BACKGROUND & AIMS: Weight loss after oesophagectomy remains an unresolved problem. We hypothesised that providing sufficient enteral nutrition (EN) during the first 3 months postoperatively would attenuate weight loss until adequate oral intake resumed. This study aimed to compare postoperative weight loss between patients who received home EN therapy and those who relied on oral intake alone. METHODS: This single-centre, randomised controlled trial enrolled patients with oesophageal cancer who underwent oesophagectomy and assigned them to either the EN group or the oral ingestion (OI) group. The EN group received 900 kcal/day of enteral nutrition for 90 days. The primary endpoint was the percentage change in BMI at 3 months postoperatively. Secondary endpoints included perioperative complications, body composition, and nutritional parameters. RESULTS: Sixty patients treated between 2020 and 2023 were randomised. Baseline characteristics and postoperative complications were comparable between the two groups. In the intention-to-treat population, the percentage change in BMI at 3 months was significantly smaller in the EN group than in the OI group (-6.8% vs -10.9%; mean difference 4.1%, 95% CI 0.8-7.4; P = 0.015). After excluding protocol discontinuations, 51 patients (EN, n = 27; OI, n = 24) were analysed in the protocol-defined evaluable population, with consistent results (mean difference 4.7%, 95% CI 1.1-8.3; P = 0.012). The EN group tended to show a smaller decrease in body fat mass (-9.5% vs -18.3%; P = 0.189), while experiencing a comparable loss of skeletal muscle mass (-14.4% vs -17.5%; P = 0.475). Concentrations of retinol-binding protein and prealbumin, as well as white blood cell counts, were significantly higher in the EN group. By 12 months postoperatively, BMI and laboratory parameters had converged to comparable levels in both groups. CONCLUSION: Home enteral nutrition attenuated weight loss and contributed to improved short-term nutritional status during the first 3 months after oesophagectomy. REGISTRATION NUMBER OF CLINICAL TRIAL: UMIN000047828 (http://www.umin.ac.jp/).

BACKGROUND: Advanced esophageal squamous cell carcinoma (ESCC) may require combined resection or result in non-curative resection, increasing the risk of severe complications related to the posterior mediastinal dead space created after esophagectomy, such as airway instability and mediastinitis. Although filling this space with the greater omentum via the posterior mediastinal route is commonly used, this approach may impair gastric conduit alignment and function due to intrathoracic negative pressure. We developed a novel technique to overcome these limitations. METHODS: We retrospectively reviewed 20 patients who underwent esophagectomy with gastric conduit reconstruction and additional omental transposition using a novel "waterfall" method between 2012 and 2022. Omental transposition was selectively added in cases involving combined resection of adjacent organs or non-curative resection, in which the posterior mediastinal dead space was considered to increase postoperative complication risk. In this technique, the greater omentum is elevated to the neck with the gastric conduit via the retrosternal route and then pulled down from the anterior mediastinum to fill the posterior mediastinal dead space. Surgical outcomes, postoperative complications, and conduit-related symptoms were evaluated. RESULTS: Sixteen patients had cT4b disease and four had cT3 disease. Curative resection was achieved in 12 patients, while 8 underwent non-curative resection. No serious complications such as airway necrosis, airway-mediastinal fistula, or mediastinitis were observed, and no patients developed gastric conduit dysfunction. CONCLUSIONS: The waterfall method is a safe and feasible technique for filling the posterior mediastinal dead space after esophagectomy while preserving gastric conduit alignment and function in high-risk ESCC cases.

Esophagectomy is a highly invasive and curative procedure for esophageal cancer. Although minimally invasive techniques reduce the incidence of pulmonary complications, postoperative dysphagia remains a common and clinically significant issue. Preoperative expiratory muscle training (EMT) may improve swallowing function by strengthening the relevant muscles; however, its effectiveness in patients with esophageal cancer has not been widely studied. This phase II randomized, controlled, double-blind trial has been designed to evaluate the effects of preoperative EMT on postoperative swallowing function in patients undergoing esophagectomy for thoracic esophageal squamous cell carcinoma. Forty patients will be randomly assigned (1:1) to either the EMT or sham-EMT group. EMT will be performed using the EX-1 Medic® device at 50-70% maximal expiratory pressure, whereas the control group will receive minimal resistance (10 cmH₂O). The primary outcome is the Penetration-Aspiration Scale score on the postoperative video-fluoroscopic swallowing study, targeted at postoperative days 10 (allowable window: postoperative days 6-14). The secondary outcomes will be assessed perioperatively (preoperative and/or postoperative, depending on the measure) and include tongue pressure, the Repetitive Saliva Swallowing Test, T he eating assessment test-10, respiratory muscle strength, appendicular skeletal muscle index, and exercise tolerance. This study has been registered at University Hospital Medical Information Network (UMINID:000057795). Recruitment began on June 10, 2025, is expected to continue until September 30, 2028. This trial will clarify whether preoperative EMT can improve swallowing function and reduce postoperative dysphagia in patients with esophageal cancer, potentially establishing a novel prehabilitation strategy in surgical care. Trial registration: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000057795. Registered on May 8, 2025. https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000065994.

BACKGROUND: Postoperative pulmonary complications (PPCs) significantly influence clinical outcomes following esophagectomy for esophageal cancer. Identifying reliable preoperative predictors is essential for optimizing surgical outcomes. Although chronic obstructive pulmonary disease (COPD) is an established risk factor, the role of preoperative quantitative emphysema assessment using low-attenuation area percentage (LAA%) on computed tomography (CT) remains unclear. We retrospectively investigated the association of preoperative LAA% with PPCs and postoperative prognosis in patients undergoing thoracic esophagectomy for esophageal cancer. METHODS: We enrolled 334 patients who underwent esophagectomy for esophageal cancer at Kindai University Hospital between January 2016 and March 2024. Preoperative LAA% was quantified using specialized software, and PPCs were defined as events occurring within 2 weeks after esophagectomy and classified according to the Clavien-Dindo classification. The association between bilateral LAA% and PPCs was assessed using logistic regression analyses, while long-term prognosis was evaluated using Kaplan-Meier survival analysis. RESULTS: The incidence of PPCs was 32.9% (110/334 patients). Multivariable logistic regression analysis demonstrated that preoperative bilateral LAA% ≥ 5% was significantly associated with an increased risk of PPCs (odds ratio [OR]: 3.81, 95% confidence interval [CI] 1.01-14.4, p = 0.04). Kaplan-Meier survival analysis showed that patients with bilateral LAA% ≥ 5% had significantly lower 5-year overall survival than those with bilateral LAA% < 5% (p = 0.03). CONCLUSION: Preoperative LAA% is a predictor of PPCs and postoperative prognosis after esophagectomy for esophageal cancer. Quantitative CT analysis of emphysema can improve the preoperative risk stratification. Future multicenter studies are needed to validate these results, particularly for minimally invasive esophagectomies.

We investigated the role of the intraperitoneal immune microenvironment in the therapeutic response of gastric cancer with peritoneal metastasis to intraperitoneal paclitaxel. Gastric cancer with peritoneal metastasis has a poor prognosis, even with systemic chemotherapy. Although intraperitoneal paclitaxel administration has demonstrated clinical benefit, treatment resistance remains a major hurdle. Between 2017 and 2023, 30 patients undergoing staging laparoscopy were prospectively enrolled. Immune cell subsets and checkpoint marker expression in peritoneal lavage fluid were analyzed using flow cytometry and immunohistochemistry. Their associations with clinical outcomes were assessed using univariable and multivariable analyses, including Kaplan-Meier, logistic regression, and Ridge regression analyses. Elevated CD4+ T and CD19+ B cell levels were associated with inferior progression-free survival, whereas increased natural killer T-like cell levels correlated with improved survival. High FOXP3 and CTLA-4 expression were linked to worse outcomes. Ridge regression identified CD4+ T cell levels and CTLA-4 expression as unfavorable factors, while the presence of natural killer cells emerged as a favorable factor. An immunoregulatory-dominant immune landscape may drive resistance to intraperitoneal paclitaxel. Immune profiling of ascitic fluid could identify patients likely to benefit from immune-modulating strategies, including those targeting FOXP3+ and CTLA-4+ regulatory cells.

BACKGROUND: Preoperative chemotherapy with cisplatin, fluorouracil, and docetaxel (DCF) is one of the neoadjuvant treatments for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal number of DCF cycles remains unknown. This multi-institutional, randomized, phase II trial aimed to investigate the long-term survival outcomes of two versus three courses of DCF. METHODS: A total of 180 patients with locally advanced ESCC from six institutions were randomly assigned to receive either two (N = 91) or three (N = 89) courses of DCF administered every 3 weeks prior to surgery. Long-term survival outcomes were compared between the two regimens. RESULTS: Baseline characteristics were well balanced between the two groups. The 5-year overall survival (OS) and progression-free survival (PFS) rates for the three and two course groups were 70.7% vs. 63.8% (hazard ratio (HR) = 0.91, p = 0.717) and 63.3% vs. 60.0% (HR = 0.94, p = 0.810) respectively, with no significant differences observed. The per-protocol analysis exhibited similar results, with OS rates of 71.1% vs. 68.8% (HR = 0.90, p = 0.702) and PFS rates of 63.6% vs. 65.4% (HR = 0.92, p = 0.773). Recurrence patterns were also similar between the groups. Subgroup analysis revealed that non-responders in the three course DCF group had significantly worse long-term survival outcomes, whereas the two course DCF group exhibited minimal trends in this regard. Conversely, patients aged < 65 years or those with favorable clinical responses in the three course group demonstrated improved long-term survival outcomes. CONCLUSION: Two courses of preoperative DCF followed by radical esophagectomy can be one of the potential treatment strategies for locally advanced ESCC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: UMIN 000015788.

During surgery for thoracic esophageal cancer, the resected esophagus remains in the thoracic cavity, allowing fluid to leak from the specimen. If this fluid contains cancer cells, they may spread throughout the cavity. However, the presence and prognostic impact of free cancer cells in leaked fluid from the esophagus (LF-E) remain unclear. We conducted a prospective cohort study of 96 patients with thoracic esophageal cancer who underwent radical subtotal esophagectomy. After the thoracic procedure, the esophagus was placed in a bag and removed following the abdominal and cervical procedures. Fluid collected from the bag, combined with saline used to rinse the specimen, was defined as LF-E and examined cytologically. We evaluated the clinicopathological characteristics and prognosis of LF-E-positive (LF-E [+]) patients. LF-E (+) was observed in 5 of 96 patients (5.2%), all of whom had pT3 or higher squamous cell carcinoma with nodal metastasis and vascular invasion. Among the 44 patients with pT3-4a disease, those in the LF-E (+) group had significantly poorer regression-free survival (RFS) (P < 0.001) and overall survival (OS) (P < 0.001) than those in the LF-E-negative group. Multivariate Cox regression analysis identified LF-E positivity as an independent prognostic factor for RFS (hazard ratio [HR]: 4.57, 95% confidence interval [CI]: 1.21-16.2, P = 0.026) and OS (HR: 11.9, 95% CI: 2.04-69.1, P = 0.008). The presence of free cancer cells in LF-E indicated a poor prognosis in patients with pT3 or higher esophageal cancer. LF-E positivity may serve as a new prognostic biomarker.

BACKGROUND: Systemic chemotherapy is the standard treatment for esophageal cancer with synchronous distant metastasis including para-aortic lymph node (PALN) metastasis. The significance of conversion surgery for esophageal cancer with synchronous PALN metastasis remains controversial. OBJECTIVE: The current study aimed to investigate the clinical outcome of conversion surgery for esophageal cancer with synchronous PALN metastasis after induction therapy. METHODS: This multi-institutional retrospective study included 48 patients with esophageal cancer who exhibited synchronous PALN metastasis and who received induction chemotherapy or chemoradiotherapy followed by conversion surgery between 2005 and 2022. The short- and long-term treatment outcomes were examined. RESULTS: Among the 48 patients, 45 and 3 received chemotherapy and chemoradiotherapy, respectively, as the initial treatment. Moreover, all patients underwent subtotal esophagectomy. The incidence rate of postoperative complications was 48% and the in-hospital mortality rate was 2%. The 3- and 5-year overall survival rates of all patients were 36.1% and 25.2%, respectively. The overall survival rates of patients with pN2-3 and final PALN status (fM1) were significantly lower than that of patients with pN0-1 (p = 0.0025) and fM0 (p = 0.0043). The multivariate analysis showed that pathological nodal status (hazard ratio 2.44, p = 0.0488) and fM status (hazard ratio 2.53, p = 0.0246) were independent prognostic factors. CONCLUSIONS: Conversion surgery for esophageal cancer with synchronous PALN metastasis is feasible and promising. In addition, conversion surgery for patients with controlled nodal status including PALN metastasis is important for long-term prognosis.

