研究等業績 - 原著論文 - 脇田 晃行
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Imai K.
Cancer Imaging ( Cancer Imaging ) 24 ( 1 ) 2024年12月 [査読有り]
研究論文（学術雑誌） 国内共著
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Takahashi Y.
Physiotherapy Research International ( Physiotherapy Research International ) 29 ( 4 ) e2138 2024年10月 [査読有り]
研究論文（学術雑誌） 国内共著
INTRODUCTION: Frailty is significantly correlated with a higher incidence of medical complications during hospitalization after esophagectomy. As frailty is thought to be a reversible condition, improving the reserve capacity through preoperative physical therapy is expected to reduce the risk of postoperative pulmonary complications (PPCs). Herein, we report our experience with preoperative physical therapy in a patient with esophageal cancer who was considered to have inadequate fitness for surgery owing to poor physical performance. CASE PRESENTATION: A 72-year-old man (height: 169.5 cm, weight: 54.7 kg, body mass index: 18.9 kg/m2) with esophagogastric junction tumors (cStage IIIA) was hospitalized and scheduled to undergo surgery based on preoperative screening. He was categorized as frail according to the revised Japanese version of the Cardiovascular Health Study criteria and the Mini Nutritional Assessment Short-Form indicated severe malnutrition. We focused on physical therapy to improve exercise tolerance and prevent PPCs and devised a short-term intensive physical therapy program comprising minimal exercises that the patient could perform efficiently. The program consisted of only inspiratory muscle training and aerobic exercises. His maximal inspiratory pressure (MIP) and 6-min walking distance improved by 30 cm H2O and 145 m, respectively, on the day before surgery compared with those on day 8. The percentage predicted value of the MIP improved from 56.6% at the start of physical therapy to 102.9% on the day before surgery. On day 43, the patient underwent subtotal esophagectomy and was able to ambulate on postoperative day 5 without respiratory complications. CONCLUSION: We conducted a short-term, intensive, and minimal preoperative physical therapy program for a patient with esophageal cancer who had physical frailty. Preoperative physical therapy to increase the reserve capacity may result in a favorable postoperative course even in patients with physical frailty.
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Nozaki S.
Esophagus ( Esophagus ) 21 ( 2 ) 120 - 130 2024年 [査読有り]
研究論文（学術雑誌） 国内共著
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Okura K.
Journal of Surgical Oncology ( Journal of Surgical Oncology ) 128 ( 8 ) 1259 - 1267 2023年12月 [査読有り]
研究論文（学術雑誌） 国内共著
OBJECTIVE: We examined whether preoperative inspiratory muscle weakness (IMW) is a risk factor for postoperative pulmonary complications (PPCs) in patients with esophageal cancer who underwent subtotal esophagectomy. METHODS: This single-center retrospective cohort study enrolled patients with esophageal cancer who underwent a scheduled subtotal esophagectomy between June 2020 and May 2022. Maximal inspiratory pressure (MIP) was measured as inspiratory muscle strength using a respiratory dynamometer, and we defined IMW as MIP < 80% of the predicted value. Our primary outcome comprised overall PPCs. We investigated the relationship between IMW and PPCs using the Bayesian logistic regression model. RESULTS: After exclusion, 72 patients were included in this study. IMW was identified in 26 patients (36%), and PPCs developed in 28 patients (39%). Among patients with IMW, 15 (58%) developed PPCs. Preoperative IMW was associated with PPCs (mean odds ratio [OR]: 3.58; 95% credible interval [95% CrI]: 1.29, 9.73) in the unweighted model. A similar association was observed in the weighted model adjusted for preoperative and intraoperative contributing factors (mean OR: 4.15; 95% CrI: 2.04, 8.45). CONCLUSIONS: Preoperative IMW was associated with PPCs in patients with esophageal cancer who underwent subtotal esophagectomy. This association remained after adjusting for preoperative and intraoperative contributing factors.
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Sato Y.
Current Oncology ( Current Oncology ) 30 ( 5 ) 4724 - 4735 2023年05月 [査読有り]
研究論文（学術雑誌） 国内共著
Most so-called "beneficial bacteria" in gut microbiota are Gram-positive, and TLR6 recognizes the peptidoglycan (PGN) present in their cell walls. We hypothesized that a high TLR6 expression status predicts a more favorable prognosis after esophagectomy. We used an ESCC tissue microarray (TMA) to examine TLR6 expression status in ESCC patients and to determine whether TLR6 expression status correlates with prognosis after curative esophagectomy. We also examined whether PGN influences the cell proliferation activity of ESCC lines. Clinical ESCC samples from 177 patients tested for the expression of TLR6 were categorized as 3+ (n = 17), 2+ (n = 48), 1+ (n = 68), or 0 (n = 44). High TLR6 expression (3+ and 2+) correlated with significantly more favorable 5-year overall survival (OS) and disease-specific survival (DSS) after esophagectomy than a lower TLR6 expression (1+ and 0). Univariate and multivariate analyses showed that TLR6 expression status is an independent prognostic factor that affects 5-year OS. PGN significantly inhibited the cell proliferation activity of ESCC lines. This is the first study to show that high TLR6 expression status predicts a more favorable prognosis in locally advanced thoracic ESCC patients after curative esophagectomy. PGN released from "beneficial bacteria" seems to have potential to inhibit the cell proliferation activity of ESCC.
