-1 (PROX-1) is crucial for the embryonic development of various organs and cell fate specification. It exhibits either an oncogenic or tumor suppressive activity depending on cancer types. However, the relationship between PROX-1 and hepatocellular carcinoma (HCC) remains obscure. This study was conducted to investigate the effect of PROX-1 on the invasive and oncogenic phenotypes of human HCC cells. Materials and Methods: The effect of PROX-1 on tumor cell behavior was investigated by using a pcDNA-myc vector and a small interfering RNA in HepG2 and Huh7 human HCC cell lines. Flow cytometry, migration, invasion, proliferation, and tube formation assays were performed. PROX-1 expression in human HCC cells was explored by western blotting. Results: PROX-1 overexpression enhanced tumor cell proliferation and inhibited apoptosis and cell cycle arrest by modulating the activities of caspase-3, PARP, and cyclin-dependent kinase inhibitors, including p21, p27, and p57 in HCC cells. After PROX-1 overexpression, the number of migrating and invading HCC cells significantly increased, and the expression levels of N-cadherin and Snail increased in HCC cells. PROX-1 overexpression enhanced angiogenesis through increased VEGF-A and VEGF-C expression and decreased angiostatin expression. PROX-1 overexpression also increased the phosphorylation of glycogen synthase

Background and Objectives: Colorectal endoscopic submucosal dissection (ESD) is an effective technique for removing colorectal neoplasms with large or cancerous lesions. However, there are few studies on post-ESD electrocoagulation syndrome (PECS), a complication of colorectal ESD. Therefore, this study aimed to investigate the various risk factors for PECS after colorectal ESD. Materials and Methods: We retrospectively analyzed the medical records of 1413 lesions from 1408 patients who underwent colorectal ESD at five tertiary hospitals between January 2015 and December 2020. We investigated the incidence and risk factors associated with PECS. Based on the data, we developed a risk-scoring model to predict the risk of PECS after colorectal ESD. Results: The incidence rate of PECS was 2.6% (37 patients). In multivariate analysis, the use of anti-platelet agents (odds ratio (OR), 2.474; 95% confidence interval (CI), 1.088–5.626; p < 0.031), a lesion larger than 6 cm (OR 3.755; 95% CI, 1.237–11.395; p = 0.028), a deep submucosal invasion (OR 2.579; 95% CI, 1.022–6.507; p = 0.045), and an ESD procedure time ≥ 60 min (OR 2.691; 95% CI, 1.302–5.560; p = 0.008) were independent risk factors of PECS after colorectal ESD. We developed a scoring model for predicting PECS using these four factors. As the score increased, the incidence of PECS also increased, from 1.3% to 16.6%. PECS occurred more frequently in the high-risk group (≥2) (1.8% vs. 12.4%, p < 0.001). Conclusions: In this study, the risk factors for PECS after colorectal ESD were the use of anti-platelet agents, a lesion larger than 6 cm, a deep submucosal invasion, and an ESD procedure time ≥ 60 min. The risk-scoring model developed in this study using these factors could be effective in predicting and preventing PECS.

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.

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.