Comparison of antimicrobial therapy termination in febrile and afebrile patients with acute cholangitis after drainage.

The standard treatment duration for acute cholangitis (AC) involves a 4-7-day antimicrobial treatment post-biliary drainage; however, recent studies have suggested that a ≤ 2-3 days is sufficient. However, clinical practice frequently depends on body temperature as a criterion for discontinuing antimicrobial treatment. Therefore, in this study, we assessed whether patients with AC can achieve successful outcomes with a ≤ 7-day antimicrobial treatment, even with a fever, assuming the infection source is effectively controlled. We conducted a single-center retrospective study involving patients with AC, defined following the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a ≤ 7-day antimicrobial treatment. Patients were categorized into the febrile and afebrile groups based on their body temperature within 24 h before completing antimicrobial treatment. The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 post-biliary drainage without recurrence or death by day 30. The secondary outcome was a 3-month recurrence rate. Logistic regression with inverse probability of treatment weighting was used. Overall, 408 patients were selected, among whom 40 (9.8%) were febrile. The two groups showed no significant differences in the clinical cure and 3-month recurrence rates. Notably, the subgroups limited to patients with a ≤ 3-day antibiotic treatment duration also showed no differences in these outcomes. Therefore, our results suggest that discontinuing antibiotics within the initially planned treatment period was sufficient for successful drainage cases of AC, regardless of the patient's fever status during the 24 h leading up to termination.

A Phase 1b Study of Lenvatinib plus Pembrolizumab in Patients with Unresectable Hepatocellular Carcinoma: Extended Analysis of Study 116.

Introduction: Lenvatinib (dosing for patients who weigh ≥60 kg was 12 mg/day; for patients who weigh <60 kg, the dose was 8 mg/day) plus pembrolizumab 200 mg once every 3 weeks demonstrated antitumor activity and a manageable safety profile in patients with first-line unresectable hepatocellular carcinoma (uHCC) in the open-label phase 1b Study 116/KEYNOTE-524 (primary analysis data cutoff date: October 31, 2019; median follow-up: 10.6 months). This analysis (updated data cutoff date: March 31, 2021) reports efficacy results from 17 months of additional follow-up time. Methods: 100 patients with uHCC were included in the primary analysis (median follow-up: 27.6 months). Endpoints included overall survival (OS), investigator-assessed progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) per modified RECIST. Landmark analyses of OS by the best response at 3 and 9 months were performed. Pembrolizumab antidrug antibodies (ADAs) and concentrations were also measured (cutoff date: August 7, 2020). Results: ORR was 43.0% (95% CI 33.1-53.3%) and median DOR was 17.1 months (95% CI 6.9-19.3 months). Median PFS and OS were 9.3 months (95% CI 7.4-9.8 months) and 20.4 months (95% CI 14.4-25.9 months), respectively. No treatment-emergent ADAs were detected. Conclusion: Results show a sustained treatment effect with lenvatinib plus pembrolizumab in patients with uHCC in the first-line setting.

Resection of a retroperitoneal lumbar vein aneurysm: A case report.

We present a rare case involving a 54-year-old man with a history of pancreatitis who developed a retroperitoneal lumbar vein aneurysm that was initially misidentified as a pancreatic pseudocyst. Subsequent imaging revealed an enlarged mass and retroperitoneal perforation. Despite initial hesitation, the patient eventually underwent radical surgery that enabled the successful removal of the mass, which was near the inferior vena cava. Pathological examination confirmed varicose veins, and the final diagnosis was lumbar vein aneurysm in the retroperitoneum. The patient's postoperative recovery was uneventful, with no symptoms or recurrence observed on 6-month follow-up imaging. We investigated a potential link between pancreatitis and recurrent bleeding due to weakened venous walls. The findings from this case underscore the rarity of venous aneurysms and the diagnostic and treatment challenges due to the limited number of cases; furthermore, they emphasize that surgery should be carefully considered based on the lesion location and associated risks.

An in vitro study of metformin adsorption to activated charcoal.

