Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive squamous cell carcinomas and is highly prevalent in Asia. Alcohol and its metabolite, acetaldehyde, are considered definite ...carcinogens for the esophagus. Polymorphisms in the aldehyde dehydrogenase 2 gene, which encodes an enzyme that eliminates acetaldehyde, have been associated with esophageal carcinogenesis. Studies of the mutagenic and carcinogenic effects of acetaldehyde support this observation. Several recent large-scale comprehensive analyses of the genomic alterations in ESCC have shown a high frequency of mutations in genes such as TP53 and others that regulate the cell cycle or cell differentiation. Moreover, whole genome and whole exome sequencing studies have frequently detected somatic mutations, such as G:C→A:T transitions or G:C→C:G transversions, in ESCC tissues. Genomic instability, caused by abnormalities in the Fanconi anemia DNA repair pathway, is also considered a pathogenic mechanism of ESCC. Advances in diagnostic techniques such as magnifying endoscopy with narrow band imaging or positron emission tomography have increased the accuracy of diagnosis of ESCC. Updated guidelines from the National Comprehensive Cancer Network standardize the practice for the diagnosis and treatment of esophageal cancer. Patients with ESCC are treated endoscopically or with surgery, chemotherapy, or radiotherapy, based on tumor stage. Minimally invasive treatments help improve the quality of life of patients who undergo such treatments. We review recent developments in the diagnosis and treatment of ESCC and advances gained from basic and clinical research.
The Japan Gastroenterological Endoscopy Society has developed endoscopic submucosal dissection/endoscopic mucosal resection guidelines. These guidelines present recommendations in response to 18 ...clinical questions concerning the preoperative diagnosis, indications, resection methods, curability assessment, and surveillance of patients undergoing endoscopic resection for esophageal cancers based on a systematic review of the scientific literature.
Over the last two decades, molecular-targeted agents have become mainstream treatment for many types of malignancies and have improved the overall survival of patients. However, most patients ...eventually develop resistance to these targeted therapies. Recently, immunotherapies such as immune checkpoint inhibitors have revolutionized the treatment paradigm for many types of malignancies. Immune checkpoint inhibitors have been approved for treatment of melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, Hodgkin’s lymphoma, bladder cancer and gastric cancer. However, oncologists have been faced with immune-related adverse events caused by immune checkpoint inhibitors; these are generally mild but can be fatal in some cases. Because immune checkpoint inhibitors have distinct toxicity profiles from those of chemotherapy or targeted therapy, many oncologists are not familiar with the principles for optimal management of immune-related adverse events, which require early recognition and appropriate treatment without delay. To achieve this, oncologists must educate patients and health-care workers, develop checklists of appropriate tests for immune-related adverse events and collaborate closely with organ specialists. Clinical questions that remain include whether immune checkpoint inhibitors should be administered to patients with autoimmune disease and whether patients for whom immune-related adverse events lead to delays in immunotherapy should be retreated. In addition, the predicted use of combination immunotherapies in the near future means that oncologists will face a higher incidence and severity of immune-related adverse events. This review provides an overview of the optimal management of immune-related adverse events attributed to immune checkpoint inhibitors.
Abstract
Background
This review focuses on the current status of endoscopic detection, characterization and tumour category staging of oesophagealsquamous cell carcinoma.
Detection
The diagnostic ...yield of white-light imaging is limited and narrow-band imaging has demonstrated a better performance for detecting oesophageal cancer. Narrow-band imaging has also shown similar sensitivity and superior specificity to iodine staining.
Characterization
Accurate differentiation between cancerous and non-cancerous lesions can be achieved by magnifying narrow-band imaging or iodine staining with confirmation of a pink-colour sign. A per-patient analysis of a randomized study showed similar sensitivities, specificities and overall accuracies of magnifying narrow-band imaging and iodine staining of 82.2%, 95.1% and 91.2%, and 80.5%, 94.3% and 90.5%, respectively.