AIM: Upfront chemotherapy (uCT) or upfront chemoradiotherapy (uCRT) followed by surgery is generally accepted as the standard treatment for patients with locally advanced esophageal cancer. A substantial proportion of patients achieve a pathological complete response (pCR) of the primary tumor with upfront treatment. This retrospective study aimed to clarify the prognostic factors of patients with esophageal cancer who achieve pCR in the primary tumor after upfront treatment and whether the prognosis of patients with pCR who receive uCT differs from that of patients who receive uCRT. METHODS: This study included 121 patients who achieved pCR of the primary tumor after uCT and 40 patients after uCRT. Univariate and multivariate survival analyses were performed. RESULTS: Multivariate analysis of overall survival demonstrated that gender, upfront treatment, and pathological lymph node metastasis were independent prognostic factors (p = 0.0086, 0.011, and 0.031, respectively). Multivariate analysis of relapse-free survival demonstrated that gender, cM status, and pathological lymph node metastasis were independent prognostic factors (p = 0.033, 0.014, and 0.0010, respectively). Among patients without pathological lymph node metastasis, the uCT group showed significantly better both overall and relapse-free survival than the uCRT group (p = 0.014 and 0.037, respectively). Recurrence occurred in 24 patients in the uCT group and 9 in the uCRT group. All of local treatment (chemoradiotherapy and surgery) for recurrent lesions was performed in the uCT group. CONCLUSIONS: Male genders and pathological lymph node metastasis are independent poor prognostic factors in patients with esophageal cancer who receive upfront treatment followed by surgery and achieved pCR of the primary tumor.

BACKGROUND: Preoperative treatment has become widely recognized for improving survival in patients with esophageal cancer. The present study aimed to compare the prognosis between patients with pathological node-negative status treated with surgery alone (SA-pN0) and those who were clinically node-positive but converted to ypN0 following neoadjuvant chemotherapy (NAC-ypN0) in cases of advanced thoracic esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective analysis used a multicenter database of 4849 consecutive patients who underwent treatment for esophageal cancer. Patients with clinical T2 or more advanced ESCC who underwent standard subtotal esophagectomy between 1990 and 2017 were included. The NAC-ypN0 group was compared with the SA-pN0 group in terms of patient characteristics, recurrence patterns, and survival outcomes using propensity score-matched analysis. RESULTS: In total, 109 patients were classified as NAC-ypN0 and 137 as SA-pN0. Propensity score matching resulted in the selection of 87 patients per group. Compared with the SA-pN0 group, the NAC-ypN0 group had a significantly more advanced clinical TNM stage and underwent significantly more three-field lymphadenectomies. Pathological findings showed downstaging of the pT stage in the NAC-ypN0 group, resulting in an equivalent distribution between the two groups. Additionally, the NAC-ypN0 group had significantly lower rates of lymphatic invasion (33% vs. 56%) and venous invasion (21% vs. 52%). Recurrence rates (21% vs. 22%) and survival outcomes (5-year overall survival: 83.9% vs. 76.1%, P = 0.110) were comparable between the two groups. CONCLUSIONS: The NAC-ypN0 group demonstrated reduced lymphovascular invasion and showed a prognosis comparable to that of the SA-pN0 group.

BACKGROUND: Early response of the primary tumor (PT) to neoadjuvant chemotherapy (NAC) in patients with esophageal squamous cell carcinoma (ESCC) is considered a potential predictor of postoperative prognosis. However, the role of metastatic lymph nodes (LNs) remains poorly understood. This study aimed to compare the predictive value of early response in PT and LNs for postoperative prognosis. METHODS: We enrolled 124 consecutive patients who received NAC-docetaxel, cisplatin, 5-fluorouracil (DCF) followed by surgery for ESCC between April 2010 and March 2020. Initial tumor reduction of the PT (ITR-PT) and LN (ITR-LN), defined as the percentage decrease in tumor shorter diameter after the first course of NAC-DCF, was evaluated using computed tomography. The optimal cut-off values of ITRs were determined using receiver operating characteristic curves and Cox regression models, and their relationship with recurrence-free survival (RFS) was analyzed. RESULTS: The median ITR-PT and ITR-LN were 21.77% and -0.88%, respectively. The optimal cut-off values for predicting prognosis were approximately 10% for ITR-PT (hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.84-5.64) and -10% for ITR-LN (HR, 2.20; 95% CI, 1.27-3.80). ITR-PT showed a greater impact on RFS (3-year RFS: ITR-PT ≥ 10%, 66.1%; ITR-PT < 10%, 18.4%; log-rank P < 0.001) compared with ITR-LN (3-year RFS: ITR-LN ≥ -10%, 64.1%; ITR-PT < -10%, 34.3%; log-rank P = 0.004). Multivariate analysis of RFS identified ypN, ITR-PT, and ITR-LN as independent prognostic factors. CONCLUSIONS: Both ITR-PT and ITR-LN are promising predictors of survival in patients with ESCC who underwent NAC-DCF plus surgery. ITR-PT may be a stronger prognostic factor than ITR-LN.

BACKGROUND: Preoperative inspiratory muscle training (IMT) enhances diaphragmatic excursion (DE) in patients with esophageal cancer; however, the postoperative effects of IMT on DE have not yet been evaluated. This study aimed to investigate the effect of preoperative IMT on perioperative diaphragmatic function as measured by DE, inspiratory muscle strength, lung function, and exercise tolerance. METHODS: This was a parallel, randomized-controlled trial. Patients with thoracic or abdominal esophageal cancer scheduled for esophagectomy were randomized into either the incentive spirometry (IS) or IMT group. Each intervention was performed during preoperative neoadjuvant chemotherapy (NAC). The primary outcome was the DE, and the secondary outcomes were maximal inspiratory pressure (MIP), lung function, and exercise tolerance, which were measured before and 1-3 months after esophagectomy. RESULTS: Thirty-two patients were included in the analysis. The DE in the IMT group (n = 15) increased from baseline to pre-operation, and the rate of change was significantly greater than that in the IS group (n = 17). Although the DE and MIP decreased in both groups after esophagectomy, the decline in the DE after esophagectomy was significantly lower in the IMT group than that in the IS group (p < 0.05). Furthermore, significant differences in DE persisted at least until 3 months post-esophagectomy, whereas MIP did not differ significantly at any time point. Pulmonary function and exercise tolerance were not significantly different between the two groups. CONCLUSIONS: The IMT before esophagectomy enhanced diaphragmatic function, which was preserved for more than 3 months after esophagectomy.

INTRODUCTION: This study aimed to evaluate the efficacy of perioperative dysphagia rehabilitation in older adult patients diagnosed with gastric cancer who underwent gastrectomy. MATERIALS AND METHODS: This retrospective study included 149 patients over 80 years who underwent gastrectomies between January 2000 and December 2020. The patients were divided into two groups based on the intervention of the dysphagia rehabilitation team (DRT group: n = 101) and the non-intervention control group (C group: n = 48). Inverse probability weighting (IPW) analysis was used to reduce bias caused by potential confounding. RESULTS: The incidence of overall complications was significantly lower in the DRT group (odds ratio [OR]; 0.27[0.08-0.93]), among which the incidence of postoperative pneumonia (OR; 0.07[0.01-0.43]) and aspiration pneumonia (OR; 0.05[0.01-0.44] was significantly reduced. Ten patients developed postoperative pneumonia; seven were in the C group, and three were in DRT group. Sixty percent of these patients had preoperative comorbidities related to the respiratory system. Regarding the time of onset of aspiration pneumonia, two patterns were observed: onset within a short period after surgery and onset after the start of eating. In contrast, five patients underwent preoperative dysphagia rehabilitation in the DRT group. Among them, postoperative aspiration pneumonia was prevented in four patients, and the others were prevented from severe pneumonitis by the intervention of the dysphagia rehabilitation team. DISCUSSION: Perioperative intervention in dysphagia rehabilitation is not only associated with reduced postoperative pneumonia but also creates awareness in the medical staff and promotes careful observation of swallowing in patients, thereby controlling the incidence of postoperative pneumonia. The perioperative intervention of the dysphagia rehabilitation team is useful for older adult patients with gastric cancer.

BACKGROUND: The association between recurrence timing and prognosis in patients with locally advanced resectable esophageal cancer undergoing neoadjuvant chemotherapy (NAC) followed by esophagectomy remains unclear. This study aimed to clarify this association using multicenter prospective clinical trial data. METHODS: Among 162 patients enrolled in a NAC phase II study comparing the efficacy of cisplatin and fluorouracil plus docetaxel with cisplatin and fluorouracil plus adriamycin, 64 patients with recurrence after R0 resection were included in this study. We evaluated the association between recurrence timing and overall survival after recurrence (OSr), along with clinicopathological factors associated with recurrence timing and OSr. RESULTS: Among 64 patients, 46 (71.9%) and 59 (92.2%) experienced recurrence within 1 and 2 years after surgery, respectively. Groups based on recurrence timing, including ≤ 6, 6-12, and > 12 months, had median OSr of 3.6, 13.9, and 13.4 months, respectively. The prognosis was significantly poorer for patients with recurrence ≤ 6 months after surgery than for other patients (P < 0.001). Multivariate analysis revealed pathological lymph node staging as an independent factor associated with early recurrence (odds ratio: 3.46, 95% confidence interval: 1.47-8.02, P = 0.0045). On the other hand, multivariate analysis for factors associated with OSr revealed pT (hazard ratio [HR]: 1.91, 95%CI 1.26-2.88, P = 0.0022), early recurrence (HR: 6.88, 95%CI 2.68-17.6, P < 0.001), and treatment after recurrence, with both local treatment (HR: 0.47, 95%CI 0.22-0.98, P = 0.043) and chemotherapy (HR: 0.25, 95%CI 0.11-0.58, P = 0.0011) as independent prognostic factors. CONCLUSION: Patients with advanced esophageal cancer experiencing recurrence within 6 months after esophagectomy following NAC have an extremely poor prognosis, suggesting that an advanced pN stage is associated with early recurrence.

BACKGROUND: Inspiratory muscle training (IMT) has preventive effects against postoperative pulmonary complications (PPCs) after upper abdominal surgery. However, its impact on diaphragmatic function has not been evaluated. This study investigated the effect of preoperative IMT on diaphragmatic excursion (DE) and prevention of PPCs for patients with esophageal cancer. METHODS: This study was an unblinded, parallel, randomized controlled trial. Patients with thoracic or abdominal esophageal cancer scheduled for esophagectomy were randomized into the incentive spirometry (IS) or IMT group. During preoperative neoadjuvant chemotherapy, IS or IMT intervention was performed. The inspiratory resistance of the IMT group was consistently set at 50% maximal inspiratory pressure. The primary outcome was the amount of change in DE evaluated with ultrasonography, and the secondary outcome was the incidence of Clavien-Dindo grade II or higher PPCs. RESULTS: This study recruited 42 patients. Among these patients 21 were randomized into the IS or IMT group, and 2 patients dropped out from the study. Finally, 40 patients were included in this analysis. The DE of the IMT group increased significantly after the intervention. The IMT group had significantly larger DE changes than the IS group. Of the 39 patients analyzed for postoperative outcome, 5 experienced grade II PPCs. The IMT group had a lower incidence of PPCs than the IS group. CONCLUSIONS: Patients with thoracic and abdominal esophageal cancer scheduled for surgery who had preoperative IMT have increased DE, which may have an important role in prevention of PPCs.

BACKGROUND: Second primary esophageal cancer often develops in patients with head and neck cancer, and esophagectomy in patients with a history of total pharyngolaryngectomy (TPL) is challenging. However, the clinical outcomes of these patients have yet to be examined in a multicenter setting. METHODS: We evaluated the surgical outcomes of a nationwide cohort of 62 patients who underwent esophagectomy for esophageal cancer with a history of TPL. RESULTS: Ivor-Lewis and McKeown esophagectomies were performed in 32 (51.6%) and 30 (48.4%) patients, respectively. Postoperatively, 23 patients (37.1%) developed severe complications, and 7 patients (11.3%) required reoperation within 30 days. Pneumonia and anastomotic leakage occurred in 13 (21.0%) and 16 (25.8%) patients, respectively. Anastomotic leakage occurred more frequently in the McKeown group than in the Ivor-Lewis group (46.7% vs. 6.2%, P < 0.001). The adjusted odds ratio for anastomotic leakage in the McKeown group was 9.64 (95% confidence intervals (CI), 2.11-70.82, P = 0.008). Meanwhile, the 5-year overall survival rates were comparable between the groups (41.8% for Ivor-Lewis and 42.7% for McKeown), and the adjusted hazard ratio of overall survival was 1.44 (95% CI, 0.64-3.29; P = 0.381; Ivor-Lewis as the reference). CONCLUSIONS: In our cohort, anastomotic leakage occurred more frequently after McKeown than Ivor-Lewis esophagectomy, and almost half of patients in the McKeown group experienced leakage. Ivor-Lewis esophagectomy is preferred for decreasing anastomotic leakage when oncologically and technically feasible.

