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.
Stomach cancer; Neoplasm metastasis; Esophagus
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.
Hepatocellular carcinoma; Sorafenib; Portal vein thrombosis; Complete remission
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.
Cytokeratin 19; Hepatocellular carcinoma; Intrahepatic cholangiocarcinoma; Liver cancers; Hepatectomy
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.
Liponeurocytoma; Ki-67 index; Radiotherapy
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.
Giant choledocholithiasis; Mechanical lithotripsy; Bezoar basket; Common bile duct stone; Endoscopic papillary balloon dilatation
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.
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.
Leptomeningeal metastasis; Malignant ascites; Ventriculoperitoneal shunt
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.
Choledocholithiasis; Common bile duct; Cholecystectomy; Recurrence; Endoscopic retrograde cholangio pancreatography
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.
Cavernous hemangioma; Cavernous angioma; Gamma knife; Radiosurgery; Radiation-induced tumor
Sorafenib; Hepatocellular carcinoma; Stellate cell
The purpose of this study is to validate the recently published Breast–Graded Prognostic Assessment (GPA) and propose a new prognostic model and nomogram for patients with brain parenchymal metastases (BM) from breast cancer (BC). We retrospectively investigated 171 consecutive patients who received a diagnosis of BM from BC during 2000–2008. We appraised the recently proposed Sperduto's BC-specific GPA in training cohort through Kaplan-Meier survival curve using log-rank test and area under the curve for the BC-GPA predicting overall survival at 1 year and developed a new nomogram to predict outcomes using multivariate Cox-regression analysis. By putting the Sperduto's Breast-GPA together with our nomogram, we developed a new prognostic model. We validated our new prognostic model with an independent external patient cohort from 2 institutes for the same period. On the basis of our Cox-regression analysis, therapeutic effect of trastuzumab and status of extracranial systemic disease control were incorporated into our new prognostic model in addition to Karnofsky performance status, age, and hormonal status. Our new prognostic model showed significant discrimination in median survival time, with 3.7 months for class I (n = 15), 7.8 months for class II (n = 82), 10.7 months for class III (n = 42), and 19.2 months for class IV (n = 32; P < .0001). The new prognostic model accurately predicted survival among patients with BC from BM in an external validation cohort (P < .0001). We propose a new prognostic model and a nomogram reflecting the different biological features of BC, including treatment effect and status of extracranial disease control, which was excellently validated in an independent external cohort.
brain metastasis; breast cancer; HER2; prognosis; trastuzumab
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.
Ruptured hepatocellular carcinoma; Surgery; Transarterial embolization
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.
Hemangioblastoma; von Hippel-Lindau Disease; Central Nervous System
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.
Multiple; Brain metastases; Gamma knife radiosurgery; Prognostic factor
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.
Multisession radiosurgery; Gamma knife; Visual complication
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.
Gamma knife radiosurgery; Arteriovenous malformation; Outcome
While gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea.
The data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated.
The initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001).
The clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis.
Gastric variceal bleeding; Rebleeding; Mortality; Cirrhosis
Repetitive transcranial magnetic stimulation (rTMS) modulates central neuropathic pain in some patients after stroke, but the mechanisms of action are uncertain.
The authors used diffusion tensor imaging (DTI) and functional MRI (fMRI) to evaluate the integrity of the thalamocortical tract (TCT) and the activation pattern of the pain network in 22 patients with poststroke central pain.
Each patient underwent daily 10-Hz rTMS sessions for 1000 pulses on 5 consecutive days over the hotspot for the first dorsal interosseus muscle. Pain severity was monitored using the Visual Analogue Scale (VAS). Mood was assessed by the Hamilton Depression Rating Scale.
Clinical data from all participants along with the DTI and fMRI findings from 10 patients were analyzed. VAS scores decreased significantly, if modestly, following administration of rTMS in 14 responders, which lasted for 2 weeks after the intervention. Regression analysis showed a significant correlation between less initial depression and higher antalgic effect of rTMS. Integrity of the superior TCT in the ipsilesional hemisphere showed significant correlation with change of VAS score after rTMS. fMRI showed significantly decreased activity in the secondary somatosensory cortex, insula, prefrontal cortex, and putamen in rTMS responders, whereas no change was noted in nonresponders.
