Successful Antimicrobial Therapy of Esophageal Stenosis Because of Actinomycosis.

Esophageal stenosis can cause vomiting or dysphagia in children and is commonly treated with esophageal balloon dilation. However, surgery may be required if the stenosis does not respond to dilation. Although esophageal actinomycosis can cause severe esophageal strictures and be refractory to balloon dilation, it has been reported to respond effectively to antimicrobial therapy in adults. However, the course of the disease and appropriate treatment strategies in children are not well understood. We present a case of a previously healthy 2-year-old boy diagnosed with esophageal stenosis because of actinomycosis. The patient was treated with intravenous penicillin G, followed by oral amoxicillin for 8 weeks and 6 months, respectively. After completion of the antimicrobial treatment, the patient showed improvement in symptoms and endoscopic findings. At the 1-year follow-up, the patient showed consistent weight gain and normal growth without further intervention. This case highlights the importance of considering esophageal actinomycosis as a potential cause of esophageal stenosis in children and the potential effectiveness of antimicrobial therapy in avoiding surgical intervention.

Warm Ischemia Induces Spatiotemporal Changes in Lysophosphatidylinositol That Affect Post-Reperfusion Injury in Normal and Steatotic Rat Livers.

Warm ischemia-reperfusion injury is a prognostic factor for hepatectomy and liver transplantation. However, its underlying molecular mechanisms are unknown. This study aimed to elucidate these mechanisms and identify the predictive markers of post-reperfusion injury. Rats with normal livers were subjected to 70% hepatic warm ischemia for 15, 30, or 90 min, while those with steatotic livers were subjected to 70% hepatic warm ischemia for only 30 min. The liver and blood were sampled at the end of ischemia and 1, 6, and 24 h after reperfusion. The serum alanine aminotransferase (ALT) activity, Suzuki injury scores, and lipid peroxidation (LPO) products were evaluated. The ALT activity and Suzuki scores increased with ischemic duration and peaked at 1 and 6 h after reperfusion, respectively. Steatotic livers subjected to 30 min ischemia and normal livers subjected to 90 min ischemia showed comparable injury. A similar trend was observed for LPO products. Imaging mass spectrometry of normal livers revealed an increase in lysophosphatidylinositol (LPI (18:0)) and a concomitant decrease in phosphatidylinositol (PI (18:0/20:4)) in Zone 1 (central venous region) with increasing ischemic duration; they returned to their basal values after reperfusion. Similar changes were observed in steatotic livers. Hepatic warm ischemia time-dependent acceleration of PI (18:0/20:4) to LPI (18:0) conversion occurs initially in Zone 1 and is more pronounced in fatty livers. Thus, the LPI (18:0)/PI (18:0/20:4) ratio is a potential predictor of post-reperfusion injury.

Perioperative outcomes of laparoscopic fundoplication for gastroesophageal reflux disease in children with or without scoliosis.

PURPOSE: This study aimed to evaluate the perioperative outcomes of laparoscopic fundoplication (LF) for gastroesophageal reflux disease (GERD) in children with scoliosis. METHODS: Data of consecutive patients with GERD who underwent LF from January 2015 to December 2020 at a single pediatric institution were retrospectively analyzed. RESULTS: Eighty-two patients underwent laparoscopic Nissen fundoplication. The median [interquartile range (IQR)] body weight was 9.3 [7; 14] kg. Seventy-five patients were neurologically impaired (91%), and other comorbidities included scoliosis (n = 33), lung disease (n = 39), and cardiac disease (n = 14). The median (IQR) operative time including the creation of the gastrostomy and volume of bleeding were 160 [143; 190] min and 2 [1; 5] mL, respectively. There were no significant differences between patients with and those without scoliosis (p = 0.17 and p = 0.90, respectively). Patients with cardiac disease had a longer operative time (167 [161; 193] vs. 157 [141; 190] min, p = 0.01). There were three post-operative complications in children with neurological impairment; however, there was no clear relationship between the severity of scoliosis and complications. CONCLUSION: Severity of scoliosis did not correlate with perioperative results and post-operative complications. This suggests that the same LF technique can be used regardless of the presence or absence of scoliosis in children.

