Clinical benefit of subsequent chemotherapy after drug-induced interstitial lung disease in pancreatic cancer patients: a multicenter retrospective study from Japan.

PURPOSE: Drug-induced interstitial lung disease (ILD) is not a rare adverse event in the current chemotherapy strategy for pancreatic ductal adenocarcinoma (PDAC). Thus, we aimed to find the optimal management for PDAC patients with a history of ILD induced by a gemcitabine-based regimen. METHODS: We conducted a multicenter retrospective study. The primary endpoint was the overall survival (OS) of patients who underwent either S-1 monotherapy or FOLFOX after the onset of ILD. Toxicity data was also analyzed in the 2 groups. RESULTS: Twenty-four patients were diagnosed with ILD and 17 patients who received subsequent chemotherapy were enrolled in the study. Among 17 patients who were managed with subsequent chemotherapy after recovering from ILD, we did not observe significant difference in OS between S-1 and FOLFOX (290.0 days vs. undefined, p = 0.39). Relapse of drug-induced ILD was not observed in all cases during the course. Overall, severe adverse events (CTCAE Grade 3 or 4) were observed in 3 patients (23.1%) in S-1 treatment group and 1 patient (25.0%) in FOLFOX treatment group (p = 0.93). CONCLUSIONS: S-1 monotherapy and FOLFOX are comparable as the subsequent chemotherapy after gemcitabine-based chemotherapy-induced ILD in unresectable PDAC.

Risk of Pancreatitis Following Biliary Stenting With/Without Endoscopic Sphincterotomy: A Randomized Controlled Trial.

BACKGROUND & AIMS: The efficacy of endoscopic sphincterotomy (ES) before endoscopic transpapillary biliary drainage in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) has not been established. The aim of this study was to evaluate the effect of performing ES before biliary stent/tube placement on the occurrence of PEP. METHODS: Three hundred seventy patients with biliary stricture requiring endoscopic biliary stenting were enrolled and randomly allocated to the ES group (n = 185) or non-ES group (n = 185). All participants were followed up for 30 days after the procedure. The data and occurrence of adverse events were prospectively collected. The primary outcome measure of this study was the incidence of PEP within 2 days of initial transpapillary biliary drainage. Secondary outcome measures were the incidence of other adverse events related to biliary stent/tube placement. RESULTS: PEP occurred in 36 patients (20.6%) in the non-ES group and in 7 patients (3.9%) in the ES group (P < .001). The difference in the incidence of PEP between the 2 groups in the per-protocol population was 16.7% (95% confidence interval, 10.1%-23.3%), which was not within the noninferiority margin of 6%. Except for bleeding, the incidences of other adverse events were not significantly different between the groups. CONCLUSION: ES before endoscopic biliary stenting could have the preventive effect on the occurrence of PEP in patients with biliary stricture. University Hospital Medical Information Network Number, UMIN000025727.University Hospital Medical Information Network Clinical Trial Registry URL: https://www.umin.ac.jp/ctr/index.htm.

Validity of Endoscopic Ultrasound Findings of Chronic Pancreatitis: Evaluation from the Viewpoint of Disease Risk Factors.

BACKGROUND: The diagnosis of chronic pancreatitis (CP) using endoscopic ultrasound (EUS) criteria, referred to as the Rosemont classification (RC), has been widely performed. However, the validity of the RC, which was based on expert opinion, is still controversial. If EUS findings are associated with CP, then they should be associated with risk factors for CP. In this study, to verify the appropriateness of the RC and each EUS finding, we performed a retrospective analysis from the viewpoint of risk factors for CP. SUMMARY: Three hundred and forty-four patients were enrolled in this study. Clinical background characteristics that associate with CP were alcohol intake, smoking, history of acute pancreatitis (AP), and age. The correlation between EUS criteria for CP and clinical background was investigated. All EUS findings except the presence of cysts showed significant correlations with one or 2 of the 3 following factors: ethanol (EtOH) intake, smoking status, and history of AP. Results of the univariate and multivariate analyses showed that 3 factors (EtOH intake, smoking, and history of AP) other than age were positively correlated with the RC. Moreover, the risk of progression from normal to consistent CP to indeterminate and suggestive CP was found to increase with increasing EtOH intake. Key Messages: The RC and each EUS finding was validated from the viewpoint of risk factors for CP.

