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Background: Sentinel node navigation surgery reduces the extent of gastric and lymph node dissection, and may improve quality of life. The benefit and harm of laparoscopic sentinel node navigation surgery (LSNNS) for early gastric cancer is unknown. The SENORITA (SEntinel Node ORIented Tailored Approach) trial investigated the pathological and surgical outcomes of LSNNS compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection., Methods: The SENORITA trial was an investigator-initiated, open-label, parallel-assigned, non-inferiority, multicentre RCT conducted in Korea. The primary endpoint was 3-year disease-free survival. The secondary endpoints, morbidity and mortality within 30 days of surgery, are reported in the present study., Results: A total of 580 patients were randomized to LSG (292) or LSNNS (288). Surgery was undertaken in 527 patients (LSG 269, LSNNS 258). LSNNS could be performed according to the protocol in 245 of 258 patients, and a sentinel node basin was detected in 237 (96·7 per cent) Stomach-preserving surgery was carried out in 210 of 258 patients (81·4 per cent). Postoperative complications occurred in 51 patients in the LSG group (19·0 per cent) and 40 (15·5 per cent) in the LSNNS group (P = 0·294). Complications with a Clavien-Dindo grade of III or higher occurred in 16 (5·9 per cent) and 13 (5·0 per cent) patients in the LSG and LSNNS groups respectively (P = 0·647)., Conclusion: The rate and severity of complications following LSNNS for early gastric cancer are comparable to those after LSG with lymph node dissection. Registration number: NCT01804998 ( http://www.clinicaltrials.gov)., (© 2020 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Some clinicopathological variables are known to influence the survival of patients with advanced gastric cancer. A comprehensive model based on these factors is needed for prediction of an individual's survival and appropriate patient counseling., Methods: A nomogram for predicting 1-year survival in patients with advanced gastric cancer in the palliative chemotherapy setting was developed using clinicopathological data from 949 patients with unresectable or metastatic gastric cancer who had received first-line doublet cytotoxic chemotherapy from 2001 to 2006 at the National Cancer Center, Korea (Baseline Nomogram). For 836 patients whose initial response to chemotherapy is known, another nomogram (ChemoResponse-based Nomogram) was constructed using the response to chemotherapy as additional variable. Nomogram performance in terms of discrimination and calibration ability was evaluated using the C statistic and Hosmer-Lemeshow-type χ 2 statistics., Results: Two different nomograms were developed and subjected to internal validation. The baseline nomogram incorporated 13 baseline clinicopathological variables, whereas the chemoresponse-based nomogram was composed of 11 variables including initial response to chemotherapy. Internal validation revealed good performance of the two nomograms in discrimination: C statistics = 0.656 (95% confidence interval, 0.628-0.673) for the baseline and 0.718 (95% confidence interval, 0.694-0.741) for the chemoresponse-based nomogram, which showed significantly better discrimination performance than the baseline nomogram (Z statistics = 3.74, p < 0.01)., Conclusion: This study suggests that individual 1-year survival probability of patients receiving first-line doublet cytotoxic chemotherapy for advanced gastric cancer can be reliably predicted by a nomogram-based method incorporating clinicopathological variables and initial response to chemotherapy.

Objective: This randomized, phase II, multicenter clinical trial was conducted to evaluate the feasibility of laparoscopy-assisted distal gastrectomy (LADG) with D2 lymph node dissection compared with open distal gastrectomy (ODG) for the treatment of advanced gastric cancer (AGC)., Summary of Background Data: D2 lymph node dissection has been accepted as standard treatment for AGC. Although LADG is widely performed in early gastric cancer (EGC), the feasibility of LADG in AGC has not been proven yet., Methods: Patients with cT2-T4a and cN0-2 (AJCC 7 staging system) distal gastric cancer were randomly but not blindingly assigned to LADG or ODG groups using fixed block sizes with a 1:1 allocation ratio. The primary endpoint was the noncompliance rate of the lymph node dissection, which was used to evaluate feasibility. Secondary endpoints included 3-year disease-free survival (DFS), 5-year overall survival, complications, and surgical stress response., Results: Between June 2010 and October 2011, 204 patients enrolled and underwent either LADG (n = 105) or ODG (n = 99). Of these, 196 patients (100 in LADG and 96 in ODG) were included in the intention-to-treat analysis. There were no significant differences in the overall noncompliance rate of lymph node dissection between LADG and ODG groups (47.0% and 43.2%, respectively; P = 0.648). In the subgroup analysis, the noncompliance rate in the LADG group was significantly higher than the ODG group for clinical stage III disease (52.0% vs 25.0%, P = 0.043). No difference was found in the 3-year DFS rate between the groups (LADG, 80.1%; ODG, 81.9%; P = 0.448). Differences in postoperative complication rates and surgical stress response were found to be insignificant between the 2 arms., Conclusions: LADG was feasible for AGC treatment based on the noncompliance rate of D2 lymph node dissection. Subgroups analysis data suggest that further studies are needed for stage III gastric cancer.

