Endoscopic resection for local residual or recurrent cancer after definitive chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma.

Chemoradiotherapy (CRT) and radiotherapy (RT) are treatment options for esophageal squamous cell carcinoma (ESCC), but local residual/recurrent cancer after CRT/RT is a major problem. Endoscopic resection (ER) is an effective treatment option for local residual/recurrent cancer. To ensure the efficacy of ER, complete removal of endoscopically visible lesions with cancer-free vertical margins is desired. This study aimed to identify the endoscopic parameters associated with the complete endoscopic removal of local residual/recurrent cancer. In this single-center, retrospective study, we used a prospectively maintained database to identify esophageal lesions that were diagnosed as local residual/recurrent cancer after CRT/RT and treated by ER between January 2012 and December 2019. We evaluated the associations of endoscopic R0 resection with findings on conventional endoscopy and endoscopic ultrasonography (EUS). In total, 98 lesions (83 cases) were identified from our database. The rate of endoscopic R0 resection was higher for flat lesions (100% versus 77%, P = 0.00014). EUS was performed for 24 non-flat lesions, and endoscopic R0 resection was achieved for 94% of lesions with an uninterrupted fifth layer. Flat lesions on conventional endoscopy and lesions with an uninterrupted fifth layer on EUS are good candidates for ER.

Efficacy and safety of intensive downstaging polypectomy (IDP) for multiple duodenal adenomas in patients with familial adenomatous polyposis: a prospective cohort study.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) risk developing multiple duodenal adenomas (MDAs), leading to duodenal cancer and death. We investigated the efficacy and safety of intensive downstaging polypectomy (IDP) for MDAs integrated with new-generation procedures. METHODS: This prospective phase II study, conducted at a tertiary cancer center, enrolled patients with FAP who had MDAs. We performed IDP including cold snare/forceps polypectomy (CSP/CFP) and underwater endoscopic mucosal resection (UEMR). The primary end point was the downstaging of Spigelman stage at 1-year follow-up. RESULTS: 2424 duodenal polyps in 58 patients with FAP underwent IDP, including 2413 CSPs in 57 patients, seven CFPs in one patient, and four UEMRs in four patients. Only one major adverse event was observed (grade 3 hyperamylasemia) without clinical manifestations. We performed additional UEMR, CSP, and CFP for one, 12, and 22 patients, respectively, during initial follow-up. Overall, 55 patients completed protocol examination; the Spigelman stage was significantly reduced at the 1-year follow-up endoscopy (P < 0.001), with downstaging observed in 39 patients (71 %). Among the 26 patients with Spigelman stage IV at initial examination and protocol completion, 23 (88 %) showed downstaging. There was no major change in Spigelman stages from 1-year follow-up esophagogastroduodenoscopy to a median of 37 months (range 3-56). CONCLUSIONS: IDP, including new-generation procedures, showed significant downstaging with acceptable adverse events for MDA in patients with FAP, even those with advanced-stage disease. Lesion selection for different resection techniques may be important for suitable and sustainable management of MDA in patients with FAP.

Impact of endoscopic surveillance on mortality of metachronous esophageal and head and neck cancer after esophageal endoscopic resection.

BACKGROUND AND AIM: As more superficial esophageal cancer (EC) patients are being treated with endoscopic resection (ER), it is important to understand the outcomes, including survival data, of patients who develop metachronous EC and head and neck cancer (HNC). We aimed to evaluate the long-term surveillance and survival outcomes of metachronous EC and HNC after esophageal ER. METHODS: This study included 627 patients who underwent ER of superficial esophageal squamous cell carcinoma from 2008 to 2016 and were generally followed by annual or biannual esophagogastroduodenoscopy up to 2019 at Osaka International Cancer Institute. Data on metachronous cancer development and causes of death were collected from an integrated database of hospital-based cancer registry and Vital Statistics of Japan. RESULTS: During a median (range) follow-up period of 67.4 (3.8-142.7) months, 230 patients (36.7%) developed 500 metachronous ECs and 126 patients (20.1%) developed 239 metachronous HNCs, post-ER of index EC. The 3-year, 5-year, and 7-year cumulative incidences were 25.8%, 36.0%, and 43.6% for metachronous EC and 10.9%, 16.0%, and 26.9% for metachronous HNC, respectively. No patients died of metachronous EC, and only seven patients (1.1%) died of metachronous HNC. The 3-year, 5-year, and 7-year disease-specific survival rates were 99.8%, 99.6%, and 98.6%, respectively. CONCLUSIONS: The incidences of metachronous EC and HNC increase with time over 5 years after esophageal ER; therefore, surveillance endoscopy should be continued over 5 years. Endoscopic surveillance is useful for survivors after esophageal ER given the high incidence and extremely low mortality of metachronous EC and HNC.

Clinical features of superficial esophagus squamous cell carcinoma according to alcohol-degrading enzyme ADH1B and ALDH2 genotypes.

