Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis.

OBJECTIVES: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomised into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day, and IVMP 1.0 g/day. The primary outcome was all-cause death, and the secondary outcomes were composite all-cause death and kidney failure, severe relapse, and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. RESULTS: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (2.8%) died, 4 (2.0%) had kidney failure, 11 (5.3%) had severe relapse, and 40 (19.8%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause death = 0.46 (95% confidence interval [95%CI]: 0.07-2.81) and 0.07 (95%CI: 0.01-0.41); all-cause death/kidney failure = 1.18 (95%CI: 0.26-5.31) and 0.59 (95%CI: 0.08-4.52); subdistribution HRs for severe relapse = 1.26 (95%CI: 0.12-13.70) and 3.36 (95%CI: 0.49-23.29); and serious infection = 1.88 (95%CI: 0.76-4.65) and 0.94 (95%CI: 0.28-3.13). CONCLUSIONS: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.

Kidney damage relates to agonal bacteremia: a single-center retrospective study.

BACKGROUND: Agonal bacteremia, diagnosed with postmortem positive blood culture results, is considered a possible contributing factor to death. We hypothesized that some premortem organ damage, such as kidney damage, can enhance agonal bacteremia. METHODS: We performed a postmortem blood and alveolar fluid culture study in 30 cadavers and evaluated the relationship between blood culture results and clinical parameters, including organ damage (brain, heart, lung, kidney, liver and gastrointestinal tract). RESULTS: A total of 23 cases (76.7%) were positive for blood culture; the number of cultured species was one in 12 cases, two in 7 cases, and three in 4 cases. The ratio of agonal bacteremia was significantly higher in patients with heart damage (100%, n = 13) and those with kidney damage (end-stage kidney damage, acute kidney injury, obstructive kidney failure, or metastatic kidney tumours) (100%, n = 13). The mean number of cultured species was 0.67 ± 0.98 in heart or kidney damage, 1.40 ± 0.55 in heart damage only, 1.40 ± 0.55 in kidney damage only, and 2.00 ± 0.93 in heart and kidney damage. As the number of damaged organs increased (0 organs, no heart/kidney damage; 1 organ, heart or kidney damage; and 2 organs, heart and kidney damage), the mean number of cultured species increased significantly (p for trend = 0.001964). CONCLUSION: Premortem kidney damage relates to agonal bacteremia.

Cystatin C as a Potential Blood Biomarker for Sarcoidosis: A Case Report.

Sarcoidosis is a multi-organ medical condition that is characterized by the formation of granulomas. We aimed to identify a correlation between each sarcoidosis blood biomarker and cystatin C (Cys-C) in sarcoidosis patients. We report a case of a 60-year-old man with sarcoidosis. The correlation between his Cys-C and each blood biomarker level and that between each blood biomarker and serum creatinine levels were determined using linear regression. Serum Cys-C correlated with each blood biomarker of sarcoidosis, while creatinine did not. These findings suggest that Cys-C is a potential blood biomarker for sarcoidosis.

Seasonal Influence on Development of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Retrospective Cohort Study Conducted at Multiple Institutions in Japan (J-CANVAS).

OBJECTIVE: To clarify seasonal and other environmental effects on the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We enrolled patients with new-onset eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and granulomatosis with polyangiitis (GPA) registered in the database of a Japanese multicenter cohort study. We investigated the relationship between environmental factors and clinical characteristics. Seasons were divided into 4 (spring, summer, autumn, and winter), and the seasonal differences in AAV onset were analyzed using Pearson chi-square test, with an expected probability of 25% for each season. RESULTS: A total of 454 patients were enrolled, with a mean age of 70.9 years and a female proportion of 55.5%. Overall, 74, 291, and 89 patients were classified as having EGPA, MPA, and GPA, respectively. Positivity for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA was observed in 355 and 46 patients, respectively. Overall, the seasonality of AAV onset significantly deviated from the expected 25% for each season (P = 0.001), and its onset was less frequently observed in autumn. In ANCA serotypes, seasonality was significant in patients with MPO-ANCA (P < 0.001), but not in those with PR3-ANCA (P = 0.97). Additionally, rural residency of patients with AAV was associated with PR3-ANCA positivity and biopsy-proven pulmonary vasculitis. CONCLUSION: The onset of AAV was influenced by seasonal variations and was less frequently observed in autumn. In contrast, the occurrence of PR3-ANCA was triggered, not by season, but by rural residency.