Adverse events of endoscopic ultrasound-guided fine-needle aspiration for histologic diagnosis in Japanese tertiary centers: Multicenter retrospective study.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is used for the histopathological diagnosis of any type of gastrointestinal disease. Few adverse events are experienced with this procedure; however, the actual rate of adverse events remains unclear. This study aimed to clarify the current status of cases that experienced adverse events related to the EUS-FNA procedure used for histopathologic diagnoses. METHODS: A retrospective analysis of cases with EUS-FNA-related adverse events in Japanese tertiary centers was conducted by assessing the following clinical data: basic case information, FNA technique, type of procedural adverse events, and prognosis. RESULTS: Of the 13,566 EUS-FNA cases overall, the total number of cases in which adverse events related to EUS-FNA occurred was 234. The incidence of EUS-FNA-related adverse events was ~1.7%. Bleeding and pancreatitis cases accounted for ~49.1% and 26.5% of all adverse events, respectively. Bleeding was the most common adverse event with only seven cases requiring blood transfusion. In cases with neuroendocrine tumors, pancreatitis was the most frequent adverse event. Needle tract seeding because of EUS-FNA was observed during the follow-up period in only ~0.1% of cases with pancreatic cancer. There was no mortality because of adverse events caused by EUS-FNA. CONCLUSIONS: This study revealed that the adverse events-related EUS-FNA for histopathologic diagnoses were not severe conditions, and had low incidence.

Endoscopic ultrasound-guided coil deployment with sclerotherapy for isolated gastric varices: Case series of feasibility, safety, and long-term follow-up.

The purpose of the present study is to report our experience of endoscopic ultrasound-guided coil deployment with sclerotherapy (EUS-CS) for isolated gastric varices (IGV) through a case series. Eight consecutive patients who had risky IGV were prospectively enrolled. EUS-CS was performed according to the following procedures: (i) several coils were first deployed in the IGV under EUS guidance; (ii) contrast medium was subsequently injected without removing the needle; (iii) if the infused contrast medium stayed in the IGV and feeding vein, sclerosant was then injected to obliterate the IGV and feeders. Coil deployment in the IGV was successfully performed in all cases. Sclerosant was injected both into the IGV and feeders in seven patients (87.5%). There was no adverse event during the procedure. During a median follow-up of 57 months, one patient who could not inject the sclerosant into IGV and feeders had an early hemorrhagic recurrence. Our case series showed that EUS-CS could be a feasible and safe procedure for the treatment of IGV.

Relapse of Ulcerative Colitis with Immune Thrombocytopenia and Pyoderma Gangrenosum Subsequent to Receiving COVID-19 Vaccination.

This case illustrates the complex interactions of the immune responses after vaccination and highlights their potential connections to various autoimmune conditions. A 22-year-old man with quiescent ulcerative colitis (UC) presented with abdominal pain, rectal bleeding, and thrombocytopenia 7 days after receiving the third coronavirus disease 2019 mRNA vaccination. Laboratory data confirmed the diagnosis of immune thrombocytopenia. High-dose intravenous immunoglobulin administration boosted the patient's platelet count. Simultaneously, colonoscopy revealed that his UC had relapsed. Although salazosulfapyridine briefly improved his symptoms, his stool frequency worsened one week later. The patient also developed pyoderma gangrenosum. Subsequent treatment with infliximab notably improved both pyoderma gangrenosum and UC.

Percutaneous endoscopic necrosectomy for walled-off necrosis in the retroperitoneal space of the elderly: A case report.

