Background
It will be important for the Japan Esophageal Society (JES) to show an evident advantage of its institution certification system. To achieve this essential task, we used nationally ...acquired big data to re-analyze 5-year survival information.
Methods
In 2008–2009, there were 4897 thoracic esophageal cancer patients who underwent esophagectomy and were registered in the National Database of Hospital-based Cancer Registries. We divided these patients into two groups, those who underwent surgery at an Authorized Institute for Board Certified Esophageal Surgeons (AIBCES) or a Non-AIBCES. We then compared the patient backgrounds and 5-year survival rates between these two groups, with and without propensity score matching.
Results
There were 3080 (63%) patients who underwent esophagectomy at an AIBCES and 1817 (37%) who underwent surgery at a Non-AIBCES. Comparison of the Kaplan–Meier survival curves using log-rank tests indicated a significant difference between the AIBCES and Non-AIBCES groups at all cStages (cStages I–IV). Multivariable Cox proportional hazard analysis stratified by clinical stage and adjuvant treatment revealed that AIBCES vs. Non-AIBCES is a significant independent factor (adjusted HR 0.78) for survival. After propensity score matching ensuring the backgrounds of the two groups being equivalent, there were significant differences in the 5-year survival rates for patients with cStages I–III disease between the AIBCES and Non-AIBCES groups.
Conclusions
There is a survival advantage to undergoing esophagectomy at an AIBCES. The institute certification system from the JES will contribute to the future establishment of a more appropriate surgery delivery system for thoracic esophageal cancer.
Background
Hoarseness is one of the classical symptoms in patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC), and it results from recurrent laryngeal nerve palsy, which ...is caused by nodal metastasis along the recurrent laryngeal nerve or by main tumors. We reviewed the short-term and long-term results of esophagectomy for patients with locally advanced ESCC and hoarseness at diagnosis.
Patients
Patients who initially presented with hoarseness from recurrent laryngeal nerve palsy between 2009 and 2018 and underwent esophagectomy for thoracic ESCC were eligible for this study. Pharyngolaryngectomy or cervical ESCC were exclusionary.
Results
A total of 15 patients were eligible, and 14 underwent resection of the recurrent laryngeal nerves. The remaining patient had nerve-sparing surgery. Nine patients (60%) had post-operative complications ≥ Clavien–Dindo class II and, pulmonary complications were most common. Two patients (13%) died in the hospital. The 5-year overall survival rate for all patients was 16%. Age (≤ 65 years), cT1/T2 tumor, and remarkably good response to neoadjuvant treatment were likely related to longer survival; however, these relationships were not statistically significant.
Conclusions
Esophagectomy for ESCC patients who are diagnosed with recurrent laryngeal nerve paralysis at initial presentation could be a treatment option if the patient is relatively young, has a cT1/T2 tumor, or shows a remarkably good response to neoadjuvant treatment. However, clinicians should be aware of the possibility of postoperative pulmonary complications, which were frequently observed with the procedure.
Objective In recent years, circulating tumor cells (CTCs) have attracted attention for prediction of metastasis in breast, prostate, and colon cancers. This study aimed to investigate whether ...detection of CTCs could be prognostic factor in esophageal cancer.Methods This study involved 38 patients treated at Juntendo University from May 2010 to April 2013 who provided consent. CTCs were measured using CellSearch® system in preoperative peripheral blood. Clinicopathological parameters and prognostic factors were retrieved from our medical records.Results CTCs were detected in 6 of 38 patients (15.8%). Among patients’ characteristics and clinicopathological features, CTC-positive group had higher serum SCC levels and tended to have more advanced cStages than the CTC-negative group. The CTC-negative group showed better survival curves than CTCs positive-group in both overall survival (OS) and disease-free survival (DFS) although the differences were not statistically significant. CTCs positivity has a possibility to be prognostic marker according to multivariable analysis of OS and DFS.Conclusion Although this study has some limitations, our results suggest that CTCs in preoperative peripheral blood has potential to be a prognostic marker for esophageal cancer.