Liver Function in Older Patients With Unresectable Hepatocellular Carcinoma After Administration of Lenvatinib.

BACKGROUND: The age of patients with advanced hepatocellular carcinoma (HCC) eligible for molecular-targeted drug treatment is increasing. We assessed liver function after lenvatinib administration according to age in patients with advanced HCC. PATIENTS AND METHODS: In this retrospective, multicenter, observational study, we reviewed the records of patients with HCC who received lenvatinib treatment (March 2018-March 2020). Liver function was measured using the Albumin-Bilirubin Index (ALBI). RESULTS: Of 119 patients, with a median age of 72.0 years, median overall survival was 15.3 months. Overall survival was significantly better in the group which maintained liver function (p=0.02). Older age (≥72 years) was associated with liver-function deterioration within 8 weeks (odds ratio=2.47, 95% confidence interval=1.06-5.75, p=0.035). The ALBI score was significantly higher in the older group at 4 and 8 weeks after lenvatinib administration. CONCLUSION: Lenvatinib administration was more likely to adversely affect liver function in older patients; dose adjustment should be considered in such patients.

Comprehensive Prospective Analysis of the Factors Contributing to Aspiration Pneumonia Following Endoscopic Submucosal Dissection in Patients with Early Gastric Neoplasms.

Endoscopic submucosal dissection (ESD) has become the first-line treatment for early gastric neoplasms; however, a subset of patients treated by this method develop aspiration pneumonia. We conducted a comprehensive prospective analysis of the factors contributing to post-ESD aspiration pneumonia in early gastric neoplasms in this study, with special focus on whether pre-treatment oral care can prevent aspiration pneumonia. Sixty-one patients who underwent ESD for gastric neoplasms were randomly assigned to the oral care or control groups. ESD was performed under deep sedation. Of 60 patients whose data were available for analysis, 5 (8.3%) experienced pneumonia confirmed either by chest radiography or computed tomography. Although no difference in the rate of pneumonia was found between the control and oral care groups, the post-oral care bacteria count was significantly higher in the saliva of patients who developed pneumonia compared to those without pneumonia. In addition, the presence of vascular brain diseases and the dose of meperidine were also significantly associated with the occurrence of pneumonia. These results suggest that the number of oral bacteria as well as pre-existing vascular brain diseases and high-dose narcotics can affect the incidence of post-ESD pneumonia.

Imaging Mass Spectrometry Reveals the Changes in the Taurine Conjugates of Dihydroxycholanoic Acid During Hepatic Warm Ischemia and Reperfusion in a Rat Model.

Warm ischemia and reperfusion injury (IRI) is a prognostic factor in donation after cardiac death donor transplantation. However, a reliable method to predict IRI before transplantation has not been established. The aim of this study was to identify predictive markers of hepatic IRI by simultaneous measurement of endogenous molecules using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Rats were subjected to hepatic warm ischemia (70%) for 30 or 90 minutes and subsequent reperfusion. The livers were collected at the end of ischemia and 1 hour, 6 hours, and 24 hours after reperfusion. The liver tissue sections were applied to IMS (m/z 200-2000). Candidate molecules were identified by tandem mass spectrometry. Imaging mass spectrometry (IMS) revealed a significant increase in the taurine conjugates of dihydroxycholanoic acid (TDHCA) during ischemia and a tendency to return to the basal level after reperfusion. Notably, high-resolution measurements revealed focal accumulation of TDHCA in the intrahepatic bile duct with ischemic time. In conclusion, IMS is a useful method to detect minute changes provoked by ischemia, which are barely detectable in assays involving homogenization. Accordingly, focal accumulation of TDHCA during ischemia may be a candidate marker for predicting later IRI.

