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Background: Laparoscopic surgery for gastric cancer has become widely used; minimally invasive surgery has become the mainstream of treatment. This randomized controlled trial (RCT) aimed to compare long-term quality of life (QoL) and weight loss rates in patients who underwent single-port laparoscopic gastrectomy (SLG) or multi-port laparoscopic gastrectomy (MLG) for gastric cancer., Methods: This single-center RCT compared MLG and SLG in patients with clinical stage I gastric cancer, all of which underwent distal gastrectomy between April 2016 and September 2018. A total of 101 patients were evaluated for eligibility; all were randomized into either the SLG group (n = 50) or MLG group (n = 51). Blood tests, weight measurements, and postoperative questionnaires (DAUGS20, EORTC QLQ-C30, PGSAS-45) were performed at 3, 6, 12, and 36 months after surgery to compare the QoL., Results: At six months postoperatively, there was a higher trend toward lower weight loss in the SLG group compared with the MLG group. At 1, 3, 6, and 36 months postoperatively, the neutrophil-to-lymphocyte ratio was significantly lower in the SLG group than that in the MLG group. The QoL, as measured using the postoperative questionnaires, was generally comparable. However, some favorable results, such as fewer diarrheas, were achieved., Conclusions: SLG was partially superior to MLG in terms of long-term QoL, in addition to assurance of esthetics and reduced pain. In addition, systemic inflammatory markers and weight loss rates were lower, suggesting a potential long-term benefit. SLG may be an option for stage I gastric cancer surgery. Further follow-up and multicenter studies should be considered., Competing Interests: Declarations Disclosures Kohei Fujita, Takeshi Omori, Hisashi Hara, Naoki Shinno, Masayoshi Yasui, Hiroshi Wada, Hirofumi Akita, Masayuki Ohue, Hiroshi Miyata, and Shuji Takiguchi have declared no conflict of interests. Ethical approval This study was approved by the Institutional Review Board of the Osaka International Cancer Institute (number 1512046225) and follows the Declaration of Helsinki (1975). Written informed consent was obtained from all patients. The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000022218)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Dysphagia caused by tumor strictures is a major symptom in patients with advanced esophageal cancer. However, the prognostic effect of dysphagia in resectable cases is insufficiently investigated. This study aimed to investigate the prognostic value of dysphagia scores in resectable advanced esophageal cancer who underwent radical esophagectomy after preoperative treatment., Methods: This retrospective study enrolled 302 consecutive patients with advanced resectable esophageal cancer who received preoperative treatment. The preoperative dysphagia score was used to assess the relationship between tumor stricture and clinical outcomes., Results: Almost half of the patients had dysphagia scores of 2 to 4 (n = 152 [50.3%]). Lower body mass index, circumferential tumors, and noncurative resection were significantly more common as dysphagia scores worsened. Patients with dysphagia had significantly more advanced ypT stage and worse histopathologic response than those without dysphagia. The 5-year disease-free survival and overall survival (OS) rates for dysphagia scores of 0 to 1, 2 to 3, and 4 were 52.9%, 35.3%, and 26.7% and 60.7%, 40.4%, and 26.7%, respectively. Multivariate analysis identified dysphagia score as an independent factor of OS, similar to surgical curability and ypN stage. The postoperative recurrence rate was significantly higher among patients with dysphagia scores of 2 to 3 (56%) and 4 (67%) than among those with dysphagia scores of 0 to 1 (36%) (P < .001 and P = .037, respectively). Furthermore, distant recurrence in dysphagia scores of 2 to 3 and 4 was higher than in dysphagia scores of 0 to 1 (26%, 46%, and 42%, respectively)., Conclusion: The dysphagia score before initial treatment is associated with postoperative survival in patients with resectable advanced esophageal cancer., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: S-588410, a cancer peptide vaccine (CPV), comprises five HLA-A*24:02-restricted peptides from five cancer-testis antigens. In a phase 2 study, S-588410 was well-tolerated and exhibited antitumor efficacy in patients with urothelial cancer. Therefore, we aimed to evaluate the efficacy, immune response, and safety of S-588410 in patients with completely resected esophageal squamous cell carcinoma (ESCC)., Methods: This phase 3 study involved patients with HLA-A*24:02-positive and lymph node metastasis-positive ESCC who received neoadjuvant therapy followed by curative resection. After randomization, patients were administered S-588410 and placebo (both emulsified with Montanide™ ISA 51VG) subcutaneously. The primary endpoint was relapse-free survival (RFS). The secondary endpoints were overall survival (OS), cytotoxic T-lymphocyte (CTL) induction, and safety. Statistical significance was tested using the one-sided weighted log-rank test with the Fleming-Harrington class of weights., Results: A total of 276 patients were randomized (N = 138/group). The median RFS was 84.3 and 84.1 weeks in the S-588410 and placebo groups, respectively (P = 0.8156), whereas the median OS was 236.3 weeks and not reached, respectively (P = 0.6533). CTL induction was observed in 132/134 (98.5%) patients who received S-588410 within 12 weeks. Injection site reactions (137/140 patients [97.9%]) were the most frequent treatment-emergent adverse events in the S-588410 group. Prolonged survival was observed in S-588410-treated patients with upper thoracic ESCC, grade 3 injection-site reactions, or high CTL intensity., Conclusions: S-588410 induced immune response and had acceptable safety but failed to reach the primary endpoint. A high CTL induction rate and intensity may be critical for prolonging survival during future CPV development., (© 2024. The Author(s).)

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., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: Real-world clinical outcomes of and prognostic factors for nivolumab treatment for esophageal squamous-cell carcinoma (ESCC) remain unclear. This study aimed to evaluate real-world outcomes of nivolumab monotherapy in association with relevant clinical parameters in recurrent/unresectable advanced ESCC patients., Methods: This population-based multicenter cohort study included a total of 282 patients from 15 institutions with recurrent/unresectable advanced ESCC who received nivolumab as a second-line or later therapy between 2014 and 2022. Data, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively collected from these patients., Results: Objective response and disease control rates were 17.0% and 47.9%, respectively. The clinical response to nivolumab treatment significantly correlated with development of overall immune-related adverse events (P < .0001), including rash (P < .0001), hypothyroidism (P = .03), and interstitial pneumonia (P = .004). Organ-specific best response rates were 20.6% in lymph nodes, 17.4% in lungs, 15.4% in pleural dissemination, and 13.6% in primary lesions. In terms of patient survival, the median OS and PFS was 10.9 and 2.4 months, respectively. Univariate analysis of OS revealed that performance status (PS; P < .0001), number of metastatic organs (P = .019), C-reactive protein-to-albumin ratio (CAR; P < .0001), neutrophil-lymphocyte ratio (P = .001), and PMI (P = .024) were significant. Multivariate analysis further identified CAR [hazard ratio (HR) = 1.61, 95% confidence interval (CI) 1.15-2.25, P = .0053)] in addition to PS (HR = 1.65, 95% CI 1.23-2.22, P = .0008) as independent prognostic parameters., Conclusions: CAR and PS before nivolumab treatment are useful in predicting long-term survival in recurrent/unresectable advanced ESCC patients with second-line or later nivolumab treatment., Trial Registration: UMIN000040462., (© 2024. The Author(s).)

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., (© 2024. Society of Surgical Oncology.)