We aimed to determine the frequency and prognosis of supraclavicular (#104) lymph node (LN) metastasis compared with other LN stations in patients with advanced thoracic esophageal cancer and to identify risk factors for metastasis to delineate the indications for three-field lymphadenectomy (3FL). The study cohort of 567 eligible patients with esophageal cancer had undergone subtotal esophagectomy from 2003 to 2020. LN metastasis was defined as pathologically proven metastasis or positron emission tomography-positive LNs. The efficacy index (EI), calculated from the frequency of LN metastases and survival rates, was used as prognostic value of each LN station dissection for patient survival. Risk factors for #104 LN metastasis were determined by multivariable logistic regression. The frequency of #104 LN metastasis was 11.6% overall, 31.7% in upper and 8.3% in middle/lower third lesion. Neoadjuvant chemotherapy was administered to 71% of patients and chemo-radiation to 11%. The 5-year overall survival was 45.8%. The EI for #104 LNs (5.3) was similar to that for #101 LNs. Risk factors were age < 65 years, upper third lesion, clinical N2-3, #101/106rec LN metastasis and poorly differentiated carcinoma. The 5-year overall survival of patients with middle/lower lesions was 38% (EI 3.1), similar to that for #101 and #8/9/11 LNs. The prognosis of patients with #104 LN metastases is similar to that of patients with metastases in other regional LN stations. Therefore, we recommend 3FL exclusively for patients at a high risk of #104 LN metastasis due to the overall metastatic rate not being high.

BACKGROUND: While a neoadjuvant chemotherapy regimen using docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is considered the standard treatment for locally advanced esophageal cancer (EC) in Japan, a reliable marker for early prediction of treatment efficacy remains unclear. We investigated the utility of the tumor response after a first course of NAC-DCF as a post-surgery survival predictor in patients with EC. METHODS: We enrolled 150 consecutive patients who underwent NAC-DCF followed by surgery for EC between September 2009 and January 2019. The initial tumor reduction (ITR), defined as the percentage decrease in the shorter diameter of the tumor after the first course of NAC-DCF, was evaluated using computed tomography. We analyzed the relationship between ITR, clinicopathological parameters, and survival. RESULTS: The median ITR was 21.07% (range -11.45 to 50.13%). The optimal cut-off value for ITR for predicting prognosis was 10% (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.98-5.51), based on univariate logistic regression analyses for recurrence-free survival (RFS). Compared with patients with ITR <10%, patients with ITR ≥10% showed a significantly higher proportion of ypM0 (80.0% vs. 92.5%) and responders in terms of overall clinical response (50.0% vs. 80.8%). Multivariate analysis for RFS revealed that ypN2-3 (HR 2.78, 95% CI 1.67-4.62), non-response in terms of overall clinical response (HR 1.87, 95% CI 1.10-3.18), and ITR <10% (HR 2.48, 95% CI 1.42-4.32) were independent prognostic factors. CONCLUSIONS: Tumor response after the first course of NAC-DCF may be a good predictor of survival in patients with EC who underwent NAC-DCF plus surgery.

BACKGROUND: The standard treatment for advanced esophageal cancer with synchronous distant metastasis is systemic chemotherapy or immunotherapy. Conversion surgery is not established for esophageal cancer with synchronous distant metastasis. This study aimed to investigate the clinical impact of conversion surgery for esophageal cancer with synchronous distant metastasis after induction therapy. METHODS: This multi-institutional retrospective study enrolled 66 patients with advanced esophageal cancer, including synchronous distant metastasis, who underwent induction chemotherapy or chemoradiotherapy followed by conversion surgery between 2005 and 2021. Short- and long-term outcomes were investigated. RESULTS: Distant lymph node (LN) metastasis occurred in 51 patients (77%). Distant organ metastasis occurred in 15 (23%) patients. There were 41 patients with metastatic para-aortic LNs, and 10 patients with other metastatic LNs. Organs with distant metastasis included the lung in seven patients, liver in seven patients, and liver and lung in one patient. For 61 patients (92%), R0 resection was achieved. The postoperative complication rate was 47%. The in-hospital mortality rate was 1%, and the 3- and 5-year overall survival (OS) rates for all the patients were 32.4% and 24.4%, respectively. The OS rates were similar between the patients with distant LN metastasis and the patients with distant organ metastasis (3-year OS: 34.9% vs. 26.7%; P = 0.435). Multivariate analysis showed that pathologic nodal status is independently associated with a poor prognosis (hazard ratio, 2.43; P = 0.005). CONCLUSIONS: Conversion surgery after chemotherapy or chemoradiotherapy for esophageal cancer with synchronous distant metastasis is feasible and promising. It might be effective for improving the long-term prognosis for patients with controlled nodal status.

Recent reports have described the practicality of laparoscopic intragastric surgery (l-IGS) as an alternative for resecting submucosal tumors (SMTs) near the esophagogastric junction (EGJ), where excision using an exogastric approach would be difficult. However, even using IGS to perform a full-thickness resection of SMTs that are in or extremely close to the EGJ is very difficult to do safely and avoid disrupting or causing stenosis of the EGJ, without advanced experience. This study retrospectively examined the usefulness of l-IGS for gastric SMTs located in or extremely close to the EGJ. Fourteen patients with gastric SMTs < 2 cm of the EGJ and underwent l-IGS were eligible for this study. We examined the tumor location, operative time, intraoperative hemorrhage, degree of deformation, gastroesophageal reflux disease, perioperative complications, and recurrence. Furthermore, we compared patients with tumors in the EGJ with those with tumors near the EGJ and patients in whom three-port l-IGS was performed with those who underwent single-incision laparoscopic surgery. The average tumor size, operative time, intraoperative hemorrhage, and postoperative hospitalization of the 14 patients were 30.9 ± 21.3 mm, 125.2 ± 31.1 min, 30.7 ± 103.3 mL, and 9.2 ± 3.1 d, respectively. No differences in these parameters according to the type of l-IGS or tumor location were observed. All patients underwent l-IGS without complications and were free from EGJ deformation or esophagitis. We believe that l-IGS is useful for gastric SMTs located < 2 cm of the EGJ as it can be safely performed for difficult tumor locations and does not cause deformation of the EGJ.

The low attenuation area percentage (LAA%) is gaining popularity. LAA% is an index of quantitative emphysema on computed tomography (CT) imaging of the chest. This study aims to retrospectively investigate whether preoperative LAA% is associated with postoperative prognosis in patients with esophageal cancer who were scheduled for esophagectomy. From January 2016 to March 2020, 105 patients with esophageal cancer underwent esophagectomy via right thoracotomy and neoadjuvant chemotherapy. A Synapse Vincent volume analyzer (Fujifilm Medical, Tokyo, Japan) was used for measurement. The software automatically quantified LAA% using a threshold of less than - 950 Hounsfield units on CT images of lung regions. Cox proportional hazard analyses were performed in univariable and multivariable forms. Estimates of the receiver operating curve are used to determine the cutoff value for death of LAA%, and the binary value is then inserted into Cox proportional hazard analyses. The preoperative LAA% cutoff value was ≥ 6.3%. Patients with a preoperative LAA% ≥6.3% had a significantly worse prognosis than those with a preoperative LAA% of < 6.3%. LAA% ≥6.3% (hazard ratio: 6.76; 95% confidence interval: 2.56-17.90, P < .001) was the most influential preoperative factor for overall survival after esophagectomy in multivariate Cox proportional hazard analyses. LAA% is one of the preoperative risk factors for survival after esophagectomy and an indicator of lung condition using routinely performed preoperative CT images. We quantified the extent of preoperative emphysema in patients with esophageal cancer, who were scheduled for surgery, and for the first time, reported LAA% as one of the preoperative risk factors for survival after esophagectomy.

PURPOSE: Gastric cancer patients with peritoneal metastasis (PM) are generally treated with systemic chemotherapy. When PM has disappeared because of chemotherapy, radical gastrectomy (so-called conversion surgery) is usually performed. We have previously reported the efficacy of conversion surgery, but there are no reports examining the efficacy of palliative gastrectomy for patients with residual PM after chemotherapy. The purpose of this study was to investigate the efficacy of palliative surgery for gastric cancer patients with PM who still have residual peritoneal dissemination after chemotherapy. METHODS: Twenty-five gastric cancer patients with PM confirmed by laparoscopy and who had received chemotherapy but who still had residual PM were included in this study. Among the 25 patients, palliative surgery was performed in 20 patients (PS group) and chemotherapy was continued in 5 patients (CTx group), and their therapeutic outcomes were compared. RESULTS: In the PS group, total and distal gastrectomies were performed. Clavien-Dindo grade I postoperative complications occurred in two patients (10%). There were no treatment-related deaths. Postoperative chemotherapy was performed all cases. In the PS group, the median survival time (MST) reached 22.5 months, with 1- and 2-year overall survival (OS) rates of 95% and 45%, respectively, whereas in the CTx group, the MST was 15.8 months, and the 1- and 2-year OS rates were 60% and 0%, respectively. The PS group had significantly longer OS than the CTx group (P=0.044). CONCLUSIONS: Palliative surgery is safe and may prolong survival in gastric cancer patients with residual PM after chemotherapy.

BACKGROUND: We report the long-term results as primary endpoint in a multicentre randomized prospective Phase 2 trial which compared chemoradiotherapy (CRT) and triplet chemotherapy (CT) as the initial therapy for conversion surgery (CS) in T4b esophageal cancer (EC). METHODS: Patients with T4b EC were randomly assigned to the CRT group or CT group as initial treatment. CS was performed if resectable after initial or secondary treatment. The primary endpoint was 2-year overall survival, analysed by intention-to-treat. RESULTS: The median follow-up period was 43.8 months. The 2-year survival rate was higher in the CRT group (55.1%; 95% CI: 41.1-68.3%) compared to the CT group (34.7%; 95% CI: 22.8-48.9%), although the difference was not significant (P = 0.11). Local and regional lymph node recurrence in patients undergoing R0 resection was significantly higher in the CT group compared to the CRT group (local: 30% versus 8%, respectively, P = 0.03; regional: 37% versus 8%, respectively, P = 0.002). CONCLUSIONS: Upfront CT was not superior to upfront CRT as induction therapy for T4b EC in terms of 2-year survival and was significantly inferior to upfront CRT in terms of local and regional control. REGISTRATION: The Japan Registry of Clinical Trials (s051180164).

BACKGROUND: Three-course neoadjuvant chemotherapy (NAC) followed by surgery has become a standard of care for locally advanced esophageal cancer (EC). However, some patients occasionally experience a poor tumor response to the third course and have a poor clinical outcome. METHODS: An exploratory analysis of data from the authors' recent multicenter randomized phase 2 trial compared patients with locally advanced EC who received two courses (n = 78) and those who received three courses (n = 68) of NAC. The association between tumor response and clinico-pathologic factors, including survival, was evaluated to identify risk factors in the three-course group. RESULTS: Of 68 patients who received three courses of NAC, 28 (41.2%) had a tumor reduction rate lower than 10% during the third course. This rate was associated with unfavorable overall survival (OS) and progression-free survival (PFS) compared with a tumor reduction rate of 10% or higher (2-year OS rate: 63.5% vs. 89.3%, P = 0.007; 2-year PFS rate: 52.6% vs. 79.7%, P = 0.020). The independent prognostic factors for OS were tumor reduction rate lower than 10% during the third course (hazard ratio [HR], 2.735; 95% confidence interval [CI] 1.041-7.188; P = 0.041) and age of 65 years or older (HR, 9.557, 95% CI 1.240-73.63; P = 0.030). Receiver operating characteristic curve and multivariable logistic regression analyses identified a tumor reduction rate lower than 50% after the first two courses as an independent predictor of a tumor reduction rate lower than 10% during the third course of NAC (HR, 4.315; 95% CI 1.329-14.02; P = 0.015). CONCLUSION: Continuing NAC through a third course may worsen survival for patients who do not experience a response to the first two courses in locally advanced EC.

