Min A Kim

Yonsei University Hospital, Sŏul, Seoul, South Korea

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Publications (115)357.51 Total impact

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    ABSTRACT: The extent to which metastatic tumors further evolve by accumulating additional mutations is unclear and has yet to be addressed extensively using next-generation sequencing of high-grade serous ovarian cancer. Eleven spatially separated tumor samples from the primary tumor and associated metastatic sites and two normal samples were obtained from a Stage IIIC ovarian cancer patient during cytoreductive surgery prior to chemotherapy. Whole exome sequencing and copy number analysis were performed. Omental exomes were sequenced with a high depth of coverage to thoroughly explore the variants in metastatic lesions. Somatic mutations were further validated by ultra-deep targeted sequencing to sort out false positives and false negatives. Based on the somatic mutations and copy number variation profiles, a phylogenetic tree was generated to explore the evolutionary relationship among tumor samples. Only 6% of the somatic mutations were present in every sample of a given case with TP53 as the only known mutant gene consistently present in all samples. Two non-spatial clusters of primary tumors (cluster P1 and P2), and a cluster of metastatic regions (cluster M) were identified. The patterns of mutations indicate that cluster P1 and P2 diverged in the early phase of tumorigenesis, and that metastatic cluster M originated from the common ancestral clone of cluster P1 with few somatic mutations and copy number variations. Although a high level of intratumor heterogeneity was evident in high-grade serous ovarian cancer, our results suggest that transcoelomic metastasis arises with little accumulation of somatic mutations and copy number alterations in this patient.
    BMC Cancer 12/2015; 15(1):1077. DOI:10.1186/s12885-015-1077-4 · 3.32 Impact Factor
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    ABSTRACT: Moyamoya disease (MMD) occurs predominantly in Korean and Japanese women. The aim of this study was to investigate clinical features and pregnancy outcomes in women with MMD. We conducted a retrospective chart review of women with MMD who visited our Department of Obstetrics and Gynecology between January 2005 and October 2013. For all study subjects, clinical features, demographic characteristics, and perinatal outcomes were recorded. We identified 28 pregnancies in 22 patients who had been diagnosed with MMD. The mean maternal age at delivery was 31.9±3.5 years old. The mean gestational age at delivery was 38.0±0.9 weeks. Among the 28 pregnancies, 25 (92.5%) underwent cesarean section; 19 (76.0%) of them were performed under regional anesthesia and six (24.0%) under general anesthesia. The mean newborn weight was 3233.7±348.2 g. The 5-minute Apgar score in 85% of the newborns was higher than 8, with no other apparent complications. During the puerperal period, transient ischemic attack symptom or seizure occurred in 4 cases, although patients recovered within a few days. For pregnant women with MMD, it is important to control blood pressure and prevent hyperventilation during the intrapartum period, and the best methods of delivery and anesthesia should be considered to avoid unfavorable sequelae. Additionally, a multidisciplinary approach (i.e., neurosurgery) is necessary to constantly manage underlying diseases.
    Yonsei medical journal 05/2015; 56(3):793-7. DOI:10.3349/ymj.2015.56.3.793 · 1.26 Impact Factor
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    ABSTRACT: Although nerve-sparing radical surgery (NSRS) is an emerging technique for reducing surgery-related dysfunctions, its efficacy is controversial in patients with cervical cancer. Thus, we performed a meta-analysis to compare clinical outcomes, and urinary, anorectal, and sexual dysfunctions between conventional radical surgery (CRS) and NSRS. After searching PubMed, Embase, and the Cochrane Library, two randomized controlled trials, seven prospective and eleven retrospective cohort studies were included with 2,253 patients from January 2000 to February 2014. We performed crude analyses and then conducted subgroup analyses according to study design, quality of study, surgical approach, radicality, and adjustment for potential confounding factors. Crude analyses showed decreases in blood loss, hospital stay, frequency of intraoperative complications, length of the resected vagina, duration of postoperative catheterization (DPC), urinary frequency, and abnormal sensation in NSRS, whereas there were no significant differences in other clinical parameters and dysfunctions between CRS and NSRS. In subgroup analyses, operative time was longer (standardized difference in means, 0.948; 95% confidence interval [CI], 0.642 to 1.253), while intraoperative complications were less common (odds ratio, 0.147; 95% CI, 0.035 to 0.621) in NSRS. Furthermore, subgroup analyses showed that DPC was shorter, urinary incontinence or frequency, and constipation were less frequent in NSRS without adverse effects on survival and sexual functions. NSRS may not affect prognosis and sexual dysfunctions in patients with cervical cancer, whereas it may decrease intraoperative complications, and urinary and anorectal dysfunctions despite long operative time and short length of the resected vagina when compared with CRS.
