Purpose
To compare the diagnostic performance of ring-type dedicated breast PET (dbPET), whole-body PET (WBPET), and DCE-MRI for predicting pathological complete response (pCR) after neoadjuvant ...chemotherapy (NAC).
Methods
This prospective study included 29 women with histologically proven breast cancer on needle biopsy between July 2016 and July 2019 (age: mean 55 years; range 35–78). Patients underwent WBPET followed by ring-type dbPET and DCE-MRI pre- and post-NAC for preoperative evaluation. pCR was defined as an invasive tumor that disappeared in the breast. Standardized uptake values corrected for lean body mass (SULpeak) were calculated for dbPET and WBPET scans. Maximum tumor length was measured in DCE-MRI images.
Reduction rates were calculated for quantitative evaluation. Two radiologists independently evaluated the qualitative findings. Reduction rates and qualitative findings were compared between the pCR (
n
= 7) and non-pCR (
n
= 22) groups for each modality. Differences in quantitative and qualitative data between the two groups were analyzed statistically.
Results
Significant differences were observed in the reduction rates of dbPET and DCE-MRI (
P
= 0.01 and 0.03, respectively) between the two groups. Univariate and multiple logistic regression analyses revealed that SULpeak reduction rates in WBPET and dbPET (
P
= 0.02 and
P
= 0.01, respectively) and in dbPET (odds ratio, 16.00; 95% CI 1.57–162.10;
P
= 0.01) were significant indicators associated with pCR, respectively. No between-group differences were observed in qualitative findings in the three modalities.
Conclusion
SULpeak reduction rate of dbPET > 82% was an independent indicator associated with pCR after NAC in breast cancer.
Reduction of elastin in the skin causes various skin diseases as well as wrinkles and sagging with aging. Sialidase is a hydrolase that cleaves a sialic acid residue from sialoglycoconjugate. ...Cleavage of sialic acid from microfibrils by the sialidase isozyme Neu1 facilitates elastic fiber assembly. In the present study, we showed that a lower layer of the dermis and muscle showed relatively intense sialidase activity. The sialidase activity in the skin decreased with aging. Choline and geranate (CAGE), one of the ionic liquids, can deliver the sialidase subcutaneously while maintaining the enzymatic activity. The elastin level in the dermis was increased by applying sialidase from Arthrobacter ureafaciens (AUSA) with CAGE on the skin for 5 days in rats and senescence-accelerated mice prone 1 and 8. Sialidase activity in the dermis was considered to be mainly due to Neu2 based on the expression level of sialidase isozyme mRNA. Transdermal administration of Neu2 with CAGE also increased the level of elastin in the dermis. Therefore, not only Neu1 but also Neu2 would be involved in elastic fiber assembly. Transdermal administration of sialidase is expected to be useful for improvement of wrinkles and skin disorders due to the loss of elastic fibers.
Osimertinib is a standard of care therapy for previously untreated epidermal growth factor receptor mutation-positive non-small cell lung cancer. However, limited data exist regarding the efficacy ...and safety of osimertinib as a first-line therapy for elderly patients aged 75 years or older. To assess the potential clinical benefits of osimertinib in this population, this retrospective multi-institutional observational study included 132 patients with non-small cell lung cancer (age ≥ 75 years), who received osimertinib as first-line treatment. The proportion of patients with 1-year progression-free survival was 65.8% (95% confidence interval 57.1-73.5). The median progression-free survival was 19.4 (95% confidence interval 15.9-23.9) months. The median overall survival was not reached (95% confidence interval 24.6-not reached). The frequency of pneumonitis was 17.4%, with a grade 3 or higher rate of 9.1%. More than two-thirds of treatment discontinuations due to pneumonitis occurred within 3 months of starting osimertinib, and the prognosis of patients with pneumonitis was unsatisfactory. Osimertinib is one of the effective first-line therapeutic options for patients aged 75 years or older; however, special caution should be exercised due to the potential development of pneumonitis.
Immunotherapies targeting interleukin (IL)‐17 greatly improve plaque psoriasis. Most previous studies on IL‐17 focused on the T‐helper (Th)17 immune response, but investigation of the effects of ...IL‐17A on psoriatic epidermal structure are limited. Using an in vitro 3‐D human epidermis model, we investigated the effects of IL‐17A and IL‐17C on morphological changes and gene expression. IL‐17A directly suppressed the formation of the granular layer, whereas IL‐17C did not. IL‐17A significantly downregulated the gene expression of profilaggrin (FLG), which is a major component of keratohyalin granules in the granular layer. Global gene expression analysis of this 3‐D epidermis model showed that both IL‐17A and IL‐17C upregulated S100A7A and type 1 interferon‐related genes including MX1, IFI44L, XAF1 and IFIT1. However, only IL‐17A directly downregulated keratinocyte differentiation‐related and cornified envelope‐related genes including FLG, LOR, C1ORF68, LCE1E, LCE1B, KRT10, CST6 and RPTN. In conclusion, IL‐17A, a systemic inflammatory cytokine, affected keratinization in our 3‐D epidermis model. In contrast, IL‐17C, a locally produced cytokine, did not have strong effects on keratinization. Targeting IL‐17A does not only reduce inflammation but it may also directly affect epidermal differentiation in psoriasis.
