Serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody.

Immune-oncology (IO) drug therapy is effective against various types of cancer. Although several, potential, clinical predictive markers have been identified, none so far have proven reliable. Herein we evaluated changes in serum alanine aminotransferase (ALT), which is upregulated by the accumulation of activated CD8+T cells in the liver, as a potentially reliable predictive marker. We retrospectively analyzed 265 patients with advanced malignancies at three institutions between 2016 and 2019. The patients received IO drug therapy. We defined the ALT ratio (ALR) as the serum ALT value at baseline / the highest serum ALT during IO drug therapy, then determined whether the ALR correlated with the objective response rate or progression-free survival. The median follow-up was 3.1 months. We observed objective responses in 65 patients. The ALR ranged from 0.19 to 32.2 (median 1.5), and a significant ALR increase was observed in responders (p < 0.001). In receiver operating characteristic analysis, ALR = 1.55 had the highest sensitivity and specificity. The patients with ALR < 1.55 had a significantly poorer PFS than those with ALR ≥ 1.55. A high ALR was associated with a tumor response and good PFS in patients with advanced malignancies. The ALR based on activated cytotoxic T lymphocyte dynamics is therefore a reliable predictive marker.

Effect of dutasteride on castration-resistant prostate cancer.

It has previously been demonstrated that the intratumoral generation of the potent androgen dihydrotestosterone (DHT), contributes critically to the progression of prostate cancer and its castration-resistant form, castration-resistant prostate cancer (CRPC). Circulating testosterone is converted into DHT by 5α-reductase (SRD5A). Dutasteride is a dual inhibitor of type I and II SRD5A. The present study assessed the effectiveness of dutasteride in the treatment of CRPC. Between 2010 and 2013, CRPC was diagnosed in 41 patients at the Tokyo Metropolitan Tama Medical Center. Following diagnosis, the patients received 0.5 mg dutasteride daily. The patients' median age was 77.3 years (range, 63-90). Bone metastases were recognized in 12 patients. All the patients received dexamethasone. Twenty-four (59%) patients had previously undergone chemotherapy, while 11 (27%) received docetaxel, and 24 (59%) estramustine. The prostatic-specific antigen (PSA) level declined in 17 (41%) patients from the baseline value, following dutasteride treatment. The median value for the PSA decrease was 23% (range, 4.3-89.8%), and the median duration of the response was 4 months (range, 1-10). The PSA response rate (defined as >50% decline in PSA from the baseline value) was recognized in 7 (17%) patients. The median duration of the response was 3 months (range, 2-10). Dutasteride was efficacious against CRPC in certain patients and may be a promising option in CRPC treatment. A prospective randomized trial is necessary to verify the efficacy of dutasteride.

The safety and effect of chemotherapy with short hydration for urothelial cancer on patients' quality of life.

OBJECTIVE: Our aim was 2-fold: first, to assess the safety of short hydration treatment for urothelial cancer; and second, to assess the resultant quality of life of patients who received the treatment. METHODS: We assessed 61 patients including 31 outpatients and 30 inpatients, who received a combination of gemcitabine and cisplatin chemotherapy with short hydration. The serum creatinine (Cr) level and the estimated glomerular filtration rate were measured to assess renal function using linear mixed model analysis. To assess quality of life, the patients were asked to respond to the Functional Assessment of Cancer Therapy-General questionnaire. The responses were then analyzed using the paired t-test. RESULTS: Patients who received short hydration chemotherapy showed no significant change in serum Cr level (P = 0.423) or estimated glomerular filtration rate  (P = 0.582). There was also no significant change in serum Cr level or estimated glomerular filtration rate between patients who received short hydration chemotherapy and those who received consecutive hydration chemotherapy (P = 0.154 and 0.311, respectively). In every patient, the Functional Assessment of Cancer Therapy-General total score and subscale scores both improved as a result of outpatient chemotherapy with short hydration (P < 0.01). CONCLUSIONS: The short hydration gemcitabine and cisplatin regimen for patients with urothelial cancer was safe. Further, the outpatient chemotherapy was found not only to be safe, but also to have improved the patients' quality of life.

