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1.  Efficacy of the Mineral Oil and Hyaluronic Acid Mixture Eye Drops in Murine Dry Eye 
Purpose
To investigate the therapeutic effects of mineral oil (MO) and hyaluronic acid (HA) mixture eye drops on the tear film and ocular surface in a mouse model of experimental dry eye (EDE).
Methods
Eye drops consisting of 0.1% HA alone or mixed with 0.1%, 0.5%, or 5.0% MO were applied to desiccating stress-induced murine dry eyes. Tear volume, corneal irregularity score, tear film break-up time (TBUT), and corneal fluorescein staining scores were measured at 5 and 10 days after treatment. Ten days after treatment, goblet cells in the conjunctiva were counted after Periodic acid-Schiff staining.
Results
There was no significant difference in the tear volume between desiccating stress-induced groups. The corneal irregularity score was lower in the 0.5% MO group compared with the EDE and HA groups. The 0.5% and 5.0% MO groups showed a significant improvement in TBUT compared with the EDE group. Mice treated with 0.1% and 0.5% MO mixture eye drops showed a significant improvement in fluorescein staining scores compared with the EDE group and the HA group. The conjunctival goblet cell count was higher in the 0.5% MO group compared with the EDE group and HA group.
Conclusions
The MO and HA mixture eye drops had a beneficial effect on the tear films and ocular surface of murine dry eye. The application of 0.5% MO and 0.1% HA mixture eye drops could improve corneal irregularity, the corneal fluorescein staining score, and conjunctival goblet cell count compared with 0.1% HA eye drops in the treatment of EDE.
doi:10.3341/kjo.2015.29.2.131
PMCID: PMC4369516  PMID: 25829831
Dry eye; Hyaluronic acid; Mineral oil; Ocular surface
2.  Whole genome sequence analysis of the TALLYHO/Jng mouse 
BMC Genomics  2016;17:907.
Background
The TALLYHO/Jng (TH) mouse is a polygenic model for obesity and type 2 diabetes first described in the literature in 2001. The origin of the TH strain is an outbred colony of the Theiler Original strain and mice derived from this source were selectively bred for male hyperglycemia establishing an inbred strain at The Jackson Laboratory. TH mice manifest many of the disease phenotypes observed in human obesity and type 2 diabetes.
Results
We sequenced the whole genome of TH mice maintained at Marshall University to a depth of approximately 64.8X coverage using data from three next generation sequencing runs. Genome-wide, we found approximately 4.31 million homozygous single nucleotide polymorphisms (SNPs) and 1.10 million homozygous small insertions and deletions (indels) of which 98,899 SNPs and 163,720 indels were unique to the TH strain compared to 28 previously sequenced inbred mouse strains. In order to identify potentially clinically-relevant genes, we intersected our list of SNP and indel variants with human orthologous genes in which variants were associated in GWAS studies with obesity, diabetes, and metabolic syndrome, and with genes previously shown to confer a monogenic obesity phenotype in humans, and found several candidate variants that could be functionally tested using TH mice. Further, we filtered our list of variants to those occurring in an obesity quantitative trait locus, tabw2, identified in TH mice and found a missense polymorphism in the Cidec gene and characterized this variant’s effect on protein function.
Conclusions
We generated a complete catalog of variants in TH mice using the data from whole genome sequencing. Our findings will facilitate the identification of causal variants that underlie metabolic diseases in TH mice and will enable identification of candidate susceptibility genes for complex human obesity and type 2 diabetes.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-016-3245-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s12864-016-3245-6
PMCID: PMC5106808  PMID: 27835940
Whole genome sequencing; Obesity; Type 2 diabetes; Mouse model; TALLYHO; Quantitative Trait Loci
3.  Chemotherapy for colorectal cancer in the elderly 
Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the elderly. However, elderly patients with CRC tend to be under-presented in clinical trials and undertreated in clinical practice. Advanced age alone should not be the only criteria to preclude effective therapy in elderly patients with CRC. The best guide about optimal cancer treatment can be provided by comprehensive geriatric assessment. Elderly patients with stage III colon cancer can enjoy the same benefit from adjuvant chemotherapy with 5-fluorouracil/leucovorin or capecitabine as younger patients, without a substantial increase in toxicity. With conflicting results of retrospective studies and a lack of data available from randomized studies, combined modality treatment should be used with great caution in elderly patients with locally advanced rectal cancer. Combination chemotherapy can be considered for older patients with metastatic CRC. For elderly patients who are frail or vulnerable, however, monotherapy or a stop-and-go strategy may be desirable. The use of targeted therapies in older patients with metastatic CRC appears to be promising in view of their better efficacy and toxicity. Treatment should be individualized based on the nature of the disease, the physiologic or functional status, and the patient’s preference.
doi:10.3748/wjg.v21.i17.5158
PMCID: PMC4419056  PMID: 25954089
Adjuvant chemotherapy; Colorectal cancer; Elderly; Palliative chemotherapy; Review
4.  Comparison of RECIST 1.0 and RECIST 1.1 in Patients with Metastatic Cancer: A Pooled Analysis 
Journal of Cancer  2015;6(4):387-393.