INTRODUCTION: Metformin is a biguanide used to manage patients with type 2 diabetes mellitus. However, metabolic acidosis with an elevated lactate concentration and death caused by metformin overdoses are toxicological concerns. Although activated charcoal has been widely used for gastrointestinal decontamination in cases of acute poisoning, there is no evidence regarding its efficacy in treating metformin overdoses. We therefore evaluated the adsorptive capacity of activated charcoal for metformin in vitro. METHODS: Activated charcoal (specific surface area: 1,080 m2/g) mixed with various concentrations of metformin solution was dissolved in simulated gastric and intestinal fluids at 37° Celsius. The suspension was then filtered and the metformin concentration in the filtrate was determined using high-performance liquid chromatography. The maximum adsorptive capacity for metformin was calculated using the Langmuir adsorption isotherm equation. RESULTS: The amount of metformin adsorbed per gram of activated charcoal ranged from 0.7 to 8.1 mg/g at pH 1.2, and from 8.4 to 48.2 mg/g at pH 6.8. The corresponding maximum adsorptive capacities were 10.6 mg/g and 55.9 mg/g respectively. DISCUSSION: The maximum adsorptive capacity of activated charcoal for metformin was similar to that of its capacity for other poorly adsorbed substances. This is likely because metformin is water-soluble and has high polarity-factors that correlate with poor adsorption on activated charcoal. CONCLUSIONS: The maximum adsorption of metformin by activated charcoal was low. Therefore, activated charcoal may not be effective for treating patients with metformin overdose.

Antimicrobial therapy outcomes in acute cholangitis: Hilar multiple obstructions versus single hilar and common bile duct obstructions.

Background and Aim: The appropriate duration of antimicrobial therapy for acute cholangitis (AC) arising from multiple hilar biliary obstructions as opposed to simple obstruction in the extrahepatic bile duct has not been established. This study assessed the efficacy of the duration of antimicrobial treatments in the Tokyo Guidelines 2018 for AC based on the cause and site of obstruction. Methods: This single-center retrospective study involved patients with AC who underwent successful biliary drainage and completed a 7-day or shorter antimicrobial treatment. Patients were categorized into three groups: Group 1, bile duct stone or benign obstruction; Group 2, simple biliary obstruction due to malignancy; and Group 3, multiple hilar biliary obstruction due to malignancy. The primary outcome was clinical cure rate, and the secondary outcomes were 3-month recurrence rate and length of hospital stay. Results: A total of 373 patients were selected. Patients in Group 3 were younger or had Charlson Comorbidity Index ≥4, and had fewer positive blood cultures. In Group 3, the clinical cure rate (87.1%) and 3-month recurrence rate (32.3%) were less favorable than those in the other groups. In Group 1, the clinical cure rate was significantly higher (98.1%, P = 0.02) with a much lower 3-month recurrence rate of only 3.4% (P < 0.001) than that in the other groups. The median hospital stay for all groups was 7 days. Conclusion: This study suggests that the outcomes in Group 3 may be worse than those in Groups 1 or 2, regardless of the duration of the antibiotic treatment.

Association of short-course antimicrobial therapy and bacterial resistance in acute cholangitis: Retrospective cohort study.

Background and study aims Although the number of resistant bacteria tends to increase with prolonged antimicrobial therapy, no studies have examined the relationship between the duration of antimicrobial therapy and increase in the number of resistant bacteria in acute cholangitis. We hypothesized that the short-term administration of antimicrobial agents in acute cholangitis would suppress bacterial resistance. Patients and methods This was a single-center, retrospective, observational study of patients with acute cholangitis admitted between January 2018 and June 2020 who met the following criteria: successful biliary drainage, positive blood or bile cultures, bacteria identified from cultures sensitive to antimicrobials, and subsequent cholangitis recurrence by January 2022. The patients were divided into two groups: those whose causative organisms at the time of recurrence became resistant to the antimicrobial agents used at the time of initial admission (resistant group) and those who remained susceptible (susceptible group). Multivariate analysis was used to examine risk factors associated with the development of resistant pathogens. Multivariate analysis investigated antibiotics used with the length of 3 days or shorter after endoscopic retrograde cholangiopancreatography (ERCP) and previously reported risk factors for the development of bacterial resistance. Results In total, 89 eligible patients were included in this study. There were no significant differences in patient background or ERCP findings between the groups. The use of antibiotics, completed within 3 days after ERCP, was associated with a lower risk of developing bacterial resistance (odds ratio, 0.17; 95% confidence interval, 0.04-0.65; P =0.01). Conclusions In acute cholangitis, the administration of antimicrobials within 3 days of ERCP may suppress the development of resistant bacteria.