Influence of Naftopidil on Plasma Monoamine Levels and Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia.

OBJECTIVES: To clarify the influence of naftopidil, an α1D/A -adrenergic receptor antagonist, on the autonomic nervous system, we examined the relation between lower urinary tract symptoms (LUTS) and the plasma monoamine levels before and after naftopidil treatment in benign prostatic hyperplasia (BPH) patients. METHODS: A total of 43 patients with BPH were studied. The frequency of urination, international prostate symptom score (IPSS), quality of life (QOL) index, overactive bladder symptom score (OABSS), and plasma monoamine levels (adrenaline, noradrenaline, dopamine, and serotonin) were evaluated before and after naftopidil treatment. RESULTS: Naftopidil significantly improved urinary frequency in daytime and nighttime, IPSS, QOL index and OABSS in all patients, and decreased the plasma adrenaline level at 8 weeks. When the patients were divided into two groups based on the median adrenaline level (40.5 pg/mL) before treatment, urinary frequency in daytime and/or nighttime, incomplete emptying and poor flow in the IPSS, and the QOL index were significantly improved in the high adrenaline (HA) group, but not in the low adrenaline (LA) group. The pretreatment plasma serotonin level was significantly lower in the HA group than in the LA group, but it increased gradually after the start of treatment until there was no difference between the groups. CONCLUSIONS: The modulation of plasma adrenaline and serotonin levels by naftopidil in patients with increased sympathetic activity contributed to improvement of LUTS associated with BPH, in addition to its antagonistic effects of α1D/A -adrenergic receptor on the detrusor and prostatic urethral smooth muscle, the urothelium, and the central nervous system.

[Effect of distigmine at 5 mg daily in patients with detrusor underactivity].

PURPOSE: Since distigmine can cause the serious side effect of cholinergic crisis, its dosage regimen has been reduced to 5 mg/day for patients with difficulty in urination due to detrusor underactivity. Therefore, the efficacy and safety of add-on therapy with distigmine at 5 mg daily were examined in patients with persistent urination problems due to detrusor underactivity despite administration of alpha1-blockers. PATIENTS AND METHODS: The subjects were 39 patients with underactive bladder (18 men and 21 women with an average age of 75 years) who showed no improvement of difficulty in urination or had a residual urine volume > or = 50 ml despite the administration of alpha1-blockers for more than 4 weeks. They received treatment with distigmine (5 mg daily after breakfast) in addition to their alpha1-blockers for 8 weeks. The international prostate symptom score (IPSS), quality-of-life (QOL) score, residual urine volume, blood pressure, and biochemistry tests were investigated before and after addition of distigmine. RESULTS: After four and eight weeks of distigmine administration, all items of the IPSS and QOL score, as well as the residual urine volume, showed a significant decrease. In contrast, the pressure and pulse rate were unchanged. Serum creatinine showed a slight but significant decreased. As adverse events, frequent defecation, fecal incontinence, diarrhea, frequent urination and poor physical condition were recognized in 4 patients, but there was no serious event. CONCLUSION: For difficulty in urination due to detrusor underactivity, the combination of an alpha1-blocker with distigmine at 5 mg daily showed early efficacy and good safety.

Preoperative neutrophil-lymphocyte ratio as an independent prognostic marker for patients with upper urinary tract urothelial carcinoma.

