Classification Of Esophageal Cancer Research Articles

Brief introduction of surgical development of esophageal cancer in Japan

Esophageal cancer surgery originated in the early 20(th) century. However, the true meaning of trans-thoracic esophagectomy and digestive tract reconstruction began in the 1930s. Almost at the same time, Japan and Western countries began the surgical exploration of esophageal cancer. Based on the pathological type of esophageal cancer in Asia, squamous cell carcinoma is the majority, and its biological characteristics and treatment strategies are different from those of European and American patients. After more than eighty years of development, the surgical treatment of esophageal cancer in Japan has been developed from the initial attempt, deep cultivation practice to the pursuit of excellence, and explored a set of more advanced surgical techniques and diagnostic strategies, which is unique in the world. On the basis of the establishment of the Japanese Society of Esophagus, Japanese scholars have developed and irregularly updated the Japanese Classification of Esophageal Cancer and published the professional academic journal Esophagus. The Japanese Clinical Oncology Group organized a number of phase Ⅲ clinical studies on esophageal cancer, providing strong evidence for the diagnosis and treatment of esophageal squamous carcinoma. Focused on the origin, development, current situation and future of esophageal cancer surgery in Japan, this paper summarized the development of esophageal cancer surgery in Japan through literature review, interviews with senior experts and Hot topics of esophageal cancer surgery-questionnaire survey of Japanese experts.

Prognostic Analysis and Treatment Model of Newly Diagnosed Patients with Stage IVB Thoracic Esophageal Squamous Cell Carcinoma

To retrospectively assess the clinical characteristics, short-term efficacy, and side effects of newly diagnosed stage IVB thoracic esophageal squamous cell carcinoma (ESCC). 199 patients with stage ⅣB (according to UICC / AJCC 8th edition) newly diagnosed thoracic ESCC, which had been treated in the fourth hospital of Hebei medical university between January 2010 to December 2016, were retrospectively investigated. The difference of TNM classification between Japanese Esophagus Society (JES) 11th edition and UICC/AJCC 8th edition in predicting the prognosis of patients with advanced ESCC. Short-term efficacy: The objective response rate of primary lesion (pORR) was 82.4%. Univariate analysis showed that the tumor location (χ2=7.882，P=0.019) and treatment modalities (χ2=24.218, P =0.000) were the main factors for pORR. The pORR of upper thoracic esophagus was significantly higher than that of middle and lower thoracic esophagus (χ2=7.846, P =0.005; χ2=6.236, P =0.013). The pORR of chemotherapy group, radiotherapy group, and radiochemotherapy group were 37.5%, 86.0%, and 86.5%, respectively. The improvement rate of dysphagia (DIR) was 77.2%. Univariate analysis showed that the type of metastasis (χ2=13.513, P=0.001) and treatment modalities (χ2=13.790, P=0.001) were the main factors for DIR. The DIR of distant lymph node metastasis only was significantly higher than that of solid organ metastasis only (χ2=12.812, P =0.000). The DIR of chemotherapy alone , radiotherapy alone and radiochemotherapy were 30.0%, 77.5%, and 81.5%, respectively. The median OS (mOS) of the entire cohort was 14.0 months (95% CI: 11.826-16.174m), and the survival rates for 1 year, 3 years, and 5 years were 53.2%, 15.8%, and 10.7%, respectively. Multivariate analysis showed that tumor length, the number of metastatic organs, and chemotherapy were independent prognostic factors for OS. According to TNM classification of esophageal cancer of JES 11th edition, there was no significant difference for OS between stage Ⅲ and stage Ⅳ(χ2=0.521, P=0.470). For metastatic esophageal cancer, compared with chemotherapy and radiotherapy alone, radiotherapy combined with chemotherapy could obtain good local control, improve dysphagia and might prolong survival. For patients with good performance status, radiotherapy could be considered on the basis of systemic chemotherapy to participate in the comprehensive treatment of stage Ⅳ esophageal cancer as far as possible, and individualized choice of sequential or simultaneous radiotherapy and chemotherapy mode.

