Significant Risk Factors For Lymph Node Metastasis Research Articles

Papillary thyroid microcarcinoma with and without nodal metastasis: A comparative analysis.

To assess the demographics and clinical factors of papillary thyroid microcarcinoma (PTMC) patients in Saudi Arabia and compared and analyzed the differences between the patients with and without lymph node metastasis (LNM). Papillary thyroid microcarcinoma (PTMC) is a common thyroid cancer and is not usually detectable clinically but found incidentally after pathologic evaluation of thyroid tissue following surgery for benign thyroid disorders. However, these tumors have a significant risk of LNM. All PTMC patients who underwent surgery at King Abdulaziz University Hospital, King Fahad Medical City, and King Abdulaziz Medical City from 2012 to 2022 were included. The incidence rate of LNM was 9.17%. The patients' average age was 44.05. Most of the patients were female. Prevalence of LNM among PTMC patients is 9.17% (n=31). The PTMC patients showed the following significant risk factors for LNM: higher Bethesda class, type of pathology, extrathyroidal extension, extracapsular extension, lymphovascular invasion, and residual tumors in patients who had received radioactive iodine. Presence of thyroiditis, multifocality, goitrous thyroid, neural invasion, and tumor size were unrelated to the LNM in the PTMC patients. Higher Bethesda class, pathology type, extrathyroidal extension, extracapsular extension, lymphovascular invasion, and RAI-treated residual tumors were strongly linked to LNM.

The Impact of Total Tumor Diameter on Lymph Node Metastasis and Tumor Recurrence in Papillary Thyroid Carcinomas

(1) Introduction: The impact of multifocality/bilaterality on the prognosis of papillary thyroid carcinoma (PTC) is a matter of debate. In order to clarify this debate, several studies have attempted to identify additional parameters associated with poor prognosis, including total tumor diameter (TTD), in the context of multifocal PTCs. In this context, this study was carried out to investigate the impact of TTD on tumor recurrence and lymph node metastasis (LNM) in PTCs. (2) Materials and Methods: The sample of this single-center retrospective study consisted of 706 patients diagnosed with PTC. TTD was calculated as the sum of the largest diameters of tumor foci in multifocal tumors. The resulting TTDs were grouped into TTDs ≤ 10 mm, TTDs > 10 mm, TTDs ≤ 20 mm, and TTDs > 20 mm, using 10 mm and 20 mm as cutoff values. (3) Results: There was no significant difference between multifocal papillary microcarcinomas (PTMCs) with a TTD of >10 mm and unifocal PTCs with a primary tumor diameter (PTD) of >10 mm except for advanced age and lymphovascular invasion (LVI). In addition, perineural invasion (PNI) and TTD > 10 mm were found to be significant risk factors for LNM, and PNI, TTD > 10 mm, TTD > 20 mm, and bilaterality were found to be significant risk factors for recurrence. LVI, and TTD > 10 mm were found to be independent significant predictors for recurrence, and LVI and extrathyroidal extension (ETE) were found to be independent significant predictors for LNM. (4) Conclusions: Considering TTD > 10 mm in recurrence risk categorization models and adopting a clinical approach that takes into account multifocal PTMCs with TTD > 10 mm along with unifocal PTCs with PTD > 10 mm may be more useful in terms of clinical management of the disease.

Feasibility study fulfilling expanded endoscopic resection criteria in mucosal undifferentiated gastric cancer.

The indication of endoscopic submucosal dissection (ESD) for mucosal undifferentiated early gastric cancer (EGC) remains controversial because of risk of lymph node metastasis (LNM). The aim of this study was to identify risk factors for lymph node metastasis (LNM) in mucosal undifferentiated EGC, and further to confirm feasibility of the ESD for the treatment of mucosal undifferentiated EGC. We retrospectively reviewed data of patients who underwent surgical resection with lymph node dissection of T1a stage primary gastric adenocarcinoma at three medical centers between 2012 and 2022. We evaluated the frequency of lymph node metastasis and the associated risk factors, as well as the lymph node metastasis rate in the expanded indication of mucosal undifferentiated EGC. A total of 100 surgically treated patients with mucosal undifferentiated EGC were enrolled. LNM was irrelevant to the age, tumor size, location, and macroscopic type (all P>0.05), while it was significantly associated with lymphovascular invasion (LVI, P ＜0.001). And logistic regression analysis showed that the LVI was the only significant risk factors for LNM (OR: 0.34, 95%CI: 0.06-0.204; P ＜0.001). Of 44 mucosal undifferentiated EGC patients satisfying the expanded indication of ESD, 3 patients (6.8%) showed LN metastasis, all of them with undifferentiated cancer without ulceration, less than 2.0cm in size. Because LNM is present in mucosal undifferentiated EGC patients who satisfied the expanded indication of ESD, ESD cannot be considered a better choice than surgery for all undifferentiated EGC patients. LVI was significant risk factors for LNM in patients with mucosal undifferentiated EGC.