BACKGROUND: To predict the prognosis, we evaluated the significance of the preoperative neutrophil-lymphocyte ratio (NLR) in patients with upper urinary tract urothelial carcinoma (UUTUC). PATIENTS AND METHODS: A cohort of 137 patients diagnosed with UUTUC from 1994 to 2008 at Tokyo Metropolitan Tama Medical Center was enrolled in this retrospective study. Log-rank test and Cox proportional hazards regression models were used for univariate and multivariate analyses. RESULTS: On univariate analysis, pathologic T stage, grade, lymphovascular invasion, C-reactive protein (CRP) level, and NLR were significantly associated with recurrence-free survival (RFS) and cancer-specific survival (CSS). The RFS rates for an NLR < 2.5 and for one ≥ 2.5 at 5 years were 74.3% and 30.4%, respectively. The CSS rates for an NLR < 2.5 and for one ≥ 2.5 at 5 years were 81.3% and 29.4%, respectively. The multivariate Cox proportional hazards regression models showed that the NLR could be an independent predictor for RFS and CSS. Based on the results of multivariate analysis, the scoring model was developed. RFS and CSS rates at 5 years were as follows: 0 risk factor, 97.1% and 97.0%, respectively; 1 risk factor, 91.1% and 90.9%, respectively; 2 risk factors, 39.5% and 58.6%, respectively; 3 risk factors, 26.6% and 28.6%, respectively; and 4 risk factors, 6.0% and 5.6%, respectively. CONCLUSIONS: The preoperative NLR is an independent prognostic predictor. The model based on the NLR and pathologic factors can be useful in clinical practice.

Metastatic renal cell carcinoma change vascularity.

Several molecular targeted agents have been approved for clinical use for metastatic renal cell carcinoma (mRCC). A case of a 32-year-old woman with mRCC is presented. These tumors could change vascularity by administration of molecular agents. We could select a drug timely based on findings of computed tomography. To our knowledge, this is the first report that tumor's character change induced by molecular targeted agents can be detected and the efficacy of molecular targeted agents can be predicted.

Primary mucinous adenocarcinoma of the testis.

Ovarian-type surface epithelial neoplasms of the testis and paratestis are uncommon, and the mucinous subtype is particularly rare. These tumors represent a counterpart to ovarian cancer. Malignant tumors have the potential for metastatic spread and are often fatal. The case of a 59-year-old man with testicular mucinous adenocarcinoma is presented. Computed tomography indicated involvement of the paraaortic and pelvic lymph nodes, so chemotherapy was initiated. To the best of our knowledge, this is the second paper regarding responsiveness to chemotherapies used in ovarian cancer.

Neutrophil number after interferon-alfa treatment is an independent predictive marker of overall survival in metastatic renal cell carcinoma.

BACKGROUND: The purpose of this study was to assess the outcome in patients treated by immunotherapy using interferon-alpha (IFN-α) and to evaluate the significance of the neutrophil count after IFN-α immunotherapy as a predictive marker for metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: We identified 84 patients with metastatic RCC who underwent immunotherapy with IFN-α between 1998 and 2006. The predictive values of the neutrophil count before and after IFN-α treatment as well as other clinical and laboratory parameters were assessed retrospectively. RESULTS: On univariate analysis, the significant correlation with overall survival (OS) was recognized in the Eastern Cooperative Oncology Group (ECOG) performance score (PS), lactate dehydrogenase (LDH) levels, corrected calcium levels, interval from diagnosis to treatment, and the ratio of neutrophil number before and after treatment with INF-α. Multivariate analysis showed that ECOG PS, corrected calcium levels, interval from diagnosis to treatment and neutrophil number after IFN-α treatment were independent factors for OS. Using the number of neutrophils after IFN-α treatment, subgroups were identified using the Memorial Sloan-Kettering Cancer Center (MSKCC) model. The 1-year survival rate was 93% vs. 63% in the intermediate-risk group and 34% vs. 8% in the poor-risk group. In the favorable-risk group, all patients had a good decrease in neutrophil number after treatment with IFN-α. CONCLUSION: Neutrophil number after IFN-α treatment can be a good predictive marker for OS in metastatic RCC. By combining MSKCC score with neutrophil number after treatment with IFN-α, we can subdivide each group.