Background:We conducted this pooled analysis to investigate the impact of RECIST 1.1 on the selection of target lesions and classification of tumor response, in comparison with RECIST 1.0.
Methods: We searched MEDLINE and EMBASE for articles with terms of RECIST 1.0 or RECIST 1.1. We looked into all abstracts and virtual meeting presentations from the conferences of ASCO and ESMO between 2009 and 2013.
Results: There were six articles in the literature comparing the clinical impacts of RECIST 1.0 and RECIST 1.1 in patients with metastatic cancer. A total of 359 patients were recruited from the six trials; 217 with non-small cell lung cancer, 61 with gastric cancer, 58 with colorectal cancer, and 23 with thyroid cancer. The number of target lesions by RECIST 1.1 was significantly lower than that by RECIST 1.0 (P<0.001). Because of new lymph node criteria, fourteen patients (3.1%) had no target lesions when adopting RECIST 1.1. RECIST 1.1 showed high concordance with RECIST 1.0 in the assessment of tumor responses (k = 0.903). Sixteen patients (4.8%) showed disagreement between the two criteria.
Conclusion: This pooled study demonstrated that RECIST 1.1 showed a highly concordant response assessment with RECIST 1.0 in patients with metastatic cancer.
doi:10.7150/jca.11316
PMCID: PMC4349880  PMID: 25767610
RECIST 1.0; RECIST 1.1; Target lesion; Tumor response
5.  Comparison of the RECIST 1.0 and RECIST 1.1 in Non-Small Cell Lung Cancer Treated with Cytotoxic Chemotherapy 
Journal of Cancer  2015;6(7):652-657.
Background : The impact of the RECIST 1.1 on the selection of target lesions and assessment of tumor response was not evaluated in patients with advanced NSCLC who received cytotoxic chemotherapy.
Methods: We reviewed medical records of patients with advanced NSCLC who received first-line chemotherapy between January 2004 and December 2013 and compared the selection of target lesions and tumor responses using the two RECIST versions.
Results: A total of 88 patients who had at least one target lesion according to the RECIST 1.0 were included in the study. The number of target lesions by the RECIST 1.1 was significantly lower than that by the RECIST 1.0. When adopting the RECIST 1.1 instead of the RECIST 1.0, 40 patients (45.4%) showed a decrease in the number of target lesions. Three patients no longer had target lesion because of the new lymph node (LN) criteria of the RECIST 1.1. Tumor responses showed a high level of concordance between the RECIST 1.0 and RECIST 1.1, with a kappa value of 0.912. Four patients (4.5%) showed disagreement of tumor responses between the two criteria, which were all due to the change of the LN criteria.
Conclusion: The RECIST 1.1 showed a high level of concordance with the RECIST 1.0 in the assessment of tumor response in advanced NSCLC patients treated with cytotoxic chemotherapy. The new LN criteria were the major cause of the reduction of target lesions and reclassification of the tumor response.
doi:10.7150/jca.11794
PMCID: PMC4466415  PMID: 26078796
RECIST 1.0; RECIST 1.1; Lung cancer; Chemotherapy; Target lesion
6.  Comparison of the RECIST and PERCIST criteria in solid tumors: a pooled analysis and review 
Oncotarget  2016;7(19):27848-27854.
The PET Response Criteria in Solid Tumors (PERCIST) is a new method for the quantitative assessment of metabolic changes in solid tumors. The assessments of tumor response between the RECIST and PERCIST have shown considerable difference in several studies. This pooled study was conducted to compare tumor response according to the two criteria in patients with solid tumors. We surveyed MEDLINE, EMBASE and PUBMED for articles with terms of the RECIST or PERCIST from 2009 and January 2016. There were six articles comparing the RECIST and PERCIST. A total of 268 patients were recruited; 81 with colorectal cancer, 60 with lung cancer, 48 with esophageal cancer, 28 with breast cancer, 14 with basal cell carcinoma, 12 with stomach cancer, 10 with head and neck cancer, and 16 with other rare cancers. The agreement of tumor response between the RECIST and PERCIST was moderate (k = 0.590). Of 268 patients, 101 (37.7%) showed discordance in the tumor responses between two criteria. When adopting the PERCIST, tumor response was upgraded in 85 patients and downgraded in 16. The estimated overall response rates were significantly different between two criteria (35.1% by RECIST vs. 54.1% by PERCIST, P < 0.0001). In conclusion, this pooled analysis demonstrates that the concordance of tumor responses between the RECIST and PERCIST criteria is not excellent. The PERCIST might be more suitable for assessing tumor response than the RECIST criteria.
doi:10.18632/oncotarget.8425
PMCID: PMC5053692  PMID: 27036043
RECIST 1.0; RECIST 1.1; PET; PERCIST; tumor response
7.  Tumor response assessment by the single-lesion measurement per organ in small cell lung cancer 
Background:
The criterion of two target lesions per organ in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is an arbitrary one, being supported by no objective evidence. The optimal number of target lesions per organ still needs to be investigated. We compared tumor responses using the RECIST 1.1 (measuring two target lesions per organ) and modified RECIST 1.1 (measuring the single largest lesion in each organ) in patients with small cell lung cancer (SCLC).