AGA Clinical Practice Update on the Utility of Endoscopic Submucosal Dissection in T1b Esophageal Cancer: Expert Review

AGA Clinical Practice Update on the Utility of Endoscopic Submucosal Dissection in T1b Esophageal Cancer: Expert Review

PS02.116: FEASIBILITY OF DOCETAXEL, CISPLATIN, AND 5-FLUOROURACIL (DCF) VERSUS RADIOTHERAPY WITH DCF (DCF-RT) AS PREOPERATIVE THERAPY FOR LOCALLY ADVANCED ESOPHAGEAL CANCER

Abstract Background In Japan, preoperative chemotherapy with cisplatin plus 5-fluorouracil (CF) followed by radical surgery has been accepted as the standard therapeutic approach for resectable esophageal squamous cell carcinoma (ESCC) result from a Japan Clinical Oncology Group randomized control trial. Whether preoperative chemoradiotherapy (CRT) followed by radical surgery is effective for Japanese ESCC patients has yet to be established. Some trials have reported usefulness of CF plus docetaxel therapy (DCF) for advanced or metastatic ESCC. Here, we have launched a randomized controlled trial to compare preoperative DCF versus DCF plus radiotherapy (DCF-RT) followed by surgery in locally advanced esophageal cancer. Methods Patients with clinical stage II/III (Japanese Classification of Esophageal Cancer, 11th Edition) are randomized to 2 groups. Patients in DCF group receive 2 courses of preoperative DCF (docetaxel, 60 mg/m2/day, day 1; cisplatin, 70 mg/m2/day, day 1; 5-FU, 700 mg/m2/day, days 1–5) repeated every 3 weeks. Patients in DCF-RT group receive preoperative chemoradiotherapy (40Gy/20fr) with 2 courses of DCF (docetaxel, 30 mg/m2/day, day 1, 15; cisplatin, 7 mg/m2/day and 5-FU, 350 mg/m2/day, days 1–5, days 8–12, days 15–19, days 22–26). The primary endpoint is overall survival and the secondary endpoints include adverse events, response rate and pathologic complete response rate. Results Twenty-seven patients were assigned to the DCF group and 26 patients to the DCF-RT group. Grade 3/4 leukopenia and febrile neutropenia occurred 37% and 19% in the DCF group, 35% and 12% in the DCF-RT group. The clinical response rates were 16.0% and 64.0% in the DCF and DCF-RT group. Twenty patients and 23 patients underwent surgery in the DCF and DCF-RT group, and the R0 resection rate was 80.0% and 91.3%. With regard to the surgical complications, the incidence of anastomotic leakage was significantly higher in the DCF-RT group compared with the DCF group. The histological effects of DCF-RT were significantly higher than those of DCF. Two-year survival rate was 46% in the DCF group and 70% in the DCF-RT group. Conclusion The DCF and DCF-RT were found to be feasible as neoadjuvant therapy, and DCF-RT demonstrated higher efficacy than DCF in clinical stage II/III esophageal cancer patients. Disclosure All authors have declared no conflicts of interest.

