Chemoradiotherapy with 3-weekly CDDP 80 mg/m2 for head and neck squamous cell carcinoma: 5-year survival data from a phase 2 study

ObjectiveThe global standard for chemoradiation therapy (CCRT) for head and neck squamous cell carcinoma is cisplatin 100 mg/m2 administered once every three weeks, although cisplatin 80 mg/m2 is also widely used as an alternative treatment to reduce adverse events in Japan. We aimed to assess the long-term survival outcomes and late adverse events associated with CCRT with a 3-weekly cisplatin dose of 80 mg/m2.MethodsA phase 2 study on CCRT with a 3-weekly cisplatin dose of 80 mg/m2 was performed in 47 patients between April 2015 and December 2016 at four centers in Japan. Survival outcomes and late adverse events at 5 years after this phase 2 trial were investigated.ResultsThe median follow-up period was 61 months. The 5-year progression-free survival/overall survival of all 47 patients was 66.0%/76.6%, while that of patients with stage III, IV disease (UICC) was 65.6%/71.9%. Seventeen patients (36%) experienced dysphagia as a late adverse event. Univariate and multivariate analyses revealed a significant association between acute mucositis/low body mass index (BMI) during CCRT and late dysphagia.ConclusionThe survival outcomes of CCRT with a 3-weekly cisplatin dose of 80 mg/m2 may be comparable to the previously reported dose of 100 mg/m2. Acute mucositis and low BMI at CCRT were risk factors for late dysphagia, indicating the importance of managing these conditions during CCRT to prevent late adverse events. Caution and care for acute mucositis and swallowing training in patients with low BMI may be important for preventing late-stage dysphagia

Asymptomatic diffuse idiopathic skeletal hyperostosis as a potential risk for severe dysphagia following partial laryngopharyngectomy

Diffuse idiopathic skeletal hyperostosis (DISH) is a common disease in which ossification lesions occur in the bones including the vertebrae. Dysphagia may occur in advanced cases, but there are few cases that require treatment. A 68-year-old man was diagnosed with hypopharyngeal cancer of the left pyriform sinus and asymptomatic DISH on the anterior cervical vertebrae. Due to prior history of radiation, partial laryngopharyngectomy was performed. After surgery, severe dysphagia and aspiration pneumonia occurred, and the patient needed to undergo total laryngectomy. It was determined that dysphagia was due to multiple factors, including insufficient laryngeal elevation and esophageal compression by osteophytes of DISH. Asymptomatic DISH can cause severe dysphagia after partial laryngopharyngectomy. We suggest that evaluation of the swallowing function and surgical options, including laryngeal suspension and cricopharyngeal myotomy should be considered when performing partial laryngopharyngectomy in patients with DISH, even if they demonstrated no difficulties in swallowing before treatment

Modified model for predicting early C-reactive protein levels after gastrointestinal surgery: A prospective cohort study.

BackgroundPostoperative serum concentration of C-reactive protein (CRP) is one of the objective quantitative indices integrating the effects of preoperative and intraoperative variables. Higher levels of CRP after gastrointestinal surgery are associated with major postoperative complications. To develop a model for predicting CRP levels on postoperative day (POD) 1 in surgical patients both with and without serious conditions and comorbidities, we modified the previous formula for prediction of CRP levels on POD1, and assessed the accuracy of our modified predictive formula for CRP levels.Material and methodsConsecutive patients of all ages undergoing gastrointestinal surgery under general anesthesia were enrolled in this single-institution prospective cohort study. We developed a modified predictive formula in a calculation cohort. Next, associations between measured CRP levels on POD1, predicted CRP levels on POD1 using the previous and modified models, and major complications after surgery were examined in a validation cohort.ResultsWe obtained the following model in the calculation cohort (n = 222): Modified model for predicting CRP levels on POD1 (mg•dL-1) = -10.13 + 0.0025 Duration of surgery (min) + 15.9 Mean Nociceptive Response (NR) + 0.66 Preoperative CRP level (mg•dL-1). In the validation cohort (n = 440), there was a significant association between measured and predicted CRP levels on POD1 (P ConclusionCRP levels predicted using duration of surgery, mean NR, and preoperative CRP levels are likely identical to measured CRP levels on POD1, being associated with major complications after gastrointestinal surgery