Occurrence of fever in cell-free and concentrated ascites reinfusion therapy is not related to the primary disease or nature of ascites.

Cell-free and concentrated ascites reinfusion therapy (CART) is a treatment for refractory ascites wherein filtered and concentrated ascitic fluid is reinfused. Although fever is one of the side effects of CART, its cause is not clear. Patients who underwent at least one CART session between June 2011 and May 2021 at our medical center were retrospectively enrolled in the study. They were classified according to the primary disease and nature of ascites. Ninety patients were included in this study. Increase in body temperature (BT) after CART was observed, regardless of the primary disease and nature of ascites. The difference in temperature before and after CART did not differ based on the primary disease [cancerous (including hepatocellular carcinoma, ovarian cancer) and non-cancerous] and nature of ascites. Elevated BT and fever after CART are not related to the primary disease and nature of the ascites.

Association between hypogammaglobulinaemia and severe infections during induction therapy in ANCA-associated vasculitis: from J-CANVAS study.

OBJECTIVES: To investigate the association between decreased serum IgG levels caused by remission-induction immunosuppressive therapy of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the development of severe infections. METHODS: We conducted a retrospective cohort study of patients with new-onset or severe relapsing AAV enrolled in the J-CANVAS registry, which was established at 24 referral sites in Japan. The minimum serum IgG levels up to 24 weeks and the incidence of severe infection up to 48 weeks after treatment initiation were evaluated. After multiple imputations for all explanatory variables, we performed the multivariate analysis using a Fine-Gray model to assess the association between low IgG (the minimum IgG levels <500 mg/dl) and severe infections. In addition, the association was expressed as a restricted cubic spline (RCS) and analysed by treatment subgroups. RESULTS: Of 657 included patients (microscopic polyangiitis, 392; granulomatosis with polyangiitis, 139; eosinophilic granulomatosis with polyangiitis, 126), 111 (16.9%) developed severe infections. The minimum serum IgG levels were measured in 510 patients, of whom 77 (15.1%) had low IgG. After multiple imputations, the confounder-adjusted hazard ratio of low IgG for the incidence of severe infections was 1.75 (95% confidence interval: 1.03-3.00). The RCS revealed a U-shaped association between serum IgG levels and the incidence of severe infection with serum IgG 946 mg/dl as the lowest point. Subgroup analysis showed no obvious heterogeneity between treatment regimens. CONCLUSION: Regardless of treatment regimens, low IgG after remission-induction treatment was associated with the development of severe infections up to 48 weeks after treatment initiation.

Treatment with vonoprazan for 3 weeks is not inferior to 8 weeks for the management of gastric ESD: a multicenter noninferiority randomized study.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker (VPZ), significantly reduces postoperative bleeding after gastric ESD; however, there is no consensus on the appropriate treatment duration. We conducted a randomized controlled study to demonstrate that the 3-week administration of VPZ is not inferior to the 8-week administration for ulcer healing. METHODS: This is a prospective, open-label multicenter randomized controlled trial. Patients aged 20-85 years undergoing gastric ESD were included in this study. The key exclusion criteria were patients with bleeding tendencies and those taking NSAIDs, steroids, PPIs, or VPZ medications. Eligible patients were randomly assigned to the VPZ 3w or 8w treatment group. The primary endpoint was the proportion of patients with complete closure of the post-ESD wound at 24 weeks after ESD. The key secondary endpoints included the proportion of patients with complete closure of the post-ESD wound at 8 weeks and the proportion of bleeding or perforation more than 3 weeks after ESD. RESULTS: From May 2018 to October 2020, 234 patients were included. The proportion of patients with complete ulcer closure was significantly lower in the 3w group than in the 8w group (70.8% vs. 90.6%) at 8 weeks post-treatment. The complete closure rates at 24 weeks in the 3w and 8w groups were 99.1% and 99.2%, respectively. The absolute difference in the closure rate at 24 weeks was - 0.059% [95% confidence interval (CI) -3.4% to 3.2], and the lower limit of the 95% CI exceeded -10%, the preset threshold. None of the patients developed delayed bleeding 3 weeks after ESD. CONCLUSION: This multicenter randomized study demonstrated that 3 weeks of treatment with VPZ is sufficient for ulcer healing. Trial registry number. UMIN000031564.

