Endoscopic placement of covered versus uncovered self-expandable metal stents for palliation of malignant gastric outlet obstruction.

OBJECTIVE: Stenting is an established endoscopic therapy for malignant gastric outlet obstruction (mGOO). The choice of stent (covered vs uncovered) has been examined in prior randomised studies without clear results. DESIGN: In a multicentre randomised prospective study, we compared covered (CSEMS) with uncovered self-expandable metal stents (UCSEMS) in patients with mGOO; main outcomes were stent dysfunction and patient survival, with subgroup analyses of patients with extrinsic and intrinsic tumours. RESULTS: Overall survival was poor with no difference between groups (probability at 3 months 49.7% for covered vs 48.4% for uncovered stents; log-rank for overall survival p=0.26). Within that setting of short survival, the proportion of stent dysfunction was significantly higher for uncovered stents (35.2% vs 23.4%, p=0.01) with significantly shorter time to stent dysfunction. This was mainly relevant for patients with extrinsic tumours (stent dysfunction rates for uncovered stents 35.6% vs 17.5%, p<0.01). Subgrouping was also relevant with respect to tumour ingrowth (lower with covered stents for intrinsic tumours; 1.6% vs 27.7%, p<0.01) and stent migration (higher with covered stents for extrinsic tumours: 15.3% vs 2.5%, p<0.01). CONCLUSIONS: Due to poor patient survival, minor differences between covered and uncovered stents may be less relevant even if statistically significant; however, subgroup analysis would suggest to use covered stents for intrinsic and uncovered stents for extrinsic malignancies.

Radiation-induced skin ulcer and rib fractures following percutaneous coronary intervention (PCI): A case of right back skin ulcer and adjacent rib fractures after single PCI.

We experienced a 75-year-old male patient with a refractory and severely painful skin ulcer on the right back. He had suffered from ischemic heart disease and undergone percutaneous coronary intervention 5 months prior to the consultation with us. The characteristic clinical appearance, location of the lesion and his past medical history led us to the diagnosis of radiation-induced skin ulcer. Magnetic resonance imaging, computed tomography as well as bone scintigraphy showed fractures of the right back rib adjacent to the ulcer, which was thought to be attributable to bone damage due to X-ray radiation and/or persistent secondary inflammation of the chronic ulcer. In the published work, there are no other reports of bone fractures associated with radiation dermatitis after coronary interventional radiology.

[Combined therapy of lapatinib and capecitabine effective against local recurrence of breast cancer].

A 67-year-old woman after mastectomy was afflicted with local recurrence of left breast cancer during adjuvant trastuzumab therapy. Oral administration of lapatinib and capecitabine served to distinguish the recurrent tumor and also reduce the patient's distressing symptoms. This combined anti-cancer therapy may be available for patients with breast cancer for whom trastuzumab therapy was not adequately effective.

[Fungal immunology in the skin; immune response to dermatophytes].

Infections with dermatophytes are generally confined to the keratinized stratum corneum. This superficial site of infection may protect the infecting dermatophytes from direct contact with some of the effector cells of the immune system; therefore, the immune system has developed a special subsystem in the skin to eliminate them.The innate immunity and acquired immunity (delayed-type hypersensitivity response) are both required for cutaneous immune surveillance against dermatophytes in the skin.Epidermal keratinocytes not only have an important structural role in forming a physical barrier to dermatophytes but also are important functionally in mediating cutaneous immune reactions. These cells can secrete proinflammatory cytokines, chemokines, and anti-microbial peptides in response to dermatophytes. The T cell-mediated delayed-type hypersensitivity response to dermatophyte antigens may play a central role in both pathogenesis of the typical skin lesions and an acquired, relative resistance that affords partial immunity to the host. However, the exact form of effector T cell immunity and the cellular and molecular mechanisms which eliminate dermatophytes from the skin are poorly understood. The literature on the immunology against dermatophyte infection is reviewed in this paper.

Clinical efficacy of basic fibroblast growth factor (bFGF) for diabetic ulcer.

Basic fibroblast growth factor (bFGF) has been shown to promote wound healing. The present trial evaluated the clinical efficacy of bFGF for diabetic ulcer, a type of refractory skin ulcer, and the dose-response relationship. This was designed as a randomized, double-blind, dose-ranging, placebo-controlled trial. A total of 150 patients with non-ischaemic diabetic ulcers measuring 900 mm2 or less were randomized into a placebo group (n = 51), a 0.001% bFGF group (n = 49) and a 0.01% bFGF group (n = 50), and 148 of these patients received treatment for 8 weeks or less. The efficacy evaluation was carried out on 139 patients who met the protocol in this trial. The primary outcome was the percentage of patients showing 75% or greater reductions in the area of ulcer. The area of ulcer decreased by 75% or more in 57.5% (27/47), 72.3% (34/47), and 82.2% (37/45) in the placebo, 0.001% bFGF and 0.01% bFGF groups, respectively, and differences were significant between the 0.01% bFGF and placebo groups (p = 0.025). The cure rate was 46.8% (22/47), 57.4% (27/47), and 66.7% (30/45) in the placebo, 0.001% bFGF and 0.01% bFGF groups, respectively. The findings obtained in this trial showed wound healing accelerating effects of bFGF on diabetic ulcers.