    Journal of Gynecologic Oncology 04/2015; 26(2):100-10. DOI:10.3802/jgo.2015.26.2.100 · 1.60 Impact Factor
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    ABSTRACT: The transcription factor signal transducers and activators of transcription 3 (STAT3) can promote cancer metastasis, but its underlying regulatory mechanisms in gastric cancer cell invasiveness still remain obscure. We investigated the relationship between STAT3 and glycogen synthase kinase-3β (GSK-3β) and its significance in metastatic potential in gastric cancer cells. Immunohistochemical tissue array analysis of 267 human gastric carcinoma specimens showed that the expressions of active forms of STAT3 (pSTAT3) and GSK-3β (pGSK-3β) were found in 68 (25%) and 124 (46%) of 267 gastric cancer cases, respectively, showing a positive correlation (p < 0.001). Cell culture experiments using gastric cancer cell lines SNU-638 and SNU-668 revealed that STAT3 suppression did not affect pGSK-3β expression, whereas GSK-3β inhibition reduced pSTAT3 expression. With respect to metastatic potential in gastric cancer cells, both STAT3 suppression and GSK-3β inhibition decreased cell migration, invasion, and mesenchymal marker (Snail, Vimentin, and MMP9) expression. Moreover, the inhibitory effects of STAT3 and GSK-3β on cell migration were synergistic. These results demonstrated that STAT3 and GSK-3β are positively associated and synergistically contribute to metastatic potential in gastric cancer cells. Thus, dual use of STAT3 and GSK-3β inhibitors may enhance the efficacy of the anti-metastatic treatment of gastric cancer. © 2015 APMIS. Published by John Wiley & Sons Ltd.
    Apmis 04/2015; 123(5). DOI:10.1111/apm.12370 · 1.92 Impact Factor
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    ABSTRACT: Adjuvant chemoradiation following primary surgery is frequently indicated in patients with Stage IB cervical cancer. The aim of this study is to evaluate the role of an MRI-based strategy in avoiding trimodality therapy. We retrospectively reviewed all patients with Stage IB cervical cancer treated initially with primary surgery at Seoul National University Hospital. We suggest an alternative triage strategy in which the primary treatment modality is determined based on preoperative MRI findings. Using this strategy, primary surgery is only indicated when there is no evidence of parametrial involvement (PMI) and lymph node metastasis (LNM) in the MRI results; when there is evidence of either or both of these factors, primary chemoradiation is selected. Assuming that this strategy is applied to our cohort, we evaluate how the rate of trimodality therapy is affected. Of the 254 patients in our sample, 77 (30.3%) had at least one Category 1 risk factor (PMI, LNM, positive resection margin) upon pathologic examination. If the MRI-based strategy had been applied to our cohort, 168 patients would have undergone primary surgery and 86 would have undergone primary chemoradiation. Only 25 patients (9.8%) would have required trimodality therapy based on an indication of at least one Category 1 pathologic risk factor following radical hysterectomy. The inclusion of MRI in the decision-making process for primary treatment modality could have reduced the number of patients requiring trimodality therapy based on the indication of a Category 1 risk factor from 30.3% to 9.8% in our cohort.