Background: The assessment of muscle mass loss, muscle strength, and physical function has been recommended in diagnosing sarcopenia. However, only muscle mass has been assessed in previous studies. Therefore, this study investigated the effect of comprehensively diagnosed preoperative sarcopenia on the prognosis of patients with esophageal cancer., Methods: The study analyzed 115 patients with esophageal cancer (age ≥ 65 years) who underwent curative esophagectomy. Preoperative sarcopenia was analyzed using the skeletal mass index (SMI), handgrip strength, and gait speed based on the Asian Working Group for Sarcopenia 2019 criteria. Clinicopathologic factors, incidence of postoperative complications, and overall survival (OS) were compared between the sarcopenia and non-sarcopenia groups. The significance of the three individual parameters also was evaluated., Results: The evaluation identified 47 (40.9%) patients with low SMI, 31 (27.0%) patients with low handgrip strength, and 6 (5.2%) patients with slow gait speed. Sarcopenia was diagnosed in 23 patients (20%) and associated with older age and advanced pT stage. The incidence of postoperative complications did not differ significantly between the two groups. Among the three parameters, only slow gait speed was associated with Clavien-Dindo grade 2 or greater complications. The sarcopenia group showed significantly worse OS than the non-sarcopenia group. Those with low handgrip strength tended to have worse OS, and those with slow gait speed had significantly worse OS than their counterparts., Conclusions: Preoperative sarcopenia diagnosed using skeletal muscle mass, muscle strength, and physical function may have an impact on the survival of patients with esophageal cancer., (© 2023. Society of Surgical Oncology.)

Introduction: There remains a lack of evidence regarding the optimal abdominal approach, including laparoscopy, hand-assisted, and open laparotomy for minimally invasive thoracoscopic esophagectomy. We aimed to compare the incidence of postoperative complications, particularly pulmonary complications, between laparoscopy and open laparotomy for minimally invasive thoracoscopic esophagectomy using nationwide Japanese databases., Methods: Data from patients in the National Clinical Database (NCD) who underwent thoracoscopic esophagectomy for esophageal cancer were analyzed. The incidence of pulmonary complications was compared between abdominal laparoscopy and laparotomy after matching the propensity scores (PS) from preoperative factors to account for confounding bias. Laparoscopic-assisted surgery (LAS) was also compared to hand-assisted laparoscopic surgery (HALS)., Results: Of the 24,790 patients who underwent esophagectomy between 2018 and 2021, data from 12,633 underwent thoracoscopic procedure. The proportion of patients who experienced pulmonary complications did not significantly differ between the laparoscopy group and the laparotomy group after matching (664/3195 patients, 20.8% versus 702/3195 patients, 22.0%; P = 0.25). No difference in the incidence of pulmonary complications was observed among patients treated using the laparoscopic approach (508/2439 patients, 20.8% in the LAS group versus 498/2439 patients, 20.4% in the HALS group; P = 0.72)., Conclusions: We observed no significant difference in the incidence of postoperative pulmonary complications between laparoscopy and laparotomy for thoracoscopic esophagectomy. Short-term outcomes were similar between the laparoscopic-assisted approach and the hand-assisted approach. This study provides valuable insights into the optimal abdominal approach for thoracoscopic esophagectomy using data from a nationwide database that reflect real-world clinical practice., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: The coronavirus disease 2019 (COVID-19) pandemic had adversely impacted cancer screening, diagnosis, and treatment. We investigated the change in medical resource, such as the intensive care unit use, and short-term outcomes after esophagectomy during the pandemic., Methods: Data of patients who underwent esophagectomy for esophageal cancer registered in the National Clinical Database (NCD) in Japan from January 2018 to December 2021 were analyzed. The time series change in the number of surgical cases; usage of intensive care unit; incidence of morbidity and mortality; standardized mortality and morbidity ratio (SMR) for 30-days mortality; surgical mortality; and morbidities for pneumonia, sepsis, unplanned intubation, and anastomotic leakage were evaluated., Results: The annual number of patients undergoing esophagectomy remained similar from 2018 to 2021. The negative impact of the pandemic on medical resources was strongly identified in the patients from an epidemic area where there is a higher cumulative number of infections per population as compared to all prefectures. The proportions of patients admitted to the intensive care unit were 91.4%, 93.0%, 91.6%, and 90.5% in 2018, 2019, 2020, and 2021, respectively. Moreover, 93.3%, 94.0%, 92.0%, and 90.9% patients who underwent surgery in an epidemic area were admitted to the intensive care unit in 2018, 2019, 2020, and 2021, respectively. However, the morbidity and mortality rates during the pandemic did not worsen according to the SMR values., Conclusions: Esophagectomy was performed during the pandemic despite limited medical resources by a systematic endeavor of the entire surgical department in Japan, without increasing the incidence rate of worse outcome., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

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., (© 2023. Society of Surgical Oncology.)

Background: Pretreatment metastatic lymph node (LN) size has been reported to be associated with prognosis in esophageal squamous cell carcinoma (ESCC). However, its relationship with response to preoperative chemotherapy or prognosis has not been clarified. We investigated the relationship between metastatic LN size and response to preoperative treatment, and prognosis in patients with metastatic esophageal cancer who underwent surgery., Patients and Methods: A total of 212 clinically node-positive patients who underwent preoperative chemotherapy followed by esophagectomy for ESCC were enrolled. Patients were stratified into three groups on the basis of the length of the short axis of the largest LN in pretreatment computed tomography images: < 10 mm (group A), 10-19 mm (group B), and ≥ 20 mm (group C)., Results: Group A had 90 patients (42%), group B had 103 patients (49%), and group C had 19 patients (9%). Group C had significantly lower percent reduction in total metastatic LN size than groups A and B (22.5% versus 35.7%, P = 0.037). Group C had significantly more metastatic LNs based on histological examination than groups A and B (10.1 versus 2.4, P < 0.001). Group C patients whose LNs responded had significantly fewer metastatic LNs than nonresponders (5.1 versus 11.9, P = 0.042). Group C had significantly poorer overall survival than groups A and B (3-year survival, 25.4% versus 67.3%, P < 0.001). However, group C patients whose LNs responded had better survival than nonresponders (3-year survival, 57.1% versus 0%, P = 0.008)., Conclusions: Patients with large metastatic LNs have poor response and poor prognosis. However, if a response is obtained, long-term survival can be expected., (© 2023. Society of Surgical Oncology.)

