Perspective beyond Cancer Genomics: Bioenergetics of Cancer Stem Cells

Hideshi Ishii,Yuichiro Doki,masaki mori 연세대학교의과대학 2010 Yonsei medical journal Vol.51 No.5

Although the notion that cancer is a disease caused by genetic and epigenetic alterations is now widely accepted, perhaps more emphasis has been given to the fact that cancer is a genetic disease. It should be noted that in the post-genome sequencing project period of the 21st century, the underlined phenomenon nevertheless could not be discarded towards the complete control of cancer disaster as the whole strategy, and in depth investigation of the factors associated with tumorigenesis is required for achieving it. Otto Warburg has won a Nobel Prize in 1931 for the discovery of tumor bioenergetics, which is now commonly used as the basis of positron emission tomography (PET), a highly sensitive noninvasive technique used in cancer diagnosis. Furthermore, the importance of the cancer stem cell (CSC) hypothesis in therapy-related resistance and metastasis has been recognized during the past 2 decades. Accumulating evidence suggests that tumor bioenergetics plays a critical role in CSC regulation; this finding has opened up a new era of cancer medicine, which goes beyond cancer genomics.

Surgical Treatment of Gastroesophageal Junction Cancer

Tadayoshi Hashimoto,Yukinori Kurokawa,Masaki Mori,Yuichiro Doki 대한위암학회 2018 Journal of gastric cancer Vol.18 No.3

Although the incidence of gastroesophageal junction (GEJ) adenocarcinoma has been increasing worldwide, no standardized surgical strategy for its treatment has been established. This study aimed to provide an update on the surgical treatment of GEJ adenocarcinoma by reviewing previous reports and propose recommended surgical approaches. The Siewert classification is widely used for determining which surgical procedure is used, because previous studies have shown that the pattern of lymph node (LN) metastasis depends on tumor location. In terms of surgical approaches for GEJ adenocarcinoma, a consensus was reached based on two randomized controlled trials. Siewert types I and III are treated as esophageal cancer and gastric cancer, respectively. Although no consensus has been reached regarding the treatment of Siewert type II, several retrospective studies suggested that the optimal treatment strategy includes paraaortic LN dissection. Against this background, a Japanese nationwide prospective trial is being conducted to determine the proportion of LN metastasis in GEJ cancers and to identify the optimal extent of LN dissection in each type.

Surgical Treatment of Gastroesophageal Junction Cancer

Hashimoto, Tadayoshi,Kurokawa, Yukinori,Mori, Masaki,Doki, Yuichiro The Korean Gastric Cancer Association 2018 Journal of gastric cancer Vol.18 No.3

Although the incidence of gastroesophageal junction (GEJ) adenocarcinoma has been increasing worldwide, no standardized surgical strategy for its treatment has been established. This study aimed to provide an update on the surgical treatment of GEJ adenocarcinoma by reviewing previous reports and propose recommended surgical approaches. The Siewert classification is widely used for determining which surgical procedure is used, because previous studies have shown that the pattern of lymph node (LN) metastasis depends on tumor location. In terms of surgical approaches for GEJ adenocarcinoma, a consensus was reached based on two randomized controlled trials. Siewert types I and III are treated as esophageal cancer and gastric cancer, respectively. Although no consensus has been reached regarding the treatment of Siewert type II, several retrospective studies suggested that the optimal treatment strategy includes paraaortic LN dissection. Against this background, a Japanese nationwide prospective trial is being conducted to determine the proportion of LN metastasis in GEJ cancers and to identify the optimal extent of LN dissection in each type.

Is simply covering the patient's mouth with a surgical mask during transnasal endoscopy sufficient as an anti-COVID-19 measure?

