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1.  Prognosis of hepatocellular carcinoma expressing cytokeratin 19: Comparison with other liver cancers 
AIM: To investigate whether expressing biliary phenotype predicted poor outcome after the surgical treatment in primary liver cancers.
METHODS: Out of 204 patients that underwent liver resection due to hepatocellular carcinoma (HCC), liver specimens of 70 patients with HCC were evaluated for biliary components by cytokeratin (CK) 19 immunostain (CK19- HCC and CK19+ HCC). CK19 positivity was defined as membranous and/or cytoplasmic expression in ≥ 5% of tumor cells with moderate or strong intensity. Patients with other primary liver cancers, such as combined HCC and cholangiocarcinoma (cHCC-CC), intrahepatic cholangiocarcinoma (ICC) who received curative liver resection, were also included in the study. Clinical characteristics of CK19- HCC and CK19+ HCC patients, including survival outcome after curative liver resection, were compared with that of cHCC-CC and ICC patients.
RESULTS: The overall survival (OS) rate of CK19- HCC (n = 49) after the curative surgical treatment was 90.7%, and 80.4% at 1 and 5 years after the resection. OS rate of CK19+ HCC (n = 21) was 74.3%, 28.9% and OS rate of cHCC-CC (n = 22) was 66.7%, 32.2% at 1 and 5 years after the surgery. For ICC (n = 19), 1 and 5-year-OS rate was 50.2% and 14.3% after the curative resection. The OS rates of CK19+ HCC and cHCC-CC were significantly lower than that of CK19- HCC, but higher than the OS rate of ICC (P = 0.000). There was no statistically significant difference in OS rate between CK19+ HCC and cHCC-CC. The disease free survival (DFS) rate of CK19- HCC was 72.0% and 54.5% at 1 and 3 years after the surgical treatment. DFS rate of CK19+ HCC was 53.3%, 34.3% and DFS rate of cHCC-CC was 51.5%, 39.2% at 1 and 3 years after the resection. For ICC, 1 and 3-year-DFS rate was 28.0% and 14.0% after the curative resection. DFS rate of CK19- HCC was significantly higher than that of ICC (P = 0.017), but marginally higher than DFS rate of either CK19+ HCC or cHCC-CC (P = 0.097, P = 0.089, respectively). Predictors of outcome after the surgery of primary liver cancer were pathology of the resected mass, existence of microvascular invasion and accompanying satellite nodule.
CONCLUSION: Primary liver cancers with biliary components tended to show poorer surgical outcome. This suggested that immuno-phenotype of liver cancers was as important as their morphological classification.
PMCID: PMC3442214  PMID: 23002345
Cytokeratin 19; Hepatocellular carcinoma; Intrahepatic cholangiocarcinoma; Liver cancers; Hepatectomy
2.  Usefulness of the Controlled Attenuation Parameter for Detecting Liver Steatosis in Health Checkup Examinees 
Gut and Liver  2015;9(3):405-410.
The controlled attenuation parameter (CAP) implemented in FibroScan® is reported to be a non-invasive means of detecting steatosis (>10% steatosis). We aimed to evaluate the usefulness of CAP in detecting steatosis among health checkup examinees and to assess its correlation with ultrasonography (US).
Consecutive CAP results were retrospectively collected. A total of 280 subjects were included.
Fatty liver was detected in 119 subjects (42.5%) by US, whereas it was detected in 160 subjects (57.1%) by the CAP. The numbers of subjects with S0:S1:S2:S3 steatosis according to the CAP value were 120:59:58:43, respectively. The mean CAP values were 203.34±28.39 dB/m for S0, 248.83±6.14 dB/m for S1, 274.33±8.53 dB/m for S2, and 322.35±22.20 dB/m for S3. CAP values were correlated with body weight (r=0.404, p<0.001), body mass index (r=0.445, p<0.001), and the fatty liver grade by US (r=0.472, p<0.001). Among the 161 subjects with normal US findings, steatosis was detected in 65 subjects (40.4%) using the CAP.
The CAP seems to be useful for detecting very low-grade hepatic steatosis in health checkup examinees. Its role in predicting subjects with a risk of metabolic derangement needs to be evaluated.
