Publications by authors named "Hiroyuki Daiko"

114 Publications

Prognostic biomarker study in patients with clinical stage I esophageal squamous cell carcinoma: JCOG0502-A1.

Cancer Sci 2021 Dec 28. Epub 2021 Dec 28.

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

We undertook genomic analyses of Japanese patients with stage I esophageal squamous cell carcinoma (ESCC) to investigate the frequency of genomic alterations and the association with survival outcomes. Biomarker analysis was carried out for patients with clinical stage T1bN0M0 ESCC enrolled in JCOG0502 (UMIN000000551). Whole-exome sequencing (WES) was performed using DNA extracted from formalin-fixed, paraffin-embedded tissue of ESCC and normal tissue or blood sample. Single nucleotide variants (SNVs), insertions/deletions (indels), and copy number alterations (CNAs) were identified. We then evaluated the associations between each gene alteration with a frequency of 10% or more and progression-free survival (PFS) using a Cox regression model. We controlled for family-wise errors at 0.05 using the Bonferroni method. Among the 379 patients who were enrolled in JCOG0502, 127 patients were successfully analyzed using WES. The median patient age was 63 years (interquartile range, 57-67 years), and 78.0% of the patients ultimately underwent surgery. The 3-year PFS probability was 76.3%. We detected 20 genes with SNVs, indels, or amplifications with a frequency of 10% or more. Genomic alterations in FGF19 showed the strongest association with PFS with a borderline level of statistical significance of P = .00252 (Bonferroni-adjusted significance level is .0025). Genomic alterations in FGF4, MYEOV, CTTN, and ORAOV1 showed a marginal association with PFS (P < .05). These genomic alterations were all CNAs at chromosome 11q13.3. We have identified new genomic alterations associated with the poor efficacy of ESCC (T1bN0M0). These findings open avenues for the development of new potential treatments for patients with ESCC.
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http://dx.doi.org/10.1111/cas.15251DOI Listing
December 2021

Does synchronous early head and neck cancer with esophageal cancer need treatment after preoperative chemotherapy?

Gen Thorac Cardiovasc Surg 2021 Nov 27. Epub 2021 Nov 27.

Department of Esophageal Surgery, National Cancer Center Hospital, 5-5-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Objective: Treatment options for patients with resectable thoracic esophageal squamous cell cancer (ESCC) and synchronous head and neck cancer (HNC) are unclear. Little has been reported about the effects of chemotherapy on early HNC. The aim of this study was to investigate the treatment outcomes of resectable thoracic ESCC with synchronous early HNC.

Methods: We retrospectively reviewed 37 patients undergoing esophagectomy for thoracic ESCC with synchronous early HNC from January 2008 to December 2018.

Results: Among 37 patients who had synchronous early HNC, 27 patients received preoperative therapy for ESCC before HNC treatment, and 16 of 27 patients achieved a complete response for HNC by preoperative chemotherapy. Fifteen of 16 patients did not receive additional treatment, and regional recurrence of HNC was not observed. In one other case, an oral excision was performed, but no cancer cell remnants were found pathologically. No significant difference in overall survival and disease-free survival was observed between 15 patients with follow-up and 22 patients with surgery or radiation.

Conclusion: Our results indicate that early HNC with comorbid ESCC could be followed up without additional treatment if preoperative chemotherapy is successful.
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http://dx.doi.org/10.1007/s11748-021-01744-9DOI Listing
November 2021

Relevance of pharmacogenetic polymorphisms with response to docetaxel, cisplatin, and 5-fluorouracil chemotherapy in esophageal cancer.

Invest New Drugs 2021 Nov 18. Epub 2021 Nov 18.

Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.

Purpose: Docetaxel, cisplatin, and 5-fluorouracil (DCF) have high response rates, but severe neutropenia is frequently observed. The occurrence of neutropenia is associated with high histological response in solid tumors, and it might be associated with tumor shrinkage after DCF therapy. This study aimed to determine the genetic polymorphisms involved in the clinical response to preoperative DCF therapy in esophageal cancer patients.

Methods: We included 56 patients with measurable lesions who received preoperative DCF therapy for esophageal cancer. Twenty-one genetic polymorphisms were analyzed, and univariate logistic regression analysis was used to evaluate the association between genetic polymorphisms and tumor shrinkage. A multivariate logistic regression analysis adjusted for T category and tumor location and a univariate analysis for potential genetic factors with P values < 0.05 were performed to explore the predictive factors and to estimate odds ratios and their 95% confidence intervals.

Results: No patient achieved a complete response, whereas 20 patients achieved a partial response, 31 patients had stable disease, and 5 patients had progressive disease. Although no association was found between pharmacokinetic-related gene polymorphisms, XRCC3 rs17997944 was extracted as the only genetic factor that affected tumor shrinkage (P = 0.033) by univariate analysis. The multivariate analysis adjusted for T category and tumor site also showed that XRCC3 rs1799794: AA was a predictive factor that affected tumor shrinkage (odds ratio, 0.243; 95% confidence interval, 0.065-0.914; P = 0.036). Conlusions. XRCC3 rs1799794, which is involved in homologous recombination, is a genetic factor that affects clinical responses to DCF therapy.
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http://dx.doi.org/10.1007/s10637-021-01199-yDOI Listing
November 2021

Novel pathological staging for patients with locally advanced esophageal squamous cell carcinoma undergoing neoadjuvant chemotherapy followed by surgery.

Esophagus 2021 Nov 10. Epub 2021 Nov 10.

Esophageal Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji Chuo-ku, Tokyo, 104-0045, Japan.

Background: The aim of the present study was to clarify an appropriate staging system for patients with locally advanced esophageal squamous cell carcinoma (LAESCC) after neoadjuvant chemotherapy (NAC) prior to surgery.

Methods: A total of 388 patients with clinical stage II or III LAESCC who had undergone NAC followed by an esophagectomy with three-field lymphadenectomy were retrospectively reviewed.