Intraoperative Assessment of Surgical Stress Response Using Nociception Monitor under General Anesthesia and Postoperative Complications: A Narrative Review

We present a narrative review focusing on the new role of nociception monitor in intraoperative anesthetic management. Higher invasiveness of surgery elicits a higher degree of surgical stress responses including neuroendocrine-metabolic and inflammatory-immune responses, which are associated with the occurrence of major postoperative complications. Conversely, anesthetic management mitigates these responses. Furthermore, improper attenuation of nociceptive input and related autonomic effects may induce increased stress response that may adversely influence outcome even in minimally invasive surgeries. The original role of nociception monitor, which is to assess a balance between nociception caused by surgical trauma and anti-nociception due to anesthesia, may allow an assessment of surgical stress response. The goal of this review is to inform healthcare professionals providing anesthetic management that nociception monitors may provide intraoperative data associated with surgical stress responses, and to inspire new research into the effects of nociception monitor-guided anesthesia on postoperative complications

Role of eosinophilia in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab: Prediction of immune‐related adverse events and favorable outcome

Abstract Introduction Immune‐related adverse events (irAEs) are prognostic factors for patients on nivolumab. However, predictors of irAEs have not yet been identified. We aimed to investigate the predictors of irAEs occurrence and nivolumab discontinuation due to irAEs. Methods Sixty‐two patients with recurrent/metastatic head and neck squamous cell carcinoma received nivolumab therapy between June 2017 and December 2020. Treatment outcome was compared between the groups with or without irAEs. The irAE (+) group was further divided by nivolumab discontinuation. Progression‐free survival (PFS) and overall survival (OS) were compared between the groups. Predictors of irAE occurrence were analyzed. Results Twenty‐one patients (33.9%) developed irAEs, and six (28.6%) discontinued nivolumab due to severe irAEs. The irAE (+) group had significantly longer PFS and OS than the irAE (−) group (median PFS, 12.7 vs. 1.9 months; median OS, 33.1 vs. 12.8 months). The treatment outcomes in the discontinuation group were comparable to those in the non‐discontinuation group. The maximum absolute eosinophil count (AEC) during nivolumab therapy was significantly higher in the irAE (+) group than in the irAE (−) group (548.8 vs. 182) and higher in the discontinuation group than in the non‐discontinuation group (729.3 vs. 368.6). The receiver operating characteristic curve showed that the maximum AEC had a moderate‐to‐high accuracy for predicting irAE occurrence (area under the curve [AUC], 0.757) and nivolumab discontinuation (AUC, 0.893). Discussion Monitoring AEC during nivolumab therapy may be useful in predicting irAE occurrence, nivolumab discontinuation, and disease prognosis

Bacterial-excreted small volatile molecule 2-aminoacetophenone induces oxidative stress and apoptosis in murine skeletal muscle

Oxidative stress induces mitochondrial dysfunction and facilitates apoptosis, tissue damage or metabolic alterations following infection. We have previously discovered that the Pseudomonas aeruginosa (PA) quorum sensing (QS)-excreted small volatile molecule, 2-aminoacetophenone (2-AA), which is produced in infected human tissue, promotes bacterial phenotypes that favor chronic infection, while also compromising muscle function and dampens the pathogen-induced innate immune response, promoting host tolerance to infection. In this study, murine whole-genome expression data have demonstrated that 2-AA affects the expression of genes involved in reactive oxygen species (ROS) homeostasis, thus producing an oxidative stress signature in skeletal muscle. The results of the present study demonstrated that the expression levels of genes involved in apoptosis signaling pathways were upregulated in the skeletal muscle of 2-AA-treated mice. To confirm the results of our transcriptome analysis, we used a novel high-resolution magic-angle-spinning (HRMAS), proton (1H) nuclear magnetic resonance (NMR) method and observed increased levels of bisallylic methylene fatty acyl protons and vinyl protons, suggesting that 2-AA induces skeletal muscle cell apoptosis. This effect was corroborated by our results demonstrating the downregulation of mitochondrial membrane potential in vivo in response to 2-AA. The findings of the present study indicate that the bacterial infochemical, 2-AA, disrupts mitochondrial functions by inducing oxidative stress and apoptosis signaling and likely promotes skeletal muscle dysfunction, which may favor chronic/persistent infection