PMCID: PMC4413975  PMID: 25717046
Fatty liver; Controlled attenuation parameter; Ultrasonography; Early diagnosis; Metabolic syndrome
3.  Outcome of Gamma Knife Thalamotomy in Patients with an Intractable Tremor 
Tremor is a common movement disorder that interferes with daily living. Since the medication for tremor has some limitations, surgical intervention is needed in many patients. In certain patients who cannot undergo aggressive surgical intervention, Gamma Knife thalamotomy (GKT) is a safe and effective alternative.
From June 2012 to August 2013, 7 patients with an intractable tremor underwent GKT. Four of these 7 patients had medical comorbidities, and 3 patients refused to undergo traditional surgery. Each patient was evaluated with the modified Fahn-Tolosa-Marin tremor rating scale (TRS) along with analysis of handwriting samples. All of the patients underwent GKT with a maximal dose of 130 Gy to the left ventralis intermedius (VIM) nucleus of the thalamus. Follow-up brain MRI was performed after 3 to 8 months of GKT, and evaluation with the TRS was also performed.
Six patients showed objective improvement in the TRS score. Excluding one patient who demonstrated tremor progression, there was 28.9% improvement in the TRS score. However, five patients showed subjective improvement in their symptoms. On comparing the TRS scores between follow-up periods of more and less than 4 months, the follow-up TRS score at more than 4 months of GKT was significantly improved compared to that at less than 4 months of GKT. Follow-up MRI showed radiosurgical changes in 5 patients.
GKT with a maximal dose of 130 Gy to the VIM is a safe procedure that can replace other surgical procedures.
PMCID: PMC4373048  PMID: 25810859
Gamma Knife; Thalamotomy; Ventralis intermedius; Tremor
4.  Fractionated Gamma Knife Radiosurgery for Benign Perioptic Tumors: Outcomes of 38 Patients in a Single Institute 
This study was performed to evaluate the efficacy and safety of fractionated Gamma Knife radiosurgery (GKRS) for perioptic lesions.
Thirty-eight patients with perioptic tumors were treated at our institute from May 2004 to December 2008. All patients had a lesion in close contact with the optic apparatus. Twenty-four of these patients had undergone surgical resection before fractionated GKRS. Radiation was delivered in four sessions with 12 hours intervals between sessions. The mean target volume was 3,851 mm3 and the median cumulative marginal dose was 20 Gy. The median follow-up was 38.2 months. Visual acuity and visual fields were analyzed according to visual impairment score using the German Ophthalmological Society guidelines.
Tumor control was achieved in 35 (94.6%) of the 37 patients with available follow-up images. Progressive tumor growth was observed in two craniopharyngioma patients (5.4%). Favorable visual outcomes in the postoperative period were achieved in 94.7% of cases (36/38). Sixteen patients showed visual function after fractionated GKRS, twenty cases were stationary, and two patients showed visual function deterioration after GKRS.
GKRS is a safe and effective alternative to either surgery or fractionated radiotherapy for selected benign lesions that are adjacent to the optic apparatus.
PMCID: PMC4231616  PMID: 25408926
Gamma Knife radiosurgery; Fractionated radiosurgery; Stereotactic radiosurgery; Tumor control; Visual outcome
5.  Regional Diversity of Hepatitis C Virus Prevalence: Seeking for Culture Specific Mode of Transmission 
Gut and Liver  2014;8(4):337-338.
PMCID: PMC4113051  PMID: 25071897
6.  Gamma Knife Radiosurgery for Brain Metastases from Breast Cancer 
The authors conducted a retrospective cohort study to determine prognostic factors and treatment outcomes of brain metastases (BM) from breast cancer (BC) after Gamma Knife radiosurgery (GKS).
Pathologic and clinical features, and outcomes were analyzed in a cohort of 62 patients with BM from BC treated by GKS. The Kaplan-Meier method, the log-rank test, and Cox's proportional hazards model were used to assess prognostic factors.
