Cytoreductive surgery and intraperitoneal chemotherapy for peritoneal metastasis of colorectal cancer: long-term follow-up results at a single institution in Korea.

PURPOSE: This study aimed to examine the 7-year follow-up results of cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for peritoneal metastasis (PM) of colorectal cancer. METHODS: We performed 54 cases of CRS and IPC in 53 patients with PM of colorectal cancer from December 2011 to December 2013. We prospectively collected data and analyzed peritoneal carcinomatosis grade, completeness of cytoreduction, and long-term follow-up (median, 10 [range, 2-92] months) results. RESULTS: The mean peritoneal cancer index was 15 (1 ~ 35), and complete cytoreduction was possible in 35 (64.8%) patients. Excluding the four patients who died, 11 (22.4%) out of the 49 patients were alive at the time of the last follow-up, and the overall median survival period was 10.3 months. The overall 2- and 5-year survival rates were 31% and 17%, respectively. Patients with complete cytoreduction had a median survival period of 22.6 months, which was significantly longer than that for patients without complete cytoreduction (3.5 months) (P < 0.001). The 5-year survival rate for patients with complete cytoreduction was 24%, and four patients were still alive without disease. CONCLUSIONS: CRS and IPC show a 5-year survival rate of 17% in patients with PM of colorectal cancer. A possibility of long-term survival is observed in a selected group. Multidisciplinary team evaluation for careful patient selection and CRS training program to achieve complete cytoreduction are significantly important factors in improving survival rate.

Gamma Knife Radiosurgery for Choroidal Hemangioma: A Single-Institute Series.

OBJECTIVE: Choroidal hemangioma (CH) is a benign vascular tumor that induces subretinal fluid collection or exudative retinal detachment and consequent visual symptoms. Current standard treatments for CH include cryotherapy, diathermy, photocoagulation, photodynamic therapy, transpupillary thermotherapy, and radiation therapy. Stereotactic radiosurgery has recently been applied to the treatment of CH because of its characteristic stiff dose-fall-off and accuracy. We have adopted gamma knife radiosurgery (GKRS) to treat CH and have retrospectively assessed tumor volume reductions and improvements to visual acuity achieved thereby. METHODS: Fourteen patients with CHs were treated with GKRS from November 2006 to December 2017. Eight patients had circumscribed CH, and 6 exhibited diffuse CHs and were diagnosed with Sturge-Weber syndrome. The mean age of patients was 27.1 years (range: 8-68 years) and the mean duration of clinical or radiological follow-up was 40.2 months (range: 5-105 months). The mean volume of the tumors at the time of GKRS was 533.5 mm3 (range: 124-1150 mm3), and the mean prescribed marginal dose was 11.6 Gy (range: 10-16 Gy) with 50% isodose lines. RESULTS: The tumor volume decreased by the last follow-up in all patients. The visual acuity improved in 9 patients (64%) and decreased in 1 (7%). Six patients (43%) required trans-pars plana vitrectomy before or after GKRS. There were no symptomatic complications from radiation injury during the follow-up periods. CONCLUSIONS: GKRS could be an acceptable alternative treatment for symptomatic CH when standard therapy is not feasible.

Treatment response to intravitreal bevacizumab in small pigmented choroidal lesions with subretinal fluid.

BACKGROUND: To describe the effects of intravitreal bevacizumab injection (IVB) and/or transpupillary thermotherapy (TTT) in the treatment of small pigmented choroidal lesions with subfoveal fluid (SFF), and to investigate prognostic value of the therapeutic response in future tumor growth. METHODS: Retrospective chart review of 19 patients, who were diagnosed with choroidal neovascularization (CNV)-free small pigmented choroidal lesions and treated with IVB and/or TTT, was performed. RESULTS: Complete resolution of SFF was achieved in two eyes (2/14; 14.3%) after IVB, and in three eyes (3/4; 75%) after TTT. Best corrected visual acuity was improved in two eyes (2/9; 22%) after IVB, and in three eyes (3/4; 75%) after TTT. Among five patients who underwent TTT after IVB, four patients (4/5; 80%) demonstrated additional advantage. All IVBs could not reduce tumor sizes. Rather, tumor growth was detected in seven out of 14 eyes (7/14; 50%) that underwent IVB. None of the patients who underwent TTT showed tumor growth. The lack of treatment response to IVB was suggestive of malignancy, as most small pigmented lesions that had no response to IVB showed tumor growth (86%, p = 0.010). CONCLUSION: IVB was not effective in reducing tumor size and subfoveal fluid in small pigmented choroidal lesions. Therapeutic response to IVB can be used as an indicator between melanoma and nevus in small pigmented choroidal lesion.

