Publications by authors named "Takeshi Sano"

231 Publications

Anti-tumor effect of WEE1 blockade as monotherapy or in combination with cisplatin in urothelial cancer.

Cancer Sci 2021 Jul 1. Epub 2021 Jul 1.

Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Overcoming cisplatin (CDDP) resistance is a major issue in urothelial cancer (UC), in which CDDP-based chemotherapy is the first-line treatment. WEE1, a G2/M checkpoint kinase, confers chemo-resistance in response to genotoxic agents. However, the efficacy of WEE1 blockade in UC has not been reported. MK-1775, a WEE1 inhibitor also known as AZD-1775, blocked proliferation of UC cell lines in a dose-dependent manner irrespective of TP53 status. MK-1775 synergized with CDDP to block proliferation, inducing apoptosis and mitotic catastrophe in TP53-mutant UC cells but not in TP53-wild-type cells. Knocking down TP53 in TP53-wild-type cells induced synergism of MK-1775 and CDDP. In UMUC3 cell xenografts and two patient-derived xenograft lines with MDM2 overexpression, in which the p53/cell cycle pathway was inactivated, AZD-1775 combined with CDDP suppressed tumor growth inducing both M-phase entry and apoptosis, whereas AZD-1775 alone was as effective as the combination in RT4 cell xenografts. Drug susceptibility assay using an ex vivo cancer tissue-originated spheroid system showed correlations with the in vivo efficacy of AZD-1775 alone or combined with CDDP. We demonstrated the feasibility of the drug susceptibility assay using spheroids established from UC surgical specimens obtained by transurethral resection. In conclusion, WEE1 is a promising therapeutic target in the treatment of UC, and a highly specific small molecule inhibitor is currently in early phase clinical trials for cancer. Differential anti-tumor efficacy of WEE1 blockade alone or combined with CDDP may exist according to p53/cell cycle pathway activity, which may be predictable using an ex vivo 3D primary culture system.
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http://dx.doi.org/10.1111/cas.15051DOI Listing
July 2021

Preliminary prospective study of real-time post-gastrectomy glycemic fluctuations during dumping symptoms using continuous glucose monitoring.

World J Gastroenterol 2021 Jun;27(23):3386-3395

Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.

Background: Although dumping symptoms constitute the most common post-gastrectomy syndromes impairing patient quality of life, the causes, including blood sugar fluctuations, are difficult to elucidate due to limitations in examining dumping symptoms as they occur.

Aim: To investigate relationships between glucose fluctuations and the occurrence of dumping symptoms in patients undergoing gastrectomy for gastric cancer.

Methods: Patients receiving distal gastrectomy with Billroth-I (DG-BI) or Roux-en-Y reconstruction (DG-RY) and total gastrectomy with RY (TG-RY) for gastric cancer (March 2018-January 2020) were prospectively enrolled. Interstitial tissue glycemic profiles were measured every 15 min, up to 14 d, by continuous glucose monitoring. Dumping episodes were recorded on 5 patient-selected days by diary. Within 3 h postprandially, dumping-associated glycemic changes were defined as a dumping profile, those without symptoms as a control profile. These profiles were compared.

Results: Thirty patients were enrolled (10 DG-BI, 10 DG-RY, 10 TG-RY). The 47 early dumping profiles of DG-BI showed immediately sharp rises after a meal, which 47 control profiles did not ( < 0.05). Curves of the 15 late dumping profiles of DG-BI were similar to those of early dumping profiles, with lower glycemic levels. DG-RY and TG-RY late dumping profiles (7 and 13, respectively) showed rapid glycemic decreases from a high glycemic state postprandially to hypoglycemia, with a steeper drop in TG-RY than in DG-RY.

Conclusion: Postprandial glycemic changes suggest dumping symptoms after standard gastrectomy for gastric cancer. Furthermore, glycemic profiles during dumping may differ depending on reconstruction methods after gastrectomy.
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http://dx.doi.org/10.3748/wjg.v27.i23.3386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218361PMC
June 2021

[Complete Remission of Metastatic Renal Cell Carcinoma with Invasion of the Duodenum and Pancreas after Treatment with Nivolumab Plus Ipilimumab Followed by Axitinib and Surgery : A Case Report].

Hinyokika Kiyo 2021 May;67(5):197-203

The Department of Urology, Kyoto University Hospital.

A man in his 60s was diagnosed with clear cell carcinoma of the right kidney with multiple lung metastases, tumor thrombus of the inferior vena cava (IVC), and invasion of the duodenum and pancreas. Ipilimumab plus nivolumab was administered as first-line therapy. After 3 treatment courses, computed tomography (CT) demonstrated a slight decrease in the size of the primary tumor and lung metastases. However, the patient became hemodynamically unstable due to persistent duodenal bleeding during treatment despite frequent blood transfusions. Axitinib was then initiated as second-line therapy. The duodenal bleeding ceased 10 days after starting axitinib and his anemia remissed. Subsequent CT showed further decrease in the size of the primary tumor and lung metastases. The patient underwent right nephrectomy after improvement of nutrition. IVC thrombectomy, and pancreaticoduodenectomy. The lung metastases disappeared on postoperative imaging and no additional treatment was provided. Twelve months after surgery, he was in good health and showed no signs of recurrence.
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http://dx.doi.org/10.14989/ActaUrolJap_67_5_197DOI Listing
May 2021

Metabolic responses to polychromatic LED and OLED light at night.

Sci Rep 2021 Jun 11;11(1):12402. Epub 2021 Jun 11.

International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan.

