Adjuvant Chemotherapy in Patients with Node-Negative Non-Small Cell Lung Cancer with Satellite Pulmonary Nodules in the Same Lobe.

BACKGROUND: According to the eighth TNM (tumor-node-metastasis) staging system, the presence of separate tumor nodules in the same lobe is designated as a T3 descriptor. However, it remains unclear whether adjuvant chemotherapy confers survival advantages in this setting. METHODS: We retrospectively identified 142 pathologic T3N0M0 patients with additional pulmonary nodules in the same lobe from a single-institutional database from 2004 to 2019. The main outcomes were overall survival and recurrence-free survival. Multivariable Cox regression was used to identify the benefit of adjuvant chemotherapy while adjusting for other variables. RESULTS: Sixty-one patients received adjuvant chemotherapy (adjuvant group) and 81 patients did not receive adjuvant therapy after surgery (surgery-only group). There were no demonstrable differences between the 2 groups regarding hospital mortality and postoperative complications, indicating that treatment selection had not significantly occurred. However, the use of adjuvant chemotherapy was associated with improved 5-year overall survival (70% vs. 59%, p=0.006) and disease-free survival (60% vs. 46%, p=0.040). A multivariable Cox model demonstrated that adjuvant chemotherapy was associated with a survival advantage (adjusted hazard ratio, 0.54; p<0.001). In exploratory analyses of subgroups, the effect of adjuvant chemotherapy seemed to be insufficient in those with small main tumors (<4 cm). CONCLUSION: Adjuvant chemotherapy was associated with better survival in T3 cancers with an additional tumor nodule in the same lobe. However, the role of adjuvant chemotherapy in patient subgroups with small tumors or those without risk factors should be determined via large studies.

Treatment of Refractory Chylous Ascites with an Innovative Peritoneovenous Shunt: Temporary Usage of a Continuous Renal Replacement System: A Case Report.

Esophagectomy and esophageal reconstruction are commonly chosen as surgical options for esophageal cancer. However, prolonged untreated chyle leakage is associated with a poor prognosis. We report the case of a patient with refractory chylous ascites. To limit the ongoing fluid loss, we utilized the chylous ascites as an additional fluid source in a renal replacement therapy system. A continuous renal replacement therapy (CRRT) drainage system was modified to drain both the chylous ascites and venous blood. The ascites drainage rate was determined empirically and regulated by a dial-flow extension set. The CRRT mode was set to continuous venovenous hemodiafiltration and maintained for 7 days. After the patient was weaned from CRRT, ascites did not reaccumulate, and the patient's general condition improved dramatically. No infections related to the system occurred. This procedure temporarily alleviates symptoms and provides more time for alternative treatment strategies.

Daurinol blocks breast and lung cancer metastasis and development by inhibition of focal adhesion kinase (FAK).

FAK overexpression has been reported in diverse primary and metastatic tumor tissues, supporting its pro-tumorigenic and pro-metastatic roles. Therefore, we have developed a neo-treatment strategy using daurinol to effectively treat cancer metastasis. Daurinol blocked cancer cell migration and invasion in vitro and exhibited anti-metastatic activity in an experimental metastasis model of breast and lung cancer. Daurinol selectively inhibited phosphorylation of FAK at Tyr925, Tyr576/577, and Tyr397 sites in a dose- and time-dependent manner. Daurinol effectively suppressed migration and invasion of MDA-MB-231 and A549 cancer cells. These data were associated with inhibition of expression and secretion of invasion factors, including matrix metalloproteinase (MMP) 2, MMP9, and urokinase plasminogen activator (uPA). Consistent with these in vitro results, daurinol (10 mg/kg; Oral gavage) effectively inhibited breast and lung cancer metastasis in a mouse model. In addition, daurinol showed strong suppressive activity of cell survival as revealed by colony formation assays. Analysis of cellular phenotypes revealed that inhibition of FAK phosphorylation in cancer cells limited colony formation, cell migration, and invasion, thereby reducing the cell proliferation rate. Furthermore, daurinol significantly reduced tumor development in 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)/benzo(a)pyrene (BaP)-treated A/J mice. Our results suggest that daurinol suppresses lung metastasis through inhibition of migration and survival via blockade of FAK activity.

Erratum: Neutrophilic Dermatosis Confined to the Lymphedematous Area.

[This corrects the article on p. 411 in vol. 26, PMID: 24966650.].

Two histopathological patterns of postinflammatory hyperpigmentation: epidermal and dermal.

