Successful Sirolimus Treatment for Korean Patients with Activated Phosphoinositide 3-kinase δ Syndrome 1: the First Case Series in Korea

Activated phosphoinositide 3-kinase δ syndrome (APDS)1 is caused by gain-of-function mutations in PIK3CD, which encodes the catalytic p110δ subunit of phosphoinositide 3 kinase. We describe three patients with APDS1, the first thereof in Korea. Therein, we investigated clinical manifestations of APDS1 and collected data on the efficacy and safety profile of sirolimus, a mammalian target of rapamycin inhibitor and pathway-specific targeted medicine. The same heterozygous PIK3CD mutation was detected in all three patients (E1021K). After genetic diagnosis, all patients received sirolimus and experienced an excellent response, including amelioration of lymphoproliferation and improvement of nodular mucosal lymphoid hyperplasia in the gastrointestinal tract. The median trough level of sirolimus was 5.5 ng/mL (range, 2.8–7.5) at a dose of 2.6–3.6 mg/m2. Two patients who needed highdose, short-interval, immunoglobulin-replacement treatment (IGRT) had a reduced requirement for IGRT after initiating sirolimus, and the dosing interval was extended from 2 and 3 weeks to 4 weeks. The IgG trough level after sirolimus treatment (median, 594 mg/dL; range, 332–799 mg/dL) was significantly higher than that before sirolimus treatment (median, 290 mg/dL; range, 163–346 mg/dL) (p<0.001). One episode of elevated serum creatinine with a surge of sirolimus (Patient 2) and episodes of neutropenia and oral stomatitis (Patient 1) were observed. We diagnosed the first three patients with APDS1 in Korea. Low-dose sirolimus may alleviate clinical manifestations thereof, including hypogammaglobulinemia.

Identification of Significant Prognostic Tissue Markers Associated with Survival in Upper Urinary Tract Urothelial Carcinoma Patients Treated with Radical Nephroureterectomy: A Retrospective Immunohistochemical Analysis Using Tissue Microarray / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to identify prognostic tissue markers for several survival outcomes after radical nephroureterectomy among patients with upper urinary tract urothelial carcinoma using tissue microarray and immunohistochemistry. @*Materials and Methods@#Retrospectively, data of 162 non-metastatic patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy between 2004 and 2016 were reviewed to determine intravesical recurrence-free survival (IVRFS), disease-free survival (DFS), and overall survival (OS). The expression of 27 tissue markers on a tissue microarray of radical nephroureterectomy samples and prognostic values of clinicopathological parameters were evaluated using immunohistochemistry and Cox proportional hazard models after adjusting for significant prognostic clinicopathological variables. The expression of all tissue markers was categorized into a binary group with continuous H-scores (0-300). @*Results@#Median follow-up was 53.4 months (range, 3.6 to 176.5 months); and, 58 (35.8%), 48 (29.6%), and 19 (11.7%) bladder recurrence, disease progression, and all cause death, respectively, were identified. After adjusting for significant clinicopathological factors including intravesical instillation for bladder recurrence-free survival, pathologic T category and intravesical instillation for disease progression-free survival , and pathologic T category for OS (p < 0.05), IVRFS was associated with epithelial cadherin (hazard ratio [HR], 0.49), epidermal growth factor receptor/erythroblastosis oncogene B (c-erb) (HR, 2.59), and retinoblastoma protein loss (HR, 1.85); DFS was associated with cyclin D1 (HR, 2.16) and high-molecular-weight cytokeratin (HR, 0.42); OS was associated with E-cadherin (HR, 0.34) and programmed cell death 1 ligand (HR, 13.42) (p < 0.05). @*Conclusion@#Several significant tissue markers were associated with survival outcomes in upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy.

