Benefits of Adjuvant Chemotherapy for Clinical T3-4N0 Rectal Cancer After Preoperative Chemoradiotherapy / 전남의대학술지

While the guidelines for adjuvant chemotherapy (AC) for colon cancer are relatively standardized, those for early rectal cancer are still lacking. We therefore evaluated the role of AC in clinical stage II rectal cancer treatment after preoperative chemoradiotherapy (CRT). Patients diagnosed with early rectal cancer (defined by clinical stage T3/4, N0) who completed CRT followed by surgery were enrolled in this retrospective study. To evaluate the role of AC, we analyzed the risk of recurrence and survival based on clinicopathologic parameters and adjuvant chemotherapy. Of the 112 patients, 11 patients (9.8%) experienced recurrence and five patients (4.8%) died. In a multivariate analysis, circumferential resection margin involvement (CRM+) on magnetic resonance imaging at diagnosis, CRM involvement following neoadjuvant therapy (ypCRM+), tumor regression grade (≤G1) and no-AC were considered poor prognostic factors for recurrence free survival (RFS). In addition, ypCRM+ and no-AC were associated with poor overall survival (OS) in the multivariate analysis. AC including 5-FU monotherapy demonstrated the benefits of reduced recurrence and prolonged survival in clinical stage II rectal cancer, even in pathologic stage following neoadjuvant therapy (ypStage) 0-I. Further prospective studies are needed to verify the benefit of each regimen of AC and the development of a method that can accurately predict CRM status before surgery, and a vigorous treatment that can induce CRM non-involvement (CRM−) should be considered even in early stages of rectal cancer.

Prognostic Significance of the Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Neuroendocrine Carcinoma / 전남의대학술지

Extra-pulmonary neuroendocrine carcinoma is a rare and aggressive cancer. Although several biological and histological markers have been suggested as prognostic factors for this cancer, the prognostic importance of systemic inflammatory markers, including the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, is unclear. This study aimed to evaluate the association between systemic inflammatory markers and the prognosis of extra-pulmonary neuroendocrine carcinoma. We retrospectively analyzed the clinical data of 85 patients with unresectable or metastatic extra-pulmonary neuroendocrine carcinoma who received platinum-based chemotherapy as first-line chemotherapy from August 2007 to November 2019. We used time-dependent receiver operating characteristic curve analysis to determine the cut-off values. The cut-off values for the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were 3.0 and 158.5, respectively. There was no significant difference in the Eastern Cooperative Oncology Group performance status score, Ki-67 index, or response to chemotherapy between groups. The high neutrophil-lymphocyte ratio group showed significantly worse overall survival (high vs. low, median 11.1 vs. 21.0 months, log-rank p=0.004) and shorter median progression-free survival, but the latter was not statistically significant. The high platelet-lymphocyte ratio group also showed significantly worse progression-free survival and overall survival than the low platelet-lymphocyte ratio group (high vs. low:median 5.6 vs. 9.8 months, log-rank p=0.047 and median 13.8 vs. 21.0 months, log-rank p=0.013, respectively). In multivariable analysis, a high neutrophil-lymphocyte ratio was an independent prognostic factor for overall survival. The neutrophil-lymphocyte ratio is a potent and readily available prognostic factor for extra-pulmonary neuroendocrine carcinoma.

Geriatric functional assessment for decision-making on adjuvant chemotherapy in older colon cancer patients