Objective: The phase II randomized controlled trial aimed to compare the outcomes of robot-assisted surgery with those of laparoscopic surgery in the patients with rectal cancer., Background: The feasibility of robot-assisted surgery over laparoscopic surgery for rectal cancer has not been established yet., Methods: Between February 21, 2012 and March 11, 2015, patients with rectal cancer (cT1-3NxM0) were enrolled. Patients were randomized 1:1 to either robot-assisted or laparoscopic surgery, and stratified per sex and administration of preoperative chemoradiotherapy. The primary outcome was the quality of total mesorectal excision (TME) specimen. Secondary outcomes were the circumferential and distal resection margins, the number of harvested lymph nodes, morbidity, bowel function recovery, and quality of life., Results: A total of 163 patients were randomly assigned to the robot-assisted (n = 81) and laparoscopic (n = 82) surgery groups, and 139 patients were eligible for the analyses (73 vs 66, respectively). One patient (1.2%) in the robot-assisted group was converted to open surgery. The TME quality did not differ between the robot-assisted and laparoscopic groups (80.3% vs 78.1% complete TME, respectively; 18.2% vs 21.9% nearly complete TME, respectively; P = 0.599). The resection margins, number of harvested lymph nodes, morbidity, and bowel function recovery also were not significantly different. On analyzing quality of life, scores of the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ C30) and EORTC QLQ CR38 were similar in the 2 groups, but in the EORTC QLQ CR 38 questionnaire, sexual function 12 months postoperatively was better in the robot-assisted group than in the laparoscopic group (P = 0.03)., Conclusions: Robot-assisted surgery in rectal cancer showed TME quality comparable with that of laparoscopic surgery, and it demonstrated similar postoperative morbidity, bowel function recovery, and quality of life.

Background: Greater lymph node retrieval in gastric cancer improves staging accuracy and may improve survival from increased clearance of nodal micrometastasis. This retrospective cohort study investigated if more lymph nodes removed in gastric cancer increases survival and if such effect is stage-specific due to differential risks of nodal micrometastasis and systemic disease., Methods: The prospectively collected database of curatively resected gastric cancer patients in National Cancer Center, South Korea between 2000 and 2009 was reviewed. Disease-free survival (DFS) and overall survival (OS) for all patients and for each stage according to number of lymph nodes examined (1-30, 31-45, > 45) were analyzed., Results: Of 4049 patients, 96.6% and 98.4% underwent D2 (perigastric and extragastric) lymphadenectomy and had ≥ 15 lymph nodes examined. Mean number of nodes examined was 43. Five-year OS & DFS rates were 83.3% and 80.7%. Patients with > 45 nodes examined had significantly lower DFS (p = 0.002) and OS (p = 0.007) compared to those with 1-30 and 31-45 nodes. However, proportion of patients with > 45 nodes examined increased with stage (p = 0.0005). Per stage, there was no significant difference in DFS and OS according to number of nodes examined except for stage IIIA favoring more nodes (p = 0.018 and p = 0.044, respectively). Similar trend was seen in stage IIB. Number of examined nodes positively correlated with number of pathologic nodes for all patients (r = 0.144, p < .001) but not for stage IIB and IIIA. Number of nodes examined was a significant survival predictor in stage IIIA., Conclusion: Greater lymph node harvest showed improved survival in intermediate-stage gastric cancer.

Background: This study was aimed at evaluating the food intake and nutritional status of patients who underwent gastrectomy for gastric cancer based on a large-scale gastric cancer cohort., Methods: An observational prospective cohort study for gastric cancer has been conducted since 2010. From the cohort data, we selected the data for patients who completed at least 2 days of 3-day diet diaries and who underwent subtotal gastrectomy (STG) or total gastrectomy (TG). As a control group, patients who underwent endoscopic submucosal dissection were also included. The collected diet data were converted to macro- and micronutrients using computerized software, and the nutrient intakes were compared., Results: Among 6,556 patients who participated in the cohort study from 2011 to 2016, 1,289 patients who completed at least 2 days of 3-day diet diaries were included in this study. During the postoperative 3-month period, body weight was significantly decreased in the and TG groups. However, there was no difference in nutrient intake among the 3 groups except vitamin D and calcium intake. Similar results were observed during the postoperative 12 months period., Conclusions: Postoperative body weight loss and anemia might originate from altered absorptive function and metabolic change after gastrectomy rather than decreased nutrient intake., (© 2017 S. Karger AG, Basel.)

Purpose: We examined the efficacy of poziotinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with activating EGFR mutations, who developed acquired resistance (AR) to EGFR-TKIs., Materials and Methods: This single-arm phase II study included EGFR -mutant lung adenocarcinoma with AR to erlotinib or gefitinib based on the Jackman criteria. Patients received poziotinib 16 mg orally once daily in a 28-day cycle. The primary endpoint was progression-free survival (PFS). Prestudy tumor biopsies and blood samples were obtained to determine resistance mechanisms., Results: Thirty-nine patients were treated. Tumor genotyping was determined in 37 patients; 19 EGFR T790M mutations and two PIK3CA mutations were detected in the prestudy tumors, and seven T790M mutations were detected in the plasma assay. Three (8%; 95% confidence interval [CI], 2 to 21) and 17 (44%; 95% CI, 28 to 60) patients had partial response and stable disease, respectively. The median PFS and overall survival were 2.7 months (95% CI, 1.8 to 3.7) and 15.0 months (95% CI, 9.5 to not estimable), respectively. A longer PFS was observed for patients without T790M or PIK3CA mutations in tumor or plasma compared to those with these mutations (5.5 months vs. 1.8 months, p=0.003). The most frequent grade 3 adverse events were rash (59%), mucosal inflammation (26%), and stomatitis (18%). Most patients required one (n=15) or two (n=15) dose reductions., Conclusion: Low activity of poziotinib was detected in patients with EGFR -mutant non-small cell lung cancer who developed AR to gefitinib or erlotinib, potentially because of severe-toxicityimposed dose limitation., Competing Interests: Hyesun Han and Jina Jung are fulltime employees of the Hanmi Pharmaceutical Co., Ltd., Seoul, South Korea.