Results: The relapse-free survival (RFS) curves plotted using ypN grading and ypTNM staging both monotonically decreased as the classification number increased, and the groups were more clearly separated than when the Japanese Classification (JC) was applied. A multivariate analysis of relapse free survival (RFS) suggested that ypN (HR = 2.911, P < 0.001), lymphovascular invasion (LVI) (HR = 2.608, P < 0.001) were independent factors associated with OS. The LVI+/ypN+ group had a significantly poorer outcome than the other groups (P < 0.001). The 5-year RFS rates for patients with ypStage IIIA or higher among the LVI-negative cases and ypStage II or higher among the LVI-positive cases were around 0.6 or under. The novel pathological staging which was based on the present results was proposed and RFS curves of each novel stage suggested the suitability of these staging for our cohort.

Conclusions: The present results suggest that a novel pathological staging system using the ypTNM classification, in which the supraclavicular lymph node was regarded as a regional lymph node and the presence of LVI was included as a category, was appropriate for patients with LAESCC after NAC prior to surgery.
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http://dx.doi.org/10.1007/s10388-021-00891-5DOI Listing
November 2021

Long-term survival of patients with T1bN0M0 esophageal cancer after thoracoscopic esophagectomy using data from JCOG0502: a prospective multicenter trial.

Surg Endosc 2021 Oct 26. Epub 2021 Oct 26.

Japan Esophageal Oncology Group of Japan Clinical Oncology Group (JCOG), Tokyo, Japan.

Background: Thoracoscopic esophagectomy (TE) is considered the standard surgery for esophageal cancer because of its superiority over open esophagectomy (OE) in terms of short-term outcomes. However, few prospective multicenter studies have evaluated its long-term survival after TE. This study aimed to investigate whether the prognosis for patients with T1bN0M0 esophageal cancer after TE is not inferior to OE using data from the Japan Clinical Oncology Group Study (JCOG0502), a prospective multicenter trial comparing esophagectomy with chemoradiotherapy.

Methods: Data of patients in JCOG0502 after esophagectomy were used to compare the overall survival (OS) and relapse-free survival (RFS) after OE versus TE. OE or TE was selected at the surgeon's discretion. A hazard ratio and 95% confidence interval (CI) were calculated via Cox proportional-hazards model.

Results: Of the 210 patients who underwent esophagectomy, 109 underwent OE, whereas 101 underwent TE. The 5-year OS was 88.9% after OE and 85.0% after TE. The hazard ratio of TE for OS was 1.53 (95% CI, 0.84-2.78; p = 0.16) and 1.10 (95% CI, 0.52-2.35; p = 0.80) in the univariable and multivariable analyses, respectively. The 5-year RFS was 85.3% after OE and 79.1% after TE. The hazard ratio of TE for RFS was 1.39 (95% CI, 0.81-2.38; p = 0.23) and 0.88 (95% CI, 0.44-1.74; p = 0.70) in the univariable and multivariable analyses, respectively.

Conclusion: The prognosis for patients with T1bN0M0 esophageal cancer after TE was not inferior to OE.
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http://dx.doi.org/10.1007/s00464-021-08768-5DOI Listing
October 2021

Salvage minimally invasive esophagectomy after definitive chemoradiotherapy for esophageal cancer can improve postoperative complications compared with salvage open esophagectomy.

Surg Endosc 2021 Oct 12. Epub 2021 Oct 12.

Division of Esophageal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, 104-0045, Japan.

Background: Although the advantage of minimally invasive esophagectomy (MIE) over open esophagectomy (OE) in planned esophagectomy is being established, the utility of salvage MIE (S-MIE) remains unclear. We aimed to investigate the feasibility and advantage of S-MIE compared with salvage OE (S-OE).

Methods: We retrospectively assessed 82 patients who underwent salvage esophagectomy after definitive chemoradiotherapy for thoracic esophageal cancer between January 2007 and April 2020. Perioperative factors and postoperative complications were compared between the S-OE group (n = 62) and the S-MIE group (n = 20). Logistic regression analysis was performed to analyze the factors associated with postoperative complications.

Results: Regarding the patients' preoperative characteristics, the S-OE group had a significant number of grade ≥ cT3 patients vs the S-MIE group (69% vs 35%, respectively; p = 0.006), whereas ycT rates were comparable. Compared with S-OE, S-MIE had comparable operative time, number of harvested thoracic lymph nodes, and R0 resection, but significantly less estimated blood loss (150 ml and 395 ml, respectively; p = 0.003). Regarding postoperative complications, total complications (79% vs 50%; p = 0.01) and pneumonia (48.3% vs 20%; p = 0.02) rates were significantly lower with S-OE vs S-MIE, respectively. On multivariate analysis, S-MIE was an independent factor associated with postoperative pneumonia (odds ratio: 0.29, 95% confidence interval: 0.06-0.99; p = 0.04) and total complications (odds ratio: 0.26, 95% confidence interval: 0.07-0.86; p = 0.02).

Conclusion: S-MIE was feasible for salvage esophagectomy, with favorable short-term outcomes vs S-OE regarding postoperative pneumonia and total complications.
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http://dx.doi.org/10.1007/s00464-021-08672-yDOI Listing
October 2021

Parallel-Group Controlled Trial of Surgery Versus Chemoradiotherapy in Patients With Stage I Esophageal Squamous Cell Carcinoma.

Gastroenterology 2021 12 10;161(6):1878-1886.e2. Epub 2021 Aug 10.

Department of Surgery, Keio University, School of Medicine, Tokyo, Japan.

Background & Aims: Surgery is the standard of care for T1bN0M0 esophageal squamous cell carcinoma (ESCC), whereas chemoradiotherapy (CRT) is a treatment option. This trial aimed to investigate the noninferiority of CRT relative to surgery for T1bN0M0 ESCC.

Methods: Clinical T1bN0M0 ESCC patients were eligible for enrollment in this prospective nonrandomized controlled study of surgery versus CRT. The primary endpoint was overall survival, which was determined using inverse probability weighting with propensity scoring. Surgery consisted of an esophagectomy with 2- or 3-field lymph node dissection. CRT consisted of 2 courses of 5-fluorouracil (700 mg/m) on days 1-4 and cisplatin (70 mg/m) on day 1 every 4 weeks with concurrent radiation (60 Gy).

