Outcomes of immune checkpoint inhibitor-induced liver toxicity managed by hepatologists in a multidisciplinary toxicity team.

AIM: To detect immune-related adverse events (irAEs) early and treat them appropriately, our institute established an irAE-focused multidisciplinary toxicity team in cooperation with various departments. This study aimed to evaluate a consultation system involving a team of hepatologists in terms of its utility for the management of severe immune checkpoint inhibitor (ICI)-induced liver toxicity. METHODS: To analyze the diagnosis and treatment of severe ICI-induced liver toxicity (Grade 2 requiring corticosteroid therapy and Grade 3 or higher), we examined patients' clinical courses before and after the hepatologist consultation system was established (pre-period, September 2014 to February 2019; post-period, March 2019 to March 2023). RESULTS: The median follow-up period was 392 days. Of the 1247 patients with advanced malignancies treated with ICIs, 66 developed severe ICI-induced liver toxicity (n = 22 and 44 in the pre- and post-periods, respectively). In the pre-period, hepatologist consultations were sought for 15/22 patients, whereas in the post-period, 42/44 patients were referred to and treated by hepatologists. The time from the onset of liver toxicity to the consultation was significantly shorter in the post-period than in the pre-period (mean 1.9 vs. 6.5 days, respectively; p = 0.012). The number of patients with a biopsy-confirmed diagnosis of ICI-induced liver toxicity was significantly higher in the post-period than in the pre-period (n = 22 vs. n = 3, respectively; p = 0.006). Finally, there were no cases of immune-related cholangitis in the pre-period, compared to five cases in the post-period. CONCLUSION: A hepatologist consultation system in an irAE-focused multidisciplinary toxicity team is useful for managing severe ICI-induced liver toxicity.

Diagnostic performance and safety of endoscopic ultrasound-guided fine-needle aspiration/biopsy for gallbladder lesions.

OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration and fine-needle biopsy (EUS-FNA/FNB) is not fully established as a pathological sampling tool for gallbladder lesions due to limited evidence. We therefore aimed to clarify the effectiveness and safety of this procedure in a large-population cohort. METHODS: This study retrospectively evaluated the diagnostic yield of EUS-FNA/FNB for accurately differentiating between benign and malignant gallbladder lesions. Puncture targets included the gallbladder mass, lymph node, and liver mass. Adverse events and factors associated with diagnostic accuracy were analyzed as well. RESULTS: In 187 patients with gallbladder lesions undergoing EUS-FNA/FNB, 18 benign lesions and 169 malignant lesions were identified. Overall sampling adequacy was 98% (184/187). The diagnostic accuracy of EUS-FNA/FNB was 97% (182/187), sensitivity was 97% (164/169), and specificity was 100% (18/18). A single postprocedural complication (minor bleeding) was recorded in one patient. In the 169 cases of malignancy, 203 sites were punctured for pathological sampling of the primary mass (n = 94), lymph node (n = 79), and metastatic liver mass (n = 30). No significant difference was found for diagnostic accuracy among the puncture sites (P = 0.70). In cases having specimens obtained from the primary mass, the accuracy of those targeting liver invasion sites was significantly higher than that of other sites (98% vs. 83%, P < 0.01). CONCLUSION: EUS-FNA/FNB demonstrated clinical usefulness and safety for the pathological diagnosis of gallbladder lesions, with high diagnostic yield and a low incidence of adverse events. Targeting the site of liver infiltration may improve the diagnostic rate of EUS-FNA/FNB in the primary mass.

Artificial intelligence using deep learning analysis of endoscopic ultrasonography images for the differential diagnosis of pancreatic masses.

