Introduction

There are insufficient data to guide clinical decision-making regarding the implementation of additional surgery following endoscopic therapy in patients with deep submucosal invasive colorectal cancer (T1b CRC) and no additional risk factors for lymph node metastasis (LNM). This investigation sought to identify factors associated with LNM in cases of T1b CRC without other risk factors.

Aims & Methods

Consecutive cases with pathologically proven T1b CRC were retrospectively collected from 2014 to 2023 at a single tertiary hospital in Korea. These patients received either surgical or endoscopic treatment. In patients who received endoscopic treatment alone, no LNM was deemed to exist if there was no recurrence after at least 3 years of follow-up. Excluded were cases with other risk factors, including poor differentiation, lymphovascular invasion, perineural invasion. The cases were compared based on the presence of LNM.

Results

A total of 305 cases were enrolled and LNM was observed in 28 cases (9.18%). In univariate analysis, differentiation, sm3 invasion, tumor growth pattern, and peri-tumoral white spots were related with LNM. Multivariate analysis identified presence of non-polypoid growth parts (odd ratio [OR] 6.39; 95% CI 2.76-14.79), and peri-tumoral white spots (OR 2.85; 95% CI 1.22-6.64) as significant predictive factors for LNM.

Table. Multivariate analysis

Conclusion

Endoscopic findings including presence of non-polypoid growth and peri-tumoral white spots were related with increased risk of LNM in T1b CRC in the absence of other pathologic risk factors. These findings may be useful in determining further treatment strategy for patients with Tb1 CRC received endoscopic resection.

References

Liselotte W. Zwager,1,2,3 Barbara A. J. Bastiaansen, et al.
Deep Submucosal Invasion Is Not an Independent Risk
Factor for Lymph Node Metastasis in T1 Colorectal Cancer:
A Meta-Analysis. Gut 2022;163:174-189

Chihiro Yasue, Akiko Chino, et al.
Pathological risk factors and predictive endoscopic factors
for lymph node metastasis of T1 colorectal cancer: a single-center
study of 846 lesions. J Gastroenterol(2019) 54: 708-717

Introduction

Several guidelines, including those from the US, Europe, and Japan, recognize "tumor differentiation" as a risk factor for lymph node metastasis (LNM) in T1 colorectal cancer. Surgical resection with lymph node dissection is recommended if poorly differentiated adenocarcinoma, signet-ring cell carcinoma, or mucinous carcinoma are observed in histological findings from endoscopically resected specimens. Recent reports suggest that moderately differentiated adenocarcinoma (tub2) may also be a risk factor for LNM.

Aims & Methods

This study aims to investigate whether tub2 is a risk factor for LNM. We initially evaluated 1,742 patients with T1 colorectal cancer who underwent surgical resection with lymph node dissection at our institution from April 2001 to April 2024. Lesions were assessed based on the worst grade of differentiation. Exclusions were made for patients with (a) metachronous or synchronous advanced cancer, (b) invasion deeper than the muscularis propria, (c) Lynch syndrome, familial adenomatous polyposis, or ulcerative colitis, (d) preoperative chemotherapy or radiotherapy, (e) missing data, or (f) lesions without surgical resection. In addition, after excluding 177 patients with poorly differentiated, mucinous, or signet-ring cell adenocarcinoma, 881 patients were enrolled for analysis. We investigated the sensitivity, specificity, and area under the receiver operating characteristics (ROC) curve of tub2 for predicting LNM, alongside correlations between pathological factors and LNM using multivariate analysis.

Results

LNM was detected in 9.9% (87/881) of patients. The sensitivity, specificity, and area under the ROC curve for tub2 were 78.2%, 42.2%, and 0.60, respectively. In the univariate analysis, tub2 was associated with LNM (p<0.001). Multivariate analysis identified lymphatic invasion, vascular invasion, and tub2 as significant risk factors for LNM, with odds ratios of 7.49, 1.97, and 1.95 (p < 0.01, < 0.01, and = 0.02, respectively).

Conclusion

Moderately differentiated adenocarcinoma (tub2) is a risk factor for LNM in T1 colorectal cancer.