Introduction. Our synbiotics (Lacticaseibacillus paracasei strain Shirota, Bifidobacterium breve strain Yakult, and galacto-oligosaccharides: LBG) helps mitigate serious adverse events such as febrile neutropenia (FN) and diarrhoea in oesophageal cancer patients receiving neoadjuvant chemotherapy (NAC). Unfortunately, LBG therapy does not benefit all patients.Hypothesis/Gap Statement. Identification of the gut microbiota species involved in adverse events during chemotherapy could help predict the onset of adverse events. Identification of the gut microbiota that influence the efficacy of LBG could also help establish a diagnostic method to identify patients who will respond to LBG before the initiation of therapy.Aim. To identify the gut microbiota involved in adverse events during NAC and that affect the efficacy of LBG therapy.Methodology. This study was ancillary to a parent randomized controlled trial in which 81 oesophageal cancer patients were recruited and administered either prophylactic antibiotics or LBG combined with enteral nutrition (LBG+EN). The study included 73 of 81 patients from whom faecal samples were collected both before and after NAC. The gut microbiota was analysed using 16S rRNA gene amplicon sequencing and compared based on the degree of NAC-associated adverse events. Furthermore, the association between the counts of identified bacteria and adverse events and the mitigation effect of LBG+EN was also analysed.Results. The abundance of Anaerostipes hadrus and Bifidobacterium pseudocatenulatum in patients with no FN or only mild diarrhoea was significantly higher (P<0.05) compared to those with FN or severe diarrhoea. Moreover, subgroup analyses of patients receiving LBG+EN showed that the faecal A. hadrus count before NAC was significantly associated with a risk of developing FN (OR, 0.11; 95 % CI, 0.01-0.60, P=0.019). The faecal A. hadrus count after NAC was positively correlated with intestinal concentrations of acetic acid (P=0.0007) and butyric acid (P=0.00005).Conclusion. Anaerostipes hadrus and B. pseudocatenulatum may be involved in the ameliorating adverse events and can thus be used to identify beforehand patients that would benefit from LBG+EN during NAC. These results also suggest that LBG+EN would be useful in the development of measures to prevent adverse events during NAC.

INTRODUCTION AND IMPORTANCE: Laparoscopic wedge resection has been widely performed for gastric gastrointestinal stromal tumors (GISTs). However, because GISTs in the esophagogastric junction (EGJ) are prone to deformity and postoperative functional disorders, laparoscopic resection is technically very difficult and rarely reported. Herein, we report a case of a GIST in the EGJ successfully treated by laparoscopic intragastric surgery (IGS). CASE PRESENTATION: A 58-year-old man with a GIST, which was intragastric growth type, 2.5 cm in diameter, located in the EGJ, and confirmed by upper gastrointestinal endoscope and endoscopic ultrasound-guided fine needle aspiration biopsy. We successfully performed IGS and the patient was discharged without complications. CLINICAL DISCUSSION: Using laparoscopic wedge resection by exogastric approach, it is problematic to resect a gastric SMT located at the EGJ because of the difficulty in viewing the surgical field and additional concerns of deformation of the EGJ. We suppose IGS as a suitable method for such tumors. CONCLUSION: Laparoscopic IGS for gastric GIST was useful in terms of safety and convenience even though the tumor was in the ECJ.

BACKGROUND: Neoadjuvant therapy followed by surgery is the standard treatment for locally advanced esophageal cancers. During neoadjuvant therapy, tumor-induced esophageal stenosis or adverse events often cause weight loss. However, little is known about the effects of weight loss during neoadjuvant therapy on postoperative complications or prognosis. We investigated the association between weight loss during neoadjuvant chemotherapy, postoperative infectious complications, and prognosis. METHODS: Data from OGSG1003, a randomized phase-II trial comparing two regimens of neoadjuvant chemotherapy, cisplatin and fluorouracil plus Adriamycin and cisplatin and fluorouracil plus docetaxel, for locally advanced esophageal squamous cell carcinoma were used. Body weight was measured before neoadjuvant chemotherapy and esophagectomy. Multivariate analysis for infectious complications and prognosis was performed. RESULTS: The study included 134 patients. The median weight loss during neoadjuvant chemotherapy was 2.83% (-2.07% to 6.29%). Postoperative infectious complications were observed in 37 patients who had a significantly higher weight loss during neoadjuvant chemotherapy (5.18% vs. 1.90%, P = 0.002). Multivariate analysis revealed that > 5% of weight loss during neoadjuvant chemotherapy was the only independent factor associated with postoperative infectious complications (odds ratio 2.69, 95% confidence interval 1.12-6.46, P = 0.027). Weight loss during neoadjuvant chemotherapy was significantly associated with worse recurrence-free survival in the univariate analysis (log-rank test, P = 0.002), but this association was marginal in the multivariate analysis (hazard ratio 1.73, 95% confidence interval 0.98-3.08, P = 0.058). CONCLUSIONS: Severe weight loss during neoadjuvant chemotherapy was an independent risk factor for postoperative infectious complications. Weight maintenance during neoadjuvant chemotherapy may reduce the incidence of postoperative infectious complications.

INTRODUCTION: This study aimed to clarify the impact of the average relative dose intensity (RDI) of neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-NAC) for resectable locally advanced esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: To identify the optimal RDI, recurrence-free survival (RFS) and cumulative incidence function (CIF) for recurrence were calculated in low and high RDI groups with any cut-off points. The optimal RDI was defined as the highest RDI administered with a significant increase in either RFS or CIF. The clinicopathological characteristics of the two groups divided by optimal RDI were investigated. The preoperative prognostic factors associated with RFS were confirmed by multivariable Cox proportional hazards model. RESULTS: Among the 150 eligible patients treated with DCF-NAC from 2010 to 2020, 3-year RFS and CIF were 56.3% and 37.8% in 90 patients in the less than 80% RDI group (<80% RDI) and 73.3% and 26.7% in 60 patients in the more than or equal to 80% RDI group (≥80% RDI), respectively. The optimal cut-off RDI was identified as 80%. The <80% RDI group included older individuals, a lower value of creatinine clearance, a higher Charlson Comorbidity Index, reduced RDI at first course, and grade 1-0 in the histopathological tumor response than the ≥80% RDI group. R0 resection and postoperative complication rates were equal in both groups. Cox proportional hazards model identified the response rate and RDI as predictors of RFS. CONCLUSION: An average RDI of more than or equal to 80% improved prognosis in patients receiving DCF-NAC for ESCC.

BACKGROUND: Neoadjuvant docetaxel plus cisplatin and 5-FU (NAC-DCF) and adjuvant nivolumab monotherapy are the standard care for locally advanced resectable esophageal squamous cell carcinoma (ESCC). However, no effective biomarkers have been found in perioperative setting. We investigated how programmed death-ligand 1 (PD-L1) changes before and after NAC-DCF and how it relates to the therapeutic effect of NAC-DCF in resectable ESCC. METHODS: PD-L1 expression in paired diagnostic biopsy and surgically resected tissues from ESCC patients who underwent surgical resection after receiving two or three NAC-DCF cycles was evaluated. PD-L1 positivity was defined as a combined positive score (CPS) of 10% ≤ . Gene expression analysis was conducted using samples before NAC-DCF. RESULTS: Sixty-six paired samples from 33 patients were included in PD-L1 expression analysis, and 33 Pre-NAC samples acquired by diagnostic biopsy were included in gene expression analysis. Pretreatment, 3 (9%), 13 (39%), and 17 (52%) patients harbored tumors with CPS ranges of < 1%, 1%-10%, and 10% ≤ , respectively. After NAC-DCF, 5 (15%), 15 (45%), and 13 (39%) tumors presented CPS ranges of < 1%, 1%-10%, and 10% ≤ , respectively. The concordance rate between Pre-and Post-NAC-DCF samples was 45%. Patients with PD-L1-negative tumors both before and after NAC-DCF (n = 9) had shorter survival and different gene expression profile characterized by upregulation in WNT signaling or neutrophils. CONCLUSIONS: A substantial PD-L1 expression alteration was observed, resulting in low concordance rate before and after NAC-DCF. Tumors persistently lacking PD-L1 had distinct gene expression profile with worse clinical outcomes, raising the need for further investigation.

Intraperitoneal chemotherapy, in which an anticancer drug is administered directly into the abdominal cavity through an intraperitoneal access port(IP port), is one of the treatment options for advanced gastric cancer with peritoneal metastasis. Herein, we report a case of sheath-like obstruction of the entire catheter of the IP port due to tissue reaction within a short period of time after IP port implantation. The case was a 35-year-old woman with advanced type 4 gastric cancer with peritoneal dissemination. The IP port was placed and intravenous and intraperitoneal chemotherapy using S-1 plus paclitaxel was started. However, in the middle of the second course, the entire catheter was covered with a fibrous capsule and a sheath-like obstruction occurred, so the IP port was removed and a new IP port was reinserted. One of the IP port troubles is obstruction, but such short-term and special obstruction is rare, and the cause is considered to be a foreign body reaction of the catheter.

BACKGROUND: Induction or adjuvant therapies are not always beneficial for thoracic esophageal squamous cell carcinoma (ESCC) patients, and it is thus important to identify patients at high risk for postoperative ESCC recurrence. We investigated the usefulness of the total metabolic tumor volume (TMTV) for predicting the postoperative recurrence of thoracic ESCC. METHODS: We retrospectively analyzed the cases of 163 thoracic ESCC patients (135 men, 28 women; median age of 66 [range 34-82] years) treated at our hospital in 2007-2012. The TMTV was calculated from the fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the primary lesion and lymph node metastases. The optimal cut-off values for relapse and non-relapse were obtained by the time-dependent receiver operating curve analyses. Relapse-free survival (RFS) was evaluated by the Kaplan-Meier method, and between-subgroup differences in survival were analyzed by log-rank test. The prognostic significance of metabolic parameters and clinicopathological variables was assessed by a Cox proportional hazard regression analysis. The difference in the failure patterns after surgical resection was evaluated using the χ2-test. RESULTS: The optimal cut-off value of TMTV for discriminating relapse from non-relapse was 3.82. The patients with a TMTV ≥3.82 showed significantly worse prognoses than those with low values (p < 0.001). The TMTV was significantly related to RFS (model 1 for preoperative risk factors: TMTV: hazard ratio [HR] =2.574, p = 0.004; model 2 for preoperative and postoperative risk factors: HR = 1.989, p = 0.044). The combination of the TMTV and cN0-1 or pN0-1 stage significantly stratified the patients into low-and high-risk recurrence groups (TMTV cN0-1, p < 0.001; TMTV pN0-1, p = 0.004). The rates of hematogenous and regional lymph node metastasis were significantly higher in the patients with TMTV ≥3.82 than those with low values (hematogenous metastasis, p < 0.001, regional lymph node metastasis, p = 0.011). CONCLUSIONS: The TMTV was a more significantly independent prognostic factor for RFS than any other PET parameter in patients with resectable thoracic ESCC. The TMTV may be useful for the identifying thoracic ESCC patients at high risk for postoperative recurrence and for deciding the patient management.

BACKGROUND: Outcomes of salvage surgery after failed definitive chemoradiation (CRT) for esophageal cancer have been well defined. However, only a few studies have focused on salvage esophagectomy for recurrent disease after CRT. METHODS: In 227 patients with esophageal cancer who underwent salvage esophagectomy after definitive CRT, consisting of 116 patients who underwent esophagectomy for persistent disease (the persistent group) and 111 patients who underwent esophagectomy for recurrent disease (the recurrent group), the short- and long-term outcomes were investigated. RESULTS: The rates of any postoperative complication were similar between the groups (49.1% in the persistent group vs. 49.5% in the recurrent group, p = 0.951), although there was a higher rate of anastomotic leakage in the recurrent group (p = 0.027). Thirty-day mortality was also similar between the groups (1.7% in the persistent group vs. 0.9% in the recurrent group, p = 0.587). The 3-year and 5-year overall survival rates were 33.7% and 28.0% in the persistent group and 48.7% and 41.7% in the recurrent group, respectively (p = 0.0175). In the recurrent group, clinically nodal status before CRT as well as pathologically nodal status and time to relapse were identified as independent prognostic factors. In the persistent group, pT and resection margin were identified as independent factors associated with survival. CONCLUSIONS: The present study showed that salvage surgery for recurrent disease can provide acceptable short- and long-term outcomes. Considering clinically and pathologically nodal status and time to relapse, adjuvant therapy might be offered for patients who underwent salvage esophagectomy for recurrent disease after definitive CRT.

BACKGROUND: Ghrelin has been reported to reduce postoperative weight loss by improving appetite and food intake in patients undergoing upper gastrointestinal surgery. OBJECTIVE: We aimed to investigate whether growth hormone induction, another essential effect of ghrelin, may attenuate skeletal muscle loss in patients during postoperative starvation. METHODS: Esophageal cancer patients were randomized to receive a continuous intravenous infusion of high-dose ghrelin (HD; 0.5 µg/kg/h), low-dose ghrelin (LD; 0.25 µg/kg/h), or placebo for 7 days after surgery. During this period, oral feeding was not introduced but the patients received the same parenteral and enteral nutrition. We investigated the effects of ghrelin on body weight, skeletal muscle mass, nutritional status, and hormone levels. RESULTS: Overall, 73 patients were enrolled in this study. The rate of weight loss on postoperative day (POD) 7 relative to that before surgery was significantly lower in the HD group than in the placebo group (HD vs. placebo: -0.61% vs. 1.8%, p = 0.030). The rate of muscle loss in the erector spinae muscle on POD 7 in the HD and LD groups was significantly lower than that in the placebo group (HD vs. placebo: 2.8% vs. 8.5%, p < 0.001; LD vs. placebo: 4.9% vs. 8.5%, p = 0.028). The levels of growth hormone on PODs 1, 3, and 7, and insulin-like growth factor 1 on PODs 3, 7, and 14 were significantly higher in patients who received ghrelin. CONCLUSION: Continuous ghrelin administration could attenuate skeletal muscle loss in esophageal cancer patients during postoperative starvation.