PS01.194: CLINICOPATHOLOGICAL EXAMINATION OF ESOPHAGOGASTRIC JUNCTIONAL CARCINOMA TREATED WITH CURATIVE SURGERY

Abstract Background Compared to Western countries, Japanese esophagogastric junctional carcinoma (JC) demonstrates different epidemiologic backgrounds; squamous cell carcinoma is dominant over Barrett adenocarcinoma, and there is no consensus on surgical approach or dissection range of lymph node. JC is defined as the cancer, that is the center of the tumor is within 2 cm from the esophagogastric junction to the esophagus and stomach respectively by the Japanese Classification of Esophageal Cancer, 11th edition. According to this definition, we examined the clinicopathological features and treatment outcomes of patients who underwent curative resection and pathologically defined as JC. Methods From 2012 to 2018, 19 consecutive patients with JC who received with curative surgery in Shiga University of Medical Science Hospital were included. Clinicopathological classification was based on Japanese Classification of Esophageal Cancer, 11th edition. Results The patients consisted of 14 males and 5 females, median age was 68 (43–91) years old. Pathological diagnoses were 15 adenocarcinoma, 1 squamous cell carcinoma, 2 mixed adenoneuroendocrine carcinoma (MANEC) and 1 malignant melanoma. Patients with Barrett's esophagus were 6 cases (31.6%). Median tumor diameter was 54 mm (5–90 mm) and tumor location was E:3 cases (15.8%), EG:6 cases (31.6%), E = G:1 case (5.2%), GE:8 cases (42.1%) and G:1 case (5.2%). Surgical procedure was esophagectomy via right thoracotomy 6 cases, esophagectomy via left thoracotomy 2 case and laparotomy 11 cases. Tumor invasion was pT1:6 (31.6%), pT2:3 (15.8%), pT3:3 (15.8%) and pT4:7 (36.8%). Lymph node metastases were observed in 13 cases (68.4%) and #1,2,3:13 cases (100%), #4,5: 2 cases (15.4%), #7,8a,9: 4 cases (30.8%), #19,20: 3 cases (23.1%) and #105–110: 3 cases (23.1%). Among 7 recurrence patients, peritonitis carcinomatosa was 4 cases. Conclusion In all positive lymph node metastasis cases, metastasis was observed in #1, 2 and 3 lymph nodes, but metastasis to the cervical lymph node was not observed. In the G, GE cases, right thoracotomy was not performed because there were no metastases to the upper mediastinal lymph nodes. In conclusion, these results suggested that surgical operation could be reduced to proximal gastrectomy for early G, GE cases. However, the number of cases is small in this study, further investigation is necessary. Disclosure All authors have declared no conflicts of interest.

PS01.128: A PROPENSITY SCORE-MATCHED ANALYSIS OF CLINICAL SIGNIFICANCE OF THE SUPRACLAVICULAR LYMPHADENECTOMY FOR SQUAMOUS CELL CARCINOMA LOCATED IN MIDDLE THORACIC ESOPHAGUS

Abstract Background Supraclavicular lymph nodes (No 104) were upgraded from group 3 to group 2, which needs to be dissected in D2 surgery, for tumors located in middle thoracic esophagus in the 11th edition of Japanese classification of esophageal cancer. However, it is not based on prospective study and the evidence level remains moderate. Current evidence regarding supraclavicular lymphadenectomy is mainly based on retrospective cohort study of efficacy index without proper control. The aim of this study is to retrospectively investigate the clinical impact of supraclavicular lymphadenectomy for middle esophageal cancer. Methods A total of 240 consecutive patients who underwent R0 esophageal resection for clinical Stage I, II, III (UICC 8th) primary esophageal squamous cell carcinoma from 2005 to 2017 in Kyoto University Hospital were investigated. Patients who underwent salvage surgery after definitive chemoradiotherapy were excluded. Among them, 99 patients had middle esophageal cancer. All patients underwent at least abdominal and mediastinal lymphadenectomy including cervical paraesophageal (No 101) and paratracheal (No 106rec) nodes. After propensity score matching, 42 patients (21 each for with (3F) and without (2F) supraclavicular lymphadenectomy) were selected for comparison. Results In the propensity-matched population (n = 42), the 5-year overall survival of clinical Stage I (n = 15)/II (n = 9)/III (n = 18) was 100%/52%/57%. Though cStage, neoadjuvant therapy, ASA-PS and date of surgery (early, middle and late period) were well matched, the 5-year overall survival in 2F and 3F were 82% and 68%. The hazard ratio (3F/2F) for overall death was 2.6 (95% CI, 0.79–9.97; P = 0.1178). In terms of short term outcomes, postoperative morbidity graded as Clavien-Dindo grade 2 or higher was 48% in the both group, while respiratory complication (Clavien-Dindo grade 2 or higher) was 14% in 2F and 29% in 3F, respectively. The odds ratio was 2.4 (95% CI, 0.51–11.3; P = 0.2593). Conclusion This observational study failed to show any clinical benefit of supraclavicular lymphadenectomy. Given the nature of retrospective study, there might be overlooked confounding factors to select 2F or 3F. Further prospective study is warranted. Disclosure All authors have declared no conflicts of interest.

