Sm Invasion Research Articles

Optimal extent of lymph node dissection in clinical early-stage right colon cancer: a retrospective analysis.

Determining the extent of radical lymphadenectomy at clinical early stage is challenging. We aimed to investigate the appropriate extent of lymphadenectomy in clinical early-stage right colon cancer. Patients with clinical stage 0 or I right colon cancer who underwent curative surgery from January 2007 to December 2021 were included in this retrospective study. The extent of lymph node (LN) metastases based on the distribution of LN metastases (LND: LND1 pericolic nodes, LND2 intermediate nodes, LND3 apical nodes), along with the depth of submucosal (SM) invasion (classed into SM1-3), were analyzed. Of the 348 patients, distribution across pathologic stages was as follows: 30 patients (8.6%) at stage 0, 207 (59.5%) at stage I, 52 (14.9%) at stage II, and 59 (17.0%) at stage III. In pT1 tumor patients, LN metastases varied by SM invasion depth: 3.6% in SM1 (all LND1), 5.1% in SM2 (all LND1), and 17.5% in SM3 (LND1 10%, LND2 5%, LND3 2.5%). For pT2, pT3, and pT4 stages, LN metastasis rates were 16.2% (LND1 11.3%, LND2 3.8%, LND3 1.3%), 39.7% (LND1 28.9%, LND2 8.4%, LND3 2.4%), and 50% (LND1 25%, LND2 25%), respectively. Tumor invasion depth and lymphovascular invasion were identified as significant risk factors for LN metastasis extending to LND2-3. Complete mesocolic excision should be considered for right-sided colon cancer because tumor infiltration deeper than SM2 could metastasize to LND2 or further. If preoperative endoscopy confirms SM1 or SM2 invasion, D2 lymphadenectomy could be a limited surgical option.

Resection of Early Colorectal Neoplasms Using Endoscopic Submucosal Dissection: A Retrospective Multicenter Cohort Study.

Background: Endoscopic submucosal dissection (ESD) is a reliable method that can replace surgery in the treatment of early colorectal cancer under certain conditions. Aim: The aim of the study was to analyze factors influencing the ESD procedure in early colorectal cancer, with the intention of improving its effectiveness. Patients and Methods: We conducted a multicenter, retrospective cohort study on 214 patients who underwent ESD procedures for early colorectal cancer from January 2016 to October 2023. Results:En bloc resection was achieved in 197 (92.1%) of ESD procedures, R0 resection in 149 (69.6%), and curative resection in 54 (40.9%). The submucosal invasion was classified as level 1 (SM1) in 96 cases (45.3%), level 2 (SM2) in 61 cases (28.8%), and level 3 (SM3) in 36 cases (17%). R0 resection was achieved more often in the rectum-92 (81.4%), compared to the right-24 (64.9%) and left colon-33 (61.1%), p = 0.009. In rectal tumors, R0 resection was achieved in 51 (98.1%) SM1 invasion, 27 (73%) SM2 invasion, and 13 (65%) SM3 invasion (p < 0.001). Lateral and vertical resection margins were positive in 12 (7.7%) and 52 (25.2%) cases, respectively. Vertical resection margins were statistically more often positive in lesions located in the right colon-11 cases (28.9%) and left colon-21 cases (38.9%), than in rectum-20 cases (17.5%); p = 0.010. Complications were found in 32 (15%) cases of ESD procedure-perforation in 12 cases (5.6%) and delayed bleeding in four cases (1.9%). Procedures performed in the right colon were associated with a significantly higher risk of any complications (30%) and perforations (15%) than those performed in the rectum (10.3% and 2.6%) or the left colon (13.8% and 5.2%; p = 0.016; p = 0.015), respectively. Conclusions: ESD for early colon cancer is a viable strategy due to its effectiveness and low complication rate. The ESD technique performed in the rectum yields the best results; however, in the right colon, it still requires careful attention.

Risk Factors of Lymph Node Metastasis and Prognosis in 891 Chinese Patients With Submucosal Early Gastric Carcinoma, Emphasizing Differences Between Gastric Cardiac and Noncardiac Origins.