Disclosure

Conflicts of interest:None

Introduction

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality and morbidity worldwide. Its tumor microenvironment is composed of a complex interplay of various monocytes, dendritic cells, macrophages and T-cells. Among them, there are various subtypes of T-cells, each of which plays a very important role and has been reported to be associated with prognosis in various cancers. In CRC, there are many reports on the association between CD8+ T-cells and Foxp3+ T-cells and prognosis. However, these are all reports mainly focused on advanced cancers. No studies on T-cells focused on early-stage CRC have been reported to date. Among early-stage CRC, submucosal deep invasive (T1b) CRC has a lymph node metastasis rate of about 10%. Although submucosal invasion depth, vascular invasion, histologic grade, or budding grade are known to be pathological risk factors of lymph node metastasis, there have been no reports evaluating the relationship between tumor microenvironment and lymph node metastasis. Therefore, in this study, we aimed to investigate the characteristics of T-cells according to the degree of CRC invasion and the association between T-cells and the risk of lymph node metastasis in T1b CRC.

Aims & Methods

Initially, 60 patients with colorectal neoplasia [20 with intramucosal neoplasia (IM group); 20 with submucosal invasive CRC (SM group); and 20 with advanced cancer (AD group)] treated at Hiroshima University Hospital from January 2011 to December 2015 were randomly selected. We examined changes in T-cells with tumor invasion. Next, 84 patients with T1b CRC who underwent initial surgical resection with lymph node dissection or additional surgical resection with lymph node dissection after endoscopic resection at Hiroshima University Hospital from March 2013 to July 2019 were selected. We examined the relationship between T-cells and lymph node metastasis in T1b CRC. For all specimens, the phenotype and number of T-cells were evaluated using the triple immunofluorescence method of CD4 (helper T-cell marker), CD8 (killer T-cell marker), and Foxp3 (regulatory T-cell marker). We counted T-cells by subtype in the center (CT) and the invasive front (IF) of the tumor and examined their association with lymph node metastasis.

Results

In the IM group, there was no significant difference in the number of any subtype between CT and IF, while in the SM and AD groups, all subtypes were more numerous in IF than CT. They were also predominantly more numerous as the degree of tumor invasion with IM, SM, and AD. The high number of Foxp3 in IF and the high ratio of Foxp3/CD4 and Foxp3/CD8 were positively correlated with lymph node metastasis.

Conclusion

High Foxp3 counts and high Foxp3/CD4 and high Foxp3/CD8 ratios in IF of T1b CRC may help predict lymph node metastasis.

Disclosure

The authors have no conflicts of interest or financial ties to disclose.

Introduction

According to the European Society of Gastrointestinal Endoscopy (ESGE) guidelines, the curative criteria of endoscopic resection (ER) for T1 colorectal cancer (CRC) are well/moderately differentiated adenocarcinoma or papillary carcinoma, no lympho-vascular invasion, submucosal invasion depth <1000μm, and budding grade (BD) 1. Although an additional surgery is recommended for non-curative ER, the incidence of lymph node metastasis (LNM) is less than 12%. Many reports on lymph node metastasis and recurrence in T1 CRC originate from academic centers, with limited reports of real-world data.

Aims & Methods

The aim of this study was to clarify clinical outcomes in patients with T1 CRC. A total of 686 consecutive patients (Male:447 Female:239) were enrolled from April 2009 to August 2019 at 10 institutions. Exclusion criteria included evidence of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or inflammatory bowel disease; presence of active, malignant diseases in any other organs; presence of synchronous or metachronous advanced CRC. Risk factors of LNM and recurrence, and survival were analyzed.

