Publications by authors named "Takashi Oshima"

256 Publications

The Prognostic Value of Lymph Node Ratio in Locally Advanced Esophageal Cancer Patients Who Received Neoadjuvant Chemotherapy.

Ann Surg Oncol 2021 Jun 10. Epub 2021 Jun 10.

Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.

Background: The lymph node (LN) ratio (LNR) has been proposed as a sensitive prognosticator in patients with esophageal squamous cell carcinoma (ESCC), especially when the number of LNs harvested is insufficient. We investigated the association between the LNR and survival in patients with locally advanced ESCC who received neoadjuvant chemotherapy (NAC) and explored whether the LNR is a prognosticator in these patients when stratified by their response to NAC.

Methods: We retrospectively reviewed 199 locally advanced ESCC patients who received curative resection after NAC between January 2011 and December 2019. The predictive accuracy of the adjusted X-tile cut-off values for LNR of 0 and 0.13 was compared with that in the Union for International Cancer Control pathological N (UICC pN) categories. The association between survival rate and clinicopathological features was examined.

Results: Multivariate analysis identified that the LNR was an independent risk factor for recurrence-free survival [RFS; hazard ratio (HR) 6.917, p < 0.001] and overall survival (OS) (HR 4.998, p < 0.001). Moreover, even when stratified by response to NAC, the LNR was a significant independent risk factor for RFS and OS (p < 0.001). The receiver operating characteristic curves identified that the prognostic accuracy of the LNR tended to be better than that of the UICC pN factor in all cases and responders.

Conclusion: The LNR had a significant prognostic value in patients with locally advanced ESCC, including in those who received NAC.
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http://dx.doi.org/10.1245/s10434-021-10240-6DOI Listing
June 2021

Machine-learning model derived gene signature predictive of paclitaxel survival benefit in gastric cancer: results from the randomised phase III SAMIT trial.

Gut 2021 May 12. Epub 2021 May 12.

Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore

Objective: To date, there are no predictive biomarkers to guide selection of patients with gastric cancer (GC) who benefit from paclitaxel. Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) was a 2×2 factorial randomised phase III study in which patients with GC were randomised to Pac-S-1 (paclitaxel +S-1), Pac-UFT (paclitaxel +UFT), S-1 alone or UFT alone after curative surgery.

Design: The primary objective of this study was to identify a gene signature that predicts survival benefit from paclitaxel chemotherapy in GC patients. SAMIT GC samples were profiled using a customised 476 gene NanoString panel. A random forest machine-learning model was applied on the NanoString profiles to develop a gene signature. An independent cohort of metastatic patients with GC treated with paclitaxel and ramucirumab (Pac-Ram) served as an external validation cohort.

Results: From the SAMIT trial 499 samples were analysed in this study. From the Pac-S-1 training cohort, the random forest model generated a 19-gene signature assigning patients to two groups: Pac-Sensitive and Pac-Resistant. In the Pac-UFT validation cohort, Pac-Sensitive patients exhibited a significant improvement in disease free survival (DFS): 3-year DFS 66% vs 40% (HR 0.44, p=0.0029). There was no survival difference between Pac-Sensitive and Pac-Resistant in the UFT or S-1 alone arms, test of interaction p<0.001. In the external Pac-Ram validation cohort, the signature predicted benefit for Pac-Sensitive (median PFS 147 days vs 112 days, HR 0.48, p=0.022).

Conclusion: Using machine-learning techniques on one of the largest GC trials (SAMIT), we identify a gene signature representing the first predictive biomarker for paclitaxel benefit.

Trial Registration Number: UMIN Clinical Trials Registry: C000000082 (SAMIT); ClinicalTrials.gov identifier, 02628951 (South Korean trial).
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http://dx.doi.org/10.1136/gutjnl-2021-324060DOI Listing
May 2021

Potential Benefits of Minimally Invasive Laparoscopy in Reducing Local Recurrence After Surgery for Low Rectal Cancer.

Anticancer Res 2021 May;41(5):2617-2623

Department of Surgery, Yokohama City University, Yokohama, Japan.

Aim: To compare the mid-term oncological results between patients with low rectal cancer who underwent minimally invasive laparoscopic surgery (MILS) and those who underwent open surgery (OS).

Patients And Methods: Overall, 262 matched patients who underwent primary resection for low rectal cancer between 2000 and 2019 were divided into MILS (n=131; n=107, conventional laparoscopic surgery; n=24, robotic surgery) and OS (n=131) groups. The short- and mid-term outcomes were compared.

Results: Similar baseline characteristics were noted. The operative time was longer and blood loss was lesser in the MILS group; the conversion rate was 3.8%. The incidence of postoperative complications was similar. The 2-year cumulative incidence of local recurrence was noted to be much lower in the MILS group (1.9%) than in the OS group (8.4%). MILS had a significantly low hazard ratio (0.208, p=0.036).

Conclusion: MILS has potential benefits in reducing local recurrence of low rectal cancer.
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http://dx.doi.org/10.21873/anticanres.15042DOI Listing
May 2021

Clinical Significance of Stanniocalcin2 mRNA Expression in Patients With Colorectal Cancer.

Anticancer Res 2021 Apr;41(4):2117-2122

Department of Gastrointestinal Surgery, Kanagawa Cancer Centre, Yokohama, Japan;

Background/aim: Stanniocalcin2 (STC2) is associated with proliferation, invasion, and metastasis in various cancers. We examined the clinical significance of STC2 mRNA expression in patients with colorectal cancer (CRC).