Background: The optimal extent of lymph-node (LN) dissection in esophageal cancer has not been established. Although the frequency and patterns of recurrence in each regional LN station after radical dissection are important in determining the regional LNs of thoracic esophageal cancer to be routinely dissected, this information has not been investigated sufficiently. We studied the significance of dissection at each LN station based on their recurrence patterns., Methods: Six hundred and twelve patients with esophageal cancer who underwent curative esophagectomy were studied. The incidence and pattern of recurrence (systemic or non-systemic) at each regional LN station were analyzed. To compare the significance of dissection among regional LNs, the efficacy index (EI) was also calculated., Results: Regional LN recurrence was diagnosed in 101 (16.5%) patients. Among the regional LNs, recurrent laryngeal nerve, paraesophageal, and perigastric LNs showed higher EIs (3.1-6.7). Pretracheal and posterior thoracic para-aortic LNs showed low EIs (0-0.2). Supraclavicular LNs had moderate EIs (1.7-2.0). The recurrence rate was highest in the pretracheal LN, followed by the supraclavicular LNs. The majority (81.8%) of the pretracheal LN had a systemic recurrence, while about half (right: 60.0%, left: 43.8%) of the supraclavicular LNs had a systemic recurrence., Conclusion: Due to the high incidence of systemic recurrence or low EI for pretracheal and posterior thoracic para-aortic LNs, we suggest that these LN stations be regarded as non-regional LNs and be excluded from routine dissection. Supraclavicular LNs may also be excluded from routinely dissected stations., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: Cervical esophageal cancer accounts for a small proportion of all esophageal cancers. Therefore, studies examining this cancer include a small patient cohort. Most patients with cervical esophageal cancer undergo reconstruction using a gastric tube or free jejunum after esophagectomy. We examined the current status of postoperative morbidity and mortality of cervical esophageal cancer based on big data., Methods: Based on the Japan National Clinical Database, 807 surgically treated patients with cervical esophageal cancer were enrolled between January 1, 2016, and December 31, 2019. Surgical outcomes were retrospectively reviewed for each reconstructed organ using gastric tubes and free jejunum., Results: The incidence of postoperative complications related to reconstructed organs was higher in the gastric tube reconstruction (17.9%) than in the free jejunum (6.7%) for anastomotic leakage (p < 0.01), but not significantly different for reconstructed organ necrosis (0.4% and 0.3%, respectively). The incidence rates of overall morbidity, pneumonia, 30-day reoperation, tracheal necrosis, and 30-day mortality using these reconstruction methods were 64.7% and 59.7%, 16.7% and 11.1%, 9.3% and 11.4%, 2.2% and 1.6%, and 1.2% and 0.0%, respectively. Only pneumonia was more common in the gastric tube reconstruction group (p = 0.03), but was not significantly different for any other complication., Conclusions: The incidence of overall morbidities and reoperation, especially anastomotic leakage after gastric tube reconstruction, suggested a necessity for further improvement. However, the incidence of fatal complications, such as tracheal necrosis or reconstructed organ necrosis, was low for both reconstruction methods, and the mortality rate was acceptable as a means of radical treatment., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: Accurate prognostic estimation is crucial; however, the prognostic value of tumor deposits in gastric cancer remains controversial. This study aimed to investigate their prognostic significance., Methods: Clinicopathological and prognostic data of 1012 gastric cancer patients who underwent R0 or R1 surgery from 2010 to 2017 at the Osaka International Cancer Institute were retrospectively reviewed., Results: Overall, 6.3% patients had tumor deposits, which were associated with Borrmann type, surgical procedure, type of gastrectomy, extent of lymphadenectomy, tumor size, histology, pT, pN, pM, pStage, lymphatic invasion, vascular invasion, preoperative chemotherapy, and postoperative chemotherapy. Tumor deposit-positive patients had worse 5-year disease-free survival (32.60% vs. 92.45%) and overall survival (41.22% vs. 89.37%) than tumor deposit-negative patients. Subgroup analysis regarding pStage II-III also showed significant differences between patients with and without tumor deposits for 5-year disease-free survival (34.15% vs. 80.98%) and overall survival (43.17% vs. 75.78%). Multivariable analysis showed that older age, undifferentiated histology, deeper tumor invasion, lymph node metastasis, distant metastasis, and presence of tumor deposits were significantly correlated with early tumor recurrence and shorter survival time; these factors were identified as independent prognostic factors. The 5-year disease-free survival of tumor deposit-positive patients was significantly worse than that of patients in the pStage III group and comparable to that of patients in the pT4, pN3, and pM1 groups. The 5-year overall survival of tumor deposit-positive patients was comparable to that of the pT4, pN3, pM1, and pStage III groups., Conclusions: Tumor deposits are strong and independent predictors of tumor recurrence and poor survival., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: Proficiency of the operating surgeon is one of the most critical factors potentially associated with reductions in complications and surgery-related mortality. With video-rating systems having shown potential for assessing laparoscopic surgeons' proficiency, the Endoscopic Surgical Skill Qualification System (ESSQS) was developed by the Japan Society for Endoscopic Surgery to subjectively assess the proficiency of laparoscopic surgeons by rating applicants' non-edited case videos. We conducted a study to evaluate how ESSQS skill-qualified (SQ) surgeon involvement influences short-term outcomes of laparoscopic gastrectomy performed for gastric cancer., Methods: Data from the National Clinical Database regarding laparoscopic distal and total gastrectomy performed for gastric cancer between January 2016 and December 2018 were analyzed. Operative mortality, defined as 30-day mortality or 90-day in-hospital mortality, and anastomotic leakage rates were compared per involvement vs. non-involvement of an SQ surgeon. Outcomes were also compared per involvement of a gastrectomy-, colectomy-, or cholecystectomy-qualified surgeon. The association between the area of qualification and operative mortality/anastomotic leakage was also analyzed with a generalized estimating equation logistic regression model used to account for patient-level risk factors and institutional differences., Results: Of 104,093 laparoscopic distal gastrectomies, 52,143 were suitable for inclusion in the study; 30,366 (58.2%) were performed by an SQ surgeon. Of 43,978 laparoscopic total gastrectomies, 10,326 were suitable for inclusion; 6501 (63.0%) were performed by an SQ surgeon. Gastrectomy-qualified surgeons outperformed non-SQ surgeons in terms of both operative mortality and anastomotic leakage. They also outperformed cholecystectomy- and colectomy-qualified surgeons in terms of operative mortality or anastomotic leakage in distal and total gastrectomy, respectively., Conclusion: The ESSQS appears to discriminate laparoscopic surgeons who can be expected to achieve significantly improved gastrectomy outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The use of minimally invasive esophagectomy (MIE) as a treatment for patients with esophageal cancer has recently become more common worldwide. However, differences in the pattern of recurrence between MIE and open esophagectomy (OE) using the transthoracic approach have not been fully investigated, particularly in patients treated with neoadjuvant chemotherapy., Methods: We searched the prospective databases of two institutes for patients with esophageal cancer who underwent neoadjuvant chemotherapy followed by esophagectomy between 2011 and 2018. Propensity score-matched analysis was performed to reduce bias from confounding patient-related variables. Operative outcomes, regionally harvested lymph nodes (LNs), recurrence pattern, and prognosis were investigated in two groups., Results: We identified 410 patients who underwent OE (n = 263) and MIE (n = 147). After propensity score matching, 131 pairs of patients were selected. There were no significant differences in baseline characteristics after matching. The total number of harvested LNs in both groups was similar (55.1 vs. 58.9, P = 0.132). The incidence of LN recurrence in the MIE group was significantly lower than that in the OE group (27% vs. 15%, P = 0.010). In particular, the incidence of mediastinal LN recurrence in the MIE group was significantly lower than that in the OE group (16% vs. 6%, P = 0.017). There were no significant differences between the two groups in hematogenous (19% vs.12%, P = 0.173), dissemination (5% vs. 4%, P = 0.769), local (4% vs. 1%. P = 0.213), and other recurrence (3% vs. 3%, P = 1.000). The 3-year disease-free and overall survival of MIE were significantly better than OE (71.4% vs. 50.5%, P = 0.004 and 80.3% vs. 61.2%, P = 0.002, respectively). Multivariate analysis showed that the thoracic approach (OE vs. MIE) (HR 1.93, P = 0.004) was an independent prognostic factor, along with the pathological N stage (HR 3.05, P < 0.001)., Conclusions: MIE has less intramediastinal LN recurrence than OE and may lead to a better long-term prognosis in patients with advanced esophageal cancer who underwent neoadjuvant chemotherapy., (© 2023. The Society for Surgery of the Alimentary Tract.)

