A female patient in her 60s tested positive for the fecal occult blood test while undergoing health screening. Colonoscopy revealed a 15-mm-sized flat elevated lesion with a central depression in the sigmoid colon. Narrow-band imaging magnification revealed a Japan Narrow-Band Imaging Expert Team classification of type 2B, whereas crystal violet staining showed a mild to severely irregular type VI pit pattern. Ultra-magnification imaging revealed an EC3a morphology in the depressed area. Endoscopic ultrasonography revealed partial disruption of the third layer, leading to the diagnosis of T1b (SM) colon cancer. Owing to the intermediate lesion size and since the patient had requested it, an endoscopic submucosal dissection was performed as an initial treatment. Pathological analysis revealed a moderately differentiated tubular adenocarcinoma with an invasive micropapillary carcinoma (IMPC) component, with deep submucosal invasion. Additional surgery was performed, and no recurrence was observed in the following three years. IMPC is known for its high rate of lymph-node metastasis and poor prognosis, as reported for breast, bladder, and lung cancers. IMPC is rare; this report presents a literature review and case details. This case represents the first reported instance of identification of a cancerous IMPC component by magnifying endoscopy at the T1b (SM) depth. Thus, even for intermediate lesions, IMPC should be considered as a differential diagnosis when endoscopic imaging suggests malignancy.

BACKGROUND: The use of 10-mm fully covered self-expandable metal stents for preoperative bile duct drainage in patients with pancreatic cancer is increasing. However, these can cause complications (cholecystitis and pancreatitis) that may affect surgical outcomes. Smaller-diameter self-expandable metal stents may reduce these risks; however, the optimal stent size is unclear. METHODS: Patients with pancreatic cancer who underwent neoadjuvant chemotherapy and placement of either 6 or 10-mm fully covered self-expandable metal stents for malignant distal biliary obstruction were included. The primary outcome was the 90-day incidence of recurrent biliary obstruction. Secondary outcomes were non-recurrent biliary obstruction and adverse events. RESULTS: Fifty-three patients were enrolled (27 and 26 patients received 6-mm and 10-mm self-expandable metal stents, respectively). The 90-day incidence of recurrent biliary obstruction of the 6-mm group was significantly higher than that of the 10-mm group (30.8% vs. 3.8%; p = 0.02). Stent migration occurred more frequently in the 6-mm group (26.9% vs. 0%; p = 0.01). Although non-recurrent biliary obstruction adverse events were less common in the 6-mm group, the difference was not statistically significant (11.1% vs. 23.0%; p = 0.29). CONCLUSIONS: The 10-mm self-expandable metal stents were more suitable for the preoperative management of pancreatic cancer.

BACKGROUND: Fibrolamellar hepatocellular carcinoma (FL-HCC) clinically occurs in young people aged 20-30 years, who often have a normal liver background. We propose a treatment for such cases in which a combination therapy of atezolizumab and bevacizumab is followed by sandwiching radiation therapy to release tumor antigens and then re-administering the combination therapy of atezolizumab and bevacizumab (ABC conversion therapy). CASE: The patient is a 15-year-old girl. On April 18, 2022, she noticed skin yellowing and visited her local doctor. Computed tomography (CT) revealed a large mass in the right lobe of the liver and bile duct obstruction due to the tumor. She also had a nodule on her chest that appeared to be a metastatic tumor and was referred to Kinki University Hospital in April 2023. She was suspected to have FL-HCC based on contrast-enhanced ultrasound and CT scan results. There were findings suggestive of lung metastasis; however, she underwent a right hepatic lobectomy on May 17, 2023, considering the risk of liver failure and intra-abdominal bleeding due to the large liver tumor. A CT scan conducted on July 25, 2022, showing increased lung metastases, and she started atezolizumab/bevacizumab combination treatment on October 20, 2022. On March 15, 2023, multiple lung metastases and new intrahepatic lesions appeared, which was diagnosed as progressive disease (PD), and lenvatinib was discontinued. On November 17, 2023, radiation therapy (25 Gy/5 Fr) was administered to the lung and intrahepatic lesions to release tumor antigens, and on November 27, 2023, atezolizumab and bevacizumab combination treatment was resumed to control the tumor. CONCLUSION: Combination therapy with atezolizumab, bevacizumab, and radiation therapy may be an option for the treatment of FL-HCC.