Patients And Methods: Relative expression levels of STC2 mRNA in CRC tissues and corresponding normal mucosa obtained from 202 patients were measured using quantitative real-time reverse transcriptase-polymerase chain reaction.

Results: Expression of STC2 mRNA was higher in the cancer tissue than in the adjacent normal mucosa. STC2 mRNA expression in cancer tissues was associated with tumour size, liver metastasis, venous invasion, and lymph node metastasis. High expression of STC2 mRNA was significantly associated with poorer postoperative survival (p=0.0003). Multivariate analysis showed that high expression of STC2 mRNA was an independent predictor of postoperative survival.

Conclusion: High expression of STC2 mRNA in CRC tissue may be a useful prognostic marker in patients with CRC.
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http://dx.doi.org/10.21873/anticanres.14983DOI Listing
April 2021

Short-Term Outcomes from a Randomized Screening Phase II Non-inferiority Trial Comparing Omentectomy and Omentum Preservation for Locally Advanced Gastric Cancer: the TOP-G Trial.

World J Surg 2021 Jun 10;45(6):1803-1811. Epub 2021 Feb 10.

Department of Surgery, Fujisawa Shonandai Hospital, Fujisawa, Japan.

Background: Omentectomy is considered an essential part of curative gastrectomy for locally advanced gastric cancer (GC), albeit without solid evidence. We conducted a randomized phase II trial (the TOP-G trial) comparing omentectomy and omentum preservation for gastric cancer. This report describes the short-term findings regarding the trial's secondary endpoints.

Methods: The trial protocol was submitted to the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ : UMIN000005421). The key eligibility criteria were histologically confirmed cT2-4a and N0-2 gastric adenocarcinoma. Short-term surgical outcomes, including morbidity and mortality, were compared between the omentectomy group (group A, control arm) and the omentum-preserving surgery group (group B, test arm). All procedures were performed via an open approach. Based on a non-inferiority margin of 7%, statistical power of 0.7, and type I error of 0.2, the sample size was set to 250 patients.

Results: A total of 251 patients were eligible and randomized (group A: 125 patients, group B: 126 patients) between April 2011 and October 2018. After excluding patients who had peritoneal metastasis or laparotomy history, safety outcomes were analyzed for 247 patients. Group A had a significantly longer median operation time (225 min vs. 204 min, p = 0.022) and tended to have greater median blood loss (260 mL vs. 210 mL p = 0.073). The incidences of morbidity were similar and < 10% in both groups (8% vs. 9%, p = 1.000). There was no mortality in either group.

Conclusions: Operative risk was generally similar between omentectomy and omentum-preserving surgery for locally advanced gastric cancer.
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http://dx.doi.org/10.1007/s00268-021-05988-7DOI Listing
June 2021

Prognostic Factors for Gastric Cancer Patients With One Stage IV Factor who Underwent Conversion Surgery.

Anticancer Res 2021 Feb;41(2):1005-1012

Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan;

Background/aim: To identify prognostic factors for patients with stage IV gastric cancer (GC) and a single stage IV factor before chemotherapy who underwent conversion surgery (R0 resection).

Patients And Methods: This study retrospectively analysed 32 GC patients with a single stage IV factor before chemotherapy and who underwent conversion surgery (R0 resection) between January 2001 and September 2015. The univariate and multivariate analyses were performed to identify independent prognostic factors.

Results: The five-year survival rate was 39.6%, and the median survival time was 47.0 months. In the univariate analysis, diffuse-type according to Lauren classification was significantly associated with worse overall survival (p<0.001). In the multivariate analysis, diffuse-type was selected as an independent prognostic factor (hazard ratio=15.970, 95% confidence interval=3.804-67.043, p<0.001).

Conclusion: Diffuse-type may be a useful prognostic factor in GC patients with a single stage IV factor who undergo conversion surgery (R0 resection).
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http://dx.doi.org/10.21873/anticanres.14855DOI Listing
February 2021

ASO Author Reflections: Pretherapeutic Naples Prognostic Score in Locally Advanced Esophageal Cancer.

Ann Surg Oncol 2021 Jan 28. Epub 2021 Jan 28.

Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.

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http://dx.doi.org/10.1245/s10434-021-09633-4DOI Listing
January 2021

[A Case of Metastatic Small Intestinal Tumor Diagnosed with Intestinal Obstruction].

Gan To Kagaku Ryoho 2020 Dec;47(13):2373-2375

Dept. of Surgery, Yokohama City University Hospital.

A 76-year-old man with a past history of liver transplantation because of liver cirrhosis visited a hospital in October 2018 because of vomiting and abdominal pain. Although the patient underwent conservative medical treatment, no improvement of the symptoms was observed, and he received consultation at our hospital. After thorough examination, and because of the policy of inpatient treatment after the diagnosis of adhesion ileus obstruction post liver transplantation surgery, intestinal decompression was performed using an ileus tube. However, there was no improvement in the symptoms even after inserting the ileus tube, and intestinal obstruction was diagnosed in November 2018. During the preoperative examination, a tumorous shadow was found in the right lung, although it became a policy of scrutiny after improvement of the bowel obstruction. During the laparotomy, a macroscopic tumor exposed on the serosal surface was observed on the anal side at 120 cm from the Treitz ligament, and this site was considered to be the blocking origin. Partial resection of the small intestine including the blockage site was performed. The pathological result revealed the diagnosis of adenosquamous carcinoma. Furthermore, immunostaining was CK7 positive, CK20 negative, TTF-1 negative, and Napsin negative, suggesting the possibility of a metastatic tumor derived from lung cancer. The postoperative course was uneventful, and the patient was discharged on postoperative day 9. On day 30 after surgery, the left pleural effusion increased and pleural effusion cytology revealed a diagnosis of primary lung adenocarcinoma Stage Ⅳ. Considering the patient's PS, it became a best supportive care(BSC)policy after consultation with the family, and it ended on postoperative day 70. Here, we report about a case diagnosed with metastatic small bowel cancer and intestinal obstruction and conduct a literature review.
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December 2020

Preoperative Utility of the Glasgow Prognostic Score on Outcomes of Patients with Locally Advanced Gastric Cancer.