Differences in risk factors (RF) of lymph node metastasis (LNM) and prognosis between submucosal early gastric cardiac (SEGCC) and noncardiac (SEGNCC) carcinomas remain unclear. In this study, we investigated and compared RF of LNM and prognosis in 891 patients with radical gastrectomy for SEGCC (n=217) or SEGNCC (n=674). Compared with SEGNCC, SEGCC displayed significantly higher proportion of elderly patients (70y or above), the elevated macroscopic type, well/moderately differentiated tubular and low-grade papillary adenocarcinomas, as well as low-grade tumor budding, but lower prevalence of the depressed macroscopic type, poorly differentiated tubular adenocarcinoma, mixed adenocarcinoma, poorly cohesive carcinoma, lymphovascular invasion (LVI), perineural invasion, and high-grade tumor budding. By univariate analysis, significant RF for LNM of the cohort included female sex, poor differentiation, SM2 invasion, LVI, intermediate-grade and high-grade tumor budding, whereas tumor size, histology type, and perineural invasion were the significant RF for LNM in SEGNCC. By multivariate analysis, significant independent RF for LNM included female sex and LVI in SEGCC but were female sex, mixed adenocarcinoma, LVI, and high-grade tumor budding in SEGNCC. The 5-year overall survival was significantly worse in SEGCC than in SEGNCC for patients with LNM, but not for those without. For overall survival, LNM was the only significant independent RF in SEGCC, whereas age 70 years or above and LNM were independent RF in SEGNCC. The results of our study provided the clinicopathologic evidence for individualized clinical management strategies for these 2 groups of patients and suggested different pathogenesis mechanisms between SEGCC and SEGNCC.

Early Gastric Cancers in Central Norway 2001 to 2016-A Population-Based Study.

Early gastric cancers (EGCs) are confined to the gastric mucosa and submucosa irrespective of lymph node metastases and constitute only a minor proportion of gastric cancer in Western countries. We aimed to characterize EGCs and assess the survival of EGC in Central Norway during 2001-2016. A retrospective population-based study on 1205 patients with gastric cancer was performed. At the time, surgical resection was the standard treatment, and 88 (7.3%) EGCs were identified. Histopathological specimens were re-examined, and the eCura score and survival were evaluated. The number of gastric cancers declined (p = 0.010), but the relative proportion of EGC was unchanged during the study period. EGCs were more often of the Lauren intestinal type (p < 0.001) compared with controls. A significant proportion (9.4%, n = 5) of the patients with a low-risk eCura had lymph node metastases, whereas further exclusion of tumors with histological ulceration or SM2 invasion identified an N0 cohort. The median survival for EGC patients was 117.1 months (95% CI 99.8-134.3) and the 5-year overall survival was 75%. Twelve deaths were cancer-related, either due to postoperative complications (5.7%, n = 5) or cancer recurrence (8%, n = 7). In conclusion, EGCs constituted a minor but constant proportion of gastric cancers. eCura alone was insufficient in predicting patients with pN0 disease.

A Nomogram for Predicting Extraperigastric Lymph Node Metastasis in Patients With Early Gastric Cancer.

There are no clear guidelines to determine whether to perform D1 or D1+ lymph node dissection in early gastric cancer (EGC). This study aimed to develop a nomogram for estimating the risk of extraperigastric lymph node metastasis (LNM). Between 2009 and 2019, a total of 4,482 patients with pathologically confirmed T1 disease at 6 affiliated hospitals were included in this study. The basic clinicopathological characteristics of the positive and negative extraperigastric LNM groups were compared. The possible risk factors were evaluated using univariate and multivariate analyses. Based on these results, a risk prediction model was developed. A nomogram predicting extraperigastric LNM was used for internal validation. Multivariate analyses showed that tumor size (cut-off value 3.0 cm, odds ratio [OR]=1.886, P=0.030), tumor depth (OR=1.853 for tumors with sm2 and sm3 invasion, P=0.010), cross-sectional location (OR=0.490 for tumors located on the greater curvature, P=0.0303), differentiation (OR=0.584 for differentiated tumors, P=0.0070), and lymphovascular invasion (OR=11.125, P<0.001) are possible risk factors for extraperigastric LNM. An equation for estimating the risk of extraperigastric LNM was derived from these risk factors. The equation was internally validated by comparing the actual metastatic rate with the predicted rate, which showed good agreement. A nomogram for estimating the risk of extraperigastric LNM in EGC was successfully developed. Although there are some limitations to applying this model because it was developed based on pathological data, it can be optimally adapted for patients who require curative gastrectomy after endoscopic submucosal dissection.

Adjuvant Radiotherapy Improves Survival for T1b Superficial Esophageal Cancer with Lymphovascular Invasion after Endoscopic Resection