Tumour-staging
The diagnostic capability of endoscopic ultrasonography after conventional and narrow-band imaging in terms of tumour depth was evaluated in a multicentre prospective study. Endoscopic ultrasonography did not significantly improve the accuracy for distinguishing between mucosal or submucosal microinvasive cancer and deeper cancers from 72.9 to 74.0%, suggesting that additional endoscopic ultrasonography did not improve the diagnostic accuracy. In addition, endoscopic ultrasonography increased the incidence of overdiagnosis, defined as a diagnosis of cancer depth greater than the actual depth, by 6.6%. The risk of overdiagnosis by endoscopic ultrasonography was reconfirmed in two systematic reviews.
Conclusions
Narrow-band imaging is currently considered as the standard modality for the detection and characterization of oesophageal cancer. The risk of overdiagnosis should be considered when applying endoscopic ultrasonography for the evaluation of tumour invasion depth of superficial oesophageal squamous cell carcinoma.
Narrow-band imaging is considered the standard modality for the detection and characterization of oesophageal cancer. The risk of overdiagnosis should be considered when applying endoscopic ultrasonography for tumour-staging.
Gastric cancer is the third leading cause of cancer death worldwide. Early detection and accurate diagnosis of mucosal cancer is desirable in order to achieve decreased mortality; cause‐specific ...survival of patients with early gastric cancer is reported to exceed 95%. Endoscopy is the functional modality to detect early cancer; however, the procedure is not definitive when using conventional white‐light imaging. In contrast, magnifying narrow‐band imaging (M‐NBI), a novel endoscopic technology, is a powerful tool for characterizing gastric mucosal lesions because it can visualize the microvascular architecture and microsurface structure. To date, many reports on the diagnosis of early gastric cancer by M‐NBI, including multicenter prospective randomized studies conducted in Japan, have been published in peer‐reviewed international journals. Based on these published data, we devised a proposal for a diagnostic strategy for gastric mucosal cancer using M‐NBI to simplify the process of diagnosis and improve accuracy. Herein, we recommend a diagnostic algorithm for early gastric cancer using magnifying endoscopy.
Background
Endoscopic resection has been limited to intestinal-type gastric cancer (cT1a) with a low risk of lymph node metastasis (T1a ≤2 cm, without ulcers). This single-arm confirmatory trial ...evaluated the efficacy and safety of endoscopic submucosal dissection (ESD) for >2 cm ulcer-negative and ≤3 cm ulcer-positive intestinal-type gastric cancer (cT1a).
Methods
The eligibility criteria included endoscopically diagnosed cT1a, a single primary intestinal-type gastric adenocarcinoma, an ulcer-negative lesion of any size or a ≤3 cm ulcer-positive lesion, cN0M0, and no prior treatment. If ESD resulted in noncurative resection, surgical resection was added. The primary endpoint was the 5-year overall survival (OS) (planned sample size was 470, with a one-sided alpha level of 2.5%). The threshold 5-year OS was 86.1%.
Results
We enrolled 470 early gastric cancer patients median tumor size, 25 (5–130) mm from 29 institutions between June 2007 and October 2010. These patients had 152 ulcer-negative lesions (>2 and ≤3 cm), 111 ulcer-negative lesions (>3 cm), and 207 ulcer-positive lesions (≤3 cm). The success rate for en block resection was 99.1% (466/470). Additional gastrectomy was conducted in 131 patients (28%) who did not fulfill the curative resection criteria. The 5-year OS of all patients was 97.0% (95% confidence interval, 95.0–98.2%), which was higher than the threshold 5-year OS (86.1%). The 317 patients who satisfied the curative resection criteria had no recurrence. There were no ESD-related grade 4 adverse events.
Conclusion
ESD for early gastric cancers that met the expanded criteria for intestinal-type gastric cancer (cT1a) was acceptable and should be the standard treatment instead of gastrectomy.
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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