Results: From December 20, 2006 to February 5, 2013, a total of 368 patients were enrolled in the nonrandomized portion of the study. The patient characteristics in surgery arm and CRT arm, respectively, were as follows: median age, 62 and 65 years; proportion of males, 82.8% and 88.1%; and proportion of performance status 0, 99.5% and 98.1%. Comparisons were made using the nonrandomized groups. The 5-year overall survival rate was 86.5% in the surgery arm and 85.5% in the CRT arm (adjusted hazard ratio, 1.05; 95% confidence interval, 0.67-1.64 [<1.78]). The complete response rate in the CRT arm was 87.3% (95% confidence interval, 81.1-92.1). The 5-year progression-free survival rate was 81.7% in the surgery arm and 71.6% in the CRT arm. Treatment-related deaths occurred in 2 patients in the surgery arm and none in the CRT arm.

Conclusions: CRT is noninferior to surgery and should be considered for the treatment of T1bN0M0 ESCC.
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http://dx.doi.org/10.1053/j.gastro.2021.08.007DOI Listing
December 2021

Feasibility of conversion thoracoscopic esophagectomy after induction therapy for locally advanced unresectable esophageal squamous cell carcinoma.

Jpn J Clin Oncol 2021 Aug;51(8):1225-1231

Department of Esophageal Surgery, National Cancer Center Hospital, Tokyo, Japan.

Background: Recently, patients with cT4b esophageal cancer often require conversion surgery following induction therapy, for which the standard procedure is open esophagectomy. However, thoracoscopic esophagectomy, including thoracoscopic esophagectomy in the prone position, is increasingly used. We compared short-term outcomes of thoracoscopic esophagectomy and open esophagectomy in this setting.

Methods: We retrospectively analyzed 14 patients who underwent thoracoscopic esophagectomy, and 10 who underwent open esophagectomy, for locally advanced unresectable esophageal cancer after induction therapy between March 2007 and July 2020.

Results: The two groups did not significantly differ in patient background. Median total and thoracic surgical times were both significantly longer for open esophagectomy than for thoracoscopic esophagectomy. Median blood loss was also greater in the open esophagectomy group than in the thoracoscopic esophagectomy group. The thoracoscopic esophagectomy group also had significantly shorter median chest drain duration; and lower C-reactive protein levels on the second and third postoperative days. The two groups did not significantly differ in total complications or postoperative hospital stay.

Conclusions: Thoracoscopic esophagectomy is as safe and feasible as open esophagectomy for conversion surgery after induction therapy for locally advanced unresectable esophageal squamous cell carcinoma.
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http://dx.doi.org/10.1093/jjco/hyab085DOI Listing
August 2021

Novel hybrid endoscopy-assisted larynx-preserving esophagectomy for cervical esophageal cancer (with video).

Jpn J Clin Oncol 2021 Jul;51(7):1171-1175

Division of Esophageal Surgery, National Cancer Center Hospital, Tokyo, Japan.

Hybrid endoscopy-assisted larynx-preserving esophagectomy is developed for cervical esophageal squamous cell carcinoma encroaching or extending above the upper esophageal sphincter. First, a cervical incision was surgically performed followed by cervical lymph node dissection. Second, the margin of cervical esophageal squamous cell carcinoma was endoscopically identified with iodine staining and marked endoscopically followed by semi-circumferential or circumferential endoscopic full-thickness excision around the lumen of the esophagus. The distal margin was surgically resected and reconstruction was performed. Among six consecutive patients with cervical esophageal squamous cell carcinoma undergoing hybrid endoscopy-assisted larynx-preserving esophagectomy, proximal surgical margin was histologically negative in five patients. During a median follow-up period of 15.5 months, all patients tolerated oral intake and were alive without evidence of recurrence. None of the patients experienced aspiration pneumonia, vocal disorder or postoperative anastomotic stricture. Hybrid endoscopy-assisted larynx-preserving esophagectomy could be a clinically feasible treatment for cervical esophageal squamous cell carcinoma providing accurate proximal resection margin with the benefit of laryngeal function preservation.
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http://dx.doi.org/10.1093/jjco/hyab045DOI Listing
July 2021

Does staged surgical training for minimally invasive esophagectomy have an impact on short-term outcomes?

Surg Endosc 2021 11 30;35(11):6251-6258. Epub 2020 Oct 30.

Division of Esophageal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, 104-0045, Japan.

Background: sophageal cancer has a low incidence, and the anatomy is difficult to understand during esophagectomy. This necessitates a precise and lengthy operation. Therefore, the establishment of a training system in esophageal surgery is of critical importance. In this study, we compared the short-term outcomes of minimally invasive esophagectomy (MIE) performed by consultants versus trainees and explored the factors that impacted the thoracic operation time for each group.

Methods: We have introduced standardized MIE surgical techniques to our trainees in 2016. Our procedure consists of a laparoscopic phase and a thoracoscopic phase and is systematically designed to be learned in a step-by-step manner in each phase. We retrospectively identified 308 patients who underwent MIE from April 2016 to April 2018. The patients were divided into those who underwent MIE by consultants and those who underwent MIE by trainees. The preoperative background factors, operation-related factors, and postoperative complications were compared between the two groups. We also assessed the association between a prolonged thoracic operation time and tumor-and patient-related factors in each of the consults and trainees.

Results: Significantly more patients had stage ≥ III cancer in the consultant than trainee group. However, the postoperative complications were comparable, specifically pneumonia (11% vs. 18%), anastomotic leakage (11% vs. 13%), and mortality (0.6% vs. 1.3%). There was no significant difference in the lymph node yield (20 vs. 17) or R0 resection rate (94% vs. 91%) between the two groups. However, the trainees had a significantly longer thoracic operation time (143 ± 34 vs. 190 ± 28 min) and significantly greater blood loss (93 vs. 183 ml). Oncological factors were correlated with a prolonged thoracic operation time in the consultants, but not in the trainees.

Conclusions: Under standardized surgical management using a stepwise educational program, performance of MIE by trainees has no impact on short-term outcomes.
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http://dx.doi.org/10.1007/s00464-020-08125-yDOI Listing
November 2021

Optimal preoperative neoadjuvant therapy for resectable locally advanced esophageal squamous cell carcinoma.

Ann N Y Acad Sci 2020 12 16;1482(1):213-224. Epub 2020 Oct 16.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide, especially in East Asia. ESCC accounts for more than 90% of esophageal cancer. Currently, neoadjuvant therapy in combination with surgical resection is the mainstay of treatment. However, the overall survival rate of patients with locally advanced ESCC is not satisfactory even when treated following the standard treatment guidelines. With neoadjuvant chemoradiotherapy, chemotherapy, or emerging immunotherapy, continuous exploration of efficacy in relation to ESCC is expected to improve overall survival further. Here, we review and summarize current evidence for efficacy of preoperative therapy for locally advanced ESCC.
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http://dx.doi.org/10.1111/nyas.14508DOI Listing
December 2020

Robotic esophagectomy with total mediastinal lymphadenectomy using four robotic arms alone in esophageal and esophagogastric cancer (RETML-4): a prospective feasibility study.