<h3>Purpose/Objective(s)</h3> Several studies, including the multicenter prospective trial JCOG 0508, have reported a higher risk of recurrence in patients with pT1b esophageal carcinoma (EC) with lymphovascular invasion (LVI) after endoscopic resection (ER). The role of adjuvant radiotherapy in this population has not been fully proven. Thus, the aim of this study was to investigate the effectiveness of adjuvant radiotherapy for T1b EC with LVI. <h3>Materials/Methods</h3> This was a multicenter retrospective study including 6 centers in China. From May 2011 to March 2019, patients with T1b EC and LVI who underwent ER with or without radiotherapy were included and analyzed. The overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method, and the log-rank test was used to analyze differences between the groups. Factors between different groups were compared using chi square test. <h3>Results</h3> A total of 42 patients were included, including 37 (88.1%) males and 5 (11.9%) females. The median age was 60 (49-80) years old. Forty (95.2%) patients were squamous cell carcinoma, and two (4.8%) were adenosquamous cell carcinoma. The number of patients with tumor of SM1 and SM2 invasion were 10 (23.8%) and 32 (76.2%), respectively. The median lesion length was 3.0 cm. Thirty-six (85.7%) Patients underwent complete ER and six (14.3%) patients were with R1 resection. Sixteen (38.1%) patients received adjuvant radiotherapy, including two received chemoradiotherapy. The factors mentioned above were well balanced between radiotherapy and non-radiotherapy groups. The median survival in the radiotherapy vs. non-radiotherapy groups were not reached vs. 80.4 months, respectively. The 3y- and 5y-OS were 91.7% and 91.7% in the radiotherapy group vs. 80.8% and 58.9% in the non-radiotherapy group, respectively (p=0.045). The median DFS time in the radiotherapy vs. non-radiotherapy groups was not reached vs. 43.8 months, respectively. The 3y- and 5y-DFS were 92.9% and 92.9% in the radiotherapy group vs. 69.2% and 43.5% in the non-radiotherapy group, respectively (p=0.011). Radiotherapy was the only prognostic factor for both OS and DFS. <h3>Conclusion</h3> Adjuvant radiotherapy improved the survival of patients with T1b EC with LVI after ER. This combined treatment strategy could cure T1b-LVI EC while preserving the esophagus.

The Risk Analyses of Lymph Node Metastasis and Recurrence for Submucosal Invasive Colorectal Cancer: Novel Criteria to Skip Completion Surgery.

Simple SummaryCompletion surgery is recommended for patients with submucosal invasive colorectal cancer (pT1 CRC) with known risk factors for lymph node metastasis (LNM). However, completion surgery would be able to be skipped for more of the population with very low risk for LNM and recurrence. The present study thus analyzed both short- and long-term outcomes for high-risk pT1 CRC patients who underwent surgery, showing that lymphovascular invasion was a potential independent risk factor for LNM, and rectal cancer and undifferentiated histology were independent risk factors for poor relapse-free survival in patients with high-risk pT1 CRC. No LNMs were observed in pT1 CRCs with an SM invasion depth ≤2000 µm that had no other risk factors except for budding. Based on the results, novel criteria to skip completion surgery for high-risk pT1 CRC have been established in the current study, which were also validated in an independent validation cohort.(1) Background: Additional surgical resection after endoscopic resection (ER) is recommended for patients with submucosal invasive colorectal cancer (pT1 CRC) who have risk factors for lymph node metastasis (LNM) (high-risk pT1 CRC). This study aimed to identify risk factors for LNM and metastatic recurrence and to determine the low-risk population for whom additional surgery can be omitted among high-risk pT1 CRCs. (2) Methods: We retrospectively identified 404 patients with pT1 CRC who underwent ER or surgery, and patients were divided into three groups: low-risk (n = 79); high-risk pT1 with ER (n = 40); and high-risk with surgery (n = 285). We also enrolled another 64 patients with high-risk pT1 CRC in an independent validation cohort. (3) Results: In the high-risk with surgery group, LNM was seen in 11.2%, and vascular and lymphatic invasions were significantly independent risk factors for LNM on multivariate analysis. No LNMs were observed in pT1 CRCs with a negative vertical margin and SM invasion depth ≤2000 µm that had no other risk factors except for budding. Five patients developed metastatic recurrence in the high-risk with surgery group, and rectal cancer and undifferentiated histology were significantly independent risk factors for poor relapse-free survival. No LNM or recurrent cases were seen in high-risk pT1 CRCs that met these criteria: differentiated adenocarcinoma, no lymphovascular invasion, colon cancer, SM invasion depth ≤2000 μm, and a negative vertical margin, which were validated in an independent validation cohort. (4) Conclusions: Completion surgery may be skipped for high-risk pT1 CRCs that meet our proposed criteria.

Long-term outcomes of esophageal squamous cell carcinoma with invasion depth of pathological T1a-muscularis mucosae and T1b-submucosa by endoscopic resection followed by appropriate additional treatment.

