Sohee Kim

Open versus laparoscopic surgery for mid-rectal or low-rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): survival outcomes of an open-label, non-inferiority, randomised controlled trial

BACKGROUND Compared with open resection, laparoscopic resection of rectal cancers is associated with improved short-term outcomes, but high-level evidence showing similar long-term outcomes is scarce. We aimed to compare survival outcomes of laparoscopic surgery with open surgery for patients with mid-rectal or low-rectal cancer. METHODS The Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial was an open-label, non-inferiority, randomised controlled trial done between April 4, 2006, and Aug 26, 2009, at three centres in Korea. Patients (aged 18-80 years) with cT3N0-2M0 mid-rectal or low-rectal cancer who had received preoperative chemoradiotherapy were randomly assigned (1:1) to receive either open or laparoscopic surgery. Randomisation was stratified by sex and preoperative chemotherapy regimen. Investigators were masked to the randomisation sequence; patients and clinicians were not masked to the treatment assignments. The primary endpoint was 3 year disease-free survival, with a non-inferiority margin of 15%. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00470951. FINDINGS We randomly assigned 340 patients to receive either open surgery (n=170) or laparoscopic surgery (n=170). 3 year disease-free survival was 72·5% (95% CI 65·0-78·6) for the open surgery group and 79·2% (72·3-84·6) for the laparoscopic surgery group, with a difference that was lower than the prespecified non-inferiority margin (-6·7%, 95% CI -15·8 to 2·4; p<0·0001). 25 (15%) patients died in the open group and 20 (12%) died in the laparoscopic group. No deaths were treatment related. INTERPRETATION Our results show that laparoscopic resection for locally advanced rectal cancer after preoperative chemoradiotherapy provides similar outcomes for disease-free survival as open resection, thus justifying its use. FUNDING National Cancer Center, South Korea.

Analysis of treatment outcomes of intraventricular chemotherapy in 105 patients for leptomeningeal carcinomatosis from non-small-cell lung cancer.

Introduction: Reports on the treatment result of leptomeningeal carcinomatosis (LMC) from a single primary cancer are rare and mixed treatment modalities make it even more difficult to interpret the results properly. Here, we report clinical outcomes of an intraventricular chemotherapy for LMC from non–small-cell lung cancer. Methods: Medical records of 105 patients were retrieved and retrospectively analyzed to find the prognostic factors of patients’ survival and symptom responses, including intracranial pressure (ICP) control. Results: There were 44 men and 61 women, with a median age of 56 years (range, 31–75 years). Patients received a median five rounds of intraventricular chemotherapy (range, 1–49 rounds). The most common presenting symptom was headache (77%) with nausea or vomiting, which showed the highest response rate of 42%. Altered mentality (36%), cranial neuropathy (15%), and cauda equina symptoms (12%) revealed 10% or less of symptom response. Only eight patients (7.6%) showed negative conversion of cerebrospinal fluid cytology. Median overall survival was 3.0 months (range, 0.5–21.5 months). Age (≥60 years), poor Karnofsky performance score (< 70), and uncontrolled ICP were found to be unfavorable prognostic factors for patient survival. A greater amount of intraventricular chemotherapy, which was evaluated as time-dependent covariate, and concurrent systemic chemotherapy significantly improved overall survival in the multivariable analysis. Conclusion: Intraventricular chemotherapy for patients with LMC from non–small-cell lung cancer could palliate associated symptoms and prolong patients’ survival. Careful selection of patients for intraventricular chemotherapy is recommended with aggressive ICP control and concurrent systemic chemotherapy.

Learning curve analysis of laparoscopic radical hysterectomy and lymph node dissection in early cervical cancer.

OBJECTIVE We aimed to evaluate the learning curve for laparoscopic radical hysterectomy and lymph node dissection (LRHND) in uterine cervical cancer and to compare the surgicopathologic outcomes of cases treated in the first half of the curve with those treated in the second half of the curve. STUDY DESIGN The medical records of LRHND patients between August 2004 and April 2011 were reviewed retrospectively. The patients were divided into two groups of the first 35 cases (phase I) and the second 35 cases (phase II). All operations were performed by the same surgeon. Demographic data and surgicopathologic parameters were analyzed. The learning curve was evaluated using the cumulative summation (CUSUM) technique. RESULTS No difference was found in demographics and histologic type between the two groups. The mean operating time (307.7±85.8 min) of phase I was significantly longer than phase II (266.3±58.8 min) (P=0.021). The number of complications in phase I patients (N=9) was significantly higher than that (N=1) of phase II patients (P=0.013). There were no significant differences between the two groups with respect to lymph node yield and likelihood of identifying positive lymph nodes, resection margins, parametrium, stromal invasion, and lymphovascular space invasion. Disease-free survival did not differ between the two groups (P=0.142). The learning period for LRHND to reach a turning point was calculated to be 40 cases. CONCLUSIONS An extended learning period can be required for LRHND, during which survival and pathologic outcome of LRHND may not be adversely affected.