BACKGROUND : There are several types of pancreatic mass, so it is important to distinguish between them before treatment. Artificial intelligence (AI) is a mathematical technique that automates learning and recognition of data patterns. This study aimed to investigate the efficacy of our AI model using endoscopic ultrasonography (EUS) images of multiple types of pancreatic mass (pancreatic ductal adenocarcinoma [PDAC], pancreatic adenosquamous carcinoma [PASC], acinar cell carcinoma [ACC], metastatic pancreatic tumor [MPT], neuroendocrine carcinoma [NEC], neuroendocrine tumor [NET], solid pseudopapillary neoplasm [SPN], chronic pancreatitis, and autoimmune pancreatitis [AIP]). METHODS : Patients who underwent EUS were included in this retrospective study. The included patients were divided into training, validation, and test cohorts. Using these cohorts, an AI model that can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions was developed using a deep-learning architecture and the diagnostic performance of the AI model was evaluated. RESULTS : 22 000 images were generated from 933 patients. The area under the curve, sensitivity, specificity, and accuracy (95 %CI) of the AI model for the diagnosis of pancreatic carcinomas in the test cohort were 0.90 (0.84-0.97), 0.94 (0.88-0.98), 0.82 (0.68-0.92), and 0.91 (0.85-0.95), respectively. The per-category sensitivities (95 %CI) of each disease were PDAC 0.96 (0.90-0.99), PASC 1.00 (0.05-1.00), ACC 1.00 (0.22-1.00), MPT 0.33 (0.01-0.91), NEC 1.00 (0.22-1.00), NET 0.93 (0.66-1.00), SPN 1.00 (0.22-1.00), chronic pancreatitis 0.78 (0.52-0.94), and AIP 0.73 (0.39-0.94). CONCLUSIONS : Our developed AI model can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions, but external validation is needed.

Novel drill dilator facilitates endoscopic ultrasound-guided hepaticogastrostomy.

Tract dilation is one of the most difficult stages of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS), especially for beginners. To overcome this problem, we applied a special dedicated dilator. Herein, we retrospectively evaluate the safety and usefulness of a novel drill dilator in EUS-HGS. This single-center retrospective study included 20 consecutive patients who underwent EUS-HGS with a novel drill dilator. The tip is 0.77 mm, and it becomes 7F at 3 cm from tip. The track is dilated to 7F by simple clockwise rotation. The technical success rate of both initial tract dilation and stent placement was 20/20 (100%). No cases required additional dilation such as balloon or electric cautery. In 13/20 cases (65.0%), EUS-HGS was performed by beginner endoscopists. Median time required for dilation was 62.5 s (range, 30-144 s). Median procedure time was 13 min (range, 7-25 min). Early adverse events were two cases of mild fever. There was no bile leakage or bleeding. The novel drill dilator appears to be safe and useful for EUS-HGS. As it is not necessary to press the device strongly, there is no pushback during dilation and the scope position is stable. These characteristics facilitate EUS-HGS even for beginners. This device may enable the further development and increased dissemination of EUS intervention.

Safety of endoscopic ultrasound-guided hepaticogastrostomy in patients with malignant biliary obstruction and ascites.

BACKGROUND/AIMS: Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS) is useful for patients with biliary cannulation failure or inaccessible papillae. However, it can lead to serious complications such as bile peritonitis in patients with ascites; therefore, development of a safe method to perform EUS-HGS is important. Herein, we evaluated the safety of EUS-HGS with continuous ascitic fluid drainage in patients with ascites. METHODS: Patients with moderate or severe ascites who underwent continuous ascites drainage, which was initiated before EUS-HGS and terminated after the procedure at our institution between April 2015 and December 2022, were included in the study. We evaluated the technical and clinical success rates, EUS-HGS-related complications, and feasibility of re-intervention. RESULTS: Ten patients underwent continuous ascites drainage, which was initiated before EUS-HGS and terminated after completion of the procedure. Median duration of ascites drainage before and after EUS-HGS was 2 and 4 days, respectively. Technical success with EUS-HGS was achieved in all 10 patients (100%). Clinical success with EUS-HGS was achieved in 9 of the 10 patients (90 %). No endoscopic complications such as bile peritonitis were observed. CONCLUSION: In patients with ascites, continuous ascites drainage, which is initiated before EUS-HGS and terminated after completion of the procedure, may prevent complications and allow safe performance of EUS-HGS.