PS02.187: RELATIONSHIP BETWEEN REGIONAL LYMPH NODE SIZE AND PROGNOSIS IN ESOPHAGEAL CANCER PATIENTS

Abstract Background Surgery for esophageal cancer, in many cases performed after chemotherapy or chemoradiotherapy. Because treatment policy is determined by pretreatment evaluation, improvement of diagnosis accuracy is important. Commonly, metastatic diagnosis is performed by uniformly defining the size. We examined whether evaluation of N classification reflecting more prognosis can be done by examining lymph node metastasis criteria by area in CT. Methods We surveyed 300 cases of thoracic esophageal cancer (squamous cell carcinoma) who underwent surgery at our hospital from September 2010 to December 2014. We defined lymph node with a minor axis of 5 mm or more from CT (5 mm slice) before treatment as ‘visible node’. We changed the cut off of lymph node short diameter for each area to 5 mm, 10 mm and 15 mm, and those with long diameter/short diameter ratio less than 1.5 were designated as ‘metastasis’. We examined the optimal size of lymph node which reflect prognosis. We compared the correlation with the prognosis based on the N category of the 8th edition UICC TNM classification and the 11th edition Japanese Classification of Esophageal Cancer, using the cutoff of short diameter examined for each area. Results We evaluated the cut off of each area lymph node except paraesophageal, 15 mm in the cervical, 10 mm in the recurrent nerve, 15 mm in the upper trachea, 15 mm in the lower trachea, and 10 mm in the epigastric. Classification based on the N classification of the 8th edition UICC TNM classification, overall survival declined in the order of N categories. Conclusion From this result, it was suggested that diagnosis based on lymph node size in CT reflects prognosis by prescribing cut off for each site. From now on, it would be possible to raise the diagnostic accuracy of N classification further by subdivision of cut off and accumulation of the case. Disclosure All authors have declared no conflicts of interest.

Recent advancements in esophageal cancer treatment in Japan.

The 11th edition of the Japanese Classification of Esophageal Cancer (EC) was published in 2017. Some correction was made in the depth of tumor invasion to be consistent with the TNM classification by the Union for International Cancer Control (UICC). With regard to surgery, short‐term safety and long‐term effectiveness under thoracotomy/video‐assisted thoracoscopic surgery are expected to be proven by the Japan Clinical Oncology Group (JCOG)1409 study. Results of nutritional management and countermeasures for adverse events not only during the perioperative period but also during EC chemotherapy were reported. From now on, the pursuit of low invasiveness and radicality is desired. Esophageal surgery is also expected to be safe at all institutions. To determine the optimal modality of preoperative treatment and a novel chemo(radio)therapy regimen for patients with distant metastasis, the results of the ongoing JCOG1109 and 0807 studies are being released. The effect of the addition of molecular targeted drugs on chemotherapy and concurrent chemoradiation has not yet improved overall survival. Immune checkpoint inhibitor drugs could offer a potential new treatment approach for patients with treatment‐refractory advanced squamous cell carcinoma (SCC). The Cancer Genome Atlas Research Network reported the results of a comprehensive genome analysis and molecular analysis of SCC and adenocarcinoma of the esophagus. Further differentiation of SCC and adenocarcinoma by molecular characterization analysis may be useful for the development of clinical trials and targeted drug therapies as precision medicine. The era of ultimate minimally invasive surgery and personalized treatment has begun. Large, prospective studies will be required to confirm the value of these advancements.

Comparison of two major staging systems of esophageal cancer-toward more practical common scale for tumor staging.

The latest 8th edition of TNM Classification of Malignant Tumours by Union for International Cancer Control (UICC) and 11th edition of Japanese Classification of Esophageal Cancer by Japan Esophageal Society (JES) are the two major classifications widely accepted as tools for clinical staging of esophageal cancer. Both systems consist of three main categories, i.e., T, N, and M, but large difference exists between the two. JES system has more detailed sub-classification of T1 tumors reflecting meticulous work by Japanese investigators on superficial esophageal cancer. N-category shows the largest difference. UICC defines the N-category according to only the number of the metastatic regional lymph nodes. The definition of regional nodes in UICC system is static and uniform, and supraclavicular nodes are definitely excluded. In JES system, regional nodes are subgrouped into five different patterns according to the main tumor location, and the supraclavicular nodes are always regional nodes for thoracic esophageal cancer. Japanese surgeons have described the evidence that regional nodes should be dynamically defined according to tumor location and supraclavicular nodes should be included in regional nodes. Compared to the simplified N-category, the staging matrix of UICC system is somewhat complicated. The clinical stage and pathological stage of UICC system are not identical and difference exists also between squamous cell carcinoma (SCC) and adenocarcinoma. It has another system of pathological prognostic grouping. We can imagine several reasons for the difference occurred between the two systems. One is the difference of major pathology. Another reason is the difference of basic concept of cancer treatment. The relative "dependence" on radical surgery in Japan has required the detailed definition of each lymph node station and the evaluation of "efficacy index" of each station. The strict and detailed definition of lymph node stations has been regarded as an obstacle to those who are not familiar with it. Some simplification can be done but maintaining dynamic definition of regional lymph nodes linked to tumor location. If UICC system can accept this concept, I think the two systems can be unified to realize more practical and useful staging system as an international common language.

