Hyperlipidemia as a risk factor for Trousseau syndrome-related cerebral infarction in patients with advanced gastrointestinal cancer

Trousseau syndrome-related cerebral infarction rarely occurs during chemotherapy in patients with gastrointestinal (GI) cancer, and its clinical features remain unclear. The present study aimed to examine the clinical features of Trousseau syndrome-related cerebral infarction developed during chemotherapy for GI cancer. The present retrospective cohort study consecutively enrolled 878 patients with unresectable GI cancer who received chemotherapy at the Multidisciplinary Treatment Cancer Center, Kurume University Hospital (Kurume, Japan) between April 2014 and March 2020. Patients with colorectal cancer (n=308) were the most common, followed by those with pancreatic (n=242), gastric (n=222) and biliary tract (n=59) cancer, neuroendocrine tumors (n=34) and duodenal cancer (n=11). Among the 878 patients, Trousseau syndrome-related cerebral infarction occurred in 8 (0.9%) patients with a median age of 70.5 years (range, 58–75 years), and 50% of the patients were male (4/8). In total, 3 patients had gastric cancer, 3 had pancreatic cancer and 2 had biliary tract cancer. A greater percentage of patients with Trousseau syndrome-related cerebral infarction had hyperlipidemia (38.0%) than those without (8.2%; P=0.005). Hyperlipidemia was a risk factor for occurrence of Trousseau syndrome-related cerebral infarction with an odds ratio of 7.009 (95% confidence interval, 1.785-27.513). Trousseau syndrome-related cerebral infarction developed during GI chemotherapy was rare and hyperlipidemia may predict its onset.     

Atrial Fibrillation-triggered Ventricular Fibrillation in a Patient with Early Repolarization Syndrome

A 54-year-old man with early repolarization syndrome (ERS) implanted with an implantable cardioverter-defibrillator (ICD) developed persistent atrial fibrillation (AF) three years after the implantation. Similarly, the remote monitoring system begun frequently detecting ventricular fibrillation (VF) and polymorphic ventricular tachycardia (PVT). Longer RR intervals were repeatedly observed just before the initiation of PVT/VF. Catheter ablation for AF successfully diminished both the PVT and VF events.     

Studies on post-transplant dyslipidemia in kidney transplant patients

This study was performed to retrospectively compare changes in the levels of total cholesterol, non-HDL cholesterol, triglycerides, and immunosuppressive drugs, cyclosporine A and steroids in patients with living-relation renal transplants with those from non-heart-beating donors. We experienced 11 cases of kidney transplants from non-heart-beating donors during the period from April 1995 to May 2003. We evaluated 13 cases of kidney transplants from living-relation donors during the same period. The immunosuppressants used included mainly cyclosporine A as well as mycophenolate mofetil or azathioprine, steroid and ALG, or basiliximab. Over-night fasting lipids (total cholesterol, triglycerides and HDL cholesterol) were studied before renal transplantation and repeated after renal transplantation at 1, 3, 6 and 12 months. The levels of total cholesterol and triglycerides remained in the normal range before transplantation. However, the levels of total cholesterol increased siginificantly 1 and 3 months after transplantation from non-heart-beating donors and remained at higher levels up to 12 months after transplantation. A similar pattern in the levels of triglycerides was observed. The levels of HDL cholesterol remained unchanged and stayed in the normal range before and 1, 3, 6, and 12 months after transplantation from non-heart-beating donors. On the other hand, significant increases in non-HDL cholesterol were observed 3 and 6 months after transplantation from non-heart-beating donors. After transplantation from living-relation donors, levels of total cholesterol, triglycerides, and non-HDL cholesterol remained unchanged and remained in the normal range up to 12 months after transplantation. Although there were no significant differences in the total dosage of cyclosporine A between the patients with living-relation donors and those with non-heart-beating donors, a significant increase in the total dosage of methylprednisolone was observed in patients with non-heart-beating donors compared with those in the patients with living-relation donors. Renal function recovery in patients with living-relation donors was better than in those with non-heart-beating donors. These results may suggest that significant increases in total cholesterol, especially non-HDL cholesterol and triglycerides, were probably partly due to an increased use of immunosuppressants, steroids. It is necessary to aggressively control post-transplant hyperlipidemia and important to reduce or withdraw steroids in the selected, low-risk recipients as early as possible from the viewpoint of preventing post-transplant hyperlipidemia.     