Utility of renal biopsy in differentiating idiopathic multicentric Castleman disease from IgG4-related disease.

Idiopathic multicentric Castleman disease (iMCD) is a subtype of human herpesvirus type 8 (HHV-8)-related Castleman disease that causes multi-organ damage, including kidney damage due to polyclonal lymphoproliferation and interleukin (IL)-6-induced cytokine storm. However, its renal pathological findings are unclear. We report the case of a woman in her 80 s who was diagnosed with iMCD based on renal pathological findings. Five years ago, hypergammaglobulinemia was detected, and her renal function declined. Renal biopsy revealed plasma cells infiltrating the stroma. Immunostaining revealed numerous IgG4-positive plasma cells. The serum IgG4 level was high, and she was initially diagnosed with IgG4-related disease (IgG4-RD) and treated with steroids. However, the therapeutic effect was poor. On re-examination, computed tomography revealed lymphadenopathy around the aorta and spleen. Renal histopathology showed numerous IL-6-positive plasma cells. Anemia and C-reactive protein (CRP) positivity persisted despite steroid administration. HHV-8 was negative, and polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome was not suspected. Thus, iMCD was diagnosed. Based on previous reports, there is no significant difference in IgG4 levels between iMCD and IgG4-RD, and IgG4-positive plasma cell infiltrates were observed in iMCD-affected organs. Therefore, it may be difficult to distinguish iMCD from IgG4-RD. In this case, high-serum IL-6 and CRP were observed, which are usually not seen in IgG4-RD but are common findings in iMCD, leading to the diagnosis. Patients with deep lymphadenopathy may be diagnosed with iMCD based on renal pathological findings. Renal biopsy is recommended for patients with suspected iMCD and decreased renal function.

Laparoscopic repair of diaphragmatic hernia associating with radiofrequency ablation for hepatocellular carcinoma: A case report.

BACKGROUND: Radiofrequency ablation (RFA) is an effective treatment for early-stage hepatocellular carcinoma (HCC). Although RFA is a relatively safe technique compared with surgery, several complications have been reported to be following/accompanying this treatment. Delayed diaphragmatic hernia caused by RFA is rare; however, the best surgical approach for its treatment is uncertain. We present a case of laparoscopic repair of diaphragmatic hernia due to RFA. CASE SUMMARY: An 80-year-old woman with segment VIII HCC was treated twice in 5 years with RFA; 28 mo after the second RFA, the patient complained of right hypochondriac pain. Computed tomography revealed that the small intestine was incarcerated in the right thorax. The patient was diagnosed with diaphragmatic hernia and underwent laparoscopic repair by non-absorbable running sutures. The patient's postoperative course was favorable, and the patient was discharged on postoperative day 12. The diaphragmatic hernia has not recurred 24 mo after surgery. CONCLUSION: Laparoscopic treatment of iatrogenic diaphragmatic hernia is effective and minimally invasive.

Hypertrophic pachymeningitis in ANCA-associated vasculitis: a cross-sectional and multi-institutional study in Japan (J-CANVAS).

BACKGROUND: This study investigated the characteristics of hypertrophic pachymeningitis (HP) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), using information from a multicenter study in Japan. METHODS: We analyzed the clinical information of 663 Asian patients with AAV (total AAV), including 558 patients with newly diagnosed AAV and 105 with relapsed AAV. Clinical findings were compared between patients with and without HP. To elucidate the relevant manifestations for HP development, multivariable logistic regression analyses were additionally performed. RESULTS: Of the patients with AAV (mean age, 70.2 ± 13.5 years), HP was noted in 30 (4.52%), including 20 (3.58%) with newly diagnosed AAV and 10 (9.52%) with relapsed AAV. Granulomatosis with polyangiitis (GPA) was classified in 50% of patients with HP. A higher prevalence of GPA was significantly observed in patients with HP than in those without HP in total AAV and newly diagnosed AAV (p < 0.001). In newly diagnosed AAV, serum proteinase 3 (PR3)-ANCA positivity was significantly higher in patients with HP than in those without HP (p = 0.030). Patients with HP significantly had ear, nose, and throat (ENT) (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.03-2.14, p = 0.033) and mucous membrane/eye manifestations (OR 5.99, 95% CI 2.59-13.86, p < 0.0001) in total AAV. Moreover, they significantly had conductive hearing loss (OR 11.6, 95% CI 4.51-29.57, p < 0.0001) and sudden visual loss (OR 20.9, 95% CI 5.24-85.03, p < 0.0001). CONCLUSION: GPA was predominantly observed in patients with HP. Furthermore, in newly diagnosed AAV, patients with HP showed significantly higher PR3-ANCA positivity than those without HP. The ear and eye manifestations may be implicated in HP development.