    Cancer Research and Treatment 03/2015; DOI:10.4143/crt.2014.370 · 2.98 Impact Factor
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    03/2015; 47(1):68-79. DOI:10.3947/ic.2015.47.1.68
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    ABSTRACT: Whether endometriosis affects the prognosis of ovarian clear cell carcinoma (OCCC) remains controversial despite the relationship between OCCC and endometriosis. A two-center cohort study and meta-analysis were performed to investigate the effect of endometriosis on the prognosis of OCCC. The study reviewed the clinicopathologic data of 109 patients with OCCC arising (n = 47) or not arising (n = 62) in endometriosis between 1997 and 2012 at two tertiary medical centers. Tumor response and survival were compared between the two groups. For further evaluation, PubMed, EmBase, and the Cochrane Library were searched, and a meta-analysis was conducted using 10 cohort studies published from March 1996 to May 2014, including the current cohort study. Complete response did not differ between the patients with OCCC arising in endometriosis and those without endometriosis (77.5 vs. 87.3 %; P = 0.444). Early-stage disease and optimal debulking surgery were the only independent factors that reduced the risk of noncomplete response (adjusted odds ratios 0.203 and 0.038; 95 % confidence intervals [CIs] 0.045-0.920 and 0.006-0.226, respectively). Progression-free survival (PFS) and overall survival (OS) did not differ between the two groups. Early-stage disease and optimal debulking surgery were the only favorable factors that improved PFS (adjusted hazard ratios [HRs] 0.216 and 0.332; 95 % CIs 0.099-0.469 and 0.150-0.732, respectively) and OS (adjusted HRs 0.099 and 0.339; 95 % CIs 0.039-0.252 and 0.141-0.815, respectively). Furthermore, crude and subgroup meta-analyses showed no effect of endometriosis on PFS or OS in OCCC patients. Endometriosis may not affect the tumor response or the prognosis of OCCC patients.
    Annals of Surgical Oncology 02/2015; DOI:10.1245/s10434-014-4319-9 · 3.94 Impact Factor
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    ABSTRACT: The inhibition of mitochondrial permeability transition pore opening during ischemia-reperfusion can ameliorate injuries. This study aimed to investigate the effects of cyclosporine A (CsA) in rats after hemorrhagic shock. Male Sprague-Dawley rats were subjected to pressure-controlled hemorrhagic shock (mean arterial pressure, 38 ± 1 mm Hg) for 90 minutes. After the hemorrhagic shock period, rats were randomly allocated to one of three groups as follows: a control group, a CsA10 group, or a CsA50 group. CsA for the treatment groups (10 mg/kg for the CsA10 group and 50 mg/kg for the CsA50 group) or normal saline for the control group was administered via tail vein for 10 minutes, and shed blood was transfused for 15 minutes. For the survival study, animals were observed for up to 9 hours, and their survival time was recorded until death. Separate experiments were performed to examine the effect of CsA on inflammatory responses and liver injury. Rats were sacrificed at 210 minutes after the shock period, and blood and liver tissues were harvested. Survival times were shown to be significantly longer in the CsA-treated groups (i.e., the CsA10 and CsA50 groups) than in the control group. Plasma interleukin-6 and thiobarbituric acid-reactive substances were significantly lower in the CsA50 group than in the control group and phosphorylation of Akt, GSK-3β, and Bad were significantly increased in the CsA-treated groups compared with the control group. Expressions of Bcl-2, cleaved caspase 3, and cytoplasmic cytochrome C were significantly decreased in the CsA-treated groups compared with the control group. Although histologic liver injury was not significantly different among the groups, ultrastructural changes of mitochondria were more prominent in the control group than in the CsA-treated groups. CsA increased survival time, decreased proinflammatory cytokine and lipid peroxidation, and augmented Akt survival pathways in rats subjected to pressure-controlled hemorrhagic shock.
