An autopsy case of lung adenocarcinoma with immune checkpoint inhibitor-induced pneumonia and fulminant myocarditis following pembrolizumab administration: a case report.

Immune checkpoint inhibitors (ICIs) are the current standard of care for non-small-cell lung cancer (NSCLC). Myocarditis is a rare but serious immune-related adverse event (irAE) associated with ICI therapy. We present a patient who received a single dose of pembrolizumab for NSCLC and developed ICI-associated pneumonia. Although pneumonia improved with corticosteroid therapy, the patient subsequently developed ICI-associated fulminant myocarditis. Despite high-dose corticosteroid therapy, the patient died on day 30 after pembrolizumab initiation. Even if an observed irAE was effectively treated, clinicians should remain vigilant for other irAEs, especially those that are difficult to control with low-dose corticosteroids.

Are transmembrane 6 superfamily member 2 gene polymorphisms associated with steatohepatitis after pancreaticoduodenectomy?

Aim: After pancreaticoduodenectomy, 20-40% of patients develop steatotic liver disease (SLD), and steatohepatitis can be a problem. Although patatin-like phospholipase domain-containing 3 protein (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms are involved in SLD and steatohepatitis development, whether this is the case after pancreaticoduodenectomy is unclear. Methods and Results: Forty-three patients with pancreatic cancer who underwent pancreaticoduodenectomy at our hospital between April 1, 2018, and March 31, 2021, were included. We extracted DNA from noncancerous areas of residual specimens after pancreaticoduodenectomy and determined PNPLA3 and TM6SF2 gene polymorphisms using real-time polymerase chain reaction. SLD was defined as a liver with an attenuation value of ≤40 HU or a liver-to-spleen ratio of ≤0.9 on computed tomography. We defined high hepatic fibrosis indexes (HFI) instead of steatohepatitis as a Fibrosis-4 index of ≥2.67 or nonalcoholic fatty liver disease fibrosis score of ≥0.675 in patients with SLD. The cumulative incidence of SLD (P = 0.299) and high HFI (P = 0.987) after pancreaticoduodenectomy were not significantly different between the PNPLA3 homozygous and minor allele groups. The incidences of high HFI at 1 year after pancreaticoduodenectomy were 16.8% and 27.0% in the TM6SF2 major homozygous and minor allele groups, respectively, with a significant difference in the cumulative incidence (P = 0.046). Conclusion: The TM6SF2 minor allele may contribute to steatohepatitis development after pancreaticoduodenectomy.

Calcification of a Hydrophilic Acrylic Intraocular Lens after Glaucoma Surgery.

A Japanese woman in her 70s was referred to our hospital for the evaluation and treatment of high intraocular pressure (IOP) in her right eye. She had undergone bilateral cataract surgeries and the insertion of hydrophilic acrylic intraocular lenses (IOLs). We performed trabeculotomy and trabeculectomy to lower her right IOP; thereafter, a circular opacity was observed on the right eye's IOL surface. We removed the right IOL because that eye's vision had decreased due to IOL opacification. The analysis of the removed IOL revealed that the main opacity component was calcium phosphate. This is the first post-glaucoma-surgery IOL calcification case report.

Non-liver-related mortality in the DAA era: Insights from post-SVR patients with and without previous HCC history.

BACKGROUND AND AIMS: Mortality after sustained virological response (SVR) with interferon-free direct-acting antiviral (IFN-free DAA) therapy is crucial for optimizing post-SVR patient care, but it remains unclear, especially regarding non-liver-related mortality. METHODS: Consecutive post-SVR patients from 14 institutions were stratified into three cohorts: A (without advanced fibrosis and without prior HCC), B (with advanced fibrosis and without prior HCC), and C (curative HCC treatment). We assessed mortality (per 1000 person-years [/1000PY]) post-SVR. Mortality rates were compared between cohorts A and B and the general population using age- and sex-adjusted standardized mortality ratio (SMR). Comparison of survival between each cohort was performed using propensity-score (PS) matching with sex, age, and comorbidity. RESULTS: In cohort A (n = 762; median age, 65 years), 22 patients died (median follow-up, 36 months); all-cause mortality was 10.0/1000PY, with 86.4% non-liver-related deaths. In cohort B (n = 519; median age, 73 years), 27 patients died (median follow-up, 39 months); all-cause mortality was 16.7/1000PY, with 88.9% non-liver-related deaths. In both cohorts, malignant neoplasm was the most common cause of death; all-cause mortality was comparable to that of the general population (SMR: 0.96 and 0.92). In cohort C (n = 108; median age, 75 years), 15 patients died (median follow-up, 51 months); all-cause mortality was 36.0/1000PY, with 53.3% liver-related deaths. PS matching showed no significant survival differences between cohorts A and B, both of which had better survival than cohort C. CONCLUSIONS: Mortality varies based on HCC history in the DAA era; nevertheless, attention should be paid to non-liver-related deaths in all post-SVR patients.

