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BACKGROUND: Naldemedine is an orally available peripherally acting µ-opioid receptor antagonist approved to treat opioid-induced constipation (OIC). It is contraindicated for patients with known or suspected gastrointestinal obstruction to protect against naldemedine-induced perforation. Here, we report a clinical case of suspected perforation of a diverticulum in the sigmoid colon associated with naldemedine. CASE PRESENTATION: The patient was a 65-year-old man with a history of oral cancer who had been prescribed oxycodone (20 mg/day) for cancer pain. On day 0, the patient started naldemedine 0.2 mg once daily before bedtime for OIC. The dose of oxycodone was increased for pain control up to 60 mg/day. On day 35 of naldemedine treatment, the patient developed fever and abdominal pain, and his frequency of defecation had decreased. Initial laboratory results showed a C-reactive protein (CRP) level of 28.5 mg/dL and white blood cell (WBC) count of 13,500/µL. On day 37, the patient still had tenderness in his lower abdomen. Abdominal computed tomography revealed free air in the abdominal cavity suggesting an intestinal perforation. A Hartmann procedure was performed. Histopathological findings showed numerous diverticula in the sigmoid colon, some of which were perforated. CONCLUSIONS: These results suggest that the effects of OIC may have compressed the intestinal tract, which was followed by naldemedine-activation of peristalsis, which led to the onset of intestinal perforation. In patients with pre-existing diverticular disease, we should monitor for increased WBC counts and CRP levels after the initiation of treatment with naldemedine, and consider performing appropriate tests early in the event of abdominal complaints.
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Background: Nivolumab has been shown to improve the overall survival (OS) of patients with recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, there is a need to identify factors associated with long-term survival (beyond 2 years) in these patients. This study investigated the relationship between pretreatment factors and long-term survival in patients with R/M HNSCC treated with nivolumab. Methods: Forty-nine patients with R/M HNSCC who were treated with nivolumab were retrospectively reviewed. Baseline characteristics, clinical data, and survival outcomes were evaluated. Univariate and multivariate analyses were performed to identify factors associated with long-term survival (OS ≥ 2 years). Results: The median OS in the overall cohort was 11.0 months, and the 2-year survival rate was 34.7%. Long-term survivors (OS ≥ 2 years) had significantly higher proportions of patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of 0 or 1, serum albumin levels ≥ 3.5 g/dL, and neutrophil-to-eosinophil ratio (NER) < 32.0 compared to non-long-term survivors. On multivariate analysis, serum albumin levels ≥ 3.5 g/dL, in addition to ECOG-PS score of 0 or 1, were independent predictors of long-term survival. Conclusions: Pretreatment serum albumin levels may be useful for predicting long-term survival in R/M HNSCC patients treated with nivolumab.
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Background: There is a need to develop biomarkers for a more efficient use of immune checkpoint inhibitors (ICIs). Recently, it has been reported that peripheral blood components, including eosinophils, may be effective ICI biomarkers. This study was designed to evaluate the prognostic value of eosinophils for measuring the effects of nivolumab on recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Materials and Methods: The study included 47 patients with R/M HNSCC treated with nivolumab. Eosinophil-related biomarkers, such as absolute eosinophil count (AEC), relative eosinophil count (REC), and neutrophil-to-eosinophil ratio (NER), were measured from the peripheral blood of the patients before nivolumab treatment. For each biomarker, the patients were divided into a high- and a low-value group according to their cutoff values, and these groups were compared. Results: Regarding AEC and REC, no significant improvement in the objective response rate (ORR) was observed between patients with AEC >0.9 × 103/µL and those with AEC <0.9 × 103/µL (p = 0.147) and between patients with REC >2.2% and those with REC <2.2% (p = 0.110). However, patients with NER <32 had improved ORR compared with those with NER >32 (P = 0.0361). Additionally, although patients with AEC >0.9 × 103/µL, REC >2.2%, and NER <32 had longer overall survival (OS) than those with AEC <0.9 × 103/µL, REC <2.2%, and NER >32, only patients with NER <32 showed prolonged progression-free survival (PFS) compared with those with NER >32 according to the Log rank test (p = 0.046, 0.027, and 0.035, respectively). Furthermore, the multivariate analysis revealed that baseline NER >32 (p = 0.027) was an independent prognostic factor for worse OS. Conclusion: A pretreatment feature of low NER (NER <32) may predict better clinical outcomes in patients with R/M HNSCC treated with nivolumab.