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Immune Checkpoint Inhibitors for the Treatment of Unresectable Stage III Non-Small Cell Lung Cancer: Emerging Mechanisms and Perspectives

Inoue H, Okamoto I

Lung Cancer (Auckl), 2019;10:161-170.
PMID: 32099495 DOI: 10.2147/LCTT.S184380

There has been no improvement in outcome for patients with unresectable locally advanced (stage III) non-small cell lung cancer (NSCLC) for more than 10 years. The standard treatment for these patients is definitive concurrent chemotherapy and radiation (CCRT). Although the goal of treatment in this setting is to achieve a cure, most patients progress and their prognosis is poor, with a 5-year survival rate of 15-30%. There is thus an urgent need for the development of novel anticancer treatments in this patient population. Recent advances in cancer immunotherapy have led to a marked improvement in clinical outcome for advanced NSCLC. Such immunotherapy mainly consists of the administration of immune checkpoint inhibitors (ICIs) such as antibodies to cytotoxic T lymphocyte-associated protein-4 (CTLA-4) or to either programmed cell death-1 (PD-1) or its ligand PD-L1. Durvalumab (MEDI4736) is a high-affinity human immunoglobulin G1 monoclonal antibody that blocks the binding of PD-L1 on tumor cells or antigen-presenting cells to PD-1 on T cells. The PACIFIC study recently evaluated consolidation immunotherapy with durvalumab versus placebo administered after concurrent chemoradiotherapy (CCRT) in patients with unresectable stage III NSCLC. It revealed a significant improvement in both progression-free and overall survival with durvalumab, and this improvement was associated with a favorable safety profile. This achievement has made durvalumab a standard of care for consolidation after CCRT in patients with unresectable stage III NSCLC, and it has now been approved in this setting by regulatory agencies in the United States, Canada, Japan, Australia, Switzerland, Malaysia, Singapore, India, and the United Arab Emirates. In this review, we briefly summarize the results of the PACIFIC trial, including those of post hoc analysis, and we address possible molecular mechanisms, perspectives, and remaining questions related to combined treatment with CCRT and ICIs in this patient population.
Fulltext Subcritical Water-Carbon Dioxide Pretreatment of Oil Palm Mesocarp Fiber for Xylooligosaccharide and Glucose Production

Ahmad N, Zakaria MR, Mohd Yusoff MZ, Fujimoto S, Inoue H, Ariffin H, et al.

Molecules, 2018 May 30;23(6).
PMID: 29848973 DOI: 10.3390/molecules23061310

The present work aimed to investigate the pretreatment of oil palm mesocarp fiber (OPMF) in subcritical H₂O-CO₂ at a temperature range from 150⁻200 °C and 20⁻180 min with CO₂ pressure from 3⁻5 MPa. The pretreated solids and liquids from this process were separated by filtration and characterized. Xylooligosaccharides (XOs), sugar monomers, acids, furans and phenols in the pretreated liquids were analyzed by using HPLC. XOs with a degree of polymerization X2⁻X4 comprising xylobiose, xylotriose, xylotetraose were analyzed by using HPAEC-PAD. Enzymatic hydrolysis was performed on cellulose-rich pretreated solids to observe xylose and glucose production. An optimal condition for XOs production was achieved at 180 °C, 60 min, 3 MPa and the highest XOs obtained was 81.60 mg/g which corresponded to 36.59% of XOs yield from total xylan of OPMF. The highest xylose and glucose yields obtained from pretreated solids were 29.96% and 84.65%, respectively at cellulase loading of 10 FPU/g-substrate.
An Asian consensus on standards of diagnostic upper endoscopy for neoplasia

Chiu PWY, Uedo N, Singh R, Gotoda T, Ng EKW, Yao K, et al.