Sialidase cleaves sialic acid residues from a sialoglycoconjugate: oligosaccharides, glycolipids and glycoproteins that contain sialic acid. Histochemical imaging of the mouse pancreas using a ...benzothiazolylphenol-based sialic acid derivative (BTP3-Neu5Ac), a highly sensitive histochemical imaging probe used to assess sialidase activity, showed that pancreatic islets have intense sialidase activity. The sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA) remarkably enhances glutamate release from hippocampal neurons. Since there are many similar processes between synaptic vesicle exocytosis and secretory granule exocytosis, we investigated the effect of DANA on insulin release from β-cells. Insulin release was induced in INS-1D cells by treatment with 8.3 mM glucose, and the release was enhanced by treatment with DANA. In a mouse intraperitoneal glucose tolerance test, the increase in serum insulin levels was enhanced by intravenous injection with DANA. However, under fasting conditions, insulin release was not enhanced by treatment with DANA. Calcium oscillations induced by 8.3 mM glucose treatment of INS-1D cells were not affected by DANA. Blood insulin levels in sialidase isozyme Neu3-deficient mice were significantly higher than those in WT mice under ad libitum feeding conditions, but the levels were not different under fasting conditions. These results indicate that DANA is a glucose-dependent potentiator of insulin secretion. The sialidase inhibitor may be useful for anti-diabetic treatment with a low risk of hypoglycemia.
EML4-ALK is a lung cancer oncogene, and ALK inhibitors show marked therapeutic efficacy for tumors harboring this fusion gene. It remains unsettled, however, how the fusion gene should be detected in ...specimens other than formalin-fixed, paraffin-embedded tissue. We here tested whether reverse transcription PCR (RT-PCR)-based detection of EML4-ALK is a sensitive and reliable approach.
We developed a multiplex RT-PCR system to capture ALK fusion transcripts and applied this technique to our prospective, nationwide cohort of non-small cell lung cancer (NSCLC) in Japan.
During February to December 2009, we collected 916 specimens from 853 patients, quality filtering of which yielded 808 specimens of primary NSCLC from 754 individuals. Screening for EML4-ALK and KIF5B-ALK with our RT-PCR system identified EML4-ALK transcripts in 36 samples (4.46%) from 32 individuals (4.24%). The RT-PCR products were detected in specimens including bronchial washing fluid (n = 11), tumor biopsy (n = 8), resected tumor (n = 7), pleural effusion (n = 5), sputum (n = 4), and metastatic lymph node (n = 1). The results of RT-PCR were concordant with those of sensitive immunohistochemistry with ALK antibodies.
Multiplex RT-PCR was confirmed to be a reliable technique for detection of ALK fusion transcripts. We propose that diagnostic tools for EML4-ALK should be selected in a manner dependent on the available specimen types. FISH and sensitive immunohistochemistry should be applied to formalin-fixed, paraffin-embedded tissue, but multiplex RT-PCR is appropriate for other specimen types.
In a subgroup of Japanese patients in the ARCHER 1050 randomized phase 3 trial, we evaluated the efficacy and safety and determined the effects of dose modifications on adverse events (AE) and ...therapy management of first‐line oral dacomitinib 45 mg compared with oral gefitinib 250 mg, each once daily in 28‐d cycles, in patients with EGFR‐activating mutation–positive (EGFR‐positive; exon 19 deletion or exon 21 L858R substitution mutations) advanced non‐small cell lung cancer (NSCLC). The primary endpoint was progression‐free survival (PFS; RECIST, version 1.1, by blinded independent review). In 81 Japanese patients (40 dacomitinib, 41 gefitinib), PFS was longer with dacomitinib compared with gefitinib (hazard ratio HR, 0.544 95% confidence interval {CI}, 0.307‐0.961; 2‐sided P = .0327; median 18.2 for dacomitinib 95% CI, 11.0‐31.3 mo, 9.3 95% CI, 7.4‐14.7 mo for gefitinib). The most common Grade 3 AEs were dermatitis acneiform with dacomitinib (27.5%) and increased alanine aminotransferase with gefitinib (12.2%). A higher proportion of patients receiving dacomitinib (85.0%) compared with gefitinib (24.4%) had AEs leading to dose reduction. Incidence and severity of diarrhea, dermatitis acneiform, stomatitis and paronychia were generally reduced after dacomitinib dose reductions and dacomitinib treatment duration was generally longer in patients with a dose reduction in comparison with those without a dose reduction. Our results confirmed the efficacy and safety of first‐line dacomitinib in Japanese patients with EGFR‐positive advanced NSCLC.