Median survival after GKS was 73.0 weeks (95% confidence interval, 46.0-100.1). HER2+ [hazard ratio (HR) 0.441; p=0.045], Karnofsky performance scale (KPS) ≥70 (RR 0.416; p=0.050) and systemic chemotherapy after GKS (RR 0.282; p=0.001) were found to be a favorable prognostic factor of overall survival. Actuarial local control (LC) rate were 89.5±4.5% and 70.5±6.9% at 6 and 12 months after GKS, respectively. No prognostic factors were found to affect LC rate. Uni- and multivariate analysis revealed that the distant control (DC) rate was higher in patients with; a small number (≤3) of metastasis (HR 0.300; p=0.045), no known extracranial metastasis (p=0.013, log-rank test), or the HER2+ subtype (HR 0.267; p=0.027). Additional whole brain radiation therapy and metastasis volume were not found to be significantly associated with LC, DC, or overall survival.
The treatment outcomes of patients with newly diagnosed BM from BC treated with GKS could be affected primarily by intrinsic subtype, KPS, and systemic chemotherapy. Therapeutic strategy and prognosis scoring system should be individualized based on considerations of intrinsic subtype in addition to traditionally known parameters related to stereotactic radiosurgery.
PMCID: PMC3873352  PMID: 24379946
Brain metastasis; Breast cancer; Gamma Knife radiosurgery; Intrinsic subtype; Treatment outcomes
7.  Survival outcome of patients with spontaneously ruptured hepatocellular carcinoma treated surgically or by transarterial embolization 
AIM: To evaluate clinical outcomes of patients that underwent surgery, transarterial embolization (TAE), or supportive care for spontaneously ruptured hepatocellular carcinoma (HCC).
METHODS: A consecutive 54 patients who diagnosed as spontaneously ruptured HCC at our institution between 2003 and 2012 were retrospectively enrolled. HCC was diagnosed based on the diagnostic guidelines issued by the 2005 American Association for the Study of Liver Diseases. HCC rupture was defined as disruption of the peritumoral liver capsule with enhanced fluid collection in the perihepatic area adjacent to the HCC by dynamic liver computed tomography, and when abdominal paracentesis showed an ascitic red blood cell count of > 50000 mm3/mL in bloody fluid.
RESULTS: Of the 54 patients, 6 (11.1%) underwent surgery, 25 (46.3%) TAE, and 23 (42.6%) supportive care. The 2-, 4- and 6-mo cumulative survival rates at 2, 4 and 6 mo were significantly higher in the surgery (60%, 60% and 60%) or TAE (36%, 20% and 20%) groups than in the supportive care group (8.7%, 0% and 0%), respectively (each, P < 0.01), and tended to be higher in the surgical group than in the TAE group. Multivariate analysis showed that serum bilirubin (HR = 1.09, P < 0.01), creatinine (HR = 1.46, P = 0.04), and vasopressor requirement (HR = 2.37, P = 0.02) were significantly associated with post-treatment mortality, whereas surgery (HR = 0.41, P < 0.01), and TAE (HR = 0.13, P = 0.01) were inversely associated with post-treatment mortality.
CONCLUSION: Post-treatment survival after surgery or TAE was found to be better than after supportive care, and surgery tended to provide better survival benefit than TAE.
PMCID: PMC3725379  PMID: 23901230
Ruptured hepatocellular carcinoma; Surgery; Transarterial embolization
8.  Esophageal mucosal metastasis from adenocarcinoma of the distal stomach 
Dissemination of gastric cancer may usually occur by direct spread through the perigastric tissues to adjacent organ, lymphatic spread, and hematogenous spread. We report a rare case of gastric cancer with mucosal metastastic lesion on the upper esophagus that was diagnosed by endoscopy and endosonography. A biopsy of the esophageal mass was performed and the pathologic findings with immunohistochemical stain for Mucin-5AC are proved to be identical to that of gastric adenocarcinoma, suggesting metastasis from main lesion of the gastric cancer. The lesion could not be explained by lymphatic or hematogenous spread, and its metastasis mechanism is considered to be different from previous studies. We suggest that the gastroesophageal reflux of cancer cells could be one of the possible metastatic pathways for metastasis of esophagus from an adenocarcinoma of the stomach.
