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Background: The 6-minute walk distance (6MWD) is a simple way of assessing exercise capacity. The purpose of this study was to investigate the relationship between preoperative 6MWD and long-term prognosis after esophagectomy., Methods: This retrospective cohort study involved 108 patients who underwent radical esophagectomy for esophageal cancer between 2013 and 2020. The patients were classified into the short group (SG: 6MWD < 480 m) or the long group (LG: 6MWD  ≥  480 m). To adjust for the background characteristics of both groups, propensity score matching (PSM) analysis was performed and 32 patients were matched from each group. Five-year overall survival (OS) and relapse-free survival (RFS) were analyzed by the Kaplan-Meier method. The log-rank test was used to evaluate differences in survival between the groups. After adjusting for other prognostic factors, the Cox proportional hazards model was used to investigate the impact of preoperative 6MWD on long-term prognosis., Results: The median follow-up period was 923 days. Thirty-three deaths were recorded during the study period. After PSM, 5-year OS following surgery was 29.2 and 66.1% (p = 0.003) and 5-year RFS was 27.9 and 58.6% (p  =  0.021) in the SG and LG, respectively. In Cox proportional hazards analysis, the SG was a significant independent risk factor for OS (hazard ratio 3.33; 95% confidence interval 1.37-8.11, p = 0.008) and RFS (hazard ratio 2.30; 95% confidence interval 1.08-4.88, p = 0.030)., Conclusion: The preoperative 6MWD is useful for evaluating exercise capacity and predicting the long-term outcome in patients undergoing esophagectomy., (© 2021. The Japan Esophageal Society.)

Background: Accurate diagnosis of the tracheobronchial invasion of advanced esophageal cancer is essential to select appropriate treatment and improve prognosis; however, it is difficult using the conventional modalities. This study aimed to clarify the diagnostic usefulness of convex probe endobronchial ultrasound (CP-EBUS) for the diagnosis of the tracheobronchial invasion of advanced esophageal cancer., Methods: We conducted a cadaveric study to clarify the changes in ultrasonic and histopathologic findings in the esophageal tumor and tracheal invasion models. Additionally, we examined CP-EBUS for patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected on contrast-enhanced computed tomography (CE-CT) scan. We retrospectivity evaluated the diagnosis of CP-EBUS, comparing the pathological findings and treatment outcomes., Results: Cadaveric esophageal tumor and tracheal invasion models showed the disappearance of the third layer observed with CP-EBUS and histologically proven interruption of the adventitia. This indicated that the third layer corresponded with the tracheal adventitia. We examined 40 patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected. The precise diagnosis was pathologically confirmed in 9 of 14 patients diagnosed with cT3 who underwent radical surgery. 20 of 26 cases diagnosed with cT4b received definitive chemoradiotherapy, and 4 cases received salvage surgery and pathologically confirmed precise diagnosis., Conclusion: CP-EBUS is extremely useful for diagnosing the tracheobronchial invasion of advanced esophageal cancer. It could be an effective modality for determining treatment strategies in cases with a marginal surgical indication., (© 2021. Society of Surgical Oncology.)

Background: Chemokines are major regulators of cell trafficking and adhesion. The chemokine CXCL12 and its receptors, CXCR4 and CXCR7, have been reported as biomarkers in various cancers, including esophageal cancer; however, there are few studies in esophageal adenocarcinoma (EAC). In this study, we investigated the relationship between expression of CXCL12, CXCR4, and CXCR7, and prognosis in patients with EAC., Methods: This study examined 55 patients with EAC who were treated in Toronto General Hospital from 2001 to 2010. Tissue microarray immunohistochemistry was used to evaluate the expression of CXCL12, CXCR4, and CXCR7. Evaluation of immunohistochemistry was performed by a pathologist without knowledge of patients' information and results were compared with the patients' clinicopathological features and survival., Results: High CXCR7 expression was significantly associated with lymphatic invasion (present vs absent, P = 0.005) and higher number of lymph node metastases (pN0-1 vs pN2-3, P = 0.0014). Patients with high CXCR7 expression (n = 23) were associated with worse overall (OS) and disease-free survival (DFS) (P = 0.0221, P = 0.0090, respectively), and patients with high CXCL12 (n = 24) tended to have worse OS and DFS (P = 0.1091, P = 0.1477, respectively). High expression of both CXCR7 and CXCL12 was an independent prognostic factor for OS and DFS on multivariate analysis (HR = 0.3, 95% CI: 0.1-0.9, P = 0.0246, HR = 0.3, 95% CI: 0.1-0.8, P = 0.0134, respectively)., Conclusions: High CXCR7 expression was associated with poor prognosis in patients with EAC, and high expression of CXCR7 with its ligand CXCL12 had a stronger association with prognosis. Further study of this potential biomarker using whole tissue samples and a larger sample size is warranted., (© 2021. Society of Surgical Oncology.)