J Gastrointest Cancer 2021 Jan 18. Epub 2021 Jan 18.

Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao Asahi Yokohama, Kanagawa, 241-8515, Japan.

Purpose: To assess the utility of the Glasgow Prognostic Score (GPS) obtained before curative resection for predicting outcomes in patients with advanced gastric cancer (GC).

Methods: This study retrospectively analyzed the outcomes of 337 consecutive patients with GC who underwent curative surgery for locally advanced gastric cancer between January 2003 and June 2014. GPS was assessed within 4 days prior to surgery.

Results: The number of patients with GPS scores of 0, 1, and 2 was 302, 26, and 9, respectively. There was significantly more blood loss during surgery and more postoperative complications in the GPS 1/2 group than in the GPS 0 group. Patients in the GPS 1/2 group had significantly poorer overall survival than those in the GPS 0 group (p = 0.001). On multivariate analysis, GPS 1/2 was identified as an independent factor for poor survival (p = 0.019).

Conclusion: GPS before curative resection might be a useful predictive factor for perioperative complications and survival in locally advanced GC.
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http://dx.doi.org/10.1007/s12029-021-00584-3DOI Listing
January 2021

The Impact of Pretherapeutic Naples Prognostic Score on Survival in Patients with Locally Advanced Esophageal Cancer.

Ann Surg Oncol 2021 Jan 9. Epub 2021 Jan 9.

Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.

Background: Naples prognostic score (NPS) is a scoring system based on albumin, cholesterol concentration, lymphocyte-to-monocyte ratio, and neutrophil-to-lymphocyte ratio reflecting host systemic inflammation, malnutrition, and survival for several malignancies. This study was designed to assess the prognostic significance of NPS in patients with locally advanced esophageal squamous cell carcinoma (ESCC) and to compare its prognostic accuracy with that of other systemic inflammatory and nutritional index.

Methods: We retrospectively examined 165 patients with locally advanced ESCC who underwent neoadjuvant therapy followed by curative resection between January 2011 and September 2019. Patients were divided into three groups based on their NPS before neoadjuvant therapy (Group 0: NPS = 0; Group 1: NPS = 1-2; Group 2: NPS = 3-4). We compared the clinicopathological characteristics and survival rates among the groups.

Results: The 5-year recurrence-free survival (RFS) and overall survival (OS) rates were significantly different between the groups (P < 0.001). The NPS was superior to other systemic inflammatory and nutritional index for predicting prognoses, as determined using area under the curves (P < 0.05). Multivariate analysis demonstrated that the NPS was a significant predictor of poor RFS (Group 1: hazard ratio [HR] 1.897, P = 0.049; Group 2: HR 3.979, P < 0.001) and OS (Group 1: HR 2.152, P = 0.033; Group 2: HR 3.239, P = 0.006).

Conclusions: The present study demonstrated that NPS was an independent prognostic factor in patients with locally advanced ESCC and more reliable and accurate than the other systemic inflammatory and nutritional index.
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http://dx.doi.org/10.1245/s10434-020-09549-5DOI Listing
January 2021

ASO Author Reflections: Lymph Node Staging of Patients with Remnant Gastric Cancer.

Ann Surg Oncol 2021 May 8;28(5):2877-2878. Epub 2021 Jan 8.

Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.

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http://dx.doi.org/10.1245/s10434-020-09492-5DOI Listing
May 2021

Effect of Prognostic Nutrition Index in Gastric or Gastro-oesophageal Junction Cancer Patients Undergoing Nivolumab Monotherapy.

In Vivo 2021 Jan-Feb;35(1):563-569

Department of Gastrointestinal Surgery, Kanagawa Cancer Centre, Yokohama, Japan;

Background/aim: We hypothesised that the prognostic nutrition index (PNI) is useful for evaluating host immunity and response to immune checkpoint inhibitors. We investigated the effect of PNI on nivolumab monotherapy efficacy in advanced or recurrent gastric cancer (GC) or gastro-oesophageal junction cancer (GOC) patients.

Patients And Methods: We retrospectively examined 110 patients, divided them into a high-PNI group and a low-PNI group, and compared treatment efficacy, adverse events (AEs), and survival between the groups.

Results: Median overall survival (OS) was significantly longer in the high-PNI group than in the low-PNI group (205 vs. 109 days; p<0.001). Multivariate analysis revealed that low PNI was an independent risk factor for OS (hazard ratio=2.398; 95% confidence interval=1.384-4.154; p=0.002). The overall response rate and frequency of AEs were not significantly different between the groups.

Conclusion: PNI could be a useful prognostic factor in GC or GOC patients undergoing nivolumab monotherapy.
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http://dx.doi.org/10.21873/invivo.12292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880786PMC
October 2020

Evaluation of Lymph Node Staging Systems as Independent Prognosticators in Remnant Gastric Cancer Patients with an Insufficient Number of Harvested Lymph Nodes.