Esophagus 2021 Apr 10;18(2):203-210. Epub 2020 Oct 10.

Esophageal Surgery Division, National Cancer Center Hospital East, Chiba, Japan.

Background: Robotic-assisted esophagectomy is still in the implementation phase. Robotic surgical systems refine visualization via robotically-enhanced surgical anatomy (RESA), and the stable articulated robotic arms provide precise movements. This prospective feasibility study was conducted to evaluate robotic esophagectomy with total mediastinal lymphadenectomy using four robotic arms exclusively (RETML-4).

Methods: The inclusion criterion was clinical stage I-IIIB esophageal cancer with stable general condition. Patients were positioned hemi-prone with single-lung ventilation, and the operation table was tilted until the patient was prone. The first, second, third, and fourth robotic ports were inserted into the ninth intercostal space (ICS) on the angulus inferior scapulae line, seventh ICS on the posterior axillary line, and the fifth and third ICS on the mid-axillary line, respectively. RETML-4 was performed by precise sharp dissection in wide stable operation fields, with countertraction created by a tip-up fenestrated grasper with gauze. Esophagectomy was performed separately for the middle to lower, and upper esophagus. After mobilizing the middle to lower esophagus and performing lymph node dissection, the upper esophagus was mobilized, with bilateral lymph node dissection along the recurrent laryngeal nerves. The assistant surgeon was involved only during removing gauze and collecting harvested lymph nodes in the thorax.

Results: RETML-4 was performed in all ten patients enrolled in 2018. The median postoperative hospital stay was 15 days, and the complication rate was 60%. Nine cases achieved R0 resection. Recurrence occurred in two cases.

Conclusions: RETML-4 is feasible, and may facilitate minimally invasive esophagectomy by providing precise instrument movements and RESA.
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http://dx.doi.org/10.1007/s10388-020-00788-9DOI Listing
April 2021

Novel universally applicable technique for performing bilateral transcervical mediastinoscopic-assisted transhiatal laparoscopic esophagectomy: a truly minimally invasive procedure.

Surg Endosc 2021 09 28;35(9):5186-5192. Epub 2020 Sep 28.

Esophageal Surgery Division, National Cancer Hospital East, Chiba, Japan.

Background: The procedure of mediastinoscopic-assisted transhiatal esophagectomy (MATE) is only performed in a few institutions, despite this being the ultimate form of minimally invasive surgery for performing esophagectomy for esophageal and esophagogastric cancer in that it entails no chest wall trauma. We have developed a novel, universally applicable, surgical procedure for performing bilateral transcervical mediastinoscopic-assisted transhiatal laparoscopic esophagectomy (BTC-MATLE) that is an improvement on standard MATE surgery for esophageal and esophagogastric cancer.

Methods: The patient is placed in a supine position under general anesthesia with bilateral lung ventilation. BTC-MATLE combined with mediastinoscopic and transhiatal laparoscopic esophagectomy with total mediastinal lymph node dissection are performed synchronously. After lymph node dissection along both recurrent laryngeal nerves through bilateral cervical skin incisions, bilateral transcervical mediastinoscopic esophagectomy is performed to avoid collision outside the cervical region and ensure operability even in patients with narrow mediastimun. Laparoscopic gastric mobilization and subsequent lower esophageal mobilization meet the bilateral transcervical mediastinoscopic esophagectomy at the border of the middle and lower third of the esophagus. The gastric tube is pulled up into the cervical region via a posterior mediastinal route and anastomosed in the neck.

Results: BTC-MATLE was performed on 16 high-risk patients (Charlson Comorbidity Index ≥ 3 in 14 patients and two octogenarians with complex comorbidities). Median operation time and postoperative hospital stay were 231 min and 15 days, respectively. R0 resection was achieved in 15 patients (94%), and there were no in-hospital deaths.

Conclusions: BTC-MATLE, a procedure for performing minimally invasive esophagectomy, is likely to become the applicable form of MATE surgery for esophageal and esophagogastric cancer, even in high-risk patients because it is truly minimally invasive and has excellent short-term outcomes.
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http://dx.doi.org/10.1007/s00464-020-08012-6DOI Listing
September 2021

Novel minimally invasive approach to lymph node dissection around the left renal vein in patients with esophagogastric junction cancer.

Esophagus 2021 Apr 27;18(2):420-423. Epub 2020 Sep 27.

Division of Esophageal Surgery, National Cancer Center Hospital East, Chiba, Japan.

The left renal vein lymph node (LRVLN) may be the extended locoregional node in esophagogastric junction cancer; however, only open-surgical methods of dissection have been reported. We therefore developed a novel minimally invasive laparoscopic method for LRVLN dissection. Following esophagectomy, the stomach was mobilized and LRVLN dissection was started by taping the pancreatic body using two silicone drains. The transverse mesocolon was then retracted through the superior duodenal fossa to expose the horizontal duodenum and permit LRVLN dissection. We carried out the procedure successfully in 17 patients with advanced esophagogastric cancer. The median total and laparoscopic operative times were 415 and 161 min, respectively. Postoperative esophagectomy-related complications occurred in six patients. The median estimated blood loss was 120 ml and hospital stay was 15 days. This minimally invasive laparoscopic LRVLN dissection method was safe and effective, and may support faster recovery and earlier postoperative adjuvant therapy in patients with esophagogastric junction cancer.
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http://dx.doi.org/10.1007/s10388-020-00786-xDOI Listing
April 2021

Yokukansan for Treatment of Preoperative Anxiety and Prevention of Postoperative Delirium in Cancer Patients Undergoing Highly Invasive Surgery. J-SUPPORT 1605 (ProD Study): A Randomized, Double-Blind, Placebo-Controlled Trial.

J Pain Symptom Manage 2021 01 12;61(1):71-80. Epub 2020 Aug 12.