Objectives Some previous studies reported that the levels of a low-density lipoprotein receptor relative with 11 ligand-binding repeats (LR11) was a prognostic marker in some malignant tumors; ...however, whether LR11 is related to survival in patients with esophageal cancer remains unclear.Methods In this study, we measured LR11 in the preoperative serum of 46 patients of esophageal cancer who undergoing surgery using a sandwich enzyme-linked immunosorbent assay (ELISA) method with anti-LR11 monoclonal antibodies. We investigated the correlation between the level of LR11 and survival of patients with esophageal cancer. Clinicopathological data were retrospectively retrieved from our institution’s database.Results The patients were divided into two groups (low LR11 and high LR11) based on the level of LR11. There was no statistical difference in clinicopathological factors between these two groups. The low LR11 group had a significantly longer overall survival than the high LR11 group.Conclusions LR11 can be measured with a relatively simple ELISA and is potentially a new prognostic marker for esophageal cancer.
The first and second Juntendo University and Peking University International Academic Joint Symposia were held at Juntendo University Hongo Campus in Tokyo Japan, in 2010 and 2011. The third joint ...symposium was held at Peking University Cancer Hospital in Peking China on 6th September 2012, and was organized by Juntendo University, Peking University, and Cardiff University (UK). The title of this symposium was “2012 International Joint Symposium of Clinical and Translational Studies of Gastrointestinal Malignancies” (Figure-1). In the first and second symposia, the presenters had been professors from only Juntendo University and Peking University. However, the third symposium included two professors from the National Cancer Center in Japan and five professors from Cardiff University in the UK as presenters, in addition to those from Juntendo and Peking University. The agenda is shown in Figure-2. The delegates from Japan were as follows (Figure-3). (The rest is omitted)
AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation(GCED).METHODS We retrospectively investigated data on 6 cases of early stage GCED and ...186 cases of early stage conventional gastric cancer(CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital.GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate.RESULTS Six cases(5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases(139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC(66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED(positivity, 83.3%), immunohistochemically.CONCLUSION Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this highly malignant type of cancer.
The molecular pathogenesis of esophageal carcinosarcoma (ECS) has not been fully investigated. This study includes 16 consequent cases of surgically resected ECS. Genetic alterations were ...independently examined for carcinoma in situ, carcinomatous, and sarcomatous areas. Six cases were analyzed by next-generation sequencing, and the remaining cases were analyzed by Sanger sequencing for
TP53
,
PTEN
, and
INI1
. Sarcomatous components in 3 cases showed histologically heterogenous feature of osteosarcoma. Lymph node metastasis was found in 12 out of 16 cases. Survival analysis revealed 5-year overall survival rate of 59.9%, and the median survival time was 5.37 years.
TP53
was the most frequently mutated gene, being identified in 11 of 16 patients (68.8%), 7 of whom (63.6%) had the same mutations in both carcinomatous and sarcomatous areas. Almost complete concordance was found between p53 immunohistochemistry and
TP53
missense mutations. Five-year overall survival tended to be worse for patients with p53 overexpression, although the data was not significant (
p
= 0.186). Nine of 16 patients (56.3%) showed loss of heterozygosity (LOH) at the
INI1
locus, and this LOH status was consistent with both components. However, interestingly, INI1 expression was preserved in all cases. In addition, copy number variation analysis revealed gene amplification in several tyrosine kinase receptors. Accumulation of mutations in tumor suppressor genes such as
TP53
and
INI1
seemed to occur during ECS development.
Few driver genes have been well established in esophageal squamous cell carcinoma (ESCC). Identification of the genomic aberrations that contribute to changes in gene expression profiles can be used ...to predict driver genes.
We searched for driver genes in ESCC by integrative analysis of gene expression microarray profiles and copy number data. To narrow down candidate genes, we performed survival analysis on expression data and tested the genetic vulnerability of each genes using public RNAi screening data. We confirmed the results by performing RNAi experiments and evaluating the clinical relevance of candidate genes in an independent ESCC cohort.
We found 10 significantly recurrent copy number alterations accompanying gene expression changes, including loci 11q13.2, 7p11.2, 3q26.33, and 17q12, which harbored CCND1, EGFR, SOX2, and ERBB2, respectively. Analysis of survival data and RNAi screening data suggested that GRB7, located on 17q12, was a driver gene in ESCC. In ESCC cell lines harboring 17q12 amplification, knockdown of GRB7 reduced the proliferation, migration, and invasion capacities of cells. Moreover, siRNA targeting GRB7 had a synergistic inhibitory effect when combined with trastuzumab, an anti-ERBB2 antibody. Survival analysis of the independent cohort also showed that high GRB7 expression was associated with poor prognosis in ESCC.