PMCID: PMC3691037  PMID: 23801875
Stomach cancer; Neoplasm metastasis; Esophagus
9.  Complete remission of advanced hepatocellular carcinoma by sorafenib: A case report 
Hepatocellular carcinoma (HCC) is the fifth most common malignant disease worldwide, and curative treatment remains difficult because the majority of cases are diagnosed in the advanced stage. Sorafenib is the only known effective systemic treatment, but patients rarely achieve complete remission (CR). A 66-year-old man with a history of alcoholic liver cirrhosis with a diagnosis of advanced HCC, was initially treated with transarterial chemoembolization on four occasions. However, the disease progressed with portal vein thrombosis. Therefore, sorafenib was started, and 4 mo later, the patient achieved CR. The treatment was continued for 12 mo, and CR was maintained up to 4 mo after sorafenib discontinuation.
PMCID: PMC3613770  PMID: 23556056
Hepatocellular carcinoma; Sorafenib; Portal vein thrombosis; Complete remission
10.  Cerebellar Liponeurocytoma with an Unusually Aggressive Histopathology : Case Report and Review of the Literature 
We report a rare case of cerebellar liponeurocytoma with an unusually aggressive histopathology. A 49-year-old man presented with a four-month history of headache, vertigo, and progressive swaying gait. Magnetic resonance imaging showed a 3×3.5 cm sized relatively well-demarcated round mass lesion in the fourth ventricle, characterized by high signal intensity on T2-weighted images. Postcontrast images revealed strong enhancement of the solid portion and the cyst wall. The patient underwent suboccipital craniectomy and tumor removal. The pathologic diagnosis was cerebellar liponeurocytoma. Adjuvant radiotherapy was offered due to concerns related to the high proliferative index (Ki-67, 13.68%) of the tumor. At the last routine postoperative follow-up visit (12 months), the patient complained of no specific symptom and there was no evidence of tumor recurrence. However, long-term follow-up and the analysis of similar cases are necessary because of the low number of reports and the short follow-up of cases.
PMCID: PMC3483329  PMID: 23115671
Liponeurocytoma; Ki-67 index; Radiotherapy
11.  Giant choledocholithiasis treated by mechanical lithotripsy using a gastric bezoar basket 
Mechanical lithotripsy (ML) is usually considered as a standard treatment option for large bile duct stones. However, it is impossible to retrieve oversized stones because the conventional lithotripsy basket may not be able to grasp the stone. However, there is no established endoscopic extraction method for such giant stone removal. We describe a case of successful extraction of a 4-cm large stone using a gastric bezoar basket. A 78-year-old woman had suffered from upper abdominal pain for 20 d. Contrast-enhanced computed tomogram revealed a 4-cm single stone in the distal common bile duct (CBD). Endoscopic stone retraction was decided upon and endoscopic papillary balloon dilation was performed using a large balloon. An attempt to capture the stone using a standard lithotripsy basket failed due to the large stone size. Subsequently, we used a gastric bezoar basket to successfully capture the stone. The stone was fragmented into small pieces and extracted. The stone was completely removed after two sessions of endoscopic retrograde cholangiopancreatography; each of which took 30 min. No complications occurred during or after the procedure. The patient was fully recovered and discharged on day 11 of hospitalization. ML using a gastric bezoar basket is a safe and effective retrieval method in select cases, and is considered as an alternative nonoperative option for the management of difficult CBD stones.
PMCID: PMC3391773  PMID: 22783060
Giant choledocholithiasis; Mechanical lithotripsy; Bezoar basket; Common bile duct stone; Endoscopic papillary balloon dilatation
12.  Silymarin suppresses hepatic stellate cell activation in a dietary rat model of non-alcoholic steatohepatitis: Analysis of isolated hepatic stellate cells 
Non-alcoholic steatohepatitis (NASH) is characterized by hepatocellular injury and initial fibrosis severity has been suggested as an important prognostic factor of NASH. Silymarin was reported to improve carbon tetrachloride-induced liver fibrosis and reduce the activation of hepatic stellate cells (HSC). We investigated whether silymarin could suppress the activation of HSCs in NASH induced by methionine- and choline-deficient (MCD) diet fed to insulin-resistant rats. NASH was induced by feeding MCD diet to obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Non-diabetic Long-Evans Tokushima Otsuka (LETO) rats were fed with standard chow and served as the control. OLETF rats were fed on either standard laboratory chow, or MCD diet or MCD diet mixed with silymarin. Histological analysis of the liver showed improved non-alcoholic fatty liver disease (NAFLD) activity score in silymarin-fed MCD-induced NASH. Silymarin reduced the activation of HSCs, evaluated by counting α-smooth muscle actin (SMA)-positive cells and measuring α-SMA mRNA expression in the liver lysates as well as in HSCs isolated from the experimental animals. Although silymarin decreased α1-procollagen mRNA expression in isolated HSCs, the anti-fibrogenic effect of silymarin was not prominent so as to show significant difference under histological analysis. Silymarin increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and decreased tumor necrosis factor (TNF)-α mRNA expression in the liver. Our study suggested that the possible protective effect of silymarin in diet induced NASH by suppressing the activation of HSCs and disturbing the role of the inflammatory cytokine TNF-α.