Light exposure at night has various implications for human health, but little is known about its effects on energy metabolism during subsequent sleep. We investigated the effects of polychromatic white light using conventional light-emitting diodes (LED) and an alternative light source, organic light-emitting diodes (OLED), producing reduced spectral content in the short wavelength of blue light (455 nm). Ten male participants were exposed to either LED, OLED (1000 lx), or dim (< 10 lx) light for 4 h before sleep in a metabolic chamber. Following OLED exposure, energy expenditure and core body temperature during sleep were significantly decreased (p < 0.001). Fat oxidation during sleep was significantly reduced (p = 0.001) after the exposure to LED compared with OLED. Following exposure to OLED, fat oxidation positively correlated with the 6-sulfatoxymelatonin levels, suggesting that the role of melatonin in lipolysis differs depending on the light. These findings advance our knowledge regarding the role of light in energy metabolism during sleep and provide a potential alternative to mitigate the negative consequences of light exposure at night.
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http://dx.doi.org/10.1038/s41598-021-91828-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196130PMC
June 2021

Favorable Outcomes of Neoadjuvant Chemotherapy and Limited Para-Aortic Lymph Node Dissection for Advanced Gastric Cancer with Para-aortic Lymph Node Metastasis.

World J Surg 2021 May 24. Epub 2021 May 24.

Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Background: Although para-aortic lymph node (PALN) metastasis from gastric cancer is a non-curative lesion, gastrectomy with complete PALN dissection (PAND) following neoadjuvant chemotherapy (NAC) is a tentative standard treatment in Japan, based on the results of a small-scale phase II clinical trial. However, whether complete PAND (C-PAND) is always necessary for such diseases is open to debate.

Methods: Patients who received NAC followed by R0 gastrectomy for gastric cancer with clinical PALN metastasis at the Cancer Institute Hospital in Tokyo from 2005 to 2017 were reviewed in the present study. We assessed surgical findings and long-term outcomes.

Results: In total, 44 patients receiving gastrectomy with C-PAND (n = 22) or limited PAND (L-PAND; n = 22) were included. Operation time was significantly longer in the C-PAND than in the L-PAND groups (363 min vs. 271 min, P = 0.037). There was no difference between the two groups in the ypStage classification and pattern of recurrence. The 5-year overall survival (OS) and relapse-free survival (RFS) curves were higher in the L-PAND group than the C-PAND group, without reaching a significant difference. The 5-year OS (42.9% vs. 75.7%, p = 0.017) and RFS (14.3% vs. 48.6%, p = 0.002) were significantly worse in the group of three or more, than in the group of less than three pathological PALN metastasis, whereas increasing numbers of harvested PALN were not associated with improved survival.

Conclusions: Curative gastrectomy with L-PAND following NAC for gastric cancer involving PALN may be an alternative treatment to C-PAND.
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http://dx.doi.org/10.1007/s00268-021-06184-3DOI Listing
May 2021

Revised points and disputed matters in the eighth edition of the TNM staging system for gastric cancer.

Jpn J Clin Oncol 2021 Jul;51(7):1024-1027

Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

The American Joint Committee on Cancer and the Union for International Cancer Control have now released the eighth edition of the cancer staging system, which incorporates some major revisions concerning gastric cancer. First, grouping of pathological stages has been revised in accordance with a proposal from the International Gastric Cancer Association. That revision was based on analysis of survival of more than 25 000 patients worldwide who had undergone curative gastrectomy without neoadjuvant therapy. Stratification of survival in Stage III subgroups has been improved by subdividing N3 into N3a and N3b. Second, a simplified grouping of clinical stages that differs completely from grouping of pathological stages has been proposed. Pre-treatment depth of tumour invasion is now categorized as T1/T2, T3/T4a or T4b, and lymph node status is simply categorized as N0 or N+. Additionally, a 'yp-stage' for specimens resected after neoadjuvant therapy has been newly proposed. These clinical and post-neoadjuvant stages were considered useful now that neoadjuvant chemotherapy is increasingly being administered to patients with potentially resectable gastric cancer. Third, staging of oesophagogastric junction tumours has been modified; Siewert type 3 tumours are now classified as gastric tumours and are staged according to the gastric, rather than the oesophageal, system. More appropriate staging of gastric cancers treated with neoadjuvant therapy, and/or new staging systems incorporating variables other than T/N/M, such as biological or genomic markers, are likely future developments.
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http://dx.doi.org/10.1093/jjco/hyab069DOI Listing
July 2021

Different risk factors for three major recurrence patterns of pathological stage II or III gastric cancer patients who completed adjuvant S-1 monotherapy.

Eur J Surg Oncol 2021 Apr 21. Epub 2021 Apr 21.

Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Introduction: After curative gastrectomy followed by 1-year adjuvant S-1 monotherapy for pathological stage (pStage) II or III gastric cancer, some patients experience peritoneal, hematogenous, or lymph nodal recurrence. However, risk factors for each recurrence pattern despite completed adjuvant S-1 monotherapy remain unclear. The aim of this study was to determine which factors influence each recurrence type after curative gastrectomy followed by 1-year adjuvant S-1 monotherapy.

Materials And Methods: A total of 380 patients with pStage II or III gastric cancer who completed 1-year adjuvant S-1 monotherapy after R0 gastrectomy between January 2008 and December 2013 were enrolled in this study. The risk factors that were associated with peritoneal, hematogenous, and lymph nodal recurrence were investigated by univariate and multivariate analyses.

Results: Eighty (21.1%) of 380 patients developed recurrence. As the first site, peritoneal, hematogenous, and lymph nodal recurrence occurred in 42 (11.1%), 26 (6.8%), and 12 (3.2%) patients, respectively. In multivariate analysis, peritoneal metastasis was associated with signet ring cell carcinoma (P < 0.001), pT4 (P = 0.001), and pN3 (P < 0.001), while hematogenous recurrence was associated with pN3 (P = 0.019) and later initiation of S-1 (P = 0.013), and lymph nodal recurrence was associated with pN3 (P = 0.002).

Conclusion: The risk factors for peritoneal, hematogenous, and lymph nodal recurrence in pStage II or III gastric cancer patients who complete adjuvant S-1 monotherapy differ. This information may be helpful for daily surveillance of recurrence in post-operative and chemotherapeutic patients. Furthermore, it may be a useful reference to develop novel perioperative chemotherapy.
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http://dx.doi.org/10.1016/j.ejso.2021.04.018DOI Listing
April 2021

Do Japan's Health Care Personnel Meet the Personal Health Goals of the "National Health Promotion Program"?

