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1.  Hiatal hernia in pediatric patients: laparoscopic versus open approaches 
The aim of this study was to evaluate the surgical outcomes of laparoscopic approach for hiatal hernia (HH) in pediatric patients.
This was a retrospective study of 33 patients younger than 18 years who underwent an operation for HH between January 1999 and December 2012.
The HH symptoms were various and included regurgitation, vomiting, weight loss, cough, hoarseness, and cyanosis. Among the 33 patients, there were 25 sliding types, 1 paraesophageal type, and 7 mixed types. Open surgery (OS) and laparoscopic surgery (LS) were used in 16 and 17 patients, respectively. There were no statistically significant differences in sex, age, or body weight between the groups. The median operating time was longer in the LS group (150 minutes; range, 90-250 minutes vs. 125 minutes; range, 66-194 minutes; P = 0.028). Time to oral intake was shorter in the LS group than in the OS group (1 day; range, 1-3 days vs. 2 days; range, 1-7 days; P = 0.001) and time to full feeding was shorter in the LS group than in the OS group (6 days; range, 3-16 days vs. 10 days; range, 3-33 days; P = 0.048). There were no differences in length of hospital stay and complications between the two groups. There was no perioperative mortality or recurrence of HH.
A good surgical outcome for laparoscopic correction of HH was seen in pediatric patients.
PMCID: PMC4024937  PMID: 24851228
Hiatal hernia; Child; Laparoscopy; Fundoplication; Minimal invasive surgical procedures
2.  Adrenocortical tumors in children 18 years old and younger 
Pediatric adrenocortical tumors (ACTs) are rare. We reviewed findings in 8 children, 18 years of age or younger, diagnosed with ACT in our institution over the past 15 years.
We retrospectively reviewed 8 children with ACTs treated between 1996 and 2010.
Three girls and 5 boys were treated for ACTs; their median age at presentation was 144 months (range, 28 months to 18 years). Seven patients showed signs of endocrine dysfunction, 4 with Cushing syndrome, 2 with virilization, and 1 with hyperaldosteronism. One patient, with symptoms of hematuria, underwent a computed tomography scan, which showed an adrenal mass. The median duration of symptoms prior to resection was 6 months (range, 1 to 24 months). Five patients had adenomas and 3 had carcinomas. All underwent complete resection of the tumor, with laparoscopic adrenalectomy performed on 3 patients with adenoma and 1 with carcinoma. The median tumor weight was 12.5 g (range, 1 to 130 g) and the median tumor volume was 18.3 cm3 (range, 2.2 to 299.2 cm3). At a median follow-up of 5.1 years (range, 4 months to 15 years), all 8 patients remain alive with no recurrence of disease.
The characteristics of pediatric ACTs vary considerably. Laboratory findings, clinical hormonal features, and tumor size could not distinguish adenomas from carcinomas before surgery. Complete tumor resection was successful, with no tumor recurrence. However, the small number of patients and short follow-up period limit assessments of prognosis.
PMCID: PMC3319779  PMID: 22493766
Adrenocortical adenoma; Carcinoma; Child
3.  Postoperative acute renal failure in patients with gynecologic malignancies: analysis of 10 cases and review of the literature 
Postoperative acute renal failure (PO-ARF) is an important cause of mortality among surgical patients. Although there have been many reports on PO-ARF after cardiac surgery and liver transplantation, less is known about the risk of PO-ARF after gynecologic operations. We aimed to investigate the risk of PO-ARF on gynecologic malignancy operations.
1,155 patients' medical charts were reviewed who underwent therapeutic surgery for gynecologic malignancies from January 1, 2005 to December 31, 2007, at the Asan Medical Center, Seoul, Korea.
Of these, 10 patients, comprising 0.89% of those who underwent radical hysterectomies and 0.86% of those who underwent debulking operations, were diagnosed with PO-ARF. Their mean age was 61.9±10.1 years. Five patients had preoperative risk factors. Mean operating time was 360.8±96.2 minutes. Five patients experienced intra-operative hypotension and all patients were given blood transfusions during surgery. Eight patients underwent hemodialysis, with two continuing on dialysis to date. Only two patients fully recovered.
Patients undergoing surgery for gynecologic malignancies may be at high risk for PO-ARF, because of old age, long operation times, and profuse bleeding. It is necessary to monitor these patients for postoperative renal function and urine output. If a postoperative oliguric state is detected, aggressive volume expansion should be started immediately, followed by hemodialysis.