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Wakita A.
Annals of Gastroenterological Surgery ( Annals of Gastroenterological Surgery ) 7 ( 6 ) 904 - 912 2023年 [査読有り]
研究論文（学術雑誌） 国内共著
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Kemuriyama K.
Genes to Cells ( Genes to Cells ) 28 ( 8 ) 573 - 584 2023年 [査読有り]
研究論文（学術雑誌） 国内共著
Abstract
Tumor‐derived G‐CSF is a well‐known factor to aggravate disease progression in various types of cancers. In this study, we investigated a role of G‐CSF in squamous cell carcinoma (SCC). High expression of G‐CSF in the tumor tissues of esophageal SCC (ESCC) patients correlated with poor prognosis. Murine SCC NR‐S1M cells produce considerable amount of G‐CSF, which expression is correlated with its metastatic potentials. Deletion of G‐CSF in NR‐S1M cells mitigated tumor growth and metastasis to lymph node and lung of subcutaneous NR‐S1M tumors in the mice. Mechanistically, G‐CSF enhanced cell proliferation in autocrine manner in vitro, whereas in NR‐S1M tumor‐bearing mice, accumulation of plasma G‐CSF was associated with expansion of peripheral neutrophils, which led to a decreased proportion of CD8<sup>+</sup> T cells. Antibody depletion of neutrophils restored the number of CD8+ T cells and modestly suppressed tumor outgrowth, albeit no changes in distant metastasis. We propose that G‐CSF produced by NR‐S1M cells facilitates tumor progression in mice through bi‐functional effects to promote neutrophil recruitment and tumor cell proliferation, which may render poor prognosis to the ESCC patients with high G‐CSF expression. -
Ikeda T.
Acta Medica Okayama ( Acta Medica Okayama ) 77 ( 2 ) 193 - 197 2023年 [査読有り]
研究論文（学術雑誌） 国内共著
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食道切除再建術における呼吸サルコペニアと術後肺炎の関連
坂本 理々子, 大倉 和貴, 高橋 裕介, 長谷川 翔, 畠山 和利, 長岐 雄志, 脇田 晃行, 佐藤 雄亮, 粕川 雄司, 宮腰 尚久
呼吸理学療法学 ( (一社)日本呼吸理学療法学会 ) 3 ( Suppl. ) 122 - 122 2023年
研究論文（学術雑誌） 国内共著
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食道切除再建術後の呼吸器合併症の予測モデルにおける吸気筋力と身体機能の重要度の比較
大倉 和貴, 佐藤 雄亮, 高橋 裕介, 坂本 理々子, 長谷川 翔, 畠山 和利, 長岐 雄志, 脇田 晃行, 粕川 雄司, 宮腰 尚久
呼吸理学療法学 ( (一社)日本呼吸理学療法学会 ) 3 ( Suppl. ) 117 - 117 2023年
研究論文（学術雑誌）
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食道切除再建術後の呼吸器合併症の予測モデルにおける吸気筋力と身体機能の重要度の比較
大倉 和貴, 佐藤 雄亮, 高橋 裕介, 坂本 理々子, 長谷川 翔, 畠山 和利, 長岐 雄志, 脇田 晃行, 粕川 雄司, 宮腰 尚久
呼吸理学療法学 ( (一社)日本呼吸理学療法学会 ) 3 ( Suppl. ) 117 - 117 2023年
研究論文（学術雑誌） 国内共著
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Motoyama S.
Anticancer Research ( Anticancer Research ) 42 ( 12 ) 6105 - 6112 2022年12月 [査読有り]
研究論文（学術雑誌） 国内共著
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Changes in Serum Trace Element Concentrations before and after Surgery in Resectable Breast Cancer
Takahashi E.