BACKGROUND & AIMS: Established supportive care to reduce the toxicity of neoadjuvant chemotherapy (NAC) is lacking. This multicenter randomized study compared the administration of synbiotics combined with enteral nutrition (EN) versus that of prophylactic antibiotics as supportive care treatment for patients with esophageal cancer undergoing NAC. METHODS: Patients with advanced esophageal cancer scheduled to receive NAC were randomly administered either prophylactic antibiotics (antibiotic group) or synbiotics combined with EN (Syn + EN group). The primary endpoint was the febrile neutropenia (FN) incidence during the first course, and the secondary endpoints were other adverse events, changes in intestinal environment, including fecal microbiota, organic acid concentrations, pH, and chemotherapy tolerability. RESULTS: Eighty-one patients were enrolled. The FN incidence was nonsignificantly lower (P = 0.088) in the Syn + EN group. The incidences of grade 4 neutropenia and grades 2-4 diarrhea were significantly lower in the Syn + EN group (P = 0.014 and 0.033, respectively). Relative dose intensity was significantly higher in the Syn + EN group (92.0 ± 10.9%) than in the antibiotic group (83.2 ± 18.2%) (P = 0.01). Alpfa diversity was significantly higher in the Syn + EN group than in the antibiotic after chemotherapy (P = 0.002). The numbers of Bifidobacterium (P < 0.05), Lacticaseibacillus (P < 0.001), and Enterobacteriaceae (P < 0.001) and the concentration of acetic acid (P < 0.001) were significantly higher in the Syn + EN group than in the antibiotic group after chemotherapy. The severity of diarrhea and occurrence of FN were significantly correlated with Clostridioides difficile abundance and were significantly inversely correlated with acetic acid concentration after chemotherapy. CONCLUSIONS: Synbiotics combined with EN may be an alternative supportive care treatment to prophylactic antibiotics in patients with cancer undergoing toxic chemotherapy (https://jrct.niph.go.jp; jRCTs051180153).

BACKGROUND: This study was performed to verify the superiority of a new "non-tensioning method" for avoiding stricture of the cervical esophagogastric anastomosis by circular stapling compared with the conventional method. METHODS: In total, 395 consecutive patients who underwent McKeown esophagectomy with gastric conduit (GC) reconstruction were reviewed. A 4 cm-wide GC was created and pulled up at the cervical site through the retrosternal route. The esophagogastrostomy site of the GC was planned as far caudally as possible on the greater curvature side. In the conventional technique, the stapler was fired while pulling the GC to avoid tissue slack. In the non-tensioning technique, the stapler was fired through the natural thickness of the stomach wall. The length of the blind end was changed from 4 to 2 cm in the non-tensioning technique. Anastomotic leakage and stricture formation were compared between the two techniques, and adjustment was performed using propensity score matching. RESULTS: The conventional group comprised 315 patients, and the non-tensioning group comprised 80 patients. Anastomotic leakage occurred in 22 (7%) and 2 (2.5%) patients, respectively (P = 0.134) [and in 9 (2.9%) and 2 (2.5%) patients, respectively, if leakage at the blind end was excluded]. Anastomotic stricture occurred in 92 (29.2%) and 3 (3.8%) patients, respectively (P < 0.001). The propensity score-matching analysis including 79 pairs of patients confirmed a lower stricture rate in the non-tensioning than conventional group (2.5% vs. 29.1%, P < 0.001). CONCLUSIONS: The non-tensioning technique significantly reduced the incidence of anastomotic stricture compared with the conventional technique.

BACKGROUND: The optimal number of neoadjuvant chemotherapy (NAC) cycles remains to be established for treating oesophageal squamous cell carcinoma (ESCC). We compared two versus three courses of NAC for treating locally advanced ESCC in a multi-institutional, randomised, Phase II trial. METHODS: We randomly assigned 180 patients with locally advanced ESCC at 6 institutions to either two (N = 91) or three (N = 89) courses of DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks, prior to surgery. The primary endpoint was 2-year progression-free survival (PFS) with an intention-to-treat analysis. RESULTS: Patient background parameters were well-balanced. The R0 resection rates were 98.9 and 96.5% in the two- and three-course groups, respectively (P = 0.830). In resected cases, the two- and three-course groups had comparable pN0 rates (P = 0.225) and histological responses (P = 0.898). The 2-year PFS rate was also comparable between the two groups (71.4 vs. 71.1%, P = 0.669). Among subgroups based on baseline characteristics, only patients aged under 65 years old showed a tendency for better survival with the three-course treatment (hazard ratio = 2.612, 95% confidence interval: 1.012-7.517). CONCLUSIONS: Two courses of a DCF regimen showed potential as an optional NAC treatment for locally advanced ESCC. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN 000015788).

PURPOSE: The prognosis of gastric cancer patients with peritoneal metastasis (PM) remains dismal with standard systemic chemotherapy. Intraperitoneal (i.p.) chemotherapy with paclitaxel (PTX) has local effects on intra-abdominal cancer cells. According to this phenomenon, we have developed regimens combining single i.p. PTX administration with systemic chemotherapy. This treatment strategy is very promising; however, the effect of "conversion surgery" in patients responding to this chemotherapy is unclear. Therefore, we performed a retrospective study to evaluate the safety and efficacy of conversion surgery for gastric cancer patients with PM. METHODS: We enrolled 52 gastric cancer patients with PM who were treated with single i.p. PTX plus systemic chemotherapy between 2005 and 2015. Conversion surgery was performed where PM was eliminated by combination chemotherapy. RESULTS: Among 52 gastric cancer patients, the disappearance of PM was confirmed in 33 patients (63.5%). Gastrectomy with D2 lymph node dissection was performed in all these patients. Histological response of grade ≥ 1b was achieved in 13 patients (39%). Clavien-Dindo grade II postoperative complications occurred in three patients (9%). There were no treatment-related deaths. The median survival time and 1-, 3-, and 5-year overall survival rates of the 33 patients who underwent conversion surgery were 30.7 months and 78.8%, 36.3%, and 24.2%, respectively, and those of the 19 patients who did not undergo surgery were 12.5 months and 52.6%, 5.2%, and 0%, respectively. CONCLUSION: Conversion surgery is safe and may prolong survival for gastric cancer patients with PM who have responded to single i.p. PTX plus systemic chemotherapy.

Aim: Digestive reconstruction after pharyngolaryngectomy with total esophagectomy (PLTE) remains challenging, with the optimal method remaining unclear. The current study aimed to clarify the short-term outcomes after PLTE and determine the optimal digestive reconstruction method. Methods: Based on a nationwide survey of 151 patients who underwent PLTE, outcomes of digestive reconstruction methods are described. Results: Among digestive reconstruction methods, a simple gastric tube was most frequently used (37.1%), followed by gastric tube combined with free graft transfer (FGT) (35.1%), gastric tube with microvascular anastomosis (22.5%), and other procedures (5.3%). Intraoperative evaluation of microcirculation (IOEM) was utilized in 29 patients (19.2%). Among the included patients, 66.9% developed any-grade complications, 41.0% developed severe complications, and 23.8% developed digestive reconstruction-related complications (DRRCs; leakage or necrosis). Reoperation within 30 days for any complications and DRRCs was required in 13.9% and 8.6% of the patients, respectively. Mortality within 90 days was observed in 4.6%. Among the three major methods, gastric tube combined with FGT promoted the least DRRCs in the gastric tube (P = .005), although the overall incidence of DRRCs was comparable. The use of IOEM was significantly associated with a reduction of severe DRRCs (P = .005). Conclusions: Pharyngolaryngectomy with total esophagectomy is a high-risk surgery significantly associated with the occurrence of postoperative morbidity and mortality. Nonetheless, the addition of FGT can help prevent gastric tip complications, while IOEM can be an effective method for improving outcomes.

BACKGROUND: The impact of thoracic duct (TD) resection on prognosis is controversial. This study aimed to examine the impact of TD resection. METHODS: In this six-institution, matched-cohort study, 2269 consecutive patients with esophageal squamous cell carcinoma who underwent esophagectomy between 2000 and 2017 were enrolled for analysis of long-term outcomes, including overall survival (OS), disease-free survival (DFS), cause-specific survival (CSS), and recurrence patterns. RESULTS: Based on a propensity score, 642 TD-resected and 642 TD-preserved patients with all stages of disease were selected. At 5 years, the TD-resected group had an OS of 57.7%, a DFS of 50.9%, and a CSS of 62.2%. These rates were significantly higher than the corresponding rates of 48.7% (p = 0.0078), 41.0% (p = 0.0297), and 55.3% (p = 0.0473) in the TD-preserved group. The OS in the TD-preserved and TD-resected groups was similar for the patients with cStage 1 or 2 (p = 0.6265), but it was significantly higher in the TD-resected group for the patients with cStage 3 or 4 (p = 0.0052). The incidence of total recurrence did not differ between the two groups. However, the incidence of hematogenous recurrence in the TD-resected group (19.0%) was significantly lower than in the TD-preserved group (26.2%) (p = 0.0021). For cT4a tumors, the incidence of local recurrence in the TD-resected group (2.4%) was significantly lower than in the TD-preserved group (18.4%) (p = 0.0183). CONCLUSIONS: Performance of TD resection may help to improve prognosis, especially for patients with advanced esophageal squamous cell carcinoma, by reducing hematogenous and local recurrence. Prospective trials are needed to determine whether prophylactic TD resection has a positive impact on the prognosis of patients with esophageal cancer.

BACKGROUND/AIM: An excessive postoperative inflammatory response is correlated with the development of pneumonia and an unfavourable prognosis in patients undergoing esophagectomy for esophageal cancer. We assessed the influence of OSK-0028, a synthetic human ghrelin on inflammatory response and energy metabolism, on the postoperative course of patients following radical esophagectomy. PATIENTS AND METHODS: Esophageal cancer patients were randomly assigned to low-dose (LD; 0.25 μg/kg/h) or high-dose (HD; 0.5 μg/kg/h) intravenous OSK-0028 or placebo for 7 days after esophagectomy. The primary endpoint was serum interleukin-6 level on postoperative day (POD) 3. RESULTS: A total of 75 patients were enrolled (23 LD, 26 HD, 26 placebo). The median interleukin-6 levels on POD 3 were 40.95, 35.85, and 64.50 pg/ml in the placebo, LD, and HD groups, respectively, with no significant differences (p=0.78). Postoperative complications did not differ between groups. Bodyweight loss was significantly lower in patients receiving OSK-0028 than in those receiving placebo (-0.17% vs. 1.78%, p=0.043). CONCLUSION: Although OSK-0028 did not attenuate inflammatory response after esophagectomy, it prevented postoperative bodyweight loss.

INTRODUCTION: Control of postoperative gastroesophageal reflux (GER) is a critical consideration for patients who undergo proximal gastrectomy. This report describes a new and simple reconstruction method by esophagogastrostomy with placement of the remnant stomach into the lower mediastinum (EG-PRIME). This approach not only suppresses postoperative GER, but it can also be easily performed by total laparoscopy. Detailed herein are the methods for EG-PRIME and the results for three patients with cancer of the upper gastric body. MATERIALS AND SURGICAL TECHNIQUE: At the start of the EG-PRIME surgical procedure, a pseudo-fornix and lozenge-shaped gastric conduit were made by cutting the stomach diagonally. Next, the pseudo-fornix was inserted into the esophageal hiatus to form a new angle of His. Then overlap anastomosis was performed and the entry site was closed longitudinally. The outcomes assessed were operative time, intraoperative blood loss, postoperative complications and GER according to 24-hour pH monitoring. DISCUSSION: The operative times were 339, 288 and 236 minutes; in two patients, intraoperative blood loss was 260 and 343 mL, and in the third, blood loss was minimal. No postoperative complications were observed in any of the three patients. The degree of the GER resulting in fraction time pH<4 was 9.0%, 0.3%, and 2.9%, respectively. No esophagitis by upper gastrointestinal endoscopy was observed in any patient. This EG-PRIME method was technically feasible for reconstruction after proximal gastrectomy by total laparoscopy. This approach may be as simple and useful as esophagogastrostomy for preventing postoperative GER, but more experience with this method is required.

