Pegfilgrastim for the management of neutropenia during neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in esophageal cancer patients.

BACKGROUND: Neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy is a new standard for locally advanced esophageal squamous cell carcinoma. The optimal timing of pegfilgrastim with the DCF regimen to prevent febrile neutropenia (FN) remains controversial. The effectiveness of concomitant pegfilgrastim administration with continuous 5-fluorouracil (5-FU) infusion in the DCF regimen was therefore assessed. METHODS: All patients who received neoadjuvant DCF for esophageal cancer were retrospectively assessed. Patients who had been scheduled to receive pegfilgrastim on days 3-5 (early group) or days 7-9 (regular group) of the DCF regimen were included. Uni- and multivariate analyses were used to assess risk factors for FN. RESULTS: Eighty-eight patients were included in the analysis. The 26 patients in the early group received pegfilgrastim as scheduled. In the 62 patients of the regular group, 51 received pegfilgrastim at a median of 7 days after starting DCF chemotherapy. However, 11 patients in the regular group could not receive pegfilgrastim. Twenty-two patients of the regular group and 2 patients of the early group developed FN after the first session of DCF. Early administration of pegfilgrastim and grade 4 neutropenia were significantly associated with onset of FN, with multivariate analysis identifying early administration of pegfilgrastim as an independent preventive factor and grade 4 neutropenia as a risk factor, after adjusting for sex and age. CONCLUSION: Early pegfilgrastim administration is a safe approach that reduces the incidence of FN in DCF therapy. Using pegfilgrastim with continuous 5-FU infusion in the DCF regimen represents a reasonable option to prevent FN.

Yokukansan Suppresses Gastric Hypersensitivity and Eosinophil-associated Microinflammation in Rats With Functional Dyspepsia.

Background/Aims: Herbal medicine is an important complementary therapy for functional dyspepsia (FD). However, its effect against gastric hypersensitivity in patients with FD has rarely been evaluated. Yokukansan (YKS), a traditional Japanese herbal medicine, is effective against neuropathic and inflammatory pain. This study aims to use a maternal separation (MS) stress-induced FD model to investigate the effects of YKS against gastric hypersensitivity, gastric motility, and duodenal micro-inflammation. Methods: The MS stress model was established by separating newborn Sprague-Dawley rats from their mothers for 2 hours a day from postnatal days 1 to 10. At the age of 7-8 weeks, the rats were treated with YKS at a dose of 5 mL/kg (1 g/kg) for 7 consecutive days. After YKS treatment, electromyographic activity in the acromiotrapezius muscle by gastric distention and the gastric-emptying rate were assessed. Immunohistochemical analysis of eosinophils in the duodenum and phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 in the spinal cord was performed. Results: YKS treatment suppressed MS stress-induced gastric hypersensitivity and decreased the elevated levels of p-ERK1/2 in the spinal cord. In the gastroduodenal tract, YKS inhibited eosinophil-associated micro-inflammation but did not improve gastric dysmotility. Conclusions: YKS treatment improved gastric hypersensitivity by alleviating eosinophil-associated micro-inflammation in the gastroduodenal tract. This treatment may be considered an effective therapeutic option for epigastric pain and micro-inflammation in patients with FD.

Eosinophil-associated microinflammation in the gastroduodenal tract contributes to gastric hypersensitivity in a rat model of early-life adversity.

Gastric hypersensitivity is a major pathophysiological feature of functional dyspepsia (FD). Recent clinical studies have shown that a large number of patients with FD present with gastroduodenal microinflammation, which may be involved in the pathophysiology of FD. However, no animal model reflecting this clinical characteristic has been established. The underlying mechanism between microinflammation and FD remains unknown. In this study, using a maternal separation (MS)-induced FD model, we aimed to reproduce the gastroduodenal microinflammation and reveal the interaction between gastroduodenal microinflammation and gastric hypersensitivity. The MS model was established by separating newborn Sprague-Dawley rats for 2 h a day from postnatal day 1 to day 10. At 7-8 wk of age, electromyography was used to determine the visceromotor response to gastric distention (GD) and immunohistochemistry was performed to detect distension-associated neuronal activation as well as immunohistological changes. Our results demonstrated that MS-induced FD rats underwent gastric hypersensitivity with GD at 60 and 80 mmHg, which are related to increased p-ERK1/2 expression in the dorsal horn of T9-T10 spinal cords. Eosinophils, but not mast cells, were significantly increased in the gastroduodenal tract, and the coexpression rate of CD11b and major basic protein significantly increased in MS rats. Treatment with dexamethasone reversed gastric hypersensitivity in MS-induced FD rats by inhibiting eosinophil infiltration. These findings indicated that neonatal MS stress induces eosinophil-associated gastroduodenal microinflammation and gastric hypersensitivity in adulthood in rats. Microinflammation contributes to gastric hypersensitivity; therefore, anti-inflammatory therapy may be effective in treating patients with FD with gastroduodenal microinflammation.NEW & NOTEWORTHY We showed for the first time that neonatal MS stress-induced FD rats undergo gastroduodenal eosinophil-associated microinflammation in adulthood. Suppression of microinflammation attenuated gastric hypersensitivity in MS rats. These findings established a functional link between microinflammation and gastric hypersensitivity, which may provide a potential clue for the clinical treatment of FD.

Effect of occupation-based interventions in patients with haematopoietic malignancies undergoing chemotherapy: A pilot randomised controlled trial.

BACKGROUND/OBJECTIVE: Chemotherapy for cancer negatively affects activities of daily living and quality of life. This study aimed to validate and compare the efficacy of two different interventions in patients with haematopoietic malignancies undergoing chemotherapy: (1) occupation-based interventions, designed using the Aid for Decision-making in Occupation Choice (ADOC) (an iPAD application) and (2) impairment-based interventions. ADOC helps promote decision-making during activities and participation in occupation-based goal setting. The impairment-based intervention group served as the comparison group and underwent impairment-based interventions focusing on dysfunction. METHODS: In this single-blinded pilot randomised controlled trial, 19 participants received an occupation-based intervention (n = 9) or an impairment-based intervention (n = 10). The treatment period comprised two sessions. Recruitment, compliance and outcome completion rates were calculated for the study. Effect sizes were examined for outcomes regarding physical performance, instrumental activities of daily living and quality of life as evaluated by a blinded assessor. RESULTS: In this study, 24.8% (28/113) of the eligible patients with haematopoietic malignancies were enrolled, and 67.9% (19/28) of these were retained up to the post-assessment stage. Recruitment (25%) and compliance (68%) rates were satisfactory. The Functional Assessment of Cancer Therapy-General emotional well-being and total scores were significantly higher for the occupation-based intervention group than for the impairment-based intervention group (both p < 0.05; d = 0.54, d = 0.51, respectively). Other outcomes showed no significant differences. CONCLUSION: Occupation-based interventions designed using the ADOC application were useful for patients with haematopoietic malignancies.