[Air embolism after biliary stent removal during endoscopic retrograde cholangiopancreatography for cholangitis after biliary reconstruction: a case report].

A 62-year-old male patient underwent pancreaticoduodenectomy with modified Child reconstruction for distal cholangiocarcinoma. After eight years, a contrast-enhanced computed tomography (CT) revealed a recurrent lesion at the biliojejunal anastomosis, and a biliary stent was placed for obstructive cholangitis in the right posterior segment of the liver. A right hepatectomy was planned for a local recurrent lesion;thus, percutaneous transhepatic portal embolization was performed on the portal vein's right branch to enlarge the left liver. However, he was referred to our department for endoscopic retrograde biliary drainage for the subsequent cholangitis and liver abscess appearance. A double-balloon enteroscope under CO2 insufflation was used to reach the bile duct-jejunal anastomosis. After removing the bile duct stent with grasping forceps, his general condition suddenly deteriorated, causing cardiopulmonary arrest. He was diagnosed with air embolism based on the findings of air in the heart, aorta, and brain on CT after the return of spontaneous circulation. Treatment for the air embolism and subsequent complications continued in the intensive care unit, but he eventually died 114 days after the onset of the air embolism due to his deteriorating general condition. Pathological autopsy revealed cholangiocarcinoma that extends from the porta hepatis to the posterior segment. Additionally, the proximity between the bile duct and vein extended by the adenocarcinoma and the fibrous obstruction of the vein were revealed, indicating the possibility of a bile duct-vein shunt.

Recent Advances in Endoscopic Ultrasound for Gallbladder Disease Diagnosis.

Gallbladder (GB) disease is classified into two broad categories: GB wall-thickening and protuberant lesions, which include various lesions, such as adenomyomatosis, cholecystitis, GB polyps, and GB carcinoma. This review summarizes recent advances in the differential diagnosis of GB lesions, focusing primarily on endoscopic ultrasound (EUS) and related technologies. Fundamental B-mode EUS and contrast-enhanced harmonic EUS (CH-EUS) have been reported to be useful for the diagnosis of GB diseases because they can evaluate the thickening of the GB wall and protuberant lesions in detail. We also outline the current status of EUS-guided fine-needle aspiration (EUS-FNA) for GB lesions, as there have been scattered reports on EUS-FNA in recent years. Furthermore, artificial intelligence (AI) technologies, ranging from machine learning to deep learning, have become popular in healthcare for disease diagnosis, drug discovery, drug development, and patient risk identification. In this review, we outline the current status of AI in the diagnosis of GB.

Efficacy and safety of second-line therapy of docetaxel plus ramucirumab after first-line platinum-based chemotherapy plus immune checkpoint inhibitors in non-small cell lung cancer (SCORPION): a multicenter, open-label, single-arm, phase 2 trial.