Purpose: To investigate the clinical practices of diagnosing multicystic cervical lesions as a means to develop a more appropriate diagnostic algorithm for gastric-type adenocarcinoma (GAS) and its precursors., Methods: Clinical information for 159 surgically treated patients for multicystic disease of the uterine cervix was collected from 15 hospitals. We performed a central review of the MRI and pathological findings. The MRI findings were categorized into four types including two newly proposed imaging features based on the morphology and distribution of cysts, and the diagnosis accuracy was assessed. Among the four MRI types, types 1 and 2 were categorized as benign lesions that included LEGH; type 3 were precancerous lesions (with an assumption of atypical LEGH); and type 4 were malignant lesions., Results: The central pathological review identified 56 cases of LEGH, seven with GAS, four with another form of carcinoma, and 92 with benign disease. In clinical practice, over-diagnosis of malignancy (suspicion of MDA) occurred for 12/19 cases (63.2%) and under-diagnosis of malignancy occurred for 4/11 (36%). Among the 118 patients who had a preoperative MRI and underwent a hysterectomy, type 3 or 4 MRI findings in conjunction with abnormal cytology were positively indicative of premalignancy or malignancy, with a sensitivity and specificity of 61.1% and 96.7%, respectively., Conclusions: Although the correct preoperative diagnosis of cervical cancer with a multicystic lesion is challenging, the combination of cytology and MRI findings creates a more appropriate diagnostic algorithm that significantly improves the diagnostic accuracy for differentiating benign disease from premalignancy and malignancy., (© 2023. The Author(s).)

Uric acid, the end product of purine metabolism in humans, is crucial because of its anti-oxidant activity and a causal relationship with hyperuricemia and gout. Several physiologically important urate transporters regulate this water-soluble metabolite in the human body; however, the existence of latent transporters has been suggested in the literature. We focused on the Escherichia coli urate transporter YgfU, a nucleobase-ascorbate transporter (NAT) family member, to address this issue. Only SLC23A proteins are members of the NAT family in humans. Based on the amino acid sequence similarity to YgfU, we hypothesized that SLC23A1, also known as sodium-dependent vitamin C transporter 1 (SVCT1), might be a urate transporter. First, we identified human SVCT1 and mouse Svct1 as sodium-dependent low-affinity/high-capacity urate transporters using mammalian cell-based transport assays. Next, using the CRISPR-Cas9 system followed by the crossing of mice, we generated Svct1 knockout mice lacking both urate transporter 1 and uricase. In the hyperuricemic mice model, serum urate levels were lower than controls, suggesting that Svct1 disruption could reduce serum urate. Given that Svct1 physiologically functions as a renal vitamin C re-absorber, it could also be involved in urate re-uptake from urine, though additional studies are required to obtain deeper insights into the underlying mechanisms. Our findings regarding the dual-substrate specificity of SVCT1 expand the understanding of urate handling systems and functional evolutionary changes in NAT family proteins., (© 2023. The Author(s).)

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., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: The registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes of patients who underwent any treatment during 2015 in Japan., Methods: We analyzed patients' data who had visited the participating hospitals in 2015. We collected the data using the National Clinical Database with a web-based data collection system. We used the Japanese Classification of Esophageal Cancer 10 th edition by JES and the TNM classification by the Union of International Cancer Control (UICC) for cancer staging., Results: A total of 9368 cases were registered from 355 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 86.7% and 7.4%, respectively. The 5-year survival rates of patients treated by endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.2%, 33.5%, 24.2%, and 59.9%, respectively. Esophagectomy was performed in 5172 cases. Minimally invasive approaches were selected for 60.6%, and 54.4% underwent thoracoscopic esophagectomy. The operative mortality (within 30 days after surgery) was 0.79% and the hospital mortality was 2.3%. The survival curves showed an excellent discriminatory ability both in the clinical and pathologic stages by the JES system. The survival of pStage IV was better than IIIC in the UICC system because pStage IV included the patients with supraclavicular lymph node metastasis (M1 LYM)., Conclusion: We hope this report improves all aspects of diagnosing and treating esophageal cancer in Japan., (© 2022. The Author(s).)

Background: With the aging of society and increasingly longer of life expectancy, elderly patients with esophageal cancer are more commonly encountered. This study aimed to identify the risk factors for operative mortality after esophagectomy in elderly patients., Methods: We used data from the National Clinical Database of Japan. After cleaning the data, 10,633 records obtained from 861 hospitals were analyzed. A risk model for operative mortality was developed using risk factors from the entire study population. Then, odds ratios (OR) were compared between age categories using this risk model., Results: In this study, 1959 (18.4%) patients were ≥ 75 years (defined as "elderly" in this study). Eighteen variables, including T4b, N2-N3, and M1 in the TNM classification, were included in the risk model for operative mortality. The ORs increased in age categories < 65, 65-74, and ≥ 75 years for N2-N3 (1.172, 1.200, and 1.588, respectively), and M1 (2.189, 3.164, and 4.430, respectively). Based on these results, we also focused on residual tumors, which are caused by extensive tumor development. The operative mortality in the elderly group with residual tumors increased to more than twice than that in the non-elderly groups (15.9 vs. 5.5 or 6.5%) and was much higher than that in elderly patients without residual tumors (15.9 vs. 4.6%)., Conclusion: We should carefully select the treatment for elderly patients with highly advanced tumors, which result in N2-N3 and M1, to avoid unfavorable short-term outcomes. In addition, R0 resection is important in preventing operative mortality among elderly patients., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: One upside of cervical esophageal carcinoma is that radical surgery can be performed by laryngectomy, even for tumors with tracheal invasion. However, this approach drastically reduces the quality of life, such as by losing the vocal function. Cervical esophageal carcinoma is rare, and no comprehensive reports have described the current state of surgery. Using a Japanese nationwide web-based database, we analyzed the surgical outcomes of cervical esophageal carcinoma to evaluate the impact of larynx-preserving surgery., Methods: Based on the Japan National Clinical Database, 215 surgically treated cases of cervical esophageal carcinoma between January 1, 2018, and December 31, 2019, were enrolled. Clinical outcomes were compared between the larynx-preserved group and the laryngectomy group., Results: Ninety-four (43.7%) patients underwent larynx-preserving surgery. A total of 177 (82.3%) patients underwent free jejunum reconstruction. More T4b patients and more patients who underwent preoperative radiotherapy were in the laryngectomy group. There were no significant differences in the frequency and the severity of morbidities between the two groups. However, in the laryngectomy group, in-hospital death within 30 days after surgery was observed in 1 patient, and the postoperative hospital stay was significantly longer (P = 0.030). In the larynx-preserved group, recurrent nerve paralysis was observed in 24.5%. Re-operation (35.3%, P = 0.016), re-intubation (17.6%, P = 0.019) and tracheal necrosis (17.6%, P = 0.028) were significantly more frequent in patients who underwent pharyngolaryngectomy with total esophagectomy and gastric tube reconstruction than in others., Conclusion: Larynx-preserving surgery was therefore considered to be feasible because it was equivalent to laryngectomy regarding the short-term surgical outcomes., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: Laparoscopic total gastrectomy for early proximal gastric cancer is widely performed. Recently, the number of laparoscopic proximal gastrectomies performed, a surgery limited to early proximal gastric cancer, has gradually increased. However, evidence for the long-term outcomes of laparoscopic total gastrectomy and laparoscopic proximal gastrectomy is insufficient. Therefore, this study aimed to clarify and compare the long-term outcomes of laparoscopic total gastrectomy and laparoscopic proximal gastrectomy with novel valvuloplastic esophagogastrostomy for treatment of clinical stage I proximal gastric cancer., Methods: This study included 111 patients who underwent laparoscopic total gastrectomy or laparoscopic proximal gastrectomy for the treatment of upper third clinical stage I gastric cancer between April 2004 and December 2017. After adjusting for propensity score matching analysis, we compared the postoperative complications, nutritional status, and long-term outcomes between the two groups., Results: After matching the inclusion criteria, 56 patients (28 in each group) were enrolled. No significant differences were noted in the postoperative complications between the two groups. While laparoscopic proximal gastrectomy was associated with lower albumin levels, lower body weight loss was seen by 1 year after surgery and higher hemoglobin levels by 1, 2, and 3 years after surgery. No significant differences were observed in the 3-year overall survival and 3-year recurrence-free survival between the laparoscopic total gastrectomy and laparoscopic proximal gastrectomy groups (P = 0.74 and 0.72, respectively)., Conclusion: Laparoscopic proximal gastrectomy and laparoscopic total gastrectomy for patients with upper third clinical stage I gastric cancer are feasible as regards its safety and outcomes., (© 2022. The Society for Surgery of the Alimentary Tract.)

