The Japan Gastroenterological Endoscopy Society has developed endoscopic submucosal dissection/endoscopic mucosal resection guidelines. These guidelines present recommendations in response to 18 ...clinical questions concerning the preoperative diagnosis, indications, resection methods, curability assessment, and surveillance of patients undergoing endoscopic resection for esophageal cancers based on a systematic review of the scientific literature.
Background
In elderly patients with superficial esophageal squamous cell carcinoma (ESCC), the optimal treatment strategy after non-curative endoscopic submucosal dissection (ESD) remains unclear. We ...aimed to evaluate the validity of additional treatments after non-curative ESD and post-ESD survival predictors in elderly patients with ESCC.
Methods
Elderly patients (age > 75 years) treated with ESD for ESCC between January 2010 and July 2014 at six tertiary referral hospitals in Japan were retrospectively investigated and stratified according to lymph node metastasis risk, based on histological findings (high-risk factors: positive lymphovascular invasion, submucosal invasion, and positive/indeterminate vertical margin) and post-ESD treatment strategy: group A (287 patients; low risk), group B (41 patients; high risk, without additional treatment), and group C (32 patients; high risk, with additional treatment). We evaluated 3- and 5-year overall survival and disease-specific survival, and prognostic factors for post-ESD survival.
Results
At a median follow-up of 38, 40, and 49 months, respectively, there was 1 esophageal cancer-related death in group A, 1 in group B, and none in group C, whereas 22, 9, and 3 patients in groups A, B, and C died of other diseases. The groups differed significantly in overall survival (92.4%; 87.6%; 93.4%,
p
= 0.022), although not in disease-specific survival (99.4%; 96.3%; 100%,
p
= 0.217). On multivariate analysis, Charlson Comorbidity Index (CCI) ≥ 2 was the only independent risk factor for post-ESD death (hazard ratio 7.92; 95% confidence interval 3.42–18.3;
p
< 0.001).
Conclusions
A follow-up strategy without additional treatment after ESD for ESCC may be acceptable in high-risk elderly patients, especially for CCI ≥ 2.
Prospectively collected long-term data of patients undergoing endoscopic resection for superficial esophageal squamous cell carcinoma (ESCC) are limited. The aim of this study was to determine the ...prospectively collected long-term outcomes of endoscopic resection for ESCC as a secondary analysis of the Japan Esophageal Cohort (JEC) study.
Patients who underwent endoscopic resection of intramucosal ESCC at 16 institutions between September 2005 and May 2010 were enrolled in the JEC study. All patients underwent endoscopic examination with iodine staining at 3 and 6 months after resection, and every 6 months thereafter. We investigated clinical courses after endoscopic resection, survival rates, and cumulative incidence of metachronous ESCC.
330 patients (mean age 67.0 years) with 396 lesions (mean size 20.4 mm) were included in the analysis. Lesions were diagnosed as high-grade intraepithelial neoplasia in 17.4 % and as squamous cell carcinoma in 82.6 % (limited to epithelium in 28.4 %, to lamina propria in 55.4 %, and to muscularis mucosa in 16.2 %). En bloc resection was achieved in 291 (73.5 %). The median follow-up period was 49.4 months. Local recurrences occurred in 13 patients (3.9 %) and were treated by endoscopic procedures. Lymph node metastasis occurred in two patients (0.6 %) after endoscopic resection. The 5-year overall, disease-specific, and metastasis-free survival rates were 95.1 %, 99.1 %, and 94.6 %, respectively. The 5-year cumulative incidence rate of metachronous ESCC was 25.7 %.
Our study demonstrated that endoscopic resection is an effective treatment for intramucosal ESCC, with favorable long-term outcomes.
Esophagectomy is the standard treatment for stage I esophageal squamous cell carcinoma (ESCC). We conducted a single-arm prospective study to confirm the efficacy and safety of selective ...chemoradiotherapy (CRT) based on findings from endoscopic resection (ER).
We performed a prospective study of patients with T1b (SM1–2) N0M0 thoracic ESCC from December 2006 through July 2012; 176 patients underwent ER. Based on the findings from ER, patients received the following: no additional treatment for patients with pT1a tumors with a negative resection margin and no lymphovascular invasion (group A); prophylactic CRT with 41.4 Gy delivered to locoregional lymph nodes for patients with pT1b tumors with a negative resection margin or pT1a tumors with lymphovascular invasion (group B); or definitive CRT (50.4 Gy) with a 9-Gy boost to the primary site for patients with a positive vertical resection margin (group C). Chemotherapy comprised 5-fluorouracil and cisplatin. The primary end point was 3-year overall survival in group B, and the key secondary end point was 3-year overall survival for all patients. If lower limits of 90% confidence intervals for the primary and key secondary end points exceeded the 80% threshold, the efficacy of combined ER and selective CRT was confirmed.
Based on the results from pathology analysis, 74, 87, and 15 patients were categorized into groups A, B, and C, respectively. The 3-year overall survival rates were 90.7% for group B (90% confidence interval, 84.0%–94.7%) and 92.6% in all patients (90% confidence interval, 88.5%–95.2%).
