Deep Submucosal Invasion Is Not an Independent Risk Factor for Lymph Node Metastasis in T1 Colorectal Cancer: A Meta-Analysis.

BACKGROUND & AIMS: Deep submucosal invasion (DSI) is considered a key risk factor for lymph node metastasis (LNM) and important criterion to recommend surgery in T1 colorectal cancer. However, metastatic risk for DSI is shown to be low in the absence of other histologic risk factors. This meta-analysis determines the independent risk of DSI for LNM. METHODS: Suitable studies were included to establish LNM risk for DSI in univariable analysis. To assess DSI as independent risk factor, studies were eligible if risk factors (eg, DSI, poor differentiation, lymphovascular invasion, and high-grade tumor budding) were simultaneously included in multivariable analysis or LNM rate of DSI was described in absence of poor differentiation, lymphovascular invasion, and high-grade tumor budding. Odds ratios (OR) and 95% CIs were calculated. RESULTS: Sixty-seven studies (21,238 patients) were included. Overall LNM rate was 11.2% and significantly higher for DSI-positive cancers (OR, 2.58; 95% CI, 2.10-3.18). Eight studies (3621 patients) were included in multivariable meta-analysis and did not weigh DSI as a significant predictor for LNM (OR, 1.73; 95% CI, 0.96-3.12). As opposed to a significant association between LNM and poor differentiation (OR, 2.14; 95% CI, 1.39-3.28), high-grade tumor budding (OR, 2.83; 95% CI, 2.06-3.88), and lymphovascular invasion (OR, 3.16; 95% CI, 1.88-5.33). Eight studies (1146 patients) analyzed DSI as solitary risk factor; absolute risk of LNM was 2.6% and pooled incidence rate was 2.83 (95% CI, 1.66-4.78). CONCLUSIONS: DSI is not a strong independent predictor for LNM and should be reconsidered as a sole indicator for oncologic surgery. The expanding armamentarium for local excision as first-line treatment prompts serious consideration in amenable cases to tailor T1 colorectal cancer management.

Risk Factors for Lymph Node Metastasis of Rectal Neuroendocrine Tumor and Its Prognostic Impact: A Single-Center Retrospective Analysis of 195 Cases with Radical Resection.

PURPOSE: The incidence of rectal neuroendocrine tumors (NETs) has been steadily increasing. The risk factors for and prognostic impact of lymph node (LN) metastasis were analyzed in 195 patients with stage I-III rectal NET who underwent radical surgery. METHODS: This retrospective, single-center study analyzed risk factors for LN metastasis focusing on previously identified factors and a novel risk factor: multiple rectal NETs. The association between LN metastasis and the prognosis was also analyzed. RESULTS: Pathologically, the LN metastasis rate (also the rate of stage III disease) was 39%, which was higher than the clinical LN metastasis rate of 14%. Tumor size > 10 mm, presence of central depression, tumor grade G2, depth of invasion, LN swelling on preoperative imaging (cN1), venous invasion and multiple NETs were identified as risk factors for LN metastasis. As the tumor size and risk factors increased, the rate of LN metastasis increased. Among these 7 factors, venous invasion, cN1, and multiple NETs were identified as independent predictors of LN metastasis. LN metastasis of rectal NETs was associated with significantly poor disease-free and disease-specific survival. CONCLUSIONS: As risk factors increase, the potential for rectal NETs to metastasize to the LNs increases and LN metastasis is associated with a poor prognosis. This is the first study to report multiple NETs as a risk factor for LN metastasis. A future study examining the survival benefit of radical surgery accompanying LN dissection compared with local resection is warranted.

Risk factors for vertical incomplete resection in endoscopic submucosal dissection of deep invasive submucosal colorectal cancer.