Background/Aims@#Despite the increasing need for geriatric assessment prior to chemotherapy, the method for this assessment remains inadequate for older cancer patients. We aimed to propose a simple assessment method to predict the performance of adjuvant chemotherapy in older patients after colon cancer surgery. @*Methods@#This prospective study included patients over 65 years of age who were scheduled for adjuvant chemotherapy after colon cancer surgery. Before initiating chemotherapy, their functional status was assessed on the basis of activities of daily living (ADL)/instrumental activities of daily living (IADL). These parameters were analyzed with clinical characteristics and the patterns of adjuvant chemotherapy. The focus was on the completion rate of adjuvant chemotherapy. @*Results@#A total of 89 patients with a median age of 72 years were analyzed. Among them, 54 (61%) were non-impaired and 35 (39%) were impaired regarding their ADL/IADL classification. Low body mass index and impairment of ADL/IADLs were significantly associated with chemotherapy interruption. Among toxicities, fatigue and hand-foot syndrome were independent prognostic factors for chemotherapy interruption. Impairments of ADL/IADL were significantly associated with fatigue regardless of age. Based on age and ADL/IADL stratification, younger patients (≤ 72 years) and/or those who were ADL/IADL non-impaired were significantly more likely to complete adjuvant chemotherapy than older patients (> 72 years) and ADL/IADL impaired patients (p = 0.038). This was regardless of the chemotherapy regimen. @*Conclusions@#Functional assessment using ADL/IADL is a convenient method to predict chemotherapy toxicity and performance. These results suggested that routine screening for ADL/IADLs could guide appropriate patient selection for the completion of adjuvant chemotherapy and predict expected outcomes.

Cisplatin-induced Atrioventricular Block Requiring a Pacemaker: Two Case Reports and a Literature Review

Chemotherapeutic drugs can cause cardiac toxicities such as cardiomyopathy, arrhythmia, and cardiovascular disease. The well-known side effects of cisplatin are nephrotoxicity, nausea, vomiting, and electrolyte imbalance. Cardiotoxicity induced by cisplatin is rare, and its pathophysiology is unknown. Here, we present two cases of complete and high-degree atrioventricular (AV) block that occurred during cisplatin-based chemotherapy and required pacemaker placement. A 64-year-old woman and a 75-year-old man, who had no underlying heart disease, developed dyspnea without chest pain and bradycardia during cisplatin-based chemotherapy. However, there were no significant differences in their serum electrolyte levels, cardiac enzyme levels, and echocardiography results before and after drug administration. The ECGs were confirmed with complete AV block and highdegree AV block, which requiring pacemaker placement. We assume that cisplatin directly caused the complete, high-degree AV block, which required a pacemaker placement in our cases. In such cases, a cumulative dose of cisplatin over 240 mg/m 2 is a risk factor for early symptoms of AV block. If patients complain of dyspnea without chest pain during cisplatin-based chemotherapy, arrhythmic complications should be considered. This information may be helpful for clinicians treating patients with cisplatin chemotherapy.

Immunogenicity and Optimal Timing of 13-Valent Pneumococcal Conjugate Vaccination during Adjuvant Chemotherapy in Gastric and Colorectal Cancer: A Randomized Controlled Trial / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Pneumococcal vaccination (13-valent pneumococcal conjugate vaccine [PCV13]) is recommended to cancer patients undergoing systemic chemotherapy. However, the optimal time interval between vaccine administration and initiation of chemotherapy has been little studied in adult patients with solid malignancies. @*Materials and Methods@#We conducted a prospective randomized controlled trial to evaluate whether administering PCV13 on the first day of chemotherapy is non-inferior to vaccinating 2 weeks prior to chemotherapy initiation. Patients were randomly assigned to two study arms, and serum samples were collected at baseline and 4 weeks after vaccination to analyze the serologic response against Streptococcus pneumoniae using a multiplexed opsonophagocytic killingassay. @*Results@#Of the 92 patients who underwent randomization, 43 patients in arm A (vaccination 2 weeks before chemotherapy) and 44 patients in arm B (vaccination on the first day of chemotherapy) were analyzed. Immunogenicity was assessed by geometric mean and fold-increase of post-vaccination titers, seroprotection rates (percentage of patients with post-vaccination titers > 1:64), and seroconversion rates (percentage of patients with > 4-fold increase in post-vaccination titers). Serologic responses to PCV13 did not differ significantly between the two study arms according to all three types of assessments. @*Conclusion@#The overall antibody response to PCV13 is adequate in patients with gastric and colorectal cancer during adjuvant chemotherapy, and no significant difference was found when patients were vaccinated two weeks before or on the day of chemotherapy initiation.