BACKGROUND: Inactivated alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are related to esophageal carcinogenesis. We aimed to clarify the clinical features associated with the alcohol-degrading enzyme genotypes, ADH1B and ALDH2. We also investigated the risk factors for metachronous esophageal squamous cell carcinoma (ESCC) and head and neck SCC (HNSCC). METHODS: We conducted a single-center, retrospective study including patients with ESCC treated by endoscopic resection. Patients were recruited between October 2020 and September 2021. Buccal mucosal swabs were obtained from them to analyze the genetic polymorphisms affecting ADH (ADH1B) and ALDH (ALDH2) activity. Patients were categorized into three groups: both inactivated = double-inactivated group; inactivated ADH1B or ALDH2 = single-inactivated group; and both activated = activated group. RESULTS: Among the 297 enrolled patients, patients in the double-inactivated group were significantly younger (P < 0.001) and 60% of them were ≤ 50 years old. This group also had more ESCCs located in the upper esophagus (P < 0.001) and more simultaneous multiple ESCCs (P = 0.044). More than half of the patients had multiple Lugol-voiding lesions (LVLs) (P < 0.001) and heavy alcohol consumers (P = 0.012). Metachronous ESCC and HNSCC were more common in the double-inactivated group (P < 0.001, P = 0.001). Multivariate analysis identified located in the upper esophagus, multiple LVLs and history of HNSCC as risk factors for metachronous ESCC. CONCLUSIONS: Activation patterns of alcohol-metabolizing enzymes were related to age at ESCC onset, lesion location, and metachronous ESCC and HNSCC. Different approaches to the prophylaxis and treatment of esophageal cancer should be considered, depending on the enzyme activity pattern.

Indication of emergency colonoscopy after colorectal endoscopic submucosal dissection: A proposal of hematochezia scale.

BACKGROUND AND AIM: Hematochezia is a major adverse event associated with colorectal endoscopic submucosal dissection (ESD). This study aimed to distinguish between hematochezia that required endoscopic hemostasis and hematochezia that required no hemostasis. METHODS: This retrospective study included consecutive patients who underwent ESD for colorectal tumors at the Osaka International Cancer Institute between September 2017 and August 2020. The exclusion criteria were as follows: patients with coexisting advanced colorectal cancers or inflammatory bowel diseases, patients who received incomplete ESD or emergency surgery, or patients who underwent ESD for multiple lesions. We evaluated whether the patients had hematochezia and underwent emergency colonoscopy and hemostasis during hospitalization. The degree of hematochezia in the saved photographs was assessed using the hematochezia scale and classified as mild, moderate, or severe. Blood pressure, heart rate, time from ESD to first hematochezia, and total number of hematochezia episodes were also evaluated. RESULTS: Among the 437 patients who underwent ESD, 44 were excluded, and 393 patients were evaluated. Hematochezia was observed in 100 patients (25%). Emergency colonoscopy was performed in 12 patients (3%), and hemostasis was required in six patients (2%). For patients with hematochezia, only mild hematochezia and hematochezia that developed ≤ 48 h after ESD were significantly associated with no intervention for hemostasis. The positive predictive value for no intervention for hemostasis was 100% (93-100%) for mild hematochezia and 98% (93-100%) for hematochezia ≤ 48 h. CONCLUSIONS: Mild hematochezia and hematochezia ≤ 48 h were negative predictors of hemostasis, in which emergency colonoscopy may be avoided.

Positive predictive value of the clinical diagnosis of T1a-epithelial/lamina propria esophageal cancer depends on lesion size.

OBJECTIVES: Endoscopic resection (ER) is a minimally invasive treatment for esophageal squamous cell carcinoma (ESCC). However, stricture may develop after ER for widespread lesions. Application of ER is justified if these cancers are pathological T1a-epithelial/lamina propria (pEP/LPM) cancers that can be cured by ER. We conducted a study to clarify the association between pathological invasion depth and lesion size or circumference in clinical (c) EP/LPM cancers. METHODS: From our database, we identified patients diagnosed with cEP/LPM ESCC via endoscopic examination who underwent endoscopic or surgical tumor resection. The accuracy of the cEP/LPM ESCC diagnosis was determined by histologically diagnosing cancer invasion depth as a reference standard. RESULTS: Between January 2015 and December 2019, 1271 cancer patients were diagnosed with cEP/LPM ESCC, of which 1195 (94.0%) were correctly diagnosed with pEP/LPM cancer. The positive predictive value (PPV) classified according to lesion sizes of ≤25, 26-49, and ≥50 mm was 95.8% (981/1024 lesions), 89.7% (191/213 lesions), and 67.6% (23/34 lesions), respectively. PPV according to the circumferential extent of <3/4, ≥3/4, and <1, and whole was 94.6% (1164/1230 lesions), 75.0% (24/32 lesions), and 77.8% (7/9 lesions), respectively. In multivariate analysis, the PPV of cEP/LPM ESCC was significantly associated with lesion size (P < 0.001) and male sex. CONCLUSIONS: Between January 2015 and December 2019, 1271 cancer patients were diagnosed with cEP/LPM ESCC, of which 1195 (94.0%) were correctly diagnosed with pEP/LPM cancer. The PPV of cEP/LPM ESCC was related to lesion size. Treatment should be determined considering the high risk of cancer invasion into the muscularis mucosa or deeper in cEP/LPM cancers with a lesion size of ≥50 mm.

