Remaining Issues Related to Serum Cytokines in Patients with Unresectable Hepatocellular Carcinoma Treated by Atezolizumab plus Bevacizumab Combination Treatment.

INTRODUCTION: Atezolizumab plus bevacizumab (AteBev) combination treatment is widely used as first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC). We aimed to clarify therapeutic issues regarding serum cytokines and the immune reaction in patients with uHCC treated with AteBev. METHODS: We analyzed preserved serum from a previous prospective study on adult Japanese patients with chronic liver disease and uHCC who received AteBev treatment at our hospital. In that study, AteBev were administered intravenously every 3 weeks, and blood samples were collected before and after 3 weeks' treatment. Dynamic computed tomography was performed after 6 weeks of treatment to assess response. RESULTS: In the prospective study, 21 of the 59 patients showed partial response (PR) and 19 patients showed stable disease (SD), but 19 patients showed progressive disease (PD). We found that serum levels of tumor necrosis factor-alpha, interleukin (IL)-6, and soluble IL-2 receptor (IL-2R) increased significantly in the PR group, but only soluble IL-2R increased significantly in the PD group. Regulatory T cells decreased significantly in the PD group, but there was no significant change in Th1 or Th2 cells from before to after treatment in any group. As regards soluble MHC-class I, pre-treatment levels were significantly lower in the PD group than in the PR group, and serum levels increased significantly with treatment in the PD group. CONCLUSION: These findings reveal a need to further improve T-cell priming and to further make T-cells recognize tumor antigens in uHCC.

Role of advanced endoscopy in the management of inflammatory digestive diseases (pancreas and biliary tract).

The progress of endoscopic diagnosis and treatment for inflammatory diseases of the biliary tract and pancreas have been remarkable. Endoscopic ultrasonography (EUS) and EUS-elastography are used for the diagnosis of early chronic pancreatitis and evaluation of endocrine and exocrine function in chronic pancreatitis. Notably, extracorporeal shock wave lithotripsy and electrohydraulic shock wave lithotripsy have improved the endoscopic stone removal rate in patients for whom pancreatic stone removal is difficult. Studies have reported the use of self-expanding metal stents for stent placement for pancreatic duct stenosis and EUS-guided pancreatic drainage for refractory pancreatic duct strictures. Furthermore, EUS-guided drainage using a double-pigtailed plastic stent has been performed for the management of symptomatic pancreatic fluid collection after acute pancreatitis. Recently, lumen-apposing metal stents have led to advances in the treatment of walled-off necrosis after acute pancreatitis. EUS-guided biliary drainage is an alternative to refractory endoscopic biliary drainage and percutaneous transhepatic biliary drainage for the treatment of acute cholangitis. The placement of an inside stent followed by switching to uncovered self-expanding metal stents in difficult-to-treat cases has been proposed for acute cholangitis by malignant biliary obstruction. Endoscopic transpapillary gallbladder drainage is an alternative to percutaneous transhepatic gallbladder drainage for severe and some cases of moderate acute cholecystitis. EUS-guided gallbladder drainage has been reported as an alternative to percutaneous transhepatic gallbladder drainage and endoscopic transpapillary gallbladder drainage. However, it is important to understand the advantages and disadvantages of each drainage method and select the optimal drainage method for each case.

[Epstein-Barr virus-associated gastritis with perigastric lymphadenopathy accompanied by infectious mononucleosis:a case report].

A 28-year-old female patient with no particular medical history had a sore throat seven days before admission. Subsequently, she developed malaise, right abdominal pain, and a fever of 38°C and visited our hospital. A blood test revealed a mild inflammatory response and elevated liver enzymes, and she was admitted to the hospital for detailed examination and acute liver injury treatment. Various viral tests and autoantibody measurements revealed elevated Epstein-Barr virus (EBV) immunoglobulin M and negative EB nuclear antigen antibodies. Therefore, she was diagnosed with primary infectious mononucleosis-associated EB viral hepatitis. Abdominal computed tomography upon admission revealed swollen lymph nodes around the stomach;thus, esophagogastroduodenoscopy (EGD) was performed. A histopathological examination revealed severe lymphocytic infiltration, and EB encoding region in situ hybridization demonstrated that 10-20% of the lymphocytes were EBV-infected. Drip and rest treatment improved the patient's liver enzymes, and her symptoms resolved. Repeat EGD after two months revealed improved gastric erosions. Here, we report a case of EBV-associated gastritis that was discovered due to perigastric lymphadenopathy accompanied by infectious mononucleosis. This report includes a review of the literature because a few studies reported EBV-associated gastritis.

Variceal bleeding following treatment with atezolizumab plus bevacizumab in two patients with unresectable hepatocellular carcinoma.