PMCID: PMC2676502  PMID: 19471672
Postoperative acute renal failure; Gynecologic malignancy
4.  Asian Society of Gynecologic Oncology International Workshop 2014 
The Asian Society of Gynecologic Oncology International Workshop 2014 on gynecologic oncology was held in Asan Medical Center, Seoul, Korea on the 23rd to 24th August 2014. A total of 179 participants from 17 countries participated in the workshop, and the up-to-date findings on the management of gynecologic cancers were presented and discussed. This meeting focused on the new trends in the management of cervical cancer, fertility-sparing management of gynecologic cancers, surgical management of gynecologic cancers, and recent advances in translational research on gynecologic cancers.
PMCID: PMC4302288  PMID: 25609163
Endometrial Neoplasms; Fertility Preservation; Laparoscopy; Ovarian Neoplasms; Uterine Cervical Neoplasms
5.  A Genome-Wide Association Study Identifies Potential Susceptibility Loci for Hirschsprung Disease 
PLoS ONE  2014;9(10):e110292.
Hirschsprung disease (HSCR) is a congenital and heterogeneous disorder characterized by the absence of intramural nervous plexuses along variable lengths of the hindgut. Although RET is a well-established risk factor, a recent genome-wide association study (GWAS) of HSCR has identified NRG1 as an additional susceptibility locus. To discover additional risk loci, we performed a GWAS of 123 sporadic HSCR patients and 432 unaffected controls using a large-scale platform with coverage of over 1 million polymorphic markers. The result was that our study replicated the findings of RET-CSGALNACT2-RASGEF1A genomic region (rawP = 5.69×10−19 before a Bonferroni correction; corrP = 4.31×10−13 after a Bonferroni correction) and NRG1 as susceptibility loci. In addition, this study identified SLC6A20 (adjP = 2.71×10−6), RORA (adjP = 1.26×10−5), and ABCC9 (adjP = 1.86×10−5) as new potential susceptibility loci under adjusting the already known loci on the RET-CSGALNACT2-RASGEF1A and NRG1 regions, although none of the SNPs in these genes passed the Bonferroni correction. In further subgroup analysis, the RET-CSGALNACT2-RASGEF1A genomic region was observed to have different significance levels among subgroups: short-segment (S-HSCR, corrP = 1.71×10−5), long-segment (L-HSCR, corrP = 6.66×10−4), and total colonic aganglionosis (TCA, corrP>0.05). This differential pattern in the significance level suggests that other genomic loci or mechanisms may affect the length of aganglionosis in HSCR subgroups during enteric nervous system (ENS) development. Although functional evaluations are needed, our findings might facilitate improved understanding of the mechanisms of HSCR pathogenesis.
PMCID: PMC4195606  PMID: 25310821
6.  Analysis and Comparison of Somatic Mutations in Paired Primary and Recurrent Epithelial Ovarian Cancer Samples 
PLoS ONE  2014;9(6):e99451.
The TP53 mutations have been proved to be predominated in ovarian cancer in a study from The Cancer Genome Atlas (TCGA). However, the molecular characteristics of recurrent ovarian cancers following initial treatment have been poorly estimated. This study was to investigate the pattern of somatic point mutations in matched paired samples of primary and recurrent epithelial ovarian cancers, using the OncoMap mutation detection protocol. We have adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. OncoMap v.4.4 was used to evaluate genomic DNA isolated from a set of 92 formalin-fixed, paraffin-embedded (FFPE) tumors, consisting of matched paired samples of initially diagnosed and recurrent tumors from 46 epithelial ovarian cancer (EOC) patients. Mutations were observed in 33.7% of the samples, with 29.3% of these samples having a single mutation and the remaining 4.3% having two or more mutations. Among the 41 genes analyzed, 35 mutations were found in four genes, namely, CDKN2A (2.2%), KRAS (6.5%), MLH1 (8.2%) and TP53 (20.7%). TP53 was the most frequently mutated gene, but there was no correlation between the presence of mutation in any gene and clinical prognosis. Furthermore, somatic mutations did not differ between primary and recurrent ovarian carcinomas. Every mutation present in recurrent samples was detected in the corresponding primary sample. In conclusion, these OncoMap data of Korean EOC samples provide that somatic mutations were found in CDKN2A, KRAS, MLH1, and TP53. No differences in mutational status between primary and recurrent samples were detected. To understand the biology of tumor recurrence in epithelial ovarian cancer, more studies are necessary, including epigenetic modifications or additional mutations in other genes.