Efficacy of Brentuximab Vedotin in Relapsed or RefractoryHigh-CD30–Expressing Non-Hodgkin Lymphomas:Results of a Multicenter, Open-Labeled Phase II Trial / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The treatment outcome of brentuximab vedotin (BV) has not been related with CD30 expressionin previous studies enrolling patients with a wide range of CD30 expression level.Thus, this study explored the efficacy of BV in high-CD30–expressing non-Hodgkin lymphoma(NHL) patients most likely to benefit. @*Materials and Methods@#This phase II study (Clinicaltrials.gov: NCT02280785) enrolled relapsed or refractory high-CD30–expressing NHL, with BV administered intravenously at 1.8 mg/kg every 3 weeks.The primary endpoint was > 40% disease control rate, consisting of complete response(CR), partial response (PR), or stable disease. We defined high CD30 expression as ! 30%tumor cells positive for CD30 by immunohistochemistry. @*Results@#High-CD30-expressing NHL patients (n=33) were enrolled except anaplastic large cell lymphoma.The disease control rate was 48.5% (16/33) including six CR and six PR; six patients(4CR, 2PR) maintained their response over 16 completed cycles. Response to BV and survivalwere not associated with CD30 expression levels. Over a median of 29.2 months offollow-up, the median progression-free and overall survival rates were 1.9 months and 6.1months, respectively. The most common adverse events were fever (39%), neutropenia(30%), fatigue (24%), and peripheral sensory neuropathy (27%). In a post-hoc analysis forthe association of multiple myeloma oncogene 1 (MUM1) on treatment outcome, MUM1-negative patients showed a higher response (55.6%, 5/9) than MUM1-positive patients(13.3%, 2/15). @*Conclusion@#BV performance as a single agent was acceptable in terms of disease control rates and toxicityprofiles, especially MUM1-negative patients.

Retrospective Study of the Significant Predictive Role of Inflammatory Degree in Initial and Repeat Prostate Biopsy Specimens for Detecting Prostate Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to determine whether histologic inflammation (HI) in initial and repeat prostate biopsy specimens was significantly associated with the detection of prostate cancer. MATERIALS AND METHODS: Between 2005 and 2017, the clinicopathological records of patients with high prostate-specific antigen (PSA) levels who underwent initial and repeat prostate biopsies were retrospectively reviewed. The presence of HI and its degree in each biopsied specimen were interpreted by one uropathologist with 20 years of experience. The association between HI and cancer diagnosis was statistically assessed, with p 0%) on biopsied specimens, respectively. Comparison of the cancer and noncancer groups revealed that a greater rate of HI specimens in the initial biopsy was associated with fewer prostate cancer diagnoses following repeat biopsy (p < 0.001). Other comparisons between the cancer and non-cancer groups showed that the cancer group had a significantly higher rate of hypertension, whereas those non-cancer group had a significantly higher rate of benign prostatic hyperplasia and prostatitis (p < 0.05). CONCLUSION: A finding of a lesser degree of HI in the initial and a greater degree of HI in the repeat biopsied specimens was associated with the higher probability of cancer diagnosis in patients with high PSA levels.

PLAG1, SOX10, and Myb Expression in Benign and Malignant Salivary Gland Neoplasms

BACKGROUND: Recent findings in molecular pathology suggest that genetic translocation and/or overexpression of oncoproteins is important in salivary gland tumorigenesis and diagnosis. We investigated PLAG1, SOX10, and Myb protein expression in various salivary gland neoplasm tissues. METHODS: A total of 113 cases of surgically resected salivary gland neoplasms at the National Cancer Center from January 2007 to March 2017 were identified. Immunohistochemical staining of PLAG1, SOX10, and Myb in tissue samples was performed using tissue microarrays. RESULTS: Among the 113 cases, 82 (72.6%) were benign and 31 (27.4%) were malignant. PLAG1 showed nuclear staining and normal parotid gland was not stained. Among 48 cases of pleomorphic adenoma, 29 (60.4%) were positive for PLAG1. All other benign and malignant salivary gland neoplasms were PLAG1-negative. SOX10 showed nuclear staining. In normal salivary gland tissues SOX10 was expressed in cells of acinus and intercalated ducts. In benign tumors, SOX10 expression was observed in all pleomorphic adenoma (48/48), and basal cell adenoma (3/3), but not in other benign tumors. SOX10 positivity was observed in nine of 31 (29.0%) malignant tumors. Myb showed nuclear staining but was not detected in normal parotid glands. Four of 31 (12.9%) malignant tumors showed Myb positivity: three adenoid cystic carcinomas (AdCC) and one myoepithelial carcinoma with focal AdCC-like histology. CONCLUSIONS: PLAG1 expression is specific to pleomorphic adenoma. SOX10 expression is helpful to rule out excretory duct origin tumor, but its diagnostic value is relatively low. Myb is useful for diagnosing AdCC when histology is unclear in the surgical specimen.