Tracheostomy abolishes paradoxical activation of the vocal cord adductor in multiple system atrophy

OBJECTIVES: Inspiratory activation of the vocal cord adductor, which causes paradoxical vocal cord motion, develops in patients with multiple system atrophy (MSA). To confirm the hypothesis that airway reflexes trigger such paradoxical activation, we investigated the effects of tracheostomy on the adductor activation in a MSA patient. METHODS: We compared the adductor electromyograms before and after breathing was diverted to a tracheostoma under propofol anesthesia. RESULTS: The adductor inspiratory activation disappeared during tracheostoma breathing. CONCLUSION: Airway reflexes as well as MSA-related damage to the respiratory center contribute to the generation of paradoxical adductor activation in MSA patients.     

Clinical outcomes of definitive radiotherapy for patients with cT1aN0M0 esophageal cancer unsuitable for endoscopic resection and surgery

BackgroundStudies on the clinical outcomes of radiotherapy for clinical (c)T1aN0M0 (UICC-TNM Classification, Eighth Edition) esophageal cancer (EC) are limited. Therefore, this retrospective study aimed to clarify the clinical outcomes of definitive radiotherapy (RT) or chemoradiotherapy (CRT) for cT1aN0M0 EC unsuitable for endoscopic resection and surgery.MethodsPatients with cT1aN0M0 esophageal squamous cell carcinoma who underwent definitive RT or CRT between January 2009 and December 2020 were retrospectively reviewed. The initial response, toxicities, survival rates, recurrence patterns, and salvage treatments of the patients were evaluated. Initial response was measured using the Response Evaluation Criteria in Solid Tumors guideline. Toxicity was assessed and documented following the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Survival rates from the date of initiation of treatment were measured using the Kaplan–Meier method.ResultsTwenty patients treated with definitive RT or CRT were included in the study. The median follow-up duration was 55 months (range, 13–131 months). All patients achieved complete response to the initial treatment. Grade 3 acute toxicities observed esophagitis (10%), pneumonitis (5%), and leukopenia (5%). Late toxicities higher than grade 3 were not observed. The 1-, 3-, and 5-year overall and disease-specific survival rates were 100% and 100%, 83% and 100%, and 67% and 100%, respectively. No treatment-related deaths occurred. Among the 20 patients, 6 showed local recurrence and 2 showed metachronous recurrence. Seven patients underwent salvage endoscopic submucosal dissection (ESD), and one underwent argon plasma coagulation treatment. After the endoscopic treatment, no recurrences were observed.ConclusionsDefinitive RT or CRT was considered an alternative initial treatment for patients with cT1aN0M0 EC who were unsuitable for endoscopic resection and surgery.     

Analysis of T Cell Receptor Variability in Fresh Tumor-infiltrating Lymphocytes from Human Head and Neck Cancer

In this study, we analyzed T cell receptor (TCR) gene rearrangements in tumor-infiltrating lymphocytes (TIL) freshly obtained from 15 patients with head and neck cancer using the reversely transcribed polymerase chain reaction (RT-PCR) method. These TILs showed preferential expression of Vα10, Vα8 and Vα1, detected in 13 (87%), 11 (73%), and 9 cases (60%), respectively. The TCRVβ gene revealed diversity without preferential usage. The head and neck region is exposed to bacteria and viruses, so it is possible that the tumor site can become infected and accumulate T cells involved in infection and inflammation. Therefore, we also investigated TCR gene usage in T cells infiltrating in chronic sinusitis mucosa to address the question of whether the Vα1, Vα8, and Vα10 subfamilies are characteristic in TIL from squamous cell carcinoma of head and neck. TCR Vα10 gene usage was also the most common in Vα segment in T cells infiltrating the sinus mucosa, but Vα and Vα8 were not detected in the T cells in sinusitis. These results indicate that the Vα10 subfamily, the preferred T cell population in both TIL and T cells in inflammatory disease, might he involved mainly in inflammation or infection. On the other hand, Vα1 and Vα8 appear to be relatively specific populations for antitumor immunity in head and neck cancer.     

