Correlation of UGT1A1 Gene Polymorphisms or Prior Irinotecan Treatment and Treatment Outcomes of Nanoliposomal-Irinotecan plus 5-Fluorouracil/Leucovorin for Pancreatic Ductal Adenocarcinoma: A Multicenter, Retrospective Cohort Study (HGCSG2101).

The effects of UGT1A1 gene polymorphisms or prior irinotecan treatment on treatment outcomes of nanoliposomal-irinotecan plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with unresectable pancreatic ductal adenocarcinoma (PDAC) are not established. This multicenter, retrospective cohort study compared treatment outcomes in patients with UGT1A1*1/*1 and those with UGT1A1*1/*6 or *1/*28 genotypes. We also analyzed the impact of prior irinotecan treatment on survival outcomes in 54 patients treated with nal-IRI+5-FU/LV. Comparable effectiveness was found regardless of the UGT1A1 genotypes. While no significant differences were found, grade ≥3 neutropenia and febrile neutropenia were more frequent in patients with UGT1A1*1/*6 or *1/*28 than in those with UGT1A1*1/*1 genotypes (grade ≥3 neutropenia, 50.0% vs. 30.8%, p = 0.24; febrile neutropenia, 9.1% vs. 0.0%, p = 0.20, respectively). No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between irinotecan-naïve-patients and other patients. However, irinotecan-resistant patients showed significantly shorter PFS (hazard ratio (HR) 2.83, p = 0.017) and OS (HR 2.58, p = 0.033) than other patients. Our study indicated that patients with UGT1A1*1/*6 or *1/*28 may be prone to neutropenia, though further study is needed. The survival benefit of nal-IRI+5-FU/LV could be maintained in patients without disease progression after irinotecan therapy.

Usefulness of ultrasonography and elastography in diagnosing oxaliplatin-induced sinusoidal obstruction syndrome.

BACKGROUND: Sinusoidal obstruction syndrome (SOS) refers to liver injury caused by hematopoietic stem cell transplantation (HSCT) and anticancer drugs including oxaliplatin. Increased splenic volume (SV) on computed tomography (CT) indicates oxaliplatin-induced SOS. Similarly, ultrasonography and liver stiffness measurement (LSM) by shear-wave elastography (SWE) can help diagnose SOS after HSCT; however, their usefulness for diagnosing oxaliplatin-induced SOS remains unclear. We investigated the usefulness of the Hokkaido ultrasonography-based scoring system with 10 ultrasonographic parameters (HokUS-10) and SWE in diagnosing oxaliplatin-induced SOS early. METHODS: In this prospective observational study, ultrasonography and SWE were performed before and at 2, 4, and 6 months after oxaliplatin-based chemotherapy. HokUS-10 was used for assessment. CT volumetry of the SV was performed in clinical practice, and an SV increase ≥ 30% was considered the diagnostic indicator of oxaliplatin-induced SOS. We assessed whether HokUS-10 and SWE can lead to an early detection of oxaliplatin-induced SOS before an increased SV on CT. RESULTS: Of the 30 enrolled patients with gastrointestinal cancers, 12 (40.0%) with an SV increase ≥ 30% on CT were diagnosed with SOS. The HokUS-10 score was not correlated with an SV increase ≥ 30% (r = 0.18). The change in rate of three HokUS-10 parameters were correlated with an SV increase ≥ 30% (r = 0.32-0.41). The change in rate of LSM by SWE was correlated with an SV increase ≥ 30% (r = 0.40). CONCLUSIONS: The usefulness of HokUS-10 score was not demonstrated; however, some HokUS-10 parameters and SWE could be useful for the early diagnosis of oxaliplatin-induced SOS.

Analysis of the Pancreatic Cancer Microbiome Using Endoscopic Ultrasound-Guided Fine-Needle Aspiration-Derived Samples.

OBJECTIVES: Most previous studies have analyzed bacteria in tumors using resected pancreatic cancer (PC) tissues, because it is difficult to obtain tissue samples from unresectable advanced PC. We aimed to determine whether minimal tissue obtained by endoscopic ultrasound-guided fine-needle aspiration is useful for microbiome analysis. METHODS: Thirty PC and matched duodenal and stomach tissues (N = 90) were prospectively collected from 30 patients who underwent endoscopic ultrasound-guided fine-needle aspiration. Bacterial DNA was extracted, and 16S rRNA sequencing was performed. The primary outcome was the success rate of bacterial detection in tumors. Bacterial diversity and structure were investigated. RESULTS: The bacterial detection rates were 80%, 100%, and 97% in PC, gastric, and duodenal samples, respectively. Pancreatic cancer tissues showed a lower α-diversity and a significantly different microbial structure than stomach and duodenal tissues. Proteobacteria were more abundant, whereas Firmicutes, Bacteroidetes, and Fusobacteria were less abundant in PC tissues than in stomach and duodenal tissues. Acinetobacter was more abundant in PC tissues than in stomach and duodenal tissues, and Delftia was more frequently detected in resectable PC. CONCLUSIONS: Endoscopic ultrasound-guided fine-needle aspiration samples were valuable for PC microbiome analysis, revealing that the bacterial composition of PC is different from that of the stomach and duodenum.

Interferon-free therapy with sofosbuvir plus ribavirin for successful treatment of genotype 2 hepatitis C virus with lichen planus: a case report.

Hepatitis C virus (HCV) infection remains the main cause of liver disease and can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HCV may also develop extrahepatic manifestations in the skin, eyes, joints, kidneys, nervous system, and immune system. In fact, several studies reported that up to 70% of HCV patients experienced extrahepatic manifestations. Lichen planus (LP), which is an immune system disorder that is triggered by viral infections, allergens, and stress, can affect the skin, mouth, nails, and scalp. The association of LP with HCV has been reported, but the effect of HCV treatment on LP remission is controversial. We encountered a 53-year-old man with HCV genotype 2a and LP that were successfully treated with sofosbuvir and ribavirin for 12 weeks. After treatment, he achieved sustained virological response against HCV and remission of erosive LP lesions on the lip. In the era of interferon (IFN)-based treatment for HCV, exacerbation of autoimmune diseases is a common adverse event. Therefore, use of an IFN-free regimen of direct-acting antivirals for HCV might prevent the extrahepatic manifestation of an immune disorder.

Effects of automated external lubrication on tablet properties and the stability of eprazinone hydrochloride.

We investigated the advantages of an external lubrication technique for tableting. A newly developed external lubricating system was applied to tableting in a rotary tablet press using magnesium stearate. The resulting tablets were compared with tablets produced by the conventional internal lubrication method, in which lubricant is blended before tableting. As a model API, we chose eprazinone hydrochloride, because it is easily hydrolyzed by alkaline lubricant. The amount of lubricant required to prevent sticking with external lubrication was only 1/13th of that required with internal lubrication. External lubrication increased tablet crushing strength by 40%, without prolonging tablet disintegration time, and improved the residual ratio of eprazinone hydrochloride in tablets stored under stress conditions for 4 weeks by 10%. The distribution of lubricant on the surface of externally lubricated tablets was observed by scanning electron microscopy after the preparation by focused ion beam milling. The lubricant had formed a layer on the tablet surface. At the central part of the tablet surface, this layer was much thinner than at the edges, and remained extremely thin even when there was excess magnesium stearate. This is the first report to describe the distribution of lubricant on the surface of externally lubricated tablets.