Differential induction of Th1-prone immunity by human dendritic cells activated with Sporothrix schenckii of cutaneous and visceral origins to determine their different virulence.

Sporotrichosis is caused by a thermo-dependent dimorphic fungus, Sporothrix schenckii. The major clinical manifestations occur in the skin; however, cases of visceral manifestations have also been increasingly reported with some being observed in immune compromised patients. Different virulence of individual S. schenckii strain as well as immune status of the host could contribute to form such different clinical manifestations. Thus, the purpose of the study was to investigate whether different virulence of individual S. schenckii could be a factor for such clinical difference. We investigated the interactions between human monocyte-derived dendritic cells (MoDCs) and S. schenckii, assessed by (i) morphological features, (ii) surface marker expressions, cytokine productions, (iii) signaling pathways and (iv) allostimulatory activity of the activated MoDCs. Immature MoDCs, obtained from peripheral blood monocytes supplemented with granulocyte macrophage colony-stimulating factor and IL-4, were stimulated with S. schenckii strains of both yeasts and conidia forms of different origins (cutaneous isolates: KMU4649, IFM5906 and IFM46010; visceral isolates: KMU4648, IFM41598 and ATCC26331) to be used for various assays. Through the analysis, we found that the cutaneous S. shenckii of cutaneous origins were more potent to activate MoDCs to induce strong T(h)1 response, as evidenced by abundant IFN-gamma production, while the S. shenckii of visceral origins induced only minimal dendritic cell activation and T(h)1 induction. The p38 mitogen-activated protein kinase and c-Jun N-terminal kinase signaling pathways appeared to be associated with the differential activation of the MoDCs by S. schenckii of cutaneous and the visceral origins. Overall, we concluded that the differential activation of MoDCs by S. schenckii of cutaneous and visceral origins to induce T(h)1 response, other than immune status or the host, may be a factor for their different clinical manifestations.

Expression of p16 and hTERT protein is associated with the presence of high-risk human papillomavirus in Bowenoid papulosis.

BACKGROUND: High-risk human papillomavirus (hrHPV) type E6 and E7 oncoproteins contribute to oncogenesis in multiple ways by modulating the activities of host components in cell-cycle regulation including the expression of p16 protein (p16) and human telomerase reverse transcriptase (hTERT). The expression of p16 and hTERT protein in Bowenoid papulosis (BP) has not been studied. METHODS: Biopsy samples of BP from 26 patients were subjected to in situ hybridization for various HPV strains and immunohistochemical staining for p16 and hTERT. RESULTS: Among the 26 biopsy specimens, in situ hybridization using DNA probes for HPV 16/18 revealed positivity in 18 specimens (69.2%), one of which also showed positivity with the probes for HPV 6/11. HPV 31/33/35 was found in three specimens (11.5%). Two specimens (7.7%) were positive for unclassified HPV. Twenty-one BP specimens that were infected with hrHPV were positive for p16 and/or hTERT. Moderate or strong and diffuse immunostaining was observed for p16 in 15 hrHPV-infected specimens and for hTERT in 16 hrHPV-infected specimens. The expression of p16 or hTERT was each significantly associated with the presence of hrHPV. CONCLUSIONS: hrHPVs were involved in inducing p16 and hTERT overexpression in BP. Moreover, our results suggested that immunohistochemical p16 and hTERT expression might be a useful marker of hrHPV infection in BP.

beta-Catenin mutation and its nuclear localization are confirmed to be frequent causes of Wnt signaling pathway activation in pilomatricomas.

BACKGROUND: beta-Catenin has been shown to play an important role in the formation of hair follicle-related tumors, including pilomatricomas. Several investigators have shown that beta-catenin gene mutation is observed in pilomatricomas. However, the relationship between the pattern of beta-catenin localization in the cell and beta-catenin gene mutation is still controversial. OBJECTIVES: This work was performed to determine the frequency of beta-catenin nuclear localization in pilomatricoma, the relationship between the pattern of beta-catenin localization and beta-catenin mutation, and the involvement of APC mutation. METHODS: Typical 32 pilomatricomas were examined for beta-catenin expression by immunostaining. Genomic DNA was extracted, amplified and sequenced from 23 pilomaticomas with nuclear beta-catenin staining and 4 pilomaticomas without nuclear beta-catenin staining. Mutations of beta-catenin gene were confirmed by subcloning assay and restriction endonuclease assay. RESULTS: Using immunostaining, we found that 81% (26/32) of pilomatricomas displayed nuclear beta-catenin staining in basophilic cells. Sequence analysis revealed that 61% (14/23) contained mutations in exon 3 of beta-catenin. However, no mutations were detected in 4 pilomaticomas without beta-catenin nuclear staining. Detected mutations were adjacent to or abolished well-known regulatory phosphorylation sites of beta-catenin. APC gene mutations were not detected in 27 pilomatricomas with/without beta-catenin nuclear staining. CONCLUSIONS: These results confirmed that beta-catenin mutation and its nuclear localization are frequent causes of Wnt signaling pathway activation and suggested that beta-catenin activation mutations contribute to tumorigenesis of pilomatricomas.