Development of hepatic impairment aggravates chemotherapy-induced peripheral neuropathy following oxaliplatin treatment: Evidence from clinical and preclinical studies.

Oxaliplatin often induces peripheral neuropathy, a dose-limiting adverse reaction, and in rare cases leads to sinusoidal obstruction syndrome. We thus conducted a retrospective cohort study to examine the relationship between oxaliplatin-induced peripheral neuropathy (OIPN) and hepatic impairment, and then perform a fundamental study to analyze the underlying mechanisms. Analysis of medical records in cancer patients treated with oxaliplatin indicated that laboratory test parameters of hepatic impairment including AST, ALT and APRI (AST to platelet ratio index) moderately increased during oxaliplatin treatment, which was positively correlated with the severity of OIPN (grades 1-4), and associated with later incidence of survivors with OIPN grades ≥2. In mice, hepatic injury induced by CCl4 or ethanol accelerated OIPN in mice, an effect prevented by inactivation of high mobility group box 1 (HMGB1), known to participate in OIPN, by the neutralizing antibody or thrombomodulin alfa capable of promoting its thrombin-dependent degradation. Oxaliplatin also aggravated the hepatic injury in mice. CCl4 released HMGB1 from cultured hepatic parenchymal cells, and oxaliplatin at clinically achievable concentrations released HMGB1 from hepatic parenchymal and non-parenchymal cells. Our clinical and preclinical data suggest that the development of mild hepatic impairment during oxaliplatin treatment is associated with later aggravation of OIPN.

Estrogen decline is a risk factor for paclitaxel-induced peripheral neuropathy: Clinical evidence supported by a preclinical study.

We performed clinical retrospective study in female cancer patients and fundamental experiments in mice, in order to clarify risk factors for paclitaxel-induced peripheral neuropathy (PIPN). In the clinical study, 131 of 189 female outpatients with cancer undergoing paclitaxel-based chemotherapy met inclusion criteria. Breast cancer survivors (n = 40) showed significantly higher overall PIPN (grades 1-4) incidence than non-breast cancer survivors (n = 91). Multivariate sub-analyses of breast cancer survivors showed that 57 years of age or older and endocrine therapy before paclitaxel treatment were significantly associated with severe PIPN (grades 2-4). The age limit was also significantly correlated with overall development of severe PIPN. In the preclinical study, female mice subjected to ovariectomy received repeated administration of paclitaxel, and mechanical nociceptive threshold was assessed by von Frey test. Ovariectomy aggravated PIPN in the mice, an effect prevented by repeated treatment with 17ß-estradiol. Repeated administration of thrombomodulin alfa (TMα), known to prevent chemotherapy-induced peripheral neuropathy in rats and mice, also prevented the development of PIPN in the ovariectomized mice. Collectively, breast cancer survivors, particularly with postmenopausal estrogen decline and/or undergoing endocrine therapy, are considered a PIPN-prone subpopulation, and may require non-hormonal pharmacological intervention for PIPN in which TMα may serve as a major candidate.

The C-Reactive Protein/Albumin Ratio Is Useful for Predicting Short-Term Survival in Cancer and Noncancer Patients.

Objective and Background: Survival predictions by subjective evaluations are important for end-stage patients. However, subjective evaluations based on experience are difficult. Therefore, we investigated whether the Glasgow prognostic score (GPS), prognostic nutritional index (PNI), and C-reactive protein (CRP)/albumin ratio (CRP/Alb ratio) calculated from the laboratory values of objective evaluations are useful for predicting survival times in end-stage patients. Methods: We retrospectively investigated the age, sex, death cause, CRP levels, Alb levels, and lymphocyte counts in 363 cancer and noncancer patients who died in the 12-month period between April 2015 and March 2016. A multivariate analysis was performed to calculate GPS, PNI, and the CRP/Alb ratio from laboratory values and adjusted for confounding factors. Results: PNI and CRP/Alb ratio exhibited negative and positive correlations with survival days, respectively. All GPS, PNI, and CRP/Alb ratio were useful to predict two to four remaining weeks. Interestingly, CRP/Alb ratio, but not GPS or PNI, was higher in patients with predicted short-term survival of zero to two weeks than in that of two to four weeks (odds ratio 2.32; 95% confidence interval 1.61-3.34). Discussion: These results suggest that the CRP/Alb ratio is an independent factor that is beneficial to predict short-term survival of within two weeks.

[Usefulness of measuring serum procalcitonin levels by immunochromatographic assay in febrile neutropenia].

In order to clarify the usefulness of measuring procalcitonin (PCT) values under the extreme condition called febrile neutropenia (FN), PCT was measured with immunochromatographic assay (ICA) and electro-chemi-luminescence immunoassay (ECLIA) at two time points: upon FN occurrence and 12 to 24 hours after FN occurrence, and correlations and associations between the two methods were reviewed. A strong correlation between the ICA and ECLIA results was observed when Spearman's rank correlation coefficient was 0.878, and the association was also demonstrated by Fisher's direct test since P=4.68×10(-10). Special equipment is not required, the operations are simple, and the ICA method currently adopted by many facilities can be used as the standard method even for the clinical condition known as FN.