    Journal of Trauma and Acute Care Surgery 02/2015; 78(2):370-377. DOI:10.1097/TA.0000000000000511 · 1.97 Impact Factor
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    ABSTRACT: Endoscopic ultrasound-guided fine needle aspiration cytology (EUS-FNAC) is currently the most commonly used procedure for obtaining cytologic specimens of the pancreas. It is accurate, minimally invasive, safe and cost-effective. However, there is discrepancy between cytological and surgical diagnoses. This study was aimed at evaluating the diagnostic accuracy of EUS-FNAC of the pancreas. We performed a retrospective review of 191 cases of pancreatic lesions initially diagnosed by EUS-FNAC with subsequent histological diagnosis between 2010 and 2012 in the Department of Pathology, Seoul National University Hospital. Cytologic and surgical diagnoses were categorized into five groups: negative, benign, atypical, malignant, and insufficient for diagnosis. Subsequently, 167 cases with satisfactory yield in both surgical and cytology specimens were statistically analyzed to determine correlations with diagnosis. In comparison to surgical diagnoses, cytologic diagnoses were true-positive in 103 cases (61.7%), true-negative in 28 cases (16.8%), false-positive in 9 cases (5.4%), and false-negative in 27 cases (16.1%). The diagnostic accuracy was 78.4%, sensitivity was 79.2%, and specificity was 75.7%. The positive predictive value was 92.0%, and negative predictive value was 50.9%. EUS-FNAC has high accuracy, sensitivity, specificity and positive predictive value. Overcoming the limitations of EUS-FNAC will make it a useful and reliable diagnostic tool for accurate evaluation of pancreatic lesions.
    01/2015; 49(1):52-60. DOI:10.4132/jptm.2014.10.26
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    ABSTRACT: Purpose The purpose of this study is to compare the MRI features of intestinal and endocervical mucinous borderline ovarian tumors (MBOT). Methods Fifty seven and 17 patients with histologically proven intestinal (n = 62) and endocervical (n = 22) MBOT, respectively, underwent preoperative MRI which were reviewed by two radiologists blinded to histology. An array of MRI features and clinical factors (age, cancer antigen 125 [CA-125]) were compared between intestinal and endocervical subtypes using the t test and Chi-square test. Univariate and multivariate logistic regression analyses were performed to evaluate for significant predictors of subtype. Results There was no significant difference in patient age of intestinal and endocervical MBOT (P = 0.423). CA-125 levels were higher in endocervical MBOT (P = 0.022). Regarding MR features, intestinal MBOT was larger, had more septations, more frequently demonstrated honeycomb loculi, and signal intensity discrepancy while endocervical MBOT was more frequently bilateral with papillary projections (P P = 0.034) and the presence of papillary projections (OR 11.441, P = 0.024) were the only independent predictive factors of endocervical MBOT. Conclusion Intestinal and endocervical subtypes of MBOT demonstrated significantly different features on MRI. The presence of papillary projection was the only independent MRI feature predictive of endocervical MBOT.
    Abdominal Imaging 12/2014; DOI:10.1007/s00261-014-0325-4 · 1.73 Impact Factor
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    ABSTRACT: Success factors of laparoscopic nerve-sparing radical hysterectomy (LNRH) to preserve bladder function are little known despite its widespread use. Thus, we conducted a protocol-based prospective cohort study to evaluate clinicopathologic factors for preserving autonomic nerves and its impact on duration of postoperative catheterization (DPC). From 2012 to 2014, 30 patients with stage IB1 to IIA2 cervical cancer were recruited prospectively to undergo LNRH. All procedures were performed on the left side of the patients by one gynecologic oncologist. Extent of resection and preservation of autonomic nerves were documented in the protocol during LNRH. All patients received laparoscopic type C1 radical hysterectomy, where extent of resection and preservation of autonomic nerves were not different between the right and left sides. Stage IB1 disease was associated with the reduced risk of injury of the left junctions between the hypogastric and the splanchnic nerves; between the splanchnic nerve and the vesical branch of the pelvic plexus (S-V junction) (adjusted odds ratios, 0.06 and 0.06; 95 % confidence intervals, 0.01-0.92 and 0.01-0.48); the right S-V junction with marginal significance (adjusted odds ratio, 0.18; 95 % confidence interval, 0.03-1.06). Furthermore, bilateral preservation of autonomic nerves decreased DPC significantly when compared with failure or unilateral preservation (median, 6 days vs. 34 days or 57 days; P < 0.05). LNRH has a higher likelihood of its success in stage IB1 than in stage IB2 to IIA disease. Moreover, preservation of bilateral autonomic nerves reduces DPC significantly in comparison with failure or unilateral preservation.
