Background
The size of the superior thoracic aperture (STA) may be associated with the incidence of cervical anastomotic leakage after esophagectomy. Using computed tomography (CT) images, we ...retrospectively investigated relationships between the size of the STA and anastomotic leakage following esophagectomy using the retrosternal or posterior mediastinal reconstruction routes.
Methods
Patients who underwent cervical esophagogastrostomy after esophagectomy between 2009 and 2015 were enrolled in this retrospective study (
n
= 326). The size of the STA was measured at the level of the sternal notch using preoperative CT images, and it was determined as the anteroposterior diameter of the STA minus the diameter of the trachea. Associations between clinical factors, including the size of the STA, and anastomotic leakage were determined.
Results
Anastomotic leakage occurred in 44 patients (13.5%). The size of the STA ranged from 0 to 49 mm (median, 16 mm). In univariate analyses, the duration of the operation, tumor location, anastomotic procedure, and the size of the STA were significantly associated with anastomotic leakage. In multivariate analysis, only the size of the STA was independently related to leakage (odds ratio 1.05; 95% confidence interval 1.002–1.107;
p
= 0.027). The size of the STA affected the incidence of leakage more frequently with the posterior mediastinal route than with the retrosternal route.
Conclusions
The size of the STA was significantly associated with the incidence of anastomotic leakage after esophagectomy, especially when using the posterior mediastinal route.
Objective: In the Vienna classification, esophageal non-invasive neoplasms are classified as low-grade dysplasia (LGD), high-grade dysplasia (HGD), CIS and suspicion of invasive carcinoma. Polycomb ...group proteins EZH2 and Bmi-1 are involved in the transactivation of p16 INK4a and p53, and have been implicated in the carcinogenesis, progression, and poor prognosis of several cancers;however, their role in early esophageal carcinogenesis has not yet been elucidated. Therefore, in the current study, we examined the expression of EZH2 and Bmi-1 in association with p53 and p16 INK4a during esophageal squamous carcinogenesis.Materials: We used a series of 60 esophageal squamous intraepithelial lesions (58 patients), resected endoscopically or surgically at Juntendo University Hospital between 2007 and 2011. The 58 patients comprised 50 males and 8 females, with a mean age of 67.1 years (range, 51-81 years). According to the Vienna classification, we classified the lesions into LGD (category 3), HGD (category 4.1), and CIS (category 4.2) to identify possible biological differences between these lesions, 14 low-grade dysplasia (LGD), 23 high-grade dysplasia (HGD), and 23 carcinoma in situ (CIS) specimens.Methods: Immunohistochemical analysis was performed on 3-μm sections of formalin-fixed, paraffin-embedded tumor tissues. Monoclonal antibodies used in the present study were against EZH2, Bmi-1, p16 INK4a, p53, and Ki-67. Immunohistochemical results of each protein were scored as immunolabeling scores (ILSs) from 0 to 3 points according to each quarter of occupation of the squamous epithelium, and were analyzed on the basis of the clinicopathologic variables.Results: All of these lesions had male predominance. Tumor size in CIS was significantly larger than that in LGD (p<0.05). ILSs for all proteins but p16 INK4a showed significant stepwise increases from LGD to HGD to CIS (p < 0.05-0.001). Furthermore, the expressions of all proteins but p16 INK4a were positively related to each other. However, 3 lesions of LGD (21%), 8 lesions of HGD (35%), and 6 lesions of CIS (26%) demonstrated p16 INK4a expression, even under the co-expression of EZH2 and Bmi-1. In HGD, high-EZH2 ILS was significantly associated with larger tumor size (p < 0.05). In addition, high-p53 ILS was associated with larger tumor in CIS (p<0.05).Conclusions: This study indicates that the overexpression of polycomb group proteins EZH2 and Bmi-1, along with p53 and Ki-67, but not p16 INK4a, has an important role during the early stages of esophageal squamous carcinogenesis. Interestingly, unlike other malignant tumors, for example, squamous cell lung cancer, cholangiocarcinoma and colorectal cancer, a minor subset of cases of esophageal squamous intraepithelial neoplasia exhibit the p16 expression, even under the coexpression of EZH2 and Bmi-1.