Results

The mean age of patients was 69.3±10.2 years old. The mean tumor size was 20.3±12.4mm. The location of the lesion was 439(64%) and 247(36%) in the colon and rectum, respectively. The histopathological types included 681 cases of differentiated type and 5 cases of undifferentiated type. A number of patients with ER without additional SR (ER alone) were 176(curative resection 86, non-curative resection 90), those with SR (SR alone) were 510, and those with ER and additional SR (ER + additional SR) were 116.
(i) Risk factor of LNM: LNM was found in 13(11.2%) patients with ER + additional SR and in 40(10.6%) patients with SR alone. In multivariate analysis, positive lymphatic invasion and tumor size were significant independent risk factor for LNM (OR 5.9, 95% CI [2.2-16], p<0.01, OR 1.04, 95%CI［1.00-1.07］p=0.028, respectively).
(ii) Recurrence: During the mean observation period of 45.5±34.3 months, recurrence was found in 27(3.9%) patients. No recurrence was found in the ER curative resection group. Although 43% (90/206) patients with ER non-curative resection did not receive additional SR, there was no significant difference in recurrence rate between ER alone with non-curative resection and ER + additional SR groups (5.6% (5/90) vs. 2.6% (3/116), respectively; p=0.3). In the SR alone group, recurrence was found in 4.8% (19/394). The significant independent risk factor for recurrence was tumor size (OR 1.12, 95% CI [1.05-1.2], p<0.01).
(iii) Survival: There were 50 deaths (7.3%, 76.2±6.6 years old) during the observation period of 45.5±34.3 months, but CRC-related death was found in only 6 cases (0.8%); one case was ER alone with non-curative resection and the other cases were SR alone.

Conclusion

This study suggests that the possibility of expanding the indication for ER of T1 CRC, because positive lymphatic invasion and tumor size were the only risk factor for LNM and better long-term outcomes were shown despite including significant number of patients with ER alone with non-curative resection. Fifty cases of death showed a higher average age and fewer deaths from CRC. Therefore, even in cases of non-curative resection for T1 CRC after ER, avoiding additional SR may be considered due to advanced age or comorbidities.

Introduction

Although sigmoid volvulus is potentially life-threatening condition in elderly patients, prognostic factors for sigmoid volvulus are not well known.

Aims & Methods

The aim of this study is to evaluate clinical outcomes and investigate prognostic factors for patients with sigmoid volvulus. We retrospectively reviewed 85 patients who were treated with sigmoid volvulus from January 2005 to January 2023 at a single tertiary referral center. After exclusion of patients who received emergency bowel resection surgery or improved by conversative treatment alone, a total of 59 patients were included. Patient and abdominal computed tomography (CT)-related factors potentially associated with clinical outcomes were analyzed by logistic and Cox regression analyses.

Results

The mean age of the patients was 72.4 years, and 74.3% were male. 49 patients (83.1%) were improved on initial endoscopic decompression therapy. Regarding factors related with failure of initial endoscopic decompression therapy, suspected bowel ischemia on initial CT (odds ratio 8.847, 95% CI 0.666–117.462), age<65 (odds ratio 5.138, 95% CI 0.574–46.025), larger (>85 mm) cross-sectional diameter of distended colon (odds ratio 25.400, 95% CI 1.015–635.804) were related with endoscopic treatment failure. On the other hand, of the 35 patients without previous volvulus episode who improved after initial endoscopic decompression therapy, 14 patients (40.0%) had recurrence of sigmoid volvulus during a mean follow-up of 411 days. Patients showing larger cross-sectional diameter of distended colon (>85mm, hazard ratio 9.925, 95% CI 1.618–60.863), larger maximal long (>230mm, hazard ratio 4.456, 95% CI 0.931–21.327) and short (>150mm, hazard ratio 2.828, 95% CI 0.639–12.505) axis length of overall twisted sigmoid colon were related with volvulus recurrence.

Conclusion

Prognostic factors unravelled in our study may be useful in management of patients with sigmoid volvulus. Early surgical backup consultation may be needed in patients having factors related with failure of endoscopic decompression therapy. Meanwhile, elective surgical treatment after improvement on initial endoscopic therapy may be considered in patients showing high risk features for recurrence on CT scan.

References

1. R. Kusunoki et al, Initial Computed Tomography Findings of Long and Distended Colon Are Risk Factors for the Recurrence of Sigmoid Volvulus, Digestive Diseases and Sciences (2021) 66:1162–1167
2. C. Humbert et al, Stratification of sigmoid volvulus early recurrence risk using a combination of CT features, Diagnostic and Interventional Imaging 103 (2022) 79-85
3. Z. Slack et al, Prognostic factors in the decision-making process for sigmoid volvulus: results of a single-centre retrospective cohort study, BMC Surgery (2022) 22:95
4. EM Kim et al, Clinical outcomes of sigmoid volvulus and risk factors for its recurrence: a multicenter study in Korea, International Journal of Colorectal Disease (2020) 35:1841–1847
5. A Abdelrahim et al, Dilemma of sigmoid volvulus management, Ann R Coll Surg Engl 2021; 104: 95–99

Introduction

T1 colorectal cancer can be managed either by surgery or interventional endoscopy. High-risk features after endoscopic resection (G3, submucosal invasion >1000 µm, lympho-vascular invasion, tumour budding+, or R1 resection) increase the risk of lymphnode metastasis (10-15%), often requiring additional surgery. However, the benefits of surgery versus endoscopic resection alone remain unclear, particularly in elderly or frail patients.