PMCID: PMC3573753  PMID: 22710359
non-alcoholic steatohepatitis; methionine- and choline-deficient diet; insulin resistance; hepatic stellate cell; silymarin
13.  Glioblastoma Following Radiosurgery for Meningioma 
We report a patient who underwent gamma knife radiosurgery to treat recurrent meningioma after microsurgery and thereafter developed secondary malignancy adjacent to the original tumor. A 47-year-old woman had underwent resection of the olfactory groove meningioma. Then radiosurgery was done three times over 4 year period for the recurrent tumor. After 58 months from the initial radiosurgery, she presented with headache and progressive mental dullness. Huge tumor in bifrontal location was revealed in MRI. Subsequent operation and pathological examination confirmed diagnosis of glioblastoma. This case fits the criteria of radiation-induced tumor and the clinical implication of the issue is discussed.
PMCID: PMC3322216  PMID: 22500202
Glioblastoma; Radiosurgery
14.  Malignant Ascites after Subduroperitoneal Shunt in a Patient with Leptomeningeal Metastasis 
Leptomeningeal metastasis is a devastating complication of advanced stage cancer. It is frequently accompanied by hydrocephalus and intracranial hypertension that must be treated by ventriculoperitoneal shunts. However, there are actual risks of peritoneal seeding or accumulation of malignant ascites after the cerebrospinal fluid diversion procedure, though it has not been reported. Here, we present the case of a patient with non-small cell lung cancer with leptomeningeal metastasis in whom malignant ascites developed after a subduroperitoneal shunt.
PMCID: PMC3243845  PMID: 22200024
Leptomeningeal metastasis; Malignant ascites; Ventriculoperitoneal shunt
15.  Does the bile duct angulation affect recurrence of choledocholithiasis? 
AIM: To investigate whether bile duct angulation and T-tube choledochostomy influence the recurrence of choledocholithiasis.
METHODS: We conducted a retrospective study inclu-ding 259 patients who underwent endoscopic sphincterotomy and cholecystectomy for choledocholithiasis between 2000 and 2007. The imaginary line was drawn along the center of the bile duct and each internal angle was measured at the two angulation sites of the bile duct respectively. The values of both angles were added together. We then tested our hypothesis by examining whether T-tube choledochostomy was performed and stone recurrence occurred by reviewing each subject’s medical records.
RESULTS: The overall recurrence rate was 9.3% (24 of 259 patients). The mean value of sums of angles in the recurrence group was 268.3° ± 29.6°, while that in the non-recurrence group was 314.8° ± 19.9° (P < 0.05). Recurrence rate of the T-tube group was 15.9% (17 of 107), while that of the non T-tube group was 4.6% (7 of 152) (P < 0.05). Mean value of sums of angles after T-tube drainage was 262.5° ± 24.6° and that before T-tube drainage was 298.0° ± 23.9° in 22 patients (P < 0.05).
CONCLUSION: The bile duct angulation and T-tube choledochostomy may be risk factors of recurrence of bile duct stones.
PMCID: PMC3203364  PMID: 22039327
Choledocholithiasis; Common bile duct; Cholecystectomy; Recurrence; Endoscopic retrograde cholangio pancreatography
16.  The Role of Radiosurgery in Patients with Brain Metastasis from Small Cell Lung Carcinoma 
The purpose of this retrospective study was to evaluate the outcome of gamma knife radiosurgery (GKRS) and/or whole brain radiation therapy (WBRT) for the treatment of small cell lung carcinoma (SCLC) metastasis to the brain.