Endoscopic resection (ER) is indicated for a wide range of superficial esophageal squamous cell carcinomas (ESCCs). We examined the long-term outcomes in patients with pathological (p) invasion of ESCC into the T1a-muscularis mucosae (MM) and T1b-submucosa (SM) after ER, for which data on prognosis are limited. Of the 1217 patients with superficial ESCC who underwent ER, 225 patients with a pathological diagnosis of ESCC invasion into the MM, minute submucosal invasion ≤200 µm (SM1), or massive submucosal invasion (SM2) were included. In patients with lymphovascular invasion, droplet infiltration, or SM2 invasion, additional treatments, including chemoradiation (CRT) or esophagectomy with two- to three-field lymph node dissection, were recommended. The median observation period was 66 months (interquartile range 48-91 months). In total, there were 151, 28, and 46 pT1a-MM, pT1b-SM1, and pT1b-SM2 cases, respectively. Metastatic recurrence was observed in 1.3%, 10.7%, and 6.5% patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Of the eight patients with metastatic recurrence, six were successfully treated, and two died of ESCC. The 5-year overall survival rates were 84.1%, 71.4%, and 67.4%, the 5-year relapse-free survival rates were 82.8%, 64.3%, and 65.2%, and the 5-year disease-specific survival rates were 100%, 96.4%, and 99.1% in patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Multivariate analysis showed that additional CRT and esophagectomy, and T1b-SM2 were positively and negatively associated with overall survival, respectively. Endoscopic resection preceding appropriate additional treatments resulted in favorable outcomes. Many cases of metastatic recurrence in this cohort could be successfully treated.

305 RISK OF GENERALIZATON IN PATIENTS WITH HIGH-RISK EARLY ESOPHAGEAL CANCER: RETROSPECTIVE ANALYSIS OF PROSPECTIVELY COLLECTED DATA INCLUDING LYMPH-NODE MICROMETASTASES ASSESSMENT

Abstract Esophagectomy is a standard of care for patients with "high-risk" early esophageal cancer (HRC) despite a growing evidence that endoscopic treatment may be a safe alternative. Our aims were 1. to prospectively evaluate the long-term results of endoscopic and surgical treatments in consecutive patients with HRC and 2. to determine the risk of lymph node (LN) metastases and micrometastases in patients with HRC. Methods HRC was defined as any cancer with submucosal (sm) invasion or mucosal cancer with at least one of the following: poor differentiation, invasion to blood or lymphatic vessels and high tumor cell dissociation (TCD3). All patients (n = 69) underwent endoscopic resection (ER or ESD) and after the histopathological diagnosis of HRC, patients without contraindications were referred to surgery (n = 30). The remaining patients (n = 39) continued in endoscopic treatment, if necessary. All resected LNs were stained for hematoxylin–eosin to evaluate metastases and immunohistochemistry was used for the detection of micrometastases or isolated tumor cells. Results Eighteen patients (26%) had T1a and 51 (74%) had T1b cancer; 51 had adenocarcinoma (AC) and 18 had squamous cell carcinoma (SCC). The median follow-up was 32 months (3–120). No patient with mucosal invasion (15 AC, 3 SCC) experienced LN involvement. Among 17 patients with sm1 invasion, only 2 (12%, both AC)experienced generalization or LN involvement. The further rates of LN involvement were 0% (0/5) in sm2 AC, 50% (3/6) in sm2 SCC, 25% (4/16) in sm3 AC and 29% (2/7) in sm3 SCC. 60% (18/30) of surgically treated patients would have been completely cured by endoscopy (Table 1). Conclusion The risk of LN metastases/micrometastases was lower than expected. No patients with high-risk mucosal cancer or low-risk sm1 cancer experienced lymph node involvement. Endoscopic treatment provided long-term remission (or cure) in considerable number of patients and it may represent a valid alternative to surgery in patients with high-risk early esophageal cancer.

390 STRATEGY FOR TREATMENT OF EARLY ADENOCARCINOMA (T1) OF THE ESOPHAGOGASTRIC JUNCTION ACCORDING TO LYMPH NODE METASTASIS STATUS AND VASCULAR INVASION

Abstract Incidence of adenocarcinoma of the esophagogastric junction is increasing in Japan. However, in early cases (T1), there is no consensus on treatment strategy. The purpose of this study was to determine the optimal range of resection and lymph node dissection according to lymph node metastasis status and vascular invasion in early adenocarcinoma (T1) of the esophagogastric junction. Methods We investigated patient characteristics, surgical procedures, recurrence pattern, and optimum extent of lymph node dissection in 22 patients who underwent surgery in our hospital from 2000 to 2016 and were diagnosed with early adenocarcinoma of the esophagogastric junction (by Nishi’s classification). Results Four patients with lymph node metastasis, the depth of invasion was sm2 and lymphatic invasion was positive (ly1–ly3, focal lymphatic invasion to prominent lymphatic invasion). In all cases, the site of lymph node metastasis was the lesser gastric curvature. None of the patients developed postoperative lymph node recurrence. An examination of the outcomes revealed that the metastases were hematogenous in all patients with a depth of invasion of sm2 and a positive venous invasion (v1, focal vascular invasion). Conclusion We conclude that transhiatal esophagectomy should be selected as a minimal requirement, and that dissection of the abdominal lymph node (particularly on the lesser curvature side of the superior part of the stomach) is sufficient, for patients with early adenocarcinoma of the esophagogastric junction. In cases where the depth of invasion is sm2 or greater and vascular invasion is present, patients may require adjuvant therapy regardless of lymph node metastasis status.