Background and Aims: Excellent long-term outcome is expected for early gastric cancers (EGCs) after endoscopic submucosal dissection (ESD). However, if ESD is considered noncurative at the pathologic evaluation, additional surgery is recommended. We evaluated whether long-term outcome is compromised if additional surgery is not performed for EGCs that are out-of-indication., Methods: We retrospectively analyzed a cohort of patients with EGC not meeting ESD indications whose initial treatment was either ESD (n = 219) or surgery (n = 1799). Among them, 127 patients who underwent additional surgery after initial ESD and 67 patients who did not were matched using propensity scores to patients who initially underwent standard surgery, at a 1:1 ratio. Overall mortality and gastric cancer recurrence were compared., Results: The overall mortality and gastric cancer recurrence rates were not significantly different between the 127 patients who underwent initial ESD with additional surgery and the corresponding initial standard surgery patients. However, the overall mortality of the 67 patients who underwent ESD without additional surgery (5-year mortality, 26.0%; 95% CI, 13.5%-49.9%) was higher than that of the matched initial standard surgery patients (5-year mortality, 14.5%; 95% CI, 6.3%-33.6%; P = .04). Gastric cancer recurrence was also higher in ESD patients without additional surgery (5-year recurrence, 17.0%; 95% CI, 7.6%-37.8%) than in the matched initial surgery group (0%; P = .002). In multivariate analyses, ESD without additional surgery was a significant risk factor for overall mortality and gastric cancer recurrence., Conclusions: Additional surgery should be encouraged after non-curative ESD to obtain long-term outcomes comparable with those of initial standard surgery. (Clinical trial registration number: NCC2015-0093.)., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Five-weekly S-1 plus cisplatin (SP5) is one of the standard first-line regimens for advanced gastric cancer (GC), proven in a Japanese phase III study. To enhance the dose intensity of cisplatin, 3-weekly S-1 plus cisplatin (SP3) was developed., Patients and Methods: This multicenter, randomized, open-label, phase III study evaluated whether SP3 (S-1 80 mg/m(2)/day on days 1-14 and cisplatin 60 mg/m(2) on day 1) was noninferior/superior to SP5 (S-1 80-120 mg/day on days 1-21 and cisplatin 60 mg/m(2) on day 1 or 8) in terms of progression-free survival (PFS). Chemotherapy-naive patients with metastatic, recurrent gastric or gastroesophageal junction adenocarcinoma were randomized 1 : 1 to receive either SP3 or SP5. The trial is registered at ClinicalTrials.gov (NCT00915382)., Results: Between February 2009 and January 2012, 625 patients were randomized at 42 sites in Korea and Japan. With a median follow-up duration of 32.4 months (range, 13.3-48.6 months) in surviving patients, SP3 was not only noninferior but also superior to SP5 in terms of PFS [median 5.5 versus 4.9 months; hazard ratio (HR) = 0.82; 95% confidence interval (CI) 0.68-0.99; P = 0.0418 for superiority). There was no difference in overall survival (OS) between the groups (median 14.1 versus 13.9 months; HR = 0.99; 95% CI 0.81-1.21; P = 0.9068). In patients with measurable disease, the response rates were 60% in the SP3 arm and 50% in the SP5 arm (P = 0.065). Both regimens were generally well tolerated, but grade 3 or higher anemia (19% versus 9%) and neutropenia (39% versus 9%) were more frequent in SP3., Conclusions: SP3 is superior to SP5 in terms of PFS. However, since the improvement in PFS was only slight and there was no difference in OS, both SP3 and SP5 can be recommended as first-line treatments for patients with advanced GC., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The aim of this study was to investigate the expression of two commonly altered genes ERG and PTEN in prostate cancer (PC) and evaluate their prognostic significance. Despite conflicting published results, TMPRSS2-ERG gene fusion and PTEN loss are generally considered unfavorable markers for PC progression., Materials and Methods: Of the 762 prostatic adenocarcinoma specimens obtained from radical prostatectomy, 613 without neoadjuvant hormone therapy were included in tissue microarrays for quantitatively assessment of ERG and PTEN expression via immunohistochemistry. Statistical analysis of the association between such expression and clinicopathological parameters, including clinical prognosis, was performed with a p-value of <0.05 considered significant., Results: During a median follow-up period of 44.0 months, 132 (21.5%) patients developed biochemical recurrence (BCR). ERG overexpression and PTEN loss were observed in 145 (23.7%) and 253 (41.3%) cases, respectively. BCR-free survival was significantly better in patients with ERG overexpression (p=0.005), but unfavorable among those with PTEN loss (p=0.142). Sub-group analysis revealed that patients with PTEN loss and negative ERG expression had the worst BCR-free survival outcome (p=0.021). Furthermore, multivariate analysis identified prostate-specific antigen level (≥10 ng/mL), Gleason score (>6), pathologic T stage (≥T3), positive surgical margin, and extraprostatic capsule extension as significant risk factors for BCR (p<0.05)., Conclusions: Our results indicated that ERG overexpression was associated with favorable BCR-free survival after radical prostatectomy for PC, whereas PTEN loss was with unfavorable outcomes.

