Phase II trial of capecitabine plus oxaliplatin (CAPOX) as perioperative therapy for locally advanced rectal cancer

Abstract

Purpose

The standard strategy for locally advanced lower rectal cancer is chemoradiotherapy followed by total mesorectal excision (TME) in Western countries and TME followed by adjuvant chemotherapy without preoperative treatment in Japan.

Methods

This phase II trial evaluated the efficacy of a preoperative CAPOX chemotherapy regimen without radiation therapy for patients with locally advanced rectal cancer. The primary endpoint was 2-year disease-free survival.

Results

The trial enrolled 45 patients from 9 institutions between 2012 and 2014. The mean age was 63.5 (29–74) years; 31 patients were male. Most patients (n = 41) received preoperative chemotherapy (CTx), and the preoperative CTx completion rate was 95.2%. R0 resection after CTx was performed in 41 patients. The pathological complete response rate was 7.3% (3/41). After surgery, 35 patients (85.3%) received adjuvant CTx, and 22 of 35 completed the protocol treatment. The follow-up period ranged from 0.71 to 4.68 years (median 2.86 years). There was recurrence in 13 of 40 patients who underwent R0 resection, and the 2-year disease-free survival rate and overall survival rate were 71.6 and 92.7%, respectively.

Conclusions

Here we report the completion rates for neoadjuvant CTx and adjuvant CTx, the pathological complete response rate, and the mid-term prognosis. The results indicate that CAPOX followed by TME may be a safe treatment strategy for locally advanced rectal cancer.

https://ift.tt/2AFgbhU

Intranasal endoscopic prelacrimal recess approach for maxillary sinus inverted papilloma

Abstract

Purpose

This study aims to determine the indications and effectiveness of transnasal endoscopic prelacrimal recess approach (PLRA) in patients with maxillary sinus inverted papilloma (IP).

Methods

We retrospectively analyzed 71 patients treated in our institution for maxillary sinus IP between August 2008 and April 2015. 20 patients underwent endoscopic surgery via PLRA. All the patients who had postoperative follow-up for 3 years were enrolled. Demographic data, surgical technique, location of IP attachment, intra- and postoperative complications, follow-up duration and recurrence were recorded.

Results

The outpatient follow-up period was 3–10 years after surgery. Recurrence of IP was seen in 6 (8.5%) of 71 patients, including 1 patient in the PLRA group. The recurrence rate was 5% in the PLRA group. Six of 71 patients experienced postoperative complications, but none was observed in the PLRA group.

Conclusion

Transnasal endoscopic PLRA is a minimally invasive, safe and effective method for maxillary sinus IP. The indication for PLRA is tumor pedicle located on the antero-inferior or infero-lateral wall or at multiple attachment sites of the maxillary sinus.

https://ift.tt/2OJ0sBm

Association between CTLA-4 + 49A > G and – 318C > T single-nucleotide polymorphisms and susceptibility to thyroid neoplasm

Abstract

Purpose

Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4 or CD152) is among the immune checkpoint molecules and its abnormal expression in cancer predisposed individuals might make the person more susceptible to tumor initiation and progression. Considering the implication of single-nucleotide polymorphisms (SNPs) in CTLA-4 gene expression and probably protein function, one can assume the involvement of these SNPs in neoplastic diseases. rs5742909 ( − 318C > T) and rs231775 ( + 49 A > G) are among the most commonly studied SNPs and have been considered as genetic factors related to thyroid diseases. In this cross-sectional study, we aimed to elucidate the association between these SNPs and susceptibility to various types of thyroid cancers.

Methods

We investigated the genetic polymorphisms of − 318C > T and + 49 A > G in the CTLA-4 gene by means of ARMS-PCR and RFLP-PCR, respectively, in 167 patients with thyroid carcinomas (papillary, follicular, and anaplastic). The results were then compared with a group of 100 age-sex matched healthy individuals.

Results

A statistically significant association was observed between the presence of G allele in + 49 A > G locus and thyroid carcinoma, when comparing cases and controls (OR = 2.10; 95% CI = 1.35–3.28; P = 0.001) and the frequency of heterozygotes (AG) was higher than homozygotes for allele A (AA), in patients with and papillary thyroid carcinoma (PTC). Regarding Hashimoto's thyroiditis, the frequencies of A allele and AA genotype in PTC patients were higher than Hashimoto patients with no history of cancer (OR = 4.67, 95% CI = 2.70–8.08, P < 0.0001; and, OR = 4.68, 95% CI = 1.84–11.91, P = 0.0012; respectively). However; we observed no difference among allele/genotype frequencies in regards to locus – 318C > T.