In a prospective study of patients with T1b (SM1–2) N0M0 thoracic ESCC, we confirmed the efficacy of the combination of ER and selective CRT. Efficacy is comparable to that of surgery, and the combination of ER and selective CRT should be considered as a minimally invasive treatment option. UMIN-Clinical Trials Registry no.: UMIN000000553.
Curative management after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC), which invades the muscularis mucosa (pMM-ESCC) or shallow submucosal layer (pSM1-ESCC), has been ...controversial.
We identified patients with pMM-ESCC and pSM1-ESCC treated by ER. Outcomes were the predictive factors for regional lymph node and distant recurrence, and survival data were based on the depth of invasion, lymphovascular invasion (LVI), and additional treatment immediately after ER.
A total of 992 patients with pMM-ESCC (n = 749) and pSM1-ESCC (n = 243) were registered. According to the multivariate Cox proportional hazards analysis, pSM1-ESCC (hazard ratio = 1.88, 95% confidence interval 1.15-3.07, P = 0.012) and LVI (hazard ratio = 6.92, 95% confidence interval 4.09-11.7, P < 0.0001) were associated with a risk of regional lymph node and distant recurrence. In the median follow-up period of 58.6 months (range 1-233), among patients with risk factors (pMM-ESCC with LVI or pSM1-ESCC), the 5-year overall survival rates, relapse-free survival rates, and cause-specific survival rates of patients with additional treatment were significantly better than those of patients without additional treatment; 85.4% vs 61.5% ( P < 0.0001), 80.5% vs 53.3% ( P < 0.0001), and 98.5% vs 93.1% ( P = 0.004), respectively. There was no difference in survival rate between the chemoradiotherapy and surgery groups.
pSM1 and LVI were risk factors for metastasis after ER for ESCC. To improve the survival, additional treatment immediately after ER, such as chemoradiotherapy or surgery, is effective in patients with these risk factors.
Abstract
Background
Second primary head and neck cancers after endoscopic resection of esophageal squamous cell carcinoma adversely affect patients’ outcomes and the quality of life; however, an ...adequate surveillance schedule remains unclear.
Methods
We analyzed 330 patients with early esophageal squamous cell carcinoma who underwent endoscopic resection and were registered in the multicenter cohort study to evaluate adequate surveillance for detection of second primary head and neck cancers. Gastrointestinal endoscopists examined the head and neck regions after 3–6 months of endoscopic resection for esophageal squamous cell carcinoma and subsequently every 6 months. An otolaryngologist also examined the head and neck regions at the time of endoscopic resection for esophageal squamous cell carcinoma and at 12 months intervals thereafter.
Results
During the median follow-up period of 49.4 months (1.3–81.2 months), 33 second primary head and neck cancers were newly detected in 20 patients (6%). The tumor site was as follows: 22 lesions in the hypopharynx, eight lesions in the oropharynx, two lesions in larynx and one lesion in the oral cavity. The 2-year cumulative incidence rate of second primary head and neck cancers was 3.7%. Among them, 17 patients with 29 lesions were treated by transoral surgery. One patient with two synchronous lesions was treated by radiotherapy. Two lesions in two patients were not detected after biopsy. All patients were cured with preserved laryngeal function.
Conclusions
Surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months could detect second primary head and neck cancers at an early stage, thereby facilitating minimally invasive treatment.
Background & Aims Some patients develop multiple squamous cell carcinomas (SCCs) in the upper aerodigestive tract, attributed to field cancerization; alcohol consumption has been associated with this ...process. We examined the association between multiple areas of dysplastic squamous epithelium with the development of SCC of the esophagus or head and neck cancer, as well as alcohol consumption and smoking. Methods We examined 331 patients with early stage esophageal SCC using Lugol chromoendoscopy to evaluate the dysplastic squamous epithelium in the esophagus. Patients then were assigned to 3 groups, based on the number of Lugol-voiding lesions: A, no lesion; B, 1–9 lesions; or C, 10 or more lesions. Participants completed lifestyle surveys on their history of drinking, smoking, and diet. All participants were evaluated by laryngopharyngoscopy before registration; only those without head and neck cancer were included, except for patients with superficial SCC limited to the subepithelial layer. Lesions detected in the esophagus and head and neck by surveillance were considered to be metachronous. The study end point was the cumulative incidence of metachronous SCCs in the esophagus and head and neck after endoscopic resection of esophageal SCC, according to the grade of Lugol-voiding lesions. At study entry, all patients were instructed to abstain from alcohol and smoking. Results Over the 2-year study period, metachronous SCCs of the esophagus were detected in 4% of patients in group A, in 9.4% of patients in group B, and in 24.7% of patients in group C ( P < .0001 for patients in group A vs B or B vs C). Head and neck SCCs were detected in none of the patients in group A, in 1.7% of the patients in group B, and in 8.6% of the patients in group C ( P = .016 for patients in group A vs C and P = .008 for patients in group B vs C). SCC of the esophagus or head and neck developed in 4.0% of patients in group A, in 10.0% of patients in group B, and in 31.4% of patients in group C ( P < .0001 for group A vs B or A vs C). Alcohol abstinence decreased the risk of multiple SCCs of the esophagus (adjusted hazard ratio, 0.47, 95% confidence interval, 0.25–0.91; P = .025), whereas smoking abstinence did not. Conclusions Multiple dysplastic lesions in the esophagus increase the risk of multiple SCCs. Alcohol abstinence reduces the risk of metachronous SCCs. Clinical Trials registry: UMIN000001676 and UMIN000005466.