BACKGROUND: Walled-off necrosis (WON) is a late complication of acute pancreatitis possibly with a fatal outcome. Even for WON spreading to the retroperitoneal space, percutaneous endoscopic necrosectomy (PEN) can be an alternate approach to surgical necrosectomy, particularly for the older individuals or patients with poor condition because of WON. CASE SUMMARY: An 88-year-old man was admitted to our hospital with a jaundice. Endoscopic retrograde cholangiopancreatography (ERCP) was performed to improve jaundice; however, post-ERCP pancreatitis developed. The inflammation of pancreatitis spread widely from the right retroperitoneal cavity to the pelvis, and WON was formed 4 wk later. A percutaneous drainage tube was placed into the WON under computed tomography guidance. However, the drainage did not ameliorate clinical symptoms including fever, which assured less invasive necrosectomy. A metallic stent for the upper gastrointestinal (GI) tract was placed from the percutaneous drainage route. An upper GI endoscope was inserted into the inside of the WON through the metallic stent, and the necrotic tissues were bluntly removed with a snare forceps. Ten times of these necrosectomies resulted in the near-complete removal of necrotic tissues. These procedures consequently abated his fever and remarkable improvement in blood tests. CONCLUSION: PEN for WON occurring in the retroperitoneal space was safe and effective for very old individuals.

Guide Wire Selection (Straight vs. Angled) in Endoscopic Retrograde Cholangiopancreatography Using a Normal Contrast Catheter Performed by a Trainee: A Single-Center Prospective Randomized Controlled Cross-Over Study.

INTRODUCTION: Wire-guided cannulation (WGC) during endoscopic retrograde cholangiopancreatography (ERCP) is a selective biliary cannulation technique aimed at improving the successful selective biliary cannulation rate and reducing the rate of post-ERCP pancreatitis (PEP) incidence. This study aimed to evaluate the effectiveness of angled-tip guidewires (AGW) vs. straight-tip guidewires (SGW) for biliary cannulation via WGC by a trainee. METHODS: We conducted a prospective, single-center, open-labeled, randomized, and controlled trial. Fifty-seven patients were enrolled in this study and assigned randomly to two groups (Group A to S and Group S to A). In this study, we started selective biliary cannulation via WGC with an AGW or an SGW for 7 min. If cannulation was unsuccessful, the other guidewire was used, and cannulation was continued for another 7 min (cross-over method). RESULTS: The selective biliary cannulation success rate over 14 min was significantly higher with an AGW compared with an SGW over 14 min (57.8% vs. 34.3%, p = 0.04) and for the second 7-min segment (36.4% vs. 0%, p = 0.04). No significant difference was found for adverse events such as pancreatitis between the two guidewires. CONCLUSIONS: Our results suggest that an AGW is recommended for WGC performed by a trainee.

A multicenter comparative study of endoscopic ultrasound-guided fine-needle biopsy using a Franseen needle versus conventional endoscopic ultrasound-guided fine-needle aspiration to evaluate microsatellite instability in patients with unresectable pancreatic cancer.

BACKGROUND/AIMS: Immune checkpoint blockade has recently been reported to be effective in treating microsatellite instability (MSI)-high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for MSI evaluation in patients with UR-PC. METHODS: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB using 22-G needles at three hospitals in Japan (2018-2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33) were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patients who underwent EUS-FNB and those who underwent EUS-FNA. RESULTS: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwent EUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained using EUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariate analysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. CONCLUSION: EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.

Clinical Differences in c-Myc Expression in Early-Stage Gastric Neoplasia: A Retrospective Study Based on the WHO Classification.

c-Myc is an oncogene that is dysregulated in various cancers. Early gastric neoplasia with c-Myc expression has been reported as a more malignant lesion. This study clarifies the differences in c-Myc expression in early gastric neoplasia based on the WHO classification. Samples from 100 patients with differentiated-type early gastric neoplasia, who underwent endoscopic submucosal dissection between March 2020 and January 2021, were stained for c-Myc. One hundred lesions were classified as low-grade dysplasia, high-grade dysplasia, or intramucosal adenocarcinoma. The staining intensity and extent were scored. A hierarchical cluster analysis for a clinicopathological analysis among the groups, the chi-square test, Bonferroni correction, and residual analysis were performed. Subgroup one and two consisted of 39 patients; while subgroup three consisted of 22. Significant differences among various characteristics were observed between these subgroups. The frequency of low-grade dysplasia was significantly higher, while that of high-grade dysplasia was significantly lower in subgroup three. The frequency of intramucosal adenocarcinoma was significantly higher in subgroup one. The c-Myc positivity rate was significantly higher in subgroup one compared with that in subgroup three. c-Myc expression distinctly differed in early gastric neoplasia. c-Myc-negative low-grade dysplasia may be separately categorized from c-Myc-positive low-grade dysplasia, high-grade dysplasia, and intramucosal adenocarcinoma.