Methods:
We reviewed medical records of patients with SCLC who received first-line treatment between January 2004 and December 2014 and compared tumor responses according to the two criteria using computed tomography.
Results:
There were a total of 34 patients who had at least two target lesions in any organ according to the RECIST 1.1 during the study period. The differences in the percentage changes of the sum of tumor measurements between RECIST 1.1 and modified RECIST 1.1 were all within 13%. Seven patients showed complete response and fourteen showed partial response according to the RECIST 1.1. The overall response rate was 61.8%. When assessing with the modified RECIST 1.1 instead of the RECIST 1.1, tumor responses showed perfect concordance between the two criteria (k=1.0).
Conclusions:
The modified RECIST 1.1 showed perfect agreement with the original RECIST 1.1 in the assessment of tumor response of SCLC. Our result suggests that it may be enough to measure the single largest target lesion per organ for evaluating tumor response.
doi:10.21147/j.issn.1000-9604.2016.02.03
PMCID: PMC4865608  PMID: 27199513
Target lesion; Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1); modified Response Evaluation Criteria in Solid Tumors; tumor response 1.1 (modified RECIST 1.1); small cell lung cancer (SCLC)
8.  Comparison of the RECIST 1.0 and RECIST 1.1 in patients treated with targeted agents: a pooled analysis and review 
Oncotarget  2016;7(12):13680-13687.
Patients treated with targeted agents were not included in the data warehouse when the RECIST 1.1 was revised in 2009. We conducted this pooled analysis to investigate the impact of the RECIST 1.1 on the assessment of tumor response in cancer patients treated with targeted agents. We surveyed MEDLINE, EMBASE and PubMed for articles with terms of the RECIST 1.0 or RECIST 1.1. We searched for all the references of relevant articles and reviews using the ‘related articles’ feature in the PubMed. There were six articles in the literature comparing the clinical impacts of the RECIST 1.0 and RECIST 1.1 in patients treated with targeted agents for advanced or metastatic cancer. A total of 322 patients were recruited from the six trials; 217 with non-small cell lung cancer, 23 with thyroid cancer, 20 with gastrointestinal stromal tumor, and 62 with renal cell carcinoma. Because of new lymph node criteria, eight patients (2.5%) had no target lesions when adopting the RECIST 1.1. The number of target lesions by the RECIST 1.1 was significantly lower than that by the RECIST 1.0 (P < 0.001). However, the RECIST 1.1 showed high concordance with the RECIST 1.0 in the assessment of best tumor responses (k = 0.908). Seventeen patients (5.6%) showed discrepancy in the best tumor response between the RECIST 1.0 and RECIST 1.1. This pooled study demonstrates that the RECIST 1.1 shows the highly concordant response assessment with the RECIST 1.0 in patients treated with targeted agents.
doi:10.18632/oncotarget.7322
PMCID: PMC4924670  PMID: 26885610
RECIST 1.0; RECIST 1.1; targeted agent; tumor response; target lesion
9.  Chemotherapy in Elderly Patients with Gastric Cancer 
Journal of Cancer  2016;7(1):88-94.
Gastric cancer (GC) is one of the most frequent malignant diseases in the elderly. Systemic chemotherapy showed an improvement of quality of life and survival benefit compared to supportive care alone in patients with advanced GC. Because comorbidities or age-related changes in pharmacokinetics and pharmacodynamics may lead to higher toxicity, however, many oncologists hesitate to recommend elderly patients to receive chemotherapy.
Available data suggest that elderly patients with GC are able to tolerate and benefit from systemic chemotherapy to the same extent as younger patients. The age alone should not be the only criteria to preclude effective chemotherapy. However, proper patient selection is extremely important to deliver effective treatment safely. A comprehensive geriatric assessment (CGA) is a useful method to assess life expectancy and risk of morbidity in older patients and to guide providing optimal treatment. Treatment should be personalized based on the nature of the disease, the life expectancy, the risk of complication, and the patient's preference. Combination chemotherapy can be considered for older patients with metastatic GC who are classified as non-frail patients by CGA. For frail or vulnerable patients, however, monotherapy or only symptomatic treatment may be desirable. Targeted agents seem to be promising treatment options for elderly patients with GC considering their better efficacy and less toxicity.
doi:10.7150/jca.13248
PMCID: PMC4679385  PMID: 26722364
Gastric cancer; Chemotherapy; Elderly; Review
10.  Clinical Practice in the Use of Adjuvant Chemotherapy for Patients with Colon Cancer in South Korea: a Multi-Center, Prospective, Observational Study 
Journal of Cancer  2016;7(2):136-143.