Background: Since esophageal carcinoma progresses asymptomatically, for many patients, the disease is already advanced at the time of diagnosis. Compared with other digestive organ cancers, ...esophageal carcinoma progresses rapidly and has a poor prognosis, making early diagnosis important. There is a need to develop a diagnostic method using clinical markers that is non-invasive while being both highly sensitive and specific. Method: Exhaled breath was collected from 17 patients with esophageal squamous cell carcinoma, as well as 9 healthy subjects (control group) with no history of cancer. For each fasting subject, 1 L of exhaled breath was collected in a gas sampling bag. Volatile organic compounds (VOCs) were then extracted from each sample using Solid-Phase Micro-Extraction (SPME) fibers and analyzed by gas chromatography. Results: Comparison of the principal component analyses of the VOCs showed a significant difference between the patient group and the healthy control group. In the patient group, significant increases were observed in 4 VOCs, namely, acetonitrile, acetic acid, acetone, and 2-butanone. Receiver operating characteristic (ROC) curves were drawn for acetonitrile, acetic acid, acetone, and 2-butanone. The calculated area-under-the-curve (AUS) indicated that esophageal carcinoma patients can be identified with a high probability of 0.93. Conclusions: It was confirmed that there are significant differences in the contents of certain VOCs contained in the exhaled breath of esophageal carcinoma patients compared with that of healthy subjects. The analysis for these VOCs is inexpensive, simple and non-invasive, causing no adverse reactions, and it has potential as a new tool for detecting early-stage esophageal carcinoma.
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.
Aims
This study was performed to elucidate the clinicopathological characteristics, genetic alterations and therapeutic targets of primary malignant melanoma of the oesophagus (PMME).
Methods and ...Results
The clinicopathology and molecular pathology of 13 PMME cases and 10 skin malignant melanoma (SKMM) cases were analysed with next‐generation sequencing (NGS) and immunohistochemistry. The 3‐year overall survival rate and the median survival time for PMME patients were 23.1% and 11.9 months, respectively. Three (23.1%) and eight (61.5%) PMME cases showed a papillary structure and lymph node metastasis, respectively. DNA and RNA hybridization capture‐based NGS analysis revealed that NF1 was the most frequently mutated gene (30%) in 10 of the PMME cases. Other mutations detected in PMME included SF3B1 (20%), KRAS (10%), BRCA2 (10%), KIT (10%) and TP53 (10%) mutations. Commonly detected BRAF mutations in SKMM were not detected in PMME. Immunohistochemistry and mutation status were concordant between p53/c‐Kit and TP53/KIT, respectively. Focal expression of programmed death‐ligand 1 was observed in one PMME sample. The tumour mutation burden in PMME was significantly lower than that in SKMM (P = 0.030). No PMME case showed high microsatellite instability. RNA sequencing revealed a distinctive pattern with respect to RNA expression. T‐cell co‐stimulation differed between PMME and SKMM.
Conclusions
The RAS–mitogen‐activated protein kinase pathway is one of the main pathways involved in PMME. The genetic profile of PMME was similar to that of mucosal/acral melanoma, but differed from the SKMM profile. A subset of PMMEs may contain actionable mutations. Immunotherapy seemed to be less effective for most PMMEs in this series.
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(R) 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.
