PURPOSE: CKD-516 is a newly developed vascular disrupting agent. This phase I dose-escalation study of CKD-516 was conducted to determine maximum-tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor efficacy in patients with advanced solid tumors. MATERIALS AND METHODS: Patients received CKD-516 intravenously on D1 and D8 every 3 weeks, in a standard 3+3 design. Safety was evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.02 and response was assessed by Response Evaluation Criteria in Solid Tumor ver. 1.1. RESULTS: Twenty-three patients were treated with CKD-516 at seven dosing levels: 1 mg/m2/day (n=3), 2 mg/m2/day (n=3), 3.3 mg/m2/day (n=3), 5 mg/m2/day (n=3), 7 mg/m2/day (n=3), 9 mg/m2/day (n=6), and 12 mg/m2/day (n=2). Mean age was 54 and 56.5% of patients were male. Two dose-limiting toxicities, which were both grade 3 hypertension, were observed in two patients at 12 mg/m2/day. The MTD was determined as 12 mg/m2/day. Most common adverse events were gastrointestinal adverse events (diarrhea, 34.8% [30.4% grade 1/2, 13.0% grade 3]; nausea, 21.7% [all grade 1/2]; vomiting, 21.7% [all grade 1/2]), myalgia (17.4%, all grade 1/2), and abdominal pain (21.7% [21.7% grade 1/2, 4.3% grade 3]). The pharmacokinetic study showed the dose-linearity of all dosing levels. Among 23 patients, six patients (26.1%) showed stable disease. Median progression-free survival was 39 days (95% confidence interval, 37 to 41 days). CONCLUSION: This study demonstrates feasibility of CKD-516, novel vascular disrupting agent, in patients with advanced solid tumor. MTD of CKD-516 was defined as 12 mg/m2/day on D1 and D8 every 3 weeks.
Abdominal Pain ; Disease-Free Survival ; Humans ; Hypertension ; Male ; Myalgia ; National Cancer Institute (U.S.) ; Nausea ; Pharmacokinetics ; Vomiting

PURPOSE: For several decades, the low anterior resection (LAR) with total mesorectal excision (TME) has been the gold standard for treating patients with rectal cancer. Up to 90% of patients undergoing sphincter-preserving surgery will have changes in bowel habits, so-called 'anterior resection syndrome.' This study examined patients' continence after a LAR for the treatment of rectal cancer. METHODS: This prospective study was performed between September 2014 and August 2015 at the National Cancer Institute and included 30 patients who underwent anorectal manometry preoperatively and at 3 and 4 months after a LAR, but 10 were excluded from further evaluation for various reasons. Wexner score was recorded preoperatively and 4 months after LAR (1 month after ileostomy repair). RESULTS: Postoperatively, 70% of patients complained of some degree of soiling (incontinence to liquid stool), and 30% experienced urgent defecation. Four months after surgery, these symptoms had somewhat abated. The anal resting pressure and the maximum squeezing pressure did not change significantly. Rectal capacity and compliance were reduced in all patients. The majority of patients demonstrated manometric anorectal changes and clinical anorectal function disorders during the first 4 months after surgery. The Wexner scores and the manometric findings showed no correlation. CONCLUSION: Many patients undergoing a LAR with TME for the treatment of rectal cancer experience some degree of incontinence postoperatively. Anorectal manometry may be used as an additional tool for evaluating problems with continence after a LAR. No correlation between the Wexner score and the manometric findings was observed.
Compliance ; Defecation ; Humans ; Ileostomy ; Manometry* ; National Cancer Institute (U.S.) ; Prospective Studies ; Rectal Neoplasms ; Soil