Background: Adjuvant chemotherapy is a crucial part of treatment for patients with locally advanced colon cancer. This study was conducted to investigate the actual practice in the use of adjuvant chemotherapy for patients with high-risk stage II or stage III colon cancer in South Korea.
Methods: This was a 24-month open-label, prospective, observational study conducted at 12 centers across South Korea. Patients with high-risk stage II and stage III colon cancer receiving adjuvant chemotherapy after curative surgery were included, and data were collected at baseline, third, and sixth month.
Results: A total of 246 patients were included in the analyses. Of five available regimens (FOLFOX, CAPOX, 5-FU/LV, capecitabine, and UFT/LV), FOLFOX was most commonly used (82.5%). Investigators indicated the “efficacy” as the major cause for selecting FOLFOX or CAPOX. For 5-FU/LV, capecitabine, or UFT/LV, the “safety” or “patient's characteristics (age, comorbidity, and stage)” was one of the most important selecting factors. Patients receiving 5-FU/LV, capecitabine, or UFT/LV had older age, worse PS and lower disease stage (stage II) than patients receiving FOLFOX or CAPOX. Hematologic toxicities were the most common cause of dose adjustment and treatment delay.
Conclusions: In South Korea, FOLFOX was the most commonly used regimen for adjuvant chemotherapy and its efficacy was the main cause for selecting this regimen. Patients receiving 5-FU/LV, capecitabine, or UFT/LV had older age, worse PS and lower disease stage (stage II) than patients receiving FOLFOX or CAPOX.
doi:10.7150/jca.13405
PMCID: PMC4716845  PMID: 26819636
Adjuvant chemotherapy; Colon cancer; Capecitabine; 5-fluorouracil; Oxaliplatin
11.  Current Status and Perspective of Immunotherapy in Gastrointestinal Cancers 
Journal of Cancer  2016;7(12):1599-1604.
Cancer immunotherapy is at dawn of the Renaissance after the Medieval Dark Ages. Recent advances of understanding tumor immunology and molecular drug development are leading us to the epoch of cancer immunotherapy. Some types of immunotherapy have shown to provide survival benefit for patients with solid tumors such as malignant melanoma, renal cell carcinoma, or non-small cell lung cancer. Several studies have suggested that immune checkpoint inhibition might be effective in some patients with gastrointestinal cancers. However, the era of cancer immunotherapy in gastrointestinal cancers is still in an inchoate stage. Here we briefly review the current status and perspective of immunotherapeutic approaches in patients with gastrointestinal cancers.
doi:10.7150/jca.16208
PMCID: PMC5039380  PMID: 27698896
Gastrointestinal cancers; Immunotherapy; Cancer vaccines; Immune checkpoint inhibitors; Review.
12.  Is Preoperative Biochemical Testing for Pheochromocytoma Necessary for All Adrenal Incidentalomas? 
Medicine  2015;94(45):e1948.
Abstract
This study examined whether imaging phenotypes obtained from computed tomography (CT) can replace biochemical tests to exclude pheochromocytoma among adrenal incidentalomas (AIs) in the preoperative setting.
We retrospectively reviewed the medical records of all patients (n = 251) who were admitted for operations and underwent adrenal-protocol CT for an incidentally discovered adrenal mass from January 2011 to December 2012. Various imaging phenotypes were assessed for their screening power for pheochromocytoma. Final diagnosis was confirmed by biopsy, biochemical tests, and follow-up CT.
Pheochromocytomas showed similar imaging phenotypes as malignancies, but were significantly different from adenomas. Unenhanced attenuation values ≤10 Hounsfield units (HU) showed the highest specificity (97%) for excluding pheochromocytoma as a single phenotype. A combination of size ≤3 cm, unenhanced attenuation values ≤ 10 HU, and absence of suspicious morphology showed 100% specificity for excluding pheochromocytoma.
Routine noncontrast CT can be used as a screening tool for pheochromocytoma by combining 3 imaging phenotypes: size ≤3 cm, unenhanced attenuation values ≤10 HU, and absence of suspicious morphology, and may substitute for biochemical testing in the preoperative setting.
doi:10.1097/MD.0000000000001948
PMCID: PMC4912259  PMID: 26559265
13.  The Assessment of Tumor Response by Measuring the Single Largest Lesion per Organ in Metastatic Tumors: A Pooled Analysis of Previously Reported Data 
Journal of Cancer  2015;6(2):169-176.
Background: The RECIST 1.1 adopted a total of five target lesions to be measured, with a maximum of two lesions per organ. To the best of our knowledge, the criterion of two target lesions per organ in the RECIST 1.1 is arbitrary and has not been supported by any objective evidence. Recently, we reported that the modified RECIST 1.1 (measuring the single largest lesion in each organ) showed a high level of concordance with the original RECIST 1.1 in patients with advanced or metastatic non-small cell lung cancer (NSCLC), gastric cancer (GC), and colorectal cancer (CRC). However, each study had a major limitation of a small number of patients.
Methods: We conducted a pooled analysis using the data from the three individual studies to improve statistical power. Tumor responses were compared according to the RECIST 1.1 and modified RECIST 1.1 (mRECIST 1.1).