Abstract A 53-year-old woman was diagnosed with liver dysfunction in August 20XX. Computed tomography (CT) revealed multiple hepatic AV shunts, and she was placed under observation. In March 20XX + 3, she developed back pain, and CT performed during an emergency hospital visit showed evidence of intrahepatic bile duct dilatation. She was referred to our gastroenterology department in May 20XX + 3. We conducted investigations on suspicion of hereditary hemorrhagic telangiectasia (HHT) with hepatic AV shunting based on contrast-enhanced CT performed at another hospital. HHT is generally discovered due to epistaxis, but there are also cases where it is diagnosed during examination of liver damage.

BACKGROUND: Immune checkpoint inhibitors have been reported to have excellent therapeutic effects on various malignant tumors. However, immune-related adverse events can occur, targeting various organs. CASE PRESENTATION: A 49-year-old male with lung carcinoma was started on carboplatin + pemetrexed + nivolumab (every 3 weeks) + ipilimumab (every 6 weeks), and nivolumab/ipilimumab was administered in the 3rd course. Subsequently, fever and fatigue developed, and grade 3 liver damage was also noted, so he was admitted to Kindai University Hospital. A bone marrow aspirate examination was performed on the third day of illness, and a definitive diagnosis of hemophagocytic lymphohistiocytosis (HLH) was made. It was determined that immediate therapeutic intervention was necessary, and pulse therapy with methylprednisolone was started on the third day of illness. After 3 days of pulse treatment, a rapid recovery of platelet values, a decrease in ferritin levels, and a decrease in lactate dehydrogenase were observed. Subjective symptoms such as fever and fatigue also quickly improved. CONCLUSION: Early diagnosis and treatment for HLH resulted in a positive response. The number of HLH cases may increase in the future due to the expansion of immune checkpoint inhibitor indications.

BACKGROUND AND AIMS: To compare endoscopic retrograde cholangiopancreatography using balloon-assisted endoscope (BE-ERCP) with endoscopic ultrasonography-guided antegrade treatment (EUS-AG) for removal of common bile duct (CBD) stones in patients with Roux-en-Y (R-Y) gastrectomy. METHODS: Consecutive patients with R-Y gastrectomy undergoing BE-ERCP or EUS-AG for CBD stones in 16 centers were retrospectively analyzed. RESULTS: BE-ERCP and EUS-AG were performed in 588 and 59 patients, respectively. Baseline characteristics were similar, except for CBD diameter and angle. Technical success rate was 83.7% vs. 83.1% (P = 0.956), complete stone removal rate was 78.1% vs. 67.8% (P = 0.102), and early adverse event rate was 10.2% vs. 18.6% (P = 0.076) in BE-ERCP and EUS-AG. The mean number of endoscopic sessions was smaller in BE-ERCP (1.5±0.8 vs. 1.9±1.0 sessions, P = 0.01), whereas the median total treatment time was longer (90 vs. 61.5 minutes, P = 0.001). Among patients with biliary access, complete stone removal rate was significantly higher in BE-ERCP (93.3% vs. 81.6%, P = 0.009). CBD diameter ≥15-mm (Odds ratio [OR], 0.41) and an angle of CBD <90-degree (OR, 0.39) were negative predictive factors in BE-ERCP, and a stone size ≥10-mm (OR, 0.07) and an angle of CBD <90-degree (OR, 0.07) in EUS-AG. The 1-year recurrence rate was 8.3% in both groups. CONCLUSIONS: Effectiveness and safety of BE-ERCP and EUS-AG were comparable in CBD stone removal for patients after R-Y gastrectomy, but complete stone removal after technical success was superior in BE-ERCP.