Asia Pac J Public Health 2021 Apr 19:10105395211008749. Epub 2021 Apr 19.

Saitama Medical University, Iruma-gun, Saitama, Japan.

To improve health among the population and reduce the societal burden of care and health-related costs in a rapidly aging environment, the Japanese government launched the "National Health Promotion Program in the 21st Century" (HJ21), which contains goals concerning areas such as lifestyle behavior and the use of preventive medicine. While health care personnel are responsible for guiding others' health choices, they may not maintain healthy lifestyles themselves. Whether these individuals are meeting the HJ21 goals has not yet been examined. This study aims to determine whether certified specialists in health management are meeting such goals, and to compare their performance with the national average. This is a cross-sectional survey study. Study participants, sourced from all prefectures in Japan, were specialists certified in health management. We measured data concerning demographic information, lifestyle (physical activity, nutrition, diet, sleep, rest, smoking, and alcohol use), and the use of preventive medicine. The study participants exhibited many characteristics of high health literacy. They had an overall healthy lifestyle and met most of the HJ21 goals of healthy lifestyle, and a high proportion underwent health maintenance examinations and cancer screenings. These practices and behaviors maybe associated with high health literacy and social engagement activities.
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http://dx.doi.org/10.1177/10105395211008749DOI Listing
April 2021

Advantageous Short-Term Outcomes of Esophagojejunostomy Using a Linear Stapler Following Open Total Gastrectomy Compared with a Circular Stapler.

World J Surg 2021 Aug 1;45(8):2501-2509. Epub 2021 Apr 1.

Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Background: Esophagojejunostomy is one of the most important surgical procedures in total gastrectomy. In the past, esophagojejunostomy was exclusively performed using a circular stapler in open total gastrectomy (OTG). With the increasing frequency of its use in laparoscopic gastrectomy, esophagojejunostomy using a linear stapler has been performed in OTG. However, it is still unclear whether the use of a linear stapler in esophagojejunostomy following OTG has any advantages compared with the conventional use of a circular stapler.

Methods: A total of 298 patients who underwent OTG for gastric cancer between 2014 and 2019 were enrolled in this study. Patients were categorized into circular and linear groups (group C and group L) according to the stapler type used for the esophagojejunostomy. After propensity score matching, 136 patients (68 each in groups C and L) were selected to compare the surgical outcomes including incidence of esophagojejunostomy-related complications and postoperative nutritional status.

Results: The median operation time was significantly longer in group L than in group C (261.5 min versus 325.5 min; P < 0.001). The incidence of esophagojejunostomy-related complications did not differ between the two groups (5.9% versus 2.9%; P = 0.68); however, no anastomotic stricture and bleeding occurred in group L. Bodyweight loss was significantly lower in group L than in group C at 6 months (15.9% versus 12.6%; P = 0.007) after surgery.

Conclusions: Esophagojejunostomy using a linear stapler following OTG is equally safe and possibly advantageous in anastomotic stricture, bleeding and nutritional status compared with the use of a circular stapler.
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http://dx.doi.org/10.1007/s00268-021-06100-9DOI Listing
August 2021

Short- and long-term oncological outcomes of totally laparoscopic gastrectomy versus laparoscopy-assisted gastrectomy for clinical stage I gastric cancer.

Gastric Cancer 2021 Mar 15. Epub 2021 Mar 15.

Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Background: Totally laparoscopic gastrectomy (TLG), which involves a complete intracorporeal gastric transection and the creation of an anastomosis, has been gradually adopted. However, a potential limitation of intracorporeal transection is the lack of tactile feedback, and whether this limitation influences oncological outcomes is unclear. The aim of this study is to evaluate the short- and long-term oncological safety of TLG using endoscopy-guided intracorporeal gastric transection for clinical stage (cStage) I gastric cancer.

Methods: A total of 1875 consecutive patients who underwent laparoscopic gastrectomy for cStage I gastric cancer between January 2007 and March 2015 were enrolled in this study. Marking clips were preoperatively placed and a transection line was determined by perceiving it tactually in laparoscopy-assisted gastrectomy (LAG) or endoscopically in TLG. After propensity score matching, 1366 patients (683 each for LAG and TLG groups) were selected to primarily test the non-inferiority of TLG to that of LAG for relapse-free survival (RFS).

Results: In the propensity-matched population, the 5-year RFS rates of the LAG and TLG groups were 94.3% (95% confidence interval (CI) 92.2-95.8%), and 95.6% (95% CI 93.8-96.9%), respectively. The hazard ratio (TLG/LAG) was 0.77 (95% CI 0.48-1.24, P for non-inferiority < 0.01). There were no significant differences in the recurrence profiles. The incidence of the remnant of marking clips or tumor tissue did not differ (LAG: 1.0% vs. TLG: 1.9%, P = 0.177).

Conclusions: TLG using preoperative markings and intraoperative endoscopic guidance provides cStage I gastric cancer patients with comparable oncological outcomes to the conventional method.
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http://dx.doi.org/10.1007/s10120-021-01181-wDOI Listing
March 2021

Features of the complications for intracorporeal Billroth-I and Roux-en-Y reconstruction after laparoscopic distal gastrectomy for gastric cancer.

Langenbecks Arch Surg 2021 Feb 18. Epub 2021 Feb 18.

Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Purpose: Recently, the Roux-en-Y procedure (R-Y) and delta-shaped Billroth-I anastomosis (DB-I) have become prevalent as intracorporeal gastroenteric anastomosis methods after laparoscopic distal gastrectomy (LDG) for gastric cancer. However, the differences in postoperative outcomes between the two methods have not been clarified. Hence, this retrospective study aimed to reveal the features of the complications of the R-Y versus DB-I after LDG.

Methods: The study cohort comprised patients with gastric cancer who underwent DB-I or R-Y after LDG from January 2013 to May 2016. Patient characteristics and surgical and postoperative variables were analyzed. To compensate for intergroup differences in baseline characteristics, estimated propensity scores were used to perform one-on-one matching between the groups.