Results: A total of 153 patients who had at least two target lesions in any organ according to the RECIST 1.1 were included in this pooled study: 64 with NSCLC, 51 with GC, and 38 with CRC. Regardless of primary sites, the number of target lesions according to the mRECIST 1.1 was significantly lower than that according to the RECIST 1.1 (P<0.001). The assessment of tumor responses showed a high concordance between the two criteria (k = 0.908). Only eight patients (5.2%) showed disagreement in the tumor response assessment between the two criteria. The overall response rates of chemotherapy were not significantly different between the two criteria (33.3% versus 33.3%, P=1.0).
Conclusions: The modified RECIST 1.1 was comparable to the original RECIST 1.1 in the tumor response assessment of patients with advanced or metastatic NSCLC, GC, and CRC. Our results suggest that it may be possible to measure the single largest lesion per organ for assessing tumor response in clinical practice.
doi:10.7150/jca.10912
PMCID: PMC4280400  PMID: 25561982
RECIST 1.1; modified RECIST 1.1; Target lesion; Tumor response; Single-lesion measurement
14.  The Factors Affecting Pain Pattern after Arthroscopic Rotator Cuff Repair 
Clinics in Orthopedic Surgery  2014;6(4):392-400.
Background
We evaluated the factors that affect pain pattern after arthroscopic rotator cuff repair.
Methods
From June 2009 to October 2010, 210 patients underwent arthroscopic rotator cuff repair operations. Of them, 84 patients were enrolled as subjects of the present study. The evaluation of postoperative pain was conducted by visual analog scale (VAS) scores during postoperative outpatient interviews at 6 weeks, 3 months, 6 months, and 12 months. The factors that were thought to affect postoperative pain were evaluated by dividing into three categories: preoperative, operative, and postoperative.
Results
Pain after arthroscopic rotator cuff repair surgery showed a strictly decreasing pain pattern. In single analysis and multiple regression tests for factors influencing the strictly decreasing pain pattern, initial VAS and pain onset were shown to be statistically significant factors (p = 0.012, 0.012, 0.044 and 0.028, respectively). With regard to the factors influencing lower than average intensity pain pattern for each period, the stiffness of internal rotation at 3 months postoperatively was shown to be a statistically significant factor in single and multiple regression tests (p = 0.017 and p = 0.004, respectively).
Conclusions
High initial VAS scores and the acute onset of pain affected the strictly decreasing postoperative pain pattern. Additionally, stiffness of internal rotation at postoperative 3 months affected the higher than average intensity pain pattern for each period after arthroscopic rotator cuff repair.
doi:10.4055/cios.2014.6.4.392
PMCID: PMC4233217  PMID: 25436062
Arthroscopy; Rotator cuff repair; Stiffness; Postoperative pain; Visual analog scale
15.  Ideal number of target lesions per organ to measure in metastatic colorectal cancer 
Oncology Letters  2014;8(4):1896-1900.
The Response Evaluation Criteria in Solid Tumors (RECIST 1.1) guideline states that the two largest lesions per organ should be measured as target lesions for assessment of the tumor response. This criterion is considered to be arbitrary and, to the best of our knowledge, has not been supported by any objective evidence. The present study hypothesized that measuring the single largest lesion in each organ into which the cancer had metastasized (termed the modified RECIST; mRECIST 1.1) may yield the same response classification as measuring the two target lesions per organ (as per the RECIST 1.1 guideline). The medical records of patients with metastatic colorectal cancer (CRC), who received first-line chemotherapy between January 2004 and June 2013 were reviewed. The tumor responses of the patients were compared according to the two criteria using computed tomography. A total of 38 patients were included in the present study, all of whom had at least two target lesions in any one organ according to the RECIST 1.1 guidelines. When adopting the mRECIST 1.1, rather than the RECIST 1.1, 18 patients (47.4%) demonstrated an increase in the rate of change of the sum of the tumor measurements. The overall response rates of chemotherapy were 39.4% and 34.2% according to the RECIST 1.1 and the mRECIST 1.1, respectively, and the difference between the two criteria was not identified to be significantly different (P=0.226). The tumor response showed near perfect agreement between the RECIST 1.1 and mRECIST 1.1 criteria (κ=0.905). Only two patients (5.3%) showed a disagreement with regard to the tumor responses between the two criteria. Therefore, it was identified that the mRECIST 1.1 showed a high level of concordance with the original RECIST 1.1 guidelines in the tumor response assessment of metastatic CRC patients to chemotherapy. The present results indicate that the mRECIST 1.1, with a decreased number of target lesions to be measured, may be more convenient in clinical practice for the assessment of tumor response.
doi:10.3892/ol.2014.2409
PMCID: PMC4156276  PMID: 25202433
target lesion; Response Evaluation Criteria in Solid Tumors 1.1; tumor response; colorectal cancer
16.  Risk factors for renal impairment revealed after unilateral adrenalectomy in patients with primary aldosteronism 
Medicine  2016;95(27):e3930.
