Purpose: The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC. Materials and Methods: Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed. Results: PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035). Conclusion Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.

Purpose: Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy. Materials and Methods: We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA. Results: Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker. Conclusion Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.

Purpose: Desmoid tumor, also known as aggressive fibromatosis, is well-characterized by abnormal Wnt/β-catenin signaling. Various therapeutic options, including imatinib, are available to treat desmoid tumor. However, the molecular mechanism of why imatinib works remains unclear. Here, we describe potential roles of NOTCH2 and HES1 in clinical response to imatinib at genome and transcriptome levels. Materials and Methods: We identified somatic mutations in coding and noncoding regions via whole-genome sequencing. To validate the genetic interaction with expression level in desmoid-tumor condition, we utilized large-scale whole-genome sequencing and transcriptome datasets from the Pan-Cancer Analysis of Whole Genomes project. RNA-sequencing was performed using prospective and retrospective cohort samples to evaluate the expressional relevance with clinical response. Results: Among 20 patients, four (20%) had a partial response and 14 (66.7%) had stable disease, 11 of which continued for ≥ 1 year. With gene-wise functional analyses, we detected a significant correlation between recurrent NOTCH2 noncoding mutations and clinical response to imatinib. Based on Pan-Cancer Analysis of Whole Genomes data analyses, NOTCH2 mutations affect expression levels particularly in the presence of CTNNB1 missense mutations. By analyzing RNA-sequencing with additional desmoid tumor samples, we found that NOTCH2 expression was significantly correlated with HES1 expression. Interestingly, NOTCH2 had no statistical power to discriminate between responders and non-responders. Instead, HES1 was differentially expressed with statistical significance between responders and non-responders. Conclusion Imatinib was effective and well tolerated for advanced desmoid tumor treatment. Our results show that HES1, regulated by NOTCH2, as an indicator of sensitivity to imatinib, and an important therapeutic consideration for desmoid tumor.

BACKGROUND: Previously, cutaneous lymphomas were classified according to either the European Organization for the Research and Treatment of Cancer (EORTC) or the World Health Organization (WHO) classification paradigms. The aim of this study was to determine the relative frequency of Korean cutaneous lymphoma according to the new WHO-EORTC classification system. METHODS: A total of 517 patients were recruited during a recent 5 year-period (2006-2010) from 21 institutes and classified according to the WHO-EORTC criteria. RESULTS: The patients included 298 males and 219 females, and the mean age at diagnosis was 49 years. The lesions preferentially affected the trunk area (40.2%). The most frequent subtypes in order of decreasing prevalence were mycosis fungoides (22.2%), peripheral T-cell lymphoma (17.2%), CD30+ T-cell lymphoproliferative disorder (13.7%), and extranodal natural killer/T (NK/T) cell lymphoma, nasal type (12.0%). Diffuse large B-cell lymphoma accounted for 11.2% of cases, half of which were secondary cutaneous involvement; other types of B-cell lymphoma accounted for less than 1% of cases. CONCLUSIONS: In comparison with data from Western countries, this study revealed relatively lower rates of mycosis fungoides and B-cell lymphoma in Korean patients, as well as higher rates of subcutaneous panniculitis-like T-cell lymphoma and NK/T cell lymphoma.
Academies and Institutes ; Classification* ; Diagnosis ; Female ; Humans ; Korea ; Lymphoma* ; Lymphoma, B-Cell ; Lymphoma, T-Cell ; Lymphoma, T-Cell, Peripheral ; Lymphoproliferative Disorders ; Male ; Mycosis Fungoides ; Prevalence ; T-Lymphocytes ; World Health Organization

BACKGROUND: Various regimens have been studied in extension of a preexisting labor epidural for emergency cesarean section. Lumbar epidural analgesia for delivery is safe and efficient. We compared retrospectively 0.5% ropivacaine with fentanyl and 0.75% ropivacaine in extension of a preexisting labor epidural for emergency cesarean section. METHODS: We investigated medical records of 61 parturients in extension of a preexisting labor epidural for emergency cesarean section. There were two regimens which was 0.5% ropivacaine with fentanyl (group 1) and 0.75% ropivacaine (group 2). We recorded demographic data, local anesthetic dose, surgical readiness time, maximum level of sensory block, surgery time, intravenous supplementation, number of hypotension and total dose of ephedrine between two groups. RESULTS: There were no differences between the study groups in demographic data, surgical readiness time, maximum sensory block level, intravenous supplementation, incidence of hypotension and total dose of ephedrine. Local anesthetic volume was larger in group 1 than group 2, but local anesthetic doses were lower in group 1 than group 2. CONCLUSIONS: 0.5% Ropivacaine with fentanyl regimen is as fast and efficacious as 0.75% ropivacaine in extension of a preexisting labor epidural for cesarean section and reduces the requiring total local anesthetic dose.
Analgesia, Epidural ; Cesarean Section* ; Emergencies* ; Ephedrine ; Female ; Fentanyl* ; Hypotension ; Incidence ; Medical Records ; Pregnancy ; Retrospective Studies*