Background: Endoscopic resection (ER) of early gastric cancer (EGC) meeting the absolute indication has excellent long-term outcomes., Objective: To compare long-term outcomes of ER with those of surgery in patients with EGC who met the absolute indication for ER., Design: Retrospective cohort study., Setting: A specialized center for the treatment of cancer., Patients and Interventions: We retrospectively reviewed data from patients who underwent gastrectomy or ER for EGC between 2002 and 2007. Gastric cancers were differentiated-type adenocarcinoma without ulceration confined to the mucosal layer and 2 cm or smaller in size., Main Outcome Measurements: The primary outcome was overall survival (OS). Metachronous cancer rates and adverse event rates were compared. Kaplan-Meier plots and Cox proportional hazard regression analyses were applied for comparisons. Differences in baseline characteristics were adjusted by propensity score., Results: Among 375 patients, 261 underwent ER and 114 underwent surgery. The median follow-up duration was 76.4 months. The 5-year OS rates did not significantly differ between the ER and surgery groups (95.7% vs 93.6%, respectively; P = .725 by log-rank test). There were no gastric cancer-related deaths in either group. Metachronous gastric cancer developed more frequently in the ER group (6.1%, 16/261) than in the surgery group (0.9%, 1/114) (P = .024). However, most patients (93.8%, 15/16) in the ER group were curatively treated with repeat ER. Adverse event rates were higher in the surgery group than those in the ER group (7.9% vs 2.7%, P = .028)., Limitations: Retrospective, single-center study., Conclusions: The OS rate after ER for mucosal gastric cancer that met the absolute indication was comparable to that achieved with surgery. Although metachronous cancers were more common after ER, they were usually treatable and did not affect survival., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: The possibility of lymph node metastasis is critical to the assessment of the indication for endoscopic submucosal dissection. The differentiation of tumors is an important predicting factor for lymph node metastasis. Even though gastric cancers frequently show intratumoral heterogeneity, most studies have not considered the effects of the minor histologic components. The purpose of this study was to investigate the relationship between the presence of undifferentiated type histology (UD-min) within differentiated type tumors and lymph node metastases in early gastric cancer confined to the mucosal layer., Methods: A retrospective study of 847 patients who underwent surgery for differentiated early gastric cancer, confined to mucosa, was conducted. We analyzed the proportion of the undifferentiated type components of the tumor and their relationship with lymph node metastasis., Results: The overall rate of lymph node metastasis was 1.7 % (14/847 patients) and 215 differentiated tumors (25.4 %) have UD-min. UD-min was associated with female sex, younger age, larger tumor size, and the presence of ulcer. Lymph node metastasis rate with or without UD-min was 5.1 % (11/215) versus 0.5 % (3/632), respectively (p < 0.001). UD-min was found to be associated with lymph node metastasis in the multivariate analyses (odds ratio [OR] = 4.39, CI 1.08-17.89). When three risk factors (tumor size >2 cm, ulcer, and UD-min) were present concurrently, the rate of lymph node metastasis was high (10 %)., Conclusions: The presence of an UD-min component should be considered when assessing curative resection status of endoscopic submucosal dissection for differentiated type mucosal cancer.

Background: There is no consensus on the optimal method of primary tumor control, determined by preoperative clinical factors, during sentinel node (SN) navigation surgery for early gastric cancer (EGC). In this study, we investigated the accuracy of clinical diagnosis based on preoperative examination in patients with EGC and proposed surgical options for primary tumor control during SN navigation surgery., Methods: We analyzed 815 patients with clinical stage IA gastric cancer who underwent gastrectomy at the National Cancer Center in Korea between March 2001 and February 2011. The clinical stage was determined by endoscopy, endoscopic ultrasonography, and abdominal computed tomography., Results: The preoperative assessment of tumor depth and tumor size was accurate in 57.5 and 70.8 % of patients, respectively. Tumor depth and size were underestimated in 8 and 25.3 % of patients. The overall accuracy of histologic diagnosis by endoscopic biopsy was 87.2 %. Of those tumors diagnosed preoperatively as differentiated, 20.5 % revealed mixed histology of undifferentiated type., Conclusions: The recommendation for SN biopsy may be limited to tumors sized 3 cm or smaller to avoid positive lateral margins and to minimize the risk of skip metastases. Endoscopic resection may safely be applied to small mucosal cancers, but other surgical options should be employed for undifferentiated large mucosal lesions, given their tendency for diffuse invasion. Full-thickness resection is preferable for submucosal cancers, to secure clear vertical margins.