Conclusion

In this study, we observed that G allele in + 49 A > G and possibly lower expression of mutated CTLA-4 molecule, is associated with higher susceptibility to thyroid carcinoma. Although the G allele frequency was higher in thyroid cancer patients, when justified for the presence of lymphocytic thyroiditis, the presence of A allele seemed to increase the odds for PTC in patients with Hashimoto's disease.

https://ift.tt/2MezQX9

Increased antitumor activities of glypican-3-specific chimeric antigen receptor-modified T cells by coexpression of a soluble PD1–CH3 fusion protein

Abstract

Our recent clinical study demonstrated that glypican-3 (GPC3)-specific chimeric antigen receptor-modified T (CAR-T) cells are a promising treatment for hepatocellular carcinoma (HCC). However, the interaction of programmed cell death 1 (PD-1) and PD-L1-mediated T-cell inhibition is involved in immune evasion in a wide range of solid tumors, including HCC. To overcome this problem, we introduced a fusion protein composed of a PD-1 extracellular domain and CH3 from IgG4 into GPC3-specific CAR-T cells (GPC3-28Z) to block the PD-1/PD-L1 pathway. GPC3-specific CAR-T cells carrying the PD-1–CH3 fusion protein (sPD1) specifically recognized and lysed GPC3-positive HCC cells. The proliferation capacity of GPC3-28Z-sPD1 T cells after weekly stimulation with target cells was much higher than that of control GPC3-28Z T cells. Additionally, the coexpression of sPD1 could protect CAR-T cells from exhaustion when incubated with target cells, as phosphorylated AKT and Bcl-xL expression levels were higher in GPC3-28Z-sPD1 T cells than in GPC3-28Z cells. Importantly, in two HCC tumor xenograft models, GPC3-28Z-sPD1 T cells displayed a significantly higher tumor suppression capacity than GPC3-28Z T cells. In addition, an increased number of CD3⁺ T cells in the circulation and tumors and increased granzyme B levels and decreased Ki67 expression levels in the tumors were observed in the mice treated with GPC3-28Z-sPD1 T cells. Together, these data indicated that GPC3-specific CAR-T cells carrying sPD1 show promise as a treatment for patients with HCC.

https://ift.tt/2OIFH92

Association between CTLA-4 + 49A > G and – 318C > T single-nucleotide polymorphisms and susceptibility to thyroid neoplasm

Abstract

Purpose

Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4 or CD152) is among the immune checkpoint molecules and its abnormal expression in cancer predisposed individuals might make the person more susceptible to tumor initiation and progression. Considering the implication of single-nucleotide polymorphisms (SNPs) in CTLA-4 gene expression and probably protein function, one can assume the involvement of these SNPs in neoplastic diseases. rs5742909 ( − 318C > T) and rs231775 ( + 49 A > G) are among the most commonly studied SNPs and have been considered as genetic factors related to thyroid diseases. In this cross-sectional study, we aimed to elucidate the association between these SNPs and susceptibility to various types of thyroid cancers.

Methods

We investigated the genetic polymorphisms of − 318C > T and + 49 A > G in the CTLA-4 gene by means of ARMS-PCR and RFLP-PCR, respectively, in 167 patients with thyroid carcinomas (papillary, follicular, and anaplastic). The results were then compared with a group of 100 age-sex matched healthy individuals.

Results

A statistically significant association was observed between the presence of G allele in + 49 A > G locus and thyroid carcinoma, when comparing cases and controls (OR = 2.10; 95% CI = 1.35–3.28; P = 0.001) and the frequency of heterozygotes (AG) was higher than homozygotes for allele A (AA), in patients with and papillary thyroid carcinoma (PTC). Regarding Hashimoto's thyroiditis, the frequencies of A allele and AA genotype in PTC patients were higher than Hashimoto patients with no history of cancer (OR = 4.67, 95% CI = 2.70–8.08, P < 0.0001; and, OR = 4.68, 95% CI = 1.84–11.91, P = 0.0012; respectively). However; we observed no difference among allele/genotype frequencies in regards to locus – 318C > T.

Conclusion

In this study, we observed that G allele in + 49 A > G and possibly lower expression of mutated CTLA-4 molecule, is associated with higher susceptibility to thyroid carcinoma. Although the G allele frequency was higher in thyroid cancer patients, when justified for the presence of lymphocytic thyroiditis, the presence of A allele seemed to increase the odds for PTC in patients with Hashimoto's disease.

https://ift.tt/2MezQX9

Plaque psoriasis following Kawasaki disease and varicella

We describe the case of a 15-month-old boy with Kawasaki disease who developed varicella 7 days after the beginning of the disease and diffuse plaque psoriasis after 43 days. Associations between Kawasaki disease and psoriasis, between Kawasaki disease and varicella and between varicella and psoriasis have all been reported in the literature. The triple association of Kawasaki disease, varicella and psoriasis is very rare. Neither the double nor the triple associations are well known among a diverse group of practitioners.

https://ift.tt/2MkKRGn

A differential diagnosis for annular lesions: contact dermatitis to transdermal rivastigmine patches

Description

During an appointment for an unrelated condition at a dermatology clinic, a 75-year-old man was noted to have a number of annular lesions on his trunk. The patient mentioned that he had been prescribed transdermal rivastigmine patches (Alzest 4.6mg/24h) for memory impairment 4 months previously. These were applied and left on for 24 hours before being replaced. He noticed that each patch left a red, pruritic area.

The patient was otherwise well, his only medication being an antihypertensive. He did not have any drug allergies or sensitivity to plasters.

On examination, there were multiple annular lesions scattered over his trunk with a predilection for the flanks (figure 1). These demonstrated an evolution of clinical features; more recent lesions were erythematous, inflamed plaques (figure 1A) which progressed into brown, postinflammatory patches (figure 1B) which gradually faded. All the lesions were well demarcated, circular and approximately 40 mm in diameter.

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https://ift.tt/2LZN1i2