Results: A total of 564 patients were included, and propensity score matching created a matched cohort of 149 pairs in the DB-I and R-Y groups. The incidence of short-term complications such as gastrointestinal fistula classified as Clavien-Dindo grade IIIa or above was significantly greater in the DB-I group than the R-Y group (14.1% versus 4.7%, p=0.004). In contrast, the R-Y was associated with long-term complications such as internal hernia and tended to result in a slightly higher readmission rate in the R-Y group compared with the DB-I group (2.7% versus 6.0%, p=0.128).

Conclusion: DB-I after LDG was associated with a significantly higher rate of short-term complications compared with the R-Y, whereas characteristic long-term complications tended to be observed after the R-Y. These differences should be considered during the selection of the reconstruction method and postoperative management of LDG.
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http://dx.doi.org/10.1007/s00423-021-02136-6DOI Listing
February 2021

Oncological outcomes in patients with pT1N0-3 or pT2-3N0 gastric cancer after curative resection without adjuvant chemotherapy.

Langenbecks Arch Surg 2021 Mar 30;406(2):419-426. Epub 2021 Jan 30.

Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Purpose: The survival outcomes of pT1N0-3 or pT2-3N0 gastric cancer after curative resection are favorable without adjuvant chemotherapy. However, some patients develop recurrence and details of these recurrences remain unclear. This study aimed to evaluate the prognostic factors in patients with pT1N0-3 or pT2-3N0 gastric cancer.

Methods: We retrospectively reviewed the medical records of 1219 patients with pT1N0-3 or pT2-3N0 gastric cancer who underwent curative gastrectomy without neoadjuvant or adjuvant chemotherapy between April 2007 and March 2012 at Cancer Institute Hospital.

Results: This cohort included 895 pT1N0, 73 pT1N1, 23 pT1N2, 6 pT1N3, 130 pT2N0, and 92 pT3N0 patients. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) for pT1N0-3 and pT2-3N0 gastric cancer were 98.9% (95% CI 98.1-99.4) and 97.7% (95% CI 96.7-98.4), respectively. Age (HR 3.56, 95% CI 2.10-6.03) and lymphovascular involvement (hazard ratio (HR) 2.98, 95% CI 1.76-5.04) were independent prognostic factors in a multivariate analysis for RFS. The 5-year RFS for patients aged ≥75 years or with lymphovascular involvement were 94.4% (95% CI 89.8-97.0) and 95.1% (95% CI 92.5-96.8), respectively.

Conclusion: The survival outcomes of pT1N0-3 and pT2-3N0 were excellent, even in patients with aged >75 years or lymphovascular involvement which were risk factors. However, the sample size of T1N3 gastric cancer is small, so larger sample size and risk factor analysis are required.
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http://dx.doi.org/10.1007/s00423-021-02084-1DOI Listing
March 2021

Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer.

Nat Commun 2021 01 8;12(1):184. Epub 2021 Jan 8.

Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.

Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.
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http://dx.doi.org/10.1038/s41467-020-20493-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794518PMC
January 2021

Key Factors for Maintaining Postoperative Skeletal Muscle Mass After Laparoscopic Proximal Gastrectomy with Double-Flap Technique Reconstruction for Early Gastric Cancer.

J Gastrointest Surg 2021 06 23;25(6):1569-1572. Epub 2020 Nov 23.

Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

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http://dx.doi.org/10.1007/s11605-020-04846-6DOI Listing
June 2021

Gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer (JCOG0501): an open-label, phase 3, randomized controlled trial.

Gastric Cancer 2021 Mar 16;24(2):492-502. Epub 2020 Nov 16.

Department of Surgery, Yodogawa Christian Hospital, Osaka, Japan.

Background: Specific treatment strategies are sorely needed for scirrhous-type gastric cancer still, which has poor prognosis. Based on the promising results of our previous phase II study (JCOG0210), we initiated a phase III study to confirm the efficacy of neoadjuvant chemotherapy (NAC) in type 4 or large type 3 gastric cancer.

Methods: Patients aged 20-75 years without a macroscopic unresectable factor as confirmed via staging laparoscopy were randomly assigned to surgery followed by adjuvant chemotherapy with S-1 (Arm A) or NAC (S-1plus cisplatin) followed by D2 gastrectomy plus adjuvant chemotherapy with S-1 (Arm B). The primary endpoint was overall survival (OS).

Results: Between October 2005 and July 2013, 316 patients were enrolled, allocating 158 patients to each arm. In Arm B, in which NAC was completed in 88% of patients. Significant downstaging based on tumor depth, lymph node metastasis, and peritoneal cytology was observed using NAC. Excluding the initial 16 patients randomized before the first revision of the protocol, 149 and 151 patients in arms A and B, respectively, were included in the primary analysis. The 3-year OS rates were 62.4% [95% confidence interval (CI)  54.1-69.6] in Arm A and 60.9% (95% CI  52.7-68.2) in Arm B. The hazard ratio of Arm B against Arm A was 0.916 (95% CI  0.679-1.236).

Conclusions: For type 4 or large type 3 gastric cancer, NAC with S-1 plus cisplatin failed to demonstrate a survival benefit. D2 surgery followed by adjuvant chemotherapy remains the standard treatment.
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http://dx.doi.org/10.1007/s10120-020-01136-7DOI Listing
March 2021

Is laparoscopic and endoscopic cooperative surgery (LECS) for gastric subepithelial tumor at the esophagogastric junction safe?

Asian J Endosc Surg 2021 Apr 13;14(2):223-231. Epub 2020 Oct 13.

Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Introduction: With technique improvements, indications for laparoscopic and endoscopic cooperative surgery (LECS) for gastric subepithelial tumor (SET) are gradually expanding for tumors technically difficult to resect. However, surgical outcomes of LECS, including for esophagogastric junction (EGJ) tumors requiring advanced skills, remain unknown.