Anticancer Research ( Anticancer Research ) 42 ( 11 ) 5323 - 5334 2022年11月 [査読有り]
研究論文（学術雑誌） 国内共著
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食道切除再建術における術前の横隔膜筋厚変化率と術後呼吸器合併症の関連
大倉 和貴, 高橋 裕介, 坂本 理々子, 長谷川 翔, 斉藤 公男, 粕川 雄司, 脇田 晃行, 佐藤 雄亮
呼吸理学療法学 ( (一社)日本呼吸理学療法学会 ) 8th.Meeting O - 01 2022年11月
研究論文（学術雑誌） 国内共著
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食道癌手術における術後肺炎リスク要因としての栄養指標の比較
坂本 理々子, 大倉 和貴, 高橋 裕介, 畠山 和利, 脇田 晃行, 佐藤 雄亮
日本呼吸ケア・リハビリテーション学会誌 ( (一社)日本呼吸ケア・リハビリテーション学会 ) 32 ( Suppl. ) 156s - 156s 2022年10月
研究論文（学術雑誌） 国内共著
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Motoyama S.
Annals of Surgery ( Annals of Surgery ) 276 ( 1 ) E16 - E23 2022年07月 [査読有り]
研究論文（学術雑誌） 国内共著
OBJECTIVE: To determine whether esophagectomy provides a survival advantage in octogenarians with resectable thoracic esophageal cancer. SUMMARY BACKGROUND DATA: Elderly patients with thoracic esophageal cancer do not always receive the full standard treatment; however, advanced age alone should not preclude the use of effective treatment that could meaningfully improve survival. METHODS: We retrieved the 2008 to 2011 data from the National Database of Hospital-based Cancer Registries from the National Cancer Centerin Japan, divided the patients into a ≥75 group (75-79 years; n = 2935) and a ≥80 group (80 years or older; n = 2131), and then compared the patient backgrounds and survival curves. A multivariable Cox proportional hazards regression model was developed to compare the effects of esophagectomy and chemoradiotherapy in the 2 groups. RESULTS: A significantly greater percentage of patients were treated with esoph-agectomy in the ≥75 group (34.6%) than the ≥80 group (18.4%). Among patients who received esophagectomy, the 3-year survival rate was 51.1% in the ≥ 75 group and 39.0% in the ≥80 group (P < 0.001). However, among patients who received chemoradiotherapy, there was no difference in survival curve between the 2 groups (P = 0.17). Multivariable Cox proportional hazard analysis revealed that esoph-agectomy for clinical Stage ii-iii patients was significantly associated to better survival (adjusted HR: 0.731) (95%CI: 0.645-0.829, P < 0.001) in the ≥75 group but not the ≥ 80 group when compared with chemoradiotherapy. CONCLUSIONS: Many octogenarians do not necessarily get a survival benefit from esophagectomy. However, patients should be evaluated based on their overall health before ruling out surgery based on age alone.
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Fujita K.
Esophagus ( Esophagus ) 19 ( 1 ) 146 - 152 2022年01月 [査読有り]
研究論文（学術雑誌） 国内共著
BACKGROUND: Platinum agents are taken up into cells by copper transporter (CTR) 1 (gene code: SLC31A1) and are excreted from cells by copper-transporting P-type adenosine triphosphatase (ATP7B) and multidrug resistance-associated protein (MRP) 2 (gene code: ABCC2). In addition, glutathione S transferase (GST) P1 is involved in the metabolism of platinum agents. The present study aimed to determine whether the rate of grade 3-4 hematological toxicity associated with platinum plus 5-fluorouracil (5-FU) therapy in 239 patients with esophageal cancer was affected by the SLC31A1 rs10981694A>C and rs12686377G>T, ATP7B rs9535828A>G, GSTP1 rs1695A>G, and ABCC2 -24C>T polymorphisms. METHODS: Chemotherapy consisted of protracted infusion of 5-FU (800 mg/m2/day) on days 1-5 and cisplatin or nedaplatin (80 mg/m2/day) on day 1. RESULTS: A total of 82 of 239 patients developed grade 3-4 hematological toxicity after chemotherapy. Univariate analysis showed that ABCC2 -24C/T + T/T genotypes (P = 0.038), radiation therapy (P = 0.013), baseline white blood cell count < 6000/μL (P = 0.003), and baseline neutrophil count < 3900/μL (P = 0.021) were statistically significant predictors of grade 3-4 hematological toxicity. Multivariate analysis revealed that ABCC2 -24C/T + T/T genotypes (P = 0.036), radiation therapy (P = 0.005), and baseline white blood cell count < 6000/μL (P < 0.001) were significant risk factors. CONCLUSIONS: We determined that ABCC2 -24C>T is significantly associated with grade 3-4 hematological toxicity after platinum plus 5-FU therapy. These findings might contribute to improved treatment strategies for patients with esophageal cancer.
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Fujita H.