INTRODUCTION: It has been recently reported that deep invasive submucosal (T1b) colorectal cancer (CRC) without other pathological risk factors for lymph node metastasis has a low rate of lymph node metastasis, increasing the possibility of endoscopic submucosal dissection (ESD) in the future. However, ESD for T1b CRC is technically difficult, and some lesions cannot be resected en bloc. This study aimed to identify the risk factors associated with vertical incomplete ESD in T1b CRC. METHODS: We retrospectively studied 140 pathological T1b CRC lesions that underwent initial ESD at our institution between January 2011 and October 2020, and categorized them into positive vertical margin (PVM) and negative vertical margin (NVM) groups. The risk factors for PVM were examined using univariate and multivariate analyses, and a subgroup analysis for T1b CRC with an obvious depressed surface was performed. RESULTS: Multivariate analysis revealed obvious depression (hazard ratio [HR]: 7.4; 95% confidence interval [CI]: 2.47-22.5) and severe fibrosis (HR: 11.4; 95% CI: 3.95-33.0) as significant risk factors for PVM. Length of depressed surface ≥12 mm (HR: 6.19; 95% CI: 1.56 -24.6) was identified as an independent predictor of PVM for T1b CRC with an obvious depression. CONCLUSION: Pathological T1b CRC cases with an obvious depression and severe fibrosis are at a high risk of vertical incomplete ESD.

Training program using a traction device improves trainees' learning curve of colorectal endoscopic submucosal dissection.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) requires advanced endoscopic skill. For safer and more reliable ESD implementation, various traction devices have been developed in recent years. The purpose of this research was to evaluate whether an ESD training program using a traction device (TD) would contribute to the improvement of trainees' skill acquisition. METHODS: The differences in treatment outcomes and learning curves by the training program were compared before and after the introduction of TD (control group: January 2014 to March 2016; TD group: April 2016 to June 2018). RESULTS: A total of 316 patients were included in the analysis (TD group: 202 cases; control group: 114 cases). The number of cases required to achieve proficiency in ESD techniques was 10 in the TD group and 21 in the control group. Compared to the control group, the TD group had a significant advantage in ESD self-completion rate (73.8% vs. 58.8%), dissection speed (19.5 mm2/min vs. 15.9 mm2/min), en bloc resection rate (100% vs. 90%), and R0 resection rate (96% vs. 83%). CONCLUSIONS: The rate of colorectal ESD self-completion by trainees improved immediately after the start of the training program using a traction device compared to the conventional method, and the dissection speed tended to increase linearly with ESD experience. We believe that ESD training using a traction device will help ESD techniques to be performed safely and reliably among trainees.

Clinical utility of the pocket-creation method with a traction device for colorectal endoscopic submucosal dissection.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) is technically demanding while ensuring safety, especially in cases with fibrosis and/or poor maneuverability. To overcome such difficulties, we developed a novel method called the pocket-creation method with a traction device (PCM with TD). We then evaluated the effectiveness and safety of PCM with TD in colorectal ESD compared to other conventional methods. METHODS: In total, 324 colorectal lesions treated with ESD from July 2018 to June 2019 were included. The following three treatment strategies were used: conventional ESD (CE), CE with TD, and PCM with TD. Patient backgrounds and treatment outcomes were retrospectively compared and analyzed. RESULTS: As ESD methods, CE, CE with TD, and PCM with TD account for 58% (187/324), 24% (78/324), and 18% (59/324), respectively. No significant difference was observed among the three groups in en bloc and R0 resection rates or adverse events. The rate of lesions with fibrosis and poor maneuverability was significantly higher in the PCM with TD group (CE group vs CE with TD group vs PCM with TD group: fibrosis, 24% vs 47% vs 64%, p < 0.001; poor maneuverability, 5.3% vs 13% vs 20%, p = 0.002). Dissection speed was significantly higher in the PCM with TD than in the CE with TD group (p = 0.003). CONCLUSIONS: PCM with TD can achieve a stable en bloc resection rate and R0 dissection rate without adverse events even in the hands of trainees, irrespective of the size and location of the lesion, presence of fibrosis, and under poor maneuverability conditions.

Effects of L-Menthol and Carbon Dioxide on the Adenoma Detection Rate during Colonoscopy: L-Menthol and Carbon Dioxide on Colonoscopy.