A Prospective Multicenter Randomized Feasibility Trial of Double-guidewire Techniques for Difficult Biliary Cannulation Comparing a New Double-guidewire-supported Sphincterotome (MagicTome) to a Conventional Device.

Objective To evaluate the effectiveness and safety of the double-guidewire technique (DGT) using a new double-guidewire-supported sphincterotome (MagicTome) for patients who required endoscopic retrograde cholangiopancreatography (ERCP) for biliary cannulation. Methods This prospective multicenter randomized feasibility trial involved patients with difficult biliary cannulation at any of the three study sites from June 2017 to October 2018. Patients were assigned to the DGT with MagicTome (MDGT) initially performed group and the conventional DGT (CDGT) initially performed group. The success rates of biliary cannulation by MDGT and CDGT and the ERCP-related complications were evaluated. Results Twenty-eight patients were included in this study. No significant difference was observed in the success rates of first attempts and crossover attempts between the groups (p=0.69 and p=1.00). Furthermore, no significant difference was observed in the success rate of biliary cannulation between MDGT and CDGT (62.5% and 75.0%, respectively; p=0.48). CDGT was successful in two of four patients with malignant biliary obstruction. MDGT was successful in all four patients with malignant biliary obstruction, including the two for whom CDGT was unsuccessful. Post-ERCP pancreatitis occurred in only one MDGT case. Conclusion MDGT is safe for biliary cannulation and can be used in cases where biliary cannulation by CDGT is difficult.

ATP assay-guided chemosensitivity testing for gemcitabine with biopsy specimens obtained from unresectable pancreatic cancer using endoscopic ultrasonography-guided fine-needle aspiration.

OBJECTIVES: This study evaluates the feasibility of chemosensitivity testing by use of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) samples and determines the optimum cut-off value for gemcitabine. METHODS: Thirty-four consecutive patients with unresectable pancreatic cancer were enrolled. Chemosensitivity (treated/control ratio: T/C ratio) was calculated as the quantity of adenosine triphosphate for a tumor treated with gemcitabine as a percentage of that for the control. To identify the cut-off value sufficient to predict 180 days of progression-free survival (PFS), the receiver operating characteristic curve and the corresponding area under the curve (AUC) were calculated. RESULTS: The success of this assay was 88.2% (30/34); therefore, 30 patients were assessable and included in the population of analyzable patients.. The response was 6.7%. Median PFS was 96 days and median overall survival was 241 days, respectively. The cut-off value was determined as 74% (AUC, 0.745; p = 0.053; 95% CI 0.485-1.005). According to this cut-off value, we predicted 180 days PFS with a sensitivity and specificity of 71.4 and 91.3%, respectively. When patients were divided into two groups at T/C ratio 74%, a significant difference was found in PFS (median 77 vs. 205 days, p = 0.0036). Moreover, T/C ratio < 74% and decrease of CA19-9 were significant and independent prognostic factors by multivariate analysis. CONCLUSION: Chemosensitivity testing by use of EUS-FNA samples in patients with unresectable pancreatic cancer is feasible. This definition emphasizes the possibility of selecting patients for whom favorable results from gemcitabine treatment can be expected.

Autoimmune neutropenia associated with autoimmune pancreatitis.