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., (© 2022. Society of Surgical Oncology.)

Background: In laparoscopic total gastrectomy, esophago-jejunal anastomosis is still considered a complicated procedure, even though laparoscopic surgery has become widespread. Esophagojejunostomy leakage can be fatal and adversely affect postoperative cancer treatment. The leakage rate has been reported to be 2.4-5.5%, and a safer and more reliable technique needs to be established. In this multi-media article, we describe the technique of laparoscopic esophagojejunostomy using a simple and safe T-shaped esophagojejunostomy., Methods: We performed laparoscopic total gastrectomy with ante-colic Roux-en-Y reconstruction using a T-shaped anastomosis. First, insertion holes are made on the right side of the esophageal stump and the opposite side of the mesentery of the lift-up jejunal stump. Second, a linear stapler is inserted into each insertion hole, and a 40-45-mm V-shaped esophageal jejunal anastomosis is performed. Third, three temporary sutures are added for closing the common edge. Finally, a second stapling is used to close the entry hole and resect the esophageal stump., Results: We performed this procedure in 35 patients between May 2016 and December 2018. The median duration of surgery was 338 min (range, 248-542 min) and median bleeding was 20 mL (range, 0-240 mL). There were no esophagojejunostomy-related complications higher than Clavien-Dindo grade II. Additionally, no postoperative stenosis occurred during the follow-up period (median: 48 months, range: 4-68 months)., Conclusion: Considering the present results, T-shaped esophago-jejunal anastomosis is a simple and safe procedure and a promising laparoscopic total gastrectomy option., (© 2022. The Society for Surgery of the Alimentary Tract.)

Objective: The Endoscopic Surgical Skill Qualification System (ESSQS) was developed by the Japan Society for Endoscopic Surgery as a means of subjectively assessing the proficiency of laparoscopic surgeons. We conducted a study to evaluate how involvement of an ESSQS skill-qualified (SQ) surgeon influences short-term outcomes of laparoscopic cholecystectomy performed for acute cholecystitis. Previous reports suggest that assessment of the video-rating system is a potential tool to discriminate laparoscopic surgeons' proficiency and top-rated surgeons face less surgical mortality and morbidity in bariatric surgery., Methods: Data from the National Clinical Database regarding laparoscopic cholecystectomy performed for acute cholecystitis between January 2016 and December 2018 were analyzed. Outcomes were compared between patients grouped according to involvement vs. non-involvement of an SQ surgeon. Outcomes were also compared between patients grouped according to whether their operation was performed by biliary tract-, stomach-, or colon-qualified surgeon., Results: Of the 309,998 laparoscopic cholecystectomies during the study period, 65,295 were suitable for inclusion in the study and 13,670 (20.9%) were performed by an SQ surgeon. Patients' clinical characteristics did not differ between groups. Thirty-day mortality was significantly lower in the SQ group (0.1%) 16/13,670 than in the non-SQ group (0.2%) 140/51,625 (P = 0.001). Thirty-day mortality was [0.1% (9/7173)] in the biliary tract-qualified group, [0.2% (5/3527)] in the stomach-qualified group, and [0.1% (2/3240)] in the colon-qualified group., Conclusion: Surgeons with ESSQS certification outperform the non-skilled surgeons in terms of surgical mortality in 30 and 90 days. Further verification of the value of the ESSQS is warranted and similar systems may be needed in countries across the world to ensure patient safety and control the quality of surgical treatments., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The benefits of robotic gastrectomy (RG) over laparoscopic gastrectomy (LG) remain controversial. This single-center, propensity score-matched study aimed to compare the outcomes of RG with those of LG for treating gastric cancer., Methods: We searched the prospective gastric cancer database of our institute for patients with gastric cancer who underwent RG or LG between January 2014 and December 2019, excluding patients with remnant stomach cancer and those who underwent concurrent surgery for comorbid malignancies. One-to-one propensity score matching was performed to reduce bias from confounding patient-related variables, and short- and long-term outcomes were compared between the groups., Results: We identified 1189 patients who underwent LG (n = 979) or RG (n = 210). After propensity score matching, we selected 210 pairs of patients who underwent LG (distal gastrectomy, 138; total or proximal gastrectomy, 72) or RG (distal gastrectomy, 143; total or proximal gastrectomy, 67). RG was associated with a significantly shorter operative time (RG = 201 min vs. LG = 231 min, p = 0.0051), less blood loss (RG = 13 mL vs. LG = 42 mL, p < 0.0001), lower postoperative morbidity (RG = 1.0% vs. LG = 4.8%, p = 0.0066), and a shorter postoperative hospital stay (p = 0.0002) than LG. Drain amylase levels on postoperative Days 1 and 3 in the RG group were significantly lower than those in the LG group (p < 0.0001)., Conclusions: RG is a safe and feasible treatment for gastric cancer, with a shorter operative time, less blood loss, and lower postoperative morbidity than LG. The application of robotics in minimally invasive gastric cancer surgery may offer an alternative to conventional surgery. Multicenter, prospective, randomized controlled trials comparing RG with conventional LG are needed to establish the feasibility and efficacy of minimally invasive gastric cancer surgery., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2022. Society of Surgical Oncology.)