The Bethesda System (TBS) was first developed in 1988 for the need to enhance the communication of the cytopathologic findings to the referring physician in unambiguous diagnostic terms. The terminology used in this reporting system should reflect current understanding of the pathogenesis of cervical/vaginal disease, so the framework of the reporting system should be flexible enough to accommodate advances in medicine, including virology, molecular biology, and pathology. Three years after the introduction of TBS, the second Bethesda workshop was held to set or amend diagnostic criteria for each categories of TBS. TBS 1991 is now widely used. The third Bethesda workshop, The Bethesda System 2001 Workshop, was held in National Cancer Institute, Bethesda, Maryland from April 30 to May 2, 2001. Again, the goals of this workshop were to promote effective communication and to clarify in reporting cervical cytopathology results to clinicians and to provide with the information to make appropriate decisions about diagnosis and treatment. Nine forum groups were made and there were Web-based bulletin board discussions between October, 2000 and the first week of April, 2001. On the basis of bulletin board comments and discussions, the forum moderators recommended revised terminologies in the Workshop. Hot discussions were followed after the presentation by forum moderators during the workshop. Terminologies confusing clinicians and providing no additional informations regarding patient management were deleted in the workshop to clarify the cervicovaginal cytology results. Any informations related to the patient management were encouraged to add. So 'Satisfactory for evaluation but limited by' of 'Specimen Adequacy' catergory was deleted. Terminology of 'Unsatisfactory' was further specified as 'Specimen rejected' and 'Specimen processed and examined, but unsatisfactory'. Terminologies of 'Benign Cellular Change' and 'Within Normal Limits' were combined and terminology was changed to 'Negative for intraepithelial lesion
Diagnosis ; Education* ; Humans ; Maryland ; Molecular Biology ; National Cancer Institute (U.S.) ; Pathology ; Virology

Fine needle aspiration biopsy (FNAB) is an accurate and cost effective diagnostic tool for differentiating malignant and benign thyroid nodules. Despite the efforts of the Papanicolaou group to standardize thyroid cytopathology reporting, no universal standard reporting system exists to date. Pathologists believe that clinicians sufficiently understand FNAB cytological reports. However, this is not necessarily the case. There is often a significant gap between pathologists' beliefs and the clinicians' understanding. As a result, we propose "The Bethesda System for Reporting Thyroid Cytopathology" by the National Cancer Institute. In this editorial, we briefly introduce the Bethesda System for Reporting Thyroid Cytopathology.
Biopsy ; Biopsy, Fine-Needle ; Collodion ; National Cancer Institute (U.S.) ; Thyroid Gland ; Thyroid Nodule

Neuroendocrine carcinomas of the uterine cervix are very rare cervical neoplasms. It has frequent distant metastasis at diagnosis and high recurrent rate against multimodality therapies such as surgery, chemotherapy and radiation therapy. In 1997, four categories of endocrine tumors of uterine cervix were recommended by the Cancer Committee of the College of American Pathologists and the National Cancer Institute. It has been suggested that infection of human papillomavirus and molecular biologic abnormalities in genomic level are causes of this disease. Although a lot of studies about this disease concerning therapies and prognostic factors have been reported, there is no standard therapeutic regimens because of low incidence and difficulties of histologic diagnosis, so further studies about this issues are required. We report a case of large cell neuroendocrine uterine cervical carcinoma treated with chemotherapy followed by surgery.
Carcinoma, Neuroendocrine* ; Cervix Uteri* ; Diagnosis ; Drug Therapy ; Female ; Humans ; Incidence ; National Cancer Institute (U.S.) ; Neoplasm Metastasis ; Uterine Cervical Neoplasms