Retinal fluid changes and therapeutic effects in symptomatic circumscribed choroidal hemangioma patients: a long-term follow up study.

BACKGROUND: Changes in retinal fluid patterns associated with circumscribed choroidal hemangioma (CCH) have not been investigated yet. A long-term follow-up study was performed to evaluate the changes of retinal fluid patterns and treatment responses. METHODS: We retrospectively reviewed medical records of all CCH patients diagnosed between November 2005 and March 2017. Enrolled patients had visual symptoms, were treatment-naïve, and had been followed-up for more than 2 years. Best corrected visual acuities (BCVA) and the presence, severity, and pattern change of the subretinal fluid (SRF) and intraretinal fluid (IRF) in the macula on optical coherence tomography (OCT) were analyzed at initial presentation and follow-up visits. RESULTS: Twenty-six patients were enrolled. All patients received one or more of the following treatments: PDT, TTT, and intravitreal bevacizumab (Avastin) injection (IVB). Primary therapy consisted of PDT in 9 patients (34.6%), TTT in 7 patients (26.9%) and IVB in 10 patients (38.5%). At initial presentation, the SRF-only pattern was mostly observed. Despite treatment, IRF occurred over time; eventually, advanced cystoid macular oedema (CME) developed. In terms of retinal fluid reduction, PDT was most efficacious (9/9, 100%), and TTT and IVB showed moderate efficacy (TTT: 4/7, 57.1%; IVB: 5/10, 50%) as a primary therapy. After advanced CME developed, IVB and TTT showed no or minimal effect (TTT: 0/1, 0%; IVB: 0/19, 0%), and PDT was the only effective therapy (6/10, 60%). CONCLUSION: The pattern of retinal fluid accompanied by CCH evolved from an SRF-only pattern initially to an advanced CME pattern. The effectiveness of treatments decreased over time, and advanced CME generally showed resistance to treatments. PDT would be the most recommended treatment.

Ruthenium-106 Brachytherapy with or without Additional Local Therapy Shows Favorable Outcome for Variable-Sized Choroidal Melanomas in Korean Patients.

PURPOSE: The purpose of this study was to report clinical outcomes of ruthenium-106 (106Ru) brachytherapy with or without additional local therapy for choroidal melanomas in Korean patients. MATERIALS AND METHODS: A total of 88 patients diagnosed with choroidal melanomas were treated with 106Ru brachytherapy between 2006 and 2012. Patients were divided into two groups according to their tumor height: a large group (≥ 6 mm, n=50) and a small group (< 6 mm, n=38). Most patients in the large group received combined therapy with local excision and/or transpupillary thermotherapy. In general, 85-95 Gy was administered to the apex of the tumor, while 100 Gy was administered to the point 2-6 mm from the outer surface of the sclera for patients undergoing combined therapy. RESULTS: The median follow-up duration was 30 months. The 3-year local control rate was significantly higher in the small group than in the large group (94% vs. 70%, p=0.047). The free from distant metastasis (FFDM) rate and the overall survival (OS) rate were also higher in patients in the small group (3-year FFDM, 97% vs. 76%; p=0.031 and 3-year OS, 97% vs. 72%; p=0.036). A total of 13 patients underwent enucleation. The eye-preservation rate was also higher in the small group (3-year eye-preservation rate, 94% vs. 70%; p=0.050), and tumor height was a significant prognostic factor for eye-preservation. CONCLUSION: 106Ru brachytherapy showed favorable outcomes in small choroidal melanomas in Korean patients. Although additional local treatment could improve eye-preservation rate for large tumors, other strategies should be considered for disease control.