Background: Transcription-reverse transcription concerted reaction (TRC) is recognized as a useful method for detecting free cancer cells in the peritoneal cavity and predicting peritoneal recurrence in patients with gastric cancer. Nonetheless, the clinical significance of TRC in laparoscopic surgery remains unclear. This study aimed to evaluate the clinical importance of carcinoembryonic antigen (CEA) messenger RNA (mRNA) level in peritoneal lavage fluids measured by TRC in laparoscopic surgery for locally advanced gastric cancer., Methods: We enrolled patients with locally advanced gastric cancer who underwent laparoscopic gastrectomy. Peritoneal lavage fluids were collected prior to gastrectomy, and the TRC method was employed to quantify CEA mRNA in peritoneal washes. Overall survival (OS), recurrence-free survival (RFS), and peritoneal recurrence-free survival (PRFS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Adjusted Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) for CEA mRNA positivity., Results: A total of 100 patients were analyzed in this study. Overall, 22 patients (22%) exhibited CEA mRNA positivity in peritoneal lavage fluids, as measured by TRC. No significant association between CEA mRNA levels and clinicopathological characteristics was observed. Patients who were CEA mRNA-positive in peritoneal lavage fluids had significantly worse OS, RFS, and PRFS than those who were CEA mRNA-negative (p = 0.0059, p < 0.0001, and p = 0.0022, respectively). In the univariate Cox model, the HR for all-cause mortality in CEA mRNA-positive versus CEA mRNA-negative patients was 3.60 (95% CI, 1.33-9.55; p = 0.0129). Multivariate analysis revealed that CEA mRNA positivity was a significant independent factor for recurrence., Conclusions: TRC enables the detection of free cancer cells in the peritoneal cavity and CEA mRNA levels can help predict the prognosis, even in laparoscopic gastrectomy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes annually., Methods: We analyzed the data of patients who had visited the participating hospitals in 2014. We collected the data with a web-based data collection system using the National Clinical Database. We used the Japanese Classification of Esophageal Cancer 10th edition by JES and the TNM classification 7th edition by the Union of International Cancer Control (UICC) for cancer staging., Results: A total of 9026 cases were registered from 344 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.9% and 7.1%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.1%, 33.7%, 25.3%, and 59.3%, respectively. Esophagectomy was performed in 5204 cases. Concerning the approach used for esophagectomy, 48.1% of the cases were treated thoracoscopically. The operative mortality (within 30 days after surgery) was 0.75%, and the hospital mortality was 2.0%. The survival curves showed an excellent discriminatory ability both in the clinical and pathologic stages by the JES system. The survival of pStage IV was better than IIIC in the UICC system, because pStage IV included the patients with supraclavicular lymph-node metastasis (M1 LYM)., Conclusion: We hope that this report contributes to improving all aspects of diagnosing and treating esophageal cancer in Japan., (© 2021. The Author(s).)

Background: Endoscopic treatment is one of the options for superficial esophageal cancer, but additional therapy such as esophagectomy or chemoradiotherapy (CRT) is sometimes needed due to noncurative resection. However, the outcome of additional therapy after endoscopic treatment has not been fully evaluated., Methods: In 160 patients with superficial esophageal cancer, including 37 patients who underwent esophagectomy and 123 patients who underwent CRT after noncurative endoscopic resection, outcomes were investigated., Results: The CRT group included more elderly patients than the surgery group, although there were no significant differences in tumor depth or lymphovascular invasion between the two groups. Overall survival was significantly better in the surgery group than in the CRT group (5-year overall survival: 94.3% vs. 79.9%; p = 0.039). Two (5.4%) patients in the surgery group who developed lymph node recurrence achieved complete response by chemotherapy or CRT, and 9 of 16 patients (13.0%) in the CRT group who developed recurrence underwent salvage esophagectomy or lymphadenectomy. As a result, the 5-year cause-specific survival was 100% in the surgery group and 92.8% in the CRT group. SM2 invasion (≥ SM2) was significantly associated with recurrence after CRT, while lymphatic invasion was associated with lymph node metastasis in the surgery group., Conclusion: Endoscopic treatment combined with esophagectomy or CRT can be a curative treatment option in patients with superficial esophageal cancer. However, esophagectomy rather than CRT should be recommended for patients with massive submucosal tumor invasion due to the risk of recurrence after CRT., (© 2021. Society of Surgical Oncology.)

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/m 2 intravenous docetaxel and 70 mg/m 2 intravenous cisplatin on day 1, and a continuous 700 mg/m 2 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)., (© 2021. The Japan Esophageal Society.)

In the COVID-19 era, movement restrictions are crucial to slow virus transmission and have been implemented in most parts of the world, including Japan. To find new insights on human mobility and movement restrictions encouraged (but not forced) by the emergency declaration in Japan, we analyzed mobility data at 35 major stations and downtown areas in Japan-each defined as an area overlaid by several 125-meter grids-from September 1, 2019 to March 19, 2021. Data on the total number of unique individuals per hour passing through each area were obtained from Yahoo Japan Corporation (i.e., more than 13,500 data points for each area). We examined the temporal trend in the ratio of the rolling seven-day daily average of the total population to a baseline on January 16, 2020, by ten-year age groups in five time frames. We demonstrated that the degree and trend of mobility decline after the declaration of a state of emergency varies across age groups and even at the subregional level. We demonstrated that monitoring dynamic geographic and temporal mobility information stratified by detailed population characteristics can help guide not only exit strategies from an ongoing emergency declaration, but also initial response strategies before the next possible resurgence. Combining such detailed data with data on vaccination coverage and COVID-19 incidence (including the status of the health care delivery system) can help governments and local authorities develop community-specific mobility restriction policies. This could include strengthening incentives to stay home and raising awareness of cognitive errors that weaken people's resolve to refrain from nonessential movement., (© 2021. The Author(s).)

Objective: This prospective randomized trial compared the invasiveness of laparoscopic gastrectomy using a single-port approach with that of a conventional multi-port approach in the treatment of gastric cancer. The benefit of single-port laparoscopic gastrectomy (SLG) over multi-port laparoscopic gastrectomy (MLG) has yet to be confirmed in a well-designed study., Methods: One hundred and one patients who were scheduled to undergo laparoscopic distal gastrectomy for histologically confirmed clinical stage I gastric cancer between April 2016 and September 2018 were randomly allocated to SLG (n = 50) or MLG (n = 51). The primary endpoints were the postoperative visual analog scale pain scores. Secondary endpoints were frequency of use of analgesia, short-term outcomes, such as operating time, intraoperative blood loss, inflammatory reactions, postoperative morbidity, and 90-day mortality., Results: The postoperative pain score was significantly lower in the SLG group than in the MLG group (p < 0.001) on the operative day and the postoperative day 1-7. Analgesics were administered significantly less often in the SLG group than in the MLG group (1 vs. 3 days, p = 0.0078) and the duration of use of analgesics was significantly shorter in the SLG group (2 vs. 3 days, p = 0.0171). The operating time was significantly shorter in the SLG group than in the MLG group (169 vs. 182 min, p = 0.0399). Other surgical outcomes were comparable between the study groups., Conclusions: SLG was shown to be safe and feasible in the treatment of gastric cancer with better short-term results in terms of less severe pain and may be suitable for treatment of cStage I gastric cancer., Clinical Trial Registration: UMIN000022218.