Background: Immune checkpoint inhibitors (ICI) plus platinum-based chemotherapy has been recognized as a standard first-line therapy in non-small cell lung cancer (NSCLC); however, no prospective clinical trials of docetaxel (DTX) plus ramucirumab (RAM) following first-line ICI plus platinum-based chemotherapy has been reported. Methods: In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients with NSCLC from eight centres in Japan. Patients with metastatic NSCLC with disease progression after platinum-based chemotherapy plus ICI were eligible for the study. Patients were intravenously treated with 60 mg/m2 of DTX and 10 mg/kg of RAM on day 1 with a strong recommendation of pegfilgrastim administration on day 2 every 3 weeks. The primary end point was objective response rate (ORR) in efficacy analysis population. Safety was assessed in all patients treated at least one dose. The ORR of the null and alternative hypotheses were 10% and 30%, with α error of 0.1 and ß error of 0.1. This trial is registered with the Japan Registry for Clinical Trials, jCRTs041190077. Findings: Between 16 January, 2020, and 24 August, 2021, 33 patients (median age 66 [range 42-79] years) were enrolled. Thirteen patients (41%) had Eastern Cooperative Oncology Group performance status of 1. Twenty-five patients (78%) had an interval of <60 days after the last administration of ICI. In the efficacy analysis population (n = 32), the primary endpoint was met as 11 patients achieved partial response (PR), with ORR of 34.4% (80% CI, 23.1-47.2). Grade ≥3 anaemia and febrile neutropenia were observed in 2 (6%) and 3 (9%) patients, respectively. No treatment-related deaths and no new safety signals were observed. Interpretation: DTX plus RAM demonstrated encouraging antitumor activity with a manageable safety profile in patients who have progressed on front-line ICIs plus platinum-based chemotherapy. The results of this trial can be a helpful reference in conducting further phase III trials of new second-line treatment options. Funding: Eli Lilly Japan K.K.

Comparison of the novel Franseen needle versus the fine-needle aspiration needle in endoscopic ultrasound-guided tissue acquisition for cancer gene panel testing: A propensity score-matching analysis.

Background and Aim: Reports have indicated that a surface area of 4 mm2 or more of collected tissue sections could provide the recommended total DNA for the OncoGuide NCC Oncopanel system, which is a cancer gene panel test developed in Japan. We wished to compare the percentage of tissue sections collected by endoscopic ultrasound-assisted tissue acquisition (EUS-TA) with surface areas of ≥4 mm2 between a conventional needle, namely the EZ Shot 3 Plus (Olympus Medical Japan, Tokyo, Japan) (EZ3), and the recent SonoTip TopGain (MediGlobe, Rohrdorf, Germany) (TopGain). Method: From April 2010 to December 2021, among 693 EUS-TA cases, EZ3 was used in 390 cases and TopGain in 45. The EZ3 and TopGain groups were matched in a 1:1 ratio with a tolerance of 0.2, with 35 patients each matched using propensity score analysis. Results: The TopGain group had a significantly higher percentage of cases with a tissue area of ≥4 mm2 than the EZ3 group (42.9% vs 68.6%, P = 0.030). Multivariate analysis revealed an association between TopGain and tissue areas of ≥4 mm2 (odds ratio 2.996, 95% confidence interval 1.068-8.403, P = 0.037). Conclusions: EUS-TA using TopGain significantly collected more ≥4 mm2 tissue area compared with EZ3, suggesting its usefulness for cancer gene panel testing.

Clinicopathological Characteristics and Prognosis of Mucinous Gastric Cancer.

BACKGROUND/AIM: Mucinous gastric carcinoma (MGC) has a poor prognosis. Due to the differences in clinicopathology factors between MGC and non-MGC (NMGC), it is difficult to compare them. In this study, we compared the clinicopathological characteristics and prognosis of MGC and NMGC patients. PATIENTS AND METHODS: For gastric carcinoma (GC), 3,042 gastrectomy patients were included in the study and divided into the MGC (n=86) and NMGC (n=2,956) groups. The characteristics and prognoses of patients in both groups were compared before and after (both groups, n=86) propensity score matching. RESULTS: Significant differences were observed in the tumor location (upper) (MGC group: 28.0% vs. NMGC group: 24.7%, p=0.003), tumor diameter (median) [65 mm (8-200 mm) vs. 40 mm (2-75 mm), p<0.001], lymph node metastasis (70.9% vs. 37.3%, p<0.001), venous invasion (57.0% vs. 40.4%, p<0.001), and lymphatic invasion (62.8% vs. 34.9%, p<0.001) before propensity score matching. The 5-year overall survival (OS) (70.9% vs. 76.2%, p=0.006) and cancer-specific survival (CSS) (75.5% vs. 82.4%, p=0.014) rates were significantly lower in the MGC group. After propensity score matching, there were no significant differences in either the 5-year OS (70.9% vs. 73.7%, p=0.230) or CSS (75.5% vs. 75.7%, p=0.587) rates. In addition, no substantial difference was observed in either of the recurrence forms. CONCLUSION: MGC is rare and usually diagnosed at a more advanced stage. However, MGC and NMGC have similar prognoses.