Cisplatin-induced Atrioventricular Block Requiring a Pacemaker: Two Case Reports and a Literature Review

Chemotherapeutic drugs can cause cardiac toxicities such as cardiomyopathy, arrhythmia, and cardiovascular disease. The well-known side effects of cisplatin are nephrotoxicity, nausea, vomiting, and electrolyte imbalance. Cardiotoxicity induced by cisplatin is rare, and its pathophysiology is unknown. Here, we present two cases of complete and high-degree atrioventricular (AV) block that occurred during cisplatin-based chemotherapy and required pacemaker placement. A 64-year-old woman and a 75-year-old man, who had no underlying heart disease, developed dyspnea without chest pain and bradycardia during cisplatin-based chemotherapy. However, there were no significant differences in their serum electrolyte levels, cardiac enzyme levels, and echocardiography results before and after drug administration. The ECGs were confirmed with complete AV block and highdegree AV block, which requiring pacemaker placement. We assume that cisplatin directly caused the complete, high-degree AV block, which required a pacemaker placement in our cases. In such cases, a cumulative dose of cisplatin over 240 mg/m 2 is a risk factor for early symptoms of AV block. If patients complain of dyspnea without chest pain during cisplatin-based chemotherapy, arrhythmic complications should be considered. This information may be helpful for clinicians treating patients with cisplatin chemotherapy.

Treatment Patterns and Changes in Quality of Life during First-Line Palliative Chemotherapy in Korean Patients with Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC). MATERIALS AND METHODS: Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians. RESULTS: Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients' QOL was maintained to a similar degree, regardless of their actual response to chemotherapy. CONCLUSION: This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

Full-blown hyperparathyroidism

No abstract available.

FGFR4 Arg388 Is Correlated with Poor Survival in Resected Colon Cancer Promoting Epithelial to Mesenchymal Transition / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of FGFR4 polymorphism in patients with resected colon cancer, including the underlying mechanism. MATERIALS AND METHODS: FGFR4 polymorphism was characterized in patientswho received curative resection for stage III colon cancer. FGFR4-dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines. RESULTS: Among a total of 273 patients, the GG of FGFR4 showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele. CONCLUSION: The Arg388 allele of FGFR4 may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.

FGFR4 Arg388 Is Correlated with Poor Survival in Resected Colon Cancer Promoting Epithelial to Mesenchymal Transition / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of FGFR4 polymorphism in patients with resected colon cancer, including the underlying mechanism. MATERIALS AND METHODS: FGFR4 polymorphism was characterized in patientswho received curative resection for stage III colon cancer. FGFR4-dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines. RESULTS: Among a total of 273 patients, the GG of FGFR4 showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele. CONCLUSION: The Arg388 allele of FGFR4 may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.

The Prognostic Significance of FGFR4 Gly388 Polymorphism in Esophageal Squamous Cell Carcinoma after Concurrent Chemoradiotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to investigate the role of fibroblast growth factor receptor 4 (FGFR4) polymorphism in esophageal cancer after chemoradiotherapy (CRT). MATERIALS AND METHODS: Peripheral blood samples from 244 patients treated with CRT for esophageal squamous cell carcinoma were assessed for the role of FGFR4 genotype on treatment response and survival. RESULTS: A total of 94 patients were homozygous for the Gly388 allele, and 110 were heterozygous and 40 homozygous for the Arg388 allele. No significant association was found between the FGFR4 genotype and clinicopathological parameters. However, patients carrying the Gly388 allele showed a better overall response rate than Arg388 carriers (p=0.038). In addition, Gly388 allele patients at an earlier stage showed better overall survival (OS) and progression-free survival than Arg388 carriers. Among these, the Gly388 allele showed significantly improved OS compared to Arg388 carriers in the lymph node (LN) metastasis group (p=0.042) compared to the no LN metastasis group (p=0.125). However, similar survival outcomes were observed for advanced-stage disease regardless of genotype. CONCLUSION: This result suggests that the role of FGFR4 Gly388 in treatment outcomes differs according to esophageal cancer stage. It showed a predictive role in the response of esophageal cancer patients to CRT with a better trend for OS in Gly388 than Arg388 carriers in the early stages. In particular, LN-positive early-stage patients carrying the Gly388 allele showed improved OS compared to those carrying Arg388.