    Annals of Surgical Oncology 12/2014; DOI:10.1245/s10434-014-4197-1 · 3.94 Impact Factor
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    ABSTRACT: We investigated MET mRNA expression status using RNA in situ hybridization (ISH) technique in primary and metastatic lesions of 535 surgically resected gastric carcinoma (GC) cases. We compared the results with those of immunohistochemistry and silver in situ hybridization, and examined the association with clinicopathologic characteristics and prognosis. Among 535 primary GCs, 391 (73.1%) were scored 0, 87 (16.3%) were scored 1, 38 (7.1%) were scored 2, 12 (2.2%) were scored 3 and 7 (1.3%) were scored 4 by RNA ISH. High MET mRNA expression (score ≥3) was associated with lymph node metastasis (P = .014), distant metastasis (P = .001), and higher TNM stage (P<.001). MET mRNA expression was correlated with protein expression (r = 0.398; P<.001) and gene copy number (r = 0.345; P<.001). The patients showing high-MET mRNA in primary or metastatic lesions had shorter overall survival than those showing low-MET mRNA (primary tumors, P = .002; metastatic lymph nodes, P<.001). The patients showing positive conversion of MET mRNA status in metastatic lymph node had shorter overall survival than those with no conversion (P = .011). Multivariate analysis demonstrated that high MET mRNA expression in metastatic lymph node was an independent prognostic factor for overall survival (P = .007). Therefore, this study suggests that MET mRNA expression assessed by RNA ISH could be useful as a potential marker to identify MET oncogene-addicted GC.
    PLoS ONE 11/2014; 9(11):e111658. DOI:10.1371/journal.pone.0111658 · 3.53 Impact Factor
  • Placenta 09/2014; 35(9):A89. DOI:10.1016/j.placenta.2014.06.288 · 3.29 Impact Factor
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    ABSTRACT: Diabetic patients with endometrial cancer had more lymph node metastasis than non-diabetic patients with endometrial cancer. L1 cell adhesion molecule (L1CAM) could be possibly associated with lymph node metastasis in diabetic patients with endometrial cancer via epithelial-mesenchymal transition. We aimed to investigate the association between L1CAM expression and lymph node metastasis in diabetic patients with endometrial cancer.
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    ABSTRACT: Purpose: The aim of this study is to evaluate the safety of fertility-sparing surgery as the treatment for patients with primary mucinous epithelial ovarian cancer. Materials and Methods: A retrospective study of patients with mucinous ovarian cancer between 1991 and 2010 was performed. The demographics and survival outcomes were compared between patients who underwent fertility-sparing surgery and those who underwent radical surgery. Results: A total of 110 patients underwent primary surgery. At the time of surgery, tumors appeared to be grossly confined to the ovaries in 90 patients, and evidence of metastasis was definite in 20 patients. Of the 90 patients with tumors that appeared to be grossly confined to the ovaries at surgical exploration, 35 (38.9%) underwent fertility-sparing surgery. The Kaplan- Meier curve and the log rank test showed no difference in either recurrence-free survival (p=0.792) or disease-specific survival (p=0.706) between the two groups. Furthermore, there was no significant difference in recurrence-free survival (p=0.126) or disease-specific survival (p=0.377) between the two groups, even when the analysis was limited to women below the age of 40. In a multivariate Cox model, fertility-sparing surgery had no effect on either recurrence-free survival (recurrence hazard ratio [HR], 1.20; 95% confidence interval [CI], 0.25 to 5.71) or disease-specific survival (death HR, 0.88; 95% CI, 0.17 to 4.60). Conclusion: Fertility-sparing surgery in primary mucinous cancer grossly confined to the ovaries may be a safe option and one not associated with an increase in recurrence or mortality.