Second Primary Cancer Risk among Kidney Cancer Patients in Korea: A Population-Based Cohort Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Secondary primary cancers (SPCs) commonly arise in patients with renal cell carcinoma (RCC). We designed the present study to estimate the SPC incidence in Korean patients with RCC. MATERIALS AND METHODS: The study cohort was population-based and consisted of 40,347 individuals from the Korean Central Cancer Registry who were diagnosed with primary renal cancer between 1993 and 2013. Standardized incidence ratios (SIRs) for SPCs were estimated for different ages at diagnosis, latencies, diagnostic periods, and treatments. RESULTS: For patients with primary RCC, the risk of developing a SPC was higher than the risk of developing cancer in the general population (SIR, 1.13; 95% confidence interval, 1.08 to 1.18). Most cancer types showed higher incidences in patients with RCC than in the general population. However, the relative incidence of gastric cancer as an SPC varied by age. Gastric cancer incidence was elevated in young patients (< 30 years) with RCC, but reduced in older (≥ 30) patients with RCC. Patients with advanced RCC died prematurely, regardless of SPC development. In contrast, those with early-stage RCC survived for longer periods, although SPC development affected their post-RCC survival. After SPC development, women had better survival than men. CONCLUSION: In Korean patients with primary RCC, the incidence of SPC was 13% higher than the incidence of cancer in the general population. These findings may play important roles in the conduct of follow-up evaluations and education for patients with RCC.

Prostatectomy Provides Better Symptom-Free Survival Than Radiotherapy Among Patients With High-Risk or Locally Advanced Prostate Cancer After Neoadjuvant Hormonal Therapy

PURPOSE: The purpose of this study is to compare the radiation therapy (RT) and radical prostatectomy (RP) of high-risk or locally advanced prostate cancer (PC) patients after neoadjuvant hormonal therapy (NHT). MATERIALS AND METHODS: This retrospective study evaluated patients underwent RT (42 patients) or RP (152 patients) after NHT at a single center during 2003–2014. Times to biochemical recurrence (BCR), pelvic local recurrence (PLR), metastasis, clinical painful symptom progression (CPSP), castration-resistant PC (CRPC), and overall survival were compared between the RT and RP groups, after adjustment for TN stage, using the Kaplan-Meier method and log-rank test. RESULTS: Significant inter-group differences were observed for age, Gleason score, initial PSA, and clinical and pathological T stages (all p 0.05). The independent predictor of CPSP was RP (hazard ratio, 0.291; p=0.013). CONCLUSIONS: Despite significantly different baseline parameters, RP provided better CPSP-free survival than RT among patients with localized high-risk or locally advanced PC.