Background: Anastomotic leakage (AL) is a serious complication after esophagectomy. The retrosternal (RS) route has been selected majorly to reduce reflux and related pneumonia and considering mediastinal recurrences. AL has been developed more in RS than posterior mediastinal (PM) route reconstruction. Therefore, we suspected the sterno-tracheal distance (STD) might be related to AL and started the selection according to the STD from 2009., Methods: A total of 221 patients who underwent a subtotal esophagectomy with gastric tube reconstruction during January 2004-April 2017 were investigated. The patients were classified into the 'after STD selection' (A; n = 144) group and the 'before STD selection' (B, n = 77) group. The incidences of and the risk factors for AL between the two groups were compared., Results: The incidence of AL was high in the B group (18.2%), and 78.6% of the patients who developed AL were treated with RS route reconstruction. The median STDs of the patients with AL and no AL were 10.3 mm and 14.5 mm, respectively (p = 0.001). These results demonstrated that the STD was a risk factor for AL in the RS route. Based on these results, 13 mm was set as the cutoff value. After STD selection, the median STD increased from 14.0 to 17.3 mm (p = 0.001), and the incidence of AL decreased significantly from 26.2 to 11.1% in the RS route (p = 0.037)., Conclusion: The STD was the independent risk factor for AL in the RS route. RS route reconstruction should be avoided for the patients with STD < 13 mm.

Esophageal cancer (EC) is one of the most lethal malignancies of the digestive tract and remains to be improved poor prognosis. Two histological subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), are major characteristics of EC. Deep understanding about both subtypes is essential to overcome EC. Here, we focus on chemokines and their receptors as biomarkers and their current applications for the prognosis in EC. We reviewed relevant articles identified using PubMed database for the chemokines and their receptors in EC analyzed by immunohistochemistry. The primary objective is to summarize evidences for them as prognostic biomarkers in EC. A total of twenty-one articles were reviewed after exclusion. Most studies have been done in ESCC, and less in EAC. CXCL12 and its receptor CXCR4 have been shown in both subtypes as biomarkers. CXCR7, CXCL8 and its receptor CXCR2, and CCL21 and its receptor CCR7 have been examined in ESCC. Although it was a small number of reports, CXCL10, CCL4, and CCL5 have been indicated to have anti-tumor effects in ESCC. Chemokines and their receptors have the potential to be the biomarkers in EC. Comparative studies between ESCC and EAC will reveal the similarity and difference in these two subtypes of EC. These studies may indicate whether these molecules play important roles in both subtypes or are unique to one or another.

Background: Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients., Methods: Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery., Results: We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups., Conclusions: TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.

Background: Chemokines and their receptors are known to play important roles in the tumorigenesis of many malignancies. The chemokine CXCL12 and its receptors CXCR4 and CXCR7 were suggested to be involved in cancer invasion and metastasis. The aim of this retrospective study was to evaluate the prognostic impact of the expressions of CXCL12, CXCR4 and CXCR7 in patients with esophageal squamous cell carcinoma (ESCC)., Methods: We used immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate the expressions of CXCL12, CXCR4, and CXCR7 in ESCC patients' tumor biopsy specimens obtained during preoperative endoscopy or surgery. These results were compared with the patients' clinicopathological parameters and survival., Results: IHC was conducted for 172 patients. High expression of CXCR4 in the cytoplasm and nuclei and that of CXCR7 were associated with poor cause-specific survival (CSS) (P= .002 and .010, respectively). The specimens from 52 of the 172 patients were examined by RT-PCR and quantitative real-time PCR. The expression levels of messenger RNA (mRNA) of CXCR4 and CXCR7 were significantly increased in the tumors compared with normal esophageal mucosae (P < .0001). The expression level of mRNA of CXCR4 was associated with poor recurrence-free survival and CSS (P = .012 and .038, respectively)., Conclusions: CXCR4 expression is associated with poor prognosis in patients with ESCC.