Gut, 2019 02;68(2):186-197.
PMID: 30420400 DOI: 10.1136/gutjnl-2018-317111

BACKGROUND: This is a consensus developed by a group of expert endoscopists aiming to standardise the preparation, process and endoscopic procedural steps for diagnosis of early upper gastrointestinal (GI) cancers.
METHOD: The Delphi method was used to develop consensus statements through identification of clinical questions on diagnostic endoscopy. Three consensus meetings were conducted to consolidate the statements and voting. We conducted a systematic literature search on evidence for each statement. The statements were presented in the second consensus meeting and revised according to comments. The final voting was conducted at the third consensus meeting on the level of evidence and agreement.
RESULTS: Risk stratification should be conducted before endoscopy and high risk endoscopic findings should raise an index of suspicion. The presence of premalignant mucosal changes should be documented and use of sedation is recommended to enhance detection of superficial upper GI neoplasms. The use of antispasmodics and mucolytics enhanced visualisation of the upper GI tract, and systematic endoscopic mapping should be conducted to improve detection. Sufficient examination time and structured training on diagnosis improves detection. Image enhanced endoscopy in addition to white light imaging improves detection of superficial upper GI cancer. Magnifying endoscopy with narrow-band imaging is recommended for characterisation of upper GI superficial neoplasms. Endoscopic characterisation can avoid unnecessary biopsy.
CONCLUSION: This consensus provides guidance for the performance of endoscopic diagnosis and characterisation for early gastric and oesophageal neoplasia based on the evidence. This will enhance the quality of endoscopic diagnosis and improve detection of early upper GI cancers.
Fulltext Practice of endoscopy during COVID-19 pandemic: position statements of the Asian Pacific Society for Digestive Endoscopy (APSDE-COVID statements)

Chiu PWY, Ng SC, Inoue H, Reddy DN, Ling Hu E, Cho JY, et al.

Gut, 2020 Jun;69(6):991-996.
PMID: 32241897 DOI: 10.1136/gutjnl-2020-321185

Coronavirus-19 (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Risk of transmission may occur during endoscopy and the goal is to prevent infection among healthcare professionals while providing essential services to patients. Asia was the first continent to have a COVID-19 outbreak, and this position statement of the Asian Pacific Society for Digestive Endoscopy shares our successful experience in maintaining safe and high-quality endoscopy practice at a time when resources are limited. Sixteen experts from key societies of digestive endoscopy in Asia were invited to develop position statements, including patient triage and risk assessment before endoscopy, resource prioritisation and allocation, regular monitoring of personal protective equipment, infection control measures, protective device training and implementation of a strategy for stepwise resumption of endoscopy services after control of the COVID-19 outbreak.
Recovery of endoscopy services in the era of COVID-19: recommendations from an international Delphi consensus

Bhandari P, Subramaniam S, Bourke MJ, Alkandari A, Chiu PWY, Brown JF, et al.

Gut, 2020 11;69(11):1915-1924.
PMID: 32816921 DOI: 10.1136/gutjnl-2020-322329

The COVID-19 pandemic has had a profound impact on provision of endoscopy services globally as staff and real estate were repurposed. As we begin to recover from the pandemic, a cohesive international approach is needed, and guidance on how to resume endoscopy services safely to avoid unintended harm from diagnostic delays. The aim of these guidelines is to provide consensus recommendations that clinicians can use to facilitate the swift and safe resumption of endoscopy services. An evidence-based literature review was carried out on the various strategies used globally to manage endoscopy during the COVID-19 pandemic and control infection. A modified Delphi process involving international endoscopy experts was used to agree on the consensus statements. A threshold of 80% agreement was used to establish consensus for each statement. 27 of 30 statements achieved consensus after two rounds of voting by 34 experts. The statements were categorised as pre-endoscopy, during endoscopy and postendoscopy addressing relevant areas of practice, such as screening, personal protective equipment, appropriate environments for endoscopy and infection control precautions, particularly in areas of high disease prevalence. Recommendations for testing of patients and for healthcare workers, appropriate locations of donning and doffing areas and social distancing measures before endoscopy are unique and not dealt with by any other guidelines. This international consensus using a modified Delphi method to produce a series of best practice recommendations to aid the safe resumption of endoscopy services globally in the era of COVID-19.
Fulltext Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction

Sugano K, Spechler SJ, El-Omar EM, McColl KEL, Takubo K, Gotoda T, et al.

Gut, 2022 Aug;71(8):1488-1514.
PMID: 35725291 DOI: 10.1136/gutjnl-2022-327281

OBJECTIVE: An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ.
DESIGN: Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised.
RESULTS: Twenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett's oesophagus (BO).
CONCLUSIONS: This international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.