Current Trends in the Incidence and Survival Rate of Urological Cancers in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This descriptive study assessed the current trends in the incidence of urological cancers and patient survival in Korea. MATERIALS AND METHODS: In this nationwide retrospective observational study based on the data from the Korea National Cancer Incidence Database (KNCIDB), this study analyzed the age-standardized incidence rates (ASRs) and annual percentage changes (APCs) of kidney, bladder, prostate, testicular, and penile cancers as well as cancer of the renal pelvis and ureter between 1999 and 2012. The relative survival rates (RSRs) were calculated for urological cancer patients diagnosed between 1993 and 2012 from the KNCIDB data. RESULTS: Prostate cancer was diagnosed in 66,812 individuals followed by bladder (41,549) and kidney (36,836) cancers. The overall ASR (18.26 per 100,000) increased with age because of the higher ASRs of bladder and prostate cancers in the elderly. The ASR for kidney cancer was highest in the 40-59-year-old group, whereas testicular cancer occurred most frequently before the age of 40. The incidence of most urological cancers increased (overall APC, 6.39%; p < 0.001), except for penile (APC, –2.01%; p=0.05) and bladder (APC, –0.40%; p=0.25) cancers. The overall survival increased steadily (5-year RSR, 66.4% in 1993-1995 vs. 84.2% in 2008-2012; p < 0.001), particularly for prostate (by 34.10%) and kidney (by 16.30%) cancers, but not for renal pelvis and ureter cancers (–7.20%). CONCLUSION: The most common urological cancer in Korea was prostate cancer followed by bladder and kidney cancers. The incidence of most urological cancers, except for penile and bladder cancers, increased. Survival also increased, particularly for prostate and kidney cancers.

A Case of Disseminated Infection with Skin Manifestation due to Non-neoformans and Non-gattii Cryptococcus in a Patient with Refractory Acute Myeloid Leukemia

Cryptococcus spp. other than Cryptococcus neoformans or Cryptococcus gattii were previously considered saprophytes and thought to be non-pathogenic to humans. However, opportunistic infections associated with non-neoformans and non-gattii species, such as Cryptococcus laurentii and Cryptococcus albidus, have increased over the past four decades. We experienced a case of cryptococcosis caused by non-neoformans and non-gattii spp. in a 47-year-old female with refractory acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. The patient underwent salvage chemotherapy with fluconazole prophylaxis and subsequently developed neutropenic fever with multiple erythematous umbilicated papules. A skin biopsy revealed fungal hyphae and repetitive blood cultures showed yeast microorganisms that were identified later as C. laurentii by Vitek-II®. Skin lesions and fever began to improve with conventional amphotericin B therapy. The treatment regimen was continued for 21 days until the disseminated cryptococcosis was completely controlled.

The Retrospective Analysis of Prognostic Significance of Smoking Status in Bladder Cancer

PURPOSE: This study aimed to evaluate the prognostic significance of smoking status in muscle invasive bladder cancer (MIBC) and non-MIBC in recurrence-free (RFS), progression-free (PFS), disease-free survival (DFS), and cancer-specific survival (CSS). MATERIALS AND METHODS: We retrospectively evaluated 541 patients with MIBC and non-MIBC who were surgically treated during 2002–2013. Smoking status was defined as never smokers (NS; n=160, 30%), former smokers (FS; smoking cessation for ≥1 year, n=176, 33%), and current smokers (CS; >100 cigarettes, n=198, 37%). We statistically compared these groups' clinicopathological facCtors for the predictive factors for RFS and PFS for non-MIBC (NMIBC) and DFS for MIBC, and CSS using multivariate model. RESULTS: The CS, FS, and NS groups exhibited insignificantly different pathological staging, grades, and immunohistological characteristics (p>0.05). Among the 441 patients with NMIBC, pathologic tumor size was a significant risk factor for RFS (1–3 cm: hazard ratio [HR], 1.88; >3 cm: HR, 2.21; p < 0.05); age (HR, 1.06), intravesical therapy (HR, 0.25), and high-grade cancer (HR, 8.33) significant for PFS; and age (HR, 1.08), intravesical instillation (HR, 0.26), and smoking status (FS: HR, 0.40; CS: HR, 0.44) significant for CSS (p < 0.05). The 93 patients with MIBC had no significant risk factors for DFS, although their significant risk factors for CSS were age (HR, 1.05), female sex (HR, 2.64), and carcinoma in situ (HR, 4.72) (p < 0.05). CONCLUSIONS: Smoking status only significantly affected CSS in patients with NMIBC.