BACKGROUND AND AIMS: We examined the efficacy of the combined use of L-menthol spraying (L-mentholS) as an antispasmodic agent and carbon dioxide insufflation (CO2I) on the adenoma detection rate (ADR) in a prospective, single-center trial with a 2 × 2 factorial design. METHODS: We randomly assigned 611 patients scheduled to undergo colonoscopy to 4 groups: (1) the L-mentholS + CO2I (n = 153), (2) L-mentholS + air insufflation (AI; n = 156), (3) CO2I (n = 153), and (4) AI (n = 149) groups. We used 20 mL of 0.8%-L-menthol solution for the L-mentholS. The primary outcome was the difference in the ADR, and the secondary outcomes were the differences in colonic peristalsis and abdominal pain. -Results: The ADRs were not different among the groups: 1/2/3/4; 39.9%/43.6%/41.2%/51.0%. CO2I was associated with a significant decrease in the ADR (OR 0.57; 95% CI 0.35- 0.93) with a multiple logistic regression. The interaction between L-mentholS and CO2I was associated with a suppression of the decrease in the ADR. Both L-mentholS and CO2I were associated with a significant decrease in abdominal pain, and L-mentholS was associated with a significant improvement of peristalsis. CONCLUSIONS: The fact that CO2I was associated with significant decreases in the ADR was a problem. The combined use of L-mentholS and CO2I could help to suppress the decrease in the ADR.

Pregnant woman with non-comatose autoimmune acute liver failure in the second trimester rescued using medical therapy: A case report.

We present the case of a 25-year-old woman at 16 weeks of gestation who presented with non-comatose autoimmune acute liver failure and was at high risk of developing fulminant hepatitis. Predictive formulas indicated a high probability of developing fulminant hepatitis. Unenhanced computed tomography showed marked hepatic atrophy and broadly heterogeneous hypoattenuating areas. The course of her illness was subacute, and the etiology of liver injury was unclear. Considering all of the above, we predicted a poor prognosis. Plasma exchange (PE) and continuous hemodiafiltration (CHDF) therapy were initiated just after admission. A few days after admission, a high titer (×80) of antinuclear antibody was noted. Because autoimmune hepatitis (AIH) was considered a cause of liver failure, treatment with moderate prednisolone (30 mg/day) doses was administrated, with careful consideration of her pregnancy. Thereafter, her laboratory findings and clinical course gradually improved without the need for liver transplantation. A liver biopsy at 18 days after admission indicated a diagnosis of AIH. She continued the pregnancy and delivered a healthy baby without any complications. Eventually, prednisolone doses were decreased to 10 mg, after which her liver function worsened. The second liver biopsy also indicated a diagnosis of AIH. Accordingly, low-dose prednisolone and azathioprine doses (50 mg/day) were administrated to recover her liver function, after which her liver function regained normalcy. This case illustrates that a pregnant woman with non-comatose autoimmune acute liver failure in the first or second trimester of pregnancy and her fetus can be rescued by PE/CHDF therapy and safe moderate doses of prednisolone.

Efficacy of the pocket-creation method with a traction device in endoscopic submucosal dissection for residual or recurrent colorectal lesions.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) for residual or recurrent colorectal lesions after incomplete resection is challenging because of severe fibrosis. This study aimed to compare the efficacy of the pocket-creation method (PCM) with a traction device (TD) with that of conventional ESD for residual or recurrent colorectal lesions. METHODS: We retrospectively studied 72 patients with residual or recurrent colorectal lesions resected using ESD. Overall, 31 and 41 lesions were resected using PCM with TD and conventional ESD methods, respectively. We compared patient background and treatment outcomes between the PCM with TD and conventional ESD groups, respectively. The primary endpoints were en bloc resection and R0 resection rates. The secondary endpoints were the dissection speed and incidence of adverse events. RESULTS: En bloc resection was feasible in all cases with PCM with TD, but failed in 22% of cases of conventional ESD. The R0 resection rates for PCM with TD and conventional ESD were 97% and 66%, respectively. Dissection was significantly faster in the PCM with TD group (13.0 vs. 7.9 mm2/min). Perforation and postoperative bleeding were observed in one patient in each group. CONCLUSION: PCM with TD is an effective method for treating residual or recurrent colorectal lesions after incomplete resection.