BACKGROUND: A challenge in esophageal reconstruction after esophagectomy is that the distance from the neck to the abdomen must be replaced with a long segment obtained from the gastrointestinal tract. The success or failure of the reconstruction depends on the blood flow to the reconstructed organ and the tension on the anastomotic site, both of which depend on the reconstruction distance. There are three possible esophageal reconstruction routes: posterior mediastinal, retrosternal, and subcutaneous. However, there is still no consensus as to which route is the shortest. METHODS: The length of each reconstruction route was retrospectively compared using measurements obtained during surgery, where the strategy was to pull up the gastric conduit through the shortest route. The proximal reference point was defined as the left inferior border of the cricoid cartilage and the distal reference point was defined as the superior border of the duodenum arising from the head of the pancreas. RESULTS: This study involved 112 Japanese patients with esophageal cancer (102 men, 10 women). The mean distances of the posterior mediastinal, retrosternal, and subcutaneous routes were 34.7 ± 2.37 cm, 32.4 ± 2.24 cm, and 36.3 ± 2.27 cm, respectively. The retrosternal route was significantly shorter than the other two routes (both p < 0.0001) and shorter by 2.31 cm on average than the posterior mediastinal route. The retrosternal route was longer than the posterior mediastinal route in only 5 patients, with a difference of less than 1 cm. CONCLUSION: The retrosternal route was the shortest for esophageal reconstruction in living Japanese patients.

BACKGROUND & AIMS: Reductions in skeletal muscle mass during neoadjuvant therapy can have a negative effect on short- and long-term outcomes in patients with esophageal cancer. However, effective treatment for suppressing reductions in skeletal muscle mass during neoadjuvant therapy has not been established. METHODS: Eighty-seven patients were included in this study who were enrolled in a previous randomized study comparing the effects of enteral nutrition (EN) and parenteral nutrition (PN) on chemotherapy-related toxicities during neoadjuvant chemotherapy in esophageal cancer patients. Changes in skeletal muscle mass during neoadjuvant therapy were compared between the two groups. RESULTS: Skeletal muscle mass index (SMI) decreased from 45.8 cm2/m2 before treatment to 43.7 cm2/m2 after neoadjuvant chemotherapy in 87 patients (p = 0.092). The total calorie intake during neoadjuvant therapy was equal between the two groups. SMI reduction was significantly smaller in the EN group than in the PN group (-1.4 cm2/m2 vs -3.0 cm2/m (Gebski et al., 2007) [2], p < 0.001). EN support was identified as the only independent factor adversely associated with severe SMI reduction (p < 0.001). Patients with low SMI after neoadjuvant chemotherapy were more susceptible to postoperative complications than patients with moderate SMI (47.6% vs 16.7%, p = 0.007), especially pulmonary complications (31.8% vs 10.8%, p = 0.003). Patients with low SMI after neoadjuvant chemotherapy tended to show worse prognosis than patients with moderate SMI (5-year overall survival rate: 43.8% vs 62.1%, p = 0.194). CONCLUSIONS: Compared with PN support, EN support during neoadjuvant chemotherapy suppressed reductions in skeletal muscle mass in patients with esophageal cancer.

INTRODUCTION: We compare planned salvage surgery after definitive chemoradiotherapy (SALV) versus neoadjuvant chemoradiotherapy plus surgery (NCRS) for borderline resectable T4 esophageal squamous cell carcinoma. PATIENTS AND METHODS: A total of 37 patients underwent planned SALV, and 20 underwent NCRS from 2004 to 2017. The short-term outcome measures were the R0 resection rate, complications, and treatment-related mortality. The long-term outcome measures were the 5-year overall survival rate and causes of death. RESULTS: R0 resection rate was similar between the SALV and NCRS groups (81% versus 85%). The incidence of postoperative pneumonia (35% versus 18%) and treatment-related mortality rate (9% versus 0%) tended to be higher in the SALV. ypT grade 2-3 (65% versus 30%, p = 0.012) and Clavien-Dindo grade ≥ IIIb complications (32% versus 0%, p = 0.008) were significantly more frequent in the SALV group. The groups had similar 5-year overall survival (26% versus 27%). The causes of death in the SALV and NCRS groups were primary esophageal cancer in 35% and 55% of patients, respectively, and pulmonary-related mortality in 24% and 5%, respectively. Multivariable Cox regression analysis revealed the following significant poor prognostic factors: stable disease as the clinical response, preoperative body mass index (BMI) of < 18.5 kg/m2, ypN stage 1-3, and R1-2 resection. CONCLUSIONS: SALV was associated with a higher incidence of late pulmonary-related mortality but had a stronger antitumor effect than NCRS. Consequently, the survival rate was similar between the groups. Surgery is recommended for patients with a partial response and preoperative BMI of ≥ 18.5 kg/m2.

OBJECTIVE: To compare short-term outcomes between two- vs. three courses of neoadjuvant chemotherapy (NAC) to clarify the optimal treatment for esophageal squamous cell cancer (ESCC) in a multicenter, randomized, phase II trial. BACKGROUND: An optimal number of NAC cycles remains to be established for locally advanced ESCC. METHODS: Patients with locally advanced ESCC were randomly assigned to either two (N = 91) or three (N = 89) courses of DCF (70 mg/m2 intravenous docetaxel and 70 mg/m2 intravenous cisplatin on day 1, and a continuous 700 mg/m2 fluorouracil infusion for 5 days) every 3 weeks followed by surgery. We compared the two groups for perioperative parameters, adverse events, and the response to NAC. RESULTS: The two- and three-course groups showed similar completion rates and overall NAC dose reductions. Although the two-course group showed significantly lower overall grades 3-4 leukopenia and anemia compared to the three-course group, the two groups had similar overall toxicity rates. Postoperative complications were not significantly different between the two groups, except arrhythmia (13 vs. 0%, P = 0.0007). Only two postoperative in-hospital deaths occurred in the three-course group, due to sepsis following severe pneumonia. Compared to the two-course group, the three-course group was associated with a significantly better clinical response (42.9 vs. 65.2%, P = 0.0027) and a relatively higher rate of pathological complete response (9.1 vs. 15.3%, P = 0.212). CONCLUSION: Both two- and three-course DCF regimens in the NAC setting seemed to be equally feasible in locally advanced ESCC patients. Additional DCF courses led to a better NAC response without increasing the incidence of adverse events or postoperative morbidity. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (Identification Number UMIN 000015788).

PURPOSE: The purpose of this study is to determine the clinical significance of micrometastases after neoadjuvant chemotherapy (NAC) and the difference in controlling micrometastases using different NAC regimens in resectable advanced esophageal squamous cell carcinoma (ESCC). METHODS: We analyzed patients with ESCC who underwent esophagectomy with lymph node dissection after NAC with Adriamycin + cisplatin + 5-fluorouracil (ACF) or docetaxel + cisplatin + 5-fluorouracil (DCF). Micrometastasis was defined as a single isolated cancer cell or cluster of cancer cells on the cervical, recurrent nerve, or abdominal LNs as shown by immunohistochemical staining with anti-cytokeratin antibody (AE1/AE3). The associations between micrometastases, recurrence, prognosis, and regimen differences were investigated. RESULTS: One hundred and one cases (ACF group: 51 cases; DCF group: 50 cases) were analyzed. Micrometastases occurred in 24 patients (23.8%): 17/51 (33.3%) in the ACF group and 7/50 (13.5%) in the DCF group (p = 0.0403). The 5-year recurrence-free survival (RFS) rates for patients without (n = 77) and with (n = 24) micrometastases were 62 and 32%, respectively, (hazard ratio, 2.158; 95% confidence interval, 1.170-3.980; stratified log-rank test, p = 0.0115). A multivariate analysis showed that stage pN1 or higher and micrometastases were significant risk factors affecting RFS. CONCLUSION: In resectable advanced ESCC, controlling micrometastases in the LNs after NAC varied by regimen and may be associated with preventing ESCC recurrence.

Aim: The aim is to report the long-term outcomes of preoperative cisplatin and fluorouracil plus docetaxel (DCF) vs Adriamycin (ACF) for resectable esophageal squamous cell carcinoma (ESCC). Previously, this trial showed that DCF is associated with prolonged recurrence-free survival (RFS). Methods: Patients were randomly assigned to two cycles of ACF (35 mg/m2 of Adriamycin, 70 mg/m2 of cisplatin intravenously on day 1, and 700 mg/m2 of fluorouracil infusion for 7 days) every 4 weeks or DCF (70 mg/m2 of docetaxel, 70 mg/m2 of cisplatin intravenously on day 1, and 700 mg/m2 of fluorouracil infusion for 5 days) every 3 weeks, followed by surgery. The primary endpoint was RFS. The secondary endpoint was overall survival (OS). Results: Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, 162 of whom were eligible and randomly assigned to the two groups. The median follow-up for surviving patients was 69.8 months. The 5-year RFS was significantly better in the DCF group than in the ACF group (59.9% vs 40.7%, hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.35-0.86; P = .009) and the 5-year OS was significantly better in the DCF group than in the ACF group (63.5% vs 49.4%, HR, 0.61; 95% CI, 0.38-0.96; P = .03). The benefit of DCF chemotherapy on survival was significantly greater in the subgroups with more advanced clinical T and N stage. Conclusions: Cisplatin and fluorouracil plus docetaxel are associated with better RFS and OS than ACF in resectable ESCC patients.

BACKGROUND: Feeding jejunostomy (FJ) is a common treatment to support patients with esophageal cancer after esophagectomy. However, severe FJ-related complications, such as bowel obstruction, occasionally occur. We investigated the ability of our simple, novel FJ technique, the "curtain method," to prevent bowel obstruction. METHODS: In laparoscopic surgery, the main mechanism of bowel obstruction involves torsion of the mesentery accompanied by migration of the intestine across the fixed FJ through the space surrounded by a triangle comprising the ligament of Treitz, fixed FJ, and spleen rather than adhesion. Our "curtain method" involves closure of this triangle zone with omentum, and the appearance of the lifted omentum resembles a curtain. Sixty patients treated with this modified FJ were retrospectively compared with 13 patients treated with conventional FJ in terms of the incidence of bowel obstruction, peritonitis, stoma site infection, and catheter obstruction. RESULTS: From 2013 to 2017, 60 patients underwent esophagectomy and gastric conduit reconstruction accompanied by modified laparoscopic FJ. The median observation period, including the period after tube removal, was 644 days. No FJ-associated bowel obstruction, the prevention of which was the primary aim, occurred in any patient. Likewise, no peritonitis or dislodgement occurred. Eight patients (13%) developed a stoma site infection with granulation. The feeding tube became occluded in 11 patients (18%); however, a new feeding tube was reinserted under fluoroscopy for all of these patients. From 2003 to 2012, 13 patients underwent conventional FJ. The median observation period was 387 days. Three patients (23%) developed bowel obstruction by torsion 71 to 134 days after the first surgery, and all were treated by emergency operations. Other FJ-related complications were not different from those in the modified FJ group. CONCLUSION: Our simple, novel technique, the "curtain method," for prevention of laparoscopic FJ-associated bowel obstruction after esophagectomy is a safe additional surgery.

OBJECTIVE: We conducted a multicenter randomized prospective phase 2 trial of chemoradiotherapy (CRT) versus chemotherapy (CT) as initial induction therapy for conversion surgery (CS) in clinical T4b esophageal cancer. We compared treatment effects and adverse events. SUMMARY BACKGROUND DATA: Although induction followed by CS is potentially curative for T4b esophageal cancer, the optimal initial induction treatment is unclear. METHODS: Ninety-nine patients with T4b esophageal cancer were randomly allocated to chemoradiotherapy (Group A, n = 49) or CT (Group B, n = 50) as initial induction treatment. CRT consisted of radiation (50.4 Gy) with cisplatin and 5-fluorouracil. CT consisted of 2 cycles of docetaxel plus cisplatin and 5-fluorouracil (DCF). CRT or CT was followed by CS if resectable. If unresectable, the patient received the other treatment as secondary treatment. CS was performed if resectable after secondary treatment. The primary end point was 2-year overall survival. RESULTS: In Group A, CS was performed in 34 (69%) and 7 patients (14%) after initial and secondary treatment. In Group B, CS was performed in 25 (50%) and 17 patients (34%) after initial and secondary treatment. The R0 resection rate after initial and secondary treatment was similar (78% vs 76%, P = 1.000). Adverse events including leukopenia, neutropenia, febrile neutropenia, and diarrhea were significantly more frequent in Group B. Group A had better histological complete response of the primary tumor (40% vs 17%, P = 0.028) and histological nodal status (P = 0.038). CONCLUSIONS: Upfront CRT was superior to upfront CT in terms of pathological effects and adverse events. The Japan Registry of Clinical Trials (s051180164).