Risk factors for lymph node metastasis in patients with pT2 colon cancer in Denmark from 2016 to 2019-A nationwide cohort study.

The majority of patients with pT2 colon cancer have no lymph node metastasis (LNM). Knowledge of risk factors for LNM in pT2 colon cancer could identify patients at low risk and thereby potential candidates for local tumour excision. The aim of this work was to identify risk factors for LNM in pT2 colon cancer and describe a subgroup of low-risk patients. This is a retrospective cohort study of patients with pT2 colon cancer from a nationwide Danish colorectal cancer database. Age, tumour size, location, histological type, mismatch repair protein status and venous, lymphatic and perineural invasion were included as potential risk factors in multivariate analysis. The primary outcome was LNM. We identified 1306 patients with pT2 colon cancer. LNM was present in 244 (19%). Demographic data were comparable in patients with and without LNM, and 864 patients who had complete histological data were included for multivariate analysis. Lymphatic (OR=3.60, 95% CI 2.14-5.9), venous (OR=1.70, 95% CI 1.03-2.74) and perineural (OR=4.61, 95% CI 1.60-13.5) invasion were independent risk factors for LNM. Patients with deficient mismatch repair protein tumours had a decreased risk of LNM (OR=0.55, 95% CI 0.31-0.95). Patients with clinical Stage I colon cancer and without risk factors had a 10.5% (47/443) risk of LNM. For patients with tumours with deficient mismatch repair protein status and no risk factors, the risk was 7.9%. Lymphatic, venous and perineural invasion are significant risk factors for LNM, and we identified a subgroup of patients with a low risk of LNM.

Risk Factors for Neck Nodal Metastasis in Papillary Thyroid Cancer With BRAF V600E Mutation.

BackgroundThe BRAF V600E mutation is the most common genetic variant in papillary thyroid cancer (PTC), but the relationship between the BRAF V600E mutation in PTC and cervical lymph node metastasis (LNM) remains controversial.ObjectiveTo estimate risk factors for neck nodal metastasis in PTC with BRAF V600E mutation.PatientsA total of 292 patients diagnosed with BRAF V600E mutation related PTC were admitted.DesignIn this retrospective study, data from 292 patients, including clinical, molecular, and ultrasonic characteristics, were analyzed. Univariate and multivariate logistic regression analyses were applied to identify risk factors for LNM in PTC with the BRAF V600E mutation.ResultsIn the univariate analysis of all PTC patients with the BRAF V600E mutation, the LNM was found to be significantly associated with age (P = 0.010), size (P = 0.000), bilaterality (P = 0.000), multifocality (P = 0.002), LNM in ultrasound (US) (P = 0.000), and capsular invasion (P = 0.010). In ultrasonic image characteristics, margin (P = 0.036), shape (P = 0.046), and microcalcification (P = 0.002) were significantly associated with LNM. In multivariate analysis, LNM in PTCs with BRAF V600E mutation was significantly associated with age ≤ 45 years (OR = 1.869, P = 0.020, 95% CI = 1.106 - 3.158), size ≥ 1cm (OR = 3.131, P = 0.001, 95% CI = 1.578 - 6.212), LNM in US (OR = 6.962, P = 0.000, 95% CI = 2.924 - 16.572), bilaterality (OR = 1.626, P = 0.007, 95% CI = 1.142 - 2.314), ill-defined margins in US (OR = 1.980, P = 0.033, 95% CI = 1.057 - 3.709), and microcalcification in US (OR = 2.786, P = 0.002, 95% CI = 1.464 - 5.303).ConclusionThis study revealed that several significant risk factors for LNM in PTCs with the BRAF V600E mutation included: age ≤ 45 years, size ≥ 1cm, LNM in US, bilaterality, ill-defined margins in US, and microcalcification in US.