BACKGROUND AND AIMS: The diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNAB) for pancreatic ductal adenocarcinoma (PDAC) ≤ 10 mm in diameter is relatively low. Pancreatic juice cytology (PJC) has gained attention owing to its high sensitivity for small PDAC. We aimed to clarify the diagnostic ability of EUS-FNAB and the salvage ability of PJC for PDAC ≤ 10 mm. METHODS: The data obtained from attempted EUS-FNAB for patients with EUS-confirmed pancreatic tumors ≤ 10 mm (excluding pancreatic metastases/malignant lymphomas) were retrospectively analyzed. Patients who experienced technical failure/negative EUS-FNAB result and had a strong likelihood of PDAC based on imaging characteristics underwent PJC. PDAC was diagnosed using resected histological specimens, EUS-FNAB-positive tumor growth on the imaging examination, or additional EUS-FNAB-positive results after increase in tumor size. The primary endpoint was the diagnostic ability of EUS-FNAB for PDAC ≤ 10 mm. The salvage ability of PJC was also assessed. RESULTS: Overall, 86 patients were diagnosed with PDAC of 271 patients with pancreatic tumors ≤ 10 mm who underwent attempted EUS-FNAB. The technical success rate, sensitivity, specificity, and accuracy of EUS-FNAB for PDAC ≤ 10 mm was 80.8%, 82.3%, 94.9%, and 91.3%, respectively. Among the 35 PDAC patients who experienced technical failure/false-negative result of EUS-FNAB, 26 (74.3%) were correctly diagnosed using salvage PJC. CONCLUSIONS: The true success rate/sensitivity of EUS-FNAB for PDAC ≤ 10 mm was relatively low. When EUS-FNAB for a pancreatic lesion ≤ 10 mm strongly suspected to be PDAC is unsuccessful or yields a negative result, PJC is recommended.

BACKGROUND: Although reports of gastrointestinal perforation after immune-related adverse events (irAE) enteritis are rare, the anti- vascular endothelial growth factor (VEGF) effect of bevacizumab may be involved in gastrointestinal perforation. We report a rare case of gastrointestinal perforation in a patient with hepatocellular carcinoma treated with atezolizumab/bevacizumab combination therapy and infliximab before steroid use. CASE: A 72-year-old man, who received seven courses of atezolizumab/bevacizumab for hepatocellular carcinoma due to hepatitis B, was admitted to our department with idiopathic abdominal pain and diarrhea (grade 2 [G2]). Computed tomography (CT) and colonoscopy confirmed edema in the gastrointestinal tract. Perforation of the jejunum was observed in a CT performed on the third day and an emergency operation was performed. Intraoperative findings showed severe edema of the jejunum and leakage of feces into the abdominal cavity. The patient was diagnosed with irAE enteritis comprehensively with severe wall thickening on CT and colonoscopy, negative stool culture, and pathological findings of CD8-positive cells. Infliximab was administered before initiating steroids, to prevent reperforation. The enteritis improved by the 22nd day; however, CT performed on the 35th day of illness showed relapse of gastrointestinal wall thickening and G2 diarrhea symptoms; therefore, prednisolone (PSL) 60 mg/day was started on the 36th day of illness. After introducing PSL, enteritis did not reoccur, and the patient was discharged on the 63rd day of illness after admission. CONCLUSION: There are no reports of gastrointestinal perforation by atezolizumab/bevacizumab for hepatocellular carcinoma, and prior administration of infliximab. We therefore report the clinical course and management.

AIM: The risk of hepatitis B virus (HBV) reactivation with immune checkpoint inhibitors (ICIs) is an important issue that has not yet been fully investigated. ICI is also expected to have an antiviral effect on HBV due to its immune tolerance inhibitory effect. We herein investigated the risk of HBV reactivation and the antiviral effect of ICI administration. METHODS: This study included 892 patients on ICIs between September 2014 and May 2021 at our hospital. The frequency of HBV reactivation and antiviral effects were investigated. RESULTS: Among the 892 patients who underwent ICI, 27 were hepatitis B surface antigen (HBsAg) positive. HBV reactivation was evaluated in 24 cases, among which 4.1% (1/24) had HBV reactivation. Nucleic acid analog prophylaxis was not administered to patients with reactivation. In a study of 15 cases, the amount of HBsAg decreased from baseline; 2.18 ± 0.77 log to 48 weeks later; 1.61 ± 1.38 log (p = 0.17). Forty-eight weeks after the start of ICI, disappearance of HBsAg was observed in two out of 15 cases (13.3%), and one case each with and without nucleic acid analog. CONCLUSION: In rare cases, HBsAg-positive patients may be reactivated by ICI administration. On the other hand, when ICI is administered, it is expected to have an antiviral effect on HBV due to its immune tolerance inhibitory effect, and future drug development is expected.