CONTEXT: We report a rare case of autoimmune neutropenia associated with autoimmune pancreatitis. CASE REPORT: A 61-year-old man was referred to our hospital with slight epigastralgia. He had been admitted to another hospital with exacerbation of diabetes and jaundice. Blood tests showed low white blood cell and neutrophil counts (1,800 µL-1 and 3%, respectively), and elevated transaminase, biliary enzyme, amylase and lipase levels. Serum IgG and IgG4 levels were elevated to 2,693 mg/dL and 454 mg/dL, respectively. Abdominal CT showed diffuse pancreatic swelling, and MRCP revealed diffuse narrowing of the main pancreatic duct and dilation of the common bile duct. An additional EUS-FNA was performed in our hospital. Laboratory data, imaging and histopathological findings confirmed the diagnosis of autoimmune pancreatitis. However, the low white blood cell count continued. For additional investigation, a bone marrow examination was performed, indicating a granulocyte maturation disorder. Moreover, anti-neutrophil antibodies were positive. Therefore, a diagnosis of autoimmune neutropenia associated with autoimmune pancreatitis was made. After steroid therapy, the anti-neutrophil antibodies disappeared and the white blood cell count was within the reference limit. No recurrence of disease has been observed since then. CONCLUSION: Autoimmune neutropenia, which is positive for anti-neutrophil antibodies, can be associated with autoimmune pancreatitis.

Pilot Study of Acupuncture's Antispasmodic Effect on Upper Gastrointestinal Tract during Endoscopic Submucosal Dissection for Early Gastric Cancer: Controlled Clinical Trial.

A prospective study was conducted in patients with early-stage gastric cancer to determine the efficacy and safety of acupuncture stimulation as an antispasmodic compared with conventional medication during the procedure of endoscopic submucosal dissection (ESD) of the upper gastrointestinal tract. This study was a prospective single blinded quasi-randomized controlled trial. Seventy-three patients who were scheduled to undergo ESD for gastric cancer at Aizu Medical Center between 19 February 2016 and 30 June 2016 were assessed for eligibility for the study. Sixty out of 73 patients were included in the study and assigned into two intervention groups: medication group (MG) and acupuncture group (AG). Ease of the procedure was evaluated using modified NIWA classification (MNC) by endoscopist considering the frequency and amplitude of the upper gastrointestinal peristalsis. For the statistical analysis, Mann-Whitney test was used to compare the differences of MNC values (baseline and end of procedure) between two groups. The difference of MNC found in the AG (-2.00 (-3.0 to -2.0)) was significantly greater than that in the MG (-1.00 (-2.0 to -1.0), p < 0.0001, Mann-Whitney test). We consider that acupuncture to the abdomen could be an alternative antispasmodic method during upper gastrointestinal endoscopic procedure.

Complete response of anaplastic pancreatic carcinoma to paclitaxel treatment selected by chemosensitivity testing.

A 58-year-old woman was admitted to our institute in June 2007 because of obstructive jaundice. A mass in the pancreatic head and multiple swollen lymph nodes surrounding the common hepatic artery were identified using computed tomography (CT). Subsequently, endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNA) was done. Histopathologic results revealed anaplastic carcinoma of the pancreas. Using specimens obtained with EUS-FNA, chemosensitivity testing with adenosine triphosphate assay was performed. Testing indicated high chemosensitivity to paclitaxel (PTX). According to this result, chemotherapy using PTX was performed, and the primary lesion and lymph node metastases disappeared completely on CT. The patient has been doing well with no recurrence for 1 year and 11 months since initial chemotherapy.

Duodenal Stenosis Due to Carcinoma of the Lower Bile Duct: A Case Report.

An 83-year-old man was referred to our hospital for a detailed evaluation for vomiting. Esophagogastroduodenoscopy and abdominal computed tomography showed duodenal stenosis with wall thickness. Biopsy including endoscopic ultrasound-guided fine-needle aspiration of the thickened wall showed inflammation without malignancy. During the clinical course, wall thickening of the distal bile duct appeared. Biopsy under endoscopic retrograde cholangiography showed papillary adenocarcinoma. Surgery revealed that the tumor had widely invaded the duodenal wall from the outside; therefore, only gastrojejunostomy was performed. It was hypothesized that the cholangiocarcinoma had progressed to the serosal side, disseminated in the peritoneum, infiltrated the duodenal serosa, and caused duodenal stenosis.