Introduction
Despite the remarkable progress achieved in the research on Alzheimer's disease (AD), its exact pathogenesis is not fully understood and effective therapies do not currently exist. In ...order to find effective therapy for AD, I ranged extensively over the literature and found an important paper by Tiffany and colleagues.
Results and Conclusion
Neuroinflammation has been proposed as a possible cause or driving force of AD. The discovery by Tiffany et al. that amyloid β (Aβ) is a formylpeptide receptor 2 agonist indicated that Aβ is a potent chemoattractant for phagocytic leukocytes. Therefore, in all likelihood Aβ attracts peripheral blood neutrophils, monocytes, as well as microglia cells in brain parenchyma, and activates them. However, the role of microglia cells and their precursor monocytes in AD pathogenesis remains elusive. Recently, neutrophils were found to be present in areas with Aβ deposits in AD brain and in transgenic AD model mice. Because brain is vulnerable to the effects of reactive oxygen species (ROS) and neutrophils secrete a large amount of ROS, neutrophils look like a driving force of AD. Therefore, a possibility arises that anti‐IL‐17A and anti‐IL‐23 antibodies are effective against AD, because these antibodies can be thought to interfere with neutrophil trafficking from the bone marrow to the blood circulation and thus inhibit neutrophil infiltration into AD brain. Clinical studies using anti‐IL‐17A and anti‐IL‐23 antibodies in patients with AD are required.
IL‐17A mediates neutrophil migration from the bone marrow. Anti‐IL‐17A antibody inhibits it.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Purpose
Prior to publication of the Clavien-Dindo classification in 2004, there were no grading definitions for surgical complications in either clinical practice or surgical trials. This report ...establishes supplementary criteria for this classification to standardize the evaluation of postoperative complications in clinical trials.
Methods
The Japan Clinical Oncology Group (JCOG) commissioned a committee. Members from nine surgical study groups (gastric, esophageal, colorectal, lung, breast, gynecologic, urologic, bone and soft tissue, and brain) specified postoperative complications experienced commonly in their fields and defined more detailed grading criteria for each complication in accordance with the general grading rules of the Clavien-Dindo classification.
Results
We listed 72 surgical complications experienced commonly in surgical trials, focusing on 17 gastroenterologic complications, 13 infectious complications, six thoracic complications, and several other complications. The grading criteria were defined simply and were optimized for surgical complications.
Conclusions
The JCOG postoperative complications criteria (JCOG PC criteria) aim to standardize the terms used to define adverse events (AEs) and provide detailed grading guidelines based on the Clavien-Dindo classification. We believe that the JCOG PC criteria will allow for more precise comparisons of the frequency of postoperative complications among trials across many different surgical fields.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional ...fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC.
In this phase II or III trial (JCOG0603), patients age 20-75 years with confirmed CRC and an unlimited number of liver metastatic lesions were randomly assigned to hepatectomy alone or 12 courses of adjuvant mFOLFOX6 after hepatectomy. The primary end point of phase III was disease-free survival (DFS) in intention-to-treat analysis.
Between March 2007 and January 2019, 300 patients were randomly assigned to hepatectomy alone (149 patients) or hepatectomy followed by chemotherapy (151 patients). At the third interim analysis of phase III with median follow-up of 53.6 months, the trial was terminated early according to the protocol because DFS was significantly longer in patients treated with hepatectomy followed by chemotherapy. With median follow-up of 59.2 months, the updated 5-year DFS was 38.7% (95% CI, 30.4 to 46.8) for hepatectomy alone compared with 49.8% (95% CI, 41.0 to 58.0) for chemotherapy (hazard ratio, 0.67; 95% CI, 0.50 to 0.92; one-sided
= .006). However, the updated 5-year overall survival (OS) was 83.1% (95% CI, 74.9 to 88.9) with hepatectomy alone and 71.2% (95% CI, 61.7 to 78.8) with hepatectomy followed by chemotherapy. In the chemotherapy arm, the most common grade 3 or higher severe adverse event was neutropenia (50% of patients), followed by sensory neuropathy (10%) and allergic reaction (4%). One patient died of unknown cause after three courses of mFOLFOX6 administration.