Risk factors for lymph node metastasis and indication of local resection in duodenal neuroendocrine tumors.

Background and AimThe risk factors for lymph node metastasis (LNM) of duodenal neuroendocrine tumors (DNETs) are not well identified, and a definitive standard of treatment for DNETs has not been established. In this study, we aimed to identify the risk factors for LNM and establish the indication of local resection for DNETs.MethodsWe retrospectively reviewed 55 patients with 60 non‐ampullary and nonfunctional DNETs. We evaluated the risk factors for LNM and compared the outcomes between endoscopic resection (ER) for DNETs <5 mm and laparoscopy and endoscopy cooperative surgery (LECS) for DNETs ≥5 mm.ResultsLNM was present in four (8.7%) patients. Univariate analysis revealed that tumor size ≥10 mm, positive lymphovascular invasion (LVI), and 0‐Is morphology were significantly associated with LNM (P = 0.008, P = 0.037, and P = 0.045, respectively). ER and LECS were performed for 18 and 11 DNETs, respectively. All lesions treated with ER or LECS were confined to the submucosal layer. The median tumor size was 3 mm in ER and 6 mm in LECS. Although there was no significant difference in the R0 (no residual tumor) resection rate, R0 resection was completely achieved in the LECS. No significant differences were observed in terms of complication rates. No recurrence was observed in any of the groups.ConclusionsTumor size ≥10 mm, positive LVI, and 0‐Is morphology were significant risk factors for LNM. We demonstrated that ER is feasible and could be safely applied for DNETs <5 mm, and LECS could be applied for DNETs 5–10 mm in size.

S427 Predictors for Lymph Node Metastasis and Survival of Patients With T1b Esophageal Adenocarcinoma Treated With Surgery and Endoscopic Therapy: An Analysis of Surveillance, Epidemiology, and End Results Database

Introduction: There have been a few population-based studies to compare the long-term outcomes of patients those received surgery versus with endotherapy (ET) for T1b esophageal adenocarcinoma (EAC). In this study, we aimed to determine the risk factors of lymph node metastasis (LNM) and evaluate the long-term survival of patients with T1b EAC who underwent ET or surgery. Methods: We used the Surveillance Epidemiology and End Result database to identify patients with T1b histologically confirmed EAC diagnosed between 2004-2018. Patients were grouped based on whether they received ET (n=185) or surgery (n=935). Prevalence of LNM at initial diagnosis was analyzed. Multivariate logistic regression was performed to identify factors associated with LNM and endoscopic therapy. A Cox proportional hazards model was performed to examine the association of treatment options and survival after controlling for potential confounders. Results: Overall, 16% of cases had LNM at the time of diagnosis. The risk factors for LNM included lesion size ≥20 mm (OR 1.7, 95%CI 1.2-2.4) and poor tumor differentiation (OR 1.6, 95%CI 1.2-2.3). The use of ET increased progressively, from 0.8% in 2008 to 1.6% in 2018. ET was more commonly performed in patients with age >65 yr (OR 2.7, 95%CI 1.5-4.6), tumor size ≤20mm (OR 2.1, 95%CI 1.3-3.7), recent year of diagnosis (2008-2018 vs 2004-2007; OR 3.1, 95%CI 1.7-5.7) and those without LNM. Three-year overall survival was higher in surgery group than in the ET group (65.4% vs 54.4%, p = 0.04). Of 946 patients with T1bN0M0 EAC, 177 underwent ET and 769 had radical surgery. After adjusting for patient and tumor specific factors, patients with T1bN0M0 EAC treated by ET had a worse overall survival outcome (HR 1.4, 95% CI 1.06-1.97, P=0.01) compared to those received surgery. ET and surgery resulted in statistically equivalent in esophageal cancer mortality [HR 0.98, 95%CI 0.62-1.56, P=0.96]. Conclusion: In T1b EAC, tumor size ≥20mm and poor differentiation are the significant risk factors for LNM. Cancer specific survival in patients with T1bN0M0 EAC treated with ET appears to be similar to those treated with surgery. We found that patients who have significant coexisting conditions such as older age, are less likely to undergo surgery, as reflected in our study that older patients were more likely to have ET, which could partly explain higher overall mortality in ET group.Figure 1.: A: In a multivariate Cox proportional hazards model, adjusted for clinical and tumor-related factors, ET was associated with increased cumulative hazard (HR 1.4, 95% CI 1.06-1.97) compared to surgery. B: No difference was noted in cancer specific survival between the treatment groups when adjusted for age, sex, race, tumor size, tumor differentiation, and year of diagnosis.