PMCID: PMC4060993  PMID: 24936796
7.  Impact of body mass index on the prognosis of Korean women with endometrioid adenocarcinoma of the uterus: A cohort study 
Obstetrics & Gynecology Science  2014;57(2):115-120.
To analyze how pretreatment body mass index relates to known endometrial cancer prognostic factors and how it impacts the disease-free survival and cause-specific survival of Korean women with endometrial cancer.
The patients were divided into the non-obese (<25 kg/m2) and obese groups (≥25 kg/m2) according to their pretreatment body mass index. The 25 kg/m2 body mass index cut-off was based on the World Health Organization criteria for Asian people. The two groups were compared in terms of their clinicopathological characteristics and survival outcomes.
A total of 213 consecutive patients with endometrioid adenocarcinoma of the uterus met the eligibility criteria of this study and were included in the analysis. Of these patients, 105 patients had a body mass index less than 25 kg/m2 (non-obese group) and 108 patients had a body mass index equal to or more than 25 kg/m2 (obese group). The two groups did not differ in terms of age, menopause, parity, height, FIGO (International Federation of Obstetrics and Gynecology) stage, tumor grade, tumor size, myometrial invasion, lymphovascular space invasion, cytology, and lymph node metastasis. Body mass index was not a significant factor for disease-free and cause-specific survival in univariate analysis, and after adjusting for all prognostic factors that were significant in univariate analysis, it did not associate significantly with disease-free and cause-specific survival.
In Korean women with endometrioid adenocarcinoma of the uterus, a high pretreatment body mass index did not associate with other prognostic factors and had little impact on the disease-free survival and cause-specific survival of these women.
PMCID: PMC3965694  PMID: 24678484
Body mass index; Endometrial neoplasms; Obesity; Prognosis
8.  Reproductive outcomes after laparoscopic radical trachelectomy for early-stage cervical cancer 
The objective of this study was to estimate the reproductive outcome of young women with early-stage cervical cancer who underwent fertility-sparing laparoscopic radical trachelectomy (LRT).
We performed a retrospective review of the medical records of patients with early-stage cervical cancer who underwent LRT. Clinicopathological data were obtained from patient medical records, and reproductive outcome data were obtained from patient medical records and telephone interviews.
Fifty-five patients who underwent successful LRT were included in this study. The median age of patients was 32 years (range, 22 to 40 years), and the median follow-up time after LRT was 37 months (range, 3 to 105 months). Menstruation resumed in all patients after LRT, with fifty patients (90.9%) and five patients (9.1%) reporting regular and irregular menstruation, respectively. Six patients (10.9%) presented with cervical stenosis, which was manifested by regular but decreased menstrual flow and newly-developed dysmenorrhea. These patients underwent cervical cannulation and dilatation. Eighteen patients (32.7%) attempted to conceive, with six out of 18 patients receiving fertility treatments. Fourteen pregnancies (i.e., four missed abortions, six preterm births and four full-term births) occurred in 10 patients after LRT. Nine out of 10 patients gave birth to 10 healthy babies. The pregnancy rate after LRT was 55.6% (10/18). The spontaneous abortion rate and live birth rate were 28.6% (4/14) and 71.4% (10/14), respectively. The preterm birth rate was 60% (6/10).
Pregnancy and live birth rates after LRT were promising; however, the preterm birth rate was relatively high. Cervical stenosis also occurred in a small percentage of patients.
PMCID: PMC3893680  PMID: 24459575
Cervical cancer; Fertility; Laparoscopic radical trachelectomy; Pregnancy outcome; Reproductive outcome
9.  Liver transplantation in a child with acute liver failure resulting from drug rash with eosinophilia and systemic symptoms syndrome 
Korean Journal of Pediatrics  2013;56(5):224-226.