Evans' syndrome induced by atezolizumab plus bevacizumab combination therapy in advanced hepatocellular carcinoma.

An 86-year-old man presented with recurrence of hepatocellular carcinoma (HCC) after surgery. Atezolizumab plus bevacizumab was initiated. After the third course of atezolizumab plus bevacizumab therapy, petechial purpura appeared on the extremities and trunk. Laboratory tests revealed isolated severe thrombocytopenia without evidence of combined coagulopathy. He was diagnosed with immune thrombocytopenic purpura (ITP), and high-dose immunoglobulin and Helicobacter pylori eradication therapies were administered. Improvement in thrombocytopenia was observed; however, 20 days after the onset of ITP, laboratory data revealed hemolytic anemia. Both direct and indirect Coombs tests were positive, and he was diagnosed with Evan's syndrome complicated by ITP and autoimmune hemolytic anemia (AIHA) induced by immune-related adverse events (irAEs). After treatment with prednisolone, the hemoglobin level increased, and hemolytic findings improved on blood tests. We encountered a rare case of Evans' syndrome due to atezolizumab plus bevacizumab therapy for HCC. In atezolizumab plus bevacizumab therapy, hematologic toxicities are not rare adverse events and attention is required.

EUS-guided fine-needle biopsy sampling of solid pancreatic tumors with 3 versus 12 to-and-fro movements: a multicenter prospective randomized controlled study.

BACKGROUND AND AIMS: A novel EUS-guided fine-needle biopsy sampling (EUS-FNB) needle enabled physicians to obtain sufficient pathologic samples with fewer to-and-fro movements (TAFs) within the lesion. We compared the diagnostic yields of EUS-FNB with 3 and 12 TAFs at each puncture pass. METHODS: The primary endpoint of this multicenter, noninferiority, crossover, randomized controlled trial involving 6 centers was diagnostic sensitivity. Secondary endpoints were diagnostic accuracy and quantity and quality evaluation of EUS-FNB specimens. Length of the macroscopically visible core (MVC) and microscopic histologic quantity were used for quantitative evaluation. Macroscopic visual and microscopic histologic evaluations were performed for qualitative evaluation. RESULTS: Among 110 patients (220 punctures, 110 for 3 TAFs and 12 TAFs each), 105 (210 punctures) had malignant histology. Diagnostic sensitivity for malignancy of 3 TAFs (88.6%) was not inferior to that of 12 TAFs (89.5%; difference, -.9%; 95% confidence interval, -9.81 to 7.86). Diagnostic accuracy for malignancy was 92.7% for 3 TAFs and 94.6% for 12 TAFs. Overall median MVC length was 13.5 mm in both groups. The 3-TAF group had a significantly higher rate of score ≥3 on macroscopic visual quality evaluation than the 12-TAF group (71.8% vs 52.7%, P = .009). No significant intergroup differences existed in microscopic histologic quantity and quality evaluations (quantity evaluation, 88.2% for 3 TAFs vs 83.6% for 12 TAFs; quality evaluation, 90.0% for 3 TAFs vs 89.1% for 12 TAFs). CONCLUSIONS: Diagnostic sensitivity and accuracy of EUS-FNB with 3 TAFs were not inferior to those with 12 TAFs for solid pancreatic lesions. The 3-TAF group showed significantly less blood contamination in sampled tissues than the 12-TAF group. (Clinical trial registration number: UMIN000037309.).

Successful Treatment with Low-dose Crizotinib in a Patient with ROS1-rearranged Lung Cancer Who Developed Crizotinib-induced Heart Failure.