BACKGROUND/AIMS: This study investigated the efficacy and safety of docetaxel/cisplatin/5-fluorouracil (DCF) combination chemotherapy as a first-line treatment in patients with advanced gastric cancer. METHODS: The study enrolled 48 patients diagnosed with unresectable pathologically proven gastric cancer who received DCF combination chemotherapy between April 2006 and August 2009. The dose administered was docetaxel 75 mg/m2 for 1 h and cisplatin 75 mg/m2 for 90 min on day 2, and 5-FU 750 mg/m2 for 24 h on days 1-5, every 3 weeks. The response was assessed every three cycles. The toxicity was evaluated for every chemotherapy course according to the National Cancer Institute (NCI) toxicity criteria ver. 2.0. RESULTS: The median age of the patients was 58 years (range 31-78 years). The median overall survival was 11.5 months (2.3-28.2 months) and the median time to progression was 5.5 months (0.3-18.9 months). No complete remission occurred. Of the patients, 56% achieved a partial response, 21% stable disease, and 10% progressive disease. The overall response rate was 56%. During a total 292 cycles, anemia worse than NCI toxicity grade 3 occurred in 2%, leukopenia in 33.1%, neutropenia in 67.1%, and thrombocytopenia in 4.4%. Neutropenic fever occurred in 33 cycles (11.3%), dose reduction due to side effects in 165 cycles (56.5%), and a regimen change due to side effect in five cycles (1.7%). CONCLUSIONS: Combination chemotherapy with docetaxel, cisplatin, and 5-FU is efficacious, but has relatively high toxicity. A DCF protocol that maximizes its efficiency, while minimizing toxicity, would be more useful as a first-line treatment in patients with advanced gastric cancer.
Anemia ; Cisplatin ; Drug Therapy, Combination ; Fever ; Fluorouracil ; Humans ; Leukopenia ; National Cancer Institute (U.S.) ; Neutropenia ; Stomach Neoplasms ; Taxoids ; Thrombocytopenia

BACKGROUND: Administration of anticancer drugs may damage gastrointestinal epithelium, thereby increasing the permeability of the gastrointestinal mucosa. It is known that intestinal permeability test using 51Cr-EDTA is a useful test to assess the damage of intestine. The aim of this study was to evaluate intestinal permeability in patients who were treated with 5-fluorouracil (5-FU) based chemotherapy and to evaluate the relationship between the excretion of 51Cr-EDTA and the grading of mucositis. METHODS: Twenty eight patients who were treated with 5-FU based chemotherapy were chosen as study cases while 18 healthy volunteers as controls. Intestinal permeability was assessed by measurement of the urinary excretion of 51Cr-EDTA after oral challenge, and the National Cancer Institute common toxicity criteria were used for assessing oral mucositis. RESULTS: All except 3 patients in the chemotherapy group experienced grade 1~3 stomatitis. The median value of intestinal permeability test was significantly higher in the chemotherapy group than in control group (7.61%, range 2.10-22.92 vs 2.17%, range 1.16-2.76, respectively, p<0.001). The grading of oral mucositis did correlate with the urinary excretion of 51Cr-EDTA (p<0.001, r=0.867). CONCLUSIONS: The measurement of 51Cr-EDTA excretion after oral challenge may be a useful test for evaluating the intestinal permeability by chemotherapy induced intestinal mucosal damage. Testing of intestinal permeability using 51Cr-EDTA may be applicable to evaluate the effect of therapeutic trials in patients with chemotherapy induced mucositis.
Drug Therapy* ; Epithelium ; Fluorouracil* ; Healthy Volunteers ; Humans ; Intestines ; Mucositis* ; Mucous Membrane ; National Cancer Institute (U.S.) ; Permeability ; Stomatitis