Ann Surg Oncol 2021 May 3;28(5):2866-2876. Epub 2021 Jan 3.

Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.

Background: The lymph node (LN) ratio (LNR) and the log odds of positive LNs (LODDS) have been proposed as sensitive prognosticators in patients with primary gastric cancer, especially in patients with an insufficient number of harvested LNs. We investigated the association of LNR and LODDS with survival in patients with remnant gastric cancer (RGC) and explored whether these staging methods are prognostic factors in patients with an insufficient number of harvested LNs.

Methods: The present study retrospectively examined 95 patients with RGC who received gastrectomy between January 2000 and December 2018. The patients were classified according to the adjusted X-tile cutoff for LNR and LODDS. The association between survival rates and clinicopathological features was investigated. The predictive accuracy of the LNR and LODDS was compared with that of the Union for International Cancer Control pathological N factor.

Results: Multivariate analysis revealed that the LNR and LODDS were independent risk factors for recurrence-free survival (RFS) [hazard ratio (HR) 2.623, p = 0.020; HR 3.404, p = 0.004, respectively] and overall survival (OS) (HR 3.694, p = 0.003; HR 2.895, p = 0.022, respectively) in patients with RGC. Moreover, even in patients with 15 or fewer harvested LNs, only the LNR was a significant independent risk factor for RFS (HR 21.890, p < 0.001) and OS (HR 6.597, p = 0.002). The receiver operating characteristic curves revealed that the prognostic accuracy of the three methods was comparable (p > 0.05).

Conclusion: LNR has significant prognostic value for patients with RGC, including those with an insufficient number of harvested LNs.
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http://dx.doi.org/10.1245/s10434-020-09433-2DOI Listing
May 2021

The age-adjusted Charlson comorbidity index is an independent prognostic factor in pancreatic cancer patients who receive curative resection followed by adjuvant chemotherapy.

J Cancer Res Ther 2020 Dec;16(Supplement):S116-S121

Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan; Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan.

Background: We investigated the impact of the age-adjusted Charlson comorbidity index (ACCI) on the pancreatic cancer survival and recurrence after curative surgery followed by adjuvant chemotherapy.

Patients And Methods: This study included 155 patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer between 2005 and 2014. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified.

Results: An ACCI of 8 was regarded as the optimum critical point of classification considering the 1-, 3- and 5-year survival rates. The OS rates at 3 and 5 years after surgery were 25.7% and 19.0% in the ACCI-low group, respectively, and 7.6% and 0% in the ACCI-high group, which amounted to a statistically significant difference (P = 0.019). The RFS rates at 3 and 5 years after surgery were 17.3% and 13.8% in the ACCI-low group, respectively, and 7.1% and 0% in the ACCI-high group, which amounted to a marginally statistically significant difference (P = 0.104). A multivariate analysis showed that the ACCI was a significant independent risk factor for both the OS and RFS.

Conclusions: The ACCI was a risk factor for the OS in patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer. An effective plan is needed for determining the optimum surgical strategy according to the ACCI.
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http://dx.doi.org/10.4103/jcrt.JCRT_440_18DOI Listing
December 2020

Therapeutic results of Denver percutaneous peritoneovenous shunt in cancer patients with malignant ascites.

J Cancer Res Ther 2020 Dec;16(Supplement):S95-S98

Department of Surgery, Yokohama City University, Yokohama, Japan.

Background: Intractable ascites secondary to malignant disease deteriorates patients' quality of life. The purpose of this study was to evaluate the safety and efficacy of percutaneous peritoneovenous (Denver) shunt in treating intractable malignant ascites in cancer patients.

Materials And Methods: Thirty-five patients who had undergone Denver peritoneovenous shunt for the treatment of ascites associated with malignant tumor from October 2014 to 2017 were retrospectively analyzed. The demographic characteristics, laboratory values, and complications were recorded. Univariate and multivariate logistic regression analyses were performed.

Results: The sites of primary tumor were pancreatic cancer in 19 patients, bile duct cancer in 8, gallbladder cancer in 5, breast cancer in 2, and peritoneal malignant mesothelioma in 1. Palliation of abdominal distention was achieved in 29 patients (82.9%). Postoperative complications of Grade 2 or higher were seen in 11 patients (31.4%), and Grade 5 complications were observed in three patients (8.6%). Patients with a high American Society of Anesthesiologists (ASA) grade and high ascites drainage volume had a significantly higher incidence of postoperative complications than a low ASA grade and low ascites drainage volume, and a multivariate logistic analysis showed that the intraoperative ascites drainage volume was an independent risk factor for all complications.

Conclusions: The Denver shunt for malignant ascites is useful for improving patients' quality of life if the indications are selected properly. Drainage of intraoperative ascites was a risk factor for postoperative complications after the Denver shunt technique in cancer patients with malignant ascites. Further experience and discussion are necessary to establish the patient selection criteria.
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http://dx.doi.org/10.4103/jcrt.JCRT_606_18DOI Listing
December 2020

Short-term results of a phase II study of preoperative docetaxel/cisplatin/S-1 therapy for locally advanced gastric cancer.

Jpn J Clin Oncol 2021 Mar;51(3):371-378

Department of Surgery, Yokohama City University, 3-9, Fukuura, Kanazawa-ku, Yokohama City, Kanagawa, 236-0004 Japan.