Surgery (United States) ( Surgery (United States) ) 171 ( 6 ) 1535 - 1542 2022年 [査読有り]
研究論文（学術雑誌） 国内共著
BackgroundThe mechanism underlying cancer cell metastasis from the tumor to regional lymph nodes is not yet fully understood. We hypothesized that peritumoral neutrophil accumulation promotes regional lymph node metastasis in thoracic esophageal squamous cell cancer.MethodsBetween 2010 and 2019, 126 thoracic esophageal squamous cell cancer patients received curative (R0) esophagectomy without preoperative treatment in our hospital. Using paraffin-embedded resected tumors, we performed immunohistochemical analysis of CD16b-positive neutrophil accumulation in the peritumoral area, which was defined as a 1-mm region centered on the border separating the malignant cell nests from the host tissue. The relationship between the density of peritumoral CD16b staining and pathological lymph node metastasis or 5-year overall survival was evaluated.ResultsAlthough the clinicopathological characteristics of CD16b-high and CD16b-low patients did not differ, greater pathological lymph node metastasis (P < .001) and lymphatic invasion by the tumor (P = .024) and a poorer 5-year survival (P = .010) were seen in CD16b-high patients. Moreover, CD16b-positive neutrophil density was generally higher in the peritumoral area than within the tumor itself. Univariate and multivariate analyses showed that CD16b-positive neutrophil accumulation was an independent factor for lymph node metastasis with an odds ratio >25 (P < .001). On the other hand, blood neutrophil counts did not correlate with lymph node metastasis.
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Motoyama S.
Scientific Reports ( Scientific Reports ) 11 ( 1 ) 2021年12月 [査読有り]
研究論文（学術雑誌） 国内共著
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Nagaki Y.
World Journal of Surgical Oncology ( World Journal of Surgical Oncology ) 19 ( 1 ) 105 - 105 2021年12月 [査読有り]
研究論文（学術雑誌）
BACKGROUND: A pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) ensures long-term survival in esophageal squamous cell carcinoma (ESCC) patients following esophagectomy, but pCR patients are a minority. The aim here was to identify prognostic factors in patients with non-pCR ESCC after NACRT. METHODS: This is a retrospective study. Investigated were 5-year overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) among non-pCR ESCC patients divided into pT0N0, primary site pCR (pT0N+), lymph node pCR (pT+N0), and non-pCR in both the tumor and lymph node (pT+N+) subgroups after NACRT and esophagectomy. Focusing on the SUVmax reduction rate in the primary tumor in 88 patients who underwent FDG-PET before and after NACRT, we used univariate and multivariate Cox proportional hazard models to identify prognostic factors. RESULTS: Although there were no significant survival differences among non-pCR ESCC patients with pT0N+, pT+N0, or pT+N+, survival rate among pT+N+patients was the poorest. After setting a 60% cutoff for the SUVmax reduction rate in the tumor, RFS curves for non-pCR patients significantly differed between patients above the cutoff and those below it. For pT+N+ patients, the SUVmax reduction rate (<60% vs ≥ 60%) was an independent prognostic factor of OS, DSS, and RFS. CONCLUSION: Because ESCC patients with SUVmax reduction rates of <60% in the tumor after NACRT and categorized as pT+N+ after NACRT had significantly poorer prognoses, even after esophagectomy, a change in treatment strategy may be an option to improve survival.
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Nagaki Y.
BMC Cancer ( BMC Cancer ) 21 ( 1 ) 1192 - 1192 2021年12月 [査読有り]
研究論文（学術雑誌） 国内共著
BACKGROUND: Tumor regression grade (TRG) after neoadjuvant therapy is reportedly predictive of prognosis in esophageal cancer patients, as lack of a response to neoadjuvant therapy is associated with a poor prognosis. However, there is little information available on the timing and pattern of recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma (TESCC) that takes into consideration TRG after neoadjuvant chemoradiotherapy (NACRT). Here, in an effort to gain insight into a treatment strategy that improves the prognosis of NACRT non-responders, we evaluated the patterns and timing of recurrence in TESCC patients, taking into consideration TRG after NACRT. METHODS: A total of 127 TESCC patients treated with NACRT and esophagectomy between 2009 and 2017 were enrolled in this observational cohort study. TRGs were assigned based on the proportion of residual tumor cells in the area (TRG1, ≥1/3 viable cancer cells; 2, < 1/3 viable cancer cells; 3, no viable cancer cells). We retrospectively investigated the timing and patterns of recurrence and the prognoses in TESCC patients, taking into consideration TRG after NACRT. RESULTS: The 127 participating TESCC patients were categorized as TRG1 (42 patients, 33%), TRG2 (56 patients, 44%) or TRG3 (29 patients, 23%). The locoregional recurrence rate was higher in TRG1 (36.4%) patients than combined TRG2-3 (7.4%) patients. Patients with TRG3 had better prognoses, though a few TRG3 patients experienced distant recurrence. There were no significant differences in median time to first recurrence or OS among patients with locoregional or distant recurrence. There was a trend toward better OS in TRG2-3 patients with recurrence than TRG1 patients with recurrence, but the difference was not significant. CONCLUSIONS: NACRT non-responders (TRG1 patients) experienced higher locoregional recurrence rates and earlier recurrence with distant or locoregional metastasis. TRG appears to be useful for establishing a strategy for perioperative treatments to improve TESCC patient survival, especially among TRG1 patients. (303 words).