Clinical Outcome of Additional Esophagectomy After Endoscopic Treatment for Superficial Esophageal Cancer

Endoscopic treatment is one of the options for superficial esophageal cancer, but additional therapy such as esophagectomy or chemoradiotherapy (CRT) is sometimes needed due to noncurative resection. However, the outcome of additional therapy after endoscopic treatment has not been fully evaluated. In 160 patients with superficial esophageal cancer, including 37 patients who underwent esophagectomy and 123 patients who underwent CRT after noncurative endoscopic resection, outcomes were investigated. The CRT group included more elderly patients than the surgery group, although there were no significant differences in tumor depth or lymphovascular invasion between the two groups. Overall survival was significantly better in the surgery group than in the CRT group (5-year overall survival: 94.3% vs. 79.9%; p = 0.039). Two (5.4%) patients in the surgery group who developed lymph node recurrence achieved complete response by chemotherapy or CRT, and 9 of 16 patients (13.0%) in the CRT group who developed recurrence underwent salvage esophagectomy or lymphadenectomy. As a result, the 5-year cause-specific survival was 100% in the surgery group and 92.8% in the CRT group. SM2 invasion (≥ SM2) was significantly associated with recurrence after CRT, while lymphatic invasion was associated with lymph node metastasis in the surgery group. Endoscopic treatment combined with esophagectomy or CRT can be a curative treatment option in patients with superficial esophageal cancer. However, esophagectomy rather than CRT should be recommended for patients with massive submucosal tumor invasion due to the risk of recurrence after CRT.

Risk of Lymph Node Metastasis and Feasibility of Endoscopic Treatment in Ulcerative Early Gastric Cancer

BackgroundWhen the risk of lymph node metastasis (LNM) is considered minimal in patients with early gastric cancer (EGC), endoscopic submucosal dissection (ESD) is an effective alternative to radical resection. This study aims to estimate the feasibility of ESD for EGC with ulceration.Patients and MethodsWe retrospectively reviewed data from 691 patients who underwent gastrectomy for EGC with ulceration. Subsequently, a stratification system for lesions was created based on the expanded ESD criteria, and the associations between the subgroups and the rate of LNM were analyzed.ResultsLNM was confirmed in 16.5% (114/691) of patients. Univariate analysis demonstrated that age, sex, tumor size, macroscopic features, depth of invasion, tumor differentiation, Lauren type, lymphovascular invasion (LVI), and perineural invasion were associated with LNM. Multivariate analysis showed that LVI [odds ratio (OR) = 16.761, P < 0.001], SM1 invasion (OR = 2.159, P = 0.028), and SM2 invasion (OR = 3.230, P < 0.001) were independent risk factors for LNM. LNM occurred in undifferentiated mucosal tumors, with ulceration being 1.7% (2/116) when the lesion was smaller than 20 mm. Further stratification revealed that among lesions < 30 mm in size, undifferentiated tumors with SM1 invasion had a higher rate of LNM and a lower disease-free survival rate than differentiated tumors with SM1 invasion and tumors limited to the mucosal layer.ConclusionsDepth of invasion and LVI were strongly associated with LNM in ulcerative EGC. Endoscopic resection may be applicable for undifferentiated mucosal ulcerative EGC < 30 mm in size, and additional investigation is needed to evaluate its safety.

Very low risk of lymph node metastasis in Epstein-Barr virus-associated early gastric carcinoma with lymphoid stroma

