Underwater EMR in the reconstructed gastric conduit after esophagectomy.

Video 1Three cases of underwater EMR for small gastric neoplasms in the reconstructed gastric conduit after esophagectomy.

High incidence of lung cancer death after curative endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Following treatment of superficial esophageal squamous cell carcinoma (ESCC), surveillance for a second primary malignancy (SPM) is necessary. However, detailed evidence regarding the timing and prognosis of SPMs is insufficient. We aimed to clarify the details of SPMs and their effects on patient outcomes. METHODS: This retrospective, multicenter study involved 11 hospitals. Patients with superficial ESCC curatively resected using endoscopic submucosal dissection between May 2005 and December 2012, were included in this study. RESULTS: The 5-year survival rate of 187 patients was 92.6% during a median follow-up duration of 96.8 months. Thirty-one patients died, 14 of whom died of SPMs. Compared to patients with SPMs detectable by esophagogastroduodenoscopy (EGD), patients with SPMs detectable only by modalities other than EGD had a significantly higher mortality rate (p < 0.001). Patients with second primary lung cancer (LC) had a high mortality rate (56.3%). Univariate and multivariate analyses showed that multiple Lugol-voiding lesions (LVLs) tended to be associated with SPMs (p = 0.077, hazard ratio [HR] 4.43, 95% confidence interval [CI]: 0.91-6.50), and metachronous ESCC was an independent risk factor for the incidence of second primary LC (p = 0.037, HR 3.51, 95% CI: 1.08-11.41). CONCLUSIONS: SPMs that cannot be detected by EGD, such as LC, must be considered after the curative resection of ESCC. We suggest strict screening by both EGD and computed tomography for patients with multiple LVLs or metachronous ESCC to detect SPMs in their early stages.

A machine learning model for predicting the lymph node metastasis of early gastric cancer not meeting the endoscopic curability criteria.

BACKGROUND: We developed a machine learning (ML) model to predict the risk of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) who did not meet the existing Japanese endoscopic curability criteria and compared its performance with that of the most common clinical risk scoring system, the eCura system. METHODS: We used data from 4,042 consecutive patients with EGC from 21 institutions who underwent endoscopic submucosal dissection (ESD) and/or surgery between 2010 and 2021. All resected EGCs were histologically confirmed not to satisfy the current Japanese endoscopic curability criteria. Of all patients, 3,506 constituted the training cohort to develop the neural network-based ML model, and 536 constituted the validation cohort. The performance of our ML model, as measured by the area under the receiver operating characteristic curve (AUC), was compared with that of the eCura system in the validation cohort. RESULTS: LNM rates were 14% (503/3,506) and 7% (39/536) in the training and validation cohorts, respectively. The ML model identified patients with LNM with an AUC of 0.83 (95% confidence interval, 0.76-0.89) in the validation cohort, while the eCura system identified patients with LNM with an AUC of 0.77 (95% confidence interval, 0.70-0.85) (P = 0.006, DeLong's test). CONCLUSIONS: Our ML model performed better than the eCura system for predicting LNM risk in patients with EGC who did not meet the existing Japanese endoscopic curability criteria. We developed a neural network-based machine learning model that predicts the risk of lymph node metastasis in patients with early gastric cancer who did not meet the endoscopic curability criteria.

Thrombospondin-1 is an endogenous substrate of cereblon responsible for immunomodulatory drug-induced thromboembolism.

ABSTRACT: Immunomodulatory drugs (IMiDs) are key drugs for treating multiple myeloma and myelodysplastic syndrome with chromosome 5q deletion. IMiDs exert their pleiotropic effects through the interaction between cell-specific substrates and cereblon, a substrate receptor of the E3 ubiquitin ligase complex. Thus, identification of cell-specific substrates is important for understanding the effects of IMiDs. IMiDs increase the risk of thromboembolism, which sometimes results in fatal clinical outcomes. In this study, we sought to clarify the molecular mechanisms underlying IMiDs-induced thrombosis. We investigated cereblon substrates in human megakaryocytes using liquid chromatography-mass spectrometry and found that thrombospondin-1 (THBS-1), which is an inhibitor of a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13, functions as an endogenous substrate in human megakaryocytes. IMiDs inhibited the proteasomal degradation of THBS-1 by impairing the recruitment of cereblon to THBS-1, leading to aberrant accumulation of THBS-1. We observed a significant increase in THBS-1 in peripheral blood mononuclear cells as well as larger von Willebrand factor multimers in the plasma of patients with myeloma, who were treated with IMiDs. These results collectively suggest that THBS-1 represents an endogenous substrate of cereblon. This pairing is disrupted by IMiDs, and the aberrant accumulation of THBS-1 plays an important role in the pathogenesis of IMiDs-induced thromboembolism.

Impact of AI-aided colonoscopy in clinical practice: a prospective randomised controlled trial.