BACKGROUND: The Bethesda classification system for reporting on thyroid fine-needle aspiration (FNA) cytology was recently proposed by the National Cancer Institute, USA. We aimed to report our experience with applying this system for thyroid FNA, with a focus on comparing it with the four categorical system. METHODS: We retrospectively reviewed the 4,966 thyroid FNAs that were performed at the Seoul St. Mary's Hospital between October 2008 and September 2009. All the FNAs were classified according to the Bethesda system and the four tier system. RESULTS: The cytologic diagnoses of the Bethesda system included 10.0% unsatisfactory, 67.7% benign, 3.1% atypia of undetermined significance, 0.6% follicular neoplasm, 0.5% follicular neoplasm, Hurthle cell type, 5.1% suspicious for malignancy and 13.0% malignancy. Using four tier system, 10.1%, 67.6%, 9.3%, and 13% were diagnosed as unsatisfactory, negative for malignancy, atypical cells and malignancy, respectively. Of the 4,966 nodules, 905 were histologically confirmed. The specificity of the Bethesda system and the four tier system for diagnosing malignancy was 99.6% and 82.6%, respectively. CONCLUSIONS: The Bethesda system can classify indeterminate thyroid nodules into more detailed categories and provide clinicians with useful information for management.
Biopsy, Fine-Needle ; Diagnostic Techniques and Procedures ; National Cancer Institute (U.S.) ; Retrospective Studies ; Sensitivity and Specificity ; Thyroid Gland ; Thyroid Neoplasms ; Thyroid Nodule

BACKGROUND: The Bethesda classification system for reporting on thyroid fine-needle aspiration (FNA) cytology was recently proposed by the National Cancer Institute, USA. We aimed to report our experience with applying this system for thyroid FNA, with a focus on comparing it with the four categorical system. METHODS: We retrospectively reviewed the 4,966 thyroid FNAs that were performed at the Seoul St. Mary's Hospital between October 2008 and September 2009. All the FNAs were classified according to the Bethesda system and the four tier system. RESULTS: The cytologic diagnoses of the Bethesda system included 10.0% unsatisfactory, 67.7% benign, 3.1% atypia of undetermined significance, 0.6% follicular neoplasm, 0.5% follicular neoplasm, Hurthle cell type, 5.1% suspicious for malignancy and 13.0% malignancy. Using four tier system, 10.1%, 67.6%, 9.3%, and 13% were diagnosed as unsatisfactory, negative for malignancy, atypical cells and malignancy, respectively. Of the 4,966 nodules, 905 were histologically confirmed. The specificity of the Bethesda system and the four tier system for diagnosing malignancy was 99.6% and 82.6%, respectively. CONCLUSIONS: The Bethesda system can classify indeterminate thyroid nodules into more detailed categories and provide clinicians with useful information for management.
Biopsy, Fine-Needle ; Diagnostic Techniques and Procedures ; National Cancer Institute (U.S.) ; Retrospective Studies ; Sensitivity and Specificity ; Thyroid Gland ; Thyroid Neoplasms ; Thyroid Nodule

BACKGROUND AND OBJECTIVES: To evaluate the usefulness of fine needle aspiration (FNA) for thyroid nodule using the new Bethesda classification. SUBJECTS AND METHOD: Patient cytology data were reviewed by retrospective search of thyroid FNA. Cytologic diagnoses were classified as unsatisfactory, benign/negative for malignancy, indeterminate (ID), follicular neoplasm (FN), suspicious for malignancy (SM), and positive for malignancy (PM) according to the proposing of The National Cancer Institute. We analyzed the follow-up FNA diagnoses and the cytologic-histologic correlations. RESULTS: Of 1983 patients, 16.8% was classified as unsatisfactory, 73.6% as benign, 1.1% as ID, 0.4% as FN, 1.4% as SM, and 6.8% as PM. After the cytologic follow-up, the groups designated as unsatisafactory (80.2%) and ID (50%) mainly showed significant change in diagnosis. Two hundred fifty patients had surgical follow-up. Sensitivity, specificity, and accuracy, positive predictive values and negative predictive values for malignancy of thyroid were 87.6%, 97.2%, 91%, 98.3% and 81.2%, respectively. The cytologic-histologic diagnostic discrepancy rate was 13.6%. CONCLUSION: FNA for thyroid nodule using the new Bethesda classification was an accurate and sensitive method for the diagnosis of thyroid nodule, and can provide useful information for the management of thyroid nodule.
Biopsy, Fine-Needle ; Follow-Up Studies ; Humans ; National Cancer Institute (U.S.) ; Retrospective Studies ; Sensitivity and Specificity ; Thyroid Gland ; Thyroid Nodule