Risk factors for lymph node metastasis in early gastric cancer without lymphatic invasion after endoscopic submucosal dissection

BackgroundLymphatic invasion (LI) is a potent risk factor for lymph node metastasis (LNM) in early gastric cancer (EGC) after endoscopic submucosal dissection (ESD). However, there are also other risk factors for LNM. Hence, to identify the need for additional surgery in some case of EGC without LI, the present study aimed to identify the risk factors for LNM in patients with EGC without LI. MethodsData from 2284 patients diagnosed with EGC who underwent curative surgery at National Cancer Center in Korea from January 2012 to May 2019 were collected. The clinicopathological characteristics of patients with EGC without LI were compared on the basis of LNM status. ResultsThere were 339 (17.1%) and 1648 (82.9%) patients with and without LI respectively. Among these patients with and without LI, 118 (34.8%) and 91 (5.5%) patients presented with LNM, respectively. In patients with EGC without LI, tumor size larger than 3 cm (OR = 2.12, 95% CI = 1.22–3.68; p = 0.007), submucosal invasion (OR = 4.14, 95% CI = 2.57–6.65; p < 0.001), and undifferentiated histologic type (OR = 2.33, 95% CI = 1.45–3.76; p < 0.001) were significant risk factors for LNM. Rates of LNM in patients meeting absolute, expanded, and beyond expanded criteria without LI were 0%, 1.5% (OR = 3.27, 95% CI = 0.18–59.41; p = 0.423), and 7.3% respectively. When the expanded criteria were divided into four subtypes patients with EGC, without LI within each subtype did not show significant risk of incidence of LNM compared to the absolute criteria. ConclusionsThe current expanded criteria for endoscopic resection (ER) are tolerable in cases without LI, even though minimal risk LNM exists. Therefore, additional surgery may not be needed for patients meeting expanded criteria for ER.

Risk for lymph node metastasis in Epstein-Barr virus-associated gastric carcinoma with submucosal invasion.

Epstein-Barr virus-associated gastric cancer (EBVGC) has been reported to be associated with a low risk for lymph node metastasis (LNM). However, the curative criteria for endoscopic submucosal dissection (ESD) for submucosal EBVGC (pT1b-EBVGC) remain unclear. Our study aimed to investigate the risk factors for LNM in pT1b-EBVGC. This was a retrospective multicenter study at five institutes in Japan. We reviewed medical records and extracted all pT1b-EBVGC cases that met the following criteria: (i) histologically proven submucosal gastric cancer; (ii) surgical or endoscopic resection between January 2000 and December 2016; and (iii) presence of Epstein-Barr virus (EBV) in tumor cells verified by EBV-encoded small RNA in situ hybridization (EBER-ISH). The association between clinicopathological factors and LNM were assessed using multivariable logistic regression analysis. A total of 185 pT1b-EBVGC cases were included in the analysis. LNM was found in nine cases (4.9%). Multivariable logistic regression analysis demonstrated that lymphatic invasion (OR 9.1; 95% CI 2.1-46.1) and submucosal invasion ≥4000μm (OR 9.2; 95% CI 1.3-110.3) were significant risk factors for LNM. When we focused on pT1b-EBVGC without lymphatic invasion and with submucosal invasion <2000μm, the rate of LNM was 0% (0/96, 95% CI 0-3.8%). Our findings indicated that lymphatic invasion and submucosal invasion ≥4000μm were significant risk factors for LNM. ESD could be an appropriate option for pT1b-EBVGC without lymphatic invasion and with submucosal invasion <2000μm.