A 34-year-old female with multiple sclerosis (MS) was scheduled Cesarean section. She had been suffering from MS for 10 years and the symptoms of MS were paraplegia and urinary incontinence. After informed consent, anesthesia was induced with propofol and maintained with nitrous oxide, sevoflurane and fentanyl. Rocuronium was used for muscle relaxation and tracheal intubation. Train of four (TOF) ratio and bispectral index scale were monitored for adequate muscle relaxation and depth of anesthesia. She gave birth to a baby within 7 minutes after skin incision. When operation was over, TOF ratio was 0.8. She emerged from general anesthesia smoothly and was extubated. There was no febrile event or exacerbation of MS after Cesarean section under general anesthesia. We report a safe anesthetic management of the parturient with MS, using sevoflurane.
Adult ; Androstanols ; Anesthesia ; Anesthesia, General ; Cesarean Section ; Female ; Fentanyl ; Humans ; Informed Consent ; Intubation ; Methyl Ethers ; Multiple Sclerosis ; Muscle Relaxation ; Nitrous Oxide ; Paraplegia ; Parturition ; Pregnancy ; Propofol ; Skin ; Stress, Psychological ; Urinary Incontinence

BACKGROUND: Subarachnoid block is a widely used technique for cesarean section. To improve the quality of analgesia and prolong the duration of analgesia, addition of intrathecal opioids to local anesthetics has been encouraged. We compared the effects of sufentanil 2.5 microg and 5 microg, which were added to intrathecal hyperbaric bupivacaine. METHODS: We enrolled 105 full term parturients were randomly divided into 3 groups: Group 1 (control), Group 2 (sufentanil 2.5 microg), and Group 3 (sufentanil 5 microg). In every group, 0.5% heavy bupivacaine was added according to the adjusted dose regimen. We determined the maximum level of sensory block and motor block, the quality of intraoperative analgesia, the duration of effective analgesia and side effects. RESULTS: There were no significant differences among the 3 groups in the maximum level of the sensory block and motor block. Recovery rate of the sensory block, however, was significantly slower in Group 3 than Group 1. Quality of intraopertive analgesia, muscle relaxation, and duration of effective analgesia were enhanced by increasing the dosage of intrathecal sufentanil. Frequencies of hypotension, maximum sedation level, and pruritus were directly related to the dosage of intrathecal sufentanil, whereas nausea and vomiting occurred only in the groups using sufentanil. CONCLUSIONS: The addition of sufentanil 2.5 microg for spinal anesthesia provides adequate intraoperative analgesia and good postoperative analgesia with minimal adverse effects on the mother.
Analgesia ; Analgesics, Opioid ; Anesthesia, Spinal ; Anesthetics, Local ; Bupivacaine ; Cesarean Section ; Female ; Humans ; Hypotension ; Mothers ; Muscle Relaxation ; Nausea ; Pregnancy ; Pruritus ; Sufentanil ; Vomiting

BACKGROUND: The aim of study was to determine the relative frequency of malignant lymphoma according to World Health Organization (WHO) classification in Korea. METHODS: A total of 3,998 cases diagnosed at 31 institutes between 2005 and 2006 were enrolled. Information including age, gender, pathologic diagnosis, site of involvement and immunophenotypes were obtained. RESULTS: The relative frequency of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) was 95.4% and 4.6%, respectively. B-cell lymphomas accounted for 77.6% of all NHL, while T/natural killer (T/NK)-cell lymphomas accounted for 22.4%. The most frequent subtypes of NHL were diffuse large B-cell lymphoma (42.7%), extranodal marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (19.0%), NK/T-cell lymphoma (6.3%) and peripheral T-cell lymphoma (PTCL), unspecified (6.3%), in decreasing order. The relative frequency of HL was nodular sclerosis (47.4%), mixed cellularity (30.6%), and nodular lymphocyte predominant (12.1%) subtypes. Compared with a previous study in 1998, increase in gastric MZBCL and nodular sclerosis HL, and slight decrease of follicular lymphoma, PTCL, and NK/T-cell lymphoma were observed. CONCLUSIONS: Korea had lower rates of HL and follicular lymphoma, and higher rates of extranodal NHL, extranodal MZBCL, and NK/T-cell lymphoma of nasal type compared with Western countries. Changes in the relative frequency of lymphoma subtypes are likely ascribed to refined diagnostic criteria and a change in national health care policy.
Academies and Institutes ; Delivery of Health Care ; Hodgkin Disease ; Korea ; Lymphocytes ; Lymphoid Tissue ; Lymphoma ; Lymphoma, B-Cell ; Lymphoma, B-Cell, Marginal Zone ; Lymphoma, Follicular ; Lymphoma, Non-Hodgkin ; Lymphoma, T-Cell, Peripheral ; Sclerosis ; World Health Organization