Deep learning analysis of clinical course of primary nephrotic syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. METHODS: Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder-decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. RESULTS: Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. CONCLUSIONS: Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

Predictors of early remission of proteinuria in adult patients with minimal change disease: a retrospective cohort study.

Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein < 0.3 g/day (or g/gCr) was observed in 104 (96.3%) patients. Of 97 patients with remission within 6 month of IST, 42 (43.3%) developed relapse defined as ≥ 1.0 g/day (or g/gCr) or dipstick urinary protein of ≥ 2+. Serum albumin concentration was significantly associated with remission (multivariable-adjusted hazard ratio [95% confidence interval] per 1.0 g/dL, 0.57 [0.37, 0.87]), along with eGFR (per 30 mL/min/1.73 m2: 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m2) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR (< 60 mL/min/1.73 m2) and high albumin concentration (> 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.

Intra vitam assays for detecting fish infected with cyprinid herpesvirus 3 (CyHV-3).

Koi carp is one of the most sensitive variants of common carp Cyprinus carpio to cyprinid herpesvirus 3, commonly known as koi herpesvirus (KHV). Given that this species is traded at high prices throughout the world, intra vitam assays for detecting KHV in targeted fish with a high detection efficiency are essential. In this study, 4 intra vitam assays were compared with regard to their efficiency of detecting KHV in koi carp on each day after viral exposure via experimental infection. The results indicated that PCR from the gills and scales sampled by biopsy using dissecting scissors and forceps, respectively, can detect KHV for apparently longer periods than the other assays. This study also suggests that a PCR detection assay for environmental samples could be developed as a convenient intra vitam assay to confirm the presence of virus in environments inhabited by virus-shedding fish.

IgA Nephropathy that Developed as an Immune-related Adverse Event of Pembrolizumab Complicated with Interstitial Nephritis.

A 70-year-old man received pembrolizumab as a second-line treatment for squamous cell lung cancer of the lower right lobe. After three courses, proteinuria and hematuria were observed, which worsened after seven courses. He was diagnosed with a combination of IgA nephropathy and active interstitial nephritis. Steroid pulse therapy was started, and the dose of prednisolone was gradually reduced from 60 mg/day. Renal dysfunction as an immune-related adverse event of pembrolizumab monotherapy for non-small cell lung cancer has been reported previously. Therefore, establishing a system for the early detection and treatment that distinguishes immune-related glomerular diseases is essential.

Detection of Autosomal Dominant Polycystic Kidney Disease by Medical Checkup at an Early Stage.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease. Although abdominal echography during medical checkup may be effective for the early detection of ADPKD, there are no reports of the early detection of ADPKD during medical checkup. We investigated whether there was a difference in renal function and total kidney volume (TKV) at the time of diagnosis due to differences in diagnostic triggers for ADPKD. METHODS: A total of 34 patients diagnosed with ADPKD between January 1, 2010, and December 31, 2020, at the Department of Nephrology, Shimane University Hospital, were included. The triggers for diagnosis of the renal cyst(s) were usually unintentional findings. These included findings observed upon routine medical checkups, computed tomography, or abdominal echography during examination for other diseases (incidental detection group) and cases referred to our department for renal dysfunction (renal dysfunction group), and "other" group. We compared the renal dysfunction group and the incidental detection group. RESULTS: The estimated glomerular filtration rate (eGFR) at diagnosis was significantly higher in the incidental detection group. The TKV was significantly lower in the incidental detection group than in the other group. The number of patients with eGFR > 45 mL/min/1.73 m2, for which tolvaptan was safe and effective, was significantly higher in the incidental detection group than in the renal dysfunction group. CONCLUSION: Our study shows that medical checkup enables early detection of ADPKD. This is important because ADPKD may have serious complications. The present study did not examine the age at which abdominal echography screening for the early detection of ADPKD was more useful or cost-effective; thus, further research is needed to ascertain this.

[Investigation of the safety and usefulness of a renal biopsy for older elderly patients ≥75 years old].