Methods: We reviewed patients in whom LECS had initially been attempted for gastric SET at the Cancer Institute Hospital in Tokyo from June 2006 to May 2018. Indications for LECS at the EGJ have gradually expanded during the study period to include tumors with esophageal invasion up to 2 cm, or less than half the EJG circumference, preoperatively. Surgical outcomes and risk factors for conversion to other procedures were investigated.

Results: Twenty (9.3%) of the 214 total patients had EGJ tumors. Four patients (20%) with EGJ tumors developed postoperative complications (Clavien-Dindo grade ≥ II). Among 12 patients in whom LECS could be completed for EGJ tumors, only one non-serious complication occurred. Eight patients required conversion to another operation for EGJ tumors (two laparotomy, six proximal gastrectomy). Among conversion cases with EGJ tumors, anastomotic leakage occurred in both patients undergoing laparotomy after LECS, necessitating additional defect closure. There was only one non-serious complication in six proximal gastrectomy patients. On multivariate analysis, EGJ tumor was an independent risk factor for conversion to another operation.

Conclusion: LECS at the EGJ may be a risk factor for conversion operation, and when performing LECS at the EGJ is difficult, conversion to proximal gastrectomy, which can be performed safely, should be considered.
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http://dx.doi.org/10.1111/ases.12857DOI Listing
April 2021

Immunogenic characteristics of microsatellite instability-low esophagogastric junction adenocarcinoma based on clinicopathological, molecular, immunological and survival analyses.

Int J Cancer 2021 03 10;148(5):1260-1275. Epub 2020 Oct 10.

Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.

Microsatellite instability (MSI) is categorized by mutation frequency: high MSI (MSI-H), low MSI (MSI-L) and microsatellite stable (MSS). MSI-H tumors have a distinct immunogenic phenotype, with immunotherapies using checkpoint inhibitors already approved for the treatment of MSI-H gastroesophageal adenocarcinoma (GEA); this is not observed for MSI-L or MSS. Here, we tested the hypothesis that MSI-L tumors are also a distinct phenotype and potentially immunogenic. MSI-PCR assays (BAT25, BAT26, BAT40, D2S123, D5S346 and D17S250) were performed on 363 Epstein-Barr virus-negative, surgically resected esophagogastric junction (EGJ) adenocarcinoma samples. Tumors were characterized as MSI-H (≥2 markers), MSI-L (1 marker) or MSS (0 markers). CD8+ cell counts, PD-L1 and HER2 expression levels, TP53 mutations, epigenetic alterations and prognostic significance were also examined. All pathological and molecular experiments were conducted using serial, whole-tumor sections of chemo-naïve surgical specimens. MSI-H and MSI-L were assigned to 28 (7.7%) and 24 (6.6%) cases, respectively. Compared to MSS cases, MSI-L cases had significantly higher intratumoral CD8+ cell infiltration (P = .048) and favorable EGJ cancer-specific survival (multivariate hazard ratio = 0.35, 95% CI, 0.12-0.82; P = .012). MSI-L tumors were also significantly associated with TP53-truncating mutations as compared to MSI-H (P = .009) and MSS (P = .012) cases, and this trend was also observed in GEA data from The Cancer Genome Atlas (TCGA). Indel mutational burden among TCGA MSI-L tumors was significantly higher than that of MSS tumors (P = .016). These results suggest that MSI-L tumors may have a distinct tumor phenotype and be potentially immunogenic in EGJ adenocarcinoma.
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http://dx.doi.org/10.1002/ijc.33322DOI Listing
March 2021

Solitary recurrence of prostate cancer surrounded by seminal vesicle/vas deferens-like epithelium.

IJU Case Rep 2020 Sep 30;3(5):171-173. Epub 2020 Jul 30.

Department of Nephro-urologic Surgery Mie University Hospital Tsu Japan.

Introduction: Clinical recurrence of prostate cancer after curative treatment with a limited number of metastases is often termed as oligorecurrence. We report a case of solitary recurrence of prostate cancer surrounded by epithelium of the seminal vesicle or vas deferens.

Case Presentation: A 54-year-old man diagnosed with localized prostate cancer underwent radiation therapy. Six years later, imaging studies detected a solitary recurrence. We performed metastasectomy, and histopathological examination revealed the metastatic lesion surrounded by the epithelium of the seminal vesicle or vas deferens. Surgical resection achieved a complete biochemical response.

Conclusion: We presented with a case of prostate cancer metastasis surrounded by the epithelium of the seminal vesicle or vas deferens.
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http://dx.doi.org/10.1002/iju5.12168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469812PMC
September 2020

Pancreatic atrophy after gastrectomy for gastric cancer.

Surg Today 2021 Mar 3;51(3):432-438. Epub 2020 Sep 3.

Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Purpose: To investigate the phenomenon of pancreatic atrophy after gastrectomy for gastric cancer, using computed tomography (CT) volumetry.

Methods: The subjects of this retrospective study were 77 patients who underwent distal gastrectomy (DG) or total gastrectomy (TG) for pStage I gastric cancer in 2014. The relative pancreatic volume ratio was assessed preoperatively, and then 1 and 5 years postoperatively and the results were compared between surgical procedures RESULTS: A total of 14 patients underwent TG with Roux-en-Y (RY) reconstruction, 24 underwent DG with Billroth-I (BI) reconstruction, and 39 underwent DG with RY reconstruction. We observed that the pancreatic volume continued to decrease over the 5 years after DG or TG. Furthermore, the incidence of pancreatic atrophy 5 years postoperatively was significantly greater after TG than after DG. In patients who underwent DG, a greater incidence of pancreatic atrophy was observed after RY reconstruction than after BI reconstruction, 5 years postoperatively.

Conclusion: The pancreatic volume continued to decrease after DG and TG for gastric cancer 5 years after treatment. TG was associated with a significantly greater incidence of pancreatic atrophy than DG 5 years postoperatively, as was RY reconstruction vs. BI reconstruction after DG.
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http://dx.doi.org/10.1007/s00595-020-02131-2DOI Listing
March 2021

Computed tomography detected pyelovenous backflow associated with complete ureteral obstruction.