Bleeding-related adverse events may occur due to anti-vascular endothelial growth factors. Here, we report two cases of variceal rupture during atezolizumab plus bevacizumab (ATZ/BV) treatment for unresectable hepatocellular carcinoma (u-HCC).Case 1 involved a man in his 60 s with alcoholic liver cirrhosis (LC) and u-HCC. Seventy-four days after ATZ/BV administration, the patient was admitted for hematemesis. Upper esophagogastroduodenoscopy (EGD) revealed worsening of the esophageal varices (EVs) to F2 grade with active bleeding. Endoscopic variceal ligation successfully achieved hemostasis.Case 2 involved a man in his 70 s with alcoholic LC and u-HCC. The patient was admitted with hematemesis 114 days after ATZ/BV administration. During EGD, the EVs deteriorated to F3 grade, although hemostasis had already been achieved. The evaluation was discontinued during the observation stage because of the worsening hepatic reserve.Neither patient had EVs warranting prophylactic treatment before ATZ/BV administration, showed a partial tumor response, or had portal vein tumor thrombus. Both patients demonstrated increased total diameters of the collateral veins and splenic volume compared to those before treatment. These findings suggest that ATZ/BV treatment may increase portal pressure. In conclusion, the administration of ATZ/BV to patients with LC and u-HCC necessitates careful management of EVs aggravation and rupture.

Analysis of Gloss Unevenness and Bidirectional Reflectance Distribution Function in Specular Reflection.

Gloss is associated significantly with material appearance, and observers often focus on gloss unevenness. Gloss unevenness is the intensity distribution of reflected light observed within a highlight area, that is, the variability. However, it cannot be analyzed easily because it exists only within the highlight area and varies in appearance across the reflection angles. In recent years, gloss has been analyzed in terms of the intensity of specular reflection and its angular spread, or the bidirectional reflectance distribution function (BRDF). In this study, we develop an apparatus to measure gloss unevenness that can alter the angle with an angular resolution of 0.02°. Additionally, we analyze the gloss unevenness and BRDF in terms of specular reflection. Using a high angular resolution, we measure and analyze high-gloss materials, such as mirrors and plastics, and glossy materials, such as photo-like inkjet paper and coated paper. Our results show that the magnitude of gloss unevenness is the largest at angles marginally off the center of the specular reflection angle. We discuss an approach for physically defining gloss unevenness based on the BRDF.

Outcomes of 6-mm diameter fully covered self-expandable metal stents for preoperative biliary drainage in pancreatic cancer.

Background: 10-mm self-expandable metal stents (SEMSs) are commonly used for preoperative biliary drainage in pancreatic cancer. However, smaller diameter SEMSs have attracted attention with the attempt to reduce stent-related adverse events (AEs). Methods: We retrospectively analyzed consecutive borderline resectable pancreatic cancer patients who underwent neoadjuvant therapy and fully covered SEMS (FCSEMS) placement from April 2015 to May 2023. The primary outcome was stent-related non-event rate (NER), which was defined as the rate of completion of surgery without developing any preoperative events (recurrent biliary obstruction [RBO] or stent-related AEs). Secondary outcomes included stent-related AEs, causes of RBO, and cumulative incidence of RBO. Risk factors for pancreatitis, RBO, and stent migration were also examined. Results: A total of 76 patients were included (6-mm group: 23; 10-mm group: 53). Stent-related NER (57% vs. 64%, p = 0.610), stent-related AEs (4% vs. 15%, p = 0.263), overall RBO rates (39% vs. 23%, p = 0.168), cumulative incidence of RBO (hazard ratio, 2.24; 95% confidence interval, 0.95-5.25; p = 0.065) were not significantly different between the two groups. Tumor involvement of the pancreatic duct was identified as a risk-reducing factor for pancreatitis, while an FCSEMS diameter of 6 mm was not identified as a risk factor for RBO and stent migration. Conclusions: Stent-related NER was not significantly affected by FCSEMS diameter. Further studies are needed to confirm the usefulness of 6-mm diameter FCSEMS for preoperative biliary drainage in patients with borderline resectable pancreatic cancer.

Pancreatico-renal fistula associated with pancreatic cysts caused by type 1 autoimmune pancreatitis.

To our best knowledge, the formation of a pancreatico-renal fistula and the presence of pancreatic fluid collection in the renal subcapsular space have not been reported as autoimmune pancreatitis (AIP) complications. We describe a case of a pancreatico-renal fistula associated with type 1 AIP. The patient presented with abdominal and back pain accompanied by pancreatic cystic lesions during an untreated course of AIP. The diagnosis of pancreatico-renal fistula was based on the presence of a left renal subcapsular fluid collection containing pancreatic amylase, disappearance of pancreatic cysts, and a defect in the partial anterior renal fascia observed on imaging studies. Treatment with steroids and percutaneous drainage resulted in improvement. Pancreatic pseudocysts can affect other organs owing to their digestive action. Similar symptoms may occur in patients with AIP.

Symptomatic hepatic cyst treated with endoscopic ultrasound-guided drainage and minocycline hydrochloride injection: a case report.

A 72 year-old male patient with a history of a hepatic cyst presented to our hospital with epigastric pain. The cyst had enlarged to approximately 130 mm and was diagnosed as a symptomatic hepatic cyst. Percutaneous cyst drainage was deemed challenging because of the risk of intestinal perforation; therefore, transgastric endoscopic ultrasound-guided hepatic cyst drainage was performed with external nasal cyst drainage. After cyst shrinkage was confirmed, minocycline hydrochloride was injected into the cyst through the nasal drainage tube, and the nasal cyst drainage was removed. Nine months after treatment, the cyst diameter markedly reduced to 12 mm on computed tomography, and the symptoms improved. In cases where surgery is complex or it is difficult to secure a percutaneous puncture line, endoscopic ultrasound-guided drainage and minocycline hydrochloride injection may be effective if a puncture route can be secured under endoscopic ultrasound.