Clinical utility of endoscopic ultrasound-guided tissue acquisition for comprehensive genomic profiling of patients with biliary tract cancer, especially with intrahepatic cholangiocarcinoma.

BACKGROUND/AIMS: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is a standard diagnostic method for biliary tract cancer (BTC), and samples obtained in this manner may be used for comprehensive genomic profiling (CGP). This study evaluated the utility of EUS-TA for CGP in a clinical setting and determined the factors associated with the adequacy of CGP in patients with BTC. METHODS: CGP was attempted for 105 samples from 94 patients with BTC at the Aichi Cancer Center, Japan, from October 2019 to April 2022. RESULTS: Overall, 77.1% (81/105) of the samples were adequate for CGP. For 22-G or 19-G fine-needle biopsy (FNB), the sample adequacy was 85.7% (36/42), which was similar to that of surgical specimens (94%, p=0.45). Univariate analysis revealed that 22-G or larger FNB needle usage (86%, p=0.003), the target primary lesions (88%, p=0.015), a target size ≥30 mm (100%, p=0.0013), and number of punctures (90%, p=0.016) were significantly positively associated with CGP sample adequacy. CONCLUSIONS: EUS-TA is useful for CGP tissue sampling in patients with BTC. In particular, the use of 22-G or larger FNB needles may allow for specimen adequacy comparable to that of surgical specimens.

Safety and efficacy of novel oblique-viewing scope for B2-endoscopic ultrasound-guided hepaticogastrostomy.

Background/Aims: Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS) performed at the intrahepatic bile duct segment 3 (B3) is widely used for biliary drainage. Although performing post-puncture procedures is easier in the intrahepatic bile duct segment 2 (B2) when using a conventional oblique-viewing (OV) EUS scope, this method may cause transesophageal puncture and severe adverse events. We evaluated the safety and efficacy of B2 puncture using a novel OV-EUS scope. Methods: In this single-center retrospective study, we prospectively enrolled and collected data from 45 patients who consecutively underwent EUS-HGS procedures with a novel OV-EUS scope between September 2021 and December 2022 at our cancer center. Results: The technical success rates of B2-EUS-HGS and EUS-HGS were 93.3% (42/45) and 97.8% (44/45), respectively. The early adverse event rate was 8.9% (4/45) with no cases of scope changes or transesophageal punctures. The median procedure time was 13 minutes (range, 5-30). Conclusions: B2-EUS-HGS can be performed safely with the novel EG-740UT (Fujifilm) OV-scope without transesophageal puncture and with a high success rate. B2-EUS-HGS using this novel OV scope may be the preferred strategy for EUS-HGS.

Safety and feasibility of opening window fistulotomy as a new precutting technique for primary biliary access in endoscopic retrograde cholangiopancreatography.

BACKGROUND/AIMS: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common and serious complication of endoscopic retrograde cholangiopancreatography. To prevent this event, a unique precutting method, termed opening window fistulotomy, was performed in patients with a large infundibulum as the primary procedure for biliary cannulation, whereby a suprapapillary laid-down H-shaped incision was made without touching the orifice. This study aimed to assess the safety and feasibility of this novel technique. METHODS: One hundred and ten patients were prospectively enrolled in this study. Patients with a papillary roof size ≥10 mm underwent opening window fistulotomy for primary biliary access. In addition, the incidence of complications and success rate of biliary cannulation were evaluated. RESULTS: The median size of the papillary roof was 6 mm (range, 3-20 mm). Opening window fistulotomy was performed in 30 patients (27.3%), none of whom displayed PEP. Duodenal perforation was recorded in one patient (3.3%), which was resolved by conservative treatment. The cannulation rate was high (96.7%, 29/30 patients). The median duration of biliary access was 8 minutes (range, 3-15 minutes). CONCLUSION: Opening window fistulotomy demonstrated its feasibility for primary biliary access by achieving great safety with no PEP complications and a high success rate for biliary cannulation.