IJU Case Rep 2019 Nov 1;2(6):321-323. Epub 2019 Sep 1.

Department of Urology Otsu City Hospital Otsu Japan.

Introduction: Pyelovenous backflow is a rare condition resulting from an increase in pressure in the renal pelvis due to urinary obstruction.

Case Presentation: A 49-year-old woman developed high-grade fever and right-sided hydronephrosis after undergoing hysterectomy. Although the hydronephrosis was mild, retrograde pyelography revealed complete obstruction of the right ureter. Excretory phase scans of contrast-enhanced computed tomography showed pyelovenous backflow, which presumably decompressed the hydronephrosis. The pyelovenous backflow immediately disappeared after ureteroneocystostomy.

Conclusion: We were presented with a patient showing pyelovenous backflow detected by contrast-enhanced computed tomography, which completely disappeared after ureteral obstruction release.
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http://dx.doi.org/10.1002/iju5.12117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292095PMC
November 2019

Survival outcomes of elderly patients with pathological stages II and III gastric cancer following curative gastrectomy.

Ann Gastroenterol Surg 2020 Jul 24;4(4):433-440. Epub 2020 Apr 24.

Department of Gastroenterological Surgery Cancer Institute Hospital Japanese Foundation for Cancer Research Tokyo Japan.

Aim: Survival outcomes in elderly patients with pathological stages (pStages) II and III gastric cancer remain inadequately elucidated. We retrospectively analyzed outcomes of elderly and nonelderly patients who underwent curative gastrectomy for this cancer and considered clinical results of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) scoring system for prediction.

Methods: Among 1041 patients who underwent gastrectomy for pStages II and III gastric cancer between 2008 and 2013 consecutively, 898 patients were enrolled. Of these, 158 patients (17.6%) were elderly and 740 patients (82.4%) were nonelderly.

Results: Disease-specific survival (DSS) in the elderly group with pStage III cancer was significantly worse than that in the same stage nonelderly group ( = .001), while there was no difference in DSS for pStage II cancer between the groups ( = .45). Overall survival (OS) was significantly worse in elderly patients for both pStages II and III. Elderly patients with pStage II cancer had larger survival gaps between OS and DSS compared with those with pStage III cancer. OS for elderly patients with comprehensive risk score (CRS) > 0.159 was significantly worse than that for elderly patients with CRS ≤ 0.159 in pStage II cancer.

Conclusions: Compared with nonelderly patients, different characteristics were observed in the survival outcomes of elderly patients between pStages II and III gastric cancer. The survival gap between OS and DSS of elderly patients was larger in pStage II cancer than in pStage III cancer. The E-PASS scoring system could be a relatively useful predictor in elderly patients.
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http://dx.doi.org/10.1002/ags3.12339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382424PMC
July 2020

Correction to: Intraoperative conversion from laparoscopic gastrectomy to an open procedure: a decade of experience in a Japanese high‑volume center.

Surg Endosc 2021 Apr;35(4):1843

Department of Gastroenterological Surgery, Cancer Institute Hospital of JFCR, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

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http://dx.doi.org/10.1007/s00464-020-07774-3DOI Listing
April 2021

Is endoscopic resection appropriate for type 3 gastric neuroendocrine tumors? Retrospective multicenter study.

Dig Endosc 2021 Mar 11;33(3):408-417. Epub 2020 Sep 11.

Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Background: Gastrectomy with lymphadenectomy is recommended for type 3 gastric neuroendocrine tumors (G-NETs). This study aimed to identify the risk factors for lymph node metastasis (LNM) arising from G-NETs to assess the suitability of endoscopic resection (ER).

Methods: Nationwide clinicopathological data of patients with type 3 G-NETs who underwent surgery or ER were collected. A single pathologist graded the histological tumor specimens.

Results: Among 176 cases from 53 institutions, 144 were eligible for analysis (90 NET-G1 and 54 NET-G2 grade, 8-mm median-size tumors). Of these, 63 patients had undergone ER (15 with additional surgeries). Histological data regarding LNM were available for 93 surgical patients. LNM was confirmed in 15 (16%) tumors and was correlated with tumor diameter, invasion depth, and tumor grade. LNM was negative in six tumors ≤5 mm, confined to the mucosa or submucosa, with a grade of G1, and without lymphovascular invasion, but the number of cases was too small to propose ER indications. Among 48 patients treated with ER alone, only one developed recurrence; no mortality was observed at follow-up, although many patients were classified with SM2/NET-G2/tumors >5 mm. This suggests that not all LNMs arising from small G-NETs are fatal.

Conclusion: Gastrectomy with lymphadenectomy for type 3 G-NETs is recommended on the basis of LNM. However, ER for type 3 G-NETs ≤10 mm, confined to the mucosa or submucosa, with a grade of G1 has shown excellent survival outcomes despite the risk of LNM, and therefore, could be an alternative treatment option.
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http://dx.doi.org/10.1111/den.13778DOI Listing
March 2021

Posttherapy topographical nodal status, ypN-site, predicts survival of patients who received neoadjuvant chemotherapy followed by curative surgical resection for non-type 4 locally advanced gastric cancer: supplementary analysis of JCOG1004-A.

Gastric Cancer 2021 Jan 22;24(1):197-204. Epub 2020 Jun 22.

Yodogawa Christian Hospital, Osaka, Japan.

Background: Perioperative treatment is an accepted standard approach for treating locally advanced gastric cancer (LAGC). Histopathological tumor regression with < 10% residual tumor is a globally accepted prognosticator in LAGC patients who received neoadjuvant chemotherapy (NAC) and curative surgery. However, despite a response of the primary tumor, a significant percentage of patients dies from recurrence and identification of those at risk for relapse remains challenging. We re-estimated the value of histopathological tumor regression as a prognosticator alongside other factors, especially posttherapy topographical nodal status, ypN-site.