We evaluated the efficacy and safety of first‐line dacomitinib compared with gefitinib in a subgroup of Japanese patients with EGFR‐activating mutation–positive advanced non‐small cell lung cancer who were enrolled in the ARCHER 1050 randomized phase 3 trial. Results for the primary efficacy endpoint in the Japanese patients (n = 81) were consistent with the results in the overall ARCHER 1050 population; there was a clinically meaningful prolongation of median PFS by 8.9 mo favoring dacomitinib. The safety profile of dacomitinib was manageable by dose reduction or temporary dose interruption and no new safety signals were observed in the population of Japanese patients compared with the overall ARCHER 1050 study population.
Women with estrogen deficiency are at the risk of suffering from neurological symptoms such as memory impairment. In the present study, we investigated the effect of garlic, Allium sativum L. ...(Asparagales: Amaryllidaceae), treated with subcritical water on memory impairment in ovariectomized (OVX) rats. OVX rats were administered garlic powder for 84 d. Hippocampus-dependent spatial memory was assessed using the Morris water maze test. Escape latency of the OVX rats increased compared with that of sham-operated rats. The prolonged escape latency of the OVX rats decreased to the level of that of sham-operated rats upon the administration of garlic powder (0.5% in feed). The weights of the body, uterus, and brain were not affected by the garlic powder administration. These results suggest that garlic powder treated with subcritical water mitigates memory impairment in OVX rats.
Background
A subset analysis of the CA031 trial showed significant improvement in the overall response rate after administration of carboplatin plus weekly albumin-bound paclitaxel compared to ...carboplatin plus paclitaxel for squamous cell carcinoma of the lung (SQ). We conducted this phase II study to compare carboplatin plus weekly albumin-bound paclitaxel (CnP) to cisplatin plus gemcitabine (CG), a standard regimen for SQ.
Methods
Chemotherapy-naïve patients with SQ were randomly assigned to receive cisplatin (80 mg/m
2
) on day 1 plus gemcitabine (1000 mg/m
2
) on days 1 and 8 every 3 weeks or carboplatin (area under the curve: 6 mg/mL/min) on day 1 plus nab-paclitaxel (75 mg/m
2
) on days 1, 8, and 15 every 3 weeks. The primary endpoint was overall response rate. The secondary endpoints were progression-free survival, overall survival, disease control rate, and toxicity.
Results
Between June 2013 and October 2018, 71 patients were enrolled and assigned to either the CG arm (
n
= 35) or the CnP arm (
n
= 36) of the study. The overall response rate was 43% 95% confidence interval (CI) 27.3–58.5 in the CG arm and 47% (95% CI 31.7–62.7) in the CnP arm. Although drug combination efficacies did not differ, there were differences in toxicity: hematologic toxicities (leukopenia, neutropenia, and thrombocytopenia) were found mostly in the CG arm, whereas anemia and sensory neuropathy were more common in the CnP arm.
Conclusions
CnP had similar response as CG despite being a carboplatin-based regimen and toxicities differed between arms. Regarding ORR, CnP was comparable to CG for SQ.
Background
Postoperative nausea and vomiting (PONV) following atrial fibrillation (AF) ablation can cause considerable distress.
Aim
Continuous intravenous propofol sedation with adaptive ...servo‐ventilation (ASV) with or without an analgesic, pentazocine, during AF ablation was studied in 272 consecutive patients with paroxysmal, persistent, and long‐standing persistent AF. The study objectives were to determine the incidence of PONV after AF ablation and to assess the predictive value of factors for PONV using the area under the receiver operating characteristic curve (AUC).
Results
The present sedation maneuver was successfully accomplished with a low incidence of hypotension and without discontinuation of ablation or switching to general anesthesia, while maintaining an acceptable procedural time (102 ± 32 min). The incidence of PONV was 5.5% (15/272). Nausea occurred in nine patients after an average of 4.6 ± 3.5 h (range: 2–12 h) postablation, and vomiting with nausea occurred in six patients after an average of 4.5 ± 3.1 h (range: 1–9 h) postablation. The postablation interval did not differ significantly between the occurrence of nausea and nausea accompanied by vomiting. AUCs based on various factors, including the Apfel score, ranged from 0.55 to 0.67, indicating low accuracy in predicting PONV occurrence.
Conclusions
The incidence of PONV after propofol sedation with ASV was the lowest (5.5%) reported to date. Scoring systems, which included the Apfel score, were ineffective in predicting PONV. The low PONV incidence in addition to the efficacy of propofol sedation with ASV revealed the adequacy of this regimen for AF ablation.
The present study is the first to show that the incidence of nausea and/or vomiting was low (5.5%) after deep sedation with propofol combined with adaptive‐servo ventilation for atrial fibrillation ablation. The scoring system, which included the Apfel score, was not effective in predicting PONV.
PDF