Background: The purpose of this study was to evaluate laparoscopy-assisted distal gastrectomy (LADG) compared to open distal gastrectomy (ODG) in the treatment of early gastric cancer with respect to survival, surgical outcomes, complications, and quality of life (QOL)., Methods: One hundred sixty-four patients with cT1N0M0 and cT1N1M0 distal gastric cancer were randomly assigned to either the LADG group or the ODG group. The primary end point was the 5-year disease-free survival (DFS) rate. Complications were classified using the accordion severity classification of postoperative complications scheme. QOL was measured using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-STO22 preoperatively and postoperatively during regular follow-up visits. This trial is registered at ClinicalTrials.gov (NCT00546468)., Results: The median (range) follow-up period was 74.3 (24.8-90.8) months. The LADG and ODG groups showed similar survival [5-year DFS rate: 98.8 % vs. 97.6 %, respectively (P = 0.514), 5-year overall survival (OS) rate: 97.6 vs. 96.3 %, respectively (P = 0.721)] or overall complication rate (29.3 vs. 42.7 %, respectively; P = 0.073). Mild complications were significantly less frequent in the LADG group than in the ODG group (23.2 vs. 41.5 %; P = 0.012). The rates of moderate, severe, and long-term complications (i.e., 31 days to 5 years after surgery) did not differ significantly between groups. No clinically meaningful differences were detected between the two groups in long-term QOL., Conclusion: LADG showed similar DFS and OS compared to ODG in treating early gastric cancer. Marginal benefits in mild complications were observed with LADG. LADG did not show advantages over ODG regarding other complications and long-term QOL.

Background: Hypofractionated radiotherapy potentially offers therapeutic gain for prostate cancer. We investigated the feasibility of hypofractionated proton therapy (PT)., Material and Methods: Eighty-two patients with biopsy-proven T1-3N0M0 prostate adenocarcinoma and no history of androgen deprivation therapy were randomly assigned to five different dose schedules: Arm 1, 60 CGE (cobalt gray equivalent = proton dose in Gy × 1.1)/20 fractions/5 weeks; Arm 2, 54 CGE/15 fractions/5 weeks; Arm 3, 47 CGE/10 fractions/5 weeks; Arm 4, 35 CGE/5 fractions/2.5 weeks; or Arm 5, 35 CGE/5 fractions/5 weeks., Results: The median follow-up duration was 42 months (11-52 months). The acute GI and GU grade ≥ 2 toxicity rates were 0 and 5%, respectively. The late GI and GU grade ≥ 2 toxicity rates were 16% and 7%, respectively. The best arm for acute GU toxicity was Arm 3, while that for late GI toxicity was Arm 2 in which none had grade ≥ 2 toxicity. The four-year American Society for Therapeutic Radiology and Oncology and Nadir + 2ng/ml BCF free survival (BCFFS) rates were 85% and 86%, respectively., Conclusions: Hypofractionated PT for patients with prostate adenocarcinoma as used in this study is feasible with an acceptable toxicity profile. As the BCFFS rates do not seem to be inferior to those produced using conventional fractionation, the application of hypofractionated PT may save patients time and money.