Nucleotide sequence analysis of the coat protein genes of two Korean isolates of sweet potato feathery mottle potyvirus

SummaryThe coat protein (CP) genes of the genomic RNA of two Korean isolates of sweet potato feathery mottle potyvirus (SPFMV), SPFMV-K1 and SPFMV-K2, were cloned and their complete nucleotide sequences were determined. Sequence comparisons of the two Korean isolates showed 97.8% amino acid identity in the CP cistron, and 79.9% to 99.0% identity with those of 6 other known SPFMV strains. Of 74 amino acid changes totally among the SPFMV strains, 39 changes were located at the N-terminal region. Pairwise amino acid sequence comparison revealed sequence similarities of 48.6 to 70.2% between SPFMV and 20 other potyviruses, indicating SPFMV to be a quite distinct species. Multiple alignment of the CP cistrons from other potyviruses showed that most of the conserved amino acid residues of the genus Potyvirus are well preserved in the corresponding locations.

Prediction Model for Gastric Cancer Incidence in Korean Population.

Background Predicting high risk groups for gastric cancer and motivating these groups to receive regular checkups is required for the early detection of gastric cancer. The aim of this study is was to develop a prediction model for gastric cancer incidence based on a large population-based cohort in Korea. Method Based on the National Health Insurance Corporation data, we analyzed 10 major risk factors for gastric cancer. The Cox proportional hazards model was used to develop gender specific prediction models for gastric cancer development, and the performance of the developed model in terms of discrimination and calibration was also validated using an independent cohort. Discrimination ability was evaluated using Harrell’s C-statistics, and the calibration was evaluated using a calibration plot and slope. Results During a median of 11.4 years of follow-up, 19,465 (1.4%) and 5,579 (0.7%) newly developed gastric cancer cases were observed among 1,372,424 men and 804,077 women, respectively. The prediction models included age, BMI, family history, meal regularity, salt preference, alcohol consumption, smoking and physical activity for men, and age, BMI, family history, salt preference, alcohol consumption, and smoking for women. This prediction model showed good accuracy and predictability in both the developing and validation cohorts (C-statistics: 0.764 for men, 0.706 for women). Conclusions In this study, a prediction model for gastric cancer incidence was developed that displayed a good performance.

Incidence and risk factors for leptomeningeal carcinomatosis in breast cancer patients with parenchymal brain metastases.

Objective The objective of study is to evaluate the incidence of leptomeningeal carcinomatosis (LMC) in breast cancer patients with parenchymal brain metastases (PBM) and clinical risk factors for the development of LMC. Methods We retrospectively analyzed 27 patients who had undergone surgical resection (SR) and 156 patients with whole brain radiation therapy (WBRT) as an initial treatment for their PBM from breast cancer in our institution and compared the difference of incidence of LMC according to clinical factors. The diagnosis of LMC was made by cerebrospinal fluid cytology and/or magnetic resonance imaging. Results A total of 27 patients (14%) in the study population developed LMC at a median of 6.0 months (range, 1.0-50). Ten of 27 patients (37%) developed LMC after SR, whereas 17 of 156 (11%) patients who received WBRT were diagnosed with LMC after the index procedure. The incidence of LMC was significantly higher in the SR group compared with the WBRT group and the hazard ratio was 2.95 (95% confidence interval; 1.33-6.54, p<0.01). Three additional factors were identified in the multivariable analysis : the younger age group (<40 years old), the progressing systemic disease showed significantly increased incidence of LMC, whereas the adjuvant chemotherapy reduce the incidence. Conclusion There is an increased risk of LMC after SR for PBM from breast cancer compared with WBRT. The young age (<40) and systemic burden of cancer in terms of progressing systemic disease without adjuvant chemotherapy could be additional risk factors for the development of LMC.

Pretreatment Prognostic Nutritional Index Is an Independent Predictor of Survival in Patients With Metastatic Renal Cell Carcinoma Treated With Targeted Therapy

&NA; In the present study we examined the effect of the Prognostic Nutritional Index (PNI) on the overall survival (OS) of patients with metastatic renal cell carcinoma. Cox proportional hazards models were used to assess the correlation between pretreatment PNI and OS. The PNI was an independent prognostic factor for OS. The PNI increases the prognostic accuracy of established factors and could be a valuable tool for tailoring surveillance. Background: In the present study we examined the effect of the Prognostic Nutritional Index (PNI) on the overall survival (OS) and progression‐free survival (PFS) of patients with metastatic renal cell carcinoma (RCC) treated with targeted therapy. Patients and Methods: The study included 125 patients with metastatic RCC. Pretreatment PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). Univariable and multivariable Cox proportional hazards models were used to assess the correlation between pretreatment PNI and OS and PFS. Harrell concordance index was used to measure discrimination. Results: The median follow‐up time was 45.3 months (interquartile range, 23.7‐77.3 months). Decreased PNI was significantly associated with older female patients, poor Eastern Cooperative Oncology Group performance status, types of initial drug, and increased Memorial Sloan Kettering Cancer Center (MSKCC) and Heng risk score (P < .05). An increase in the PNI of 1 unit was associated with a 10% decrease in the risk of death from RCC (hazard ratio, 0.90; P < .001). In the multivariable analysis, the PNI was an independent prognostic factor for OS (P < .001). In intermediate‐risk patients according to MSKCC and Heng risk criteria, OS was better in the high PNI group than in the low PNI group (P = .0136 and P = .0009, respectively). Conclusion: PNI is an independent prognostic factor in patients with metastatic RCC treated with targeted therapy. When used as an adjunct, it increases the prognostic accuracy of established factors and could be a valuable tool for tailoring surveillance, patient counseling, and clinical trial design.