Department of Psycho-Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan; Behavioral Sciences and Survivorship Research Group, Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, Chuo-ku, Tokyo, Japan; Innovation Center for Supportive, Palliative and Psychosocial Care, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan. Electronic address:

Context: No standard preventive or therapeutic methods have been established for preoperative anxiety and postoperative delirium in patients with cancer.

Objectives: To clarify the therapeutic effect of yokukansan for perioperative psychiatric symptoms in patients with cancer as well as to confirm its safety profile.

Methods: This is a randomized, double-blind, and placebo-controlled trial conducted at a single center in Tokyo, Japan. About 195 patients with cancer scheduled to undergo tumor resection took one packet of the study drug, which was administered orally. Coprimary outcomes were change in preoperative anxiety assessed with the Hospital Anxiety and Depression Scale-Anxiety and incidence of postoperative delirium assessed with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Interim analysis was performed with one-third (n = 74) of the target number of registered patients.

Results: Because this trial was canceled based on the results of the interim analysis and the protocol treatment was discontinued in patients who were already registered, conclusions were based on the full analysis set of 160 participants. There were no significant differences between groups in the change of mean Hospital Anxiety and Depression Scale-Anxiety score (intervention group [SD] 0.4 [3.0] vs. placebo group 0.5 [3.0]; P = 0.796) or the incidence of postoperative delirium (32% vs. 30%; P = 0.798). There were no serious adverse events in either group.

Conclusion: In patients with cancer undergoing highly invasive surgeries, yokukansan demonstrated no significant efficacy for the treatment of preoperative anxiety or the prevention of postoperative delirium. Yokukansan is already used in daily practice in Japan, but we should be careful with its future use.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.07.009DOI Listing
January 2021

Totally Mechanical Collard Technique for Cervical Esophagogastric Anastomosis Reduces Stricture Formation Compared with Circular Stapled Anastomosis.

World J Surg 2020 Dec 11;44(12):4175-4183. Epub 2020 Aug 11.

Division of Esophageal Surgery, National Cancer Center Hospital East, Chiba, Japan.

Background: The optimal technique for cervical esophagogastric anastomosis in esophagectomy has not yet been established. Using circular stapled (CS) technique effectively reduces the incidence of anastomotic leakage and shortens the operating time; however, anastomotic stricture has been reported to be more common. The present study was performed to compare the clinical outcomes of the recently developed totally mechanical Collard (TMC) and CS anastomosis.

Methods: We retrospectively reviewed consecutive esophageal cancer cases who are undergoing transthoracic extended esophagectomy with gastric conduit reconstruction using cervical CS or TMC anastomosis from December 2013 to December 2016. Propensity score matching and multivariate regression were used to adjust for differences in baseline characteristics.

Results: Among 313 patients, 93 underwent CS anastomosis and 220 underwent TMC anastomosis. Stricture formation occurred in 59 patients (18.8%), significantly more often with the CS than TMC anastomosis (30.1% vs. 14.1%, p = 0.001). No significant differences were observed in the refractory stricture rate (9.7% vs. 5.0%, p = 0.134) or the anastomotic leakage rate (11.8% vs. 10.9%, p = 0.845) between the two groups. The propensity score matching cohort study including 86 pairs of patients confirmed a significantly lower stricture formation rate with the TMC than CS technique (27.9% vs. 14.0%, p = 0.038). In the multivariable analysis, anastomotic leakage, the CS technique, and a body mass index of ≥25 mg/m were independently associated with a risk of stricture formation.

Conclusion: TMC technique contributed to a reduced rate of stricture formation compared with CS technique in cervical esophagogastric anastomosis.
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http://dx.doi.org/10.1007/s00268-020-05729-2DOI Listing
December 2020

ABCB1 and ABCC2 genetic polymorphism as risk factors for neutropenia in esophageal cancer patients treated with docetaxel, cisplatin, and 5-fluorouracil chemotherapy.

Cancer Chemother Pharmacol 2020 08 3;86(2):315-324. Epub 2020 Aug 3.

Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.

Purpose: The combination of docetaxel, cisplatin and 5-fluorouracil (DCF) is a newly developed chemotherapy regimen for esophageal cancer. Severe neutropenia is dose-limiting toxicity of docetaxel and it is well known to be frequently occurred during DCF chemotherapy. This study aimed to investigate the relationship between severe neutropenia and genetic polymorphisms in patients treated with preoperative DCF chemotherapy.

Methods: A total of 158 patients were investigated for their absolute neutrophil count (ANC) within the first cycle of DCF chemotherapy at the National Cancer Center (NCC) Hospital East. DNA samples obtained from the NCC Biobank Registry were used for the analysis of nine genetic polymorphisms related to docetaxel pharmacokinetics. These genotypes were evaluated for their association with severe neutropenia, and further their risk factors were examined using a multivariate logistic regression.

Results: A total 81 (51.3%) patients developed severe neutropenia. Multivariate analysis revealed that age (OR 1.054; CI 1.008-1.102, P = 0.022), baseline ANC (OR 1.019; CI 1.002-1.037, P = 0.030), ABCB1 3435C>T (OR 2.191; CI 1.087-4.417, P = 0.028) and ABCC2 *+9383C>G (OR 2.342; CI 1.108-4.948, P = 0.026) were significant risk factors for severe neutropenia development. The results from this study showed that age, ANC, ABCB1 3435C>T, and ABCC2 *+9383 G>C increased the incidence of severe neutropenia with the number of identified risk factors.

Conclusions: In addition to age and baseline ANC, ABCB1 3435C>T and ABCC2 *+9383C>G were identified as independent predictors for severe neutropenia in esophageal cancer patients treated with DCF chemotherapy.
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http://dx.doi.org/10.1007/s00280-020-04118-9DOI Listing
August 2020

Lymph node dissection and recurrent laryngeal nerve protection in minimally invasive esophagectomy.

Ann N Y Acad Sci 2020 12 15;1481(1):20-29. Epub 2020 Jul 15.