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is characterized by a severe idiosyncratic reaction including rash and fever, often with associated hepatitis, arthralgias, lymph node enlargement, or hematologic abnormalities. The mortality rate is approximately 10%, primarily owing to liver failure with massive or multiple disseminated focal necrosis. Here, we report a case of a 14-year-old girl treated with vancomycin because of a wound infection by methicillin-resistant Staphylococcus aureus, who presented with non-specific symptoms, which progressed to acute liver failure, displaying the hallmarks of DRESS syndrome. With the presence of aggravated hepatic encephalopathy and azotemia, the patient was refractory to medical treatments, she received a living-donor liver transplantation, and a cure was achieved without any sign of recurrence. Vancomycin can be a cause of DRESS syndrome. A high index of suspicion and rapid diagnosis are necessary not to miss this potentially lethal disease.
PMCID: PMC3668204  PMID: 23741237
DRESS syndrome; Vancomycin; Acute liver failure; Liver transplantation
10.  Comparison of outcomes between radical hysterectomy followed by tailored adjuvant therapy versus primary chemoradiation therapy in IB2 and IIA2 cervical cancer 
Journal of Gynecologic Oncology  2012;23(4):226-234.
To compare survival outcomes and treatment-related morbidities between radical hysterectomy (RH) and primary chemoradiation therapy (CRT) in patients with bulky early-stage cervical cancer.
We selected 215 patients with stage IB2 and IIA2 cervical cancer (tumor diameter > 4 cm on magnetic resonance imaging) who underwent RH followed by tailored adjuvant therapy (n=147) or primary CRT (n=68) at two tertiary referral centers between 2001 and 2010.
About twenty nine percent of patients were cured by RH alone and these patients experienced the best survival outcomes with the lowest morbidity rates. After the median follow-up times of 40 months, 27 RH (18.4%) and 20 CRT (29.4%) patients had recurrence (p=0.068) and 23 (15.6%) and 17 (25%) patients died of disease (p=0.101). The 5-year progression-free survival were 77% and 66% (p=0.047), and the 5-year overall survival were 78% and 67% (p=0.048) after RH and primary CRT, respectively. In multivariate analysis, patients who received primary CRT was at higher risk for tumor recurrence (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.24 to 4.14; p=0.008) and death (OR, 3.02; 95% CI, 1.53 to 5.98; p=0.001) than those who received RH. Grade 3-4, early (17% vs. 30.9%, p=0.021) and late (1.4% vs. 8.8%, p=0.007) complications were significantly less frequent after RH than primary CRT.
Thirty percent of patients were cured by RH alone. A treatment outcome was better in this retrospective study in terms of morbidity and survival. Randomized trials are needed to confirm this result.
PMCID: PMC3469857  PMID: 23094125
Bulky early-stage cervical cancer; Chemoradiation therapy; Radical hysterectomy; Stage IB2; Stage IIA2
11.  The surgical experience for retroperitoneal, mesenteric and omental cyst in children 
Intra-abdominal cystic masses originating from the retroperitoneum, mesentery or omentum are very rare and mostly benign tumors, but sometimes present as a complicated cyst encasing the major organs.
We analyzed the clinical findings, histologic diagnosis, and surgical outcomes in children who underwent operation for retroperitoneal, omental, and mesenteric cyst from 1998 to 2010, retrospectively.
Twenty-three patients (male, 12; female, 11) underwent the operation at a median age of 46 months (range, 9 days to 16 years). Among them, 17 cysts presented one or two symptoms such as abdominal mass, abdominal pain or abdominal distension. The median duration of symptoms was 7 days (range, 1 day to 365 days). Five were detected prenatally. Ten cysts were found in retroperitoneum, 8 in the omentum and 5 in the mesentery. The median diameter was 13 cm (range, 3 to 30 cm). Twenty cysts were completely removed. Five mesenteric cysts required bowel resection and anastomosis. Three of retroperitoneal cysts were impossible to complete excise because of location and extensiveness. Pathologically, 20 cysts were lymphangioma and 3 were pseudocyst. The morbidity was one of adhesive ileus and the mortality was one who had extensive retroperitoneal cyst with mesenteric cyst. He died from sepsis. During follow-up period, there was no recurrence.
Preoperative diagnosis and localization for these cysts are very difficult. Complete excision was possible in almost all cases despite the size, bringing a favorable outcome. The possibility of this disease entity should be considered as the cause of acute abdomen.
PMCID: PMC3412181  PMID: 22880185
Retroperitoneal cyst; Mesenteric cyst; Omental cyst; Lymphangioma; Pseudocyst
12.  Clinical experience with persistent cloaca 
Persistent cloaca is one of the most severe types of anorectal malformation. Appropriate initial drainage is difficult due to their various malformations and hydrocolpos or dilated urinary bladder. Corrective surgery also differs among individual patients. We describe our experiences with the surgical management of children with persistent cloaca.