Pathological risk factors and predictive endoscopic factors for lymph node metastasis of T1 colorectal cancer: a single-center study of 846 lesions.

BACKGROUND: Determining the depth of invasion of early stage colorectal cancer has been emphasized as a means of improving endoscopic diagnostic accuracy. Recent studies have focused on other pathological risk factors for lymph node metastasis (LNM). We investigated the significance of depth of invasion and predictive properties of other endoscopic findings. METHODS: We retrospectively investigated 846 patients with submucosal invasive (T1) colorectal cancer who received an accurate pathological diagnosis and were treated between January 2005 and December 2016. Pathological risk factors associated with LNM were reviewed. We divided patients into groups: low-risk T1 colorectal cancer (LRC; no risk factors) and high-risk T1 colorectal cancer (HRC; exhibiting lymphovascular invasion, tumor budding grade of 2/3, and/or poor differentiation) and studied predictive endoscopic factors for HRC. RESULTS: Significant risk factors for LNM in multivariate analysis were lymphovascular invasion [odds ratio (OR) 8.09; 95% confidence interval (CI) 3.84-17.1], tumor budding (OR 1.89; 95% CI 1.09-3.29), and histological differentiation (OR 2.09; 95% CI 1.12-3.89). The LNM-positive rate with only deep submucosal invasion was 1.6%. Significant predictive factors for HRC in multivariate analysis identified rectal tumor location (OR 1.92; 95% CI 1.35 -2.72, depression (OR 2.73; 95% CI 1.96 -3.80), protuberance within the depression (OR 2.58; 95% CI 1.39- 4.78), expansiveness (OR 2.39; 95% CI 1.27- 4.50), and loss of mucosal patterns (OR 1.90; 95% CI 1.20 -3.01) as significant factors. CONCLUSIONS: Rectal tumor location, depression, protuberance within the depression, expansiveness, and loss of mucosal patterns could be predictive factors for HRC.

Colorectal endoscopic submucosal dissection can be efficiently performed by a trainee with use of a simple traction device and expert supervision.

Background and study aims Colorectal endoscopic submucosal dissection (ESD) is technically challenging owing to submucosal fibrosis and difficult endoscope manipulation. Therefore, various traction methods have been reported. We often use a simple looped nylon thread attached to a clip to assist with dissection. We assessed the feasibility of mentor-guided colorectal ESD using this traction device (TD). Patients and methods From December 2017 to March 2018, we retrospectively reviewed outcomes of 101 colorectal ESDs performed by two groups of endoscopists (A, 5 endoscopists with colorectal ESD experience of < 50 cases; B, 5 endoscopists with experience of > 300 cases). Group A was further divided into two subgroups that performed ESD with or without TD. Results No significant difference was observed in ESD completion rates (86.1 % [62/72] vs. 96.6 % [28/29]; odds ratio [OR], 0.22; 95 % confidence interval [CI], 0.005 - 1.71; P  = 0.17) or procedure times (52.0 min vs. 40.0 min; P  = 0.27) and adverse event rates between groups A and B. The rate of TD use was significantly higher in group A than in group B (44.4 % [32/72] vs. 20.7 % [6/29]; OR, 3.03; CI, 1.04 - 10.23; P  = 0.03). The completion rate was not different between the two subgroups of group A (with vs. without TD) (81.2 % [26/32] vs. 90.0 % [36/40]; OR, 0.49; CI, 0.09 - 2.29; P  = 0.32); however, the proportion of fibrosis cases was significantly higher in the TD-use group (46.8 % [15/32] vs. 22.5 % [9/40]; OR, 2.99; CI, 0.98 - 9.59; P  = 0.03). Conclusion Mentor-guided colorectal ESD using TD was performed efficiently, safely, and in a manner comparable to that of experts.