Department of Thoracic Surgery, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Until now, neoadjuvant therapy plus surgical resection of the primary tumor and potential metastatic lymph nodes (LNs) has been the current optimal treatment for locally advanced thoracic esophageal cancer (EC). LN metastasis is one of the most negative prognostic factors for thoracic esophageal squamous cell carcinoma (ESCC). However, the extent of LN dissection for thoracic ESCC has long been controversial worldwide. LNs along the recurrent laryngeal nerve (RLN) were reported to have the highest frequency of metastases in thoracic ESCC, so lymphadenectomy along the bilateral RLN is necessary but quite challenging because of a high frequency of recurrent nerve palsy and related postoperative complications. With the development of minimally invasive devices and techniques in recent years, minimally invasive esophagectomy (MIE) has been widely applied in EC surgery. The topics of what the optimal extent of lymphadenectomy is and how the recurrent nerve should be well protected during MIE have been debated in recent years. The purpose of our review is specifically to address the patterns of LN metastasis, the extent of LN dissection, and the protection of the RLN in MIE for thoracic ESCC.
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http://dx.doi.org/10.1111/nyas.14427DOI Listing
December 2020

Minimally invasive hybrid surgery: A salvage tumor enucleation for local recurrence of thoracic esophageal carcinoma after definitive chemoradiotherapy.

Asian J Endosc Surg 2021 Jan 6;14(1):77-80. Epub 2020 Jul 6.

Esophageal Surgery Division, National Cancer Center Hospital, Tokyo, Japan.

Local recurrence after definitive chemoradiation for esophageal carcinoma is associated with poor outcomes. Although salvage esophagectomy is a standard treatment that offers a chance of long-term survival, the procedure is associated with high morbidity and mortality. Minimally invasive hybrid surgery (MIHS) employs thoracoscopic and esophagoscopic procedures and is generally used to treat benign esophageal submucosal tumors. A 64-year-old man with thoracic esophageal carcinoma experienced local relapse after definitive chemoradiation. He underwent MIHS and was discharged 18 days after surgery with a slight degree of stricture. Pathological findings revealed squamous cell carcinoma with no residual tumor in the resection margins, and the patient remains free from cancer relapse 24 months after surgery. Here, we report the findings in this patient, in whom MIHS was successfully performed as a salvage tumor enucleation for local recurrence of esophageal carcinoma after definitive chemoradiotherapy.
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http://dx.doi.org/10.1111/ases.12830DOI Listing
January 2021

Updates in the 8th edition of the TNM staging system for esophagus and esophagogastric junction cancer.

Jpn J Clin Oncol 2020 Aug;50(8):847-851

Department of Head and Neck Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.

The tumor-node metastasis (TNM) classification, originally developed in 1943 and subsequently adopted by the Union for International Cancer Control and the American Joint Committee on Cancer, is regularly updated based on new information and developments. The TNM classification system is the main tool used for both clinical and pathological staging of cancers worldwide. The 8th edition of the TNM classification for esophageal and esophagogastric junction (EGJ) cancer, released in 2017, was updated from the 7th edition based on additional data supplied by the Worldwide Esophageal Cancer Collaboration group. We summarize the main changes between the 7th and 8th editions of this TNM classification. Notable changes included separate clinical, pathological and pathological prognostic staging for adenocarcinomas and squamous cell carcinomas. Pathological prognostic staging was also improved by updating the T- and N-factors regarding histopathological differentiation and tumor location, respectively. The definition of EGJ cancer was changed from tumors centered within 5 cm to tumors within 2 cm of the EGJ. These updates to the TNM classification will help to improve the personalized management and treatment of patients with esophageal and EGJ cancers.
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http://dx.doi.org/10.1093/jjco/hyaa082DOI Listing
August 2020

Distribution of lymph node metastases in locally advanced adenocarcinomas of the esophagogastric junction (cT2-4): comparison between Siewert type I and selected Siewert type II tumors.

Langenbecks Arch Surg 2020 Jun 8;405(4):509-519. Epub 2020 Jun 8.

Department of Esophageal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku Tokyo, 104-0045, Japan.

Introduction: The distribution of lymph node metastases in locally advanced Siewert type I and type II AEG (adenocarcinoma of the esophagogastric junction) remains unclear. The diversity of data in the literature reflects the non-uniformity of tumor stages and surgical procedures in previous studies.

Materials And Methods: Based on a retrospective analysis from our single-center database, we examined distributions of lymph node metastases in types I and II cT2-4 AEG. The dataset comprised 44 patients; 19 and 25 patients had type I and type II, respectively. All patients underwent subtotal esophagectomy and total mediastinal lymphadenectomy, which included dissection of the upper mediastinal lymph nodes. The histological data of the surgical specimens were analyzed to evaluate metastasis rates in each lymph node station according to the Japanese Esophageal Society (JES) and American Joint Committee on Cancer (AJCC) guidelines.

Results: Lymph node metastases were observed in 75.0% cases (n = 33/44). There was no significant difference in the total lymph node metastasis rate between the two groups (type I 73.7% versus type II 76.0%). On comparing each lymph node region separately, no statistically significant differences were noted between the groups: upper mediastinal (type I 31.6% versus type II 24.0%), middle and lower mediastinal (type I 31.6% versus type II 44.0%), paragastric (type I 61.1% versus type II 76.0%), and celiac lymph nodes (type I 16.7% versus type II 25.0%).

Conclusion: In advanced clinical stages, the metastasis rate is high at all mediastinal lymph node regions in both type I and type II AEGs.
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http://dx.doi.org/10.1007/s00423-020-01894-zDOI Listing
June 2020

Influence of preoperative chemotherapy-induced leukopenia on survival in patients with esophageal squamous cell carcinoma: exploratory analysis of JCOG9907.

Esophagus 2021 Jan 8;18(1):41-48. Epub 2020 Jun 8.

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Background: The relationship between chemotherapy-induced leukopenia (CIL) and survival has not been investigated in patients undergoing preoperative chemotherapy for esophageal squamous cell carcinoma (ESCC). We analyzed the association of CIL with survival outcomes using data from JCOG9907 on the efficacy of preoperative chemotherapy for stage II/III ESCC.

Methods: Preoperative chemotherapy consisted of two courses of 5-FU (800 mg/m days 1-5) and cisplatin (80 mg/m day 1) repeated every 3 weeks. Patients in the preoperative chemotherapy arm receiving at least one course of chemotherapy and undergoing subsequent surgery in JCOG9907 were divided into two subgroups: CIL ( +), those with grade 2-4 leukopenia at least once during preoperative chemotherapy; and CIL (-), those with grades 0-1. The association of CIL with overall survival (OS) and progression-free survival (PFS) was analyzed.