Background and Study Aim: Chemotherapy has been suggested to affect the outcome of pyloric stent placement. This study aimed to investigate the association between the response to chemotherapy and pyloric stent outcome., Patients and Methods: Data from 113 patients with inoperable gastric cancer who received chemotherapy after pyloric stent placement at the National Cancer Center hospital were analyzed retrospectively. Chemotherapy response was assessed using the Response Evaluation Criteria in Solid Tumors. A Cox proportional hazards model was used to evaluate the effect of chemotherapy response on the complications of stents., Results: The stent migration rate was 15.9% (18/113) and the re-stenosis rate was 30.1% (34/113). The response rates to chemotherapy were higher in the first-line group than in the salvage chemotherapy group (second-line or more) (44.8% [26/58] vs. 3.6% [2/55], respectively; P < 0.001). The proportion of patients with long time-to-progression (> 8 weeks) was also higher in the first-line than the salvage chemotherapy group (81.0% [47 /58] vs. 61.8% [34 /55], respectively; P = 0.036). Although, the response to chemotherapy was not associated with stent migration or re-stenosis, a long time-to-progression (adjusted hazard ratio [aHR] = 0.29, 95% confidence interval [CI] 0.13-0.67) and first-line chemotherapy (aHR = 0.45, 95%CI 0.22-0.93) were protective factors against re-stenosis in the multivariate analysis. In patients who received first-line chemotherapy, the median duration of patency of covered and uncovered stents was 20 weeks (95%CI 11-29) and 33 weeks (95 %CI 18-48), respectively (P = 0.317)., Conclusions: A long time-to-progression and first-line chemotherapy were significant protective factors against re-stenosis. In chemotherapy-naïve gastric cancer patients with pyloric obstruction, placement of an uncovered stent followed by chemotherapy can be considered to increase stent patency., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Multiple gastric cancers (MGCs) were found in 4-10% of gastric cancer patients. The aim of this study was to identify pretreatment risk factors associated with MGC and missed lesions., Methods: A total of 4,797 patients who underwent gastrectomies for gastric cancer from 2000 to 2010 were included in this study. Pretreatment characteristics of patients and tumors and independent risk factors related to MGC and missed lesions were evaluated., Results: Of the 4,797 patients, 322 (6.7%) were diagnosed with MGC. Logistic regression analysis showed that old age, being male, having a family history of cancer, being located in the upper third of the stomach, and early T stage tumors were risk factors for MGC. Missed lesions were detected in 95 of the 322 MGC patients, and the risk factor for missed lesions was large-sized main lesion. Fifty-four of the 322 MGC patients had early gastric cancer in the upper third of the stomach, and 37.0% of those tumors were candidates for endoscopic submucosal dissection., Conclusion: Physicians should keep pretreatment risk factors for MGC in mind to avoid missing a synchronous lesion. Meticulous examination is required after a detection of large-sized main lesion., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: S-1 or capecitabine plus oxaliplatin are considered active and tolerable in gastric cancer patients. We conducted a randomized phase II trial in gastric cancer patients to compare the activity and safety of these combinations., Methods: The patients received S-1 at 80 mg/m2 for 14 days, followed by a 7-day rest period within a 3-week schedule in the S-1/oxaliplatin (SOX) arm, and capecitabine at 2000 mg/m2 for 14 days, followed by a 7-day rest period within a 3-week schedule in the capecitabine/oxaliplatin (CAPOX) arm. Oxaliplatin 130 mg/m2 was administered every 3 weeks in both arms., Results: One hundred twenty-nine patients were randomly assigned to SOX (N=65) or CAPOX (N=64). The median time to progression and the overall survival were 6.2 and 12.4 months with SOX, respectively; and 7.2 and 13.3 months with CAPOX, respectively. The overall response rates were 40% and 44% for SOX and CAPOX, respectively. The most frequent grade 3 or 4 toxicities were thrombocytopenia (15.4%) for SOX and neutropenia (18.8%) for CAPOX. The median time to 10% deteriorations in global health scores was similar in both arms (SOX, 4.3 months, CAPOX, 4.9 months)., Conclusion: Both the SOX and CAPOX regimens were equally active and well tolerated in advanced gastric cancer patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate whether human papillomavirus (HPV) viral load measured in cervical smear and HPV type 18 are associated with radiotherapy outcomes in uterine cervical cancer. PATIENTS AND METHODS HPV DNA: was semiquantitatively measured in the cervical smears of 169 radiotherapy patients. HPV viral load was classified as low or high according to median HPV DNA titer and examined for its prognostic value. The multivariable Cox proportional hazards model was used to adjust for covariates. A relapse-predicting model was constructed to classify three risk groups for disease-free survival (DFS), which were used for internal validation., Results: Patients with lower HPV viral load showed worse DFS in univariate analysis. HPV type 18, younger patient age, stage group, nodal status, histologic grade, and histologic type were other prognostic factors for poor DFS. Among these factors, all except stage group were associated with HPV viral load. Multivariate analysis showed the strong influence of HPV viral load for poor DFS. The prognostic model developed using our outcome data performed well in predicting the risk of relapse., Conclusion: Our data suggest that HPV viral load is a strong independent prognostic factor for DFS. HPV type 18 showed a significant relationship with poor radiotherapy outcome in univariate analysis, but not in multivariate analysis.

Background: Lymph node metastasis is the most important factor to consider when deciding on the modality of resection in patients with early gastric cancer. The aim of the present study was to assess the relationship between preoperative serum angiopoietin-2, a lymphangiogenic growth factor, and lymph node metastasis in patients with early gastric cancer., Methods: A total of 62 preoperative serum samples from patients diagnosed with early gastric adenocarcinoma, and 30 serum samples from healthy donors were obtained. The serum levels of angiopoietin-2 (Ang-2) were quantified by immunoassay. Intra- and peritumor lymphatic vessel density (I-LVD and P-LVD) were counted after immunohistochemical staining. The relationship between the serum Ang-2 levels and other prognostic variables (tumor size, histological type, depth of tumor invasion, I-LDV, P-LDV, presence of lymph node involvement, and distant metastasis) were then examined by univariate and multivariate linear regression analyses., Results: The median serum levels of Ang-2 in patients were higher than those of healthy controls [311.1 ng/mL, interquartile range (IQR) 256.7-311.1 ng/mL versus 286.5 ng/mL, IQR 226.9-286.5 ng/mL; Mann-Whitney test, P = 0.016]. Eight patients had metastatic lymph nodes; the Ang-2 levels from the patients with metastatic lymph nodes were higher than from those with negative lymph nodes (297.5 ng/mL, IQR 251.1-385.8 ng/mL versus 416.0 ng/mL, IQR 337.1-485.5 ng/mL; Mann-Whitney test, P = 0.019). Elevated serum Ang-2 levels were associated with positive lymph node involvement and this finding was significant on univariate (P = 0.008) and multivariate logistic regression analysis (P = 0.011)., Conclusion: Serum Ang-2 levels were clinically useful markers for lymph node metastasis in patients with early gastric cancer.