BackgroundEpstein-Barr virus-associated early gastric carcinoma with lymphoid stroma (EBV-GCLS) is a rare variant of early gastric carcinomas. Clinicopathological features of this variant remain obscure, especially in Chinese patients. Therefore, we collected EBV-GCLS cases and studied clinicopathology and prognosis.MethodsBy a retrospective review of 595 consecutive radical gastrectomies for early gastric carcinoma from 2006 to 2018, we identified 8 (1.3%, 8/595) EBV-GCLS cases. Clinicopathologic characteristics were compared between EBV-GCLSs and 109 conventional early gastric carcinomas, which were divided into intramucosal, SM1, and SM2 subgroups. The latter 2 subgroups were classified according to the submucosal invasion depth below or over 500 μm.ResultsAll 8 EBV-GCLSs occurred in male patients and invaded deep submucosa (SM2) without lymph node metastasis (LNM), four (50%) of which had synchronous non-gastric malignant tumors (3 gastric gastrointestinal stromal tumors and 1 primary clear cell renal cell carcinoma), and four (50%) arose in the proximal stomach. Compared to conventional early gastric carcinomas, EBV-GCLS was significantly more frequent with SM2 invasion, poor differentiation, and synchronous non-gastric carcinoma tumor, but not with age, gender, macroscopic type, location, size, perineural invasion, lymphovascular invasion, and pathologic stage. In invasion-depth stratified comparisons in the SM2 subgroup, the frequency of LNM in EBV-GCLS was significantly lower than that in conventional early gastric carcinomas (p < 0.05) and the 5-year survival rate of patients with EBV-GCLS was better than that with conventional early gastric carcinomas in 3 subgroups (100% vs 91.5, 85.7, 83.9%, respectively), although the differences did not reach a statistically significant level due to the small sample size. Significant differences among 4 subgroups were found in tumor grade, lymphovascular invasion, LNM, pathological stage, and synchronous tumor, but not in age, gender, macroscopic type, tumor size, location, perineural invasion.ConclusionsEven with poor differentiation and SM2 invasion, EBV-GCLS showed very low risk of LNM and may be a candidate for endoscopic therapy such as endoscopic submucosal dissection.

Clinicopathological features and risk factors for lymph node metastasis in early-stage non-ampullary duodenal adenocarcinoma.

Management strategies for primary non-ampullary duodenal adenocarcinoma (NADAC) in early stage are not well established given its low incidence. This study aimed to elucidate clinicopathological features of early NADAC, including risk for lymph nodal metastasis (LNM). In total, 166 patients with early NADAC underwent initial treatment at our institution between 2006 and 2019, of whom 153 had intramucosal (M-) and 13 had submucosal (SM-) NADAC. These endoscopic and pathological features were retrospectively analyzed. Risk factors for LNM were evaluated in 46 early NADAC patients who underwent surgery with lymph node dissection. Compared with M-NADAC, SM-NADAC was significantly more frequently located at the proximal side of the papilla, with mixed elevated and depressed macroscopic type, histologically poorly differentiated tumor and lymphovascular invasion (LVI) (85% vs. 47%, P = 0.009; 54% vs. 5%, P < 0.001; 23% vs. 0%, P < 0.001; and 46% vs. 0%, P < 0.001, respectively). The frequency of LNM was significantly higher in SM-NADAC than in M-NADAC (5/12, 42% vs. 0/34, 0%; P < 0.001). In SM-NADAC, the frequency of LNM was higher in poorly differentiated than in well to moderately differentiated tumors (3/3, 100% vs. 2/9, 22%) and higher in tumors with LVI than in those without LVI (3/5, 60% vs. 2/7, 29%). Regarding invasion depth, 2 of 4 patients with SM invasion (400 ≤ × < 500µm) showed LNM. However, in this study, no patients developed very shallow SM invasion (0 < × < 400µm). SM-NADAC showed high LNM risk. Surgical treatment with regional lymph node dissection is recommended as a treatment strategy for SM-NADAC.

Predictors of Lymph Node Metastasis and Differences Between Pure and Mixed Histologic Types of Early Gastric Signet-ring Cell Carcinomas.

The aim of this study was to investigate predictors of lymph node metastasis (LNM) in early gastric signet-ring cell carcinoma (SRCC) and determine clinicopathologic and prognostic differences of different histologic subtypes. We retrospectively analyzed 13,661 gastric cancer patients; 231 were eligible for inclusion. Data for clinical, endoscopic, and histopathologic characteristics and prognoses were collected. Patients were followed up regarding postresection survival; overall and disease-specific survival rates were estimated by the Kaplan-Meier method with a log-rank test, and prognostic factors were evaluated by Cox regression. LNM incidence in early SRCC was 16.0% (37/231) overall: 6.9% (8/116) and 25.2% (29/115) in patients with pure and mixed SRCC, respectively. Univariate and multivariate analyses revealed SM2 invasion (odds ratio [OR]=5.070, P=0.003), lymphovascular invasion (LVI) (OR=14.876, P<0.001), pathologic pattern of mixed SRCC (OR=3.226, P=0.026), ulcer presence (OR=3.340, P=0.019) and lesion size over 20 mm (OR=2.823, P=0.015) as independent risk factors for LNM. Compared with pure SRCC, the mixed subtype was associated with older age, larger lesion size, higher LVI frequency, more frequent perineural invasion, and most importantly, higher LNM incidence. Patients with pure SRCC showed significantly longer overall survival (P=0.004) and disease-specific survival (P=0.002) than mixed SRCC patients. Pathologic subtype (hazard ratio [HR]=3.682; P=0.047), age (HR=5.246; P=0.001), SM1 invasion (HR=6.192; P=0.023), SM2 invasion (HR=7.529; P=0.021) and LNM (HR=5.352; P<0.001) were independent prognostic factors. Independent risk factors for LNM in early gastric SRCC were SM2 invasion, LVI, pathologic pattern, ulcer presence and lesion size over 20 mm. Early SRCC should be further classified by the purity of the SRC component.