Benralizumab treatment in an elderly patient with eosinophilic esophagitis resulted in remission: a case report.

BACKGROUND: Interleukin-5 (IL-5) has recently been shown to play a crucial role in eosinophil-mediated diseases, implying that an IL-5 receptor alpha chain (IL-5Rα) antibody (benralizumab) can be effective against eosinophilic esophagitis (EoE). Here, we present a case in which benralizumab significantly improved the symptoms and signs of an elderly Asian woman with EoE who had inadequate response to existing treatments. Case presentation A 73-year-old woman with an 8-year history of bronchial asthma (BA) and a 7-year history of dysphagia presented to our hospital with worsening dysphagia, vomiting, chest pain, and difficulty in eating. Blood biochemical findings revealed an increase in the eosinophil fraction of white blood cells (42.2%), and a conventional chest computed tomography scan revealed esophageal wall thickening. An upper gastrointestinal endoscopy revealed mucosal edema as well as multiple esophageal rings, and esophageal biopsy specimens showed an eosinophilic infiltrate of more than 15 cells/ high power field. Based on these findings, she was diagnosed as EoE complicated by BA. We firstly administrated 20 mg/day of prednisolone, rabeprazole sodium and liquid budesonide oral suspension for 5 months; however, they were ineffective and her dysphagia worsened over time. Then, benralizumab treatment in combination with these drugs was started. Her dysphagia completely disappeared 2 weeks after starting benralizumab, and an upper endoscopy showed that the clinical findings had completely disappeared after another 6 weeks. Benralizumab was then given to her for 41 months, and her symptoms remained in remission. In addition, she had no EoE recurrence for more than 12 months after discontinuing benralizumab. CONCLUSIONS: Benralizumab in combination with other multiple drugs significantly improved the symptoms and examination findings of an elderly patients with EoE. Furthermore, she experienced no recurrence even after discontinuing benralizumab withdrawal, suggesting that benralizumab could be an appropriate therapeutic option for EoE.

Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with possible complication of thrombotic microangiopathy.

This case study illustrates a 63-year-old Japanese woman who presented with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis. She was administered a therapeutic regimen consisting of corticosteroids, tacrolimus, and cyclophosphamide. However, after a month of treatment, symptoms of confusion and depressive tendencies emerged, followed by the manifestation of hematuria, thrombocytopenia, and fragmented erythrocytes. A disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13 activity was 45%. Thrombotic microangiopathy was contemplated, yet a definitive diagnosis remained elusive. She died 2 months after admission. Although the occurrence of thrombotic microangiopathy in patients with dermatomyositis is rare, the prognosis is poor, emphasizing the importance of prompt diagnosis and treatment.

Exploration of predictors associated with bleeding in computed tomography-guided core needle splenic biopsy: A retrospective study.

Splenic diseases may be caused by infections and can be either malignant, such as lymphoma and lung cancer, or benign, such as hemangioma. In some cases, diagnostic uncertainty of imaging persists, and image-guided splenic needle biopsy is a useful diagnostic tool to avoid the disadvantages of incorrect diagnosis, including performing unnecessary splenectomy or not giving the necessary treatment. Splenic biopsies can be divided into ultrasound-guided, computed tomography (CT)-guided fine-needle aspiration, or core needle biopsy (CNB). However, few studies have focused exclusively on complications associated with CT-guided CNB of the spleen. Therefore, we assessed bleeding, the most common complication of CT-guided CNB of the spleen, and evaluated factors associated with the bleeding. Using the biopsy database maintained at the institution, all patients who underwent CT-guided CNB of the spleen between May 2012 and September 2022 were identified retrospectively. The 18 identified patients were divided into post-biopsy bleeding and non-bleeding groups for analysis. In total, 17 patients (94.4%) could be diagnosed accurately with CT-guided CNB. Bleeding complications occurred in 7 cases of CT-guided CNB; of these, 2 patients with Common Terminology Criteria for Adverse Events grade 4 disease required transcatheter arterial embolization. The bleeding group was characterized by diffuse spleen tumors in all cases, with significantly more diffuse spleen tumors than the non-bleeding group. CT-guided CNB is a useful option for neoplastic lesions of the spleen that are difficult to diagnose using imaging alone. However, consideration should be given to post-biopsy bleeding in patients with diffuse splenic tumors.