Mood may affect the modest antinociceptive effects of rTMS that we found, which may be mediated by the superior TCT through modulation of a distributed pain network.
poststroke central pain; transcranial magnetic stimulation; diffusion tensor imaging; thalamocortical tract; functional MRI; stroke rehabilitation
The aim of this study was to describe a single center's experience in the management of craniopharyngiomas in children over a 15-year period.
The clinical records of pediatric patients treated for craniopharyngiomas between December 1995 and February 2011 were reviewed. Thirty-five pediatric patients diagnosed with craniopharyngioma were treated, and their medical records and imaging data were analyzed retrospectively.
The mean follow-up duration was 76 months (range, 10-195). Overall survival and local control rates at 10 years were 94.7±5.1% and 37.1±11.9%, respectively. The female-to-male ratio was 16 : 19, and the mean age was 8.6 years (range, 1-17). Initially, gross total resection (GTR) was performed in 30 patients; subtotal resection (STR) followed by radiotherapy was performed in 5 patients. Of the 14 cases that showed recurrence after GTR, 5 patients were treated with GTR, 1 with radiation therapy (RT), 4 with gamma knife radiosurgery (GKRS), and 4 with subtotal resection followed by RT. No patients who underwent RT or GKRS had recurrences. Two cases with recurrence after STR followed by RT were treated with GTR. One patient died of hormonal insufficiency 64 months after the first surgery. The overall median time progression was 51.2 months (range, 3-182) : 49.7 months in the patients who underwent GTR and 60.2 months in the patients who underwent STR followed by RT.
If safe resection is possible, GTR at the initial treatment should be attempted to reduce the tumor recurrence. However, if the tumor recurs after the first surgery, RT or GKRS with/without reoperation may be an effective salvage treatment for recurrent craniopharyngioma.
Craniopharyngioma; Microsurgery; Radiotherapy
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.
non-alcoholic steatohepatitis; methionine- and choline-deficient diet; insulin resistance; hepatic stellate cell; silymarin
A set of proteins reflecting the prognosis of patients have clinical significance since they could be utilized as predictive biomarkers and/or potential therapeutic targets. With the aim of finding novel diagnostic and prognostic markers for glioblastoma (GBM), a tissue microarray (TMA) library consisting of 62 GBMs and 28 GBM-associated normal spots was constructed. Immunohistochemistry against 78 GBM-associated proteins was performed. Expression levels of each protein for each patient were analyzed using an image analysis program and converted to H-score [summation of the intensity grade of staining (0–3) multiplied by the percentage of positive cells corresponding to each grade]. Based on H-score and hierarchical clustering methods, we divided the GBMs into two groups (n=19 and 37) that had significantly different survival lengths (p<0.05). In the two groups, expression of nine proteins (survivin, cyclin E, DCC, TGF-β, CDC25B, histone H1, p-EGFR, p-VEGFR2/3, p16) was significantly changed (q<0.05). Prognosis-predicting potential of these proteins were validated with another independent library of 82 GBM TMAs and a public GBM DNA microarray dataset. In addition, we determined 32 aberrant or mislocalized subcellular protein expression patterns in GBMs compared with relatively normal brain tissues, which could be useful for diagnostic biomarkers of GBM. We therefore suggest that these proteins can be used as predictive biomarkers and/or potential therapeutic targets for GBM.
biomarker; therapeutic target; glioblastoma; tissue micro-array; bioinformatics; automated image analysis
Intrathecal methotrexate (MTX) therapy combined with whole brain radiotherapy (WBRT) is one of the major treatment modalities for leukemia and lymphoma involving the central nervous system (CNS). The purpose of this study was to retrospectively determine the incidences of leukoencephalopathy and disseminated necrotizing leukoencephalopathy (DNL) following intrathecal MTX therapy for CNS lymphoma or leukemia and to assess the potential risk factors.
Between January 2000 and August 2009, 143 patients with CNS lymphoma or leukemia received intrathecal MTX therapy alone or in combination with WBRT at a single institution. Patients were followed up clinically and radiologically at regular two- or three-month intervals. Medical records were reviewed to obtain information regarding the patients' demographics, medical histories, radiologic characteristics, treatments, and clinical courses.