AIM: We report a rare case of immune-related cholangitis in which the natural course could be demonstrated. CASE PRESENTATION: Eight courses of pembrolizumab maintenance therapy were given as first-line treatment for squamous cell lung cancer; however, the patient was subsequently hospitalized due to a rapid increase in hepatobiliary enzymes. On endoscopic ultrasound, the common bile duct was dilated to 11 mm, and the wall, throughout its length from the papilla, was thickened. Endoscopic retrograde cholangiopancreatography showed no obvious stenosis in the lower bile duct; however, a parapapillary diverticulum was found, and papillary incision and bile duct plastic stent insertion were carried out. However, the liver disorder did not improve and overt jaundice appeared subsequently; therefore, an immune-related cholangitis was suspected, and prednisolone (PSL) 35 mg/day was introduced from day 59 of admission. Following PSL initiation, a decrease in serum bilirubin level was observed; however, significant decrease was not observed in alkaline phosphatase. Given the history of recurrent infectious cholangitis, magnetic resonance cholangiopancreatography was carried out on day 70 of admission. The intrahepatic bile duct showed stenosis and dilated findings, which was considered to be a factor for repeated infectious cholangitis. CONCLUSION: No previous case reports have described the changes and progression in bile duct images in immune-related adverse events. Therefore, this case is noteworthy for considering the progression of immune-related cholangitis.

BACKGROUND AND AIM: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) is useful for the diagnosis of lesions inside and outside the digestive tract. This study evaluated the value of artificial intelligence (AI) in the diagnosis of gastric submucosal tumors by CH-EUS. METHODS: This retrospective study included 53 patients with gastrointestinal stromal tumors (GISTs) and leiomyomas, all of whom underwent CH-EUS between June 2015 and February 2020. A novel technology, SiamMask, was used to track and trim the lesions in CH-EUS videos. CH-EUS was evaluated by AI using deep learning involving a residual neural network and leave-one-out cross-validation. The diagnostic accuracy of AI in discriminating between GISTs and leiomyomas was assessed and compared with that of blind reading by two expert endosonographers. RESULTS: Of the 53 patients, 42 had GISTs and 11 had leiomyomas. Mean tumor size was 26.4 mm. The consistency rate of the segment range of the tumor image extracted by SiamMask and marked by the endosonographer was 96% with a Dice coefficient. The sensitivity, specificity, and accuracy of AI in diagnosing GIST were 90.5%, 90.9%, and 90.6%, respectively, whereas those of blind reading were 90.5%, 81.8%, and 88.7%, respectively (P = 0.683). The κ coefficient between the two reviewers was 0.713. CONCLUSIONS: The diagnostic ability of CH-EUS results evaluated by AI to distinguish between GISTs and leiomyomas was comparable with that of blind reading by expert endosonographers.

Liver damage affects the prognosis of patients with erythropoietic protoporphyria (EPP). However, there is no radical cure for EPP patients with severe liver damage. This study aims to investigate the effectiveness of phlebotomy in patients with severe liver damage. We examined seven patients diagnosed with EPP and liver damage between 2010 and 2020. Of the 7 cases, phlebotomy was performed in 3 cases with severe hepatic disorder, and the improvement effect of hepatic disorder was observed in all cases. In addition, as an additional study, we also investigated the mechanism by which liver damage becomes more severe. Liver biopsy samples were stained with hematoxylin and eosin and immunohistochemistry was used to examine the expression of adenosine triphosphate-binding transporter G2 (ABCG2). Liver biopsies were performed in 3 of 7 patients with EPP. Of these three patients, ABCG2 expression was low in two patients, especially in the protoporphyrin (PP) deposition area. Two patients with reduced ABCG2 expression subsequently developed severe liver damage. However, the causal relationship between the decreased expression of ABCG2 and the exacerbation of liver damage has not been directly proved, and further investigation is required in the future. This study demonstrated the effectiveness of phlebotomy in EPP patients with severe liver damage.