Blockade of VEGFR-1 and VEGFR-2 Enhances Paclitaxel Sensitivity in Gastric Cancer Cells

PURPOSE: Hypoxia-inducible factor-1alpha (HIF-1alpha) increases transcription of the vascular endothelial growth factor (VEGF) gene. Inhibition of VEGF abolishes VEGF mediated induction of HIF-1alpha. Recent reports suggested that HIF-1alpha also mediated the induction of class III beta-tubulin (TUBB3) in hypoxia. TUBB3 confers resistance to taxanes. Inhibition of VEGF may decrease the expression of HIF-1alpha and TUBB3. This study was undertaken to investigate the roles of vascular endothelial growth factor receptor (VEGFR) in gastric cancer cell behavior and to identify methods to overcome paclitaxel resistance in vitro. MATERIALS AND METHODS: The protein expression levels of HIF-1alpha and TUBB3 were measured in human gastric cancer cell lines (AGS) under normoxic and hypoxic conditions. The relationship between TUBB3 and paclitaxel resistance was assessed with small interfering TUBB3 RNA. AGS cells were treated with anti-VEGFR-1, anti-VEGFR-2, placental growth factor (PlGF), bevacizuamb, and paclitaxel. RESULTS: Hypoxia induced paclitaxel resistance was decreased by knockdown of TUBB3. Induction of HIF-1alpha and TUBB3 in AGS is VEGFR-1 mediated and PlGF dependent. Hypoxia-dependent upregulation of HIF-1alpha and TUBB3 was reduced in response to paclitaxel treatment. Expressions of HIF-1alpha and TUBB3 were most decreased when AGS cells were treated with a combination of paclitaxel and anti-VEGFR-1. AGS cell cytotoxicity was most increased in response to paclitaxel, anti-VEGFR-1, and anti-VEGFR-2. CONCLUSION: We suggest that blockade of VEGFR-1 and VEGFR-2 enhances paclitaxel sensitivity in TUBB3-expressing gastric cancer cells.

Clinical Prognostic Factors for Locally Advanced Esophageal Squamous Carcinoma Treated after Definitive Chemoradiotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Locally advanced esophageal cancers are generally treated with neoadjuvant chemoradiotherapy, followed by surgery in operable candidates. However, even if the patients were diagnosed as operable disease, surgery could not be performed on patients with poor condition or other comorbidity. In this case, definitive chemoradiotherapy (dCRT) is the other option for localized esophageal cancer. Therefore, the purpose of this study was to evaluate the efficacy and clinical prognostic factors for dCRT in locally advanced esophageal cancer. MATERIALS AND METHODS: We conducted a review of patients who received dCRT for locally advanced squamous esophageal cancer from 2004 to 2010, focusing on stages III and IVa. All patients received at least two cycles of platinum-based chemotherapy during radiation, and all tumor burdens were included in the radiation field. The treatment results were analyzed for patterns of failure and prognostic factors associated with survival. RESULTS: In total, 63 patients were enrolled in this study. The overall response rate was 84.1%. Relief from dysphagia after dCRT was achieved in 48 patients. The most frequent failure was local recurrence. The median overall survival (OS) was 23.0 months, and the 2-year survival rate was 45.4%. Similar results were observed for elderly study patients. Significant prognostic factors for OS were duration of smoking, high grade of dysphagia (score of 3 or 4), and shorter duration of progression-free and dysphagia-free survival. Maintenance chemotherapy after dCRT did not influence OS. However, "good risk" patients receiving maintenance chemotherapy showed better OS than those who did not receive maintenance chemotherapy (30.4 months vs. 12.0 months, p=0.002). CONCLUSION: dCRT has a major role in improving survival and palliation of dysphagia in inoperable advanced esophageal cancer, even in elderly patients. Maintenance chemotherapy after dCRT may be effective in prolonging survival in "good risk" patients.