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Robot-assisted thoracoscopic enucleation for a large esophageal leiomyoma: a case report.
Kohei Kemuriyama, Satoru Motoyama, Yusuke Sato, Akiyuki Wakita, Yushi Nagaki, Hiromu Fujita, Ryohei Sasamori, Kazuhiro Imai, Masaki Aokawa, Yoshihiro Minamiya
Surgical case reports 7 ( 1 ) 129 - 129 2021年05月 [査読有り]
研究論文（学術雑誌） 国内共著
BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is being used to treat esophageal submucosal tumors (SMTs) all over the world. However, this technique is difficult when the tumor is large and located on the left side wall of the esophagus, within the upper mediastinum. This is because, with VATS, the surgical forceps have a limited range of motion. Robot-assisted thoracoscopic surgery (RATS) using the da Vinci surgical system may be extremely useful for enucleation of esophageal SMTs within the narrow upper mediastinum. CASE PRESENTATION: A female in her thirties experiencing epigastric pain visited our hospital and was diagnosed with a large esophageal leiomyoma within the upper mediastinum. From its size (10 cm), it was judged to have malignant potential. We performed SMT enucleation using RATS with a da Vinci surgical system Xi. This was our second case using this system. The patient was placed in the left lateral position. Four da Vinci trocars (8 mm) were inserted into the 10th, 7th, 5th and 3rd intercostal spaces (ICS), and an assist port was added in the 5th ICS. We opened the superior mediastinal pleura cranially and caudally from the arch of the azygos vein and expanded the superior mediastinum after dividing the azygos vein. We made an incision in the muscular layer of the esophagus and, using a monopolar hook and monopolar scissors, enucleated the esophageal tumor in a protective manner so as not to damage its capsule or mucosa while applying appropriate robot-specific counter traction. We then sewed up the muscularis using 4-0 Vicryl, inserting the endoscope into the thoracic esophagus to substitute for a bougie. In addition, the pleura was sutured using barbed suture. The surgical procedure was straightforward and smooth. The patient was discharged on postoperative day 4 with no surgical complications. The tumor was definitively diagnosed pathologically from paraffin sections as a benign esophageal leiomyoma. CONCLUSIONS: RATS enables more delicate and precise esophageal SMT enucleation without surgical complications, though various challenges remain to be overcome.
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IGF2BP3 Expression Correlates With Poor Prognosis in Esophageal Squamous Cell Carcinoma
Wakita A.
Journal of Surgical Research ( Journal of Surgical Research ) 259 137 - 144 2021年03月 [査読有り]
研究論文（学術雑誌）
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Sato Y.
Cancers ( Cancers ) 13 ( 5 ) 1 - 14 2021年03月 [査読有り]
研究論文（学術雑誌）
<jats:p>Background: Neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy is now the standard treatment for patients with resectable advanced thoracic esophageal squamous cell carcinoma (ESCC) worldwide. However, the efficacy of NACRT followed by esophagectomy with three-field lymph node dissection for clinical Stage III patients and for clinical Stage IVB patients with supraclavicular LN metastasis has not yet been determined. Methods: Between 2008 and 2018, 94 ESCC patients diagnosed as clinical Stage III and 18 patients diagnosed as clinical Stage IVB with supraclavicular LN metastasis as the only distant metastatic factor were treated with NACRT followed by esophagectomy with extended lymph node dissection at Akita University Hospital. Long-term survival and the patterns of recurrence in these 112 patients were analyzed. Results: The median follow-up period of censored cases was 60 months. The five-year OS and DSS rates among the clinical Stage III patients were 57.6% and 66.6%, respectively. The five-year OS and DSS rates among the clinical Stage IVB patients were 41.3% and 51.6%, respectively. The most frequent recurrence pattern was distant metastasis (69.2%) in the Stage III patients and LN metastasis (75.0%) in the Stage IVB patients. Conclusion: NACRT followed by esophagectomy with three-field LN dissection is feasible and offers the potential for long-term survival of clinical Stage III ESCC patients and even clinical Stage IVB patients with supraclavicular LN metastasis as the only distant metastatic factor. At least in patients with upper and middle thoracic ESCC, treating supraclavicular LNs as regional LNs seems to be appropriate.</jats:p>
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Fujita K.