PURPOSE: We retrospectively investigated the risk factors for mediastinal lymph node (MLN) metastasis in esophagogastric junction (EGJ) cancer with an epicenter within 2 cm above and below the anatomical cardia, including both adenocarcinoma (AC) and squamous cell carcinoma (SCC). METHODS: Fifty patients who underwent initial surgery for EGJ cancer from January 2002 to December 2013 were included in this study. We defined metastatic lymph nodes as pathological metastases in resected specimens and recurrence within 2 years postoperatively. RESULTS: Thirty-four patients had AC and 16 had SCC; 24 patients underwent transhiatal resection and 26 underwent transthoracic resection. MLN metastasis was observed in 13 patients (26%) regardless of the histological type, 9 of whom had metastasis in the upper and middle mediastinum. Metastasis occurred when the esophageal invasion length (EIL) exceeded 20 mm. In addition, 10/13 patients had stage pN2-3 cancer. Multivariable analysis identified EIL ≥ 20 mm and stage pN2-3 as significant risk factors for MLN metastasis. The 5-year overall survival was 38% and 65% in the MLN-positive and -negative groups, respectively (p = 0.12). Multivariable Cox regression analysis showed that only stage pN2-3, and not the presence of MLN metastasis, was a significantly poor prognostic factor. CONCLUSION: MLN metastasis in EGJ cancer may have a close association with the EIL of the tumor, but the presence of MLN metastasis itself was not a poor prognostic factor. The significance and indications for MLN dissection should be clarified in prospective clinical trials.

OBJECTIVES: To elucidate the efficacy of adjuvant vaccine monotherapy using 3 Human Leukocyte Antigen (HLA)-A24-restricted tumor-specific peptide antigens for ESCC, upregulated lung cancer 10, cell division cycle associated 1, and KH domain-containing protein overexpressed in cancer 1. SUMMARY OF BACKGROUND DATA: ESCC patients with pathologically positive nodes (pN(+)) have a high risk for postoperative recurrence, despite curative resection after preoperative therapy. Subclinical micrometastases are an appropriate target for cancer vaccine. METHODS: This is a non-randomized prospective phase II clinical trial (UMIN000003557). ESCC patients curatively resected after preoperative therapy with pN(+) were allocated into the control and vaccine groups (CG and VG) according to the HLA-A status. One mg each of three epitope peptides was postoperatively injected 10 times weekly followed by 10 times biweekly to the VG. The primary and secondary endpoints were relapse-free survival (RFS) and esophageal cancer-specific survival (ECSS), respectively. RESULTS: Thirty were in the CG and 33 in the VG. No significant difference was observed in RFS between the CG and VG (5-year RFS: 32.5% vs 45.3%), but the recurrence rate significantly decreased with the number of peptides which induced antigen-specific cytotoxic T lymphocytes. The VG showed a significantly higher 5-year ECSS than the CG (60.0% vs 32.4%, P = 0.045) and this difference was more prominent in patients with CD8 and programmed death-ligand 1 double negative tumor (68.0% vs 17.7%, P = 0.010). CONCLUSIONS: Our cancer peptide vaccine might improve the survival of ESCC patients, which is warranted to be verified in the phase III randomized controlled study.

Unexpected dysphagia is an important problem affecting life prognosis in patients who have undergone an esophagectomy for esophageal cancer. For nutritional support in patients suffering from dysphagia after a previous esophagectomy, a simplified percutaneous endoscopic transgastric conduit feeding jejunostomy approach was developed that can be performed regardless of the patient's condition. The feasibility of this procedure in 25 patients with esophageal cancer who underwent three-stage esophagectomy with retrosternal gastric conduit reconstruction from April 2009 to December 2016 was evaluated retrospectively. Under fluoroscopy, a percutaneous endoscopic transgastric conduit feeding jejunostomy catheter (9 French) was introduced into the jejunum in the epigastric region using the Seldinger's technique. The following patient data were analyzed retrospectively: operating time, complications, reasons for oral intake difficulty, and clinical data describing patients' nutritional status before and 1 month after percutaneous endoscopic transgastric conduit jejunostomy treatment, such as serum albumin and clinical course. Median patients' age was 68 years (range 50-76 years). Indications for the procedure were late swallowing dysfunction (n = 12), early swallowing dysfunction secondary to surgical complication (n = 8), anastomotic leakage (n = 3), and anorexia (n = 2). Causes of late swallowing dysfunction were radiation injury (n = 8), advanced age (n = 2), or cerebral infarction (n = 2). The median operating time was 29 minutes (range 14-82 minutes). Four patients developed mild erosions at the stoma secondary to bile reflux along the side of the catheter. No patient experienced severe complications such as ileus and peritonitis. Patients were treated for a median of 160 days (range 18-3106 days) with percutaneous endoscopic transgastric conduit jejunostomy. Patient's serum albumin significantly increased from 2.8 to 3.3 g/dl in 1 month. Of the eight patients with early swallowing dysfunction, six successfully regained sufficient oral nutrition after receiving enteral feeding nutritional management. Although all except one late swallowing dysfunction patient could not discontinue tube feeding, five patients were long-term survivors at the time this report was written. This jejunostomy procedure is simple, safe, and useful for patients with unexpected dysphagia and accompanying malnutrition after esophagectomy.

BACKGROUND: Granular cell tumors (GCT) in the gastrointestinal tract are rare. Herein, we describe a case of a gastric GCT diagnosed preoperatively by endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) and successfully resected by single-incision laparoscopic surgery (SILS). CASE PRESENTATION: A 46-year-old Japanese woman had a tumor located in the angle of the stomach that was approximately 1.5 cm in diameter. Abdominal computed tomography (CT) revealed a submucosal tumor (SMT), which was finally diagnosed as a gastric GCT using EUS-FNAB. The tumor was not identified by CT 1 year and 4 months before diagnosis; therefore, because there was a possibility that the tumor was malignant, we performed surgical wedge resection using SILS. The patient had an uneventful recovery postoperatively and was discharged without complications 3 days after surgery. The tumor was pathologically diagnosed as a benign GCT that remained within the muscular layer. No recurrence or complications have occurred in the first 16 months since the surgery. CONCLUSION: Because gastric GCTs are generally benign and are rarely associated with lymph node metastasis, SILS seems to be a safe and feasible surgical approach for treating GCTs.

BACKGROUND: In Japan, pre-operative 5-FU and cisplatin(CDDP)(FP)combination therapy has been the standard neoadjuvant chemotherapy(NAC)for advanced resectable esophageal cancer(EC); furthermore, the efficacy of the docetaxel (DTX)-containing triplet regimen, FP plus DTX, has been reported. However, patients with impaired renal function should not receive high-dose CDDP. We have been developing a non-CDDP-containing triplet regimen, comprising 5-FU, DTX, and nedaplatin(NED)(UDON), on a phase Ⅰ/Ⅱtrial basis. This retrospective study aimed to investigate the safety and efficacy of NAC with UDON in advanced EC patients with impaired renal function. METHODS: Five patients with advanced resectable EC with impaired renal function were enrolled in this study. Patients received NAC(5-FU, 640mg/m / 2, days 1-5; DTX, 28 mg/m2, days 1 and 15; and NED, 72mg/m2, day 1, q28, 2 courses); following this, they underwent esophagectomy. The primary endpoint was response rate, and the secondary endpoint was adverse event(AE). RESULTS: The median age was 79 years (range: 58-80 years). The ECOG performance status was 1/2 : 3/2. The main tumor locations were Ce/Ut/Mt : 1/1/3 and the cStages were ⅡA/ⅢA/ⅢC : 1/2/2. The RR(CR/PR/SD/PD : 0/4/1/0)was 80%. The pathological response was grade 1a/1b : 2/3. Major grade 3 or 4 AEs included neutropenia(40%), febrile neutropenia(20%), diarrhea(20%), and hyponatremia( 40%). There was no treatment-related death or reoperation. CONCLUSIONS: NAC with UDON might be feasible and effective in patients with advanced resectable EC with impaired renal function, who are ineligible for high-dose CDDP administration. We are planning a phaseⅡclinical study based on the present results.

A 71-year-old man with a history of hypertension, diabetes mellitus, and cerebral infarction was admitted to our hospital with dysphagia. Gastroduodenoscopy, thoracoabdominal CT, and PET-CT findings showed type 2 advanced esophageal cancer( squamous cell carcinoma)with upper mediastinal and cervical lymph node(LN)metastasis: cT3N2M1(LYM #104L), cStage Ⅳ. Two courses of neoadjuvant UDONchemotherapy containing 5-FU(640mg/m / 2, days 1-5), docetaxel(28mg/m2, days 1 and 15), and nedaplatin(72mg/m2, day 1)were administered every 4 weeks. UDONtherapy caused grade(Gr)3 febrile neutropenia, Gr 2 diarrhea, and Gr 1 thrombopenia; the tumor and LNs partially responded to the therapy. After 2 courses of UDONtherapy, esophagectomy with right thoracotomy, 3-field LNdissection, and reconstruction of the gastric tube were performed. The postoperative course was almost uneventful besides recurrent nerve palsy, aspiration, pneumonia, and delirium, and the patient was discharged 60 days after surgery. The pathological diagnosis was ypT0N0M0, ypStage 0, and the histological response of the primary tumor and LNs were evaluated as Gr 3. Neoadjuvant UDON therapy is feasible for elderly patients with advanced esophageal cancer and renal failure or comorbidities, for whom CDDP could not be administered. We are planning a clinical trial to assess the effectiveness of neoadjuvant UDONtherapy.

The usefulness of intraperitoneal(IP)chemotherapy for gastric cancer with intraperitoneal metastasis has been examined in some clinical trials. We report a case of intestinal perforation caused by a catheter for IP ports. A 75-year-old man had undergone IP therapy for type 4 gastric cancer. After IP therapy, he underwent total gastrectomy. He had no recurrence for 3 years. He complained of high fever and abdominal pain more than 1 week ago. Based on contrast-enhanced CT, we diagnosed him with peritonitis by intestinal perforation due to the catheter, and on the same day, we removed the catheter and performed intraperitoneal drainage by emergent laparotomy. The tube penetrated the ileum 20 cm from the ileocecal portion. We resected the ileocecal area and damaged intestinal tract and removed the subcutaneous IP port. He was discharged on the 25th postoperative day. IP ports should be removed after the completion of IP chemotherapy because the incidence of perforation by IP ports was reported as 0 to 3.5%in a previous report.

AIM: To conduct a phase II study of single intraperitoneal (i.p.) administration of paclitaxel followed by paclitaxel, cisplatin, and S-1 (PCS) chemotherapy for patients with gastric cancer with peritoneal metastasis (PM). PATIENTS AND METHODS: Staging laparotomy was performed to confirm PM. Initially, patients received i.p. paclitaxel. Beginning 7 days later, PCS was given every 3 weeks followed by second-look laparoscopy. Primary and secondary endpoints were the overall survival (OS) rate, and response rate and patient safety, respectively. RESULTS: Seventeen patients were enrolled. The overall response rate was 70.5% (12/17). Grade 3/4 toxic effects included neutropenia and leukopenia. After chemotherapy, PM disappearance was confirmed in 11 patients. Gastrectomy was eventually performed in 11 patients. The 1-year OS rate was 82.4% and the median survival time was 23.9 months considering the overall cohort. CONCLUSION: Combination chemotherapy with i.p. paclitaxel and PCS is well tolerated and effective in patients with gastric cancer with PM.

BACKGROUND: An incisional hernia in a case of antethoracic pedicled jejunal flap esophageal reconstruction after esophagectomy is a very rare occurrence, and this hernia was distinctive in that the reconstructed jejunum had passed through the hernial orifice; a standard surgical treatment for such a presentation has not been established. Herein, we describe a case of repair using mesh prosthesis for an atypical and distinctive incisional hernia after antethoracic pedicled jejunal flap esophageal reconstruction. CASE PRESENTATION: A 77-year-old woman with a history of subtotal esophagectomy who had undergone antethoracic pedicled jejunal flap reconstruction complained of epigastric prominence and discomfort without pain. On examination, she had an abdominal protrusion between the xiphoid process and the umbilicus that contained the small bowel. Computed tomography showed that the fenestration of the abdominal wall that was intentionally created for jejunum pull-up was dehisced in a region measuring 9 × 15 cm and the small intestine protruded through it into the subcutaneous space without strangulation. Because the hernial orifice was too large and the reconstructed jejunum was passing through the hernial orifice in this case, we applied a parastomal hernia repair method that was modified from the inguinal hernia repair using the Lichtenstein technique. After 3 years and 5 months following surgery, the patient has recovered without hernia recurrence or other complications. CONCLUSION: We consider this to be the first case of repair using Composix mesh prosthesis for repair of an atypical and distinctive incisional hernia after an antethoracic pedicled jejunal flap reconstruction. This method seems to be useful and could potentially be widely adopted as the surgical treatment for this condition.