Aminoglycoside therapy for childhood urinary tract infection due to extended-spectrum ß-lactamase-producing Escherichia coli or Klebsiella pneumoniae.

BACKGROUND: The rate of urinary tract infections (UTIs) due to extended-spectrum ß-lactamase (ESBL)-producing bacterial strains requiring carbapenem therapy has been increasing in children. This study was conducted to evaluate the effect of non-carbapenem antibiotic therapy on childhood UTIs caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae. METHODS: Medical records of children diagnosed with febrile UTIs due to E. coli or K. pneumoniae between 2010 and 2014 were retrospectively reviewed. The enrolled children were divided into two groups: the ESBL group and the non-ESBL group. Clinical characteristics and therapeutic responses were compared between the two groups. RESULTS: A total of 211 episodes of UTI (204 caused by E. coli; seven caused by K. pneumoniae) were identified in 205 children. Twenty-two (10.4 %) episodes were categorized into the ESBL group. There was no significant difference in the type of antibiotic administered between the two groups. No carbapenems were administered; however, aminoglycosides were administered for 79.1 % of the total episodes. Although empirical antibiotics were appropriate for more episodes in the non-ESBL group compared with the ESBL group (100.0 % vs. 90.9 %, p = 0.011), there were no significant differences in the frequency of defervescence, bacterial eradication from the urine, acute pyelonephritis and vesicoureteral reflux or fever duration between the two groups. CONCLUSIONS: Non-carbapenem antibiotics showed favourable therapeutic effects on childhood UTIs caused by ESBL-producing strains. Aminoglycosides can be an alternative to carbapenems in such cases.

Association Between Choroidal Thickness and Metabolic Activity on Positron Emission Tomography in Eyes With Choroidal Melanoma.

PURPOSE: To investigate the relationship between subfoveal choroidal thickness and metabolic activity in eyes with choroidal melanoma. DESIGN: Retrospective, interventional case series. METHODS: The medical records of 16 patients with unilateral choroidal melanoma who underwent ruthenium (Ru) 106 brachytherapy with adjuvant transpupillary thermotherapy and who had available pretreatment positron emission tomography-computed tomography (PET-CT) images were retrospectively reviewed. Subfoveal choroidal thickness was measured in tumor eyes and in unaffected fellow eyes using enhanced-depth imaging spectral-domain optical coherence tomography (EDI OCT). Tumor eyes were divided into 2 groups (metabolically active and inactive) based on PET-CT findings and subfoveal choroidal thickness was compared between groups. Additionally, choroidal thickness measurements were compared before and after treatment. RESULTS: Before treatment, mean choroidal thickness was 293.31 ± 46.80 µm in tumor eyes and 242.44 ± 65.37 µm in fellow eyes, a difference that was statistically significant (P = .003). Eyes with metabolically active tumors had a significantly thicker choroid (348.00 ± 17.32 µm) than eyes with metabolically inactive tumors (280.69 ± 42.04 µm, P = .019). In tumor eyes, mean choroidal thickness significantly decreased from pretreatment values to 253.56 ± 61.27 µm 6 months after treatment (P = .018). CONCLUSION: Eyes with choroidal melanoma had thicker choroids than unaffected fellow eyes. Increased choroidal thickness was more prominent in metabolically active tumors. Choroidal thickness significantly decreased in tumor eyes 6 months after treatment.

Anti-inflammatory effects of Rubus coreanus Miquel through inhibition of NF-κB and MAP Kinase.