Medical Oncology ( Medical Oncology ) 38 ( 1 ) 6 - 6 2021年01月 [査読有り]
研究論文（学術雑誌）
The relationship between the SLC31A1 (protein: copper transporter 1) rs10981694 A > C and ATP7B (protein: P-type adenosine triphosphatase 7B) rs9535828 A > G polymorphisms on the overall survival and disease-free survival of 104 Japanese patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant chemoradiotherapy (CRT) was investigated. Chemotherapy consisted of protracted infusion of 5-fluoracil (800 mg/m2/day) on days 1-5 and cisplatin or nedaplatin (80 mg/m2/day) on day 1. The median (range) follow-up was 47 (6-127) months. The 5-year overall and disease-free survival rates were 71.2% and 60.6%, respectively. The 5-year overall survival rate was significantly higher in patients with the SLC31A1 rs10981694 C allele compared with the rs10981694 A/A genotype (91.7% vs. 65.0%, P = 0.018). The 5-year disease-free survival rate was significantly higher in patients with the SLC31A1 rs10981694 C allele compared with the rs10981694 A/A genotype (79.2% vs. 55.0%, P = 0.043). In addition, univariate and multivariate analyses showed the SLC31A1 rs10981694 A > C polymorphism to be a significant prognostic factor affecting 5-year overall survival after neoadjuvant CRT. However, the overall and disease-free survival rates after surgery did not differ significantly among the ATP7B rs9535828 genotypes. In conclusion, only the SLC31A1 rs10981694 A/A genotype was an independent predictor of a poorer 5-year overall survival. Therefore, in neoadjuvant CRT for ESCC patients, the effect of platinum was affected by the SLC31A1 rs10981694 A > C polymorphism. The presence of this polymorphism should be considered when devising neoadjuvant CRT regimens or treatment strategies for ESCC.
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Motoyama S.
Cancer Science ( Cancer Science ) 112 ( 10 ) 4281 - 4291 2021年 [査読有り]
研究論文（学術雑誌）
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Nagaki Y.
Annals of Surgical Oncology ( Annals of Surgical Oncology ) 29 ( 2 ) 1336 - 1346 2021年 [査読有り]
研究論文（学術雑誌）
BACKGROUND: Patients with 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)-positive lymph nodes before treatment have a poor prognosis after esophagectomy. This study investigated whether FDG uptake into lymph nodes on FDG-PET (PET-N) during the pre- or posttreatment stage is more predictive of survival for thoracic esophageal squamous cell carcinoma (TESCC) patients who received neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy. METHODS: Of 129 TESCC patients with clinical lymphatic metastasis who underwent curative-intent esophagectomy after NACRT between 2010 and 2018, 97 who received PET before and after NACRT were enrolled in the study. The study defined lymph nodes with a maximum standardized uptake value (SUVmax) greater than 2.5 on FDG-PET before NACRT as cPET-N(+) and after NACRT as CRT-cPET-N(+). Both the cPET-N(+) and CRT-cPET-N(-) patients were defined as PET-N responders. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazard models. RESULTS: No significant difference in survival was detected between the cPET-N(+) and cPET-N(-) patients. However, the CRT-cPET-N(-) patients had significantly better 5-year overall survival (OS) and disease-specific survival (DSS) than the CRT-cPET-N (+) patients. The PET-N responders had significantly better 5-year OS and DSS than the PET-N non-responders, and PET-N response was an independent prognostic factor for 5-year DSS. CONCLUSION: The PET-N response is a highly predictive prognostic marker for TESCC patients who undergo NACRT followed by esophagectomy. The PET-N response may help clinicians to establish a strategy for perioperative treatments that improves survival for patients with lymph node metastasis in TESCC.
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Sasamori Ryohei, Motoyama Satoru, Sato Yusuke, Wakita Akiyuki, Nagaki Yushi, Imai Kazuhiro, Minamiya Yoshihiro
Annals of Thoracic and Cardiovascular Surgery ( Annals of Thoracic and Cardiovascular Surgery 編集委員会 ) advpub ( 0 ) 97 - 102 2021年 [査読有り]
研究論文（学術雑誌）
<p>The advantages of salvage esophagectomy through robotic-assisted surgery for patients with clinically diagnosed tumor invasion of adjacent vital organs (cT4b) or patients with scar tissue from definitive chemoradiotherapy (dCRT) are still only rarely reported. A man in his 60s with middle thoracic esophageal cancer (cT4b [left main bronchus] N1 M0 cStage IIIC) received dCRT (60 Gy). After the chemoradiotherapy, upper gastrointestinal endoscopy revealed a residual primary tumor, and we performed robotic-assisted thoracoscopic subtotal esophagectomy and gastric tube reconstruction via a retrosternal route with three-field lymphadenectomy. Although it was difficult to dissect the tumor from adjacent organs, especially the left main bronchus and left inferior pulmonary vein, due to loss of the dissecting layer and scarring, R0 surgery was achieved. With robot-assisted thoracoscopic surgery, the high-magnification, high-resolution, and three-dimensional images; the stable surgical field with full countertraction made with the robotic arm forceps, which were readily adjusted; and the stable motion of the robotic arm without physiological tremor are considerable advantages for salvage esophagectomy for cT4b tumors. It goes without saying that sufficient experience with robot-assisted surgery and sufficient understanding and surgical skill in esophageal cancer surgery under suitable surgical indications and timing are required to make use of these advantages.</p>
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Sato Y.