Prostate Cancer in a Patient with a Family History of BRCA Mutation: a Case Report and Literature Review

One of the most significant risk factors for prostate cancer (PC) is a family history of the disease, with germ-line mutations in the breast cancer predisposition gene (BRCA) 2 conferring the highest risk. We here report a 56-year-old man presented with painful gait disturbance and diagnosed PC with multiple disseminated bone metastases. The patient had a strong family history of breast cancer with his 2 nieces affected. Furthermore, his aunts and uncles from both sides were diagnosed with stomach, ovarian, and colorectal cancers. His genomic sequencing analysis of the BRCA genes revealed the same BRCA2 deleterious mutation that his breast cancer-affected nieces carried. Previous studies have suggested that BRCA2-mutated PC is associated with a more aggressive phenotype and poor prognosis. Our experience in the present case also indicated the urgent needs for novel treatment modality and PC screening in this high-risk group of patients.

Mucosa-Associated Lymphoid-Tissue Lymphoma of the Cecum and Rectum: A Case Report

A colonic mucosa-associated lymphoid-tissue (MALT) lymphoma is relatively rare compared to lymphomas of the stomach or small intestine. We present a case of a MALT lymphoma in the cecum and rectum found during screening colonoscopy. A 54-year-old female, who had undergone right-breast-conserving surgery with axillary dissection due to an invasive ductal carcinoma and a left-breast excisional biopsy due to microcalcification following adjuvant chemoradiation therapy 3 years earlier, was found to have 3-mm-sized smooth elevated lesions in both the cecum and rectum. No pathologic lesion or lymphadenopathy was found at any other site, but chronic gastritis negative for Helicobacter pylori infection was found. The polyps were removed by using an endoscopic biopsy and revealed an extra nodal marginal zone B-cell MALT lymphoma, showing positive for CD3 and CD20 by immunohistochemical staining. The patient underwent close observation without any additional treatment and has shown no evidence of recurrence as of her last visit.

A Case Report of Partial Nephrectomy of Mucinous Cystadenocarcinoma in Kidney and Its Literature Review / Journal of the Korean Cancer Association, 대한암학회지

Mucinous cystadenocarcinoma (MC) of the kidney is a rare epithelial tumor originating from the renal pelvic urothelium and few study cases have been reported. Because of the rarity of these tumors and their unknown histogenesis, its diagnosis is difficult until surgical exploration. We report here on a 55-year-old man referred to the urology department from the hepatology department because of a cystic renal mass measuring approximately 5 cm in size, which was detected incidentally under ultrasonography during the routine examination of liver. The renal mass was finally diagnosed as MC originating from kidney after partial nephrectomy and the patient still showed no evidence of recurrence until 12 months postoperatively. This is the first report on a case of renal MC in a patient who underwent partial nephrectomy. The aim of this report is to present our unusual case of MC and also review the previous literature on the pathological and radiological aspects of MC of kidney.