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: Because cancers of hollow organs such as the esophagus are hard to detect even by the expert physician, it is important to establish diagnostic systems to support physicians and increase the accuracy of diagnosis. In recent years, deep learning-based artificial intelligence (AI) technology has been employed for medical image recognition. However, no optimal CT diagnostic system employing deep learning technology has been attempted and established for esophageal cancer so far., Purpose: To establish an AI-based diagnostic system for esophageal cancer from CT images., Materials and Methods: In this single-center, retrospective cohort study, 457 patients with primary esophageal cancer referred to our division between 2005 and 2018 were enrolled. We fine-tuned VGG16, an image recognition model of deep learning convolutional neural network (CNN), for the detection of esophageal cancer. We evaluated the diagnostic accuracy of the CNN using a test data set including 46 cancerous CT images and 100 non-cancerous images and compared it to that of two radiologists., Results: Pre-treatment esophageal cancer stages of the patients included in the test data set were clinical T1 (12 patients), clinical T2 (9 patients), clinical T3 (20 patients), and clinical T4 (5 patients). The CNN-based system showed a diagnostic accuracy of 84.2%, F value of 0.742, sensitivity of 71.7%, and specificity of 90.0%., Conclusions: Our AI-based diagnostic system succeeded in detecting esophageal cancer with high accuracy. More training with vast datasets collected from multiples centers would lead to even higher diagnostic accuracy and aid better decision making.

Background: Postoperative atrial fibrillation (POAF) after esophagectomy for esophageal cancer is not uncommon. The aim of this study is to examine whether preoperative transthoracic echocardiography is useful for predicting new-onset POAF in esophageal cancer., Methods: In this prospective observational study, we evaluated 200 patients with esophageal cancer who underwent esophagectomy at our hospital between January 2016 and July 2019. Conventional echocardiographic assessment and tissue Doppler imaging were performed before surgery. We investigated the utility of preoperative transthoracic echocardiography for predicting new-onset POAF in esophageal cancer., Results: New-onset POAF occurred in 51 (25.5%) of 200 patients. POAF was significantly associated with older age (p = 0.007), higher body mass index (p = 0.020), preoperative hypertensive disease (p = 0.021), and lower hemoglobin level (p = 0.028). The incidence of postoperative complications was significantly higher in patients with POAF than in patients without POAF (43.1% vs. 24.2%, p = 0.013). Transthoracic echocardiography showed that left atrial diameter (LAD) and E wave/e' wave ratio (E/e') were significantly higher in patients with POAF than in patients without POAF (34.1 vs. 31.3 mm, p < 0.001 and 11.6 vs. 10.5, p = 0.003, respectively). Multivariate analysis showed that LAD ≥ 36.0 mm, E/e' ≥ 8.4 are independent risk factors for POAF (odds ratios 2.47 and 3.64; p values 0.035 and 0.027, respectively) CONCLUSIONS: Preoperative echocardiographic evaluation is useful for predicting the onset of POAF after esophagectomy for esophageal cancer. Risk stratification using LAD and E/e' enables clinicians to identify patients at high risk for POAF before esophagectomy.

Purpose: Our aim was to compare postoperative outcomes of laparoscopic and open appendectomies for acute appendicitis in children under the circumstance of widespread use of laparoscopic surgery., Method: This study included data on laparoscopic and open appendectomies in children with acute appendicitis from the National Clinical Database, which is a Japanese nationwide surgical database, in 2015. The occurrence rates of complications within 30 days after the surgery and postoperative hospital stay were compared by univariate and multivariate analyses. p < 0.05 was considered statistically significant., Results: This study included 4489 appendectomies, of which 3166 surgeries (70.5%) were performed laparoscopically. Appendectomy was performed for complicated and uncomplicated appendicitis in 1765 (39.3%) and 2724 cases (60.7%), respectively. Postoperative complications within 30 days were observed in 246 operations (5.5%). Organ-space surgical site infection (SSI), deep wound SSIs, and superficial wound SSIs were observed in 2.3%, 1.0%, and 2.4% of operations, respectively. On multivariate analysis, the incidence of postoperative complications (odds ratio 1.21, 95% CI 0.90-1.64, p = 0.207) and the length of hospital stay (median 4 days in both groups, p = 0.835) were not significantly different between patients who underwent laparoscopic or open appendectomy. Subgroup analysis in complicated and uncomplicated appendicitis cases also demonstrated no significant differences in the incidence of postoperative complications between those who underwent laparoscopic or open appendectomy., Conclusion: This study suggested that the occurrence of postoperative complication and the length of hospital stay in pediatric patients who underwent laparoscopic appendectomy are similar with those in pediatric patients who underwent open appendectomy for acute appendicitis.

Background: Preoperative weight loss in esophageal cancer is reported to be associated with a poor prognosis. However, the impact of postoperative weight loss on the prognosis of patients with esophageal cancer remains unclear., Methods: This study included 186 patients with esophageal squamous cell carcinoma who underwent surgery between January 2012 and January 2015. The relationship between weight loss 6 months after esophagectomy as well as the clinical factors and prognosis of patients was investigated., Results: The mean weight loss rate for all the patients was 9.3% at 3 months, 10.8% at 6 months, 11.1% at 12 months, and 11.4% at 24 months after surgery. The patients with severe weight loss 6 months after surgery (≥ 12%) exhibited lower serum albumin levels and a lower prognostic nutrition index 6 months after esophagectomy than the patients with moderate weight loss (< 12%; p = 0.011 and 0.009, respectively). Although overall survival did not differ significantly between the two groups, for all the patients, severe weight loss was significantly associated with shortened overall survival for the cStages 3 and 4 patients (3-year overall survival rate, 76.6% in the moderate group vs 54.5% in the severe group; p = 0.042). The multivariate analyses identified only severe weight loss as an independent factor associated with worse overall survival for the cStages 3 and 4 patients (p = 0.034)., Conclusion: This study showed that postoperative weight loss negatively affected the prognosis for patients with advanced esophageal cancer, indicating the necessity of administering nutritional interventions to these patients to prevent postoperative weight loss.

Background: Esophageal cancer is the eighth most common cause of cancer mortality in Japan. More than 11,000 people had died from esophageal cancer in 2018. The Japan Esophageal Society has collected the data on patients' characteristics, performed treatment, and outcomes annually., Methods: We analyzed the data of patients who had first visited the participating hospitals in 2013. In 2019, the data collection method was changed from an electronic submission to a web-based data collection using the National Clinical Database (NCD). Japanese Classification of Esophageal Cancer 10th by the Japan Esophageal Society (JES) and UICC TNM Classification 7th were used for cancer staging RESULTS: A total of 8019 cases were registered from 334 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.8% and 6.3%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, or esophagectomy were 88.3%, 32.4%, 24.4%, and 59.3%, respectively. Esophagectomy was performed in 4910 cases. The operative and the hospital mortality rates were 0.77% and 1.98%, respectively. The survival curves showed a good discriminatory ability both in the clinical and pathologic stages by the JES system. The 5-year survival rate of patients with pStage IV in the UICC classification that included patients with supraclavicular node metastasis was better than that of patients with pStage IVb in JES classification., Conclusion: We hope this report contributes to improving all aspects of the diagnosis and treatment of esophageal cancer in Japan.