Crizotinib shows antitumor activity against C-ros oncogene 1-rearranged non-small-cell lung cancer (NSCLC). While corrected QT interval (QTc) prolongation and bradycardia are known as cardiac adverse effects, little is known about crizotinib-related heart failure. Our patient with C-ros oncogene 1-rearranged NSCLC on a reduced dose of crizotinib (200 mg twice daily) after initially experiencing bradycardia and QTc prolongation developed crizotinib-induced heart failure. With further dose reduction (250 mg once daily), there was no recurrence of any cardiac adverse effects, and the patient achieved a long-term response. Although crizotinib can cause heart failure, continuation of crizotinib at a low dose may be an effective treatment option.

Clinical Significance of EREG Gene Expression in Gastric Cancer Tissue After Curative Surgery.

BACKGROUND/AIM: Epiregulin (EREG) is a ligand of the epidermal growth factor receptor (EGFR) and promotes tumour progression mainly by stimulating the EGF pathway. We investigated the clinical significance of EREG mRNA expression in cancer tissues from patients with gastric cancer (GC) in pathological (p) Stage II/III who have undergone curative surgery. PATIENTS AND METHODS: Expression of EREG mRNA was measured in cancer tissues obtained from 253 patients with pStage II/III GC who underwent curative surgery. Patients were divided into groups based on high or low expression of EREG mRNA. We examined the relationship between EREG mRNA expression levels and clinicopathological features and survival. RESULTS: Clinicopathological features did not vary between the high and low EREG mRNA expression groups. Overall survival was significantly lower in the high-expression group compared to that in the low-expression group (5-year survival probability: 55.0% vs. 73.0%; p=0.005). Multivariate analysis showed EREG mRNA expression to be an independent predictor of poor survival (hazard ratio=1.794; 95% confidence interval=1.186-2.712; p=0.006). CONCLUSION: Expression of EREG mRNA in cancer tissue from patients with pStage II/III GC may be a useful prognostic marker after curative surgery.

Feasibility and Safety of Oral Nutritional Supplementation with High-Density Liquid Diet After Total Gastrectomy for Gastric Cancer.

INTRODUCTION: Patients requiring total gastrectomy for gastric cancer experience a decrease in food intake leading to severe body weight loss after surgery. This loss may be prevented using a high-density liquid diet of high caloric content and minimal volume. This phase II study evaluated the feasibility and safety of a high-density liquid diet (UpLead®; Terumo Corporation, Tokyo, Japan) after total gastrectomy. METHODS: UpLead® (1 pack, 100 mL, 400 kcal/day) was administered after surgery for 28 days. The primary endpoint was the % relative dose intensity of 28 days of UpLead intake®. The secondary endpoint was % body weight loss at 1 and 3 months after surgery. The sample size was 35 considering expected and threshold values of 80 and 60%, respectively, with a one-sided alpha error of 10% and statistical power of 80%. RESULTS: Among 35 patients enrolled before surgery between April 2018 and December 2019, 29 patients who could initiate UpLead® after surgery were analyzed. Seven patients had interrupted UpLead® intake due to taste intolerance (n = 6) and due to a duodenal stump fistula (n = 1). The remaining 22 patients completed 28 days of UpLead® intake, including temporary interruption, with no associated adverse events. The median relative dose intensity was 25.8% (95% confidence interval: 20.6-42.0%). The median body weight loss at 1 and 3 months after surgery was 7.2% (range: 3.2-13.9%) and 13.1% (range: 2.5-20.4%), respectively. CONCLUSIONS: Oral nutritional supplementation with a high-density liquid diet (UpLead®) was safely administered but was not feasible after total gastrectomy for gastric cancer. Clinical trial registration number UMIN000032291.

Epstein-Barr virus-related diffuse large B-cell lymphoma type methotrexate-associated lymphoproliferative disorders presenting in the adrenal gland.