Safety and efficacy of cold versus hot snare polypectomy including colorectal polyps ≥1 cm in size.

Cold snare polypectomy (CSP; polypectomy without electrocautery) has spread rapidly worldwide during the past decade in what has been called "Cold Revolution". We performed a PubMed literature search for studies investigating CSP outcomes for colorectal polyps. Five randomized controlled trials (RCTs) assessed the complete resection rates (CRRs). The CRRs were similar regardless of the presence or absence of electrocautery, and the efficacy of submucosal injection for better CRRs is still controversial. Eight RCTs assessed the adverse events. The incidence of intraprocedural bleeding with cold procedures was comparable to or higher than that of hot procedures. The incidences of delayed bleeding were comparable to or lower with cold procedures, especially in patients taking anticoagulants. Fifteen studies have been reported on CSP for large (≥1 cm) colorectal polyps (10 retrospective studies, four prospective single-arm studies, and one prospective RCT). These studies reported that the safe cold procedures (a low intra- and post-procedural bleeding rate without perforation) could be implemented for lesions ≥1 cm. However, considering the incision depth of CSP and the local recurrence rate based on the current evidence, only large sessile serrated lesions (SSLs) can be candidates for cold procedures, and large adenomas should not be candidates for this procedure. Based on the current evidence, CSP seems to be the appropriate standard procedure for sub-centimeter colorectal low-grade adenomas due to its safety and simplicity. Thus, large SSLs can be candidates for cold procedures; however, careful inspection and further prospective studies are warranted to confirm the procedure's clinical relevance.

Gradual onset of the Maunder Minimum revealed by high-precision carbon-14 analyses.

The Sun exhibits centennial-scale activity variations and sometimes encounters grand solar minimum when solar activity becomes extremely weak and sunspots disappear for several decades. Such an extreme weakening of solar activity could cause severe climate, causing massive reductions in crop yields in some regions. During the past decade, the Sun's activity has tended to decline, raising concerns that the Sun might be heading for the next grand minimum. However, we still have an underdeveloped understanding of solar dynamo mechanisms and hence precise prediction of near-future solar activity is not attained. Here we show that the 11-year solar cycles were significantly lengthened before the onset of the Maunder Minimum (1645-1715 CE) based on unprecedentedly high-precision data of carbon-14 content in tree rings. It implies that flow speed in the convection zone is an essential parameter to determine long-term solar activity variations. We find that a 16 year-long cycle had occurred three solar cycles before the onset of prolonged sunspot disappearance, suggesting a longer-than-expected preparatory period for the grand minimum. As the Sun has shown a tendency of cycle lengthening since Solar Cycle 23 (1996-2008 CE), the behavior of Solar Cycle 25 can be critically important to the later solar activity.

Prolonged production of 14C during the ~660 BCE solar proton event from Japanese tree rings.

Annual rings record the intensity of cosmic rays (CRs) that had entered into the Earth's atmosphere. Several rapid 14C increases in the past, such as the 775 CE and 994CE 14C spikes, have been reported to originate from extreme solar proton events (SPEs). Another rapid 14C increase, also known as the ca. 660 BCE event in German oak tree rings as well as increases of 10Be and 36Cl in ice cores, was presumed similar to the 775 CE event; however, as the 14C increase of approximately 10‰ in 660 BCE had taken a rather longer rise time of 3-4 years as compared to that of the 775 CE event, the occurrence could not be simply associated to an extreme SPE. In this study, to elucidate the rapid increase in 14C concentrations in tree rings around 660 BCE, we have precisely measured the 14C concentrations of earlywoods and latewoods inside the annual rings of Japanese cedar for the period 669-633 BCE. Based on the feature of 14C production rate calculated from the fine measured profile of the 14C concentrations, we found that the 14C rapid increase occurred within 665-663.5 BCE, and that duration of 14C production describing the event is distributed from one month to 41 months. The possibility of occurrence of consecutive SPEs over up to three years is offered.

Temporal variation of (7)Be concentrations in atmosphere for 8y from 2000 at Yamagata, Japan: solar influence on the (7)Be time series.

We have been continuously observing the daily (7)Be concentrations in surface air at Yamagata, Japan (38.25 degrees N, 140.35 degrees E) since 2000. The yearly profile of the (7)Be concentration indicates the variation in galactic cosmic rays owing to solar modulation. Over 8y, the (7)Be concentration, cosmic neutrons, and number of sunspots varied by 37.4%, 12.2%, and 92.8%, respectively. The influence of precipitation on the (7)Be variability was approximately 5%. Hence, the yearly (7)Be concentration was mainly varied by the solar modulation of the (7)Be production rates. Based on the production rates found in an EXPACS simulation, the observed variability indicates (7)Be transport from high latitudes. The daily (7)Be concentrations have two significant periodic components of 19d and 36d. The 36-d component implies a relationship between the sun's rotation and the vertical transport of air masses under quiet solar activity.