Tu1491 THE RISK FOR LYMPH NODE METASTASIS IN EPSTEIN-BARR VIRUS-ASSOCIATED GASTRIC CARCINOMA WITH SUBMUCOSAL INVASION IS QUITE LOW: A RETROSPECTIVE MULTICENTER STUDY

Epstein-Barr Virus (EBV)-associated gastric cancer (EBVGC) accounts for approximately 10% of gastric cancers. EBVGC is classified into one of the four molecular subtypes proposed by The Cancer Genome Atlas Research Network (Nature, 2014), and there have been reports which imply the relatively low risk of lymph node metastasis (LNM) in EBVGC with submucosal invasion (pT1b-EBVGC). However, a large cohort study is still lacking. The present study aims to investigate the risk of LNM in pT1b-EBVGC through a multicenter study. This is a retrospective multicenter study. 5 institutes, which have pathologists specializing in the diagnosis of EBVGC, participated in this study. We reviewed medical records and extracted all pT1b-EBVGC cases diagnosed between 2001 and 2016. Lesion characteristics, patients background factors and clinical outcomes were obtained. The diagnostic criteria for EBVGC were as follows: 1) gastric adenocarcinoma with lymphoid stroma; and 2) a positive result of in-situ hybridization for EBV encoded small RNA (EBER-ISH). For surgery cases, LNM was investigated based on the histopathological evaluation of resected LNs. For endoscopic resection (ER) cases, no LNM was defined as the case where computed tomography scan did not identify any LNM during follow-up ≥ 3 years. A total of 190 pT1b-EBVGC cases were enrolled. The number of ER and surgery cases were 30 and 160, respectively. Additional surgery was performed in 25 of 30 ER cases. LNM was identified in 9 cases (4.7%), which were all surgery cases. Table 1 shows the association between LNM and various factors according to univariate analysis. Multivariate logistic regression analysis revealed that lymphatic invasion (Ly) and deep submucosal invasion (≥ 2000 μm) are the significant risk factors for LNM (Table 2); neither lesion size nor venous invasion (V) was significantly correlated to LNM. The present study revealed that the risk for LNM in pT1b-EBVGC without Ly was 1.8% (3/163, 95%CI; 0.6-5.3%). Moreover, as for pT1b-EBVGC without Ly and submucosal invasion depth < 2000 μm, the rate of LNM was 0% (0/101, 95%CI; 0-2.9%). The present study demonstrated the relatively low risk for LNM in pT1b-EBVGC, considering that the LNM risk of all pT1b-GC is approximately 20%. This result implies that pT1b-EBVGC is a good candidate for ER or local resection.Table 2The association between LNM and clinical factors (multivariate analysis)View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Clinicopathologic Features of Submucosal Papillary Gastric Cancer Differ from Those of Other Differentiated-Type Histologies.

Background/AimsPapillary gastric cancer (GC) is classified as differentiated adenocarcinoma, together with well-differentiated (WD) and moderately differentiated (MD) adenocarcinoma. This study evaluated the risk of lymph node metastasis (LNM) in submucosal (SM) invasive papillary GC compared with other differentiated early GC types.MethodsThis retrospective study involved three tertiary hospitals and enrolled 1,798 lesions with differentiated SM invasive GC treated with curative gastrectomy between March 2001 and December 2012. All pathology slides were reviewed, and clinicopathologic findings associated with LNM, including tumor size, location, gross type, ulceration, depth and width of SM invasion, and lymphovascular invasion (LVI), were analyzed.ResultsThe proportion of SM papillary GC was 2.8% (n=51). SM papillary GC was associated with larger tumor size and deeper and wider SM invasion than other differentiated GC types. LNM was significantly higher in the papillary type than in the MD and WD types. LNM was found in 27.5% of SM papillary GC patients (WD 9.0%, MD 21.2%). LVI was the only significant risk factor for LNM in SM papillary GC. The depth or width of SM invasion was not associated with LNM in papillary GC. Lower third location or elevated gross appearance was significantly associated with LVI.ConclusionsSM papillary GC had the highest LNM rate, with features different from those of other differentiated SM invasive GCs. The treatment strategy for SM papillary GC should be carefully approached, especially for lesions located in the lower third or of the elevated gross type.