BACKGROUND: Postinflammatory hyperpigmentation (PIH) commonly occurs, but the histopathological features are not well characterized. METHODS: A total of 21 PIH patients' medical charts were reviewed. Punch biopsies from lesional and perilesional normal skin were performed. Sections were stained with hematoxylin-eosin, Fontana-Masson, NKI/beteb, microphthalmia-associated transcription factor (MITF), CD68, c-kit, factor XIIIa, MMP-2 and MMP-9. RESULTS: Fontana-Masson-stained sections suggested two obvious PIH groups: epidermal (13 cases) and dermal (8 cases) pigmentation. The epidermal pigment group had increased epidermal basal pigmentation. The dermal pigment group had marked pigmentation within the upper dermis and decreased epidermal pigmentation. More intense perivascular lymphocytic infiltration was observed in the dermal pigment group. NKI/beteb levels were increased in lesional skin in both groups. The numbers of MITF+ melanocytes were not different between lesional and perilesional normal skin in either group. The expression of CD68 and c-kit was significantly higher in the dermis of lesional skin than in normal skin in the dermal pigment group. MMP-2 expression was upregulated in lesional skin in both groups. CONCLUSION: PIH patients can be classified into two histopathological groups: epidermal and dermal pigmentation. The dermal pigment group showed decreased levels of epidermal pigmentation. This study provides histopathological information that can improve the treatment of PIH.

Increased blood flow and vasculature in solar lentigo.

Solar lentigo (SL) is a hallmark of ultraviolet (UV)-induced photoaged skin and growing evidence implicates blood vessels in UV-associated pigmentation. In this study, we investigated whether the vasculatures are modified in SL. Twenty-five women with facial SL were enrolled and colorimetric and blood flow studies were performed. There was a significant increase in erythema which was associated with increased blood flow in the lesional skin compared with perilesional normal skin. Immunohistochemical studies with 24 facial SL biopsies consistently revealed a significant increase in vessel density accompanied by increased levels of vascular endothelial growth factor expression. CD68 immunoreactivity was significantly higher in lesional skin suggesting increased macrophage infiltration in SL. In conclusion, SL is characterized by increased blood flow and vasculature. These findings suggest the possible influence of the characteristics of vasculature on development of SL.

Clinical Experience of Interferon Alfa-2a Treatment for Refractory Uveitis in Behçet's Disease.

Behçet's disease (BD) involves multisystem vasculitis of unknown origin. Ocular manifestations of BD mostly include bilateral panuveitis and retinal vasculitis, which are very challenging to treat. Interferon alfa-2a (IFN) has been recently introduced for treating refractory Behçet uveitis, mainly in Germany and Turkey. Nonetheless, there is so far no consensus about the ideal treatment regimen of IFN for Behçet uveitis. We report our experience of IFN treatment in five Korean BD patients with refractory uveitis. All patients complained of oral ulcers; one patient had a positive pathergy test and 2 showed the presence of HLA-B51. Immunosuppressive agents used prior to IFN treatment included cyclosporine and methotrexate. The IFN treatment was commenced with a dose of 6-9 MIU/day for 7 days, adjusted according to individual ocular manifestations, tapered down to 3 MIU three times in a week, and then discontinued. All patients showed positive response to IFN treatment; 50% of them showed complete response without additional major ocular inflammation during the follow-up period. Other BD symptoms also improved after IFN treatment in most cases. After treatment, the relapse rate and the required dose of oral corticosteroid were decreased in most cases, showing a significant steroid-sparing effect. However, the visual acuity was not improved in most cases due to irreversible macular sequelae. Despite the small sample size of this study, we suggest that, in Korean patients, IFN is an effective treatment modality for BD uveitis as was observed in German and Turkish patients.

A comparative study on hulled adlay and unhulled adlay through evaluation of their LPS-induced anti-inflammatory effects, and isolation of pure compounds.

Coicis semen (=the hulled seed of Coix lacryma-jobi L. var. ma-yuen (Rom.Caill.) Stapf; Gramineae), commonly known as adlay and Job's tears, is widely used in traditional medicine and as a nutritious food. Bioassay-guided fractionation of the AcOEt fraction of unhulled adlays, using measurement of nitric oxide (NO) production on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells, led to the isolation and identification of two new stereoisomers, (+)-(7'S,8'R,7″S,8″R)-guaiacylglycerol ß-O-4'-dihydrodisinapyl ether (1) and (+)-(7'S,8'R,7″R,8″R)-guaiacylglycerol ß-O-4'-dihydrodisinapyl ether (2), together with six known compounds, 3-8. Compounds 3 and 4 exhibited inhibitory activities on LPS-induced NO production with IC50 values of 1.4 and 3.7 µM, respectively, and suppressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions in RAW 264.7 macrophage cells. Simple high-performance liquid chromatography with ultraviolet detection (HPLC/UV) was used to compare the AcOEt fraction of unhulled adlays responsible for the anti-inflammatory activity in RAW 264.7 cells and the inactive AcOEt fraction of hulled adlays.

Pleiotrophin inhibits melanogenesis via Erk1/2-MITF signaling in normal human melanocytes.

Pleiotrophin (PTN) is a secreted heparin-binding protein that is involved in various biological functions of cell growth and differentiation. Little is known about the effects of PTN on the melanocyte function and skin pigmentation. In this study, we investigated whether PTN would affect melanogenesis. PTN was expressed in melanocytes and fibroblasts of human skin. Transfection studies revealed that PTN decreased melanogenesis, probably through MITF degradation via Erk1/2 activation in melanocytes. The inhibitory action of PTN in pigmentation was further confirmed in ex vivo cultured skin and in the melanocytes cocultured with fibroblasts. These findings suggest that PTN is a crucial factor for the regulation of melanogenesis in the skin.