On follow-up MR images, leukoencephalopathy was found in 95 of 143 patients (66.4%). The median time to develop leukoencephalopathy was 6.6 months. Among those with leukoencephalopathy, four patients showed seven extensive white-matter changes with strongly enhancing lesions demonstrating DNL. Histological confirmation was done in six lesions of three patients and radiological diagnosis alone in one patient. Four lesions spontaneously disappeared on MR images without any treatment, with a mean duration of 14 months before disappearance of DNL.
Leukoencephalopathy is a common phenomenon that occurs following intrathecal MTX therapy; however, DNL occurs at a very low incidence. For newly developed enhancing lesions, consideration for the occurrence of DNL should be taken to avoid unnecessary invasive procedures or therapies.
Leukoencephalopathy; Methotrexate; Intrathecal; Lymphoma; Leukemia
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.
Small cell lung carcinoma; Radiosurgery; Gamma knife; Metastasis
Adult-onset type II citrullinemia (CTLN2) is a disorder caused by an inborn error of metabolism affecting the liver. CTLN2 is an autosomal recessive disorder characterized by recurrent encephalopathy with hyperammonemia due to highly elevated plasma levels of citrulline and ammonia, caused by a deficiency of argininosuccinate synthetase in the liver. A small number of patients have undergone liver transplantation with favorable results. In Korea, the limitations of the deceased donor pool have made living donor liver transplantation a common alternative treatment option. We report the case of a patient with type II citrullinemia who was treated successfully with auxiliary partial orthotopic liver transplantation (APOLT) from a living donor. This is the first description of an APOLT for a patient with adult onset type II citrullinemia in Korea.
Citrullinemia; Auxiliary partial orthotopic liver transplantation
Diffuse large B-cell lymphoma (DLBCL) constitutes most primary central nervous system (CNS) lymphoma (PCNSL), whereas T-cell, low-grade and Burkitt’s lymphomas (BL) are rarely encountered. Due to the paucity of cases, little is known about the clinical features and treatment outcomes of PCNSL other than DLBCL. The objective of this study was to describe the clinical characteristics and outcomes for patients with PCNSL other than DLBCL. Fifteen patients, newly diagnosed with PCNSLs other than DLBCL between 2000 and 2010, were included. The male to female ratio was 0.67:1 with a median age of diagnosis of 31 years (range 18–59). Pathologic distributions were as follows: peripheral T-cell lymphoma (PTCL; n = 7), marginal zone B-cell lymphoma (MZBCL; n = 1), lymphoplasmacytic lymphoma (LPL; n = 2), Burkitt’s lymphoma (n = 1), other unspecified (T-cell lineage, n = 2; B-cell lineage, n = 2). Thirteen patients (87%) showed Eastern Cooperative Oncology Group performance score (ECOG PS) 1–2. The remaining two were one PTCL patient and one Burkitt’s lymphoma patient. Of the nine patients with T-cell lymphoma, five (56%) had multifocal lesions, and one (20%) with LPL of the five patients with B-cell lymphoma showed a single lesion. Leptomeningeal lymphomatosis was identified in two patients (one with Burkitt’s lymphoma and one with unspecified B-cell lymphoma). Two patients (22%) with T-cell lymphoma died 7.7 and 23.3 months later, respectively, due to disease progression, despite HD-MTX-based therapy. Six patients with T-cell lymphoma (6/9, 66.7%) and four patients with low-grade B-cell lymphoma (4/5, 80%) achieved complete response and have survived without relapse (Table 3). One patient with Burkitt’s lymphoma showed poor clinical features with ECOG PS 3, deep structure, multifocal, and leptomeningeal lymphomatosis, and died 7.6 months after the initiation of treatment. In comparison with previously reported DLBCLs (median OS 6.4 years, 95% CI 3.7–9.1 years), T-cell lymphoma showed equivocal or favorable clinical outcomes and low-grade B-cell lymphomas, such as MZBCL and LPL, had a good prognosis. However, primary CNS Burkitt’s lymphoma presented poor clinical outcomes and showed a comparatively aggressive clinical course. In conclusion, primary CNS lymphoma other than DLBCL occurred more in younger patients and showed a generally good prognosis, except for Burkitt’s lymphoma. Further research on treatment strategies for Burkitt’s lymphoma is needed.
Primary CNS lymphoma; Diffuse large B-cell lymphoma