Predictors of lymph node metastasis and residual tumor in early gastric cancer patients after noncurative endoscopic resection: a systematic review and meta-analysis.

Background:It is challenging to identify the prevalence of lymph node metastasis (LNM) and residual tumor in patients with early gastric cancer (EGC) who underwent noncurative endoscopic resection (ER). This present meta-analysis was aimed to establish imperative potential predictive factors in order to select the optimal treatment method.Methods:A systematic literature search of PubMed, Embase, and Cochrane Library databases was performed through 1 February 2019 to identify relevant studies, which investigated risk factors for LNM and residual tumor in patients with EGC who underwent noncurative ER. Eligible data were systematically reviewed through a meta-analysis.Results:Overall, 12 studies investigating the risk factor of LNM were included, totaling 3015 patients, 7 of which also involved cancer residues. After the present meta-analysis, six predictors, including tumor size >30 mm, tumor invasion depth (⩾500 μm from the muscularis mucosae), macroscopic appearance, undifferentiated histopathological type, positive vertical margin, and presence of lymphovascular invasion (including lymphatic invasion and vascular invasion) were significantly associated with LNM, whereas tumor size >30 mm, positive horizontal margin, and positive vertical margin were identified as significant predictors for the risk of residual tumor. No evidence of publication bias was observed.Conclusions:Six and three variables were established as significant risk factors for LNM and residual tumor in patients with EGC who underwent noncurative ER, respectively. Patients with EGC who present these risk factors after noncurative ER are strongly suggested to receive additional surgery, while others might be suitable for strict follow-up. This might shed some new light on the selection of follow-up treatment for noncurative ER.

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

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. 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. 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. Rectal tumor location, depression, protuberance within the depression, expansiveness, and loss of mucosal patterns could be predictive factors for HRC.

Risk factors of lymph node metastasis in 734 early gastric carcinoma radical resections in a Chinese population.

To investigate the risk factors of lymph node metastasis (LNM) in early gastric carcinoma (EGC) in a Chinese population. The data were analyzed to determine risk factors of LNM. The patients' characteristics, the tumor's location, gross features, histological type, differentiation, invasive depth, lymphovascular invasion (LVI), perineural invasion and the numbers of lymph nodes retrieved and involved were statistically analyzed. A total of 734 patients with EGC were finally enrolled in the study, and LNM was present in 14.2% (104/734) of them. By univariate analysis, significant risk factors for LNM included depressed or excavated gross patterns, size ≥1.0 cm, SM2, moderate/poor differentiation, histological type of hepatoid or micropapillary adenocarcinoma, LVI, perineural invasion and tumor necrosis. By multivariate analysis, independent risk factors for LNM were size ≥3.0 cm (odds ratio [OR] 4.9), SM2 (OR 2.4), moderate (OR 3.6) and poor (OR 5.0) differentiation, LVI (OR 3.1) and tumor necrosis (OR 1.7). Early gastric cardiac carcinoma (OR 0.3) had a significantly lower risk than non-cardiac carcinoma. No LNM was identified in 67 EGC of <1.0 cm in size and without poor differentiation, in 142 intramucosal EGC cases of smaller than 2.0 cm and without poor differentiation, in 129 cases of well-differentiated EGC without deep SM2 submucosal invasion, or in 54 intramucosal EGC located in the gastric cardia. Independent risk factors for LNM in EGC include tumor size ≥3.0 cm, SM2 invasion, moderate/poor differentiation, LVI and tumor necrosis. Early cardiac carcinoma had a significantly lower risk of LNM than non-cardiac EGC.

Diagnosis, Pathological Findings, and Clinical Management of Gangliocytic Paraganglioma: A Systematic Review.