Scientific Reports ( Scientific Reports ) 10 ( 1 ) 2020年12月 [査読有り]
研究論文（学術雑誌）
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Sato Y.
Esophagus ( Esophagus ) 17 ( 4 ) 408 - 416 2020年10月 [査読有り]
研究論文（学術雑誌）
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Kawakita Y.
Anticancer Research ( Anticancer Research ) 40 ( 10 ) 5715 - 5725 2020年10月 [査読有り]
研究論文（学術雑誌）
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Terata K.
Translational Cancer Research ( Translational Cancer Research ) 9 ( 8 ) 5038 - 5043 2020年08月 [査読有り]
研究論文（学術雑誌）
Advances have been made in systemic as well as locoregional treatment of primary breast cancer. Evidence, based established therapeutic strategies, for isolated locoregional lymph node recurrence is not yet sufficient. In this series, we focused especially on isolated axillary lymph node recurrence (AR) and supraclavicular lymph node recurrence (SR) in patients receiving systemic and/or radiation therapy combined with surgery. Disease free survival (DFS) in patients with AR ranged from 20 to 36 months. From 69% to 77% of all patients underwent surgical excision. The 5-year overall survival (OS) ranged from 39% to 46%. Positive lymph node metastases of primary cancer, size of the primary tumor, and R0 resection were associated with good outcomes. Longer DFS is associated with good outcomes. Limited SR data showed DFS to range from 25-27%. Median progression free survival (PFS) was 18 months, 5-year OS rates were 24-42%, and 5-year OS were 29-34 months. Combination therapy was an independent factor associated with better PFS as compared to local therapy only. Salvage treatment and grade of the primary tumor significantly were associated with OS on multivariate analysis. Available data, retrospective and not randomized, showed therapy combining systemic treatments and/or radiotherapy with surgery might contribute to good local control, better PFS, and longer OS.
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Nagaki Y.
Genes to Cells ( Genes to Cells ) 25 ( 8 ) 547 - 561 2020年08月 [査読有り]
研究論文（学術雑誌）
Esophageal squamous cell carcinoma (ESCC) is one of the most fatal types of malignant tumors worldwide. Epitranscriptome, such as N6 -methyladenosine (m6 A) of mRNA, is an abundant post-transcriptional mRNA modification and has been recently implicated to play roles in several cancers, whereas the significance of m6 A modifications is virtually unknown in ESCC. Analysis of tissue microarray of the tumors in 177 ESCC patients showed that higher expression of m6 A demethylase ALKBH5 correlated with poor prognosis and that ALKBH5 was an independent prognostic factor of the survival of patients. There was no correlation between the other demethylase FTO and prognosis. siRNA knockdown of ALKBH5 but not FTO significantly suppressed proliferation and migration of human ESCC cells. ALKBH5 knockdown delayed progression of cell cycle and accumulated the cells to G0/G1 phase. Mechanistically, expression of CDKN1A (p21) was significantly up-regulated in ALKBH5-depleted cells, and m6 A modification and stability of CDKN1A mRNA were increased by ALKBH5 knockdown. Furthermore, depletion of ALKBH5 substantially suppressed tumor growth of ESCC cells subcutaneously transplanted in BALB/c nude mice. Collectively, we identify ALKBH5 as the first m6 A demethylase that accelerates cell cycle progression and promotes cell proliferation of ESCC cells, which is associated with poor prognosis of ESCC patients.
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Surgical therapy for breast cancer liver metastases
Terata K.
