Esophageal stricture following endoscopic submucosal dissection (ESD) can be a serious complication in patients with large mucosal defects. This preliminary study examined the efficacy of using a ...polyglycolic acid (PGA) sheet with fibrin glue for the prevention of esophageal stricture after ESD.
A total of 15 patients were enrolled. After resection, PGA sheets were placed over the surgical wound. The size of the mucosal defect was estimated by dividing the circumference of the esophagus into 12 parts of equal size. The occurrence of esophageal stricture at 6 weeks, along with the proportion of patients who had PGA sheet remaining in place 1 week and 2 weeks after ESD, and the occurrence of adverse events were investigated.
The size of mucosal defects in the 15 patients were 7/12 (n = 4), 8 /12 (n = 5), 9/12 (n = 4), 10/12 (n = 1) and 11/12 (n = 1). Esophageal stricture occurred in 1/13 patients (7.7 %; two patients were not included in the analysis because they had required surgical resection during the follow-up period). The PGA sheet remained at 1 week after ESD in 13/15 patients (86.7 %) and at 2 weeks after ESD in 6/15 patients (40 %). No adverse events were observed.
PGA sheets may have the potential to prevent esophageal stricture.
Background & Aims Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer in Japan. Smoking and drinking alcohol are environmental risk factors for ESCC, whereas single ...nucleotide polymorphisms in ADH1B and ALDH2 , which increase harmful intermediates produced by drinking alcohol, are genetic risk factors. We conducted a large-scale genomic analysis of ESCCs from patients in Japan to determine the mutational landscape of this cancer. Methods We performed whole-exome sequence analysis of tumor and nontumor esophageal tissues collected from 144 patients with ESCC who underwent surgery at 5 hospitals in Japan. We also performed single-nucleotide polymorphism array-based copy number profile and germline genotype analyses of polymorphisms in ADH1B and ALDH2 . Polymorphisms in CYP2A6, which increase harmful effects of smoking, were analyzed. Functions of TET2 mutants were evaluated in KYSE410 and HEK293FT cells. Results A high proportion of mutations in the 144 tumor samples were C to T substitution in CpG dinucleotides (called the CpG signature) and C to G/T substitutions with a flanking 5′ thymine (called the APOBEC signature). Based on mutational signatures, patients were assigned to 3 groups, which associated with environmental (drinking and smoking) and genetic (polymorphisms in ALDH2 and CYP2A6 ) factors. Many tumors contained mutations in genes that regulate the cell cycle ( TP53, CCND1, CDKN2A , FBXW7 ); epigenetic processes ( MLL2, EP300, CREBBP , TET2 ); and the NOTCH ( NOTCH1 , NOTCH3 ), WNT ( FAT1 , YAP1 , AJUBA ) and receptor-tyrosine kinase−phosphoinositide 3-kinase signaling pathways ( PIK3CA , EGFR , ERBB2 ). Mutations in EP300 and TET2 correlated with shorter survival times, and mutations in ZNF750 associated with an increased number of mutations of the APOBEC signature. Expression of mutant forms of TET2 did not increase cellular levels of 5-hydroxymethylcytosine in HEK293FT cells, whereas knockdown of TET2 increased the invasive activity of KYSE410 ESCC cells. Computational analyses associated the mutations in NFE2L2 we identified with transcriptional activation of its target genes. Conclusions We associated environmental and genetic factors with base substitution patterns of somatic mutations and provide a registry of genes and pathways that are disrupted in ESCCs. These findings might be used to design specific treatments for patients with esophageal squamous cancers.
Primary malignant melanoma of the esophagus (PMME) is a rare disease with an extremely poor prognosis. Up to 2011, approximately 300 cases had been reported worldwide. The average age of onset is ...60.5 years old, with a prevalence of males (2:1). A typical finding of PMME is a lobular or polyploid, well-circumscribed and pigmented tumor, partly covered with normal mucosa. PMME represents various colors depending on its melanin quantity and commonly coexists with intramural metastases, melanocytosis or melanoma in situ. The tumor is located from the middle to lower thoracic esophagus. The accuracy of diagnosis from biopsy is approximately 80%, because many cases are misdiagnosed as a poorly differentiated carcinoma because of the absence of melanin granules. A definite diagnosis was made by immunohistochemical examination with positive results of S100 protein, HMB45 and neuron-specific enolase. PMME has a highly metastatic potential, and the incidence of distant metastasis at the initial diagnosis is around 40–80%. A metastatic tumor from cutaneous malignant melanoma is another pigmented esophageal tumor to be considered when making the differential diagnosis for PMME. Junctional activity with melanotic cells in the adjacent epithelium and the presence of in situ melanoma and/or a satellite tumor without a previous history of cutaneous melanoma are definitive. Most of the reported patients were treated with radical esophagectomy, which is believed to be an effective approach for localized PMME. Five-year survival rates have been achieved in 37% recently, while adjuvant therapy has not been proven to increase overall survival but plays a palliative role.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
In 2009, the Japan Esophageal Society (JES) established a system for certification of qualified surgeons as “Board Certified Esophageal Surgeons” (BCESs) or institutes as “Authorized ...Institutes for Board Certified Esophageal Surgeons” (AIBCESs). We examined the short-term outcomes after esophagectomy, taking into consideration the certifications statuses of the institutes and surgeons.