Huge Bowen's disease: a pitfall of topical photodynamic therapy.

Bowen's disease (BD) is one of the major histological types of nonmelanoma skin cancer. With challengeable "multiple and large" patches of BD, topical photodynamic therapy (PDT) has been considered as a first-line effective modality for decades. However, there was no general consensus among authors about the definition of "large BD". Herein, we have experienced two cases of huge BD which has over 10 cm in diameter with resistance to topical PDT. Our cases suggest that topical PDT is likely to show a much less satisfactory effect for huge BD than we have expected, and the previously specified indication of topical PDT ("multiple, larger lesion") seems the fallacy of hasty generalization. Therefore, it is required that further cut-off value of size for suitable candidate for topical PDT would be clarified.

Effects of Xanthium stramarium and Psoralea corylifolia Extracts Combined with UVA1 Irradiation on the Cell Proliferation and TGF-ß1 Expression of Keloid Fibroblasts.

BACKGROUND: Xanthium stramarium (XAS) and Psoralea corylifolia (PSC), phototoxic oriental medicinal plants, has been used in traditional medicines in Asian countries. OBJECTIVE: The effects of highly purified XAS or PSC extract combined with ultraviolet A1 (UVA1) irradiation on cell proliferation and transforming growth factor-beta1 (TGF-ß1) expression of the keloid fibroblast were being investigated to define potential therapeutic uses for keloid treatments. METHODS: The keloid fibroblasts were treated with XAS or PSC alone or in the combination with UVA1 irradiation. The cell viability, apoptosis, and expression of TGF-ß1 and collagen I were investigated. RESULTS: XAS and PSC in combination with UVA1 irradiation suppressed cell proliferation and induced apoptosis of keloid fibroblasts. Furthermore, the XAS and PSC in combination with UVA1 irradiation inhibited TGF-ß1 expression and collagen synthesis in keloid fibroblasts. CONCLUSION: These findings may open up the possibility of clinically used XAS or PSC in combination with UVA1 irradiation for keloid treatments.

Photodynamic therapy with ablative carbon dioxide fractional laser for treating Bowen disease.

BACKGROUND: Topical photodynamic therapy (PDT) has been increasingly used to treat malignant skin tumors including the Bowen disease. However, patients could be displeased with the long incubation time required for conventional PDT. OBJECTIVE: We evaluated the efficacy and safety of PDT with a short incubation time of ablative CO2 fractional laser pretreatment for treating Bowen disease. METHODS: Ten patients were included. Just before applying the topical photosensitizer, all lesions were treated with ablative CO2 fractional laser, following the application of methyl aminolevulinate and irradiation with red light (Aktilite CL 128). Histological confirmation, rebiopsy, and clinical assessments were performed. Adverse events were also recorded. RESULTS: Five of the ten (50%) lesions showed a complete response (CR) within three PDT sessions. After four treatment sessions, all lesions except one penile shaft lesion (90%) achieved clinical and histological CR or clinical CR only. The average number of treatments to CR was 3.70±1.70. The treatments showed favorable cosmetic outcomes and no serious adverse events. CONCLUSION: The results suggest that pretreatment with an ablative fractional CO2 laser before PDT has similar treatment efficacy and requires a shorter photosensitizer incubation time compared with the conventional PDT method.

Ultrastructural changes in photorejuvenation induced by photodynamic therapy in a photoaged mouse model.

BACKGROUND: Photoaging is defined as premature aging of the skin induced by ultraviolet (UV) irradiation. Photodynamic therapy (PDT) has been shown to be a non-invasive but effective technique for photoaged skin. OBJECTIVE: We observed histological and ultrastructural changes of photoaging and photorejuvenating effects of 5-aminolevulinic acid (ALA)-PDT in a UV-irradiated mice model. METHODS: A total of 20 mice were divided into a control (group A) group and a UV-irradiated (photoaging) group. The photoaging group was divided according to the following interventions: photoaging only (group B), ALA application only (group C), light-emitting diode (LED) irradiation only (group D), and ALA-PDT with a light dose of 20 J/cm(2) (group E). Serial skin biopsies were performed from day 2 to day 21, and transmission electron microscopic (TEM) studies were performed. RESULTS: After UV irradiation, the amount of dermal collagen fibers decreased, and the quantity of elastotic materials increased. Following ALA-PDT application, the amount of collagen fibers increased from day 2 to day 21 and the increased elastotic materials during the photoaging period were normalized. With TEM, the decreased collagen fibers during photoaging were restored after PDT application. Also, distended dermal fibroblasts with distended endoplasmic reticulum by UV irradiation were normalized after PDT application. CONCLUSION: This study provides histologic evidence of the beneficial effects of ALA-PDT, even in photodamaged skin. ALA-PDT induces deposition of collagen in the dermis, normalizes elastotic materials which were induced by photoaging and may even have a direct effect on the normalization of the morphology of fibroblasts.