Serum Albumin as an Independent Predictor of Long-Term Survival in Patients with Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma Treated with Nivolumab.

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.

Association of Pretreatment Neutrophil-to-Eosinophil Ratio with Clinical Outcomes in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Treated with Nivolumab.

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.

18F-FDG-PET/CT can be used to predict distant metastasis in hypopharyngeal squamous cell carcinoma.

BACKGROUND: Hypopharyngeal squamous cell carcinoma (HPSCC) has a high rate of distant metastasis, resulting in poor prognosis. The role of the maximum standardized uptake value (SUVmax), which was assessed via pretreatment 18-fluorodeoxyglucose positron emission tomography (FDG-PET), and computed tomography (CT) was examined, for predicting distant metastasis and survival. METHODS: This study included 121 patients who underwent pretreatment FDG-PET/CT scanning and subsequent treatment for HPSCC. The SUVmax was measured via FDG-PET/CT. A receiver operating characteristic (ROC) curve analysis was used to determine whether the SUVmax was a predictor of distant metastasis and to select the best cutoff value. Univariate and multivariate Cox hazard regression analyses were used in identifying associations between the SUVmax and other clinicopathological factors with distant metastasis-free survival. RESULTS: Distant metastases were identified in 33 patients during the median follow-up of 24 months after treatment. The ROC curve analysis determined that SUVmax was predictive of distant metastasis and identified a SUVmax of 13.9 as the best potential cutoff value. The univariate analysis showed that T and N classification, clinical stage, and SUVmax were significantly related to distant metastasis. However, in multivariate analysis, an SUVmax ≥ 13.9 was the only independent predictor of distant metastasis. Patients with high SUVmax values displayed significantly shorter distant metastasis-free survival and overall survival. CONCLUSIONS: SUVmax determined via pretreatment FDG-PET/CT is useful for predicting distant metastasis, distant metastasis-free survival, and overall survival in patients with HPSCC.

Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

A case of insulinoma diagnosed postpartum with hypoglycemic symptoms that were masked during pregnancy.

The diagnosis of insulinoma in perinatal women can be difficult, as hypoglycemic symptoms may be masked by pregnancy-associated insulin resistance. In addition, when multiple insulinomas are observed, it is necessary to consider the possibility not only of MEN1, but also of insulinomatosis.

Increment of plasma glucose by exogenous glucagon is associated with present and future renal function in type 2 diabetes:a retrospective study from glucagon stimulation test.

BACKGROUND: Glucagon stimulation test (GST) is often employed to assess the insulin reserve of the pancreatic beta cells in diabetic subjects. The clinical significance of the increment of plasma glucose (Δglucose) by exogenous glucagon during GST has not been elucidated. We investigated the relationship between Δglucose and clinical parameters including the liver and renal function in type 2 diabetic subjects, since we hypothesized that Δglucose is associated with the liver and renal function reflecting the capacity for gluconeogenesis in the organs. METHODS: A total of 209 subjects with type 2 diabetes who underwent GST during admission were included in this cross-sectional study. We defined the difference between plasma glucose at fasting and 6 min after intravenous injection of 1 mg glucagon as Δglucose. We assessed correlations between Δglucose and clinical parameters such as diabetic duration, BMI, HbA1c, beta cell function, serum free fatty acids (FFA) which is known to stimulate gluconeogenesis, liver function, the indices of liver function, renal function, and urinary albumin excretion (UAE). RESULTS: In correlation analysis, Δglucose positively correlated to FFA and estimated glomerular filtration rate (eGFR), but inversely to serum creatinine and cystatin C, although Δglucose showed no correlation with both liver function and the indices of residual liver function. Multiple regression analysis revealed that Δglucose was an independent determinant for the eGFR after 1 year, equally BMI, HbA1c, serum lipids, and UAE, which are known as the predictors for the development of chronic kidney disease. CONCLUSION: Our results suggest that Δglucose during GST might be related to gluconeogenesis in the kidney and could be the determinant of future renal function in type 2 diabetes.

Expression of transcription factors in MEN1-associated pancreatic neuroendocrine tumors.

MEN1-associated pancreatic neuroendocrine tumors (pNETs) may potentially express distinct hormones, but the mechanism has not been elucidated. Transcription factors such as MafA and Pdx1 have been identified to lead to beta cell differentiation, while Arx and Brn4 to alpha cell differentiation in developing pancreas. We hypothesized those transcription factors are important to produce specific hormones in pNETs, similarly to developing pancreas, and examined the expression of transcription factors in a case of MEN1 who showed immunohistological coexistence of several hormone-producing pNETs including insulinoma. A 70-year-old woman was found to manifest hypoglycemia with non-suppressed insulinemia and hypercalcemia with elevated PTH level. She was diagnosed as MEN1 based on the manifestation of primary hyperparathyroidism, pituitary adenoma and insulinoma, with genetic variation of MEN1 gene. She had pylorus-preserving pancreaticoduodenectomy because CT scan and SACI test indicated that insulinoma was localized in the head of the pancreas. Histopathological finding was MEN1-associated NET, G1. Interestingly, immunohistological examination of the resected pancreas revealed that two insulinomas, a glucagon-positive NET and a multiple hormone-positive NET coexisted. Hence, we examined the expression of transcription factors immunohistochemically to elucidate the role of the transcription factors in MEN1-associated hormone-producing pNETs. We observed homogeneous expressions of MafA and Pdx1 in insulinomas and Arx in glucagon-positive NET, respectively. Moreover, multiple hormone-positive NETs expressed several transcription factors heterogeneously. Collectively, our results suggested that transcription factors could play important roles in the production of specific hormones in MEN1-associated pNETs, similar to islet differentiation. LEARNING POINTS: To date, it has been shown that different hormone-producing tumors coexist in MEN1-associated pNETs; however, the underlying mechanism of the hormone production in MEN1-associated pNETs has not been well elucidated.Although this case presented symptomatic hypoglycemia, several hormone-producing pNETs other than insulinoma also coexisted in the pancreas.Immunohistochemical analysis showed MafA and Pdx1 expressions distinctly in insulinoma, and Arx expression particularly in a glucagon-positive NET, while a multiple hormone-positive NET expressed MafA, Pdx1 and Arx.Collectively, clinicians should consider that several hormone-producing pNETs may coexist in a MEN1 case and examine both endocrinological and histopathological analysis of pNETs, regardless of whether symptoms related to the excess of hormones are observed or not.

Anaplastic transformation of papillary thyroid carcinoma in multiple lung metastases presenting with a malignant pleural effusion: a case report.

INTRODUCTION: Anaplastic transformation of well-differentiated papillary thyroid carcinoma at distant metastasis sites is rare. To the best of our knowledge, this is the first report of an autopsy case of anaplastic transformation of papillary thyroid carcinoma in multiple lung metastases presenting with a malignant pleural effusion. CASE PRESENTATION: We report an autopsy case of a 61-year-old Japanese man with anaplastic transformation of papillary thyroid carcinoma with multiple lung metastases presenting with a malignant pleural effusion, which was difficult to diagnose by cytological examination before the autopsy. He presented with a 1-month history of progressive dyspnea, and examination of the left pleural effusion revealed a bloody exudate with an increase in thyroglobulin; however, malignant cells in the pleural fluid were negative for thyroglobulin. CONCLUSION: It is important to be aware that anaplastic transformation of differentiated thyroid carcinoma could develop in lung metastases and could be a cause of a malignant pleural effusion.