From 2000 to 2010, 50 patients underwent GKRS for metastatic brain lesions originating from SCLC. Among these patients, 11 received prophylactic cranial irradiation (PCI) before the development of metastatic lesions (PCI group), and GKRS was performed as an initial treatment for newly diagnosed lesions in 12 patients who had not received PCI (primary GKRS group). In addition, GKRS was performed as a salvage treatment for progressive lesions after WBRT in 27 patients (salvage GKRS group). The medical records and imaging data of all patients were retrospectively analyzed.
The overall survival of the 50 patients was 20.8 months (range 1-53) after the diagnosis of primary tumor and 12.0 months (range 1-47) after the development of cerebral metastasis. Median survival after GKRS was 4.8 months (range 1-15) in the PCI group, 4.6 months (range 0-18) in the primary GKRS group, and 7.6 months (range 0-33) in the salvage GKRS group. Further treatment for progressive lesions after GKRS was necessary in 15 patients, after a mean interval of 3.8 months. Causes of death were systemic organ failure in 15 patients, deterioration of neurological state in 13 patients, and unknown or combined causes in 16 patients. The local control rate of the lesions treated with GKRS was 76.4% (decreased in 13 patients and stable in 16 patients at the final imaging follow-up (mean 5.60 months).
GKRS is an effective local treatment for brain metastasis from SCLC both as an initial treatment for newly diagnosed lesions after PCI and as a salvage treatment for recurrent or progressive lesions. However, the survival benefit is not significant because most patients die of systemic multi-organ failure with a short life expectancy.
PMCID: PMC3206286  PMID: 22053227
Small cell lung carcinoma; Radiosurgery; Gamma knife; Metastasis
17.  Development of De Novo Cavernous Hemangioma after Radiosurgery for Cavernous Hemangioma 
We report a rare case of cavernous hemangioma (CH) which developed in adjacent location to a preexisting CH after gamma knife radiosurgery (GKRS). A 36-year-old woman underwent GKRS for a CH in the left lentiform nucleus. Three-and-half years after radiosurgery, MRI revealed a new CH in the left caudate nucleus. Surgical excision of the new lesion was performed. The pathological examination confirmed the diagnosis of CH. In radiosurgery for CH, it should be noted that a new CH may develop, which is likely to result from the interaction between radiation and predisposing factors of the patient.
PMCID: PMC3053549  PMID: 21430981
Cavernous hemangioma; Cavernous angioma; Gamma knife; Radiosurgery; Radiation-induced tumor
18.  The effect of sorafenib on hepatic stellate cells: implication of its effect on tumor microenvironment 
The Korean Journal of Hepatology  2010;16(4):418-419.
PMCID: PMC3304606
Sorafenib; Hepatocellular carcinoma; Stellate cell
19.  Disseminated Hemangioblastomatosis of the Central Nervous System without von Hippel-Lindau Disease: A Case Report 
Journal of Korean Medical Science  2009;24(4):755-759.
We report a very rare case of hemangioblastomatosis that developed after surgical removal of a solitary cerebellar hemangioblastoma (HB). A 51-yr-old man presented with back pain 10 yr after undergoing surgery for cerebellar HB. Magnetic resonance imaging showed numerous mass lesions along the entire neuraxis accompanied by prominent leptomeningeal enhancement. Genomic DNA analysis showed no mutation in the von Hippel-Lindau (VHL) genes. A surgical specimen obtained from a lesion in the cauda equina showed pathological findings identical to those of the cerebellar HB that had been resected 10 yr earlier. External beam radiation therapy and radiosurgery were subsequently performed; however, the patient succumbed one year after receiving the diagnosis of hemangioblastomatosis. The reduction of tumor cell spillage during surgery and regular long-term follow-up are recommended for patients with HBs.
PMCID: PMC2719216  PMID: 19654966
Hemangioblastoma; von Hippel-Lindau Disease; Central Nervous System
20.  Gamma Knife Radiosurgery for Ten or More Brain Metastases 
This study was performed to assess the efficacy of GKS in patients with ten or more brain metastases.