Laparoscopic surgery for patients with colorectal cancer produces better short‐term outcomes with similar survival outcomes in elderly patients compared to open surgery

The number of operations on elderly colorectal cancer (CRC) patients has increased with the aging of the population. The aim of this study was to evaluate surgical outcomes in elderly patients who underwent laparoscopic or open surgery for CRC. We analyzed the data of 280 patients aged 80 or over who underwent surgery for CRC between January 2001 and December 2010. Seventy‐one pairs were selected after propensity score matching for laparoscopic or open surgery. Operative time, return to normal bowel function, length of hospital stay, postoperative complications, overall survival (OS), recurrence‐free survival (RFS), and prognostic factors affecting survival were investigated. In matched cohorts, operative time in the laparoscopic group was longer than in the open group (P < 0.001). In the laparoscopic group, time to flatus passage (P < 0.001) and length of postoperative hospital stay (P = 0.037) were shorter than in the open group. The rate of operation‐related morbidity was higher in the open group (P = 0.019). There was no difference in OS and RFS between two groups. This study suggests that laparoscopic surgery for CRC in elderly patients may be safe and feasible, with better short‐term outcomes. OS and RFS, however, were not different in both groups.

A nomogram to predict brain metastasis as the first relapse in curatively resected non-small cell lung cancer patients

OBJECTIVES Development of brain metastasis results in a significant reduction in overall survival. However, there is no an effective tool to predict brain metastasis in non-small cell lung cancer (NSCLC) patients. We conducted this study to develop a feasible nomogram that can predict metastasis to the brain as the first relapse site in patients with curatively resected NSCLC. MATERIAL AND METHODS A retrospective review of NSCLC patients who had received curative surgery at National Cancer Center (Goyang, South Korea) between 2001 and 2008 was performed. We chose metastasis to the brain as the first relapse site after curative surgery as the primary endpoint of the study. A nomogram was modeled using logistic regression. RESULTS Among 1218 patients, brain metastasis as the first relapse developed in 87 patients (7.14%) during the median follow-up of 43.6 months. Occurrence rates of brain metastasis were higher in patients with adenocarcinoma or those with a high pT and pN stage. Younger age appeared to be associated with brain metastasis, but this result was not statistically significant. The final prediction model included histology, smoking status, pT stage, and the interaction between adenocarcinoma and pN stage. The model showed fairly good discriminatory ability with a C-statistic of 69.3% and 69.8% for predicting brain metastasis within 2 years and 5 years, respectively. Internal validation using 2000 bootstrap samples resulted in C-statistics of 67.0% and 67.4% which still indicated good discriminatory performances. CONCLUSION The nomogram presented here provides the individual risk estimate of developing metastasis to the brain as the first relapse site in patients with NSCLC who have undergone curative surgery. Surveillance programs or preventive treatment strategies for brain metastasis could be established based on this nomogram.

Primary Tumor Characteristics Are Important Prognostic Factors for Sorafenib-Treated Patients with Metastatic Renal Cell Carcinoma: A Retrospective Multicenter Study

We aimed to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with sorafenib. We investigated 177 patients, including 116 who received sorafenib as first-line therapy, using the Cox regression model. During a median follow-up period of 19.2 months, the PFS and OS were 6.4 and 32.6 months among all patients and 7.4 months and undetermined for first-line sorafenib-treated patients, respectively. Clinical T3-4 stage (hazard ratio [HR] 2.56) and a primary tumor size >7 cm (HR 0.34) were significant prognostic factors for PFS among all patients, as were tumor size >7 cm (HR 0.12), collecting system invasion (HR 5.67), and tumor necrosis (HR 4.11) for OS (p < 0.05). In first-line sorafenib-treated patients, ≥4 metastatic lesions (HR 28.57), clinical T3-4 stage (HR 4.34), collecting system invasion (univariate analysis HR 2.11; multivariate analysis HR 0.07), lymphovascular invasion (HR 13.35), and tumor necrosis (HR 6.69) were significant prognosticators of PFS, as were bone metastasis (HR 5.49) and clinical T3-4 stages (HR 4.1) for OS (p < 0.05). Our study thus identified a number of primary tumor-related characteristics as important prognostic factors in sorafenib-treated mRCC patients.