Comparison of the 7th and proposed 8th editions of the AJCC/UICC TNM staging system for esophageal squamous cell carcinoma underwent radical surgery

BackgroundRecently, the 8th edition of the TNM classification of esophageal cancer has come up. The present study aims to compare the 7th and the proposed 8th edition of the AJCC/UICC TNM staging system for esophageal squamous cell carcinoma (ESCC). MethodsA total of 1872 ESCC patients who underwent radical surgery with curative intent were analyzed retrospectively. Survival was analyzed using the Kaplan–Meier method, and values were compared using the log-rank test. Multivariate analysis was performed using the Cox proportional hazard model. The Akaike information criterion (AIC) and the concordance index (c-index) were applied to compare the two prognostic systems. ResultsOn univariate analysis, the 7th staging system, the proposed 8th staging system, gender, age as well as adjuvant treatment were found to have significant association with overall survival (OS). In both the current staging system and the modified version, age and gender were independent prognostic factors in a multivariate analysis. The AIC value for the proposed 8th version was smaller than that for the 7th staging system; the c-index value for the proposed 8th version was larger than that for the 7th staging system. Subgroup analysis in patients with/without nodal metastasis obtained consistent results. ConclusionBased on the data from our single center, the proposed 8th AJCC staging system seems to be superior to the 7th AJCC staging system in terms of OS for patients with thoracic ESCC who underwent radical surgery.

The Presence of Serum p53 Antibody Predicts the Pathological Tumor Response to Neoadjuvant Chemotherapy with Docetaxel, Cisplatin and Fluorouracil (DCF) in Esophageal Squamous Cell Carcinoma.

Docetaxel, cisplatin and fluorouracil (DCF) is a candidate neoadjuvant chemotherapy (NAC) regimen for esophageal squamous cell carcinoma (ESCC). Although the efficacy and safety of DCF have been reported, the markers that predict the patient's response are still unknown. The aim of this study was to identify the predictive markers for a response to NAC with DCF in patients with ESCC. A total of 79 patients who received preoperative DCF followed by esophagectomy between August 2008 and December 2014 were enrolled in this study. All of the patients completed 2 preoperative courses of DCF. The clinical and pathological responses to DCF were investigated, and the associations between the pathological response, the clinicopathological factors and the prognosis were retrospectively analyzed. Among the 79 patients, the pathological response to DCF (evaluated according to the Japanese Classification of Esophageal Cancer) was grade 3 (complete pathological response) in 7 patients (8.9%), grade 2 in 13 patients (16.5%), grade 1b in 8 patients (10.1%) and grade 1a in 51 patients (64.6%). A good pathological response (grade 2-3) was significantly associated with both favorable disease-free survival (P=0.0051) and favorable cancer-specific survival (P=0.0366). A multivariate analysis revealed that a good clinical response (HR 13.743, 95% CI 2.455-76.917) and the presence of serum p53 antibody before treatment (HR 3.987, 95% CI 1.103-14.416) were independent predictors of good pathological response. The presence of serum p53 antibody can be used as a novel, noninvasive predictor of the pathological tumor response to NAC with DCF in ESCC patients.