In vitro induction of anterior gradient-2-specific cytotoxic T lymphocytes by dendritic cells transduced with recombinant adenoviruses as a potential therapy for colorectal cancer

Anterior gradient-2 (AGR2) promotes tumor growth, cell migration, and cellular transformation, and is one of the specific mRNA markers for circulating tumor cells in patients with gastrointestinal cancer. We investigated the feasibility of AGR2 as a potent antigen for tumor immunotherapy against colorectal cancer (CRC) cells using dendritic cells (DCs) transduced with a recombinant adenovirus harboring the AGR2 gene (AdAGR2). DCs transduced with a recombinant adenovirus encoding the AGR2 gene (AdAGR2/DCs) were characterized. These genetically-modified DCs expressed AGR2 mRNA as well as AGR2 protein at a multiplicity of infection of 1,000 without any significant alterations in DC viability and cytokine secretion (IL-10 and IL-12p70) compared with unmodified DCs as a control. In addition, AdAGR2 transduction did not impair DC maturation, but enhanced expression of HLA-DR, CD80, and CD86. AdAGR2/DCs augmented the number of IFN-gamma-secreting T-cells and elicited potent AGR2-specific cytotoxic T lymphocytes capable of lysing AGR2-expressing CRC cell lines. These results suggest that AGR2 act as a potentially important antigen for immunotherapy against CRC in clinical applications.

Complete biologic response to taxane based chemotherapy confirmed by 18FFDG PET/CT and surgery in a cancer of unknown primary site / 부인종양

Cancers of an unknown primary site are heterogenous with respect to their clinical and pathologic features. They are generally very aggressive, but specific favorable subsets have a better prognosis. For these favorable subsets, taxane based chemotherapy is very effective for a subset of woman with papillary serous peritoneal adenocarcinoma. A 52 year-old woman underwent [18F]-FDG PET/CT for routine health screening. On PET/CT, multiple hypermetabolic lymph nodes were detected in the paraaortic spaces, and there were no other hypermetabolic abnormalities. The patient was diagnosed with an unknown primary cancer that probably originated from the ovary or peritoneum, according to clinical studies and biopsy results. This was not a typical case of a favorable subset of cancer of an unknown primary site, but the tumor showed complete biologic response to taxane based chemotherapy as revealed by PET/CT, and necrotic tumor cells were confirmed by surgery.

A Case of Cardiogenic Shock after Chemotherapy with 5-Fluorouracil and Leucovorin in Rectal Cancer / 대한내과학회지

A 51-year-old man with rectal adenocarcinoma was admitted to hospital for neoadjuvant concurrent chemoradiotherapy. Three days after receiving 5-fluorouracil (425 mg/m2) and leucovorin (20 mg/m2) chemotherapy, the patient complained of chest pain. The patient had no history of cardiac disease. Electrocardiography showed ST segment elevation in leads II, III, and aVF, but the cardiac enzymes were normal. Transthoracic echocardiography revealed global hypokinesia with marked systolic dysfunction (ejection fraction 21.55%) and coronary angiography showed no significant stenosis. Unfortunately, he died of cardiogenic shock, despite intensive medical treatment.

Suppressive Effect of 19-nor-1alpha-25-Dihydroxyvitamin D2 on Gastric Cancer Cells and Peritoneal Metastasis Model

The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), inhibits the growth of several types of human cancer cells in vitro, but its therapeutic use is limited because it causes hypercalcemia. Among its analogs, 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol), has fewer calcemic effects and exhibits an activity equipotent to that of calcitriol. We assessed the antitumor and anti-inflammatory effects of paricalcitol in gastric cancer cells, and evaluated the potential role of vitamin D in the treatment of peritoneal metastatic gastric cancer. In this study, treatment with paricalcitol inhibited gastric cancer cell growth and induced cell cycle arrest. Paricalcitol also induced apoptosis and showed anti-inflammatory activity. Moreover, the growth of intraperitoneal metastases in vivo was reduced in mice treated with paricalcitol. 18F-FDG uptake was significantly lower in the paricalcitol group compared to control group (SUV; control group 13.2 +/- 5.3 vs paricalcitol group 4.5 +/- 3.0). Intraperitoneal tumor volume was significantly lower in paricalcitol treated mice (control group 353.2 +/- 22.9 mm3 vs paricalcitol group 252.0 +/- 8.4 mm3). These results suggest that the vitamin D analog, paricalcitol, has anticancer activity on gastric cancer cells by regulation of the cell cycle, apoptosis, and inflammation.

