Gemcitabine plus nab-paclitaxel for pancreatic cancer and interstitial lung disease: A nationwide longitudinal study

Interstitial lung disease (ILD) is an adverse event associated with gemcitabine administration. Gemcitabine plus nab-paclitaxel, which is now a first-line chemotherapy regimen for pancreatic cancer (PC), may increase the risk of ILD; however, large-scale clinical data on this are limited. Thus, this study aimed to elucidate the incidence and risk factors of ILD in patients with PC receiving gemcitabine plus nab-paclitaxel. Through the Diagnosis Procedure Combination database, a Japanese nationwide inpatient database with outpatient data, we identified consecutive patients with PC who received gemcitabine-based chemotherapy between July 2010 and March 2019 at 205 hospitals. Competing-risk analysis was used to examine the cumulative incidence and risk factors of ILD. Among the 6163 patients who received gemcitabine plus nab-paclitaxel, we documented 168 patients (2.7%) who developed ILD with cumulative incidence rates (95% confidence intervals [CIs]) of 2.0% (1.6%–2.4%), 2.7% (2.2%–3.1%), and 3.1% (2.6%–3.6%) at 3, 6, and 12 months, respectively. Compared with patients with PC who received gemcitabine monotherapy, those who received gemcitabine plus nab-paclitaxel had an adjusted subdistribution hazard ratio (SHR) for ILD of 1.93 (95% CI: 1.51–2.47). Older age was associated with a high risk of ILD in patients receiving gemcitabine plus nab-paclitaxel (adjusted SHR comparing ≥75 to ≤74 years, 1.61; 95% CI: 1.16–2.24). In conclusion, this study demonstrated the clinical course of gemcitabine plus nab-paclitaxel-associated ILD in patients with PC. When gemcitabine plus nab-paclitaxel is administered to elderly patients with PC, symptoms associated with ILD must be monitored.     

Probiotics enhances anti-tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer

Chemotherapy drugs, such as gemcitabine and cisplatin (GC), are frequently administered to patients with advanced urothelial carcinoma, however the influence of the gut microbiota on their action is unclear. Thus, we investigated the effects of GC on the gut microbiome and determined whether oral supplementation with a probiotics mixture of Lactobacillus casei Shirota and Bifidobacterium breve enhanced the anti-tumor immune response. After subcutaneous inoculation with MBT2 murine bladder cancer cells, syngenic C3H mice were randomly allocated into eight groups. The gut microbiome cluster pattern was altered in both the GC and oral probiotics groups (p = 0.025). Both tumor-bearing conditions (no treatment) and GC chemotherapy influenced Pseudoclostridium, Robinsoniella, Merdimonas, and Phocea in the gut. Furthermore, comparison of the GC-treated and GC + probiotics groups revealed an association of four methyltransferase family enzymes and two short-change fatty acid-related enzymes with oral probiotics use. A significant difference in tumor volume was observed between the GC and GC + probiotics groups at week 2 of treatment. Additionally, decreased recruitment of cancer-associated fibroblasts and regulatory T cells, and activation of CD8⁺ T cells and dendritic cells were observed in the tumor microenvironment. Our findings reveal the positive effects of a probiotics mixture of Lactobacillus and Bifidobacterium in enhancing anti-tumor effects through the gut–tumor immune response axis. Future clinical trials are needed to evaluate the full benefits of this novel supplement with oral probiotics in patients with advanced urothelial carcinoma.     

Focal tonic seizures with asymmetrical posturing could allow voluntary movements: A lesson to not be misled for a non-epileptic event

This report documents the clinical features of supplementary motor area seizures with voluntary movements in two patients. The first case describes a 13-year-old boy with a 2-year history of nocturnal seizures, characterized by an asymmetrical brief tonic posture followed by bilateral rapid hand shaking, but without impaired awareness. Magnetic resonance imaging revealed no abnormalities. Video electroencephalogram indicated interictal focal spikes and ictal activity 2 s before clinical onset in the frontal midline area. The patient stated that he purposely shook his hands to lessen the seizure-induced upper limb stiffness. The second case describes a 43-year-old man with a 33-year history of nocturnal seizures, characterized by an asymmetric brief tonic posture, with the right hand grabbing to hold this posture, but without impaired awareness. Video electroencephalogram indicated that he voluntarily moved his right hand during the latter part of the seizures; however, no clear ictal electroencephalogram change was noted. Magnetic resonance imaging revealed a mass lesion in the right medial superior frontal gyrus. Fluorodeoxyglucose-positron emission tomography and ictal single-photon emission computed tomography indicated ictal focus in the mesial frontal area, as confirmed by invasive electroencephalogram and seizure freedom after surgery. Both patients had typical supplementary motor area seizures, except they could perform voluntary movements in the body parts. The co-occurrence of supplementary motor area seizures and voluntary movements is clinically useful, as it may help avoid the inaccurate and misleading diagnosis of non-epileptic events such as psychogenic non-epileptic seizures.