Abstract 3401: MicroRNA-503 promotes tumor progression and acts as a novel biomarker for prognosis in esophageal cancer

Abstract Background: MicroRNAs (miRNAs) are a class of small non-coding RNAs that inhibit gene expression by binding to 3` untranslated regions of mRNAs and inhibiting their translation. MiRNAs crucially affect cellular processes such as development, proliferation, differentiation and apoptosis, which are deregulated in cancer. MiR-503 is located at Xq26.3 and belongs to an extended miR-16 family of miRNAs. MiR-503 is down-regulated in several types of cancer, including oral, hepatocellular, gastric, and endometrial cancer, suggesting that it plays a tumour-suppressor role in carcinogenesis. In contrast, other recent reports have demonstrated up-regulation of miR-503 in adrenocortical carcinoma, parathyroid and retinoblastoma, compared with adjacent normal tissue. These results suggest that miR-503 shows tissue- or disease-specific expression patterns. However, miR-503 expression patterns in esophageal cancer (EC) and normal esophageal tissue have not been compared and the correlation of miR-503 expression with the clinical features of EC has not been studied. Materials and Methods: A total of 61 formalin-fixed paraffin-embedded (FFPE) tissue samples including 49 EC tissues and 12 adjacent normal esophageal tissues who underwent surgical resection at Mie University Hospital were collected from 2003 to 2013. Tagman qRT-PCR assay was performed to quantify the miR-503 expression in EC and adjacent normal tissues. We analyzed the association between miR-503 expression and clinico-pathological factors in patients with EC. Results: The median age of the patients was 66.2 years (41 - 90). The median follow up time was 24.6 months (3.8 - 80.0). There were 3 patients with stage 0, 16 with stage I, 12 with stage II, 11 with stage III, 3 with stage IVa and 4 with stage IVb by using the criteria of the Japanese Classification of Esophageal Cancer, 10th edition. Forty-four patients had esophageal squamous cell carcinoma (ESCC), five patients had esophageal adenocarcinoma (EAD). MiR-503 was remarkably up-regulated in EC tissues compared to adjacent normal tissue. High miR-503 expression in EC was significantly associated with male sex and large tumor size. Kaplan-Meier analysis showed that patients with high miR-503 expression had significantly poorer disease free and overall survival than those with low expression. Furthermore, high miR-503 expression was an independent predictor for prognosis in EC patients according to multivariate analysis. Conclusions: The results of this study provide novel evidence for associations between miR-503 expression and progression, early recurrence, and poor prognosis in EC, suggesting that it acts as an oncomiR in this type of cancer. MiR-503 may thus be a promising predictive marker for prognosis after surgery in patients with EC. Citation Format: Koichiro Mori, Yuji Toiyama, Shozo Ide, Tomofumi Noguchi, Hiroki Imaoka, Hiromi Yasuda, Susumu Saigusa, Masaki Ohi, Yasuhiro Inoue, Koji Tanaka, Yasuhiko Mohri, Tsutomu Nobori, Masato Kusunoki. MicroRNA-503 promotes tumor progression and acts as a novel biomarker for prognosis in esophageal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3401. doi:10.1158/1538-7445.AM2015-3401

The predictive role of infiltrative growth pattern in early pharyngeal cancers

Conclusion: The infiltrative growth pattern may predict tumor depth and lymph node metastasis. INF-a seems to fall into a low-risk category, and no additional treatment may be required immediately. Objectives: Tumor depth is a predictor of lymph node metastasis in early pharyngeal cancers. An infiltrative growth pattern is also a prognostic factor in other cancers. This study aimed to elucidate the predictive role of infiltrative growth pattern in early pharyngeal cancers. Methods: Thirty-eight lesions from 37 patients who had undergone trans-oral resection of pharyngeal cancers were included. According to the Japanese Classification of Esophageal Cancer, infiltrative growth pattern was classified into three groups; INF-a, INF-b, and INF-c. The correlation between infiltrative growth pattern and tumor depth, cervical lymph node metastasis was analyzed. Results: Of the 38 lesions, 25 were INF-a, nine were INF-b, and four were INF-c lesions. Lymph node metastasis was observed in three INF-b and one INF-c lesions. In contrast, no INF-a had lymph node metastasis. All INF-a lesions showed shallow invasion of the sub-epithelium; INF-b and INF-c lesions had significantly greater depth than INF-a.

Thoracoscopic radical esophagectomy and laparoscopic transhiatal lymph node dissection for superficial esophageal cancer associated with lymph node metastases in the dorsal area of the thoracic aorta.