Intravenous KITENIN shRNA Injection Suppresses Hepatic Metastasis and Recurrence of Colon Cancer in an Orthotopic Mouse Model

KITENIN (KAI1 C-terminal interacting tetraspanin) promotes invasion and metastasis in mouse colon cancer models. In the present study, we evaluated the effects of KITENIN knockdown by intravenous administration of short hairpin RNAs (shRNAs) in an orthotopic mouse colon cancer model, simulating a primary or adjuvant treatment setting. We established orthotopic models for colon cancer using BALB/c mice and firefly luciferase-expressing CT-26 (CT26/Fluc) cells. Tumor progression and response to therapy were monitored by bioluminescence imaging (BLI). In the primary therapy model, treatment with KITENIN shRNA substantially delayed tumor growth (P = 0.028) and reduced the incidence of hepatic metastasis (P = 0.046). In the adjuvant therapy model, KITENIN shRNA significantly reduced the extent of tumor recurrence (P = 0.044). Mice treated with KITENIN shRNA showed a better survival tendency than the control mice (P = 0.074). Our results suggest that shRNA targeting KITENIN has the potential to be an effective tool for the treatment of colon cancer in both adjuvant and metastatic setting.

Survival Prediction in Terminally Ill Cancer Patients: Laboratory Variables and Prospective Validation of The Palliative Prognostic Index / 대한내과학회지

BACKGROUND/AIMS: The palliative prognostic index (PPI) was designed to predict life expectancy based on clinical symptoms. In this study, a PPI was constructed and used with other biological parameters to predict 3-week survival in patients with advanced cancer. METHODS: The study included 222 patients. The PPI was constructed with five variables (performance status, oral intake, edema, dyspnea at rest, and delirium). PPI scores were grouped as follows: 4 (group 1); > 4 and 6 (group 3). At admission, seven biological variables (white blood cell count, lymphocyte, C-reactive protein [CRP], bilirubin, albumin, creatinine, and lactate dehydrogenase) were measured. RESULTS: The overall survival duration was 50 days in group 1, 22 days in group 2, and 14 days in groups 3. Using the PPI, a survival of 6 and increases in serum bilirubin and CRP levels. Furthermore, the 3-week survival rate in patients with hepatopancreatobiliary cancer was more accurately predicted using a combination of the PPI, CRP, and serum bilirubin levels. CONCLUSIONS: Although a PPI has limitations, it can be quickly applied to determine survival duration in patients admitted to hospice and accurately predicts 3-week survival. Furthermore, bilirubin and CRP are useful factors for predicting 3-week survival in patients with gastrointestinal cancer, including hepatopancreatobiliary cancer.

Efficacy and Tolerability of OROS Hydromorphone in Strong Opioid-Naive Patients: An Open Label, Prospective Study / 대한내과학회지

BACKGROUND/AIMS: OROS hydromorphone is a synthetic opioid agent. While clinical studies have tested its effectiveness at controlling cancer-associated pain in patients who have received other strong opioids, no clinical studies have tested its effectiveness at managing cancer pain in strong opioid-naive patients. We performed the present study to evaluate the efficacy and tolerability of OROS hydromorphone in strong opioid-naive cancer patients. METHODS: We administered OROS hydromorphone to patients who had not received strong opioids during the previous month. The starting dose was 8 mg/day. The dose was increased every 2 days in patients who experienced more than four episodes of breakthrough pain per day (more than four times in patients being treated with short-acting opioids). We evaluated the efficacy, safety and tolerability of ORS hydromorphone. We also evaluated patient satisfaction and investigators' global assessments. RESULTS: We enrolled 23 patients to the study. The decrease in the numeric rating scale (NRS) was 59%. NRS variation had decreased markedly during the previous 24 h. All patients achieved stable pain control. The side effects were similar to those of other strong opioids. In total, 26% of patients were very satisfied with the treatment and 47% satisfied, and 74% of the investigators deemed OROS hydromorphone to be very effective or effective at controlling cancer pain. CONCLUSIONS: OROS hydromorphone is an osmotically driven, controlled-release preparation that is very effective and safe when administered once daily to strong opioid-naive cancer patients.