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Objectives: This study investigated the effectiveness of acupuncture for improving polycythemia-vera-related symptoms and quality of life.Methods: A 56-year-old woman diagnosed with polycythemia vera received acupuncture treatment between February 19, 2021, and August 26, 2021. We observed the changes in subjective symptoms and conducted myeloproliferative neoplasm symptom assessment form total symptom score (MPN-SAF TSS) questionnaire.Results: After 13 acupuncture treatment sessions over six months, symptoms of polycythemia vera, such as fatigue, bone pain, itching, and headache, improved.Conclusion: This study suggests that acupuncture may be a helpful treatment strategy for polycythemia vera patients suffering from significant symptom burdens and reduced quality of life.

PURPOSE Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748 ) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

Background Arteriovenous malformation (AVM) which is a high-blood-flow lesion with connections between arteries and veins without an intervening capillary bed, is difficult to manage. The ear is the second most common site of extracranial AVM. However, studies regarding the management of this condition remain lacking. The purpose of this study was to share managing experiences in our center and to investigate the treatment effect through a retrospective analysis of cases. Methods Among 265 patients with AVM treated in our vascular anomalies center between January 2008 and January 2021, 10 patients with auricular AVM were included in the study to investigate the lesion distribution, clinical stage, and treatment methods by performing a retrospective evaluation. Results Among 10 patients, five patients had AVMs distributed in the upper half of the ear, one patient in the lower half of the ear, and four patients in whole ear, respectively. Seven patients had Schobinger stage II, and three had stage III. One patient received surgical treatment only, four patients received sclerotherapy only, and five patients received both surgical treatment and sclerotherapy. The posttreatment status was checked as controlled in two patients, improved in seven patients, persistent in one patient. There were no worsening patients. Conclusion Auricular AVM is a disease that is difficult to manage by one specific department, thus requiring a collaborative management effort from multidisciplinary team.

Background/Aims Lymphocytes are an important component of the cell-mediated immune system. As lymphopenia is reportedly associated with poor prognoses in patients with various cancers, we investigated this notion in patients who underwent curative gastrectomy. Methods We retrospectively analyzed the association between absolute lymphocyte count (ALC) and prognosis in patients with stage I–III gastric cancer who underwent curative surgical resection. Ever lymphopenic patients were defined as those with ALCs < 1,000/μL at any time post-diagnosis except within 30 days post-surgery. Adjusted multivariable regression models were used to evaluate the associations between lymphopenia and overall mortality, gastric cancer-specific mortality, and disease-free survival. Results We investigated 1,222 patients diagnosed between January 2011 and December 2015. Fifty-six patients (4.6%) were lymphopenic at diagnosis and nearly one-quarter (24.8%) were ever lymphopenic with a mean minimum ALC of 640/μL. Older age (odds ratio [OR], 1.02) and higher stage (stage III vs. I; OR, 3.01) were positively associated with ever lymphopenia. On multivariable analysis, ever lymphopenia predicted higher overall mortality (hazard ratio [HR], 1.83; p = 0.008), higher gastric cancer-specific mortality (HR, 1.58; p = 0.048), and shorter disease-free survival (HR, 1.83; p = 0.006). The 5-year gastric cancer-specific mortality rates for ever- and never lymphopenic patients were 10.9% and 3.7%, respectively; their 5-year cumulative recurrence rates were 15.1% and 4.6%, respectively. Conclusions This study demonstrate that ever lymphopenia is independent prognostic factor for overall mortality and recurrence in patients with potentially curable gastric cancer; hence, ALCs may be a biomarker for predicting the prognoses of patients with stage I–III gastric cancer who had curative gastrectomy.