Esophageal cancer invading the muscularis mucosa sometimes involves regional lymph node metastases. However, lymph node metastases are rare in the dorsal area of the thoracic aorta. We describe a patient with an intramucosal esophageal cancer invading the muscularis mucosa, accompanied by lymph node metastases in the dorsal area of the thoracic aorta. These lesions were successfully resected by hand-assisted laparoscopic surgery using a transhiatal approach. A 60-year-old man was diagnosed with superficial esophageal cancer during a routine health examination. Endoscopic examination and ultrasonography revealed a superficial cancer, of diameter 6.0 cm, invading the submucosal layer and intramural metastases caudal to the primary tumor. Enhanced computed tomography and F-deoxyglucose positron emission tomography demonstrated the two metastatic lymph nodes, one in the dorsal area of the thoracic aorta and the other near the left gastric artery. Thoracoscopic radical esophagectomy with three-field lymph node dissection was performed. The metastatic lymph node in the dorsal area of the thoracic aorta was successfully removed by hand-assisted laparoscopic surgery using a transhiatal approach. Histopathological examination showed primary cancer invading the muscularis mucosa and intramural metastases in the lamina propria mucosa and submucosal layer. The pathological diagnosis according to the Japanese classification of esophageal cancer was MtLt, 47 mm, 0-IIa + IIb, pT1a-MM, ie(+), INF-b, ly3, v0, pN4(4a), pIM1, M0, and pstage IVa. The patient underwent two courses of adjuvant chemotherapy, consisting of CDDP and 5-fluorouracil. At present, 1 year and 8 months after surgery, the patient remains alive without tumor recurrence. Although the lymph node in the dorsal area of the thoracic aorta is not recognized as regional nodes of thoracic esophageal cancer, solitary mediastinal metastases from a mucosal cancer may indicate the existence of direct lymphatic flow from the thoracic esophagus to the retroaortic region. Transhiatal approach by hand-assisted laparoscopic surgery is useful to dissect the metastatic lymph node in the dorsal area of the thoracic aorta.

Esophageal endocrine cell carcinoma: a report of eight cases and a review of the literature

Esophageal endocrine cell carcinoma is a rare histopathological type thought to be highly malignant and to have a poor prognosis, but its clinical behavior has not been fully analyzed. We retrospectively reviewed our cases among 386 patients with esophageal cancer in our institution. Eight patients (2.1 %) were pathologically diagnosed with endocrine cell carcinoma. Median patient age was 63 years, and the male-to-female ratio was 7:1. Cancer stage according to the Japanese Classification of Esophageal Cancer (JCEC) 10th edition, was stage II in one case, III in three, IVa in one, and IVb in three. Chromogranin-A staining was positive in six cases, synaptophysin in six, cluster of differentiation (CD)56 in seven, and neuron-specific enolase (NSE) in seven. Treatment included surgery in two cases, chemoradiotherapy in four, best-supportive case in one, and rejection in one. Prognoses were 13 months after surgery for stage II, 6–28 months after chemoradiotherapy for stage III, and 0–10 months for stage IV.

Comprehensive Registry of Esophageal Cancer in Japan, 2006

We deeply appreciate the great contributions of many physicians in the registry of esophageal cancer cases. The Comprehensive Registry of Esophageal Cancer in Japan, 2006, was published here, despite some delay. The registry complies with the Act for the Protection of Personal Information. The encryption with a HASH function is used for ‘‘anonymity in an unlinkable fashion’’. We briefly summarized the Comprehensive Registry of Esophageal Cancer in Japan, 2006. Japanese Classification of Esophageal Cancer 9th and UICC TNM Classification 6th were used for cancer staging according to the subjected year. A total of 4994 cases were registered from 239 institutions in Japan. Tumor locations were cervical: 4.2 %, upper thoracic: 13.4 %, middle thoracic: 48.7 %, lower thoracic: 26.0 % and EG junction: 6.7 %. Superficial carcinomas (Tis, T1a, T1b) were 35.9 %. As for the histologic type of biopsy specimens, squamous cell carcinoma and adenocarcinoma accounted for 90.8 and 3.9 %, respectively. Regarding clinical results, the 5-year survival rates of patients treated using endoscopic mucosal resection, concurrent chemoradiotherapy, radiotherapy alone, chemotherapy alone, or esophagectomy were 84.5, 25.8, 22.0, 3.0, and 48.0 %, respectively. Esophagectomy was performed in 2545 cases. Concerning the approach used for esophagectomy, 15.4 % of the cases were treated These data were first made available on July 1, 2013, as the Comprehensive Registry of Esophageal Cancer in Japan, 2006. Not all the pages are reprinted here; however, the original table and figure numbers have been maintained.