BACKGROUND/OBJECTIVES: Rubus Coreanus Miquel (RCM), used as a traditional Korean medicine, reduces chronic inflammatory diseases such as cancer and rheumatoid arthritis. However, its mechanism has not been elucidated. In this study, we examine the anti-inflammatory effects of RCM and their possible mechanisms using RAW 264.7 cells. MATERIALS/METHODS: Unripe RCM ethanol extract (UE), unripe RCM water extract (UH), ripe RCM ethanol extract (RE), and ripe RCM water extract (RH) were prepared. Inflammatory response was induced with LPS treatment, and expression of pro-inflammatory mediators (iNOS, COX-2, TNF-α, IL-1ß, and IL-6) and NO and PGE2 productions were assessed. To determine the anti-inflammatory mechanism of RCM, we measured NF-κB and MAPK activities. RESULTS: UE and UH treatment significantly reduced NF-κB activation and JNK and p38 phosphorylation and reduced transcriptional activities decreased iNOS, COX-2, and pro-inflammatory cytokines expressions, and NO and PGE2 productions. RE and RH treatments reduced IL-1ß and IL-6 expressions through suppressions of JNK and p38 phosphorylation. CONCLUSIONS: In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions. Especially, unripe RCM showed strong anti-inflammatory effects through suppression of NF-κB and MAPK activation. These findings suggest that unripe RCM might be used as a potential functional material to reduce chronic inflammatory responses.

VEGF rescues cigarette smoking-induced human RPE cell death by increasing autophagic flux: implications of the role of autophagy in advanced age-related macular degeneration.

PURPOSE: Cigarette smoking (CS) is the most consistent risk factor for advanced age-related macular degeneration (AMD). To verify the molecular basis for CS-induced RPE alterations, RPE cell survival levels after being exposed to CS in relation with VEGF expression and autophagic flux were evaluated. METHODS: Cigarette smoking extract (CSE) was added to ARPE-19 cells and hydrogen peroxide (HP) was used as a pure oxidant control. Cell survival was measured by flow cytometry with annexin V-fluorescein isothiocyanate. Cell survival analysis was performed after pretreatment with anti-VEGF or recombinant VEGF. The expression of VEGF-A, VEGF-R1/R2, and soluble VEGF-R1 was determined by semiquantitative RT-PCR. LC3B-I (microtubule-associated protein-1 inhibitors), LC3B-II, and phosphorylation of Akt or Erk were measured with Western blot. Autophagic flux was determined by increasing LC3B-II levels with inhibitors of lysosomal proteases. RESULTS: Incubation with 5% CSE for 16 hours induced approximately 30% cell death, which was similar to cell death levels when exposed to concentrations of 200 µM HP. Pretreatment with anti-VEGF did not decrease cell survival under CSE, unlike the decrease in cell survival shown with HP. However, supplementation with VEGF rescued CSE-induced RPE cell death. Interestingly, CSE caused an increase in autophagic flux, which was augmented with VEGF pretreatment. Cigarette smoking extract also degraded the total amounts of Akt levels, and VEGF blunted CSE-induced phosphorylation of Erk. CONCLUSIONS: Cigarette smoking extract, similar to HP, affects cell viability and induces expression of VEGF and its receptors. Increased autophagic flux accelerated by treatment of exogenous VEGF may have a role in rescuing CSE-induced RPE cell death.

Prognosis of choroidal melanoma and the result of ruthenium brachytherapy combined with transpupillary thermotherapy in Korean patients.