A Case of Drug-induced Liver Injury Considered Steroid-resistant and Histologically Diagnosed with Vanishing Bile Duct Syndrome.

Vanishing bile duct syndrome (VBDS) is characterized by bile duct degeneration and necrosis, which result in bile duct loss and bile stasis. A 70-year-old man had malaise after receiving celecoxib. Laboratory tests revealed elevated hepatobiliary enzymes. His condition worsened without response to medical treatment, and he was transferred to our hospital. A liver biopsy revealed severe bile duct injury and mild cholestasis. He was diagnosed with celecoxib-induced VBDS and underwent bilirubin adsorption therapy. However, his condition continued to deteriorate, and he died. An autopsy showed that liver regeneration was poor, and bile duct loss was exacerbated. The pathological autopsy findings were consistent with VBDS.

Efficacy and safety of postoperative preemptive use of tolvaptan for patients with cirrhosis undergoing hepatectomy for hepatocellular carcinoma.

PURPOSE: Optimal choice of diuretics in perioperative management remains unclear in enhanced recovery after liver surgery. This study investigated the efficacy and safety of tolvaptan (oral vasopressin V2-receptor antagonist) in postoperative management of patients with liver injury and hepatocellular carcinoma. METHODS: The patients clinically diagnosed with liver cirrhosis were included in this study. Clinical outcomes of 51 prospective cohort managed with a modified postoperative protocol using tolvaptan (validation group) were compared with 83 patients treated with a conventional management protocol (control group). RESULTS: Postoperative urine output were significantly larger and excessive body weight increase were reduced with no impairment in renal function or serum sodium levels in the validation group. Although the total amount of discharge and trend of serum albumin level were not significantly different among the groups, global incidence of postoperative morbidity was less frequent (19.6% vs. 44.6%, P=0.005) and postoperative stay was significantly shorter (8 days vs.10 days, P=0.008) in the validation group compared with the control group. CONCLUSIONS: Tolvaptan could be safely used for the patients with injured liver in postoperative management after hepatectomy and potentially advantageous in the era of enhanced recovery after surgery with its strong diuretic effect and better fluid management.

Quantitative analysis of powder samples using screen-printing techniques as sample preparation methods for LA-ICP-MS.

The combination of laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) offers a powerful tool for directly analyzing solid samples. However, LA-ICP-MS has a limitation in quantitative analyses owing to a requirement for matrix-matched standard materials. In this study, we have developed a sample preparation method that facilitates quantitative analyses by LA-ICP-MS. The sample powder is dispersed in a liquid resin and film-like samples are prepared from the resulting paste by a screen-printing technique. The sample includes the analyte spiked with internal standards and is prepared by mixing standard solutions in the sample paste. Because all reagents except for the sample powder are liquids, homogeneous samples can be easily obtained. The internal standard and concentration of the spiked analyte can be tailored for each sample, which is a requirement for accurate quantitative analyses. The amount of sample and concentration of the spiked analyte are controlled against an internal standard, enabling internal standardization without the need to have an element of known concentration in the sample. The accuracy of this method was evaluated by analyzing impurity elements in TiO2 powder; however, it is expected that other materials could also be analyzed. The versatility and flexibility of this method suggest great potential for quantitative analyses by LA-ICP-MS, for which reliable matrix-matched standard materials are required.

Multisystem Inflammatory Syndrome in an Adult on Hemodialysis with Markedly Elevated Procalcitonin and Ferritin Levels.