Background: Helicobacter pylori eradication is recommended in post-gastric cancer resection, but premalignant changes may prevent the detection of H. pylori. The aim of this study was to determine appropriate biopsy site for detecting H. pylori in gastric cancer patients., Materials and Methods: Consecutive patients (194) with gastric adenocarcinoma were prospectively enrolled. Helicobacter pylori was evaluated by serology, histology and rapid urease test. Biopsy sites included antrum lesser curvature, upper body lesser curvature (UBLC) and upper body greater curvature (UBGC). Two biopsy specimens were obtained from each site for histological examination. One additional specimen was obtained from UBGC for the rapid urease test., Results: The overall infection rate of H. pylori was 84.0% (95% CI 78.9-89.2). The sensitivity of histology for detecting H. pylori at various sites was: antrum (54.9%; 95% CI 45.7-63.9), UBLC (80.3%; 95% CI 72.2-87.0) and UBGC (95.1%; 95% CI 89.6-98.2). Specificities of all three biopsy sites were more than 95%. Sensitivity and specificity of the rapid urease test performed at UBGC were 96% and 100%, respectively. Sensitivities of histology decreased in correlation with increasing severity of atrophy and intestinal metaplasia (both P < 0.001 using the chi-square test for trend). The proportions of moderate to marked atrophy/intestinal metaplasia at UBGC (12.8%/14.7%) were significantly lower than those at antrum (50.0%/57.8%, P < 0.001 respectively) or UBLC (40.0%/48.9%, P < 0.001 respectively)., Conclusions: The UBGC side is the most sensitive and specific biopsy site to detect H. pylori in gastric cancer patients due to less frequent atrophy and intestinal metaplasia than at the antrum or UBLC side.

Background and Objectives: The factors associated with successful sentinel node biopsy (SNB) are limited in gastric cancer despite a wide range of sensitivities reported. This study was performed to identify the factors associated with detection failure and SNB false-negativity in gastric cancer., Methods: SNB was performed on 156 gastric cancer patients from May 2002 to April 2007 at the Korean National Cancer Center during three consecutive prospective trials. Indications for SNB were determined preoperatively in cT1-2N0 patients. Dissected SNs and non-SNs after D2 lymphadenectomy were pathologically evaluated for metastasis. Clinical, pathological, and technical factors were analyzed for detection failure and false-negativity., Results: SNs were detected in 147 patients (94.2%) and the median number of SNs detected per patient was 3 (1-12). Twenty-five of 37 with nodal metastasis were diagnosed by SNB (sensitivity, 67.6%). Surgeon's inexperience (

Objectives: This study was designed to identify the characteristics of patients with early gastric cancers that have skip metastases., Background: The possibility of lymph node metastasis is the most important factor to consider when deciding on the resection procedure for patients with early gastric cancer., Methods: From February 2003 through July 2008, 739 patients with early gastric adenocarcinoma underwent gastric resection at the National Cancer Center, Korea, and were included in this study. Patients with skip metastases were analyzed and compared with those without skip metastases., Results: Skip metastases were found in 2.8% of patients with early gastric cancer. Tumor size and the presence of lymphatic invasion were associated with skip metastases by both univariate and multivariate analysis. All skip metastases were metastases to the extraperigastric lymph nodes that skipped across the perigastric lymph nodes. Sixteen patients (66.7%) with these metastases had metastatic lymph nodes at No. 7, 8, and 9 stations., Conclusions: Tumor size should be considered during sentinel lymph node mapping to prevent false-negative results in patients with early gastric cancer. If sentinel nodes are not found in the perigastric lymph nodes, No. 7, 8, and 9 stations should be explored for prevention of false-negative sentinel node mapping results.

Objective: The purpose of this study was to evaluate the quality of life (QOL) after laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG) in patients with early gastric cancer., Summary Background Data: LADG has been beneficial in terms of pain, recovery, and morbidity when compared with open surgery with equal oncologic outcome. There has been no clinical study on QOL., Methods: From July 2003 to November 2005, 164 patients with newly diagnosed cT1N0M0 and cT1N1M0 distal gastric cancer were randomly assigned either to LADG or ODG. All patients were asked to complete the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-STO22 questionnaires preoperatively and postoperatively on regular follow-up visits., Results: Statistically significant differences were observed with a more favorable outcome noted in the LADG group with respect to intraoperative blood loss (P < 0.001), total amount of analgesics used (P = 0.019), the size of the wound (P < 0.0001), postoperative hospital stay (P < 0.0001), and QOL parameters of global health (P < 0.0001). Most of the scales on patient functioning including physical (P < 0.0005), role (P = 0.0011), emotional (P < 0.0001), social (P < 0.0001), and symptom scales such as fatigue (P < 0.0001), pain (P < 0.0001), appetite loss (P = 0.031), sleep disturbance (P = 0.003), dysphasia (P = 0.0024), gastro-esophageal reflux (P = 0.0127), dietary restriction (P = 0.0004), anxiety (P = 0.0036), dry mouth (P = 0.0007), and body image (P < 0.0001) were also significantly better in the LADG group compared with the ODG group., Conclusions: Comparison of LADG to ODG in patients with early gastric cancer resulted in improved QOL outcomes in the patients followed for up to 3 months in the LADG group.

Background: The clinical applications of sentinel node (SN) biopsies in early gastric cancer are limited because of low sensitivity. Sentinel basin (SB) dissection has been suggested as alternative to SN biopsy to improve sensitivity. The aim of this study was to examine the feasibility of laparoscopic SB dissection., Methods: Twenty-one gastric adenocarcinoma patients of cT1N0 were enrolled. Technetium 99 m human serum albumin and indocyanine green were injected into the submucosal layer around tumor using an intraoperative endoscope. Green-stained or radioactive lymphatic basins were detected and defined as SBs. After laparoscopic SB dissection, laparoscopy-assisted gastrectomy with D2 lymphadenectomy was performed. Dissected SB nodes and non-SB nodes were evaluated for metastasis pathologically., Results: The SB detection rate was 95.2%. Numbers of SBs were one in 6, two in 10, and three in 4 patients. The mean number of SB nodes was 7.0. Two patients with lymph node metastasis were diagnosed by SB dissection. Mean time of laparoscopic SB dissection procedure was 15.2 min., Conclusions: Above findings suggest that laparoscopic SB dissection is technically feasible, and it might have better sensitivity than SN biopsy. However, the validity of this procedure should be evaluated in a larger series before being clinically applied., ((c) 2008 Wiley-Liss, Inc.)