Yohei Nose,Tomo Ishida,Tomoki Makino,Tsuyoshi Takahashi,Yukinori Kurokawa,Hidetoshi Eguchi,Yuichiro Doki,Kiyokazu Nakajima 대한소화기내시경학회 2023 Clinical Endoscopy Vol.56 No.3

Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial

Kato, Ken,Cho, Byoung Chul,Takahashi, Masanobu,Okada, Morihito,Lin, Chen-Yuan,Chin, Keisho,Kadowaki, Shigenori,Ahn, Myung-Ju,Hamamoto, Yasuo,Doki, Yuichiro,Yen, Chueh-Chuan,Kubota, Yutaro,Kim, Sung-Ba ELSEVIER 2019 LANCET ONCOLOGY Vol.20 No.11

<P><B>Summary</B></P> <P><B>Background</B></P> <P>Chemotherapy for patients with advanced oesophageal squamous cell carcinoma offers poor long-term survival prospects. We report the final analysis from our study of the immune checkpoint PD-1 inhibitor nivolumab versus chemotherapy in patients with previously treated advanced oesophageal squamous cell carcinoma.</P> <P><B>Methods</B></P> <P>We did a multicentre, randomised, open-label, phase 3 trial (ATTRACTION-3) at 90 hospitals and cancer centres in Denmark, Germany, Italy, Japan, South Korea, Taiwan, the UK, and the USA. We enrolled patients aged 20 years and older with unresectable advanced or recurrent oesophageal squamous cell carcinoma (regardless of PD-L1 expression), at least one measurable or non-measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, a baseline Eastern Cooperative Oncology Group performance status of 0–1, and who were refractory or intolerant to one previous fluoropyrimidine-based and platinum-based chemotherapy and had a life expectancy of at least 3 months. Patients were randomly assigned (1:1) to either nivolumab (240 mg for 30 min every 2 weeks) or investigator's choice of chemotherapy (paclitaxel 100 mg/m<SUP>2</SUP> for at least 60 min once per week for 6 weeks then 1 week off; or docetaxel 75 mg/m<SUP>2</SUP> for at least 60 min every 3 weeks), all given intravenously. Treatment continued until disease progression assessed by the investigator per RECIST version 1.1 or unacceptable toxicity. Randomisation was done using an interactive web response system with a block size of four and stratified according to geographical region (Japan <I>vs</I> rest of the world), number of organs with metastases, and PD-L1 expression. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival, defined as the time from randomisation until death from any cause, in the intention-to-treat population that included all randomly assigned patients. Safety was assessed in all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT02569242, and follow-up for long-term outcomes is ongoing.</P> <P><B>Findings</B></P> <P>Between Jan 7, 2016, and May 25, 2017, we assigned 419 patients to treatment: 210 to nivolumab and 209 to chemotherapy. At the time of data cutoff on Nov 12, 2018, median follow-up for overall survival was 10·5 months (IQR 4·5–19·0) in the nivolumab group and 8·0 months (4·6–15·2) in the chemotherapy group. At a minimum follow-up time (ie, time from random assignment of the last patient to data cutoff) of 17·6 months, overall survival was significantly improved in the nivolumab group compared with the chemotherapy group (median 10·9 months, 95% CI 9·2–13·3 <I>vs</I> 8·4 months, 7·2–9·9; hazard ratio for death 0·77, 95% CI 0·62–0·96; p=0·019). 38 (18%) of 209 patients in the nivolumab group had grade 3 or 4 treatment-related adverse events compared with 131 (63%) of 208 patients in the chemotherapy group. The most frequent grade 3 or 4 treatment-related adverse events were anaemia (four [2%]) in the nivolumab group and decreased neutrophil count (59 [28%]) in the chemotherapy group. Five deaths were deemed treatment-related: two in the nivolumab group (one each of interstitial lung disease and pneumonitis) and three in the chemotherapy group (one each of pneumonia, spinal cord abscess, and interstitial lung disease).</P> <P><B>Interpretation</B></P> <P>Nivolumab was associated with a significant improvement in overall survivaland a favourable safety profile compared with chemotherapy in previously treated patients with advanced oesophageal squamous cell carcinoma, and might represent a new standard second-line treatment option for these patients.