A 21-year-old man on hemodialysis was hospitalized for coronavirus disease 2019 (COVID-19) pneumonia. After admission, he had a persistent high fever and developed erythema induratum on his extremities. Laboratory tests conducted 25 days after onset showed markedly increased procalcitonin (PCT) levels (>100 ng/mL). The patient developed impaired consciousness and hypotensive shock and required endotracheal intubation. Based on the presence of erythema induratum and multiorgan dysfunction, he was diagnosed with multisystem inflammatory syndrome (MIS). The MIS resolved after treatment with intravenous immunoglobulin and methylprednisolone. This report illustrates that MIS can occur in adults and may be accompanied by high PCT levels.

Endoscopic Papillary Balloon Dilation Can Be Safely Performed in Patients on Dual Antiplatelet Therapy: A Pilot Study.

BACKGROUND AND AIMS: Endoscopic papillary balloon dilation (EPBD), a low-risk procedure for bleeding, has been suggested as an alternative to endoscopic sphincterotomy for papillary dilatation in patients undergoing endoscopic stone removal who are at a higher risk of bleeding. Several guidelines recommend that combination of two antiplatelet agents should be reduced to single antiplatelet therapy when endoscopic sphincterotomy is performed. However, there is no evidence that EPBD affects the risk of bleeding in patients receiving a combination of two antiplatelet agents; thus, we aimed to explore this problem. METHODS: We included 31 patients who underwent EPBD for common bile duct stones at our hospital from May 2014 to August 2022 and received either a combination of two antiplatelet agents or single antiplatelet therapy prior to the procedure. The group receiving a combination of two antiplatelet agents included patients who underwent EPBT without antiplatelet therapy withdrawal or with a shorter withdrawal period than those recommended by the guidelines. RESULTS: In the group that received a combination of two antiplatelet agents, one of the two antiplatelet agents used was thienopyridine. No bleeding was observed after EPBD in this study. We did not find any significant between-group differences in hemoglobin levels and rate of post-endoscopic retrograde cholangiopancreatography pancreatitis. CONCLUSIONS: In patients treated with a combination of two antiplatelet agents, EPBD could be safely performed without bleeding. Therefore, future prospective studies are warranted.

Effects of Hyphomonas Strains on the Growth of Red Algae Pyropia Species by Attaching Specifically to Their Rhizoids.

Bacteria and marine macroalgae form close associations, while various bacteria affect the morphogenesis and growth of macroalgae. Hyphomonas strains exhibit normal morphogenetic activity in protoplasts of the red alga Pyropia yezoensis (nori). However, the effects of the bacteria on the growth of Pyropia from protoplast cells to regenerated thalli remain unknown. Here, we assessed the growth of P. yezoensis and Pyropia tenera using combined cultures of three Hyphomonas strains (LNM10-16, SCM-2, and LNM-9) and three algal media (artificial seawater with vitamins, artificial seawater, and natural seawater) over 7 weeks. Third week after culture, the three Hyphomonas strains showed almost similar levels of normal growth activity for both Pyropia species. However, at 7 weeks, significant differences were observed among the three Hyphomonas strains in terms of length, length-to-width ratio, and normal morphology of Pyropia thalli. LNM10-16 significantly promoted the thalli length and length-to-width ratios of both Pyropia species in artificial seawater without vitamins and natural seawater, compared with the other two Hyphomonas strains. P. yezoensis cultured in artificial seawater with vitamins showed a much higher demand for LNM10-16 in development of the thalli length than P. tenera. These results may be explained by differences in the growth activities of Hyphomonas strains and the nutrient requirements of Pyropia species. Furthermore, the bacteria were more specifically attached to the rhizoid surfaces of both species. This study is the first to reveal that Hyphomonas strains affect the growth of Pyropia species by attaching to their rhizoids.

Total pancreatectomy with remnant stomach preservation in a patient with a history of proximal gastrectomy and interposed jejunal reconstruction with right gastroepiploic conduit preservation: a case report.