BACKGROUND/AIMS: To evaluate the clinical features and prognosis of choroidal melanoma in Korean patients and the results of treatment with ruthenium (Ru) 106 plaque brachytherapy. METHODS: The medical charts of 111 patients diagnosed with choroidal melanoma who underwent Ru brachytherapy with trans-pupillary thermotherapy or local resection (61 patients) or who underwent other treatments (26 primary enucleations, 22 γ-knife radiotherapies and two lamellar sclerouvectomies) were reviewed retrospectively. RESULTS: The mean largest basal diameter (LBD) was 11.4±3.2 mm and the mean apical height was 7.8±2.9 mm. Compared with the collaborative ocular melanoma study, mean tumour height was skewed toward higher values (6.2 vs 4.8 in medium tumours, p<0.0001; 10.9 vs 9.5 mm in large tumours, p=0.034) and the LBD in large tumours was skewed toward smaller values (13.6 vs 17.3, p<0.0001). The estimated 5-year metastasis-free rate was 73.9% and the disease-specific survival rate was 84.6%. For the 61 patients that were treated with Ru brachytherapy, the 5-year metastasis-free and disease-specific survival rates were 79.0% and 87.7%, respectively, and the 5-year incidence of enucleation was 25.4%. The mean tumour regression at 6, 12 and 18 months after brachytherapy was 80.2%, 73.1% and 69.2%, respectively. CONCLUSIONS: Choroidal melanomas in Korean patients tend to grow vertically with a relatively large apical height and a small LBD. The prognosis of choroidal melanomas overall as well as prognosis after Ru brachytherapy were similar to those seen in previous studies with Caucasian patients. The enucleation rate after brachytherapy seems to be higher in Korean patients, for which a greater initial tumour height seems to be partly responsible.

Treatment of serous macular detachment associated with circumscribed choroidal hemangioma.

PURPOSE: To evaluate the effects of transpupillary thermotherapy and intravitreal bevacizumab injection on serous macular detachment and cystoid macular edema (CME) associated with circumscribed choroidal hemangioma. DESIGN: Retrospective, interventional case series. METHODS: We reviewed the records of 12 patients with circumscribed choroidal hemangioma treated with transpupillary thermotherapy and/or intravitreal injection of bevacizumab. We assessed changes in best-corrected visual acuity (BCVA), central foveal thickness by optical coherence tomography, and resolution of serous macular detachment and CME. RESULTS: Six of 8 patients treated with transpupillary thermotherapy showed complete resolution of serous macular detachment and CME and the median minimal angle of resolution (logMAR) BCVA improved from 0.85 to 0.35 (P = .026). Among these 6 patients, 1 had no recurrence for 86 months and 5 had sustained resolution of serous macular detachment for a mean duration of 32.8 months before recurrence. Among the 9 patients treated with bevacizumab (including 5 patients who had transpupillary thermotherapy as a primary treatment), 5 showed resolution of serous macular detachment and the median logMAR BCVA improved from 0.7 to 0.5 (P = .042). Among these 5 patients, 3 had sustained resolution for a mean duration of 5.7 months and 2 showed recurrent serous macular detachment after 3 and 12 months. CONCLUSION: Transpupillary thermotherapy and intravitreal bevacizumab appear effective in the management of symptomatic circumscribed choroidal hemangioma, although recurrence of serous macular detachment and CME developed after long-term follow-up of transpupillary thermotherapy, and the duration of treatment effectiveness appears to be short with bevacizumab.

Expression of 12 cytokines in aqueous humour of uveal melanoma before and after combined Ruthenium-106 brachytherapy and transpupillary thermotherapy.

PURPOSE: To determine the aqueous humour levels of 12 cytokines in eyes with uveal melanoma and whether their expression changes after combined Ru-106 brachytherapy and transpupillary thermotherapy (TTT). METHODS: Aqueous humour samples were collected from 20 patients with previously untreated uveal melanoma undergoing combined Ru-106 brachytherapy and TTT, both at the time of plaque placement and removal. Using multiplex biochip array technology, 12 different cytokines were measured, including interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α, interferon (IFN)-γ, epidermal growth factor (EGF) and monocyte chemoattractant protein (MCP)-1. Aqueous humour from 20 patients undergoing cataract surgery was used as control. RESULTS: IL-6, IL-8, IFN-γ and MCP-1 were highly expressed in uveal melanoma, whereas IL-2, IL-10 and TNF- α were low in expression. There was a positive correlation between tumour height and IL-8 level (p = 0.020). Vascular endothelial growth factor tends to be highly expressed in melanoma-containing eyes (p = 0.056). Levels of IL-6, IL-8 and IL-1ß increased after the mean 117 ± 38 hrs of brachytherapy and adjunctive TTT with a tumour apex dose of 61 ± 28 Gy and a scleral contact dose of 786 ± 226 Gy. Increase in levels of IL-6 (p = 0.003) and IL-8 (p = 0.046) positively correlated with scleral contact dose. CONCLUSIONS: Cytokines such as IL-6, IL-8, IFN-γ and MCP-1 may be implicated in the progression of uveal melanoma. Ocular irradiation from a Ru-106 plaque promoted an increase in the levels of IL-6, IL-8 and IL-1ß, modulation of which could be useful in managing radiation-related side effects.