Results: Among 164 patients enrolled in JCOG9907, 152 patients were included in this analysis, 52 in CIL ( +) and 100 patients in CIL (-) subgroups. The 3-year OS for CIL ( +) was inferior to that for CIL (-) (48.1% vs. 73.9%); hazard ratio (HR) = 1.94 (95% CI 1.18-3.16, P < .01). For 3-year PFS, a similar tendency was observed (44.2% vs. 55.8%; HR = 1.38 (95% CI 0.88-2.17, P = .16). Multivariable analysis revealed that CIL was not an independent factor for OS (HR = 1.14, 95% CI 0.63-2.07, P = .67).

Conclusion: We showed that CIL during preoperative chemotherapy might not be a prognostic factor in patients with ESCC.
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http://dx.doi.org/10.1007/s10388-020-00752-7DOI Listing
January 2021

Handgrip Strength Predicts Postoperative Pneumonia After Thoracoscopic-Laparoscopic Esophagectomy for Patients with Esophageal Cancer.

Ann Surg Oncol 2020 Sep 4;27(9):3173-3181. Epub 2020 Jun 4.

Division of Esophageal Surgery, National Cancer Center Hospital, Tokyo, Japan.

Background: Despite advances in minimally invasive surgery, postoperative pneumonia after esophagectomy remains a frequent complication. Sarcopenia, defined as low muscle strength and quantity, has been associated with adverse surgical outcomes in numerous cancers. The recent definition and diagnostic criteria for sarcopenia have emphasized muscle strength rather than muscle quantity as the primary indicator of sarcopenia, although most studies have focused only on muscle quantity. This study aimed to determine the association of muscle strength and quantity with postoperative pneumonia after thoracoscopic-laparoscopic esophagectomy (TLE).

Methods: This retrospective, single-center, observational study investigated 161 men undergoing TLE for esophageal cancer between May 2017 and October 2019. Handgrip strength (HGS) and skeletal muscle mass index (SMI) were used respectively as proxy for muscle strength and quantity. The SMI was assessed using preoperative computed tomography at the L3 vertebral level. Predictors of postoperative pneumonia were determined using multivariate analysis.

Results: The study subjects had TLE performed for squamous cell carcinoma (n = 131), adenocarcinoma (n = 24), and other cancers (n = 6). Postoperative pneumonia developed in 28 patients (17.4%). In the multivariate analysis, HGS was significantly associated with postoperative pneumonia (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.08-1.35; p = 0.001]. No association was found between SMI and postoperative pneumonia (p = 0.964). Comparison of the areas under the receiver operating characteristic curves for postoperative pneumonia prediction showed that the value for HGS was significantly higher than for SMI (0.79 vs 0.65, respectively; p = 0.012).

Conclusions: Low HGS was a significant predictor of postoperative pneumonia after TLE for esophageal cancer.
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http://dx.doi.org/10.1245/s10434-020-08520-8DOI Listing
September 2020

Feasibility study of nivolumab as neoadjuvant chemotherapy for locally esophageal carcinoma: FRONTiER (JCOG1804E).

Future Oncol 2020 Jul 12;16(19):1351-1357. Epub 2020 May 12.

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

One of the standard treatments of resectable esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemotherapy followed by surgery. Nivolumab showed efficacy for metastatic ESCC. However, the safety and efficacy of neoadjuvant nivolumab with chemotherapy for ESCC is unknown. Therefore, we will conduct FRONTiER to evaluate the safety and efficacy of nivolumab adding to neoadjuvant chemotherapy. FRONTiER comprises four experimental cohorts: (A) including nivolumab plus 5-FU+CDDP (cisplatin and 5-fluorouracil [CF]); (B) including one prior administration of nivolumab and the cohort A regimen; (C) including nivolumab plus docetaxel+ CF; (D) including one prior administration of nivolumab and the cohort C regimen; an expanded cohort. The primary end point is the incidence of dose-limiting toxicities from the initial dose to the 30th postoperative day. NCT03914443.
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http://dx.doi.org/10.2217/fon-2020-0189DOI Listing
July 2020

Efficacy of prewarming prophylaxis method for intraoperative hypothermia during thoracoscopic esophagectomy.

Esophagus 2020 10 8;17(4):385-391. Epub 2020 May 8.

Esophageal Surgery Division, Department of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Background: This study was performed to elucidate the clinical efficacy of the prewarming prophylaxis method for intraoperative hypothermia during thoracoscopic esophagectomy for esophageal cancer.

Methods: We enrolled 100 consecutive patients with esophageal cancer. Two patients in the prewarming group could not undergo thoracoscopic esophagectomy because of conversion to thoracotomy. The intraoperative core temperature was measured in 50 and 48 patients classified into the control and prewarming groups, respectively. Patients in the prewarming group wore a Bair Hugger warming gown (3 M, Maplewood, MN, USA) in the ward for 30 min before entering the operation room. The primary outcome measure was the difference in the intraoperative body core temperature between the control and prewarming groups, and the secondary outcome measure was the difference in postoperative infectious complications between the control and prewarming groups.

Results: The intraoperative core temperature was significantly different between the two groups at each 30-min time point from the starting of operation to the ending of the thoracic procedure (P < 0.001). The incidence of infectious surgical complications was not significantly different between the control and prewarming groups (30.0% vs. 14.6%, respectively; P = 0.11).

Conclusion: The prewarming prophylaxis method was effective for maintaining normothermia during thoracoscopic esophagectomy.
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http://dx.doi.org/10.1007/s10388-020-00743-8DOI Listing
October 2020

CD24 and CK4 are upregulated by SIM2, and are predictive biomarkers for chemoradiotherapy and surgery in esophageal cancer.

Int J Oncol 2020 03 17;56(3):835-847. Epub 2020 Jan 17.

Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Kashiwa, Chiba 277‑8577, Japan.