The incidence of hepatocellular carcinoma (HCC) related to non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. We analyzed 16 surgically resected HCC cases in which the background liver was pathologically diagnosed as NAFLD. Specimens with Brunt classification grade 3 or higher were assigned as the fibrotic progression group (n = 8), and those with grade 1 or lower were classified as the non-fibrosis progression group (n = 8). Comprehensive mutational and methylome analysis was performed in cancerous and noncancerous tissues. The target gene mutation analysis with deep sequencing revealed that CTNNB1 and TP53 mutation was observed in 37.5% and TERT promoter mutation was detected in 50% of cancerous samples. Furthermore, somatic mutations in non-cancerous samples were less frequent, but were observed regardless of the progression of fibrosis. Similarly, on cluster analysis of methylome data, status for methylation events involving non-cancerous liver was similar regardless of the progression of fibrosis. It was found that, even in cases of non-progressive fibrosis, accumulation of gene mutations and abnormal methylation within non-cancerous areas were observed. Patients with NAFLD require a rigorous liver cancer surveillance due to the high risk of HCC emergence based on the accumulation of genetic and epigenetic abnormalities, even when fibrosis is not advanced.

BACKGROUND: Pancreatic cancer (PC) exhibits extremely rapid growth; however, it remains largely unknown whether the early stages of PC also exhibit rapid growth speed equivalent to advanced PC. This study aimed to investigate the natural history of early PCs through retrospectively assessing pre-diagnostic images. METHODS: We examined the data of nine patients, including three patients with carcinoma in situ (CIS), who had undergone magnetic resonance cholangiopancreatography (MRCP) to detect solitary main pancreatic duct (MPD) stenosis >1 year before definitive PC diagnosis. We retrospectively analyzed the time to diagnosis and first-time tumor detection from the estimated time point of first-time MPD stenosis detection without tumor lesion. RESULTS: The median tumor size at diagnosis and the first-time tumor detection size were 14 and 7.5 mm, respectively. The median time to diagnosis and first-time tumor detection were 26 and 49 months, respectively. CONCLUSIONS: No studies have investigated the PC history, especially that of early PCs, including CIS, based on the initial detection of MPD stenosis using MRCP. Assessment of a small number of patients showed that the time to progression can take several years in the early PC stages. Understanding this natural history is very important in the clinical setting.

AIM: Both entecavir (ETV) and tenofovir alafenamide fumarate (TAF) are widely used to treat chronic hepatitis B (CHB) in Japan. However, it remains unclear whether the efficacy of TAF in decreasing the hepatitis B surface antigen (HBsAg) level, and its safety, are superior to those of ETV. This study aimed to report the long-term effects and safety of 96-week ETV and TAF treatment in patients with CHB. METHODS: A prospective comparative observational study was undertaken on the following two groups: patients with CHB who received continuous ETV (n = 32) and patients with CHB who were switched from ETV to TAF upon request (n = 48). The HBsAg, urinary β2-microglobulin (β2MG)/creatinine (Cr), urinary N-acetyl-β-D-glucosaminidase (NAG)/Cr, and serum alanine aminotransferase (ALT) levels, estimated glomerular filtration rate (eGFR), and bone mineral density (lumbar spine and femur) at 96 weeks were compared. RESULTS: The two groups did not significantly differ with respect to mean age, male / female patient ratio, or rate of hepatitis B e antigen-positive status. The mean changes in serum HBsAg level and eGFR at 96 weeks were not significantly different between the two groups. The β2MG/Cr and NAG/Cr levels at 96 weeks were similar between the two groups. Additionally, the bone mineral density of the lumbar spine and femur as well as the serum ALT did not significantly differ. CONCLUSIONS: When compared with patients who received continuous ETV, those who were introduced to TAF after ETV showed similar effects in terms of the decrease in HBsAg level and safety.