DFS did not correlate with OS for liver-only metastatic CRC. Adjuvant chemotherapy with mFOLFOX6 improves DFS among patients treated with hepatectomy for CRC liver metastasis. It remains unclear whether chemotherapy improves OS.
Backgrounds
No confirmatory randomized controlled trials (RCTs) have evaluated the efficacy of laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG). We performed ...an RCT to confirm that LADG is not inferior to ODG in efficacy.
Methods
We conducted a multi-institutional RCT. Eligibility criteria included histologically proven gastric adenocarcinoma in the middle or lower third of the stomach, clinical stage I tumor. Patients were preoperatively randomized to ODG or LADG. This study is now in the follow-up stage. The primary endpoint is relapse-free survival (RFS) and the primary analysis is planned in 2018. Here, we compared the surgical outcomes of the two groups. This trial was registered at the UMIN Clinical Trials Registry as UMIN000003319.
Results
Between March 2010 and November 2013, 921 patients (LADG 462, ODG 459) were enrolled from 33 institutions. Operative time was longer in LADG than in ODG (median 278 vs. 194 min,
p
< 0.001), while blood loss was smaller (median 38 vs. 115 ml,
p
< 0.001). There was no difference in the overall proportion with in-hospital grade 3–4 surgical complications (3.3 %: LADG, 3.7 %: ODG). The proportion of patients with elevated serum AST/ALT was higher in LADG than in ODG (16.4 vs. 5.3 %,
p
< 0.001). There was no operation-related death in either arm.
Conclusions
This trial confirmed that LADG was as safe as ODG in terms of adverse events and short-term clinical outcomes. LADG may be an alternative procedure in clinical IA/IB gastric cancer if the noninferiority of LADG in terms of RFS is confirmed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Exploring potential spintronic functionalities in resistive switching (RS) devices is of great interest for creating new applications, such as multifunctional resistive random‐access memory and novel ...neuromorphic computing devices. In particular, the importance of the spin‐triplet state of cation vacancies in oxide materials, which is induced by localized and strong O–2p on‐site Coulomb interactions, in RS devices has been overlooked. d0 ferromagnetism sometimes appears due to the spin‐triplet state and ferromagnetic Zener's double exchange interactions between cation vacancies, which are occasionally strong enough to make nonmagnetic oxides ferromagnetic. Here, for the first time, anomalous and colossal magneto‐RS (CMRS) with very high magnetic field dependence is demonstrated by utilizing an unconventional RS device composed of a Ge nanochannel with all‐epitaxial single‐crystalline Fe/MgO electrodes. The device shows colossal and unusual behavior as the threshold voltage and ON/OFF ratio strongly depend on a magnetic field, which is controllable with an applied voltage. This new phenomenon is attributed to the formation of d0‐ferromagnetic filaments by attractive Mg vacancies due to the spin‐triplet states with ferromagnetic double exchange interactions and the ferromagnetic proximity effect of Fe on MgO. The findings will allow the development of energy‐efficient CMRS devices with multifield susceptibility.
Anomalous and colossal magneto‐resistive switching with very high magnetic field dependence is demonstrated in a device composed of a Ge nanochannel with all‐epitaxial single‐crystalline Fe/MgO electrodes. The new phenomenon is attributed to the formation of d0‐ferromagnetic filaments by attractive Mg vacancies due to the spin‐triplet states with ferromagnetic double exchange interactions and the ferromagnetic proximity effect of Fe on MgO.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Backgrounds
Laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer is safe and feasible. In contrast, no prospective study evaluating the safety and efficacy of laparoscopy-assisted total ...gastrectomy (LATG) or laparoscopy-assisted proximal gastrectomy (LAPG) has been completed. We conducted a single-arm confirmatory trial to evaluate the safety of LATG/LAPG for clinical stage I (T1N0/T1N1/T2N0) proximal gastric cancer.