Aims & Methods

The aim of the study is to assess recurrence rate and overall survival in patients underwent surgery, endoscopy or both. Secondary endpoints is to evaluate incidence of adverse events and length of hospital stay
All consecutive patients diagnosed with T1 colorectal cancer from 2018 to 2024 in our institution were enrolled in this retrospective study. We divided this cohort in 3 groups: endoscopic resection plus surgery (ER-S), upfront surgery (SR), or endoscopic resection alone (ER). Demographics data, mortality, cancer recurrence rate, disease free survival and AEs were recorded.

Results

One-hundred and thirty-three patients were enrolled in the study: 34 (72 years±10) in the SR group, 65 (65 years±11) in the ER-S group and 34 (77 years±11) in ER, respectively.
Lesions were similar (p-value 0.30) for dimension: 31±15 mm (ER) vs 23±12 mm (ER-S) vs 30±13 mm (ER) such as follow-up (23 vs 24 vs 21 months) for the three groups (p-value 0.428). Hospital stay after the procedure was significantly lower in the ER group (1 day median) vs SR (median 9 days;p-value 0.0001) and ER-S group (7 days median;p-value 0.003). Cumulative 30 days adverse events were higher in the SR group (62%; p-value 0.0001) and in the ER-S group (22%; p-value 0.001) compared to ER alone (12%). During the study period, no endoscopic/radiological recurrence occurred in the SR group whereas 1 patient in the ER-S group and 2 in the ER group showed recurrence non suitable for further treatments.
Five patients in SR group died after a median of 18 months (1 for early surgical complication); 2 died in the ER-S group after a median of 34 months and 3 died in the ER group after a median of 24 months (1 for rectal cancer progression) (p-value 0.365).
Overall survival was comparable among the three groups with no significant difference (p-value 0.718) with a median of 40 months (SR), 28 (ER-S) and 26 (ER) months.

Conclusion

Endoscopic resection alone appears to be a reasonable option for high-risk T1 CRC patients, especially those with increased surgical risk due to low rate of recurrence, low adverse events and a comparable overall survival in short-mid term.

References

1. Quénéhervé, L.; Pioche, M.; Jacques, J. Curative Criteria for Endoscopic Treatment of Colorectal Cancer. Best Pract. Res. Clin. Gastroenterol. 2024, 101883, doi:10.1016/j.bpg.2024.101883.
2. Chen, Y.; Jing, W.; Chen, M.; Wang, Z.; Wu, J.; Yang, J.; Yang, L.; Deng, K. Long-Term Outcomes of Local Resection versus Surgical Resection for High-Risk T1 Colorectal Cancer: A Systematic Review and Meta-Analysis. Gastrointest. Endosc. 2023, 97, 1016-1030.e14, doi:10.1016/j.gie.2023.02.027.
3. Spadaccini M, Bourke MJ, Maselli R, et al. Clinical outcome of non-curative endoscopic submucosal dissection for early colorectal cancer. Gut. Published online January 20, 2022. doi:10.1136/gutjnl-2020-323897
4. Corre, F.; Albouys, J.; Tran, V.-T.; Lepilliez, V.; Ratone, J.-P.; Coron, E.; Lambin, T.; Rahmi, G.; Karsenti, D.; Canard, J.-M.; et al. Impact of Surgery after Endoscopically Resected High-Risk T1 Colorectal Cancer: Results of an Emulated Target Trial. Gastrointest. Endosc. 2023, S0016-5107(23)02933-4, doi:10.1016/j.gie.2023.09.027.
5. UICC. TNM. Classification of malignant tumours. eighth ed. Wiley; 2016. p. 272

Disclosure

Giuseppe Grande is consultant for Olympus, Boston Scientific, ERBE, Fujifilm