Objectives: This study was conducted to determine whether laparoscopy-assisted distal gastrectomy (LADG) with complete D2 lymph node dissection for gastric cancer is a safe and effective surgical option., Methods: During an 8-month period, 64 patients, who were diagnosed preoperatively as having T1-2, N0-1 or M0 gastric cancer, were prospectively enrolled to undergo LADG with D2 lymph node dissection; two surgeons with experience of over 50 cases of laparoscopic gastrectomy performed the procedures. The compliance rate, defined as cases with no more than one missing lymph node station according to the Japanese Research Society of Gastric Cancer (JRSGC) lymph node grouping, for the open gastrectomy with D2 lymph node dissection was 66.0% in a pilot study and was used for calculations of sample size. Compliance rate and other surgical outcomes, including the number of retrieved lymph nodes from each lymph node station, morbidities, mortalities and conversion rate, were analyzed., Results: The compliance rate was 67.2% and was similar to that of open distal gastrectomy reported in the pilot study. The mean number of retrieved lymph nodes was 50.1 (range 20-100). The most frequently missed lymph node station was no. 5 (31.2%) followed by no. 3 (25.0%). There were no missed lymph nodes at stations no. 6 and 9. The complication rate was 3.1% (2/66); there were two conversions (3.0%) and no mortalities., Conclusions: The current study suggests that LADG with D2 lymph node dissection is oncologically feasible, and phase-III clinical trials will be needed.

Background: There is a prevailing belief that both obesity and abdominal shape influence abdominal accessibility, and thus affect short-term surgical outcomes of gastric cancer surgery., Methods: We measured the thickness of subcutaneous fat (SCF), abdominal anterior-posterior diameter (APD), transverse diameter (TD), and intra-abdominal fat volume (IFV) at the umbilicus level by using the abdominal CT scans of 291 gastric cancer patients who had undergone subtotal gastrectomy and D2 lymph node dissection. Clinicopathological factors including body mass index (BMI), APD, TD, IFV, and SCF and surgical outcomes, i.e., dissected lymph node number, morbidity, and mortality were analyzed., Results: SCF thickness, APD, TD, IFV, and BMI mean values were 20.0 mm (range 2.0-64.0), 188.4 mm (range 128.0-332.0), 301.4 mm (range 160.0-651.0), 198.3 mm(2) (range 123.4-312.1), and 23.9 kg/m(2) (range 16.6-34.6), respectively. In male patients, APD was found to correlate with the number of retrieved lymph nodes (P = 0.045). Whereas in female patients, this was not the case (P = 0.093). Twenty-one patients experienced postoperative complications but no postoperative mortality occurred. Female patients who experienced postoperative complications had higher APD (32.9 +/- 10.0 mm versus 26.1 +/- 7.9 mm, P = 0.044) and BMI (27.3 +/- 4.1 kg/m(2) versus 24.3 +/- 3.5 kg/m(2), P = 0.049) values than those who did not., Conclusions: We conclude that obesity and abdominal shape of gastric cancer patients both influence the short-term surgical outcomes of subtotal gastrectomy with D2 lymph node dissection.

Purpose: This prospective trial was conducted to evaluate the role of gefitinib in never-smokers with advanced or metastatic adenocarcinoma of the lung., Patients and Methods: The main inclusion criteria were stage IIIB/IV adenocarcinoma of the lung and status as a lifetime never-smoker. Patients received a 250-mg single oral daily dose of gefitinib until disease progression, unacceptable toxicity, or patient's refusal. Tumor response was assessed after every two 4-week cycles according to the World Health Organization response criteria. Additional analyses were performed to identify predictors of response and survival., Results: Between August 2003 and March 2005, 72 Korean patients were enrolled; 55 chemotherapy naive, 17 previously treated; 6 male, 66 female; and ECOG PS 0/1/2, 24/42/4. All patients were assessed for response, toxicity, quality of life, and survival. Overall objective tumor response rate was 55.6% (95% confidence interval [CI], 43.4-67.3%). With a median follow-up of 23 months, the median survival time was 19.7 months (95% CI, 18.5-21.0 months) with a 1-year survival rate of 76.3%. The median duration of response was 6.8 months (95% CI, 4.7-9.0 months). Therapy-related improvement of symptoms and quality of life was observed within 2 to 4 weeks after the commencement of therapy in the responders. In a multivariate Cox proportional hazard model, good performance status and no prior history of chemotherapy were the two significant predictors of better survival (p = 0.005 and 0.042)., Conclusion: Gefitinib showed very promising antitumor activity and survival outcome in Korean never-smokers with adenocarcinoma of the lung. It seems to be a good alternative to standard chemotherapy as a first-line therapy for this subgroup.