Introduction

Esophageal cancer is ranked seventh in the number of new cases and sixth for the number of deaths among all cancers worldwide [1]. There are two types of esophageal cancer including esophageal squamous cell carcinoma (ESCC) and adenocarcinoma. ESCC is classified into mucosal cancer, submucosal cancer, and advanced cancer. Mucosal cancer is classified into T1a-EP (epithelial), T1a-LPM (lamina propria mucosa) and T1a-MM (muscularis mucosa) based on the classification system from the Japan Esophageal Society (JES) [2]. According to the classification system from the JES, the growth and infiltrative patterns of these tumors are classified into three groups. An expansive growth pattern of tumor nests with a well-demarcated border from surrounding tissue is INF-a, infiltrative growth of tumor nests with an ill-defined border from surrounding tissue is INF-c, and an intermediate growth pattern between INF-a and INF-c is classified as INF-b. An infiltrative growth pattern such as INF-c correlates with worse outcomes for advanced ESCC and pT1-ESCC including submucosal invasion[3-6] . However, the clinical impact of the INF pattern was unclear in patients with pT1a-LPM ESCC.

Aims & Methods

This study was conducted to clarify clinicopathological features of tumor growth patterns in pT1a-LPM type ESCC and the relationship between tumor growth patterns and magnifying endoscopic findings.
One hundred ninety-four consecutive ESCC lesions treated by endoscopic submucosal dissection (ESD) at the Saku Central Hospital from February 2012 to October 2015 were reviewed. Eighty-four patients and 87 lesions pathologically diagnosed as pT1a-LPM ESCC were included. No patients underwent ESD for locally recurrent lesions or were treated with chemoradiotherapy. Clinicopathological findings including tumor growth pattern and narrow band imaging with magnifying endoscopy (NBI-ME) based on the JES classification of magnifying endoscopy for ESCC [7] in the LPM area were investigated.

Results

Vascular pattern of LPM area (n=30)	Tumor growth pattern, n INF-a/ INF-b/ INF-c	Lymphatic invasion, n (%)
B1 (n=23)	23/ 0/ 0	0 (0%)
B2 (n=7)	2/ 4/ 1	2 (29%)
p value	< 0.05	< 0.05

Eighty-seven lesions were classified as infiltrative growth pattern-a (INF-a): expansive growth (n=81), INF-b: intermediate growth (n=4) and INF-c: infiltrative growth pattern (n=2). Lymphatic invasion was shown in one INF-b and one INF-c lesion. NBI-ME and histopathological images were matched for 30 lesions. The microvascular pattern was classified into types B1 (n=23) and B2 (n=7) using the JES classification of magnifying endoscopy for ESCC[2] . All 23 type B1 lesions were classified as INF-a without lymphatic invasion. Type B2 lesions were classified as INF-a (n=2), INF-b (n=4) and INF-c (n=1), and lymphatic invasion was present in two lesions (INF-b and INF-c). The rate of lymphatic invasion was significantly higher in type B2 than type B1 (p=0.048).

Conclusion

The tumor growth pattern of pT1a-LPM ESCC was mostly INF-a in type B1 patterns. Type B2 patterns are rarely present in pT1a-LPM ESCC, however lymphatic invasion with INF-b or INF-c was frequently observed. Careful observation before endoscopic resection with NBI-ME is important to identify B2 patterns to predict histopathology.

References

1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49
   
2. Japan Esophageal S. Japanese Classification of Esophageal Cancer, 11th Edition: part I. Esophagus : official journal of the Japan Esophageal Society. 2017;14:1-36.
3. Ooki A, Yamashita K, Kobayashi N, et al. Lymph node metastasis density and growth pattern as independent prognostic factors in advanced esophageal squamous cell carcinoma. World J Surg. 2007;31(11):2184-91.
4. Ito E, Ozawa S, Kijima H, et al. New invasive patterns as a prognostic factor for superficial esophageal cancer. J Gastroenterol. 2012;47(12):1279-89.
5. Zhao Y, Xu E, Yang X, et al. Tumor infiltrative growth pattern correlates with the immune microenvironment and is an independent factor for lymph node metastasis and prognosis in stage T1 esophageal squamous cell carcinoma. Virchows Arch. 2020;477(3):401-8.
6. Anciaux M, Demetter P, De Wind R, et al. Infiltrative tumour growth pattern correlates with poor outcome in oesophageal cancer. BMJ Open Gastroenterol. 2020;7(1).
7. Oyama T, Inoue H, Arima M, et al. Prediction of the invasion depth of superficial squamous cell carcinoma based on microvessel morphology: magnifying endoscopic classification of the Japan Esophageal Society. Esophagus. 2017;14:105-12.

Disclosure

There are no conflict of interest regarding this study.

Introduction

Features and management of post operative recurrence (POR) of Crohn’s Disease (CD) after ileocecal resection (ICR) are well defined, but POR after colectomy is scarcely described.

Aims & Methods

Multicenter, nationwide, retrospective study promoted by the Spanish Working Group on Crohn's and Colitis (GETECCU). CD patients who underwent segmental colectomy (SC) or subtotal colectomy (STC) between 2012 and 2023 were included. Primary endpoint was clinical POR, defined as CD-related symptoms requiring salvage therapy despite POR prophylaxis. Secondary endpoints included endoscopic POR (anastomotic and/or perianastomotic CD-associated lesions at endoscopy), association between clinical and endoscopic POR, comparison of clinical and endoscopic POR-free survival among different types of colectomy, surgical recurrence (need for reoperation) depending on colectomy subtypes; and identification of factors associated with post-colectomy POR.