We retrospectively reviewed 16 children diagnosed with persistent cloaca at Asan Medical Center.
Sixteen patients were managed in their neonatal period. Twelve patients had enlarged bladder or vagina at birth. Three patients, who did not undergo cystostomy or vaginostomy at first operation, had earlier complications after surgery or required drainage tube insertion. One patient who did not undergo hydrocolpos drainage died of sepsis and complications. Nine patients underwent corrective surgery; posterior sagittal anorectovaginourethroplasty using the Pena method. Three patients required additional operations due to complications after surgery.
Patients found to have anatomical malformations before colostomy, as well as hydrocolpos and bladder enlargement, require a vaginostomy with or without a cystostomy to reduce complications. Follow-up is required in patients with hydrocolpos and bladder enlargement to determine whether vaginal drainage improves dilated bladder. Continuous long-term follow-up examination is required to determine the long-term results of corrective surgery.
PMCID: PMC3204684  PMID: 22066071
Persistent cloaca; Anorectal malformation; Hydrocolpos; Posterior sagittal anorectovaginourethroplasty
13.  An 18-year experience of tracheoesophageal fistula and esophageal atresia 
Korean Journal of Pediatrics  2010;53(6):705-710.
To determine the clinical manifestations and outcomes of patients with tracheoesophageal fistula (TEF) and esophageal atresia (EA) born at a single neonatal intensive care unit.
A retrospective analysis was conducted for 97 patients with confirmed TEF and EA who were admitted to the neonatal intensive care unit between 1990 and 2007.
The rate of prenatal diagnosis was 12%. The average gestational age and birth weight were 37+2 weeks and 2.5±0.7 kg, respectively. Thirty-one infants were born prematurely (32%). Type C was the most common. The mean gap between the proximal and distal esophagus was 2 cm. Esophago-esophagostomy was performed in 72 patients at a mean age of 4 days after birth; gastrostomy or duodenostomy were performed in 8 patients. Forty patients exhibited vertebral, anorectal, cardiac, tracheoesophageal, renal, limb (VACTERL) association with at least 2 combined anomalies, and cardiac anomaly was the most common. The most common post-operative complications were esophageal stricture followed by gastroesophageal reflux. Balloon dilatation was performed for 1.3 times in 26 patients at a mean age of 3 months. The mortality and morbidity rates were 24% and 67%, respectively, and the most common cause of death was sepsis. The weight of approximately 40% patients was below the 10th percentile at 2 years of age.
Mortality and morbidity rates of patients with TEF and EA are high as compared to those of infants with other neonatal surgical diseases. Further efforts must be taken to reduce mortality and morbidity and improve growth retardation.
PMCID: PMC2994136  PMID: 21189942
Tracheoesophageal fistula; Esophageal atresia; VACTERL association; Mortality; Morbidity; Growth
14.  Necessity of Radical Hysterectomy for Endometrial Cancer Patients with Cervical Invasion 
Journal of Korean Medical Science  2010;25(4):552-556.
To determine whether radical hysterectomy is necessary in the treatment of endometrial cancer patients with cervical involvement, we reviewed the medical records of women who underwent primary surgical treatment for endometrial carcinoma and selected patients with pathologically proven cervical invasion. Among 133 patients, 62 patients underwent extrafascial hysterectomy (EH) and 71 radical or modified radical hysterectomy (RH). The decision regarding EH or RH was made at the discretion of the attending surgeon. The sensitivity of pre-operative magnetic resonance imaging for cervical invasion was 44.7% (38/85). In RH patients, 10/71 (14.1%) patients had frankly histologic parametrial involvement (PMI). All were stage III or over. Eight of 10 patients had pelvic/paraaortic node metastasis and two showed extrauterine spread. In 74 patients with stage II cancer, RH was performed in 41 and PMI was not seen. Sixty-six (89.2%) patients had adjuvant radiation therapy and there were 3 patients who had developed recurrent disease in the RH group and none in the EH group (Mean follow-up: 51 months). Although these findings cannot conclusively refute or support the necessity of radical hysterectomy in patients with cervical extension, it is noteworthy that the risk of PMI seems to be minimal in patients with a tumor confined to the uterus without evidence of extrauterine spread.