OBJECTIVE: Colorectal cancer (CRC) has a significant role in cancer-related mortality. Colonoscopy, combined with adenoma removal, has proven effective in reducing CRC incidence. However, suboptimal colonoscopy quality often leads to missed polyps. The impact of artificial intelligence (AI) on adenoma and polyp detection rate (ADR, PDR) is yet to be established. DESIGN: We conducted a randomised controlled trial at Sahlgrenska University Hospital in Sweden. Patients underwent colonoscopy with or without the assistance of AI (AI-C or conventional colonoscopy (CC)). Examinations were performed with two different AI systems, that is, Fujifilm CADEye and Medtronic GI Genius. The primary outcome was ADR. RESULTS: Among 286 patients, 240 underwent analysis (average age: 66 years). The ADR was 42% for all patients, and no significant difference emerged between AI-C and CC groups (41% vs 43%). The overall PDR was 61%, with a trend towards higher PDR in the AI-C group. Subgroup analysis revealed higher detection rates for sessile serrated lesions (SSL) with AI assistance (AI-C 22%, CC 11%, p=0.004). No difference was noticed in the detection of polyps or adenomas per colonoscopy. Examinations were most often performed by experienced endoscopists, 78% (n=86 AI-C, 100 CC). CONCLUSION: Amidst the ongoing AI integration, ADR did not improve with AI. Particularly noteworthy is the enhanced detection rates for SSL by AI assistance, especially since they pose a risk for postcolonoscopy CRC. The integration of AI into standard colonoscopy practice warrants further investigation and the development of improved software might be necessary before enforcing its mandatory implementation. TRIAL REGISTRATION NUMBER: NCT05178095.

Pediatric leukemia and maternal occupational exposure to anticancer drugs: the Japan Environment and Children's Study.

ABSTRACT: Occupational exposure to medical agents and ionizing radiation has been suggested as a possible risk factor for childhood cancer. However, the relationship between such exposure and pediatric malignant neoplasms has not yet been comprehensively studied. This cohort study aimed to investigate the association between parental occupational exposure to hazardous medical agents or ionizing radiation and the risk of childhood cancer in offspring. Data from a large birth cohort in Japan, which included 104 062 fetuses, were analyzed. The primary outcome was the development of leukemia or brain tumors diagnosed by community physicians during the first 3 years after birth. Exposure factors were medical agents, including anticancer agents, ionizing radiation, and anesthetics, handled by mothers during pregnancy or by fathers for 3 months before conception. The incidence of leukemia, but not of brain tumors, was higher in mothers exposed to anticancer drugs. Multivariable regression analysis showed that maternal exposure to anticancer drugs was associated with an increased risk of leukemia in offspring older than 1 year (adjusted relative risk, 7.99 [95% confidence interval, 1.98-32.3]). Detailed information obtained from medical certificates of patients with identified leukemia revealed no infant leukemia but acute lymphoblastic leukemias in the exposed group. Our findings suggest that maternal occupational exposure to anticancer drugs may be a potential risk factor for acute lymphoblastic leukemia in offspring older than 1 year. Effective prevention methods may be necessary to prevent maternal exposure to anticancer drugs and to reduce the risk of childhood malignant neoplasms.

[Rectal cancer with multiple metastases complicated by Crohn's disease 5 years after surgery:a case report].

In recent years, with the rising incidence of patients having long-term Crohn's disease, there has been an increase in the number of reports of carcinogenesis from dysplasia with chronic inflammation as the primary pathogenic factor. We hereby report a case of multiple metastases that appeared 5 years after surgery, in a patient with rectal cancer who had Crohn's disease. A man in his 50s was diagnosed with Crohn's disease which affected his small and large intestines 21 years back. The patient was being treated with oral steroids, 5-aminosalicylic acid, and modified nutrition. Infliximab was added to the treatment after it was introduced 11 years ago. He also had a history of rectal cancer and had undergone surgery for the same 5 years back. He was diagnosed with stage II cancer, and had not received any adjuvant chemotherapy. However, 5 years after surgery, multiple metastases recurred, and chemotherapy with mFOLFOX6 was administered. Additionally, for treating his Crohn's disease, which was also active, infliximab was changed to vedolizumab;however, the patient died a year later. Colorectal cancer accompanied with Crohn's disease has a higher risk of developing metastasis and is associated with poorer prognosis as compared to the noncomplicated colorectal cancer. Regarding treatment modalities, while searching for multidisciplinary treatment methods centered on surgical treatment in collaboration with medical oncologists and radiologists, the safety of treatment for Crohn's disease in patients with cancer must be borne in mind. The rising prevalence of cases of colorectal cancer with Crohn's disease is expected to lead to the formulation of specialized diagnostic and treatment strategies for these patients.

[A case of severe colitis induced by the administration of pembrolizumab for pulmonary adenocarcinoma in a patient with ulcerative colitis].

Pembrolizumab is an immunoglobulin G4 isotype antibody that targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes. It is used in the treatment of advanced non-small cell lung cancer (NSCLC). The safety and efficacy of immunotherapy for autoimmune disease are currently unknown;immune-related adverse events induced by immune checkpoint inhibitors (ICIs) have been reported. We report a case of severe colitis induced by the administration of pembrolizumab for pulmonary adenocarcinoma in a patient with ulcerative colitis. A 72-year-old man with a 3-year history of ulcerative colitis maintained clinical remission with mesalazine. The recurrence of lung adenocarcinoma was diagnosed and treated with pembrolizumab as second-line treatment. Diarrhea and bloody stool recurred 5 months after the first administration of pembrolizumab. The colitis did not respond to corticosteroids and infliximab. Because of the recurrence of ulcerative colitis, treatment of the lung adenocarcinoma was discontinued, and the patient died 1 year after the first administration of pembrolizumab. Few cases of severe colitis induced by the administration of pembrolizumab in patients with ulcerative colitis have been reported. This case suggests that the clinical stratification of autoimmune disease and typical standards of effectiveness of treatment are needed for patients with autoimmune disease who are treated with ICIs.