Background: A multi-institutional phase II study was conducted to evaluate the efficacy and safety of preoperative docetaxel, cisplatin and S-1 therapy in marginally resectable advanced gastric cancer.

Methods: Patients with macroscopic type 4, large macroscopic type 3 and bulky lymph node metastasis received two cycles of preoperative docetaxel, cisplatin and S-1 therapy (docetaxel 40 mg/m2 and cisplatin 60 mg/m2 on day 1, and S-1 80 mg/m2 for 14 days, every 4 weeks). The primary endpoint was the pathological response rate, with an expected value of 65%.

Results: Thirty-one patients were enrolled in this study. The pathological response rate was 54.8%, and it was higher than the threshold value but lower than the expected rate. The R0 resection rate was 93.5%. The frequencies of grade 3-4 toxicities during docetaxel, cisplatin and S-1 therapy were 41.9% for neutropenia, 6.5% for febrile neutropenia and 32.3% for nausea/vomiting. Grade 2 and 3 surgical morbidities occurred in 23.3 and 6.7% of the patients, respectively.

Conclusions: Preoperative docetaxel, cisplatin and S-1 therapy was feasible in terms of chemotherapy-related toxicities and surgical morbidity, but the effect did not achieve the expected value. The association between the pathological response rate and survival will be evaluated in the final analysis of this clinical trial.
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http://dx.doi.org/10.1093/jjco/hyaa221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937420PMC
March 2021

Is sufficient experience performing open gastrectomies necessary to start laparoscopic distal gastrectomy training?

Asian J Endosc Surg 2020 Nov 24. Epub 2020 Nov 24.

Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan.

Introduction: Laparoscopic gastrectomy has become a standard procedure for treatment of gastric cancer, and hence, the opportunity for trainees to perform open gastrectomies may decrease. We investigated whether laparoscopic distal gastrectomy, performed by surgical trainees without sufficient experience performing open gastrectomies, was feasible and safe.

Patients And Methods: We compared short-term outcomes in patients when laparoscopic distal gastrectomies were performed by experienced trainees (ET group; n = 124) and inexperienced trainees (IT group; n = 98) from 2013 to 2019.

Results: The operation time was significantly shorter in the ET group (median time: 253 minutes vs 286 minutes, P < 0.001). The incidence of grade ≥ 2 postoperative complications did not differ significantly between the groups. In the multivariate analysis, experience performing open gastrectomies was not an independent predictor of postoperative complications.

Conclusion: Laparoscopic distal gastrectomies performed by trainees, with insufficient experience performing open gastrectomies, are as feasible and safe as that performed by ET.
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http://dx.doi.org/10.1111/ases.12901DOI Listing
November 2020

Clinical Significance of Tumour CD44v and MIST1 Expression in Patients With Non-small-cell Lung Cancer.

Anticancer Res 2020 Nov;40(11):6407-6416

Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan.

Background: Cancer stem cells (CSCs) are involved in cancer metastasis and relapse. Therefore, identification of CSC biomarkers might help determine the success of a treatment. In this study, we examined the expression of four CSC markers: Cluster of differentiation 44 variant (CD44v), leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), frizzled 7 (FZD7), and muscle, intestine and stomach expression 1 (MIST1), in cancer tissues of patients with non-small-cell lung cancer at >5 years after resection, and its clinical significance.

Patients And Methods: We examined the expression of each CSC marker in 360 patients with NSCLC (n=360) who underwent curative resection by immunohistochemical analysis of tissue microarrays, and determined its relationship with survival.

Results: High expression of MIST1 was related to better overall survival (p<0.05); high CD44v expression was associated with poor overall and recurrence-free survival (p<0.001 for both) and thus, CD44v was defined as an independent prognostic factor (p<0.05), according to a multivariate analysis.

Conclusion: Tumoral CD44v expression might be a useful prognostic marker for patients after curative resection of NSCLC.
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http://dx.doi.org/10.21873/anticanres.14662DOI Listing
November 2020

Prospective analysis of tumor spread to the small bowel mesentery in cases of right-sided colon cancer.

Langenbecks Arch Surg 2020 Dec 21;405(8):1139-1145. Epub 2020 Oct 21.

Department of Surgery, Yokohama City University, Yokohama, 236-0004, Japan.

Purpose: Guidelines advocate minimal ileal resection when right hemicolectomy is performed for right-sided colon cancer. The practice, thought to prevent malabsorption syndrome, does not appear to foster local recurrence. Little evidence based on rigorous study exists, however. To understand the pattern of lymphatic spread of right-sided colon cancer toward the small bowel and thus determine the appropriate margin size, we prospectively investigated anatomical distribution of lymph nodes (LNs) in the small bowel mesentery and of metastasis to these nodes in patients with right-sided colon cancer treated by such surgery.

Methods: In each case, the mesenteric specimen, which had been dissected along the ileocolic vessels and included intermediate LNs, was divided into 2 areas: that 0-3 cm from the vessel pedicle (area 1) and that 3-5 cm from the pedicle (area 2). The peri-intestinal mesentery was cut into 9 segments.

Results: Ninety-one patients were included in the study. Overall, 3366 LNs were dissected. Four hundred fifty-three of these LNs were located in area 1 (90 cases), and 15 (3.3%) were metastatic. Only 63 LNs were located in area 2 (34 cases; average of 0.69 per patient); none was metastatic. Overall, 269 LNs were found in the small bowel mesentery (in 56 of the 91 patients). Only 4 were positive (3 cases), and all were within 5 cm of the ileocecal valve.