PMCID: PMC2844596  PMID: 20357997
Endometrial Neoplasms; Radical Hysterectomy; Cervical Invasion
15.  Infections after Living Donor Liver Transplantation in Children 
Journal of Korean Medical Science  2010;25(4):527-531.
The aim of this study was to evaluate the infectious complications after living donor liver transplantation (LDLT) in children. We enrolled 95 children (38 boys and 57 girls) who underwent LDLT from 1994 to 2004. The median age was 22 months (range, 6 months to 15 yr). We retrospectively investigated the proven episodes of bacterial, viral, and fungal infection. There occurred 150 infections in 67 (70%) of 95 patients (1.49 infections/patient); 74 in 43 patients were bacterial, 2 in 2 were fungal, and 74 in 42 were viral. The most common sites of bacterial infection were the bloodstream (33%) and abdomen (25%). Most of the bacterial infections occurred within the first month after LDLT. Bacterial and fungal infections did not result in any deaths. The most common causes of viral infection were Epstein-Barr virus in 37 patients and cytomegalovirus in 18. Seven of the 14 deaths after LDLT were associated with viral infection. Our study suggests that infection is one of the important causes of morbidity and mortality after LDLT. Especially careful monitoring and management of viral infections is crucial for improving the outcome of LDLT in children.
PMCID: PMC2844587  PMID: 20357992
Infection; Liver Transplantation; Living Donors; Child
16.  Proliferation of CD4+CD25high+Foxp3+ regulatory T lymphocytes in ex vivo expanded ascitic fluid from primary and recurrent ovarian carcinoma 
Regulatory T lymphocytes evoke the immune tolerance by suppressing and inactivating cytotoxic T lymphocytes. The objective of this study was to compare the proportion of regulatory T lymphocytes, precisely defined as CD4+CD25high+Foxp3+ T lymphocytes, in primary and recurrent ovarian carcinoma before and after ex vivo expansion of ascites with interleukin-2 (IL-2).
Ascitic fluid samples were obtained from 26 patients with ovarian carcinoma. Lymphocytes were isolated from ascites and cell markers were analyzed by flow cytometry using anti-CD3/CD4/CD8/CD16/CD56/CD25 and anti-Foxp3 antibodies. Lymphocytes were incubated for 2 to 3 weeks and expanded ex vivo by IL-2 stimulation and their phenotypes were analyzed by flow cytometry.
Following ex vivo expansion, ascitic fluid lymphocytes increased by a greater extent in the recurrent group than in the primary group. The proportion of ex vivo-expanded lymphocytes changed as follows; CD4+ T lymphocytes increased, CD8+ T lymphocytes decreased, and the proportion of CD3-CD16+56+ NK cells was unchanged. The proportion of CD4+CD25high+Foxp3+ regulatory T lymphocytes in CD4+ T lymphocytes increased after ex vivo expansion in both groups, but to a greater degree in the recurrent group.
This study showed that regulatory T lymphocytes, neither cytotoxic T lymphocytes nor NK cells, were extensively increased after ex vivo expansion, especially in recurrent ovarian carcinoma. These results may provide information that helps to guide the future development of adoptive immunotherapy against ovarian carcinoma.
PMCID: PMC2849947  PMID: 20379446
Regulatory T lymphocyte; Foxp3; Ex vivo expansion; Ovarian carcinoma; Ascites
17.  Hexamethylmelamine as Consolidation Treatment for Patients with Advanced Epithelial Ovarian Cancer in Complete Response after First-Line Chemotherapy 
Journal of Korean Medical Science  2009;24(4):679-683.
The aim of this study was to assess the efficacy of consolidation therapy with hexamethylmelamine (HMM) in patients with advanced epithelial ovarian cancer (EOC). Patients treated at our hospital between January 1997 and November 2006 and in documented clinical complete response from advanced ovarian cancer following front-line platinum-based therapy were retrospectively analyzed. The patients treated with HMM were compared to the patients of matched counterpart without consolidation therapy. Of 102 patients enrolled, 49 were treated with HMM and 53 received no consolidation treatment. For patients with HMM and observed patients, the mean age were 54.6 and 55.6 yr; the distribution of stage was similar (P=0.977); the optimal surgery was performed in 36 (73.5%) and 44 (83%) (P=0.336); the recurrence rate were 27 (55.1%) and 33 (62.3%) (P=0.463); and the median progression-free survival were 38 months and 21 months for patients with HMM and observed patients (P=0.235). No treatment-related adverse events were reported during the follow-up period. Although this study failed to show the significant survival benefit of consolidation therapy with HMM in patients with advanced EOC, we consider that our study can contribute data to investigate the effectiveness of consolidation therapy in epithelial ovarian cancer.
