研究等業績 - 原著論文 - 脇田 晃行
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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）