Systemic Treatments for Metastatic Renal Cell Carcinoma: 10-Year Experience of Immunotherapy and Targeted Therapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to compare the outcomes of first-line systemic targeted therapy (TT) and immunotherapy (IT) in patients with metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: This study was a retrospective review of the data of 262 patients treated with systemic IT or TT with tyrosine kinase inhibitors between 2003 and 2013. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed using Response Evaluation Criteria in Solid Tumor ver. 1.0 criteria and the Kaplan-Meier method with log-rank test. RESULTS: During the median 4.3-month treatment and the 24-month follow-up period, the ORR/PFS/OS of the overall first-line and second-line therapy were 41.9%/8.1 months/16.8 months and 27.5%/6.5 months/15.3 months, respectively. The first-line TT/IT/sequential IT had a PFS of 9.3/6.4/5.7 months and an OS of 15.8/16.5/40.6 months (all p < 0.05). The second-line of TT/IT had a PFS of 7.1/2.1 months (both p < 0.05) and an OS of 16.6/8.6 months (p=0.636), respectively. Pazopanib provided the best median PFS of 11.0 months (p < 0.001) and a quadruple IT regimen had a superior PFS (p=0.522). For OS, sequential treatment with IT and TT was superior compared to treatment with either IT or TT alone (40.6/16.5/15.8 months, p=0.014). The prognosis according to the Memorial Sloan Kettering Cancer Center model showed that favorable/intermediate/poor risk groups had a PFS of 8.5/10.4/2.3 months, and an OS of 43.1/20.4/5.6 months, respectively. The prognosis calculated using the Heng model showed that the favorable/intermediate/poor risk groups had a PFS of 9.2/3.9/2.7 months, and an OS of 32.4/16.5/6.1months, respectively (all p < 0.001). CONCLUSION: In patients with mRCC, TT provided a better PFS and OS compared with IT.

The Correlation of Tissue-Based Biomarkers in Primary and Metastatic Renal Cell Carcinoma Lesions: A Tissue Microarray Study

PURPOSE: The study was aimed to determine the correlations of tissue-based biomarker expressions between primary and metastatic specimens of renal cell carcinoma and with several well-known prognostic clinicopathological parameters. MATERIALS AND METHODS: The immunohistochemistry (IHC) was used to determine the expression levels of 9 tissue-based markers calculated in H-score expressed by percentage of expression multiplied by the intensity score (0, 1, 2, and 3 points). Using 17 patients' 38 specimens paired with primary renal lesion and its metastatic lesions collected between 2004 and 2015, Tissue microarray with IHC was performed with BAP1, PBRM1, pS6, PTEN, TGase2, PD-L1, CA9, PSMA, and Ki-67 on formalin-fixed paraffin-embedded sections. Pearson correlation and accuracy test were performed to analyze the correlation between primary and metastatic tissues. RESULTS: The 17 patients' mean age was 56.9 years old, mean tumor size was 7.9 cm, and the male to female ratio was 13:4 (76.5%:23.5%), respectively. Three patients had 2, 3, and 3 metastatic tissues, and the rest of 14 patients had only one metastatic tissue. The H-score (PSMA and Ki67) and intensity score (pS6 and PSMA) showed that some differential significant markers were identified which had statistical correlations of expression levels between primary and metastatic lesions among 9 markers. However, no real correlation of PSMA, Ki67, and pS6 markers were found their expressions of between primary and metastatic tissues because of their skewed expressions. CONCLUSIONS: Tissue markers failed to correlate their expression levels in primary lesions with those of metastatic lesions.

A Case of Langerhans Cell Histiocytosis Manifested as a Suprasellar Mass

Langerhans cell histiocytosis (LCH) has diverse clinical manifestations, including intracranial mass lesions. We report a case of LCH that manifested as a suprasellar mass, and initially misdiagnosed as a germ cell tumor. A 29-year-old woman presented with polyuria, polydipsia and amenorrhea. Laboratory findings revealed hypopituitarism with central diabetes insipidus, and a suprasellar mass and a pineal mass were observed on magnetic resonance imaging. Under the clinical impression of a germ cell tumor, the patient was treated with germ cell tumor chemotherapy (cisplatin and etoposide) and radiation therapy without biopsy. After initial shrinkage of the lesions, further growth of the tumor was observed and a biopsy was performed. The histopathology revealed LCH. After chemotherapy according to the LCH III protocol, the tumor disappeared. She is on regular follow up for 5 years without relapse. The present findings indicate that LCH should be included in the differential diagnosis of a suprasellar mass, even in adults, especially when it manifests with diabetes insipidus. This case also underscores the importance of a histopathologic diagnosis in patients with suprasellar tumors before the initiation of a specific therapy, even if the clinical findings are highly suggestive of a specific diagnosis.