PMCID: PMC2719200  PMID: 19654952
Altretamine; Consolidation Therapy; Advanced Epithelial Ovarian Cancer
18.  Efficacy of taxane and platinum-based chemotherapy guided by extreme drug resistance assay in patients with epithelial ovarian cancer 
Journal of Gynecologic Oncology  2009;20(2):96-100.
To evaluate the efficacy of taxane and platinum-based chemotherapy guided by extreme drug resistance assay (EDRA) in patients with epithelial ovarian cancer.
Thirty-nine patients were enrolled, who were diagnosed as epithelial ovarian cancer, tubal cancer or primary peritoneal carcinoma and received both debulking surgery and EDRA in Asan Medical Center between August 2004 and August 2006. Another thirty-nine patients were enrolled, who did not receive EDRA as control. Paclitaxel 175 mg/m2 and carboplatin AUC 5 were administered as primary combination chemotherapy to both EDRA group and the control group. In the EDRA group, paclitaxel was replaced by docetaxel 75 mg/m2 if a patient showed extreme drug resistance (EDR) to paclitaxel and not to docetaxel. Carboplatin was replaced by cisplatin 75 mg/m2 if a patient showed EDR to carboplatin and not to cisplatin. If only one drug showed low drug resistance (LDR), it was allowed to add another drug which showed LDR such as gemcitabine 1,000 mg/m2. CT scan was performed every three cycles and CA-125 was checked at each cycle.
There was no significant difference in overall response rate between EDRA group and the control group (84.5% vs. 71.8%, p=0.107). However, 93.8% of patients in EDRA group did not show EDR to at least one drug and its response rate was significantly higher than that of the control group (93.3% vs. 71.8%, p=0.023).
we could choose a combination of taxane and platinum which did not show EDR and could obtain a good response in the patients with ovarian cancer.
PMCID: PMC2705007  PMID: 19590720
Ovarian neoplasms; Antineoplastic combined chemotherapy protocol; Drug resistance; neoplasm; Biologic assay
19.  Mutational Analysis of KRAS, BRAF, and TP53 Genes of Ovarian Serous Carcinomas in Korean Women 
Yonsei Medical Journal  2009;50(2):266-272.
To assess the prevalence of KRAS, BRAF, and TP53 mutations in cases of low-grade and high-grade serous carcinomas and to evaluate the clinical outcomes of these morphologically distinct carcinomas.
Materials and Methods
Patients with primary invasive serous carcinomas were classified according to the universal grading system. Grade 2 serous tumors were excluded. A total of 100 patients were included for clinical evaluation. Thirty-seven patients, including 20 with low-grade and 17 with high-grade carcinomas, were selected for mutational analysis.
The low-grade carcinoma group was characterized by young age and premenopausal period compared with the high-grade carcinoma group, but there were no statistically significant differences in stage, metastasis of lymph node and residual disease. There were no statistically significant differences in survival rates, however, the low-grade carcinoma group showed a trend for improved progression-free survival compared with the high-grade carcinoma group of early stage (p = 0.064). Mutations in KRAS and BRAF were found in 6 (30%) and 2 (10%) patients in the low-grade carcinoma group, respectively, however, they were not found in the high-grade carcinoma group. KRAS and BRAF mutations were mutually exclusive, and both mutations were observed in 40% (8/20). The frequency of TP53 mutations in low-grade and high-grade carcinoma groups were found in 20% (4/20) and 70.6% (12/17), respectively (p = 0.009).
Low-grade serous carcinoma shows mutation pattern different from that with high-grade carcinoma. As there were no significant differences in stage distribution and survival, especially in advanced stage, we suggest that more studies are needed to segregate these patients into distinct disease entities.
PMCID: PMC2678703  PMID: 19430562
Ovary; serous carcinoma; grade; mutation
20.  Living Donor Liver Transplantation in a Korean Child with Glycogen Storage Disease Type IV and a GBE1 Mutation 
Gut and Liver  2009;3(1):60-63.