From Aug 2002 to Dec 2007, twenty-six patients (13 men and 13 women) with ten or more cerebral metastatic lesions underwent GKS. The mean age was 55 years (32-80). All patients had Karnofsky performance status (KPS) score of 70 or better. According to recursive partitioning analysis (RPA) classification, 3 patients belonged to class I and 23 to class II. The location of primary tumor was lung (21), breast (3) and unknown (2). The mean number of the lesions per patient was 16.6 (10-37). The mean cumulated volume was 10.9 cc (1.0-42.2). The median marginal dose was 15 Gy (9-23). Overall survival and the prognostic factors for the survival were retrospectively analyzed by using Kaplan Meier method and univariate analysis.
Overall median survival from GKS was 34 weeks (8-199). Local control was possible for 79.5% of the lesions and control of all the lesions was possible in at least 14 patients (53.8%) until 6 months after GKS. New lesions appeared in 7 (26.9%) patients during the same period. At the last follow-up, 18 patients died; 6 (33.3%) from systemic causes, 10 (55.6%) from neurological causes, and 2 (11.1%) from unknown causes. Synchronous onset in non-small cell lung cancer (p=0.007), high KPS score (≥80, p=0.029), and controlled primary disease (p=0.020) were favorable prognostic factors in univariate analysis.
In carefully selected patients, GKS may be a treatment option for ten or more brain metastases.
PMCID: PMC2615138  PMID: 19137079
Multiple; Brain metastases; Gamma knife radiosurgery; Prognostic factor
21.  Preliminary Report of Multisession Gamma Knife Radiosurgery for Benign Perioptic Lesions: Visual Outcome in 22 Patients 
Radiosurgery may be contraindicated for lesions adjacent to the optic pathways because of the substantial risk of visual complication. Multisession radiosurgery has been tried as a compromise between single session radiosurgery and fractionated radiotherapy. The purpose of this study is to evaluate the outcomes of multisession gamma knife radiosurgery (GKRS) in 22 patients with perioptic lesions of benign pathology.
In all 22 cases, the lesions were within 1 mm of the optic apparatus and were therefore not considered suitable for single session radiosurgery. Radiation was delivered in 3 to 4 fractions with a median cumulated marginal dose of 20 Gy (range, 15-20 Gy).
During a mean follow-up of 29 months (range, 14-44 months), tumor control was achieved in 21 patients. Visual function improved in 7 patients, remained unchanged in 14 patients, and deteriorated in 1 patient with tumor progression. No other complication was observed.
This preliminary result supports the idea that multisession GKRS may be an effective and safe alternative for treatment in perioptic lesions that are unsuitable for single session radiosurgery.
PMCID: PMC2588338  PMID: 19096695
Multisession radiosurgery; Gamma knife; Visual complication
22.  Retrospective Analysis on 76 Cases of Cerebral Arteriovenous Malformations Treated by Gamma Knife Radiosurgery 
Outcome of gamma knife radiosurgery (GKS) in the consecutive 100 cases with cerebral arteriovenous malformations (AVMs) was analyzed.
Data from initial 100 patients treated with GKS in the authors' institute were reviewed retrospectively. Spetzler-Martin grade at diagnosis were I in 18 patients, II in 27, III in 36, IV in 11, and V in 8. Thirty-five patients had experienced previous bleeding, 27 patients presented with seizure, and 31 patients presented with headache. The mean volume of the lesion was 4.3 cm3 (0.1-29.3 cm3). The median radiation dose delivered to the margin was 20.0 Gy (13-32 Gy). Mean follow-up period was 37.5 months (5-63 months).
Angiographic follow-up was performed in 48 patients at least 2 years after GKS. Sixteen patients were lost in follow up following 2 years from GKS. Twenty-eight of 48 patients (58%) showed complete obliteration and 20 patients (42%) showed partial obliteration. Seven patients presented with post-GKS hemorrhage. Adverse radiation effect (ARE) was observed at follow-up MRI in 25 of 76 patients, and it was symptomatic in 5 patients. Complete obliteration was confirmed in 24 of 31 (77%) patients with volume less than 4 cm3, meanwhile only 4 of 17 (24%) patients with volume of 4 cm3 or more showed complete obliteration. Complete obliteration rate was 67% with 20 Gy or higher marginal dose, 63% with 15-20 Gy, and 17% with less than 15 Gy.