Results

224 patients were included: 157 (70%) underwent SC and 67 (30%) underwent STC. In the SC group, patients were older [44 (SD 15) vs 39 (SD 14) years old, p=0.01] and B3 phenotype was more frequent [68/157 (43%) vs 14/67 (21%), p = 0.003]. POR prophylaxis was prescribed in 119/157 (76%) SC patients and in 47/67 (70%) STC patients, with no significant differences regarding the choice of agent (main baseline characteristics of the study population are described in Table 1). The main indication for surgery was stenosing disease [both in SC group (83/157, 53%) and STC group (34/67, (51%)]. Median follow-up was 19.5 [3.7–67.9] months to clinical POR and 14.0 [5.9–54.1] months to endoscopic POR. Clinical POR developed in 60/157 (38%) in the SC group and 42/67 (63%) in the STC group (p = 0.001). Endoscopic evaluation was available in 190/224 patients (85%) [131/157 SC (83%) and 59/67 (88%) STC]; endoscopic POR was detected in 66/131 (50%) SC patients and 42/59 (71%) STC patients (p=0.012). Among patients with endoscopic POR, 76/108 (70%) also presented clinical POR: 43/66 (65%) patients in the SC group and 33/42 (79%) in the STC group (p=0.203). Clinical and endoscopic POR-free survival was higher for SC than for STC (p log-rank <0.05). Surgical recurrence occurred in 17/157 patients (11%) in the SC group and in 8/67 patients (12%) in the STC group (p=0.992). Multivariate stepwise Cox proportional hazards regression showed significant association of STC, smoking and myenteric plexitis with both clinical POR (HR 2.36, 95%CI [1.45 - 3.82]; HR 1.34, 95%CI [1.03 - 1,75] and HR 1.71, 95%CI [1.01 - 2.91] respectively) and endoscopic POR (HR 2.47, 95%CI [1.49 - 4.10], HR 1.36, 95%CI [1.03 - 1.79] and HR 1.83, 95% CI [1.01 - 3.29], respectively); and immunomodulator prophylaxis with endoscopic POR (HR 1.72, 95%CI [1.02 - 2.90]) (all p-values <.05).

Variable	Segmental colectomy1 (n=157)	Subtotal colectomy1 (n=67)	p-value2
Age	44.1 (SD 15.2)	39.2 (SD 14.2)	0.01
Sex	Male: 71 (45%), Female: 86 (55%)	Male: 37 (55%), Female: 30 (45%)	0.2
CD phenotype (Montreal)	B1: 26 (17%), B2: 63 (40%), B3: 68 (43%)	B1: 20 (30%), B2: 33 (49%), B3: 14 (21%)	0.003
Previous surgery	None: 125 (86%), ICR: 11 (7%), EUA3: 5 (3.2%), other: 6 (3.8%)	None: 56 (84%), ICR: 5 (7.5%), EUA: 2 (3%), other: 4 (6%)	>0.9
Prior advanced therapy failure (biologics and/or JAK inhibitors)	1: 113 (72%), 2: 22 (14%), 3: 14 (8.9%), 4: 4 (2.5%), 5: 3 (1.9%), 6: 1 (0.6%)	1: 44 (66%), 2: 13 (19%), 3: 2 (3%), 4: 5 (7.5%), 5: 2 (3%), 6: 0 (0%), 7: 1 (1.5%)	0.12
Prior immunomodulator (IMM) failure	Yes: 56 (36%), No: 101 (64%) Monotherapy: 10 (1.75%)	Yes: 23 (34%), No: 43 (66%) Monotherapy: 3 (4.5%)	0.8
POR prophylaxis (biologics and/or JAK inhibitors)	Infliximab: 21 (13.4%), Adalimumab: 27 (17.2%), Certolizumab: 2 (1.3%), Ustekinumab: 7 (4.4%), Vedolizumab: 4 (2.54%)	Infliximab: 12 (17.9%), Adalimumab: 6 (8.9%), Ustekinumab: 4 (6%), Vedolizumab: 1 (1.5%), Upadacitinib: 1 (1.5%)	0.4
POR prophylaxis with added IMM (combotherapy)	Yes: 61 (39%), No: 96	Yes: 23 (34%), No: 44 (66%)	0.5
Table 1: Summary of the main characteristics of the study population. 1mean (SD), n(%); 2 Wilcoxon rank sum test; Pearson’s Chi-squared test; Fisher’s exact test 3Exploration Under Anesthesia

Conclusion

POR remains common after colectomy in patients with CD. Clinical and endoscopic POR rates are higher following STC compared to SC in patients under similar prophylactic regimes. Although prospective research is still warranted, our data support favoring segmental resection of colonic CD when feasible.

Disclosure

J.L.R.G. has received financial support for traveling and educational activities or has received fees as a speaker from Abbvie, Kern Pharma, Janssen, Takeda, Pfizer, Lilly, Galapagos, Adacyte, Ferring, Tillotts Pharma, Faes Farma, Norgine and Casen. C.S.F. has received financial support for traveling and educational activities or has received fees as a speaker or consultant from Abbvie, Kern Pharma, Lilly, Ferring, MSD, Janssen, Takeda and Tillotts Pharma. YZ has received financial support for travelling and educational activities from or has served as an advisory board member for AbbVie, Adacyte, Alfasigma, Almirall, Amgen, Boehringer Ingelheim, Dr Falk Pharma, Faes Pharma, Fresenius Kabi, Ferring, Galapagos, Janssen, Johnson&Johnson, Kern, Lilly, MSD, Otsuka, Pfizer, Sanofi, Shire, Takeda, and Tillotts Pharma. The rest of the authors have no conflicts of interest to declare regarding this study.