Methods
This study investigated patients who underwent esophagectomy for thoracic esophageal cancer and who were registered in the Japanese National Clinical Database (NCD) between 2015 and 2017. Using hierarchical multivariable logistic regression analysis adjusted for patient-level risk factors, we determined whether the institute’s or surgeon’s certification status had greater influence on surgery-related mortality or postoperative complications.
Results
Enrolled were 16,752 patients operated on at 854 institutes by 1879 surgeons. There were significant differences in the backgrounds and incidences of postoperative complications and surgery-related mortality rates between the 11,162 patients treated at AIBCESs and the 5590 treated at Non–AIBCESs (surgery-related mortality rates: 1.6% vs 2.8%). There were also differences between the 6854 patients operated on by a BCES and the 9898 treated by a Non-BCES (1.7% vs 2.2%). Hierarchical logistic regression analysis revealed that surgery-related mortality was significantly lower among patients treated at AIBCESs. The institute’s certification had greater influence on short-term surgical outcomes than the operating surgeon’s certification.
Conclusions
The certification system for surgeons and institutes established by the JES appears to be appropriate, as indicated by the improved surgery-related mortality rate. It also appears that the JES certification system contributes to a more appropriate medical delivery system for thoracic esophageal cancer in Japan.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aims: We aimed to clarify the endoscopic/clinicopathological features of superficial non-ampullary duodenal epithelial tumors (SNADETs) based on their mucin phenotypes. Methods: We analyzed 62 SNADET ...lesions and classified them based on mucin phenotypic expression. Endoscopic and clinicopathological findings were compared according to mucin phenotypes. Results: Eleven lesions had the gastric phenotype (GP) and 43 lesions had the intestinal phenotype (IP). All GP lesions were located in the first portion of the duodenum, while most IP lesions (72.1%) were located in the second portion (p < 0.01). Tumor size was significantly larger in the GP than in the IP group (14.4 mm vs. 10.2 mm, p < 0.05). Reddish color (72.7% in GP vs. 37.2% in IP, p < 0.05), type 0-I (72.7% vs. 11.6%, p < 0.01), lobular/granular pattern (81.8% vs. 4.7%, p < 0.01), and category 4/5 in Vienna classification (81.8% vs. 30.2%, p < 0.01) were observed significantly more often in the GP than in the IP group. Regarding findings of magnifying endoscopy with narrow-band imaging (M-NBI), white opaque substance (22.2% in GP vs. 89.7% in IP, p < 0.01) and light blue crest (0% vs. 43.6%, p < 0.05) were significantly less frequently observed in the GP group. Oval-shaped marginal epithelium (66.7% vs. 17.9%, p < 0.01), dense pattern (55.6% vs. 2.6%, p < 0.01), and dilatation of the intervening part (100% vs. 12.8%, p < 0.01) were more frequently observed in the GP group. Conclusions: SNADETs showed distinct endoscopic/clinicopathological features according to the mucin phenotype. Tumor location, coloration, macroscopic type, and endoscopic findings including M-NBI are useful to distinguish the mucin phenotypes of SNADETs.
Objectives The goal of the study was to examine the relationships among micrometastasis, pathological degree of differentiation and survival in patients with esophageal squamous cell carcinoma ...(SCC).Design A single-center retrospective study of patients diagnosed with thoracic esophageal SCC.Methods Immunostaining using CK13 was carried out for all lymph nodes resected by radical esophagectomy with three-field lymphadenectomy. The relationships among micrometastasis to lymph nodes, degree of differentiation and survival were investigated.Results The 25 patients included 14 (56.0%) well-differentiated and 11 (44.0%) moderately differentiated cases. In multivariate analysis, well-differentiated cases were not related to micrometastasis (odds ratio (OR): 1.5, confidence interval (CI): 0.2-12, p=0.7). In multivariate analysis of survival, cases in pStage III or higher were likely to have shorter survival (hazard ratio (HR): 2.8, CI: 0.7-12, p=0.16), and those with micrometastasis also tended to have shorter survival (HR: 2.7, CI: 0.8-9, p=0.11)); however, well-differentiated cases were not significantly related to survival (HR: 1.5, CI: 0.4-5.5, p=0.5).Conclusion Micrometastasis to lymph nodes may be a prognostic factor even in advanced esophageal cancer. The degree of differentiation was not related to micrometastasis or survival.