Follow-up studies of Japanese patients who had undergone endoscopic resection (ER) for early esophageal squamous cell carcinoma (ESCC) have reported a high prevalence of metachronous SCC in the upper ...aerodigestive tract (UAT). This prospective multicenter cohort study followed up 330 Japanese patients after ER of ESCC for a median of 49.4 months. The Alcohol Use Disorders Identification Test (AUDIT) for the 12-month period prior to study registration revealed high frequencies of high-risk drinking behaviors: 84 (25.4%) subjects had AUDIT scores of ≥15 points (suspected alcohol dependence) and 121 (36.7%) subjects had AUDIT scores of 8-14 points (hazardous drinking). Seventy-four subjects were metachronously diagnosed with ESCC, and 20 subjects with head and neck SCC (HNSCC). AUDIT scores ≥15 were associated with increases in the total number of HNSCCs per 100 person-years (0.4 for 0-7, 1.2 for 8-14 and 7.1 for ≥15; P < 0.0001). AUDIT scores were progressively associated with the grade of esophageal Lugol-voiding lesions (LVLs), a predictor of field cancerization in the UAT. Both an AUDIT score of ≥15 points and the presence of multiple LVLs were independent predictors of metachronous HNSCC multivariate hazard ratio (95% confidence interval) = 6.98 (1.31-37.09) and 3.19 (1.19-8.54), respectively. However, a high AUDIT score was not a predictor of metachronous ESCC. In conclusion, high AUDIT scores were markedly frequent in this population and increased the risk of metachronous HNSCC. The assessment of drinking behavior using the AUDIT and the completion of interventions for alcohol problems should be incorporated into the treatment strategy of ESCC. The name of the clinical trial register and the clinical trial registration number: Japan Esophageal Cohort Study, UMIN000001676.
In this study, we conducted a pharmacokinetic analysis of tapentadol (TP) in Japanese patients with cancer pain and identified covariates influencing pharmacokinetic parameters. In addition, the ...analgesic effects and adverse effects of TP were investigated. Data were collected from in-patients with cancer pain who had been administered TP as an extended-release formula. The median (range) estimated clearance (CL/F) and distribution volume (Vd/F) of TP were 86.7 (31.3–213.7) L/h and 1288 (189–6736) L, respectively. There was a strong negative correlation between CL/F and age, Child–Pugh score, and albumin-bilirubin (ALBI) score. The subjects were further divided into two groups according to the factors highly correlated with CL/F. The CL/F of patients in the Child–Pugh B group was 0.46-times that of patients in the Child–Pugh A group. In addition, the CL/F of patients with an ALBI score > −2.40 was 0.56-times that of patients with ALBI scores ≤−2.40, and both differences were statistically significant (p < 0.05). The mean intensity of pain over 24 h was investigated daily from before starting TP for the first 7 d of the treatment. TP reduced pain in six of nine patients; the mean pain visual analogue scale score decreased significantly from 59.2 mm before administration to 42.5 mm at days 5–7. Overall, the Child–Pugh and ALBI scores significantly affected the clearance of TP, which was reduced in patients with impaired liver function. These results suggest that TP is an opioid with a sufficient analgesic effect for cancer patients.
Background
Few studies have compared the outcomes of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) in patients with early gastric cancer.
Methods
We studied 780 ...lesions for which endoscopic treatment was indicated according to the Japanese Gastric Cancer Association (JGCA) criteria or the extended National Cancer Center (NCC) criteria from April 1995 to December 2007. A total of 359 lesions were treated by endoscopic aspiration mucosectomy (EAM) between April 1995 and March 2003 (EAM group), and 421 lesions were treated by ESD between April 2003 and December 2007 (ESD group). Long-term outcomes (local recurrence rate, overall survival) were compared between the groups.
Results
The median follow-up was 73 months in the EAM group and 65 months in the ESD group. Overall, the local recurrence rate was significantly lower in the ESD group (0.2 %, 1/421) than in the EAM group (4.2 %, 15/359) (
p
< 0.05). For lesions meeting the JGCA criteria, the local recurrence rate was 2.9 % in the EAM group and 0 % in the ESD group (
p
< 0.05). For lesions meeting the NCC criteria, the local recurrence rate was 12.5 % in the EAM group and 0.6 % in the ESD group (
p
< 0.05). There was no significant difference between the groups in overall survival.
Conclusions
On long-term follow-up, ESD was associated with a lower rate of local recurrence than EAM for lesions that met the JGCA or the NCC criteria. From the point of view of radical curability, ESD can be recommended for the management of lesions that meet either set of criteria.
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