Retinal break and rhegmatogenous retinal detachment after transpupillary thermotherapy as primary or adjunct treatment of choroidal melanoma.

OBJECTIVE: To report the development of retinal break or rhegmatogenous retinal detachment (RRD) after transpupillary thermotherapy (TTT) as primary or adjunct treatment of choroidal melanoma. METHODS: In this noncomparative, interventional case series, the authors reviewed medical records of 13 patients who developed retinal break or RRD following TTT. The main outcome measures were clinical features and outcome of treatment of retinal break or RRD following TTT. RESULTS: Of 1574 patients managed on the Oncology Service at Wills Eye Institute with TTT as primary or adjunct treatment of choroidal melanoma, 13 (1%) developed retinal break with or without RRD. The mean patient age at diagnosis of choroidal melanoma was 56 years. Treatment for choroidal melanoma included combined plaque radiotherapy and TTT in 10 patients and TTT alone in 3 patients. The median number of TTT sessions before development of retinal break or RRD was 2. Retinal break or RRD developed at a median of 3 months following the last TTT. All the retinal breaks were located in the TTT-treated area. Retinal breaks were atrophic in 11 eyes and horseshoe shaped in 2 cases. The extent of retinal detachment was none in 1 eye, 1 quadrant or less in 5 eyes, 2 or 3 quadrants in 4 eyes, and 4 quadrants in 3 eyes. Seven patients underwent vitrectomy, one received cryotherapy and laser photocoagulation, and five were observed without treatment. In all eight patients who received treatment for RRD, the retina was attached after a mean follow-up period of 54 months with no intraocular or local extraocular tumor dissemination. CONCLUSIONS: Development of retinal break or RRD is a rare complication of TTT for treatment of choroidal melanoma. The majority of these cases develop within 6 months of TTT and most are caused by atrophic retinal holes in the TTT-treated area.

CAZFP1, Cys2/His2-type zinc-finger transcription factor gene functions as a pathogen-induced early-defense gene in Capsicum annuum.

A pepper zinc-finger protein gene, CAZFP1 , encoding the Cys2/His2-type zinc-finger transcription factor was isolated from pepper leaves inoculated with an avirulent strain Bv5-4a of Xanthomonas campestris pv. vesicatoria . The CAZFP1 protein is a nuclear targeting protein, which functions as a transcriptional regulator. The full-length CAZFP1 had no transcriptional activation activity, whereas the C-terminal region of CAZFP1 had transactivation activity. The CAZFP1 transcripts were constitutively expressed in the pepper stem, root, flower and red fruit, but were not detectable in the leaf and green fruit. The CAZFP1 transcripts accumulated earlier than the CAZFP1 (PR-1) gene in the incompatible interaction of the pepper leaves with X. campestris pv. vesicatoria . The CAZFP1 transcripts were significantly induced in the systemic, uninoculated leaf tissues early after inoculation with bacterial pathogens, but gradually declined thereafter. The CAZFP1 transcripts were localized, and confined to the phloem cells of the vascular bundle in the pepper leaf midrib in response to Colletotrichum. coccodes infection, ethylene and abscisic acid. The CAZFP1 gene was also induced much earlier by abiotic elicitors and environmental stresses, compared with the CAZFP1 gene. Overexpression of the CAZFP1 gene in the transgenic Arabidopsis plants enhanced not only the resistance against infection by Pseudomonas syringae pv. tomato, but also the drought tolerance. These results suggest that the CAZFP1 gene functions as an early-defense gene to enhance disease resistance and drought tolerance.