Response to Lenvatinib Is Associated with Optimal RelativeDose Intensity in Hepatocellular Carcinoma: Experience in Clinical Settings.

BACKGROUND: Lenvatinib is currently available as the first-line treatment for advanced unresectable hepatocellular carcinoma. We evaluated the relationship between its relative dose intensity (RDI) and response in clinical settings. METHODS: From March 2018 to May 2019, 93 patients were administered lenvatinib at the Nagasaki University Hospital and its related facilities. Among these, 81 patients (66 men, 15 women, median age 72.0) who received lenvatinib were analyzed retrospectively. RESULTS: Fourteen patients were Child-Pugh grade B, and 15 had received other systemic therapy. According to Response Evaluation Criteria in Solid Tumors (RECIST), the objective response (OR) rate was 17.3%. The overall survival (OS) was significantly better in the OR group (p = 0.011). There was a significant difference in RDI between the OR and non-OR groups (p < 0.05). The area under the receiver operating characteristics curve for OR prediction by the 4, 8, 12, and 16-week RDI were 0.666, 0.747, 0.731, and 0.704, respectively. In the 8-week RDI 67.0% group, OS was significantly better than in the 8-week RDI< 67.0% group (p = 0.003). CONCLUSIONS: Because a sufficient RDI is required to achieve an OR, it is strongly recommended that lenvatinib should be administered to patients with good hepatic function and status.

Effect of coadministration of rifampicin on the pharmacokinetics of linezolid: clinical and animal studies.

BACKGROUND: Combination therapy of linezolid (LZD) and rifampicin (RFP) may be more effective than monotherapy for treating gram-positive bacterial infections, but several studies have suggested that RFP decreases LZD exposures, thereby increasing the risk of therapeutic failure and emergence of LZD-resistant strains. However, the mechanism of the drug-drug interaction between LZD and RFP is unknown. METHODS: We conducted a prospective, open-label, uncontrolled clinical study in Japanese patients receiving LZD and RFP to evaluate the effect of coadministered RFP on the concentration of LZD. In animal study in rats, the influence of coadministered RFP on the pharmacokinetics of LZD administered intravenously or orally was examined. Intestinal permeability was investigated with an Ussing chamber to assess whether coadministered RFP alters the absorption process of LZD in the intestine. RESULTS: Our clinical study indicated that multiple doses of RFP reduced the dose-normalized trough concentration of LZD at the first assessment day by an average of 65%. In an animal study, we found that multiple doses of RFP significantly decreased the area under the concentration-time curve, the maximum concentration and the bioavailability of orally administered LZD by 48%, 54% and 48%, respectively. In contrast, the pharmacokinetics of intravenously administered LZD was unaffected by the RFP pretreatment. However, investigation of the intestinal permeability of LZD revealed no difference in absorptive or secretory transport of LZD in the upper, middle and lower intestinal tissues between RFP-pretreated and control rats, even though RFP induced gene expression of multidrug resistance protein 1a and multidrug resistance-associated protein 2. CONCLUSIONS: Therapeutic drug monitoring may be important for avoiding subtherapeutic levels of LZD in the combination therapy. The drug-drug interaction between LZD and RFP may occur only after oral administration of LZD, but is not due to any change of intestinal permeability of LZD. TRIAL REGISTRATION: UMIN, UMIN000004322. Registered 4 October 2010.

Idiopathic thrombocytopenic purpura complicated with biliary atresia: a rare occurrence and literature review.

The association of biliary atresia (BA) and idiopathic thrombocytopenic purpura (ITP) is extremely rare, with only 2 cases being reported in the literature. This report describes the very rare case of a 1-year-old boy with BA complicated with ITP after cholangitis and the successful steroid treatment of ITP. We review the literature on this type of relationship between BA and ITP and discuss the clinical features of this complication. Furthermore, the possible cause of the onset of ITP complicated with BA was explored in this report.