Supplemental Digital Content is available in the text
Abstract
Primary aldosteronism (PA) may induce significant decline of renal function and structural damage of kidney. However, it is difficult to evaluate accurate renal function in patients with PA, because glomerular hyperfiltration and aldosterone escape can conceal renal impairment. In this retrospective cohort study, we compared changes in renal function after unilateral adrenalectomy between patients with PA and patients with other adrenal diseases. Risk factors associated with postoperative renal impairment in patients with PA were analyzed.
A total of 558 patients who received unilateral adrenalectomy between January 2002 and June 2013 were included: 136 patients with PA and 422 patients with other adrenal diseases (control). Postoperative serial changes in estimated glomerular filtration rate (eGFR) were analyzed in both groups. Multivariate analyses were performed to identify risk factors of renal impairment after adrenalectomy in all patients and the PA group. Postoperative renal impairment was defined as postoperative eGFR decline of >25% from preoperative eGFR. Chronic kidney disease (CKD) was defined as an eGFR <60 mL/min/1.73 m2.
There were no differences in preoperative eGFR between groups. The PA group showed a significant decrease in eGFR 3 days, 2 weeks, and 6 months after surgery compared to the control group. The PA group showed significant improvement of hypertension after surgery. In the PA group, 53 (39.0%) patients showed postoperative renal impairment. Multivariate regression analysis identified long-standing hypertension, low body mass index, low serum potassium, and high preoperative eGFR as risk factors for postoperative renal impairment. Among the 89 patients with preoperative eGFR ≥60 mL/min/1.73 m2, 29 (32.6%) patients developed CKD postoperatively. Age, low serum potassium, low preoperative eGFR, and high serum cholesterol or uric acid were associated with the postoperative CKD development.
Our study demonstrates that patients with PA with old age, low serum potassium, long-standing hypertension, and high serum uric acid or cholesterol are at risk of renal impairment after surgical treatment. High preoperative eGFR was also a risk factor for postoperative renal impairment, whereas low preoperative eGFR was a risk factor for postoperative CKD. Close monitoring of renal function and adequate management are required for patients with these risk factors.
doi:10.1097/MD.0000000000003930
PMCID: PMC5058795  PMID: 27399066
adrenalectomy; chronic kidney disease; primary aldosteronism; renal impairment
17.  Chitin-fibroin-hydroxyapatite membrane for guided bone regeneration: micro-computed tomography evaluation in a rat model 
Background
In guided bone regeneration (GBR) technique, many materials have been used for improving biological effectiveness by adding on membranes. The new membrane which was constructed with chitin-fibroin-hydroxyapatite (CNF/HAP) was compared with a collagen membrane (Bio-Gide®) by means of micro-computed tomography.
Methods
Fifty-four rats were used in this study. A critical-sized (8 mm) bony defect was created in the calvaria with a trephine bur. The CNF/HAP membrane was prepared by thermally induced phase separation. In the experimental group (n = 18), the CNF/HAP membrane was used to cover the bony defect, and in the control group (n = 18), a resorbable collagen membrane (Bio-Gide®) was used. In the negative control group (n = 18), no membrane was used. In each group, six animals were euthanized at 2, 4, and 8 weeks after surgery. The specimens were analyzed using micro-CT.
Results
Bone volume (BV) and bone mineral density (BMD) of the new bone showed significant difference between the negative control group and membrane groups (P < 0.05). However, between two membranes, the difference was not significant.
Conclusions
The CNF/HAP membrane has significant effect on the new bone formation and has the potential to be applied for guided bone regeneration.
doi:10.1186/s40902-016-0060-6
PMCID: PMC4803803  PMID: 27069912
Chitin-fibroin-hydroxyapatite; Guided bone regeneration; Micro-computed tomography; Rat calvarial defect
18.  Irinotecan, leucovorin and 5-fluorouracil (modified FOLFIRI) as salvage chemotherapy for frail or elderly patients with advanced gastric cancer 
Oncology Letters  2012;4(4):751-754.
We retrospectively evaluated the efficacy and safety of the modified FOLFIRI regimen in frail or elderly patients with advanced gastric cancer (AGC). We reviewed 24 frail [Eastern Cooperative Oncology Group performance status (ECOG PS) of 2] or elderly (65 years or over) patients with AGC who received the modified FOLFIRI regimen as salvage chemotherapy. Patients received irinotecan 150 mg/m2 and leucovorin (LV) 100 mg/m2 as a 2 h intravenous infusion, followed by 5-fluorouracil (5-FU) 2,000 mg/m2 as a 46 h continuous infusion. Among the 24 patients, 18 (75%) had an ECOG PS of 2, and 11 (45.8%) were aged 65 years or over. A total of 113 cycles were conducted, with a median number of 4 cycles per patient. A total of 3 patients achieved partial response (PR) and 8 demonstrated stable disease (SD). On an intent-to-treat basis, the overall response rate (RR) was 12.5% and the disease control rate (PR and SD) was 45.8%. The median time to progression (TTP) was 2 months [95% confidence interval (CI), 1.9–2.1 months] and the median overall survival (OS) was 5.4 months (95% CI, 4.1–6.7 months). Grade 3–4 hematological toxicities, including neutropenia, anemia and thrombocytopenia, were observed in 6 (25%), 4 (16.7%) and 1 (4.2%) patients, respectively. Additionally, 3 (12.5%) patients developed febrile neutropenia, of which 1 succumbed to pneumonia. Grade 3–4 gastrointestinal toxicities, including nausea, vomiting, diarrhea and mucositis, were observed in 3 (12.5%), 2 (8.3%), 1 (4.2%) and 1 (4.2%) patients, respectively. In conclusion, the modified FOLFIRI regimen as salvage chemotherapy for AGC patients over 65 years of age or with a poor PS was effective and acceptable. These results suggest that this regimen may be an effective option for frail or elderly patients with AGC.