Conclusion: Our data indicate that a surgical margin 3 cm from the ileocecal pedicle and a short (5 cm) ileal margin are oncologically reasonable for effective right hemicolectomy.
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http://dx.doi.org/10.1007/s00423-020-02016-5DOI Listing
December 2020

Focal adhesion ribonucleoprotein complex proteins are major humoral cancer antigens and targets in autoimmune diseases.

Commun Biol 2020 10 16;3(1):588. Epub 2020 Oct 16.

Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.

Despite the accumulating evidences of the significance of humoral cancer immunity, its molecular mechanisms have largely remained elusive. Here we show that B-cell repertoire sequencing of 102 clinical gastric cancers and molecular biological analyses unexpectedly reveal that the major humoral cancer antigens are not case-specific neo-antigens but are rather commonly identified as ribonucleoproteins (RNPs) in the focal adhesion complex. These common antigens are shared as autoantigens with multiple autoimmune diseases, suggesting a direct molecular link between cancer- and auto-immunity on the focal adhesion RNP complex. This complex is partially exposed to the outside of cancer cell surfaces, which directly evokes humoral immunity and enables functional bindings of antibodies to cancer cell surfaces in physiological conditions. These findings shed light on humoral cancer immunity in that it commonly targets cellular components fundamental for cytoskeletal integrity and cell movement, pointing to a novel modality of immunotherapy using humoral immunological reactions to cancers.
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http://dx.doi.org/10.1038/s42003-020-01305-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567837PMC
October 2020

Clinical Significance of Glioma-associated Oncogene 1 Expression in Patients With Locally Advanced Gastric Cancer Administered Adjuvant Chemotherapy With S-1 After Curative Surgery.

Anticancer Res 2020 Oct;40(10):5815-5821

Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan

Background/aim: Glioma-associated oncogene 1 (GLI1) is an important transcription factor in the hedgehog signalling pathway and tumour formation. We evaluated the clinical significance of GLI1 expression as a prognostic factor in patients with locally advanced gastric cancer (GC).

Patients And Methods: GLI1 expression levels were measured by quantitative real-time polymerase chain reaction analysis of cancerous and adjacent normal mucosa specimens obtained from 142 patients with Stage II/III GC administered adjuvant chemotherapy with S-1 after curative resection. The associations of GLI1 expression with clinicopathological features and survival were evaluated.

Results: Clinicopathological features and GLI1 expression showed no association. Overall survival was significantly poorer in the high compared to the low GLI1 expression group (p=0.04). Multivariate analysis revealed that GLI1 expression was a significant independent prognostic factor [p=0.019, hazard ratio (HR)=1.94, 95% confidence interval (CI)=1.70-3.38].

Conclusion: GLI1 expression may be a useful prognostic marker in patients with locally advanced GC.
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http://dx.doi.org/10.21873/anticanres.14599DOI Listing
October 2020

The Clinical Impact of the Age-adjusted Charlson Comorbidity Index on Esophageal Cancer Patients Who Receive Curative Treatment.

In Vivo 2020 Sep-Oct;34(5):2783-2790

Department of Surgery, Yokohama City University, Yokohama, Japan.

Background/aim: We investigated the impact of the age-adjusted Charlson comorbidity index (ACCI) on esophageal cancer survival and recurrence after curative treatment.

Patients And Methods: This study included 122 patients who underwent curative surgery followed by adjuvant chemotherapy for esophageal cancer between 2005 and 2017. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified.

Results: An ACCI of 5 was regarded as the optimal critical point of classification considering the survival rates. The OS rates at 3 and 5 years after surgery were 64.2% and 54.4% in the low-ACCI group, respectively, and 42.3% and 29.2% in high-ACCI group, respectively (p=0.035). The RFS rates at 3 and 5 years after surgery were 50.2% and 43.6% in the low-ACCI group, respectively, and 28.5% and 21.3% in high-ACCI group, respectively (p=0.021). A multivariate analysis demonstrated that ACCI was a significant independent risk factor for both the OS and RFS.

Conclusion: ACCI is a risk factor for survival in patients who undergo curative treatment for esophageal cancer. An effective plan for the perioperative care and surgical strategy should be developed according to ACCI.
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http://dx.doi.org/10.21873/invivo.12103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652511PMC
May 2021

The Short- and Long-term Outcomes of Gastrectomy in Elderly Patients With Gastric Cancer.

In Vivo 2020 Sep-Oct;34(5):2697-2703

Department of Surgery, Yokohama City University, Yokohama, Japan.

Background: The short- and long-term outcomes of gastrectomy in elderly patients with gastric cancer have not been fully evaluated.

Patients And Methods: Patients who underwent gastrectomy were classified into two groups: Non-elderly patients (<80 years old) and elderly patients (≥80 years old). The surgical morbidity, overall and cancer-specific survival in the two groups were compared.

Results: A total of 411 patients were evaluated. The rate of overall complication was 29.4% in the non-elderly and 32.4% in the elderly (p=0.699). In the elderly, the overall and cancer-specific survival rates at 5 years after surgery were inferior to those of the younger group (59.8% vs. 66.7%, p=0.103 and 67.9% vs. 78.2%, p=0.028, respectively).

Conclusion: The short-term outcomes after gastrectomy were almost equal for the two groups in the present study. The prognosis was poor in elderly patients, especially those with advanced gastric cancer.
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http://dx.doi.org/10.21873/invivo.12090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652480PMC
May 2021

Biomarker analysis to predict the pathological response to neoadjuvant chemotherapy in locally advanced gastric cancer: An exploratory biomarker study of COMPASS, a randomized phase II trial.