BackgroundIn esophageal cancer, lymphatic spread occurs more frequently and at an earlier stage than in other gastrointestinal cancers, and both preoperative and intraoperative diagnoses of lymph ...nodes metastases are sometimes incorrect. Our objective was to measure the sizes of lymphatic metastases and to examine the accuracy of clinical diagnosis of lymphatic spread in patients with squamous cell carcinoma of the esophagus.MethodsThe sizes of 320 metastatic lymph nodes of 9254 dissected nodes from 92 consecutive esophagectomy patients over 1 year were measured and compared with the sizes of the actual metastases within the nodes. These data allowed investigation of the correct rate of preoperative diagnosis of lymph node metastasis.ResultsThe mean diameter of the metastases was 4.8 mm, which was significantly smaller than that of the involved lymph nodes. Among the metastatic lymph nodes, 37.2% were less than 5 mm in diameter, and 63.1% of the metastases were less than 5 mm in diameter. The true-positive and true-negative diagnosis rate for all lymph node stations in three fields (neck, thorax, and abdomen) was only 23.2%, and the false-negative rate for diagnosis of lymph node metastasis was 53.7%.ConclusionsTwo-thirds of involved lymph nodes had very small metastases (<5 mm), suggesting that limited confidence should be placed in the preoperative diagnosis of lymphatic spread. Therefore, extensive lymph node dissection appears appropriate in esophageal cancer surgery, given the small sizes of many metastases and the difficulty with preoperative diagnosis.
Background
The incidence of esophageal adenocarcinoma is only 1%–2% in Japan. For this reason, many aspects of this disease have not been clarified, such as its generation, progress, and the ...potential of malignancy. It is necessary to investigate the strategy for treating this disease.
Methods
Between 1998 and 2008, 19 cases were diagnosed as adenocarcinoma with Barrett’s esophagus and treated with esophagectomy at Juntendo University: 13 cases were early stage and 6 cases were advanced stage. Distribution of lymph node metastasis and prognosis were investigated.
Results
The incidence of lymph node metastases of adenocarcinoma is statistically lower (15.4%) compared with that of squamous cell carcinoma (SCC) (44.0%) (
P
= 0.034) when the depth of the tumor is not beyond the submucosal layer. Even in the early stages of adenocarcinoma, positive nodes were found in the lower mediastinum and gastric cardia. In advanced cases, cancer had spread randomly to the upper mediastinum or celiac region. Mean survival time of superficial and advanced adenocarcinoma after esophagectomy was 3,517.5 ± 330.6 and 2,061.4 ± 451.3 days, respectively, whereas that of SCC was 2,794.7 ± 131.0 and 1,669.1 ± 101.5 days, respectively. Overall survival of superficial or advanced adenocarcinoma was better than that of SCC but was not statistically superior.
Conclusions
Endoscopic mucosal resection is limitedly proposed for mucosal tumors. Esophagectomy with a mediastinal lymphadenectomy should be conducted for tumors invading the submucosa. An individualized strategy is required that could approach the upper mediastinum based on staging and location of lymph node metastases.
Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare variant of typical squamous cell carcinoma (SCC) associated with poor survival. A characteristic feature is nuclear accumulation of ...β-catenin, without a mutation of the gene. We studied the methylation status of Wnt antagonist genes, such as secreted frizzled-related protein (sFRP) gene family members,
Wnt inhibitory factor-1
(WIF-1),
Dickkopf-1
(Dkk-1), and
human Dapper protein-1
(HDPR-1), and alterations of the
APC
,
Axin1
, and
Axin2
genes in 30 cases of esophageal BSCC. β-catenin and sFRP (sFRP-1, sFRP-2, sFRP-4, sFRP-5) protein expression was examined by immunohistochemistry.
APC
,
Axin1
, and
Axin2
gene mutations were detected in 3, 2, and 2 cases, respectively, and 6 cases (20 %) harbored at least 1 alteration in these genes. Methylation of the
sFRP-2
promoter region was observed in all cases, and methylation was frequent in
sFRP-1
and
sFRP-5
, but infrequent in
Dkk-1
,
WIF-1
,
sFRP-4
, and
HDPR-1
. sFRP-2 expression was almost completely absent in 25 cases (83 %), consistent with the methylation status. Nuclear accumulation of β-catenin was observed in all cases. sFRP-5 expression was associated with a low nuclear β-catenin labeling index. These results show that
sFRP-2
is a target gene of hypermethylation in esophageal BSCC and suggest that sFRP-2 might contribute to BSCC tumorigenesis through the Wnt/β-catenin signaling pathway.
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