The management and long-term outcomes of endoscopic and surgical treatment of early esophageal adenocarcinoma.

Endoscopic resection (ER) for early (pT1) esophageal adenocarcinoma can be justified if the rate of coexisting lymph node (LN) metastasis is less than the mortality rate from esophagectomy. This study examines endoscopic and surgical outcomes, histological assessment of submucosal (sm) disease, factors influencing LN metastasis, and the safety of treating pT1b disease endoscopically. Histopathological reexamination recorded thickness, width and depth of sm invasion, grade, presence of lymphovascular invasion (LVI), resection margin status and tumor stage. Multivariate analysis was employed to evaluate the factors influencing survival and LN metastasis. Rate of LN metastasis for pT1 low-risk (LR: sm invasion < 500μm, G1-2, no LVI) or high-risk (HR: sm invasion >500μm, G3-4 or LVI) disease were analyzed. Ninety three patients underwent ER and 96 underwent esophagectomy. We demonstrate conflicting histological methods of sm disease reporting, which may explain the difference in LN metastasis rate between reported surgical & endoscopic series. Multivariate analysis confirmed age, T stage, and presence of LN metastases were the independent factors predicting poor prognosis. Tumor thickness as well as grade, T stage, LVI were predictors of LN metastasis. Rates of LN metastasis are <2% in LR sm1 disease, and >15% in HR sm1 disease. Pathological reporting of sm invasion should be updated for uniform analysis of endoscopic and surgical specimens. Following rigorous histopathological examination and within a close endoscopic follow-up regimen, pT1a and pT1b LRsm1 disease may be treated with curative intent endoscopically, whereas pT1b HRsm1-sm3 disease should be offered surgery.

Infiltration Depth is the Most Relevant Risk Factor for Overall Metastases in Early Esophageal Adenocarcinoma.

Research in early esophageal adenocarcinoma focused on prediction of lymph node metastases in order to stratify patients for endoscopic treatment instead of esophagectomy. Although distant metastases were described in rates of up to 13% of patients within a follow-up of 3years, their prediction has been neglected so far. In a secondary analysis, a cohort of 217 patients (53 T1a and 164 T1b) treated by esophagectomy was analyzed for histopathological risk factors. Their ability to predict the combination of lymph node metastases at surgery as well as metachronous locoregional and distant metastases (overall metastatic rate) was assessed by uni- and multivariate logistic regression analysis. Tumor invasion depth was correlated with both lymph node metastases at surgery (τ = 0.141; P = .012), tumor recurrences (τ = 0.152; P = .014), and distant metastases (τ = 0.122; P = 0.04). Multivariate analysis showed an odds ratio of 1.31 (95% CI 1.02-1.67; P = .033) per increasing tumor invasion depth and of 3.5 (95% CI 1.70-6.56; P < .001) for lymphovascular invasion. The pre-planned subgroup analysis in T1b tumors demonstrated an even lower predictive ability of lymphovascular invasion with an odds ratio of 2.5 (95% CI 1.11-5.65; P = 0.028), whereas the predictive effect of sm2 (odds ratio 3.44; 95% CI 1.00-11.9; P = 0.049) and sm3 (odds ratio 3.44; 95% CI 1.00-11.9; P = 0.049) tumor invasion depth was similar. The present report demonstrates the insufficient risk prediction of histopathologic risk factors for the overall metastatic rate.

Nomogram for prediction of lymph node metastasis in patients with superficial esophageal squamous cell carcinoma.

Knowledge of lymph node metastasis (LNM) status is crucial to determine whether patients with superficial esophageal squamous cell carcinoma (ESCC) can be cured with endoscopic resection alone, without the need for additional esophagectomy. The present study aimed to identify predictive factors and develop a prediction model for LNM in patients with superficial ESCC. Clinicopathologic data from 501 patients with superficial ESCC treated with radical esophagectomy were reviewed. Stepwise logistic regression analysis determined the predictors of LNM. Using these predictors, a nomogram for predicting the risk of LNM was constructed and internally validated using a bootstrap resampling method. LNM rates of tumors invading the lamina propria, muscularis mucosa, and SM1 layers were 3.7%, 15.5%, and 40.7%, respectively. Deep tumor invasion depth, moderately or poorly differentiated histology, and lymphovascular invasion were independent predictors of LNM. ESCC with muscularis mucosa and SM1 invasion had odds ratios of 3.635 and 11.834, respectively, compared with that for ESCC confined to the lamina propria. Large tumor size (>2.0cm) and presence of tumor budding showed borderline significance for LNM prediction. These five variables were incorporated into a nomogram. A constructed nomogram showed good calibration and good discrimination with an area under the receiver-operating characteristic curve (area under the curve [AUC]) of 0.812. After bootstrapping, AUC was 0.811. We developed a nomogram that can facilitate individualized prediction of risk of LNM in patients with superficial ESCC. This model can aid in decision-making for the need for additional esophagectomy after endoscopic resection for superficial ESCC.