Introduction: Methotrexate-associated lymphoproliferative disorders appear during treatment with methotrexate as an immunosuppressive drug. However, the mechanism and frequency are still unknown, and the treatment is undefined. Case presentation: A 76-year-old woman was admitted to the hospital with back pain, and magnetic resonance imaging showed a tumor in the right adrenal region. She had received methotrexate for rheumatoid arthritis. Enhanced computed tomography showed a tumor of 90 mm in diameter on the dorsal side of the liver abutting to the inferior vena cava. The preoperative diagnosis was a hepatic invasion of right adrenocortical carcinoma and right adrenalectomy was performed. The histopathological diagnosis was diffuse large B-cell lymphoma. The final diagnosis was methotrexate-associated lymphoproliferative disorders. Conclusion: It is important to consider methotrexate-associated lymphoproliferative disorders before surgery when neoplastic lesions are found in patients taking methotrexate.

Usefulness of Surgical Staging of Gastric Cancer in Neoadjuvant Chemotherapy Candidates: A Single-center Retrospective Study.

BACKGROUND: The current expectancy of long-term survival of patients with pathological stage (pStage) III gastric cancer (GC) is not satisfactory. However, neoadjuvant chemotherapy (NAC) is expected to improve survival rates in these patients. An appropriate pretherapeutic diagnostic strategy is necessary for selecting patients who are eligible for NAC. Surgical findings can often identify serosal invasion or metastatic lymphadenopathy, thereby facilitating the selection of candidates for NAC. Therefore, we aimed to evaluate the accuracy and potential of surgical staging in improving the management and survival of patients with GC. PATIENTS AND METHODS: We assessed the accuracy of surgical staging in comparison to preoperative staging using data from patients who underwent gastrectomy for GC. In addition, differences in survival after using the surgical staging criterion were assessed. RESULTS: A total of 915 patients were evaluated in this study. The sensitivity of surgical staging in detecting pStage III in the surgical T4N0-3 plus surgical T3N1-3 group was satisfactory (79.3%). The proportion of patients with pStage I using the surgical staging criterion was 7.8%. CONCLUSION: Surgical staging using laparoscopy or laparotomy may assist in selecting candidates for enrollment in clinical trials for NAC.

Endoscopic ultrasound-guided fine-needle biopsy for the diagnosis of gastric linitis plastica.

We report two cases of patients with gastric linitis plastica (GLP), in which the histopathological diagnosis was made by endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen-tip needle. Esophagogastroduodenoscopy findings showed mucosal swelling and poor distensibility of the gastric antrum. Abdominal computed tomography findings showed significant thickening of the gastric wall at the antrum. Conventional endoscopic and bite-on-bite biopsy were attempted but resulted in failure to diagnose the lesions. We performed EUS-FNB to obtain histopathological samples from a deeper site, which confirmed the diagnosis. We considered this method safe and effective for the diagnosis of GLP.

Feasibility of gastric endoscopic submucosal dissection in elderly patients aged ≥ 80 years.

BACKGROUND: Endoscopic resection, especially endoscopic submucosal dissection (ESD), is increasingly performed in elderly patients with early gastric cancer, and lesions beyond the expanded indications are also resected endoscopically in some patients. It is essential to assess whether gastric ESD is safe and suitable for elderly patients and investigate what type of lesions carry an increased risk of ESD-related complications. AIM: To assess the efficacy and feasibility of gastric ESD for elderly patients, and define high-risk lesions and prognostic indicators. METHODS: Among a total of 1169 sessions of gastric ESD performed in Kanagawa Cancer Center Hospital from 2006 to 2014, 179 sessions (15.3%) were performed in patients aged ≥ 80 years, and 172 of these sessions were done in patients with a final diagnosis of gastric cancer. These patients were studied retrospectively to evaluate short-term outcomes and survival. The short-term outcomes included the rates of en bloc resection and curative resection, complications, and procedure-related mortality. Curability was assessed according to the Japanese Gastric Cancer Treatment Guidelines 2010. Fisher's exact test was used to statistically analyze risk factors. Clinical characteristics of each group were compared using Fisher's exact test and Mann-Whitney U test. Survival rates at each time point were based on Kaplan-Meier estimation. Overall survival rates were compared between patients with gastric cancer in each group with use of the log-rank test. To identify prognostic factors that jointly predict the hazard of death while controlling for model overfitting, we used the least absolute shrinkage and selection operator (LASSO) Cox regression model including factors curative/ noncurative, age, gender, body mass index, prognostic nutritional index, Charlson comorbidity index (CCI), Glasgow prognostic score, neutrophil-to-lymphocyte ratio, and antithrombotic agent use. We selected the LASSO Cox regression model that resulted in minimal prediction error in 10-fold cross-validation. P < 0.05 was considered statistically significant. RESULTS: The en bloc dissection rate was 97.1%, indicating that a high quality of treatment was achieved even in elderly patients. As for complications, the rates of bleeding, perforation and aspiration pneumonitis were 3.4%, 1.1% and 0.6%, respectively. These complication rates indicated that ESD was not associated with a particularly higher risk in elderly patients than in nonelderly patients. A dissection incision > 40 mm, lesions associated with depressions, and lesions with ulcers were risk factors for post-ESD bleeding, and location of the lesion in the upper third of the stomach was a risk factor for perforation in elderly patients (P < 0.05). Location of the lesion in the lower third of the stomach tended to be associated with a higher risk of bleeding. The overall survival (OS) did not differ significantly between curative and noncurative ESD (P = 0.69). In patients without additional surgery, OS rate was significantly lower in patients with a high CCI (≥ 2) than in those with a low CCI (≤ 1) (P < 0.001). CONCLUSION: Gastric ESD is feasible even in patients aged ≥ 80 years. Observation without additional surgery after noncurative ESD is reasonable, especially in elderly patients with CCI ≥ 2.