Background: Aldehyde dehydrogenase 1 (ALDH1) and CD44 act as important biomarkers in several solid tumors. However, few studies have examined the relationships between ALDH1 expression and the prognosis and clinical characteristics of esophageal squamous cell carcinoma (ESCC)., Methods: This study was a retrospective case-control study and included 152 patients with ESCC. A total of 56 patients underwent surgery (OP group), 40 patients received neoadjuvant chemotherapy involving weekly docetaxel plus 5-fluorouracil and low-dose cisplatin (DFP therapy) prior to undergoing surgery (NAC group), and 56 patients received initial systemic DFP therapy (CT group). The ALDH1 and CD44 immunohistochemical expression levels of each tumor were evaluated and compared with the prognosis and clinical characteristics of the ESCC patients., Results: In the OP and NAC groups, multivariate analysis found that ALDH1 was independently associated with postoperative recurrence and prognosis (OP group, P=0.004 and 0.016, respectively; NAC group, P=0.026 and 0.014, respectively). In addition, CD44 was found to be associated with postoperative recurrence in the OP group and prognosis in the NAC group (P=0.024 and 0.047, respectively). Among the ALDH1-negative clinical stage II/III patients, the OP and NAC groups displayed better prognoses than the CT group (P<0.001). However, among the ALDH1-positive clinical stage II/III patients, the OP and NAC groups displayed poorer prognoses than the CT group (P=0.049)., Conclusions: ALDH1 was found to be a predictor of postoperative recurrence and prognosis in ESCC, and CD44 might be a predictor of recurrence and prognosis. ALDH1 expression might affect the treatment strategy for ESCC.

Background: Laparoscopy-assisted gastrectomy (LAG) is becoming widely used for early gastric cancer. However, how the curability and long-term prognosis of LAG and open gastrectomy (OG) for early and advanced gastric cancer compare remains unclear. This study assessed short- and long-term outcomes after LAG with lymph node dissection in early and advanced gastric cancer., Methods: A total of 332 patients who underwent LAG or OG for early and advanced gastric cancer from January 2001 through December 2010 were reviewed retrospectively. The mean operating time, estimated mean blood loss, number of dissected lymph nodes, and survival rates were compared between LAG and OG for early and advanced gastric cancer., Results: Overall, 47.6% (158/332) of patients underwent LAG; D1, D1+ lymph node dissection was carried out in 77.2%, with D2 dissection in 22.8%. Only one patient required conversion to OG. Comparing LAG and OG with D1, D1+ lymph node dissection for early gastric cancer (EGC), mean operating time was significantly longer, estimated mean blood loss was significantly smaller, and the average number of retrieved lymph nodes was significantly greater with LAG. The rate of specific postoperative morbidity was 17.2% for LAG patients and 25.0% for OG patients, with no postoperative mortality. Survival and recurrence rates were not significantly different. Comparing LAG and OG with D2 lymph node dissection for advanced gastric cancer (AGC), mean operating time was significantly longer and estimated mean blood loss was significantly smaller with LAG, while the average number of retrieved lymph nodes, specific postoperative morbidity and mortality, and survival and recurrence rates were not significantly different., Conclusions: LAG with D1, D1+ lymph node dissection for EGC is safe and equivalent to open gastrectomy in curability. Moreover, LAG with D2 lymph node dissection for AGC is comparable to OG with D2 lymph node dissection with regard to short- and long-term results.

Background: The sentinel lymph node (SLN) concept has been gaining attention for gastrointestinal neoplasms but remains controversial for esophageal cancer. This study evaluated the feasibility of SLN identification using intraoperative indocyanine green (ICG) fluorescence imaging (IGFI) navigated by preoperative computed tomographic lymphography (CTLG) to treat superficial esophageal cancer., Methods: Subjects comprised 20 patients clinically diagnosed with superficial esophageal cancer. Five minutes after endoscopic submucosal injection of iopamidol around the primary lesion using a four-quadrant injection pattern with a 23-gauge endoscopic injection sclerotherapy needle, three-dimensional multidetector computed tomography was performed to identify SLNs and lymphatic routes. ICG solution was injected intraoperatively around the tumor. Fluorescence imaging was obtained by infrared ray electronic endoscopy. Thoracoscope-assisted standard radical esophagectomy with lymphadenectomy was performed to confirm fluorescent lymph nodes detected by CTLG., Results: Lymphatic vessels and SLNs were identified preoperatively using CTLG in all cases. Intraoperative detection rates were 100% using CTLG and 95% using IGFI. Lymph node metastases were found in four cases, including one false-negative case with SLNs occupied by bulky metastatic tumor that were not enhanced with both methods. The other 19 cases, including three cases of metastatic lymph nodes, were accurately identified by both procedures., Conclusions: Preoperative CTLG visualized the correct number and site of SLNs in surrounding anatomy during routine computed tomography to evaluate distant metastases. Referring to CTLG, SLNs were identified using IGFI, resulting in successful SLN navigation and saving time and cost. This method appears clinically applicable as a less-invasive method for treating superficial esophageal cancer.