Oncotarget 2020 Jul 28;11(30):2906-2918. Epub 2020 Jul 28.

Tokai Central Hospital, Kakamigahara, Gifu 504-8601, Japan.

Background: The findings of COMPASS, a randomized phase II study, suggested that the regimens and courses of neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (GC) did not affect the pathological response. However, pathological complete response was achieved in 10% patients who received four courses of either S-1/cisplatin or paclitaxel/cisplatin. We hypothesized that if relevant biomarkers could be used to predict the suitable NAC regimen before treatment initiation, further improvements could be ensured in the outcomes of locally advanced GC.

Materials And Methods: mRNA extraction, real-time polymerase chain reaction, and immunohistochemical analyses were performed using endoscopic biopsy specimens of primary tumors, collected prior to NAC, to determine the clinically relevant biomarkers.

Results: , , , , , , and were identified as biomarker candidates, since their expression was significantly associated with the pathological responses to each NAC regimen. Furthermore, and were identified as predictive biomarkers of the pathological response to each NAC regimen.

Conclusions: The effective prediction of the pathological response to NAC regimens in locally advanced GC using biomarkers identified from endoscopic biopsy specimens indicates the possibility of personalizing NAC based on biomarker analysis.
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http://dx.doi.org/10.18632/oncotarget.27658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392622PMC
July 2020

Rapidly progressed neuroendocrine carcinoma in the extrahepatic bile duct: a case report and review of the literature.

Surg Case Rep 2020 Aug 3;6(1):191. Epub 2020 Aug 3.

Department of Hepatobiliary and Pancreatic Surgery, Kanagawa Cancer Center, 1-1-2 Nakao, Asahi-Ku, Yokohama, 241-8515, Japan.

Background: Neuroendocrine carcinoma (NEC) originating from the extrahepatic bile duct (EHBD) is very rare but is known for its aggressiveness and poor prognosis. We herein report a case of rapidly progressed NEC in the extrahepatic bile duct.

Case Presentation: An 84-year-old man was referred to our facility with obstructive jaundice and abdominal pain. Imaging studies revealed an irregular filling defect in the middle bile duct by endoscopic retrograde cholangiopancreatography and an enhanced wall thickening from the middle to distal portion by enhanced computed tomography. The patient was initially diagnosed with extrahepatic cholangiocarcinoma by a bile duct biopsy and underwent pancreatoduodenectomy with lymph node dissection. The pathological findings showed an NEC with an adenosquamous carcinoma component in the extrahepatic bile duct with lymph node metastases. The patient experienced multiple liver metastases 1 month after surgery and died 3 months after surgery. Due to the rapid progression of his disease, his general condition deteriorated, and he was unable to receive any additional treatments, such as chemotherapy.

Conclusion: As shown in our case, NEC of the EHBD has an extremely poor prognosis and can sometimes progress rapidly. Multimodality treatment should be considered, even in cases of locoregional disease.
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http://dx.doi.org/10.1186/s40792-020-00945-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399003PMC
August 2020

The Impact of Severe Infectious Complications on Long-term Prognosis for Gastric Cancer.

Anticancer Res 2020 Jul;40(7):4067-4074

Department of Surgery, Yokohama City University, Yokohama, Japan.

Background: The aim of this study was to evaluate the impact of postoperative infectious complications on long-term outcomes after curative resection of gastric cancer.

Patients And Methods: Patients who underwent curative gastrectomy with lymphadenectomy for gastric cancer at Yokohama City University and Kanagawa Cancer Center from January 2000 to August 2015 were retrospectively selected from medical records. Clinicopathological factors between patients with and without infectious complications were compared. Prognostic factors of long-term survival were analyzed by univariate and multivariate Cox proportional hazards analyses.

Results: A total of 2,254 patients were eligible for inclusion in the present study. Fifty-eight patients had postoperative infectious complications (IC group); 2,196 had no postoperative infectious complications (NC group). In the IC group, the median age (p=0.031), body mass index (p=0.004), American Society of Anesthesiologists physical status (p=0.006) and percentage of male patients (p<0.001) were higher in comparison to the NC group. The operation time was longer (p<0.001) and the incidence of intestinal-type histology was higher (p=0.017) in the IC group. The 5-year overall survival rates of the IC and NC groups were 59.8% and 83.2%, respectively (p<0.001). Univariate and multivariate analyses demonstrated that postoperative infectious complications were a significant risk factor for poorer overall survival (hazard ratio=2.38; 95% confidence interval=1.47-3.85, p<0.001).

Conclusion: Perioperative management is necessary to reduce the incidence of postoperative infectious complications and improve the survival of patients after curative resection of gastric cancer.
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http://dx.doi.org/10.21873/anticanres.14404DOI Listing
July 2020

The Lymph Node Ratio Is an Independent Prognostic Factor in Esophageal Cancer Patients Who Receive Curative Surgery.

In Vivo 2020 Jul-Aug;34(4):2087-2093

Department of Surgery, Yokohama City University, Yokohama, Japan.

Background/aim: We investigated the clinical impact of the lymph node ratio (LNR) on overall survival (OS) and recurrence-free survival (RFS) in esophageal cancer patients who underwent curative surgery.

Patients And Methods: One hundred twenty patients who underwent curative surgery for esophageal cancer between 2005 and 2017 were included in this study. The LNR was defined as the ratio of the number of metastatic lymph nodes (LNs) to the total number of harvested LNs.