    Cancer Research and Treatment 08/2014; DOI:10.4143/crt.2014.004 · 2.98 Impact Factor
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    ABSTRACT: Gastric adenocarcinoma is the sixth most common and third most lethal cancer in the world. Except for HER2-targeted therapy, targeted agents against specific molecules participating in gastric carcinogenesis, including those in the mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathway have not been proved to be effective. However, some studies have suggested that dysfunction of TSC1 may augment mTOR inhibitor activity. We studied p-mTOR and TSC1 status by immunohistochemical analysis of gastric carcinoma samples using a tissue microarray method and expression values adopted from The Cancer Genome Atlas. High p-mTOR and low TSC1 expression status is associated with adverse clinicopathologic parameters. Patients with high p-mTOR levels showed poor survival. Patients with low TSC1 levels showed unfavorable survival status in the overall patients group. The combination of p-mTOR status and TSC1 status provided more strong survival information than using each parameter alone. In gastric cancer, high p-mTOR expression level is a statistically significant parameter in multivariate and Kaplan-Meier analyses (log-rank test). In addition to p-mTOR, TSC1 expression provided additional information to predict survival. We therefore suggest that evaluation of both p-mTOR and TSC1 status may be helpful in clinical trials related to mTOR inhibitors. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 06/2014; 109(8). DOI:10.1002/jso.23585 · 2.84 Impact Factor
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    ABSTRACT: The aim of this study is to identify a patient group with a low-risk of parametrial involvement (PMI) in Stage IB1 cervical cancer using preoperative magnetic resonance imaging (MRI) parameters. In total, 190 Stage IB1 cervical cancer patients with clinically visible lesions who had undergone Type C2 radical hysterectomy and preoperative MRI were included in this study. Clinical records, pathology reports, and preoperative MRI findings were reviewed retrospectively. Of the 190 patients, 19 (10%) had pathologic PMI. The largest tumor diameter identified by MRI ranged from zero (no definite mass on the cervix) to 60mm, with a median of 21mm. Patients were identified as being either low-risk (tumor size≤25mm and no evidence of PMI, n=127) or high-risk (tumor size>25mm and/or findings indicating PMI, n=63) based on MRI parameters. The rate of pathologic PMI in low- and high-risk patients was 0.0% and 30.2%, respectively (P<0.001). Five-year progression-free survival in low-risk patients was 95.9%, which is significantly better than the rate of 85.6% for patients in the high-risk group (P=0.039). Preoperative MRI parameters can help identify patients with a low-risk of PMI and, therefore, possible candidates for trials on less radical surgery.
    Gynecologic Oncology 04/2014; 134(1). DOI:10.1016/j.ygyno.2014.02.042 · 3.69 Impact Factor
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    ABSTRACT: Epithelial-mesenchymal transition (EMT) has been suggested to contribute to tumor progression and acquisition of therapeutic resistance. To assess the clinical significance of EMT-associated proteins, we evaluated the expression of Snail and Slug, the key regulators of EMT, in the primary ovarian cancer samples (n = 103) by immunohistochemistry. Snail was differentially expressed according to the histologic subtype (P = 0.001) and was predominantly expressed in serous and endometrioid types. In the serous and endometrioid adenocarcinomas, the expression of Snail remained high across the stage and grade, suggesting its role in the early phase of carcinogenesis. However, the expression of Snail and Slug was not related to chemoresistance and poor prognosis and did not serve as independent predictive or prognostic marker.