Background: Although gangliocytic paraganglioma (GP) is considered a rare benign neuroendocrine tumor, cases of mortality have been reported. Occasionally, GP is misdiagnosed as neuroendocrine tumor G1, which is associated with a poorer prognosis than GP. To avoid such misdiagnoses, it is important to understand the clinicopathological characteristics of GP. Thus, herein, we discuss the current literature on the clinicopathological characteristics of GP.Methods: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed and Japana Centra Revuo Medicina searches were used to identify papers describing GP. Inclusion criteria included confirmation of epithelioid, spindle-shaped, and ganglion-like cells in the main article and/or figures and whether the paper was cited in other studies of GP. Data were collected on age, sex, site of the primary lesion, tumor size, treatment, prognosis, lymph node metastasis (LNM), depth of tumor invasion, rate of preoperative diagnosis, and clinical symptoms.Results: In total, 162 papers containing 263 cases of GP met the criteria. The mean age at diagnosis was 53.5 years. The male-to-female ratio was 157:104. The mean tumor size was 25.7 mm. The predominant site of the primary tumor was the duodenum (89.7%). The most common clinical sign of GP was gastrointestinal bleeding (47.9%). Other signs and symptoms of GP included abdominal pain (44.7%), anemia (20.3%), incidental findings (12.9%), nausea (6.9%), weight loss (5.5%), general fatigue (5.1%), jaundice (4.6%), and incidental autopsy findings (5.1%). LNM was observed in 11.4% of patients. Liver metastasis was observed in 1.1% of patients. Depth of tumor invasion (penetrating beyond the submucosal layer or sphincter of Oddi) was by far the most significant risk factor for LNM in patients with GP. This suggests, along with histological heterogeneity, that GP may have hamartomatous characteristics. Furthermore, immunohistochemical expression of progesterone receptor and pancreatic polypeptide were useful in distinguishing between GP and neuroendocrine tumor G1, even in small biopsy specimens.Conclusions: We reveal the clinicopathological characteristics of GP, including risk factors for LNM, differential diagnostic approaches, and improvements in the clinical management of this tumor.In addition, GP may have hamartomatous characteristics.

Prognostication of superficial Barrett’s carcinoma: a Japanese multicenter study

Endoscopic resection (ER) has become the standard therapy for superficial Barrett's carcinoma (BC) in Japan and other countries. Patients undergoing ER sometimes require additional treatment because of recurrence of lymph node metastasis (LNM). We attempted to clarify the histopathologic risk factors for LNM, and the difference between these risk factors for Japanese patients and the conventional risk factors documented for Western patients. This multi-center study included 12 leading institutions belonging to the Japan Research Society for Early Esophageal Cancer and Chromoendoscopy, and was based on a questionnaire designed to gather data on the features of superficial BC cases, except for high-grade intraepithelial neoplasia, treated at those institutions. These features were assessed using the standardized pathologic approach employed in Japan, whereby surgically and endoscopically resected specimens are cut into parallel slices 4-5 mm and 2 mm thick, respectively. Seventy-four surgically resected (SR) and 201 ER specimens were analyzed separately. Significant risk factors for LNM were almost the same as conventional risk factors, such as tumor size (cut-off value; 17.5 mm) and depth, vessel infiltration, presence of poorly differentiated components, and the depth (cut-off value; 990 μm) and width (cut-off value; 4300 μm) of the submucosal component, in addition to growth pattern (a protruding or flat elevated pattern) and the presence of infiltrative growth. Histopathologic examination revealed that BC cases without invasion to the deep muscularis mucosae (DMM) had almost no risk of LNM. Detailed histopathologic evaluation of thin-slice preparations of ER specimens is considered highly important for prognostication.

Establishment of pathological quantitative method for determining undifferentiated component ratio in patients with differentiated/undifferentiated mixed-type early gastric cancer and clinical significance of this ratio.