BACKGROUND: Pancreatic head resection following proximal gastrectomy jeopardizes the blood flow of the remnant stomach owing to right gastroepiploic conduit sacrifice, thereby necessitating total gastrectomy. However, owing to its high invasiveness, concomitant remnant total gastrectomy with pancreatectomy should be avoided as much as possible. Herein, we describe our experience of total pancreatectomy with right gastroepiploic conduit preservation in a patient with a history of proximal gastrectomy and reconstruction by jejunum interposition. CASE PRESENTATION: A 78-year-old woman with a history of gastric cancer was followed up at our institute for multiple intraductal papillary mucinous neoplasm, and main pancreatic duct stricture in the pancreatic head was newly detected. The cystic lesion was extended to the pancreatic body. Proximal gastrectomy and reconstruction by jejunal interposition were previously performed, and the mesenteric stalk of the interposed jejunum was approached through the retrocolic route. We planned total pancreatectomy with right gastroepiploic conduit preservation. Following adhesiolysis, the interposed jejunum and its mesentery lying in front of the pancreas were isolated. The arterial arcade from the common hepatic artery to the right gastroepiploic artery was detached from the pancreas. Furthermore, the right gastroepiploic vein was isolated from the pancreas. The pancreatic body and tail were pulled up in front of the remnant stomach, and the splenic artery and vein were resected. The pancreatic body and tail were pulled out to the right side, and the pancreatic head was divided from the pancreatic nerve plexus to the portal vein. The jejunal limb for entero-biliary anastomosis was passed through the hole behind the superior mesenteric artery and vein, and gastrointestinal anastomosis using the antecolic route and Braun anastomosis were performed. CONCLUSIONS: To avoid remnant total gastrectomy, right gastroepiploic conduit preservation is an optional procedure for pancreatic head resection in patients who have undergone proximal gastrectomy with reconstruction by jejunal interposition.

A case of unsuccessful obliteration of percutaneous transhepatic gastric varices using the IMPEDE embolization plug.

Key Clinical Message: Embolization with IMPEDE embolization plug cannot be confirmed on site. Therefore, we propose that the diameter of the device selected be up to 50% larger than the vein diameter to prevent embolization failure and recanalization. Abstract: Balloon-occluded retrograde transvenous obliteration and percutaneous transhepatic obliteration (PTO) are performed for treating sporadic gastric varices. IMPEDE embolization plug has been recently developed for these procedures; however, no studies have reported its use. This is the first report on its use in PTO of gastric varices.

Comprehensive review on small common bile duct stones.

Common bile duct stones are among the most common conditions encountered by endoscopists. Therefore, it is well researched; however, some items, such as indications for endoscopic papillary balloon dilatation (EPBD), safety of EPBD and endoscopic sphincterotomy in patients receiving dual antiplatelet therapy or direct oral anticoagulant, selection strategy for retrieval balloons and baskets, lack adequate evidence. Therefore, the guidelines have been updated with new research, while others remain unchanged due to weak evidence. In this review, we comprehensively summarize the standard methods in guidelines and new findings from recent studies on papillary dilation, stone retrieval devices, difficult-to-treat cases, troubleshooting during the procedure, and complicated cases of cholangitis, cholecystolithiasis, or distal biliary stricture.

Comprehensive review on endoscopic ultrasound-guided tissue acquisition techniques for solid pancreatic tumor.

Pancreatic ductal adenocarcinoma is speculated to become the second leading cause of cancer-related mortality by 2030, a high mortality rate considering the number of cases. Surgery and chemotherapy are the main treatment options, but they are burdensome for patients. A clear histological diagnosis is needed to determine a treatment plan, and endoscopic ultrasound (EUS)-guided tissue acquisition (TA) is a suitable technique that does not worsen the cancer-specific prognosis even for lesions at risk of needle tract seeding. With the development of personalized medicine and precision treatment, there has been an increasing demand to increase cell counts and collect specimens while preserving tissue structure, leading to the development of the fine-needle biopsy (FNB) needle. EUS-FNB is rapidly replacing EUS-guided fine-needle aspiration (FNA) as the procedure of choice for EUS-TA of pancreatic cancer. However, EUS-FNA is sometimes necessary where the FNB needle cannot penetrate small hard lesions, so it is important clinicians are familiar with both. Given these recent dev-elopments, we present an up-to-date review of the role of EUS-TA in pancreatic cancer. Particularly, technical aspects, such as needle caliber, negative pressure, and puncture methods, for obtaining an adequate specimen in EUS-TA are discussed.