    04/2014; 2014:495754. DOI:10.1155/2014/495754
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    ABSTRACT: Melanoma that involves the upper gastrointestinal (GI) tract is rare and studies relating to endoscopic and pathologic findings with clinical outcomes are lacking. We reviewed the gross and microscopic patterns of the upper GI tract in primary and metastatic melanoma, and examined their association with clinical outcomes. Twenty-nine cases of primary esophageal (n = 19) and metastatic gastric and/or duodenal melanoma (n = 10) that were detected during upper GI endoscopy between 1995 and 2011 were retrospectively analyzed. Three types of gross patterns were recognized-nodular pattern in 7 cases, mass-forming pattern in 18 cases, and flat pigmented pattern in 4 cases. In primary esophageal melanoma, 13 patients (68.4 %) underwent surgery and 9 received palliative therapy. Of all cases, 22 patients (75.9 %) died of disease progression; the median overall survival period was 12 months (interquartile range [IQR] 4.5-24.5 months), and from recognition of upper GI tract melanoma the median overall survival period was 9 months (IQR 3.5-17.0 months). In primary esophageal cases, skin melanoma stage better discriminated the patients with good prognosis than the esophageal cancer stage. The flat pigmented gross pattern proved to be a good prognostic factor in primary and metastatic GI tract melanomas (p = 0.016 and p = 0.046, respectively). Melanoma of the GI tract is a highly aggressive disease with a poor prognosis, both in primary and metastatic cases. However, in primary esophageal melanoma, careful inspection of the mucosa during endoscopic examination followed by surgical resection may result in extended survival.
    Annals of Surgical Oncology 03/2014; 21(8). DOI:10.1245/s10434-014-3637-2 · 3.94 Impact Factor
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    ABSTRACT: Generation of reactive oxygen species (ROS) is an important mechanism of ischemia-reperfusion injury. Abrupt reoxygenation compared with slow reoxygenation has been known to increase ROS generation. Thus, slow and stepwise reperfusion can reduce ROS generation and subsequent ischemia-reperfusion injury. This study investigated the effect of slow reperfusion by blood pressure-targeted stepwise resuscitation (PSR) in hemorrhagic shock. Pressure-controlled hemorrhagic shock was induced in male Sprague-Dawley rats for 1 hour. Rats were then allocated to one of three groups (no-resuscitation group, n = 14; PSR group, n = 15; rapid normalization of blood pressure (RR) group, n = 15). Survival time and hemodynamic changes were recorded and compared. Blood samples and liver tissue were harvested after 6 hours of resuscitation in surviving rats. All of the rats in the no-resuscitation group were expired before the end of the 6-hour observation period. Survival times were significantly longer in the PSR group than in the RR group (survival rates, 11 of 15 vs. 5 of 15, log rank p = 0.032). Plasma amino alanine transferase, histologic liver injury, and ROS generation in the liver tissue were significantly lower in the PSR group than in the RR group (all findings significant, p < 0.05). In addition, PSR significantly decreased plasma nitric oxide, liver interleukin 1β, and liver interleukin 6 compared with rapid resuscitation in addition to augmenting Akt survival pathways (all p < 0.05). Slow reperfusion by PSR decreased mortality, ROS generation, and liver injury in rats undergoing hemorrhagic shock. Stepwise resuscitation also decreased inflammatory cytokine production and augmented Akt survival pathways.
    03/2014; 76(3):771-778. DOI:10.1097/TA.0000000000000106

Publication Stats

1k Citations
357.51 Total Impact Points

Institutions

  • 2007–2015
    • Yonsei University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
    • Seoul National University Bundang Hospital
      • Department of Pathology
      Seoul, Seoul, South Korea
  • 2008–2014
    • Seoul National University
      Sŏul, Seoul, South Korea
  • 2006–2014
    • Seoul National University Hospital
      • • Department of Pathology
      • • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2013
    • Kochi Medical School
      Kôti, Kōchi, Japan
    • Chung-Ang University Hospital
      Sŏul, Seoul, South Korea
  • 2004
    • Research Institute of Ophthalmology
      Al Qāhirah, Al Qāhirah, Egypt