Patients And Methods: Individual patient data including clinicopathological variables were used from the four JCOG trials investigating NAC (JCOG0001, JCOG0002, JCOG0210, JCOG0405) for analyzing prognosticators in patients with curative surgery excluding those with type 4 AGC by univariable and multivariable Cox regression analyses.

Results: Among 85 patients, 5-year overall survival (OS) was 46.0% [95% confidence interval (CI) 35.0-56.4] with a median follow-up of 3.2 years. On univariable analysis, histopathological tumor regression with ≥ 10% residual tumor and ypN-site 2-3 were negatively associated with OS [≥ 10% residual tumor: hazard ratio (HR) 2.60; 95% CI 1.22-5.54; P = 0.014; ypN2-3: HR 3.59; 95% CI 1.60-8.06; P = 0.002). On multivariable analysis, only ypN-site 2-3 was predictive of OS (HR 3.67; 95% CI 1.55-8.69; P = 0.003), whereas histopathological tumor regression with ≥ 10% residual tumor was not (HR 2.24; 95% CI 0.98-5.10; P = 0.055).

Conclusions: ypN-site may have greater impact on OS than histopathological tumor regression in patients who received NAC plus surgery for non-type 4 LAGC.
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http://dx.doi.org/10.1007/s10120-020-01098-wDOI Listing
January 2021

Serial circulating tumour DNA analysis for locally advanced rectal cancer treated with preoperative therapy: prediction of pathological response and postoperative recurrence.

Br J Cancer 2020 09 22;123(5):803-810. Epub 2020 Jun 22.

Project for Development of Liquid Biopsy Diagnosis, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.

Background: The "watch-and-wait" approach is a common treatment option amongst patients with locally advanced rectal cancer (LARC). However, the diagnostic sensitivity of clinical modalities, such as colonoscopy and magnetic resonance imaging to determine pathological response, is not high. We analysed the clinical utility of circulating tumour DNA (ctDNA) of patients with LARC to predict response to preoperative therapy and postoperative recurrence.

Methods: A serial ctDNA analysis of 222 plasma samples from 85 patients with LARC was performed using amplicon-based deep sequencing on a cell-free DNA panel covering 14 genes with over 240 hotspots.

Results: ctDNA was detected in 57.6% and 22.3% of samples at baseline and after preoperative treatment, respectively, which was significantly different (P = 0.0003). Change in ctDNA was an independent predictor of complete response to preoperative therapy (P = 0.0276). In addition, postoperative ctDNA and carcinoembryonic antigen (CEA) were independent prognostic markers for risk of recurrence after surgery (ctDNA, P = 0.0127 and CEA, P = 0.0105), with a combined analysis having cumulative effects on recurrence-free survival (P = 1.0 × 10).

Conclusions: Serial ctDNA analysis may offer clinically useful predictive and prognostic markers for response to preoperative therapy and postoperative recurrence in patients with LARC.
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http://dx.doi.org/10.1038/s41416-020-0941-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462982PMC
September 2020

Clinical outcomes of radical gastrectomy following trastuzumab-based chemotherapy for stage IV HER2-positive gastric or gastroesophageal junction cancer.

Surg Today 2020 Oct 26;50(10):1240-1248. Epub 2020 May 26.

Department of Upper Gastrointestinal Surgery, Kitasato University School of Medicine, Kanagawa, Japan.

Purpose: Patients who receive trastuzumab (T-mab) plus chemotherapy for stage IV HER2-positive gastric or gastroesophageal junction cancer sometimes respond remarkably well and can undergo radical surgery. However, the clinical outcomes of preoperative T-mab combined chemotherapy with radical gastrectomy remain unclear. We conducted this study to investigate the clinical outcomes of this multimodal treatment.

Methods: From among a total of 199 patients who received T-mab-based chemotherapy for stage IV HER2-positive gastric or gastroesophageal junction cancer between 2011 and 2018, the subjects of this retrospective analysis were 20 patients who subsequently underwent radical gastrectomy.

Results: Seven patients had gastroesophageal junction cancer and 13 had gastric cancer. Eleven patients had unresectable stage IV cancer and 9 had resectable metastatic disease. Chemotherapy regimens included capecitabine, cisplatin + T-mab (11 patients), and S-1, oxaliplatin + T-mab (nine patients). The median number of chemotherapy cycles before surgery was three (range, 2-62). During preoperative chemotherapy, grade 3/4 adverse events developed in six patients. None suffered grade ≥ 3b postoperative complications. The 3-year relapse-free survival (RFS) and overall survival (OS) rates were 58.9% and 89.5%, respectively.

Conclusion: Combined preoperative T-mab-based chemotherapy and surgery appears to be safe and effective for stage IV HER2-positive gastric or gastroesophageal junction cancer, with a clinically meaningful impact on RFS and OS.
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http://dx.doi.org/10.1007/s00595-020-02011-9DOI Listing
October 2020

Intraoperative conversion from laparoscopic gastrectomy to an open procedure: a decade of experience in a Japanese high-volume center.

Surg Endosc 2021 04 30;35(4):1834-1842. Epub 2020 Apr 30.

Department of Gastroenterological Surgery, Cancer Institute Hospital of JFCR, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Background: Although laparoscopic gastrectomy (LG) is a widely accepted treatment for gastric cancer, conversion to laparotomy is sometimes required. The current study aimed to review the time trends of intraoperative conversions to open procedures during the decade in which the LG procedure was being developed.

Methods: Cases in which LG was attempted at the Cancer Institute Hospital from 2005 to 2018 were retrospectively reviewed, and the details regarding conversions to open surgery were examined.