A Case of Langerhans Cell Histiocytosis Manifested as a Suprasellar Mass

Langerhans cell histiocytosis (LCH) has diverse clinical manifestations, including intracranial mass lesions. We report a case of LCH that manifested as a suprasellar mass, and initially misdiagnosed as a germ cell tumor. A 29-year-old woman presented with polyuria, polydipsia and amenorrhea. Laboratory findings revealed hypopituitarism with central diabetes insipidus, and a suprasellar mass and a pineal mass were observed on magnetic resonance imaging. Under the clinical impression of a germ cell tumor, the patient was treated with germ cell tumor chemotherapy (cisplatin and etoposide) and radiation therapy without biopsy. After initial shrinkage of the lesions, further growth of the tumor was observed and a biopsy was performed. The histopathology revealed LCH. After chemotherapy according to the LCH III protocol, the tumor disappeared. She is on regular follow up for 5 years without relapse. The present findings indicate that LCH should be included in the differential diagnosis of a suprasellar mass, even in adults, especially when it manifests with diabetes insipidus. This case also underscores the importance of a histopathologic diagnosis in patients with suprasellar tumors before the initiation of a specific therapy, even if the clinical findings are highly suggestive of a specific diagnosis.

Recent Advancements of Treatment for Leptomeningeal Carcinomatosis

Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in the 1970's. The marginal survival benefit and difficulty of intrathecal chemotherapy injection has hindered its wide spread use. Even after the introduction of intraventricular chemotherapy with Ommaya reservoir, frequent development of CSF flow disturbance, manifested as increased intracranial pressure (ICP), made injected drug to be distributed unevenly and thus, the therapy became ineffective. Systemic chemotherapy for LMC has been limited as effective CSF concentration can hardly be achieved except high dose methotrexate (MTX) intravenous administration. However, the introduction of small molecular weight target inhibitors for primary cancer treatment has changed the old concept of 'blood-brain barrier' as the ultimate barrier to systemically administered drugs. Conventional oral administration achieves an effective concentration at the nanomolar level. Furthermore, many studies report that a combined treatment of target inhibitor and intra-CSF chemotherapy significantly prolongs patient survival. Ventriculolumbar perfusion (VLP) chemotherapy has sought to increase drug delivery to the subarachnoid CSF space even in patients with disturbed CSF flow. Recently authors performed phase 1 and 2 clinical trial of VLP chemotherapy with MTX, and 3/4th of patients with increased ICP got controlled ICP and the survival was prolonged. Further trials are required with newly available drugs for CSF chemotherapy. Additionally, new LMC biologic/pharmacodynamic markers for early diagnosis and monitoring of the treatment response are to be identified with the help of advanced molecular biology techniques.

Low Grade Chondrosarcoma Presenting as Progressive Valgus Limb Deformity in a Growing Period / 대한골관절종양학회지

A femoral bone tumor causing a valgus deformity by affecting the growth plate was found. Long intramedullary diaphyseal tumor was separated by septum at the metapysis. Low grade chondrosarcoma was confirmed diagnosed by pathologists. Progressive limb deformity can be a sign of bone tumor in growing period.

Exclusive Endoscopic Resection of Nasopharyngeal Papillary Adenocarcinoma via Combined Transnasal and Transoral Approach

Low grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is an extremely rare variant of nasopharyngeal cancer, which exhibits distinct clinicopathological characteristics. Surgical resection has been regarded as the principal treatment. For this, transpalatal or transfacial approach has been classically used for exposure of the field. Up for now, there has been no report on applying endoscopic approach for this disease, which could be an effective alternative to minimize possible morbidities of palatotomy or maxillotomy. Endoscopic approach can be justified considering narrow extent and indolent behavior of LGNPPA. We report a patient with LGNPPA, which was successfully resected exclusively by endoscopic visualization. Our case exhibited narrow-based exophytic features with compatible immunopathologic profiles of LGNPPA. Exclusive endoscopic resection can be effective and less-morbid modality for this rare disease as in this case.