Methods
The extent of lymphadenectomy was selected based on the Japanese Gastric Cancer Treatment Guidelines. The mini-laparotomy incision was required to be ≤ 6 cm. The primary endpoint was the proportion of grade 2–4 (CTCAE ver. 4.0) esophagojejunal anastomotic leakage. The planned sample size was 245 considering a threshold of 8% and one-sided alpha of 2.5%.
Results
Between April 2015 and February 2017, 244 eligible patients were enrolled. LATG/LAPG was performed in 195/49. The proportion of conversions was 1.7%. Clinical T1N0/T1N1/T2N0 was 212/9/23. The extents of lymphadenectomy were as follows: D1+: 229; D2: 15. The median operation time was 309 min (IQR 265–353). The median blood loss was 30 ml (IQR 10–86). Grade 2–4 esophagojejunal anastomotic leakage was 2.5% (6/244; 95% CI 0.9–5.3). The overall proportion of in-hospital grade 3–4 adverse events was 29% (71/244). The proportions of intraabdominal abscess and pancreatic fistula were 3.7% and 2.0%, respectively. There were no treatment-related deaths.
Conclusions
This trial confirmed the safety of LATG/LAPG. After the non-inferiority of LADG is confirmed in our phase III trial (JCOG0912), LATG/LAPG is expected to be established as one of the standard treatments for clinical stage I gastric cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
While endoscopic submucosal dissection (ESD) is recognized as a minimally invasive standard treatment for differentiated early gastric cancers (EGCs), it has not been indicated for ...undifferentiated EGC (UD-EGC) because of a relatively high risk of lymph node metastasis (LNM). However, patients with surgically resected mucosal (cT1a) UD-EGC ≤ 2 cm in size with no lymphovascular invasion or ulceration are reported to be at a very low risk of LNM. This multicenter, single-arm, confirmatory trial was conducted to evaluate the efficacy and safety of ESD for UD-EGC.
Methods
The key eligibility criteria were endoscopically diagnosed cT1a/N0/M0, single primary lesion, size ≤ 2 cm, no ulceration and histologically proven components of undifferentiated adenocarcinoma on biopsy. Based on the histological findings after ESD, additional gastrectomy was indicated if the criteria for curative resection were not satisfied. The subjects of the primary analysis were patients with UD-EGC as the dominant component. The primary endpoint was 5-year overall survival (OS) of patients with UD-EGC.
Results
Three hundred 46 patients were enrolled from 49 institutions. The proportion of
en bloc
resection was 99%. No ESD-related Grade 4 adverse events were noted. Delayed bleeding and intraoperative and delayed perforation occurred in 25 (7.3%), 13 (3.8%), and 6 (1.7%) patients, respectively. Among the 275 patients who were the subjects of the primary analysis, curative resection was achieved in 195 patients (71%), and 5-year OS was 99.3% (95% CI: 97.1–99.8).
Conclusions
ESD can be a curative and less invasive treatment for UD-EGC for patients meeting the eligibility criteria of this study.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
In April 2016, the Japanese government introduced health technology assessment as a response to rising medical expenses due to ‘medical innovation’. This study investigates how Japanese ...breast cancer patients who received treatment in Japan consider the financial value (willingness-to-pay; WTP) for their life and health by using the contingent valuation method (CVM) prospectively. First, 168 patients (84 primary breast cancer patients and 84 metastatic breast cancer patients) were pre-examined their WTP with dichotomous-choice method survey form. Next, 1,596 patients (798 primary breast cancer patients and 798 metastatic breast cancer patients) will be surveyed to their WTP for hypothetical scenarios in CVM. Based on our results, we will construct an evaluation axis from the patients’ viewpoint for the cost-effectiveness of clinical trials to establish standard treatments for breast cancer. We believe this research can contribute to create a meaningful healthcare system for patients, clinicians, industries, and healthcare policymakers.
This study investigated how Japanese breast cancer patients who received treatment in Japan consider the willingness-to-pay for their life and health by using the contingent valuation method prospectively.
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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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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