Glycogen storage disease type IV (GSD-IV) is an autosomal recessive disease caused by a deficient glycogen branching enzyme (GBE), encoded by the GBE1 gene, resulting in the accumulation of abnormal glycogen deposits in the liver and other tissues. We treated a 20-month-old girl who presented with progressive liver cirrhosis and was diagnosed with GSD-IV, as confirmed by GBE1 gene mutation analysis, and underwent living related heterozygous donor liver transplantation. Direct sequencing of the GBE1 gene revealed that the patient was compound heterozygous for a known c.1571G>A (p.Gly264Glu) mutation a novel c.791G>A (Arg524Gln) mutation. This is the first report of a Korean patient with GSD-IV confirmed by mutation analysis, who was treated successfully by liver transplantation.
PMCID: PMC2871562  PMID: 20479904
Glycogen storage disease type IV; GBE1; DNA analysis; Liver transplantation; Living donors
21.  Comparative study of neoadjuvant chemotherapy before radical hysterectomy and radical surgery alone in stage IB2-IIA bulky cervical cancer 
To compare the efficacy of neoadjuvant chemotherapy with paclitaxel plus platinum followed by radical hysterectomy with radical surgery alone in patients with stage IB2-IIA bulky cervical cancer.
From November 1999 to September 2007, stage IB2-IIA cervical cancers with tumor diameter >4 cm, as measured by MRI, were managed with two cycles of preoperative paclitaxel and platinum. As a control group, we selected 35 patients treated with radical surgery alone.
There were no significant between group differences in age, tumor size, FIGO stage, level of SCC Ag, histopathologic type and grade. Operating time, estimated blood loss, the number of lymph nodes yielded and the rate of complications were similar in the two groups. In surgical specimens, lymph-vascular space invasion (LVSI), nodal metastasis and parametrial involvement did not differ significantly between the two groups. In the neoadjuvant group, pathologic tumor size was significantly smaller and fewer patients had deep cervical invasion. Radiotherapy, alone and in the form of concurrent chemoradiation, was administered to more patients treated with radical surgery alone (82.9% vs. 52.9%, p=0.006). No recurrence was observed in patients who could avoid adjuvant radiotherapy owing to improved risk factors after neoadjuvant chemotherapy. There were no significant differences in 5-year disease free and overall survival.
As neoadjuvant chemotherapy would improve pathologic prognostic factors, adjuvant radiotherapy can be avoided, without worsening the prognosis, in patients with locally advanced bulky cervical cancer. Neoadjuvant chemotherapy would be improving the quality of life after radical hysterectomy in patients with bulky cervical cancer.
PMCID: PMC2676495  PMID: 19471665
Locally advanced cervical cancer; Neoadjuvant chemotherapy; Radical hysterectomy
22.  Stage IIIC epithelial ovarian cancer classified solely by lymph node metastasis has a more favorable prognosis than other types of stage IIIC epithelial ovarian cancer 
Journal of Gynecologic Oncology  2008;19(4):223-228.
To verify whether it can be justified to classify patients to stage IIIC epithelial ovarian cancer based on nodal involvement only.
This study included all consecutive patients with stage IIIC epithelial ovarian cancer who underwent upfront cytoreductive surgery according to the FIGO guideline followed by platinum based chemotherapy from September 1989 to September 2006 at Asan Medical Center.
During the study period, a total of 272 patients met the inclusion criteria. Optimal cytoreduction was achieved in 213 patients, and complete cytoreduction was achieved in 85 patients. Median follow-up time was 37 months (range, 6-181 months). The 5-year disease free survival (DFS) and overall survival (OS) rate of all patients were 23% and 57%, respectively. Forty-one patients were allocated to stage IIIC by positive nodes only. Patients with stage IIIC disease due to positive nodes only had significantly longer DFS and OS compared to other stage IIIC patients (p<0.001 and p<0.001). The DFS and OS of these patients was significantly better than those of other stage IIIC patients who achieved complete or optimal cytoreduction (p<0.001 and p<0.001). The outcome was even better than that of stage IIIA and IIIB patients (p<0.05 and p<0.05).
Patients with stage IIIC epithelial ovarian cancer due to positive nodes only had a more favorable prognosis compared to other stage IIIC patients. Therefore, reevaluation of the current FIGO staging system for stage IIIC epithelial ovarian cancer is required.
PMCID: PMC2676474  PMID: 19471577
Epithelial ovarian cancer; Stage IIIC; Lymph node metastasis; Prognosis

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