Endoscopic Ultrasonography Miniature Probe Performance for Depth Diagnosis of Early Gastric Cancer with Suspected Submucosal Invasion.

Background/AimsThe accurate assessment of the depth of invasion of early gastric cancer (EGC) is critical to determine the most appropriate treatment option. However, it is difficult to distinguish shallow submucosal (SM1) invasion from deeper submucosal (SM2) invasion. We investigated the diagnostic performance of endoscopic ultrasonography (EUS) using a miniature probe for EGC with suspected SM invasion.MethodsFrom April 2008 to June 2018, EGCs with suspected SM invasion were analyzed retrospectively. The EGCs examined by a 20 MHz high-frequency miniature probe was included in our study. Esophago-gastric junction cancers and patients treated by chemotherapy before resection were excluded. The sensitivity and specificity for the detection of SM2 invasion by EUS were compared with those of white light imaging (WLI). Additionally, factors related to depth underestimation or overestimation were investigated using multivariate analysis.ResultsA total of 278 EGCs in 259 patients were included in the final analysis. The sensitivity and specificity for SM2 or deeper by EUS were 73.7% (87/118) and 74.4% (119/160), respectively. The sensitivity and specificity by WLI were 47.5% (56/118) and 68.1% (109/160), respectively. The sensitivity of EUS was significantly superior to that of conventional endoscopy (p<0.01). Multivariate analysis revealed that an anterior location of the EGC was an independent risk factor for underestimation by EUS (odds ratio, 3.3; 95% confidence interval, 1.1 to 9.8; p=0.03).ConclusionsThe depth diagnostic performance for EGCs with suspected SM invasion using EUS was satisfactory and superior to that of conventional endoscopy. Additionally, it is important to recognize factors that may lead to misdiagnosis in those lesions.

Feasibility of endoscopic treatment and predictors of lymph node metastasis in early gastric cancer.

BACKGROUNDEndoscopic submucosal dissection (ESD) has been routinely performed in applicable early gastric cancer (EGC) patients as an alternative to conventional surgical operations that involve lymph node dissection. The indications for ESD have been recently expanded to include larger, ulcerated, and undifferentiated mucosal lesions, and differentiated lesions with slight submucosal invasion. The risk of lymph node metastasis (LNM) is the most important consideration when deciding on a treatment strategy for EGC. Despite the advantages over surgical procedures, lymph nodes cannot be removed by ESD. In addition, whether patients who meet the expanded indications for ESD can be managed safely remains controversial.AIMTo determine whether the ESD indications are applicable to Chinese patients and to investigate the predictors of LNM in EGC.METHODSWe retrospectively analyzed 12552 patients who underwent surgery for gastric cancer between June 2007 and December 2018 at the Affiliated Hospital of Qingdao University. A total of 1262 (10.1%) EGC patients were eligible for inclusion in this study. Data on the patients’ clinical, endoscopic, and histopathological characteristics were collected. The absolute and expanded indications for ESD were validated by regrouping the enrolled patients and determining the positive LNM results in each subgroup. Predictors of LNM in patients were evaluated by univariate and multivariate analyses.RESULTSLNM was observed in 182 (14.4%) patients. No LNM was detected in the patients who met the absolute indications (0/90). LNM occurred in 4/311 (1.3%) patients who met the expanded indications. According to univariate analysis, LNM was significantly associated with positive tumor marker status, medium (20-30 mm) and large (>30 mm) lesion sizes, excavated macroscopic-type tumors, ulcer presence, submucosal invasion (SM1 and SM2), poor differentiation, lymphovascular invasion (LVI), perineural invasion, and diffuse and mixed Lauren’s types. Multivariate analysis demonstrated SM1 invasion (odds ration [OR] = 2.285, P = 0.03), SM2 invasion (OR = 3.230, P < 0.001), LVI (OR = 15.702, P < 0.001), mucinous adenocarcinoma (OR = 2.823, P = 0.015), and large lesion size (OR = 1.900, P = 0.006) to be independent risk factors.CONCLUSIONThe absolute indications for ESD are reasonable, and the feasibility of expanding the indications for ESD requires further investigation. The predictors of LNM include invasion depth, LVI, mucinous adenocarcinoma, and lesion size.