doi:10.3892/ol.2012.782
PMCID: PMC3506675  PMID: 23205095
advanced gastric cancer; FOLFIRI; elderly; poor performance status
19.  Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia associated with neuroendocrine carcinoma: A case report 
Oncology Letters  2012;4(1):86-88.
Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (EDTA-PTCP) is an in vitro phenomenon of EDTA-induced platelet aggregation at room temperature. This phenomenon consists of platelet clumping due to anti-platelet antibodies in blood anticoagulated with EDTA. It has been reported in patients with various diseases, including sepsis, multiple myeloma, acute myocardial infarction and breast cancer. Since unrecognized EDTA-PTCP may lead to inappropriate treatment, it should always be considered as a possible cause in patients with low platelet counts. This study identified a case of transient EDTA-PTCP in a patient with neuroendocrine carcinoma of the stomach. In the present study, a 50-year-old male presented with epigastric pain and a weight loss of 15 kg. The patient presented with EDTA-PTCP and was diagnosed with neuroendocrine carcinoma of the stomach. Following systemic chemotherapy, the tumor showed a marked regression and the EDTA-PTCP disappeared. The mechanism by which this occurred is not clear but an association of EDTA-PTCP with neuroendocrine carcinoma is strongly suggested.
doi:10.3892/ol.2012.675
PMCID: PMC3398370  PMID: 22807967
pseudothrombocytopenia; ethylenediaminetetraacetic acid; neuroendocrine carcinoma
20.  Oxaliplatin, 5-fluorouracil and leucovorin (modified FOLFOX-6) as first-line chemotherapy for advanced gastric cancer patients with poor performance status 
Oncology Letters  2011;3(2):425-428.
This study was designed to retrospectively evaluate the efficacy and safety of modified FOLFOX-6 regimen in advanced gastric cancer (AGC) patients with poor performance status (PS). From January 2005 to August 2010, 23 AGC patients with poor PS who received mFOLFOX-6 as first-line chemotherapy were reviewed. Patients received 100 mg/m2 oxaliplatin and 100 mg/m2 leucovorin (LV) as a 2-h intravenous infusion on day 1, followed by 5-fluorouracil (5-FU) at 2000 mg/m2 as a 46-h continuous infusion. A total of 22 patients received more than 3 cycles of chemotherapy and were evaluable for tumor response. Seven patients achieved partial response, giving an overall response rate of 31.8%. The median time to progression and overall survival were 3.5 and 9.2 months, respectively. Grade 3–4 hematological toxicities were noted: neutropenia in four patients (17.4%), anemia in two (8.7%) and thrombocytopenia in one (4.3%). Two patients developed febrile neutropenia and one of these patients succumbed to sepsis. Grade 3–4 gastrointestinal toxicities, such as nausea, vomiting and diarrhea were observed in less than 10% of patients. Peripheral neuropathy was observed in 9 patients (39.1%). In conclusion, the mFOLFOX-6 regimen for AGC patients with poor PS was effective with acceptable toxicity. Our results suggest that this regimen may be an effective option for these patients.
doi:10.3892/ol.2011.496
PMCID: PMC3362383  PMID: 22740925
advanced gastric cancer; modified FOLFOX-6; poor performance status
21.  High-Dose Fentanyl Patch for Cancer Pain of a Patient with Cholangiocarcinoma 
We describe here a patient who obtained a good analgesic effect with high-dose fentanyl patches for controlling cancer pain. A 52-year-old man was referred to our hospital because of severe cancer pain that was 7/10 on a numeric rating scale (NRS). He had been diagnosed with locally advanced cholangiocarcinoma 3 months previously. We prescribed weak opioids and an antidepressant, but his pain was not relieved. We introduced strong opioids (transdermal fentanyl patches for the background pain and a short-acting opioid for the breakthrough pain) and his pain was tolerable on 250 µg/hr of fentanyl patches for 3 months. With time, however, his pain intensity became worse and this reached up to 8/10 to 9/10 on the NRS. Percutaneous transhepatic biliary drainage was performed, which did not relieve his pain. We increased gradually the dose of transdermal fentanyl to 1,050 µg/hr (20 patches). At this dose, the patient was mentally alert, with good pain control (NRS 2/10 to 3/10) and no exacerbation of side effects. To the best of our knowledge, we report here on the highest dose of transdermal fentanyl that has been successfully used for treating a patient suffering from visceral cancer pain.