Translational Cancer Research ( Translational Cancer Research ) 9 ( 8 ) 5053 - 5062 2020年08月 [査読有り]
研究論文（学術雑誌）
Breast cancer is the most commonly diagnosed cancer in females worldwide. If diagnosed early, patients generally have good outcomes. However, approximately 20% to 30% of all women diagnosed with breast cancer develop metastatic disease. Metastatic breast cancer is incurable, but there is growing evidence that resection or other local therapy for breast cancer liver metastases (BCLM) may improve survival. We aimed to review indications for and outcomes of perioperative liver resection and other local therapies for BCLM. In this series, we reviewed 11 articles (605 patients) focusing on surgical resection and 7 articles (266 patients) describing radiofrequency ablation (RFA) for BCLM. Median disease-free survival (DFS) after surgical resection was 23 months (range, 14-29 months) and median overall survival (OS) was 39.5 months (range, 26-82 months). One, 3- and 5-year survivals were 89.5%, 70%, and 38%, respectively. The factors favoring better outcomes are hormone receptor positive primary breast cancer status, R0 resection, no extrahepatic metastases (EHM), small BCLM, and solitary liver metastases. On the other hand, the median DFS with RFA was 11 months, median OS was 32 months, and the 3- and 5-year OS were 43% and 27%, respectively. The clinical features that are indications for RFA are smaller tumor and higher EHM rate than those favoring surgical resection (2.4 vs. 4.0 cm and 46% vs. 27%). The merits of RFA are its high technical success rate, low morbidity, short hospital stay, and that it can be repeated. Although results are as yet limited, in carefully selected patients, resection or other local therapies such as RFA, render BCLM potentially provide prognostic improvement.
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Kawakita Y.
World Journal of Surgery ( World Journal of Surgery ) 44 ( 5 ) 1559 - 1568 2020年05月 [査読有り]
研究論文（学術雑誌）
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Wakita A.
World Journal of Surgical Oncology ( World Journal of Surgical Oncology ) 18 ( 1 ) 2020年05月 [査読有り]
研究論文（学術雑誌）
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Imai K.
Pathobiology ( Pathobiology ) 87 ( 1 ) 45 - 50 2020年03月 [査読有り]
研究論文（学術雑誌）
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Approaches to resection of recurrent solitary mediastinal lymph nodes after esophagectomy
Motoyama S.
Esophagus ( Esophagus ) 18 ( 3 ) 700 - 703 2020年 [査読有り]
研究論文（学術雑誌）
Esophageal cancer recurrence in solitary mediastinal lymph node that may possibly been left behind in the first surgery differs from other recurrence patterns because it is still local disease and offers the possibility of complete cure through resection, but it is technically difficult. We resected recurrent mediastinal lymph nodes in six cases. A left transthoracic approach was used in three patients. Other approaches were left thoracoabdominal, right open transthoracic and transcervical. R0 resections were achieved in five patients without severe surgical stress or postoperative complications. Overall survival after resection of recurrent lymph nodes was 43 (16-82) months. Approaches to resection of recurrent solitary mediastinal lymph nodes after esophagectomy should be consider to perform curative treatment safely and less invasively.
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Wakita A.
Annals of Surgical Oncology ( Annals of Surgical Oncology ) 28 ( 4 ) 2101 - 2110 2020年 [査読有り]
研究論文（学術雑誌）
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Kurihara N.
Journal of Clinical Pathology ( Journal of Clinical Pathology ) 72 ( 9 ) 603 - 608 2019年09月 [査読有り]
研究論文（学術雑誌）
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Motoyama S.
Anticancer Research ( Anticancer Research ) 39 ( 3 ) 1337 - 1342 2019年03月 [査読有り]
研究論文（学術雑誌）
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Hoshino I.
Journal of Clinical Pathology ( Journal of Clinical Pathology ) 72 ( 1 ) 25 - 30 2019年01月 [査読有り]
研究論文（学術雑誌）
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Sato Y.
American Journal of Surgery ( American Journal of Surgery ) 216 ( 2 ) 319 - 325 2018年08月 [査読有り]
研究論文（学術雑誌）
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Kawakita Y.
Surgery Today ( Surgery Today ) 47 ( 11 ) 1312 - 1320 2017年11月 [査読有り]
研究論文（学術雑誌）
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Motoyama S.
Anticancer Research ( Anticancer Research ) 37 ( 10 ) 5837 - 5843 2017年10月 [査読有り]
研究論文（学術雑誌）
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Motoyama S.
Anticancer Research ( Anticancer Research ) 37 ( 8 ) 4189 - 4194 2017年08月 [査読有り]
研究論文（学術雑誌）
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Wakita A.
Anticancer Research ( Anticancer Research ) 37 ( 3 ) 1433 - 1441 2017年03月 [査読有り]
研究論文（学術雑誌）
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Reg Iα promotes PD-L1 expression in esophageal cancer cells
Wakita A, Motoyama S, Sato Y, Yoshino K, Sasaki T, Imai K, Saito H, Minamiya Y
Akita J Med 2014年01月 [査読有り]
研究論文（学術雑誌） 単著