Lymph node dissection for esophageal cancer

The prevalence of lymph node (LN) metastasis in esophageal cancer (EC) is widely spread to all three fields, namely, to the neck region, the mediastinal region and the abdominal region. Furthermore, the status of LN metastasis has been recognized as a key factor that influences the outcome after EC surgery. Therefore, the latest version of the UICC/AJCC TNM classification (7th edition) applied the number of metastatic LNs as an N factor. However, the precise clinical diagnosis of metastatic LNs is still difficult. This is mainly because there are many micrometastases in EC. Therefore, the Japanese Classification of Esophageal Cancer (10th edition) has not incorporated the number of LN metastases into the N factor for its staging system and the accurate preoperative diagnosis of LN status is currently one of the most important issues to be resolved for EC. Given the frequency and extent of LN metastasis and its significance for the survival, controlling LN metastasis is a rational therapeutic strategy, and an extended LN dissection, such as three-field lymph node dissection may be logical, although appropriate patient selection is necessary. On the other hand, recent arguments have supported a reduction of unnecessary LN dissection in esophagectomy. To curtail unnecessary LN dissection, one of the current topics is sentinel lymph node-guided surgery and is being investigated as part of the next generation surgeries for EC. In this article, recent literatures were reviewed and we discuss the current status of lymph node dissection in EC.

A case of metachronous and multiple esophageal superficial carcinoma after surgery for esophageal achalasia

An 81-year-old man underwent surgery for esophageal achalasia at 57 years of age. He received periodical endoscopic examination annually. When 75 years old, an irregular slightly depressed lesion was detected on the left esophageal wall at 31-34 cm from the incisors, and pathological examination of a biopsy specimen revealed high grade intraepitherial neoplasia. We performed argon plasma coagulation (APC) on the lesion. When the patient was 76 years old, a superficial protruding lesion with a slightly elevated component was detected at the right esophageal wall at 21-28 cm from the incisors. Pathological examination of a biopsy specimen from this lesion revealed squamous cell carcinoma. As we diagnosed the depth of tumor invasion to be the submucosal layer, we performed chemoradiotherapy. Complete remission was achieved. Endoscopic examination when the patient was 81 years old revealed a flat reddish lesion on the left wall at 30 cm from the incisors; pathological examination of the biopsy specimen was high grade intraepitherial neoplasia. After 6 months, the lesion became a slightly depressed lesion and narrow band imaging (NBI) endoscopy showed irregular intraepithelial papillary capillary loops within a brownish area. Depth of tumor invasion was diagnosed as mucosal layer, and we performed endoscopic submucosal dissection (ESD). Although fibrous change of the submucosal layer was marked, we successfully resected the lesion without perforation or bleeding. Pathological examination of the ESD specimen was squamous cell carcinoma (SCC), INFa, pT1a-EP, ly0, v0, pHM0, pVM0 according to the Japanese Classification of Esophageal Cancer, 10th edition. The patient is well without recurrence after one year.

The Usefulness of Magnifying Endoscopy and Narrow-Band Imaging in Measuring the Depth of Invasion before Endoscopic Submucosal Dissection.

With the widespread application of endoscopic submucosal dissection for the treatment of gastrointestinal neoplasms, accurate determination of the invasion depth prior to intervention has become an indispensable part of treatment planning. Narrow-band imaging (NBI) is a novel endoscopic technique that may enhance the accuracy of diagnosis. Magnifying endoscopy with NBI has been shown to be effective for determining invasion depth for intrapapillary capillary loop classification of esophageal cancer and microvascular pattern of stomach cancer. Such precise pre-treatment staging of early neoplastic lesions in the gastrointestinal tract warrants timely initiation of disease-tailored treatment and, ultimately, better quality of life and improved patient survival.

History of the Japanese Classification of Esophageal Cancer

History of the Japanese Classification of Esophageal Cancer