doi:10.3904/kjim.2010.25.3.337
PMCID: PMC2932949  PMID: 20830233
Fentanyl; Neoplasms; Pain; Cholangiocarcinoma
22.  Second-Line Irinotecan, Leucovorin, and 5-Fluorouracil for Gastric Cancer Patients after Failed Docetaxel and S-1 
Background. This retrospective study aimed to assess the efficacy and toxicities of second-line chemotherapy with irinotecan, leucovorin, and 5-fluorouracil (5-FU) in metastatic gastric cancer (MGC) patients previously treated with docetaxel and S-1 with or without oxaliplatin (DS/DOS). Patients and Methods. We reviewed the data of patients who had previously been treated with first-line DS/DOS and received biweekly irinotecan-based chemotherapy (FOLFIRI/IFL) between October 2004 and November 2011. Results. A total of 209 cycles were administered to 35 patients, with a median of 4 (range, 1–22) cycles each. The overall response rate in 29 response-assessable patients was 17.2%, including 2 complete and 3 partial responses. The median progression-free and overall survivals were 3.81 (95% confidence interval [CI], 1.82–5.80) months and 6.24 (95% CI, 1.44–11.04) months, respectively. The major grade 3/4 toxicity was neutropenia (8.6%). Conclusion. FOLFIRI/IFL chemotherapy showed modest antitumour activity and tolerable toxicities in DS/DOS-treated MGC patients.
doi:10.1155/2016/6857625
PMCID: PMC4709667  PMID: 26839542
23.  Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently 
Endocrinology and Metabolism  2015;30(4):607-613.
A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses.
doi:10.3803/EnM.2015.30.4.607
PMCID: PMC4722418  PMID: 26248855
Adrenocortical adenoma; Hyperaldosteronism; Cushing syndrome
24.  Intraoperative Three-Dimensional Imaging in Calcaneal Fracture Treatment 
Clinics in Orthopedic Surgery  2015;7(4):483-489.
Background
To compare the effectiveness of intraoperative three-dimensional (3D) image and conventional two-dimensional (2D) fluoroscopic images, which are used in the treatment of acute calcaneal fractures.
Methods
We retrospectively analyzed 40 patients who suffered calcaneal fracture and underwent surgery at Inje University Busan Paik Hospital. The patients were divided into two groups. Only 2D fluoroscopy was used to evaluate 20 patients of group 1. On the other hand, 3D fluoroscopy was performed on the remaining 20 patients of group 2; 3D fluoroscopy was performed on these patients after they were extensively evaluated by 2D fluoroscopy during surgery. We reviewed the radiographic and clinical outcomes of these patients, whose average follow-up period was 42.6 months.
Results
In group 2, 3D fluoroscopy detected four cases (20%) of articular incongruence and screw misplacement. All these complicated cases were corrected during surgery. At the final follow-up session, the mean American Orthopedic Foot and Ankle Society (AOFAS) hind foot score was 78.3 (range, 65 to 95) in group 1 and 82.3 (range, 68 to 95) in group 2.
Conclusions
Intraoperative 3D imaging of calcaneal fractures is considered to be useful in evaluating the congruence of joints and the placement of implants.
doi:10.4055/cios.2015.7.4.483
PMCID: PMC4667117  PMID: 26640632
Calcaneus; Fracture; Treatment; Three-dimensional imaging; Fluoroscopy
25.  Duodenal Mucosa-Associated Lymphoid Tissue Lymphoma: A Case Report 
Primary duodenal mucosa associated lymphoid tissue (MALT) lymphoma is very rare, and little is known about its clinical course or effective treatment. We describe a case of primary duodenal MALT lymphoma that was resistant to Helicobacter pylori (H. pylori) eradication and regressed after chemotherapy with cyclophosphamide, vincristine, and prednisolone (CVP). A 71-year-old woman was referred to our department because of epigastric pain and dyspepsia. Gastroduodenoscopy revealed an irregular mucosal nodular lesion with ulceration extending from the bulb to the second portion of the duodenum. Histopathological examination of a biopsy specimen disclosed low-grade MALT lymphoma composed of atypical lymphoid cells with lymphoepithelial lesion. Abdominal CT scans revealed 0.5 to 1.5 cm lymph nodes in the peritoneal cavity, suggestive of lymph node metastasis. We successfully eradicated H. pylori but did not see signs of remission. We administered systemic CVP chemotherapy every 3 weeks. After 6 courses of CVP, the patient achieved complete remission and was followed up without recurrence for about a year.
doi:10.3904/kjim.2007.22.4.296
PMCID: PMC2687664  PMID: 18309692
MALT lymphoma; Duodenum; Helicobacter pylori; Chemotherapy

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