Prognostic Impact of Immune-related Adverse Events in Gastric Cancer Patients Treated With Nivolumab.

BACKGROUND/AIM: To evaluate the impact of development of nivolumab monotherapy-induced immune-related adverse events (irAEs) and continuing nivolumab with irAEs on the survival of patients with gastric cancer (GC). PATIENTS AND METHODS: Patients with unresectable advanced GC and recurrence after curative resection who received nivolumab monotherapy were included in the study. Survival was compared between patients who did and did not develop irAEs, and between those who continued and discontinued treatment due to irAEs. RESULTS: Of 110 GC patients, 22 developed irAEs. Grade ≥3 IrAEs included rash and diarrhoea associated with enteritis. Progression-free and overall survival (OS) were significantly better in patients with irAEs than in those without. The overall survival of patients who continued treatment despite irAEs was better than that of those who discontinued treatment. CONCLUSION: irAE development was associated with better survival in patients with GC who received nivolumab monotherapy. Continuing nivolumab with appropriate treatment in GC patients with irAEs may improve survival.

Peroral Cholangioscopy-Guided Targeted Biopsy versus Conventional Endoscopic Transpapillary Forceps Biopsy for Biliary Stricture with Suspected Bile Duct Cancer.

BACKGROUND: The recent improvement of peroral cholangioscopy (POCS) maneuverability has enabled the precise, targeted biopsy of bile duct lesions under direct cholangioscopic vision. However, as only small-cup biopsy forceps can pass through the scope channel, the resulting small sample size may limit the pathological diagnosis of biopsy specimens. This study compared the diagnostic abilities of POCS-guided biopsy and conventional fluoroscopy-guided biopsy for bile duct cancer. METHOD: This multicenter, retrospective cohort study included patients exhibiting bile duct stricture with suspected cholangiocarcinoma in whom POCS-guided and fluoroscopy-guided biopsies were performed in the same session. The primary endpoint was the diagnostic sensitivity for malignancy. The size and quality of the biopsy specimens were also compared. RESULT: A total of 59 patients were enrolled. The sensitivity of POCS-guided biopsy was similar to that of fluoroscopy-guided biopsy (54.0% and 64.0%, respectively). However, when the modalities were combined, the sensitivity increased to 80.0%. The mean specimen size from POCS-guided biopsy was significantly smaller than that from fluoroscopy-guided biopsy. The specimen quality using fluoroscopy-guided biopsy was also better than that using POCS-guided biopsy. CONCLUSIONS: The diagnostic sensitivity of POCS-guided biopsy is still insufficient, mainly because of the limited specimen quantity and quality. Therefore, conventional fluoroscopy-guided biopsy would be helpful to improve diagnostic sensitivity.