Our integrative analysis provided important insights into ESCC pathogenesis. We identified GRB7 as a novel ESCC driver gene and potential new therapeutic target.
•Spheroids were created from esophageal carcinoma cells using NanoCulture® Plates.•The proportion of strongly ALDH-positive cells increased in 3-D culture.•Expression of cancer stem cell-related ...genes was enhanced in 3-D culture.•CA-9 expression was enhanced, suggesting hypoxia had been induced in 3-D culture.•Drug resistance was increased. 3-D culture is useful for inducing cancer stem cells.
In recent years, research on resistance to chemotherapy and radiotherapy in cancer treatment has come under the spotlight, and researchers have also begun investigating the relationship between resistance and cancer stem cells. Cancer stem cells are assumed to be present in esophageal cancer, but experimental methods for identification and culture of these cells have not yet been established. To solve this problem, we created spheroids using a NanoCulture® Plate (NCP) for 3-dimensional (3-D) cell culture, which was designed as a means for experimentally reproducing the 3-D structures found in the body. We investigated the potential for induction of cancer stem cells from esophageal cancer cells.
Using flow cytometry we analyzed the expression of surface antigen markers CD44, CD133, CD338 (ABCG2), CD318 (CDCP1), and CD326 (EpCAM), which are known cancer stem cell markers. None of these surface antigen markers showed enhanced expression in 3-D cultured cells. We then analyzed aldehyde dehydrogenase (ALDH) enzymatic activity using the ALDEFLUOR reagent, which can identify immature cells such as stem cells and precursor cells. 3-D-cultured cells were strongly positive for ALDH enzyme activity. We also analyzed the expression of the stem cell-related genes Sox-2, Nanog, Oct3/4, and Lin28 using RT-PCR. Expression of Sox-2, Nanog, and Lin28 was enhanced. Analysis of expression of the hypoxic surface antigen marker carbonic anhydrase-9 (CA-9), which is an indicator of cancer stem cell induction and maintenance, revealed that CA-9 expression was enhanced, suggesting that hypoxia had been induced. Comparison of cancer drug resistance using cisplatin and doxorubicin in 3-D-cultured esophageal cancer cells showed that cancer drug resistance had increased. These results indicate that 3-D culture of esophageal squamous cell carcinoma lines is a useful method for inducing cancer stem cells.
Summary Basaloid squamous cell carcinoma of the esophagus is a rare variant of squamous cell carcinoma. We reviewed 878 cases of esophageal squamous cell carcinoma and detected 22 cases (3%) of ...basaloid squamous cell carcinoma. These tumors and stage-matched paired conventional squamous cell carcinomas were investigated for clinicopathologic features and immunoreactivity of cytokeratin subtypes, p53, B-cell lymphoma 2 (bcl-2), β -catenin, and epidermal growth factor receptor. Molecular aberrations in p53 , CTNNB1 (the gene encoding β-catenin), and epidermal growth factor receptor (EGFR) were also determined. Patients with basaloid squamous cell carcinomas demonstrated a 5-year survival rate of 42%, significantly worse than those with well-differentiated squamous cell carcinoma ( P < .01). Histologically, solid nests with central necrosis and a cribriform pattern were identified in almost all (≥95%) cases, and ductal differentiation was less frequent (45%) but associated with significantly better survival ( P < .05). Compared with conventional squamous cell carcinomas, the basaloid squamous cell carcinomas were less immunoreactive for cytokeratin 14, cytokeratin 903, and membranous β -catenin ( P < .01-.001) but more reactive for bcl-2, nuclear β -catenin, epidermal growth factor receptor, and Ki-67 ( P < .05-.001). Direct sequencing showed mutations of p53 (36%), EGFR (14%), but not CTNNB1 ; fluorescent in situ hybridization detected amplification of the epidermal growth factor receptor gene (22%). In basaloid squamous cell carcinomas, low-level expression of cytokeratin 14/cytokeratin 903 and mutations of p53 and EGFR had a significant influence on worse survival ( P < .05-.001). We conclude that the esophageal basaloid squamous cell carcinoma, a neoplasm with particularly aggressive biologic behavior, should be differentiated from conventional squamous cell carcinomas. In this context, immunohistochemical assessment of several markers might provide a useful adjunct diagnostic tool. Aberrations of p53 and epidermal growth factor receptor genes are possibly involved in progression of esophageal basaloid squamous cell carcinoma.
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