Kosuke Iwatani

Compared to prostate adenocarcinoma, neuroendocrine prostate carcinoma is characterized by aggressive tumor biology and a poor prognosis. Several studies have focused on tumor markers to assess neuroendocrine differentiation and treatment outcomes. However, few studies have investigated changes in tumor markers throughout the clinical course. This observational study evaluated neuroendocrine differentiation, survival outcomes, and temporal changes in neuroendocrine marker positivity in patients with prostate cancer. A total of 193 prostate cancer cases were included in this study. We measured circulating neuroendocrine tumor markers, including neuron-specific enolase (NSE) and pro-gastrin-releasing peptide (pro-GRP), and calculated their positivity rates. In relation to castration-resistant prostate cancer (CRPC), we assessed the changes in the positive rates of neuroendocrine tumor markers over time. In the cross-sectional cohort, the positivity rate of circulating neuroendocrine markers was 19.8% in hormone-sensitive prostate cancer and 64.9% in CRPC (24/37). Temporal changes in marker positivity were evaluated in a separate longitudinal CRPC follow-up cohort (n = 39) with serial NSE/pro-GRP measurements. In the context of CRPC, pro-GRP was significantly associated with prognosis. The median overall survival for patients with normal pro-GRP levels was 78 months, whereas that for patients with elevated pro-GRP levels was significantly shorter (36.5 months, p = 0.0216). In the longitudinal CRPC follow-up cohort (n = 39), the overall marker positivity rate increased from 61.5% at baseline to 92.3% at approximately four years. Neuroendocrine tumor markers were significantly elevated in CRPC and correlated with survival outcomes. The positivity rate of these tumor markers increased during CRPC treatment. This suggests that treatment-emergent neuroendocrine differentiation may occur more frequently than previously anticipated.

Serum C-reactive protein (CRP) is known to be a biomarker for systemic inflammatory reactions. In the present study, we sought to measure the predictive value of serum CRP level for metastatic renal cell carcinoma (mRCC) treated with first-line ipilimumab and nivolumab using our real-world clinical dataset including non-clear cell RCC (nccRCC). The clinical record of patients who underwent the first-line ipilimumab plus nivolumab treatment for mRCC including ccRCC and nccRCC from 2018 to 2021 was retrospectively analyzed. All patients were diagnosed with either intermediate or poor-risk group defined by IMCD (international metastatic RCC database consortium). In total, 74 patients were involved. The median age was 68 years and 24 (32.4%) patients deceased during the follow-up. Forty-five (61%) and 29 (39%) patients were classified into intermediate and poor-risk groups. The one-year overall survival (OS) rate and objective response rate were 65% and 41% for all 74 mRCC patients, respectively. The receiver operating characteristic curve identified 1.0 mg/dL of serum CRP level as an ideal cut-off for predicting overall survival (OS). Serum CRP > 1.0 mg/dL and nccRCC were the independent predictors for OS in 74 mRCC patients. OS for patients with CRP > 1 mg/dL was significantly shorter than those with CRP < 1 mg/dL in both ccRCC (58 patient: p = 0.009) and nccRCC (16 patients: p = 0.008). The present study indicated that serum CRP level is a prognostic indicator for OS in both ccRCC and nccRCC patients treated with the first-line ipilimumab plus nivolumab treatment.

Objective: To evaluate the risk factors of perioperative hemodynamic instability in pheochromocytoma, we conducted a systematic search of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-analysis. Methods: In April 2021, we systematically searched PubMed, the Cochrane library, and Scopus for relevant studies on the risk factors of perioperative hemodynamic instability of adrenalectomy in patients with pheochromocytoma, and we subjected the findings from those studies to formal meta-analysis. Results: Our systematic review identified 14 studies involving 1725 patients, of which nine studies with 967 patients were eligible for meta-analysis. The results of meta-analysis showed that tumor size (odds ratio (OR): 1.14 for each increased cm, 95% confidence interval (CI) 1.03–1.26, z = 2.57) and urinary norepinephrine (OR, 1.51: 95% CI 1.26–1.81; z = 4.50) were most closely associated with the occurrence of perioperative hemodynamic instability. Conclusion: These findings suggest that tumor size and urinary norepinephrine are important predictors and risk factors for perioperative hemodynamic instability in adrenalectomy for pheochromocytoma. Such findings may be of value to surgeons and anesthesiologists when considering or preparing for this procedure.

The impact of ABO blood type in the development of venous thromboembolism in cancer patients remains controversial. To develop a sense of the current opinion in this area, we conducted a systematic review and meta-analysis. In March 2021, we performed a systematic search of PubMed, the Cochrane library, and Scopus for studies that compared cancer patients who had a blood type of either O or non-O (A, B, and AB). Our objective was to use multivariate logistic regression analysis to determine how ABO blood type was associated with the development of venous thromboembolism. Our selection criteria were met by a total of nine studies in 25,884 patients for the systematic review and five studies in 22,777 patients for the meta-analysis. In cancer patients, we found that non-O blood type was associated with a nearly two-fold increase in risk of venous thromboembolism (pooled OR: 1.74, 95% CI: 1.44–2.10). Additionally, among the eligible patients, 21,889 patients were post-operative urological cancer patients. In these patients, the analysis also showed an association between non-O blood type and increasing risk of venous thromboembolism after pelvic surgery for malignancy (pooled OR: 1.73, 95% CI: 1.36–2.20). Our meta-analysis suggested that non-O blood type is a risk factor for venous thromboembolism among patients with cancer. As blood type is routinely determined preoperatively by objective and standardized methods, we anticipate that our results will be useful for managing venous thromboembolism in cancer patients, especially after pelvic surgery for urological cancers.