BACKGROUND: Subarachnoid block is widely used for cesarean section due to the rapid induction, the complete analgesia, the low failure rate and the prevention of aspiration pneumonia. The addition of intrathecal opioids to local anesthetics seems to improve the quality of analgesia & prolong the duration of analgesia. Therefore we compared the effects of fentanyl 20 microg and sufentanil 2.5 microg, which were added to intrathecal hyperbaric bupivacaine. METHODS: Seventy two healthy term parturients were randomly divided into three groups: Group C (control), Group F (fentanyl 20 microg) and Group S (sufentanil 2.5 microg). In every group, 0.5% heavy bupivacaine was added according to the adjusted dose regimen by Harten et al. We observed the maximal level of the sensory block and motor block, the quality of intraoperative analgesia, the duration of effective analgesia and the side effects. RESULTS: There were significant differences between the control and the fentanyl 20 microg and sufentanil 2.5 microg groups for the degree of muscle relaxation, the quality of intraoperative analgesia, the maximal sedation level and the duration of effective analgesia. The frequencies of side effects such as nausea and pruritis in the opioid groups were higher than those in the control group. But there were no differences between fentanyl 20 microg and sufentanil 2.5 microg for the frequencies of nausea and pruritis. CONCLUSIONS: The addition of fentanyl 20 microg or sufentanil 2.5 microg for spinal anesthesia provides adequate intraoperative analgesia without significant adverse effects on the mother and neonate.
Analgesia ; Analgesics, Opioid ; Anesthesia, Spinal ; Anesthetics, Local ; Bupivacaine ; Cesarean Section ; Female ; Fentanyl ; Humans ; Infant, Newborn ; Mothers ; Muscle Relaxation ; Nausea ; Pneumonia, Aspiration ; Pregnancy ; Pruritus ; Sufentanil

PURPOSE: The glutathione-S-transferase (GST)P1, GSTM1, and GSTT1 genotypes have been associated with an increased risk of prostate, bladder, and lung cancers. The aim of this study was to investigate the association between the GSTP1, GSTM1, and GSTT1 genotypes and the risk of prostate cancer in Korean men. MATERIALS AND METHODS: The study group consisted of 166 patients with histologically confirmed prostate cancer. The control group consisted of 327 healthy, cancer-free individuals. The diagnosis of prostate cancer was made by transrectal ultrasound-guided biopsy. Patients with prostatic adenocarcinoma were divided into organ-confined (< or =pT2) and non-organ-confined (> or =pT3) subgroups. The histological grades were subdivided according to the Gleason score. The GSTP1, GSTM1, and GSTT1 genotypes were determined by using polymerase chain reaction-based methods. The relationship among GSTP1, GSTM1, and GSTT1 polymorphisms and prostate cancer in a case-control study was investigated. RESULTS: The frequency of the GSTM1 null genotype in the prostate cancer group (54.2%) was higher than in the control group (odds ratio=1.53, 95% confidence interval=1.20-1.96). The comparison of the GSTP1, GSTM1, and GSTT1 genotypes and cancer prognostic factors, such as staging and grading, showed no statistical significance. CONCLUSIONS: An increased risk for prostate cancer may be associated with the GSTM1 null genotype in Korean men, but no association was found with the GSTT1 or GSTP1 genotypes.
Adenocarcinoma ; Biopsy ; Case-Control Studies ; Genotype ; Glutathione Transferase ; Humans ; Lung Neoplasms ; Male ; Neoplasm Grading ; Prostate ; Prostatic Neoplasms ; Urinary Bladder