Some of scirrhous gastric cancer are difficult to diagnose on the surface view or to take correct biopsy specimen.A 85-yearold man with dysphagia was diagnosed scirrhous gastric cancer endoscopically, but could not be taken a biopsy specimen showing cancer.We informed cases of scirrhous gastric cancer difficult to take correct biopsy specimen and recommended surgical operation to take correct specimen and to start a treatment.Patient underwent total gastrectomy after cancer diagnosis( P0CY0cT4aN0).He can eat more food and survive longer than 1 year without any chemotherapies.Scirrhous gastric cancer needs early diagnosis and treatment to improve patient prognosis.

Prognosis of locally advanced esophageal cancer is poor. The greatest prognostic factor of locally advanced esophageal cancer is a local control. We experienced a case of T4 locally advanced thoracic esophageal cancer who was successfully resected without any combined resection after multimodality therapy. A male in 75-year-old. was diagnosed with type 3 locally advanced upper thoracic esophageal cancer whose metastatic right recurrent laryngeal lymph node invaded into the trachea. Definitive chemoradiation therapy(CRT)was performed, leading to a significant shrinkage of the main tumor, but T4 lesion remained. Next, adding DCF therapy(docetaxel, CDDP and 5-FU), a relief of T4 was finally obtained. Then, salvage surgery with subtotalesophagectomy and retrosternalesophagealreconstruction with gastric tube was performed, resulting in R0 resection without any combined resection. The postoperative course was uneventful, and the patient has been alive without recurrence for 1 year after surgery. In locally advanced cancer, focusing on T4 downstaging, it is significantly important in terms of safety, curativity and organ preservation to perform surgery after a sure sign of T4 relief by multimodality therapy.

A 76-year-old man was admitted to our hospital for treatment of gastric tube cancer(cT2N0M0, cStage II A)detected by a screening upper gastrointestinal endoscopy. Seven years previously, he had undergone subtotal esophagectomy for esophageal cancer with gastric pull-up via the retrosternal route. At that time, he experienced cardiopulmonary arrest due to ventric- ular tachycardia. He was in a state of poor nutrition(BMI 15 kg/m2). Therefore, reducing operative stress as much as possible, minimizing complications after surgery, and aiming for a satisfactory postoperative course are all important goals. Based on his past history, we performed distal gastrectomy(resection of the distal part of the gastric tube)without excision of the right gastroepiploic artery. The postoperative course was uneventful. He was discharged 40 days after surgery. By considering the risks of surgery due to cardiac dysfunction and malnutrition, we were able to provide effective and safe therapy for the patient.

The usefulness and safety of imatinibfor neoadjuvant chemotherapy for resectable gastrointestinal stromal tumor(GIST) has not been established. We reported a case of a huge GIST of the stomach that was safely resected following preoperative imatinibtherapy. A 69-year-old man was hospitalized with abdominal fullness which increased rapidly from a month ago. A CT scan showed a huge tumor containing solid and cystic component which was accompanied by an extra-wall nodule. The tumor was strongly suspected to be originated from the stomach and EUS-FNA revealed GIST. We diagnosed GIST of the stomach and initiated preoperative adjuvant chemotherapy with imatinib because there was a risk for the break of tumor capsule and composite resection of the other organs without prior chemotherapy. After the administration of imatinib4 00 mg/day for 6months, the solid component was decreased in size and its' activity by PET-CT had declined, but the size of the cystic component was not changed and the patient's complaint of fullness was not reduced. Then, after a week cessation of imatinib, we performed surgical removal of the tumor with partial gastrectomy without surgical complication during and after the operation. Imatinibwas resumed 2 weeks later postoperatively and 1 year and 8 months has passed since the operation without recurrence. Neoadjuvant chemotherapy with imatinibhas the potential to become an important therapeutic option for the treatment of huge GISTs.

The patient was a 58-year-old man suffering from dysphagia. He was diagnosed with T3 cervicalesophagealcancer that invaded the posterior hypopharyngealwal lwith lymph node metastasis. The patient received neoadjuvant chemoradiotherapy (30 Gy with CDDP/5-FU), followed by larynx-preserving surgery(LPS)for cervicalesophagealcancer. Two techniques for successfulLPS consist of the dissections of cricopharyngealmuscl e and the inferior pharyngealsphincter, and the complete division of the bilateral infrahyoid muscles attached to the sternum(CDBIMS). The former technique of releasing the esophagus from the trachea at the cricoid cartilage level results in the extension of the oral surgical margin. The latter technique is expected to prevent postoperative aspiration pneumonia, as the lack of flexibility of scarred infrahyoid muscles is regarded as one of the major causes of dysfunction in swallowing. Free jejunum was transferred for cervical reconstruction. Pathological examination indicated degenerated squamous cell carcinoma(ypT2, INF b, ly0, v0, PM0, ypN0, ypStage II A). Although the patient had recurrent nerve palsy, he could eat meals without aspiration. He returned to normal life after discharge from the hospital. Five years after surgery, no recurrence had been observed.

According to the Guidelines for Diagnosis and Treatment of Carcinoma of the Esophagus in Japan, the standard treatment of esophageal cancer with cStage II / III is preoperative chemotherapy and radical resection. But when the tumor has deep ulcer, the perforation of it is sometimes occurred due of the anti-tumor effect and we are forced to change the standard treatment. In this time, we report a case of emergency resection of esophageal cancer which is on the brink of perforation after neoadjuvant chemotherapy. A 62-year-old woman had locally advanced esophageal cancer(cT4N2M0)and performed neoadjuvant chemotherapy(NAC). After 2 courses of NAC, the patient got into critical condition that the esophageal cancer was on the brink of perforation, thus we immediately performed emergency resection of the tumor. Unfortunately, the tumor was not completely resected because of invasion to the Botallo ligament, but we were able to avoid a critical state such as mediastinitis or penetration to the aorta. In multimodality therapy for locally advanced tumor, immediate response to oncologic emergency is significantly required, impacting on the prognosis and quality of life.

Patients with esophageal cancer are often treated with definitive chemoradiotherapy (dCRT). Regardless of arrival at dCRT, the risk of local/regional recurrence during follow-up is significant. Many patient are faced with limited options for therapy once dCRT has failed. Salvage surgery is the only way for complete cure of patients with local/regional recurrent esophageal cancer after dCRT. However, salvage surgery has a significant high risk of fatal complications. We examine our preventive measures to reduce the incidence of postoperative complications after salvage surgery for thoracic esophageal cancer. The points of our preventive measures are them; I. the ingenuity of surgery, II. the securement of blood supply for the respiratory tract, III. standard lymphadenectomy, IV. countermeasures of anastomotic failure, V. countermeasures of dead space, VI. countermeasures of respiratory complications, VII. perioperative managements. Salvage surgery is a reasonable option to treat patients with local/regional recurrence after failed dCRT. Our preventive mesures are effective, therefore, we have to make the further technological developments and the safety of salvage surgery.

Multi-course neoadjuvant chemotherapy (NACT) followed by surgery is a promising treatment for advanced esophageal cancer. However, non-responders may continue to receive ineffective treatment, since there are no definitive criteria for early discontinuation of NACT. In this study, we analyzed 103 advanced esophageal cancer patients treated with 2 cycles of NACT followed by surgery. Patients with >20% decrease in the size of the primary tumor as evaluated by computed tomography (CT) following the first cycle of chemotherapy, were defined as early responders and the remainder as early non-responders. Clinicopathological factors and prognosis were compared between the 2 groups. The reduction rate of the second cycle and progression-free survival (PFS) of early non-responders were significantly worse than those of early responders (p=0.0001 and 0.0375, respectively). In addition, pathological T stage, pathological assessment of tumor regression and number of metastatic lymph nodes were significantly unfavorable in early non-responders (p=0.023, 0.007 and 0.0041, respectively). Among the clinical factors that were available prior to administration of the second cycle, clinical T3 stage and early non-responder status were the only independent unfavorable factors (p=0.028 and 0.0062, respectively). Patients with both unfavorable factors had a significantly poorer PFS compared to the remaining patients and a PFS similar to those who had both factors but received only 1 cycle of NACT. In conclusion, the reduction rate of the primary tumor as evaluated by CT following the first cycle of NACT, may aid physicians in determining whether to administer a second cycle. In early non-responders bearing T3 tumors, NACT should be discontinued after the first cycle.

肝切除の合併症である胆汁漏を予防するため胆道ドレナージを用いたが、発生率に変化はないが入院期間は短縮された。

肝細胞癌発生の多くはhepatitis B virus (HBV)あるいはhepatitis C virus (HCV)感染による慢性肝炎,肝硬変が関与している.しかしHBs抗原陰性,HCV抗体陰性の非B非C型肝細胞癌は5〜10%存在し,発癌要因に関してはいまだ解明されていない.従来HBV感染は血清中HBs抗原により評価されてきたが,非B非C型肝細胞癌にはHBc抗体陽性のB型肝炎の既往例や血清中にHBV-DNAが検出される例が存在し,非B非C型肝癌のウイルス感染について再検討する必要性がある.我々は非B非C型肝細胞癌切除46例でHBV,HCVの関与をin situ hybridization法を用いて検討した.80.4%でHBV-DNAが検出され,いずれもHCV-RNAは検出されなかった.各症例でHBV-DNA発現程度に差が認められ,high group,low groupに分類し,治癒切除35例で無再発生存率について比較評価したところ,5年生存率はhigh groupで13.8%,low groupは59.2%であった.有意にhigh groupにおいて再発率が高いことが示された.本研究で非B非C型肝癌の要因にはHBVの存在が深く関与しており,血清中HBs抗原陰性ではHBV感染を否定できず,また肝組織内のウイルス量が多いものは再発予後に影響を及ぼす要因であることが示唆された.

胸部食道癌に対する食道切除術では、胸部操作終了時も食道を胸腔内に残し、引き続きの腹部もしくは頸部操作時に体外に摘出するのが一般的である。摘出までの数時間での食道標本からの遊離癌細胞の胸腹内散布が懸念されるが、実際のリスクはこれまでに報告がなく不明である。本研究では、まず食道標本を滅菌ビニール袋で密閉カバーし、食道標本から漏出する液を採取し、液中の細胞診による遊離癌細胞の有無の評価し、癌細胞の遊離が陽性となる頻度や、及び陽性症例の臨床病理学的特徴、再発率、再発形式を検討する。さらに癌細胞の散布予防策を考案・確立し、その有用性を検証することを目的としている。 これまでに30例の症例について、細胞診を提出し検討した。30例中2例（6.7％）において、食道標本をカバーした袋内に貯留した液より、癌細胞が検出された。一方で全症例において、手術開始時（開胸直後）の胸腔内洗浄細胞診、胸部操作終了時の胸腔内洗浄細胞診、腹部操作終了時（標本摘出と同時）の胸腔内洗浄細胞診では癌細胞を認めなかったため、食道標本より癌細胞が散布されていることが証明された。

食道癌術後は誤嚥のリスクが高く、重篤な肺炎に繋がる可能性からその予防は大きな課題である。嚥下運動機能障害による誤嚥は術式の改良やリハビリテーションによって改善されてきたが、嚥下反射の低下による誤嚥は未解決のままである。嚥下反射は脳の刺激で分泌されるサブスタンスP（SP）により制御されているので、術前血中SP値と無症候性脳梗塞および術前後の嚥下機能との関連を検討した。60歳以上の半数に認めると言われた無症候性脳梗塞は5%程度しか認めなかったが、血中SP低値の症例は術後の嚥下機能が悪く、誤嚥発症率は有意に高かった。以上より、血中SPの測定は術後の嚥下機能予測に有用である可能性が示唆された

本研究では、食道扁平上皮癌に対する化学療法、放射線化学療法の治療早期におけるp53-Ser46のリン酸化をバイオマーカーとした治療効果予測の有用性を検討し、実際に生検組織の検討でp53-Ser46のリン酸化の誘導を治療開始翌日の生検で初めて臨床的に確認したが、治療開始後早期のSer46リン酸化の有無と化学療法や化学放射線療法の治療効果との間には明らかな相関は認めなかった。CRが得られた症例の中にはp53 mutant/Ser-46リン酸化陰性例も認められており、今回の検討から化学療法や化学放射線療法に対する効果はp53によるアポトーシス経路のみでなく、他の要因も関わることが示唆された。

高齢者の誤嚥は、咳および嚥下反射を制御するサブスタンスP(SP)の分泌低下が原因である。そこで、高齢者に多く、術後に誤嚥のリスクの高い食道癌手術患者における術前後の血中SP値の推移を調べ、誤嚥発症との関連を検討した。術前後で有意な変動は見られなかったが、術前より低値を示す症例は有意に誤嚥を発症する率が高く(p=0.004)、術前血中SP低値(60pg/ml以下)の症例は術後誤嚥発症のハイリスク群と考えられた。