We developed a novel technique for valvuloplastic esophagogastrostomy, named tri double-flap hybrid method (TDF). TDF is shown to be simple and useful for Siewert type II esophagogastric junction carcinoma., Background: Research has found valvuloplastic esophagogastrostomy using the conventional hand-sutured double-flap (CDF) technique to be a useful anti-reflux procedure after proximal gastrectomy. However, no study has focused on this reconstruction procedure after laparoscopic transhiatal lower esophagectomy and proximal gastrectomy (LEPG) for esophagogastric junction carcinoma primarily because of its profound difficulty. Thus, we devised a novel technique for valvuloplastic esophagogastrostomy comprising triangular linear-stapled esophagogastrostomy and hand-sutured flap closure, which we term the tri double-flap hybrid (TDF) method., Methods: After reviewing our institution's prospective gastric cancer database, 59 consecutive patients with Siewert type II esophagogastric junction carcinoma who underwent LEPG with valvuloplastic esophagogastrostomy from January 2014 to August 2018 were analyzed. Short- and mid-term surgical outcomes were then compared between the LEPG-TDF and LEPG-CDF groups to evaluate the efficacy of the TDF method., Results: The median operative time was 316 min (184-613 min) and blood loss was 22.5 ml (0-180 ml). In comparison between the two groups, the LEPG-TDF group had a significantly shorter operative time (298 vs. 336 min, p = 0.041) and significantly lower postoperative anastomotic leak/stenosis rates (0 vs. 14.2%, p = 0.045), compared to the LEPG-CDF group. No patient suffered from severe gastroesophageal reflux symptoms (Visick score ≥ III)., Conclusions: This study showed that double-flap valvuloplastic esophagogastrostomy is safe and feasible for reconstruction after LEPG for Siewert type II esophagogastric junction carcinoma. Moreover, the TDF method is a simple and useful technique that offers a shorter operative time and lower morbidity compared to the CDF technique.

Background: Patients with diabetes mellitus and severe proteinuria present with poor renal prognoses, despite improvements in diabetes and kidney disease therapies. In this study, we designed a low-density lipoprotein (LDL)-cholesterol apheresis treatment for patients with diabetic nephropathy (DN)/diabetic kidney disease and severe proteinuria. This was a multicenter prospective LICENSE study to confirm the impact of LDL apheresis on proteinuria that exhibited hyporesponsiveness to treatment. In addition, we sought to determine the efficacy and safety of LDL apheresis by comparing the outcomes to those of historical controls in patients with diabetes, refractory hypercholesterolemia, and severe proteinuria., Methods: This was a prospective, multicenter study, including 40 patients with diabetes, severe proteinuria, and dyslipidemia. LDL apheresis was performed 6-12 times over a 12-week period. The primary endpoint was the proportion of patients with a decrease in proteinuria excretion of at least 30% in the 6 months after starting therapy. The secondary endpoints included serum creatinine levels and laboratory variables, which were evaluated 4, 6, 12, 18, and 24 months after therapy initiation., Results: LDL apheresis was performed on 40 registered patients with diabetes. The proportion of cases in which proteinuria decreased by 30% or more after 6 months of LDL apheresis was 25%, which was similar to that of historical controls. The overall survival and end-stage kidney disease-free survival rates were significantly higher in the LICENSE group compared to those in historical controls., Conclusion: Our results suggest that LDL apheresis may be effective and safe for patients with diabetes, proteinuria, and dyslipidemia., Trial Registration: Trial registration number: jRCTs042180076.

Background: Esophageal cancer patients sometimes have a history of previous gastrectomy. To determine whether we should resect or preserve the remnant stomach, we need to understand the frequency and sites of abdominal lymph node (LN) metastasis from esophageal cancer after gastrectomy., Patients and Methods: In 46 patients with thoracic esophageal squamous cell carcinoma (ESCC) who had a history of previous gastrectomy due to gastric cancer (n = 20) or benign disease (n = 26), the frequency and sites of any LN metastasis including LN metastasis at surgery and LN recurrence were investigated. The factors associated with abdominal LN metastasis were also examined., Results: The incidence of metastasis to cervical, mediastinal, and abdominal LNs at surgery was 10.8%, 30.4%, and 30.4%, respectively. The incidence of abdominal LN recurrence was 6.5%. Of 46 patients, 16 patients (34.8%) had any abdominal LN metastasis, including abdominal LN metastasis at surgery or abdominal LN recurrence. There was no significant difference in the incidence of any abdominal LN metastasis between the gastric cancer group and the benign disease group (25.0% vs. 42.3%, p = 0.222). Clinically, nodal status was identified as the only independent factor associated with the occurrence of any abdominal LN metastasis, although neither tumor location nor the reason for gastrectomy was., Conclusions: The present study showed that the incidence of abdominal LN metastasis from ESCC after gastrectomy was not necessarily low, regardless of the tumor location and the reason for previous gastrectomy. This result suggests that gastrectomy should not be omitted easily in ESCC patients after previous gastrectomy.

Background: The delta-shaped anastomotic technique (Delta-SA) has been accepted as a standard reconstruction method in totally laparoscopic distal gastrectomy with Billroth I reconstruction (TLDG B-I). However, some anastomosis-related surgical complications have been reported. We evaluated the safety and feasibility of modified Delta-SA, called intracorporeal triangular anastomotic technique (INTACT), in this study., Methods: From January 2010 to May 2018, we identified patients who underwent TLDG B-I with INTACT (n = 289) and Delta-SA (n = 221). Using one-to-one propensity score matching, surgical outcomes and gastrointestinal function were compared between the two groups., Results: After one-to-one propensity score matching, 177 pairs of INTACT and Delta-SA patients were selected. Patient background was closely balanced between the two groups. Operative time (186 [159, 213] min vs. 237 [213, 264] min; P < 0.001), estimated blood loss (0 [0, 10] g vs. 20 [0, 50] g; P < 0.001), and postoperative hospital stay (7 [7, 9] days vs. 10 [9, 13] days; P < 0.001) were significantly lower in the INTACT group than in Delta-SA group. There were no patients with postoperative leakage in the INTACT group and three patients in the Delta group (0.0% vs. 1.7%; P = 0.041). Endoscopic food residue grade ≥ 3 based on the Residue, Gastritis, Bile classification system at 1 year after surgery was observed in 14 patients in the INTACT group and 30 patients in the Delta group (9.6% vs. 17.0%; P = 0.052)., Conclusion: INTACT in TLDG B-I is safe and feasible for gastric cancer. Given its acceptable surgical outcomes, this alternative reconstruction method can be an option with TLDG B-I.

Intracranial aneurysm (IA) usually induced at a bifurcation site of intracranial arteries causes a lethal subarachnoid hemorrhage. Currently, IA is considered as a macrophage-mediated inflammatory disease triggered by a high wall shear stress (WSS) on endothelial cells. However, considered the fact that a high WSS can be observed at every bifurcation site, some other factors are required to develop IAs. We therefore aimed to clarify mechanisms underlying the initiation of IAs using a rat model. We found the transient outward bulging and excessive mechanical stretch at a prospective site of IA formation. Fibroblasts at the adventitia of IA walls were activated and produced (C-C motif) ligand 2 (CCL2) as well in endothelial cells loaded on high WSS at the earliest stage. Consistently, the mechanical stretch induced production of CCL2 in primary culture of fibroblasts and promoted migration of macrophages in a Transwell system. Our results suggest that distinct hemodynamic forces, mechanical stretch on fibroblasts and high WSS on endothelial cells, regulate macrophage-mediated IA formation.