DNA-loaded nano-adjuvant formed with a vitamin E-scaffold intracellular environmentally-responsive lipid-like material for cancer immunotherapy

Cytoplasmic DNA triggers cellular immunity via activating the stimulator of interferon genes pathway. Since DNA is degradable and membrane impermeable, delivery system would permit cytoplasmic delivery by destabilizing the endosomal membrane for the use as an adjuvant. Herein, we report on the development of a plasmid DNA (pDNA)-encapsulating lipid nanoparticle (LNP). The structural components include an SS-cleavable and pH-activated lipid-like material that mounts vitamin E as a hydrophobic scaffold, and dual sensing motifs that are responsive to the intracellular environment (ssPalmE). The pDNA-encapsulating LNP (ssPalmE-LNP) induced a high interferon-β production in Raw 264.7 cells. The subcutaneous injection of ssPalmE-LNP strongly enhanced antigen-specific cytotoxic T cell activity. The ssPalmE-LNP treatment efficiently induced antitumor effects against E.G7-OVA tumor and B16-F10 melanoma metastasis. Furthermore, when combined with an anti-programmed death 1 antibody, an extensive therapeutic antitumor effect was observed. Therefore, the ssPalmE-LNP is a promising carrier of adjuvants for cancer immunotherapy.     

Fasudil improves the endothelial dysfunction in the aorta of spontaneously hypertensive rats

We investigated the effects of fasudil, a Rho kinase inhibitor, in the endothelial dysfunction of aortas from spontaneously hypertensive rats (SHRs). SHRs were divided in three groups; intraperitoneally (i.p.) vehicle-treated SHRs (SHR), SHRs treated with fasudil 3mg/kg i.p. (Fas3), and SHRs treated with fasudil 10mg/kg i.p. (Fas10). Vehicle-treated Wistar rats were used as normo-tensive control group. After a six-week-treatment, blood pressure and heart rate were measured by the tail cuff method. Afterwards animals were sacrificed and aortas were examined in vitro by organ bath studies to evaluate the contraction and relaxation ability. Rho kinase activity, myosin light chain (MLC), phosphorylated MLC (phospho-MLC), eNOS, phospho-eNOS protein expression and eNOS mRNA levels were evaluated. SHR demonstrated a significant hypercontractility and impaired relaxation compared to the control. Fasudil 10mg/kg significantly corrected the hypercontractility, restored the relaxation, and significantly decreased the mean arterial blood pressure, while no change observed in the systolic blood pressure. Rho kinase activity was significantly higher in the SHR, and was significantly inhibited by the high dose of fasudil. There was a slight up-regulation in the MLC, and phospho-MLC protein levels in the SHR. eNOS and phospho-eNOS protein levels were significantly lower in the SHR, and this abnormality was significantly normalized by fasudil treatment. No significant difference was observed in the eNOS gene expression. This study suggests that fasudil by inhibiting the Rho kinase activity normalizes the eNOS expression and phosphorylation and ameliorates the endothelial dysfunction induced by hypertension in the SHR model.     

Purple corn color inhibition of prostate carcinogenesis by targeting cell growth pathways

Purple corn color is a widely used food colorant that was reported to have attenuating effects on hypertension, diabetes, and to have anti‐cancer effects on colon and breast cancer. Our study is the first on its possible chemoprevention effects against prostate cancer. For this purpose an androgen‐dependent prostate cancer cell line, LNCaP, was used to examine effects in vitro. Purple corn color inhibited the proliferation of LNCaP cells by decreasing the expression of Cyclin D1 and inhibiting the G1 stage of the cell cycle. Thirty‐six male transgenic rats for adenocarcinoma of prostate were fed basic diet or diet with purple corn color for 8 weeks. Purple corn color decreased the incidence of adenocarcinoma in the lateral prostate and slowed down the progression of prostate cancer. A lower Ki67 positive rate, a decrease of the expression of Cyclin D1, and downregulation of the activation of Erk1/2 and p38 MAPK were observed in the group consuming purple corn color in the diet. Since purple corn color is a mixture, determining its active component should help in the understanding and usage of purple corn color for prostate cancer chemoprevention. Therefore, the three major anthocyanins in purple corn color, cyanidin‐3‐glucoside, pelargonidin‐3‐glucoside and peonidin‐3‐glucoside, were tested with LNCaP cells. The results suggested that cyanidin‐3‐glucoside and pelargonidin‐3‐glucoside are the active compounds.