Unsuccessful stent replacement in transpapillary biliary drainage with plastic stents (PSs) has a significant impact on patient prognosis; thus, a safe and reliable replacement method is required. We aimed to compare the snare-over-the-guidewire (SOG) method, wherein the PS lumen is used as an access route to the biliary tract and the PS is removed with a snare inserted via the inserted guidewire, with the conventional side-of-stent (SOS) method, wherein the biliary approach is performed from the side of the PS. This retrospective single-center study included 244 consecutive patients who underwent biliary PS replacement between January 2018 and July 2020. The procedural success rates were compared between the two methods. A predictive analysis of unsuccessful PS replacement was also performed. The procedural success rate in the SOG group was significantly higher than that in the SOS group (p = 0.026). In the proximal biliary stenosis lesion, the same trend was observed (p = 0.025). Multivariate analysis also showed that the SOS method (p = 0.0038), the presence of proximal biliary stenosis (p < 0.0001), and parapapillary diverticulum (p = 0.0007) were predictors of unsuccessful PS replacement. The SOG method may be useful for biliary PS replacement, especially in cases of proximal hilar bile duct stenosis.

BACKGROUND: Colonic volvulus, a condition in which a colonic segment partially twists around its base, is the third leading cause of large bowel obstruction after colonic neoplasms and diverticular disease. However, volvulus of the transverse colon is the rarest type of large intestinal volvulus. Moreover, the occurrence of transverse colonic volvulus secondary to a benign tumor originating from outside the intestine has never been reported. We hereby report a case of transverse colonic volvulus caused by mesenteric fibromatosis. CASE PRESENTATION: A 53-year-old female with a history of rheumatoid arthritis and thyroid tumor presented with abdominal pain for 1 day. Abdominal computed tomography revealed intestinal torsion at the hepatic flexure. Twisted and obstructed mucosa of the transverse colon was observed during colonoscopy, but no tumor invasion of the mucosal surface was detected. A solid mass of a mesenteric origin with involvement of the transverse colon was observed during surgery. The mass was diagnosed surgically as transverse colonic volvulus induced by a mesenteric tumor. Hence, the patient underwent a right hemicolectomy. Histopathological results indicated mesenteric desmoid-type fibromatosis. The postoperative recovery was uneventful, and the patient was discharged 8 days after surgery. CONCLUSIONS: Although mesenteric fibromatosis is rare, this disease should be considered when managing transverse colonic volvulus resulting from nonmucosal tumors.

Neurilemmomas are benign tumors arising from the sheaths of peripheral nerves. They appear rarely in the abdominal cavity. We herein report an 80-year-old man with a multilocular cystic neurilemmoma mimicking a liver lesion. Preoperative images showed a lesion in the porta hepatis. Although a preoperative diagnosis was difficult, surgery was undertaken because of the possibility of malignancy. Histologically, the tumor consisted of spindle-shaped cells with positivity for S-100 protein. The final diagnosis was a neurilemmoma. Porta hepatic neurilemmomas are rare. When we encounter a multilocular cystic lesion of the liver, neurilemmoma should be considered in the differential diagnosis.

A 27-year-old man bearing an erythropoietic protoporphyria (EPP)-associated ferrochelatase (FECH) mutation was admitted to our hospital for general malaise and marked elevation of the serum levels of hepatobiliary enzymes and bilirubin. Initial treatment with plasma exchange did not reduce the blood protoporphyrin or serum liver enzyme levels, so phlebotomy was started. Surprisingly, weekly phlebotomy normalized the serum levels of liver enzymes, accompanied by a marked reduction in the blood protoporphyrin levels. The clinical course of this case strongly suggests that phlebotomy may be a suitable treatment option for EPP-related hepatopathy.