The role of needle-based confocal laser endoscopy in the diagnosis of pancreatic neuroendocrine tumors.

Background/Aims: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a highly accurate method for diagnosing pancreatic neuroendocrine tumors (PNETs); however, some PNETs are difficult to diagnose. Recently, the efficacy of needle-based confocal laser endomicroscopy (nCLE) in diagnosing solid pancreatic masses has been reported. However, the efficacy of nCLE in the diagnosis of PNETs remains unknown and only a small number of cases have been reported. Hence, this study aimed to evaluate the efficacy of nCLE in the diagnosis of PNETs. Methods: This single-center retrospective study evaluated 30 consecutive patients with suspected PNETs on contrast-enhanced computed tomography, who consented to nCLE combined with EUS-FNA and were diagnosed using EUS-FNA or surgical resection. The diagnostic criteria for PNETs using nCLE were based on the nesting and trabecular and glandular arrangement of tumor cell clusters surrounded by capillary vessels and fibrosis, as reported in previous studies. Results: The diagnosis using nCLE was classified into three categories: misdiagnosis in three cases (10%), non-diagnostic in six cases (20%), and diagnostic in 21 cases (70%). nCLE was able to diagnose PNET in one of the two cases with inconclusive EUS-FNA. Conclusions: Although further development of the resolution and optimization of the diagnostic criteria are required, nCLE may constitute a useful diagnostic option in cases of inconclusive EUS-FNA for PNETs.

B2 puncture with forward-viewing EUS simplifies EUS-guided hepaticogastrostomy (with video).

Background and Objectives: EUS-guided hepaticogastrostomy (EUS-HGS) is in widespread use; however, there are few dedicated devices. The B2 route is technically easier than the B3 route for guidewire insertion, dilation, and stenting but if performed with conventional oblique-viewing (OV) EUS, B2 puncture can cause transesophageal puncture and severe adverse events. The aim of this study was to assess the efficacy of forward-viewing (FV) EUS, which we have developed to improve safety for B2 puncture in EUS-HGS (B2-EUS-HGS). Patients and Methods: This single-center retrospective study included 61 consecutive patients who underwent B2-EUS-HGS with FV between February 2020 and March 2021 at Aichi Cancer Center, Japan. The patients were prospectively enrolled, and clinical data were retrospectively collected for these 61 cases. Results: The overall technical success rate of EUS-HGS was 98.3% (60/61). The rate of EUS-HGS with FV was 95.0% (58/61) after three cases converted to OV, and that of B2-EUS-HGS with FV was 88.5% (54/61). The early adverse event rate was 6.5% (4/61). There were no instances of transesophageal puncture. Median procedure time was 24 min (range, 8-70), and no patient required cautery dilation. Conclusions: B2-EUS-HGS can be performed safely using FV, without transesophageal puncture, and supportability of the device is improved as FV is coaxial with the guidewire. FV was efficacious in B2-EUS-HGS, which shows promise for clinical application in the future.

Nivolumab Effective for Gastric and Lung Cancers but Not for Multiple Myeloma in a Multiple Primary Cancer Patient.

The case of a 76-year-old man with multiple primary cancers that were treated with nivolumab is presented. Six years earlier, he was diagnosed with multiple myeloma (MM) and was treated with several chemotherapies. He was also diagnosed with gastric cancer with liver metastasis and primary lung cancer by upper gastrointestinal endoscopy and computed tomography (CT). Nivolumab treatment was given as third-line therapy, and it was effective for gastric and lung cancers. But MM worsened, and the patient died. There is no standard treatment for multiple primary cancers, and the development of effective treatments for multiple primary cancers is important.