GKS can provide high rates of obliteration with acceptable risk of morbidity in a subgroup of small AVMs. However, overall outcome in whole spectrum of AVMs, in which large proportion of cases have unfavorable characteristics for radiosurgery, is much worse. More effective therapeutic strategy needs to be developed for large AVMs that are difficult to be managed with current available treatment modalities.
PMCID: PMC2588252  PMID: 19096630
Gamma knife radiosurgery; Arteriovenous malformation; Outcome
23.  Prognosis of Non-Small Cell Lung Cancer with Synchronous Brain Metastases Treated with Gamma Knife Radiosurgery 
Journal of Korean Medical Science  2006;21(3):527-532.
The clinical outcome and prognostic factors of patients with synchronous brain metastases from non-small cell lung cancer (NSCLC) who were treated with gamma knife radiosurgery (GKS) were analyzed. A total of 35 patients with NSCLC underwent GKS as an initial treatment for metastatic brain lesions of synchronous onset. The period of survival and various prognostic factors such as age, gender, performance status, multiplicity of the brain lesions, intracranial tumor volume, and extent of the primary tumor were analyzed. The overall median survival time for this series was 12 months (range 0.75 to 43 months) from the diagnosis. Of the 21 patients who were no longer alive at the conclusion of this study, only 7 (33.3%) died of neurological causes. Multivariate analysis of these data revealed that N stage, whole-brain radiotherapy (WBRT), and chemotherapy were significant predictors for survival (p<0.05). Survival of patients with NSCLC and synchronous brain metastases is mainly dependent upon the progression of the systemic disease, provided that the cerebral lesions are treated adequately with local treatment modalities including radiosurgery. Application of radiosurgery as an initial treatment option and aggressive local and systemic modalities to control extracranial disease may improve survival.
PMCID: PMC2729962  PMID: 16778400
Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Radiosurgery
24.  Absence of MutY homologue mutation in patients with multiple sporadic adenomatous polyps in Korea 
AIM: Recently, germ-line mutation in the base excision repair gene MYH has been identified to cause a novel autosomal recessive form of familial adenomatous polyposis (FAP). Interestingly, a striking evidence for MYH mutations within different ethnic groups has been demonstrated. In this study, we screened 30 patients with multiple adenomatous polyps for MYH mutations to assess its prevalence and ethnic specificity in Korea.
METHODS: Thirty patients (21 men and 9 women; mean age 62.3 years) with multiple adenomatous polyps were examined for MYH mutations. The mean number of adenomas per patient was 10.0. Sixteen exonic regions and their intronic sequences were amplified by PCR and subjected to SSCP and DNA sequencing analyses.
RESULTS: None of the patients was identified to carry any truncating or sequence alterations in MYH. Our screening for the mutational regions, which were recognized from Caucasian patients or affected Indian families, also failed to detect sequence substitutions.
CONCLUSION: Mutation in MYH may be rarely involved in the pathogenesis of multiple sporadic colorectal adenomas in Korean population, although a large-scale analysis will be required to clarify the presence of specific MYH variants in a subset of patients and their role in the predisposition of multiple colorectal adenomas in Korean population.
PMCID: PMC4066163  PMID: 16521226
MY; Multiple adenomatous polyps; Germ-line mutation; Familial adenomatous polyposis; Ethnic difference
Neuro-Oncology  2014;16(Suppl 3):iii45-iii46.
BACKGROUND: Glioblastoma multiforme (GBM), the most common and aggressive malignant brain tumor, almost always recurs despite aggressive treatments combining surgery, radiation, and chemotherapy. Thus, understanding how individual tumors evolve in response to the standard treatments is essential for improved patient care. METHODS: Here, we describe our genomic analysis of the paired pre- and post-treatment tumors from 20 glioblastoma patients. RESULTS: Tumors also acquired diverse alterations that appeared to contribute to treatment resistance, such as the increased expression of CDK4/6 in the IDH1-mutated tumors and novel EGFR and MET mutations, in addition to TP53, RB1, and APC alterations that were previously implicated with treatment resistance. CONCLUSIONS: The patient-specific genomic alterations that arise following treatments may represent superior therapeutic targets for recurrent GBMs. This work suggests that assessing genomic changes in individual tumors after recurrence is paramount for precision neuro-oncology. SECONDARY CATEGORY: Tumor Biology.
PMCID: PMC4144628

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