Esophageal basaloid squamous cell carcinoma (EBSCC) is a poorly differentiated variant of esophageal squamous cell carcinoma (ESCC). We aimed to investigate the clinicopathological and molecular ...biological characteristics of EBSCC and enrolled 58 patients with EBSCCs. Clinicopathological factors including age, sex, tumor size and location, gross tumor type (superficial, protrusive, ulcerative, and unclassifiable), lymphovascular invasion, infiltrative growth, intramural invasion, TNM stage, and dominant histological type were examined. EBSCCs were classified into four types (solid, cribri, microcystic, and tubular) according to the dominant histology. Next-generation sequencing (NGS) of a cancer hotspot panel was performed in 19 cases. NGS identified
TP53
as the most frequently mutated gene, and copy number variation analysis revealed the most frequent loss of heterozygosity (LOH) at the ataxia telangiectasia mutated (
ATM
) and retinoblastoma 1 (
RB1
) loci. Target sequencing for
TP53
was performed for the remaining 39 cases. We also performed LOH analysis for
TP53
,
ATM
, and
RB1
and immunohistochemical staining for p53, ATM, and Rb in all cases. The rates of
TP53
mutations and LOH and p53 aberrant expression were high (79.3%, 63.2%, and 72.4%, respectively); however, the frequencies were similar to those reported for ESCC. LOH rates of the
RB1
and
ATM
loci were also high (55.3% and 67.2%, respectively). Overall survival rate was 66.5%, and recurrence-free survival rate was 55.0%. Only conventional clinicopathological factors had a prognostic impact in EBSCC; the microcystic type had the poorest prognosis. Our findings could be useful in developing novel treatment strategies for EBSCC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Background
We assessed the benefit of hepatic and pulmonary resections in patients with liver and lung recurrences, respectively, after resection of esophageal carcinoma.
Methods
The study population ...consisted of 138 consecutive patients with recurrent esophageal carcinoma after esophagectomy conducted between 2003 and 2005. The pattern, timing of appearance, and the prognosis of these recurrences were investigated, paying particular attention to those undergoing hepatic and pulmonary resections.
Results
In total, 55 and 92 patients developed locoregional and distant-organ metastases 13 and 6 months (median) after surgery, respectively, including 9 patients with both types of recurrence. The distant-organ metastases were found in the liver (
n
= 26), lung (
n
= 27), bone (
n
= 21), and other organs (
n
= 29). Patients with pulmonary recurrences had a better overall prognosis (median survival after recurrence detection 13 months) than those with hepatic metastases (5 months) or nonhepatic nonpulmonary metastases. (3 months) Hepatic and pulmonary resections were carried out in patients with oligonodular (
n
= ≤ 2) isolated liver and lung metastases (
n
= 5, respectively). Although the survivals of patients with lung metastases who were treated/not treated by pulmonary resection were different (median survival: 48 vs. 10 months,
p
< 0.01), the difference in the survivals between patients with hepatic metastases who were treated/not treated by hepatic resection reached only borderline statistical significance (13 vs. 5 months,
p
= 0.06).
Conclusions
Resection of pulmonary metastases yields a survival benefit in properly selected patients. The benefit of resection for hepatic metastases remains controversial.
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EMUNI, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, SBNM, UL, UM, UPUK
Objectives Since esophageal carcinoma progresses asymptomatically, for many patients the disease is already advanced at the time of diagnosis. The main methods that are currently used to diagnose ...esophageal carcinoma are upper gastrointestinal radiographic contrast examinations and upper gastrointestinal endoscopy, but early discovery of this disease remains difficult. There is a need to develop a diagnostic method using biomarkers that is non-invasive while both highly sensitive and specific.Materials and Methods Exhaled breath was collected from 17 patients with esophageal squamous cell carcinoma (ESCC), as well as 9 control subjects without history of any cancer. For each fasting subject, 1L 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-mass spectrometry (GC-MS).Results Levels of acetonitrile, acetic acid, acetone, and 2-butanone in exhaled breath were significantly higher in the patient group than in the control group (p = 0.0037, 0.0024, 0.0024 and 0.0037, respectively). ROC curves were drawn for these 4 VOCs, and the results for the area-under-the-curve (AUC) indicated that ESCC patients can be identified with a high probability of 0.93.Conclusion We found distinctive VOCs in exhaled breath of ESCC patients. These VOCs have a potential as new clinical biomarkers for ESCC. The measurement of VOCs in exhaled breath may be a useful, non-invasive method for diagnosis of ESCC.
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