Results: Twenty-two (0.63%) of 3,498 patients required conversion to open surgery due to technical difficulties. The major reasons for conversions were difficulties in reconstruction (seven patients; 0.20%) and intraoperative bleeding (six patients; 0.17%). All conversions due to difficulties in reconstruction occurred in the introduction period of LG during the performance of esophagojejunostomy or esophagogastrostomy in laparoscopic total gastrectomy or proximal gastrectomy using a circular stapler. Five (71.4%) of the seven patients in whom conversion was performed due to difficulties in reconstruction developed postoperative severe complications. No conversions due to difficulties in reconstruction have been experienced since 2011, possibly due to the decrease in the number of laparoscopic total gastrectomy procedures and the introduction of the use of a linear stapler in esophagojejunostomy. To manage intraoperative bleeding in LG, hemostatic procedures were systematized and conversions were considered if visualization was not maintained following the procedures. None of the six patients who required laparotomy due to intraoperative bleeding required surgical or radiological intervention postoperatively.

Conclusion: Over a decade of experience and procedural changes have markedly decreased the incidence of conversion to open surgery in LG. The main causes of conversion during the early period of LG introduction were difficulties in reconstruction and intraoperative bleeding; the incidences of these complications have been decreased by employing the appropriate procedures for LG.
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http://dx.doi.org/10.1007/s00464-020-07584-7DOI Listing
April 2021

Trp53 Mutation in Keratin 5 (Krt5)-Expressing Basal Cells Facilitates the Development of Basal Squamous-Like Invasive Bladder Cancer in the Chemical Carcinogenesis of Mouse Bladder.

Am J Pathol 2020 08 24;190(8):1752-1762. Epub 2020 Apr 24.

Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

The biological processes of urothelial carcinogenesis are not fully understood, particularly regarding the relationship between specific genetic events, cell of origin, and molecular subtypes of subsequent tumors. N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced mouse bladder cancer is widely accepted as a useful model that recapitulates the pathway of human bladder tumorigenesis from dysplasia to invasive cancer via carcinoma in situ. However, the long and variable time of tumorigenesis often hinders efficient preclinical or translational research. We hypothesized that Trp53 mutation in specific types of urothelial cells facilitates efficient development of clinically relevant bladder cancer. Using lineage tracing, we showed that Trp53 mutation in Krt5-expressing cells resulted in more efficient tumorigenesis of mouse muscle-invasive bladder cancer (MIBC) with squamous differentiation compared with Trp53 mutation in Upk2-expressing cells, or wild-type or hemizygous Trp53 in the entire urothelium. Mouse MIBC that developed at 24 weeks of BBN treatment showed morphologic and genetic similarities to the basal squamous subtypes of human MIBC, irrespective of pre-induction of Trp53 mutation or whether the cell of origin was Krt5- or Upk2-expressing cells. Our findings suggest that intermediate cells as well as basal cells also can give rise to basal-like MIBC, with pre-induction of Trp53 mutation accelerating MIBC. Thus, in BBN chemical carcinogenesis, pre-induction of Trp53 mutation in basal cells facilitates efficient modeling of the basal squamous subtype of human MIBC.
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http://dx.doi.org/10.1016/j.ajpath.2020.04.005DOI Listing
August 2020

Therapeutic value of splenectomy to dissect splenic hilar lymph nodes for type 4 gastric cancer involving the greater curvature, compared with other types.

Gastric Cancer 2020 09 19;23(5):927-936. Epub 2020 Apr 19.

Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Background: Whether splenectomy for splenic hilar lymph node (No. 10) dissection in type 4 gastric cancer involving the greater curvature is necessary is not established. Patients with type 4 gastric cancer often experience peritoneal relapse, despite curative surgery, and total gastrectomy with splenectomy is frequently associated with infectious complications.

Method: Patients with cT2-T4 gastric cancer in the upper or middle third of the stomach, or both, involving the greater curvature who underwent R0 total gastrectomy with splenectomy between 2006 and 2016 were selected. Clinicopathological findings, postoperative complications, the incidence of lymph node metastasis, and the therapeutic value index of each station were compared between type 4 and non-type 4 gastric cancer.

Results: We enrolled 50 patients with type 4 and 60 with non-type 4. The former had a significantly higher proportion of the undifferentiated type and larger and deeper tumors. The overall incidence of Grade III or higher complications was 20.9%. The incidence of No. 10 metastasis was 26.0% in type 4 and 31.7% in non-type 4. Although the therapeutic value index of the No. 10 was 13.7 in type 4 and 15.0 in non-type 4, the index of type 4 ranked just below several peri-gastric stations and seventh, while that in non-type 4 ranked second.

Conclusion: Splenectomy for No. 10 dissection may be oncologically valid for type 4 gastric cancer involving the greater curvature. A safer procedure for No. 10 dissection should be established.
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http://dx.doi.org/10.1007/s10120-020-01072-6DOI Listing
September 2020

Facilitated completion of 1-year adjuvant S-1 monotherapy for pathological stage II or III gastric cancer by medical oncologists.

Surg Today 2020 Oct 2;50(10):1197-1205. Epub 2020 Apr 2.

Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Purpose: Several factors are known to be significantly associated with a low completion rate of 1-year adjuvant S-1 monotherapy for gastric cancer. The present study investigated whether or not the specialties of physicians conducting adjuvant S-1 monotherapy affect the completion rate.

Methods: A total of 437 patients who underwent curative gastrectomy followed by adjuvant S-1 monotherapy for pathological stage II or III gastric cancer between 2008 and 2013 were retrospectively analyzed. Factors affecting completion of adjuvant S-1 monotherapy, including the physicians (medical oncologists or surgeons) administering S-1, were evaluated by a multivariate analysis. The relationship between patient factors and physicians was analyzed regarding the cumulative incidence of discontinuation. The number of times the dose was reduced, the schedule changed, or administration was suspended or delayed in patients completing adjuvant S-1 monotherapy was also counted.

Results: The multivariate analysis showed that old age (≥ 65 years old), excess body weight loss (≥ 15%), and surgeons were independently associated with discontinuation. In older patients, the cumulative incidence of discontinuation by medical oncologists was significantly lower than that by surgeons. Medical oncologists ensured that older patients continued S-1 by frequent suspension or a delay in each course.

Conclusions: Medical oncologists may facilitate completion of adjuvant S-1 monotherapy.
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http://dx.doi.org/10.1007/s00595-020-01995-8DOI Listing
October 2020