AIM: We herein report the safety and usefulness of a kidney biopsy in older elderly patients (≥75 years old). METHODS: A retrospective observational study was conducted in older elderly patients who had received a renal biopsy at the Department of Nephrology, Shimane University Hospital, from January 1, 2008, to December 31, 2018. The native renal biopsy results of 52 later-stage elderly patients were analyzed (29 men and 23 women). RESULTS: The most common indication for a renal biopsy was nephrotic syndrome (n = 22), followed by rapidly progressive glomerulonephritis (n = 12) and asymptomatic urinary abnormalities (n = 12). The most common pathological diagnosis was membranous nephropathy (n = 12), followed by ANCA-associated nephritis (n= 8), minimal change nephrotic syndrome (6 case), membranoproliferative glomerulonephritis (n = 5), IgA nephropathy (n = 4), and diabetic nephropathy (n = 3). The concordance rate between the clinical and pathological diagnoses was 53.8%. The only complication of the renal biopsy was hemorrhaging requiring blood transfusion (1 patient; 1.9%). The hemoglobin level decreased by 0.5±0.05 d/dL after the biopsy. CONCLUSION: The rate of serious complications associated with a renal biopsy was comparable to that in previous reports in younger patient. Renal biopsies can therefore be safely performed even in older elderly patients. The concordance rate of the clinical and pathological diagnoses was about 50%. Therefore, renal biopsies should be performed in older elderly patients when necessary.

Japanese amberjack Seriola quinqueradiata and red sea bream Pagrus major susceptibility to infectious hematopoietic necrosis virus (IHNV) isolate.

Infectious hematopoietic necrosis virus (IHNV) is known as a causative agent of heavy mortalities in farmed rainbow trout. However, there is limited information on its virulence for marine fish species. In this study, Japanese amberjack Seriola quinqueradiata and red sea bream Pagrus major were experimentally infected by intraperitoneal (IP) injection and immersion, with an IHNV isolate from rainbow trout in Japan, to evaluate the virulence of the virus for these fish species. The cumulative mortality for immersed rainbow trout was 15%. IHNV was isolated from all dead fish and 50% of the sequentially sampled rainbow trout. When Japanese amberjack were challenged by IP injection and immersion, the resulting cumulative mortality was 70% and 0%, respectively. The virus was isolated from all dead fish and 1 out of 3 Japanese amberjack sampled at 9 d post exposure. However, no mortality was observed in either of the red sea bream groups challenged with IHNV. IHNV was not isolated from any of the surviving red sea bream, or from any of the sequentially sampled fish. The viral titer on Japanese amberjack-derived YTF cells was in the same log range as that on FHM and RTH-149 cells, but the titers on the red sea bream cell lines SBK and GBRS were lower than the other cell lines, and were significantly different from the FHM and RTH-149 cell lines. These results suggest that Japanese amberjack has a low susceptibility to IHNV, and red sea bream has no or little susceptibility to the virus.

Recurrence after ESD curative resection for early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is gaining ground as a minimally invasive treatment for early gastric cancer (EGC) that has a negligible risk of lymph node metastasis. According to the 5th edition of Japanese gastric cancer treatment guidelines, annual or biannual follow-up with endoscopy is recommended, but follow-up with abdominal ultrasonography or computed tomography (CT) for surveillance of metastases is not recommended after the eCuraA resection. However, we experienced a case of lymph node recurrence following ESD resulting in eCuraA. CASE PRESENTATION: A 76-year-old female received ESD for EGC in a previous hospital 4 years ago. Pathological findings were tub1, 30 mm, T1a (M), UL0, Ly0, V0, pHM-, pVM- (eCuraA) according to the 15th edition of Japanese Classification of Gastric Carcinoma. Follow-up esophagogastroduodenoscopy revealed submucosal tumor, which was suspected as a swollen lymph node by CT and endoscopic ultrasound fine-needle aspiration revealed the recurrence of gastric cancer. We performed total gastrectomy with D2 lymph node dissection. Postoperative pathological examination revealed no local recurrent tumor at the ESD site in the stomach. Swollen lymph node was diagnosed as metastasis and lymph node metastasis was limited near the cardia. CONCLUSION: This case provides valuable information about tumor with a minimum poorly differentiated adenocarcinoma component may develop lymph node metastasis even satisfying the guidelines criteria for curative resection.