Results: A lymph node ratio of 10% was regarded as the optimal critical point for classification based on the overall survival rate. The 3-year and 5-year OS rates were 65.5% and 57.0%, respectively, in the LNR<10% group, and 11.8% and 0% in the LNR≥10% group; the difference was statistically significant (p<0.001). The 3-year and 5-year RFS rates were 52.6% and 44.6%, respectively, in the LNR<10% group, and 0% and 0% in the LNR>10% group; the difference was also statistically significant (p<0.001). When comparing the sites of first relapse, the incidence of distant lymph node metastasis in the LNR>10% group was significantly higher than that in the LNR<10% group.

Conclusion: The LNR was a risk factor for both OS and RFS in patients who underwent curative surgery for esophageal cancer.
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http://dx.doi.org/10.21873/invivo.12012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439888PMC
March 2020

Laparoscopic Open Surgery for Stage II/III Colon Cancer Patients With Body Mass Index >25 kg/m.

In Vivo 2020 Jul-Aug;34(4):2079-2085

Department of Surgery, Yokohama City University, Yokohama, Japan.

Aim: To compare long- and short-term outcomes of laparoscopic surgery with those of open surgery for patients with colorectal cancer and body mass index over 25 kg/m Patients and Methods: This multicentre, retrospective study analysed clinical records and identified 178 patients with body mass index over 25 kg/m who underwent surgery for colon and rectosigmoid cancer between 2000 and 2016. After applying propensity score matching, 96 patients were finally included. The primary outcome was the 3-year recurrence-free survival rate, and the secondary outcomes were short-term results during and after surgery.

Results: The 3-year recurrence-free survival rates were similar for the laparoscopic and open surgery groups. The laparoscopic surgery group had longer operative times but less blood loss and shorter periods of hospital stay. There were no differences in incidence of postoperative complications.

Conclusion: Laparoscopic and open surgeries had similar long-term outcomes for obese patients. Laparoscopic surgery is an effective option for this population.
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http://dx.doi.org/10.21873/invivo.12011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439910PMC
March 2020

The Number of Harvested LNs Is an Independent Prognostic Factor in Lymph Node Metastasis-negative Patients Who Received Curative Esophagectomy.

In Vivo 2020 Jul-Aug;34(4):2021-2027

Department of Surgery, Yokohama City University, Yokohama, Japan.

Background/aim: The aim of the present study was to evaluate the optimal number of harvested LNs (LNs) in patients who were LN metastasis-negative after curative esophagectomy for esophageal cancer.

Patients And Methods: Sixty-one patients who underwent curative surgery for esophageal cancer between 2005 and 2017 and diagnosed as lymph node metastasis-negative were included in this study.

Results: The 5-year overall survival rates were 27.8% for 0-20 harvested LNs, 35.7% for 21-30 harvested LNs, 79.4% for 31-40 harvested LNs, and 85.2% for ≥41 harvested LNs. Thirty harvested LNs was regarded as the optimal critical point of classification, considering the 5-year OS rate. The number of harvested LNs was selected as a significant prognostic factor in both univariate and multivariate analyses. The respective 3- and 5-year OS rates were 50.3% and 36.7% for <30 harvested LNs and 82.4% and 82.4% for ≥30 harvested LNs (p=0.003).

Conclusion: Thirty or more harvested LNs was a significant prognostic factor in patients with metastasis-negative LNs after curative esophagectomy for esophageal cancer. Therefore, the number of harvested LNs might be useful for predicting the LN metastasis status in esophageal cancer.
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http://dx.doi.org/10.21873/invivo.12001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439900PMC
April 2020

Hypothesis-free deep survival learning applied to the tumour microenvironment in gastric cancer.

J Pathol Clin Res 2020 10 27;6(4):273-282. Epub 2020 Jun 27.

Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.

The biological complexity reflected in histology images requires advanced approaches for unbiased prognostication. Machine learning and particularly deep learning methods are increasingly applied in the field of digital pathology. In this study, we propose new ways to predict risk for cancer-specific death from digital images of immunohistochemically (IHC) stained tissue microarrays (TMAs). Specifically, we evaluated a cohort of 248 gastric cancer patients using convolutional neural networks (CNNs) in an end-to-end weakly supervised scheme independent of subjective pathologist input. To account for the time-to-event characteristic of the outcome data, we developed new survival models to guide the network training. In addition to the standard H&E staining, we investigated the prognostic value of a panel of immune cell markers (CD8, CD20, CD68) and a proliferation marker (Ki67). Our CNN-derived risk scores provided additional prognostic value when compared to the gold standard prognostic tool TNM stage. The CNN-derived risk scores were also shown to be superior when systematically compared to cell density measurements or a CNN score derived from binary 5-year survival classification, which ignores time-to-event. To better understand the underlying biological mechanisms, we qualitatively investigated risk heat maps for each marker which visualised the network output. We identified patterns of biological interest that were related to low risk of cancer-specific death such as the presence of B-cell predominated clusters and Ki67 positive sub-regions and showed that the corresponding risk scores had prognostic value in multivariate Cox regression analyses (Ki67&CD20 risks: hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.15-1.89, p = 0.002; CD20&CD68 risks: HR = 1.33, 95% CI = 1.07-1.67, p = 0.009). Our study demonstrates the potential additional value that deep learning in combination with a panel of IHC markers can bring to the field of precision oncology.
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http://dx.doi.org/10.1002/cjp2.170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578283PMC
October 2020