Definitive chemoradiotherapy (CRT) is a less invasive therapy compared with surgery for some types of cancer; however, the 5‑year survival rate of patients with stages II‑III esophageal squamous cell carcinoma (ESCC) is only 37%. Therefore, prediction of CRT responders is necessary. Unfortunately, no definitive biomarker exists that is useful to predict survival outcome following CRT. From our previous microarray study, CD24 and keratin 4 (KRT4), which encodes cytokeratin 4 (CK4), were overexpressed in the favorable prognostic epithelial subtype with SIM bHLH transcription factor 2 (SIM2) expression. This study investigated the association between their mRNA and protein expression levels, and clinicopathological characteristics, and also investigated the functions of CD24 in SIM2‑mediated tumor differentiation and CRT sensitivity. High CD24 and KRT4 mRNA expression was associated with a favorable prognosis following CRT. Multivariate analyses revealed that high CD24 and CK4 protein expression, as determined by immunohistochemistry, and differentiated type were independent factors for predicting a favorable prognosis in response to CRT. Notably, in cases with low CD24 or CK4, surgery was suggested to be a good therapeutic modality compared with CRT. CD24 and KRT4 were expressed preferentially in differentiated layers of the normal esophageal mucosa, and their mRNA expression in 3D cultured ESCC cells was induced by SIM2 transfection, thus suggesting that CD24 and KRT4 were downstream differentiation markers of SIM2. Furthermore, CD24 small interfering RNA increased the mRNA expression levels of superoxide dismutase 2 and enhanced H2O2 resistance, thus indicating the involvement of CD24 in the radiosensitivity of patients with ESCC; however, it had no effect on cisplatin sensitivity. In conclusion, the two markers CD24 and CK4 may be considered predictive biomarkers for definitive CRT.
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http://dx.doi.org/10.3892/ijo.2020.4963DOI Listing
March 2020

Lymphangiography and focal pleurodesis treatment of chylothorax with an aberrant thoracic duct following oesophagectomy: a case report.

Surg Case Rep 2019 Dec 11;5(1):195. Epub 2019 Dec 11.

Department of Esophageal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Background: Management of postoperative chylothorax usually consists of nutritional regimens, pharmacological therapies such as octreotide, and surgical therapies such as ligation of thoracic duct, but a clear consensus is yet to be reached. Further, the variation of the thoracic duct makes chylothorax difficult to treat. This report describes a rare case of chylothorax with an aberrant thoracic duct that was successfully treated using focal pleurodesis through interventional radiology (IVR).

Case Presentation: The patient was a 52-year-old man with chylothorax after a thoracoscopic oesophagectomy for oesophageal cancer. With conventional therapy, such as thoracostomy tube, octreotide or fibrogammin, a decrease in the amount of chyle was not achieved. Therefore, we performed lymphangiography and pleurodesis through IVR. The patient appeared to have an aberrant thoracic duct, as revealed by magnetic resonance imaging (MRI); however, after focal pleurodesis, the leak of chyle was diminished, and the patient was discharged 66 days after admission.

Conclusions: Chylothorax remains a difficult complication. Focal pleurodesis through IVR can be one of the options to treat chylothorax.
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http://dx.doi.org/10.1186/s40792-019-0709-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906276PMC
December 2019

Clinical outcomes of locally advanced esophageal neuroendocrine carcinoma treated with chemoradiotherapy.

Cancer Med 2020 01 3;9(2):595-604. Epub 2019 Dec 3.

Esophageal Surgery Division, National Cancer Center Hospital, Tokyo, Japan.

Background: Neuroendocrine carcinoma (NEC) arising from the esophagus (EsoNEC) is extreme rare, accounting for approximately 1% of esophageal cancer. Even for localized NEC, multidisciplinary approach including chemotherapy is recommended in treatment guidelines because of its high rates of systemic recurrence. However, it is controversial whether adding surgery or radiotherapy is appropriate local treatment for EsoNEC. There have been few reports regarding the clinical outcomes of definitive chemoradiotherapy (dCRT) for EsoNEC. The purpose of this study was to clarify the survival outcome of patients with locally advanced EsoNEC treated with dCRT.

Methods: Clinical outcomes, feasibility, and prognostic factors of patients with locally advanced EsoNEC treated with radiotherapy (60 Gy/30 fraction) in combination with platinum plus etoposide (CE-RT) or cisplatin plus 5-fluorouracil (CF-RT) at the National Cancer Center Hospital from 2001 to 2017 were retrospectively analyzed.

Results: A total of 22 patients were identified as the subjects of this study. The overall response rate and clinical complete remission rate in all patients were 86.4% and 77.3%, respectively. The median progression-free survival and median survival time in all patients were 12.7 and 37.5 months, associated with a 5-year survival rate of 45.4%. Patients treated with CE-RT experienced more hematological adverse events, especially in neutropenia (≥grade 3) and febrile neutropenia(≥grade 3), but achieved more long-term progression-free survival than with CF-RT.

Conclusions: Definitive chemoradiotherapy can be considered as an important treatment option for locally advanced esophageal neuroendocrine carcinoma.
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http://dx.doi.org/10.1002/cam4.2708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970034PMC
January 2020

Relationship between the immune microenvironment of different locations in a primary tumour and clinical outcomes of oesophageal squamous cell carcinoma.

Br J Cancer 2020 02 25;122(3):413-420. Epub 2019 Nov 25.

Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.

Background: Tumour microenvironments can differ according to intratumoural locations. We investigated the immune status at different locations in primary tumours and its clinical significance in oesophageal squamous cell carcinoma (ESCC).

Methods: The number of CD8 tumour-infiltrating immune cells (TIICs) and PD-1 TIICs, and PD-L1 expression on tumour cells (PD-L1) were immunohistochemically examined in the surface (Surf), centre (Cent) and invasive front (Inv) of tumours surgically resected from 192 patients with ESCC.

Results: The PD-L1 rate was lower in Inv than in Cent (12.0% vs. 18.2%, P = 0.012), although the numbers of CD8 TIICs and PD-1 TIICs were comparable among intratumoural locations. High numbers of CD8 and PD-1 TIICs and positive PD-L1 were related to better overall survival (OS) only in Surf and Cent (CD8: P = 0.012 in Surf, 0.018 in Cent, and 0.165 in Inv; PD-1: P = 0.028 in Surf, 0.021 in Cent, and 0.208 in Inv; and PD-L1: 0.044 in Surf, 0.026 in Cent, and 0.718 in Inv). Positive PD-L1 in Surf and/or Cent but not in Inv demonstrated a strong tendency toward better OS (P = 0.053).

Conclusions: Immune microenvironments according to the intratumoural location have different effects on the survival of patients with ESCC.
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http://dx.doi.org/10.1038/s41416-019-0622-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000821PMC
February 2020
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