The purpose of this study was to establish a pathological quantitative method for determining the undifferentiated components ratio (UCR) in patients with differentiated/undifferentiated mixed-type (Mixed-type) early gastric cancer (EGC) and to examine the clinical significance. The subjects were 410 patients who underwent surgical resection for EGC with the invasion limited to m or sm1. Analysis 1: In 12 randomly selected patients with Mixed-type cancer, we calculated the area ratio and the ratio of the length ratio using ImageJ and analyzed the correlation between them. Analysis 2: We generated ROC curves, and determined the cutoff UCR on the basis of the predictive risk factors for lymph node metastasis (LNM). Analysis 3: We analyzed the relationship between clinicopathological factors including UCR/length of undifferentiated component (LUC=maximum dimensions of tumor×UCR) and LNM. Analysis 1: The length ratio can be used as a substitute parameter for the UCR (r=0.996). Analysis 2: The cutoff UCR as a risk factor for LNM was 58% (sensitivity=1, 1-specificity=0.404). Analysis 3: Lymphovascular invasion (p<0.0001), UCR≥58% (p=0.023), and LUC≥25mm (p=0.005) were identified as significant risk factors for LNM. No LNM was observed in patients with invasion limited to m or sm1 and negativity for lymphovascular invasion and UCR<58% (0/215). In the patients with Mixed-type EGC, the length ratio of undifferentiated components can be a substitute parameter for the UCR. LNM rarely occurs in patients without lymphovascular invasion and with an UCR<58%. The analysis of the UCR has great significance in determining whether additional surgical resection is required after endoscopic resection.

A systematic review and meta-analysis on outcomes after Rx or R1 endoscopic resection of superficial gastric cancer.

Endoscopic resection is a standard treatment for gastric superficial lesions. A positive or a nonevaluable margin is considered a noncurative criterion. We aimed to systematically review recurrence, residual disease, lymph node metastasis (LNM) and cancer-related death following Rx/R1 resection of gastric lesions in the absence of other noncurative criteria. MEDLINE systematic review and meta-analysis by July 2014. Data were extracted from 31 manuscripts. Definitions and results differed significantly. However, nonevaluable (HMx) and positive horizontal margins (HM1) were associated with 10% [95% confidence interval (CI) 5-15%] and 36% (95% CI 24-48%) rates of recurrence/residual disease, respectively, with an odds ratio of 2.85 (95% CI 1.6-5.8, P<0.01) for HM1 compared with HMx. Nonevaluable (VMx) or positive (VM1) vertical margin was associated with a 43% (95% CI 17-68%) rate of recurrence/residual. VMx/VM1 was associated with a higher risk of recurrence/residual compared with HMx/HM1 (odds ratio 3.76, 95% CI 1.71-6.82, P<0.01). The most common strategy after HMx/HM1 was endoscopic surveillance and retreatment, whereas surgery was recommended after VMx/VM1. No cases of LNM or cancer-related death were noticeable if neither submucosal invasion more than 500 µm nor lymphovascular infiltration was also reported. Rx/R1 resection in the absence of other noncurative criteria does not appear to be a significant risk factor for LNM or cancer-related death. The risk of recurrence/residual disease is higher after HM1 than HMx and higher after VMx/VM1 than HMx/HM1. However, considerable heterogeneity was found in studies. Standard definitions should be created and applied in future studies.

The short-term and long-term outcomes of the endoscopic resection for the superficial pharyngeal squamous cell carcinoma.

Background and study aims: Early detection of superficial pharyngeal squamous cell carcinoma (SPSCC) using narrow-band imaging as well as the increasing use of ER for gastrointestinal cancers may increase the number of ER for SPSCC. The aims of this study were to clarify the feasibility of ER for SPSCC and its long-term outcomes. Patients and methods: In total, 84 patients with 115 lesions were treated by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) between March 2004 and August 2012. We retrospectively assessed the en bloc and R0 resection rates, complications, lymph node metastasis (LNM), local recurrence, metachronous pharyngeal and esophageal SCC, 5-year overall and cause-specific survival rates. Results: Higher proportions of en bloc and R0 resection were achieved with ESD compared to EMR (en bloc 100 % vs. 60 %, P < 0.001; R0 59 % vs. 26 %, P < 0.005). There were no significant complications in both groups. None of the patients died from primary SPSCC during the median follow-up of 34 months (range, 3 – 115). LNM occurred in three patients and local recurrence was detected in seven patients (8.3 %) with eight lesions. Tumor thickness over 1000 μm (P < 0.005) and positive or inconclusive horizontal margins (P < 0.05) were significant risk factors for LNM and local recurrence, respectively. Twelve patients died because of co-existing clinical conditions. The 5-year overall and cause-specific survival rates were 80.7 % and 100 %, respectively. Conclusions: ER for SPSCC is a feasible treatment with promising results. Tumor thickness over 1000 μm is a significant risk factor for LNM and positive or inconclusive horizontal margin is a risk factor for local recurrence.