Objective Until recently, the transfemoral approach (TFA) was used as the primary method of arterial approach in acute ischemic stroke (AIS). However, TFA resulted in longer reperfusion times and worse outcomes in the mechanical thrombectomy (MT) of patients with complex aortic arches and significant carotid tortuosity. We found that the transradial approach (TRA) is a more favorable alternative approach for MT in such cases. Methods We performed a retrospective review of our institutional database to identify 202 patients who underwent MT for AIS between February 2015 and December 2019. Patient characteristics, cause of TFA failure, procedure time, intra-procedural complications, and outcomes were recorded. Results Eleven (5.4%) of 202 patients, who underwent MT for AIS, crossed over to TRA for recanalization, and eight (72%) of 11 achieved successful recanalization (≥modified Treatment in Cerebral Infarction 2b). The mean age (mean±standard deviation [median]) was 82.3±6.6 (76) years, and five of the 11 patients were male. The last seen normal to puncture time was 467.9±264.72 (264) minutes; baseline National Institutes of Health Stroke Scale score was 28.9±14.5 (16). Six (55%) of the 11 patients had right vertebrobasilar occlusions, and the remaining five (45%) had anterior circulation occlusive disease. The time from groin puncture to final recanalization time (overall procedural time) was 78.0±20.1 (62) minutes. The mean crossover time from TFA to TRA was 45.2±10.5 (41) minutes. The mean time from radial puncture to final recanalization was 33.8±10.5 (28) minutes. Distal thrombus migration events in previously unaffected territories occurred in 3/8 patients (37%). At 90 days, three patients (28%) had a favorable clinical outcome. Conclusion Although rare, failure of TFA has been known to occur during MT for AIS. Our results demonstrate that TRA may be an alternative option for AIS intervention for select patients with subsequent timely revascularization. However, the incidence of distal thrombus migration was high, and the first puncture to reperfusion time was prolonged because of the time taken for the crossover to TRA after failure of TFA. This study provides some evidence that the TRA may be a viable alternative option to the TFA for MT of AIS.

The role of controlling nutritional status (CONUT) score in predicting cancer survival remains uncertain. This study aimed to investigate the predictive value of the CONUT score and to develop a more appropriate scoring system beyond CONUT for gastric cancer.We retrospectively reviewed 1307 patients who underwent curative gastrectomy between 2009 and 2015. The CONUT and three modified scores with modified lipid components (L-CONUT: albumin/total lymphocyte count [TLC]/low density lipoprotein, H-CONUT: albumin/TLC/high density lipoprotein, and T-CONUT: albumin/TLC/triglyceride) were calculated. The predictive value of each scoring system on long-term survival was assessed.The values of the four nutritional scores were categorized into four groups (normal, light, moderate, and severe). The CONUT (P 0.001), L-CONUT (P 0.001), H-CONUT (P 0.001), and T-CONUT (P 0.001) scores showed significant differences in overall survival in between groups. Survival analysis according to the pathological stage showed that advanced age, Eastern Cooperative Oncology Group performance status, male sex, and moderate H-CONUT score (HR, 3.970; 95% CI, 1.826-8.633; P = 0.001) were independent worse prognostic factors for overall survival in the stage I group. In the stage II group, light CONUT score (HR, 2.230; 95% CI, 1.067-4.664; P = 0.033) and moderate CONUT score (HR, 5.077; 95% CI, 1.647-15.650; P = 0.005) were significantly associated with poor prognosis. In the stage III group, no scoring system showed significant results.In advanced gastric cancer (beyond stage II), the prognostic impact of the nutritional scoring system was uncertain. However, the H-CONUT score is a promising indicator of prognosis in stage I, and the CONUT score is useful for predicting long-term survival in stage II gastric cancer.

Background Pretreatment clinical staging is essential to select therapy. However, there have been no published pretreatment gastric cancer nomograms constructed using pretreatment clinical prognostic factors, including in nonresection patients. We aimed to develop a new pretreatment gastric cancer nomogram for individualized prediction of overall survival (OS). Methods The nomogram was developed using data of 5231 Japanese gastric cancer patients, and it was created with a Cox regression model. Fifteen clinical variables, which were obtained at pretreatment, were collected and registered. Data of two independent cohorts of patients from Seoul St. Mary's Hospital (1001 patients), and the University of Verona (389 patients) formed the external validation cohorts. The model was validated internally and externally using measures of discrimination (Harrell's C‐index), calibration, and decision curve analysis. Results The developed nomogram showed good discrimination, with a C‐index of 0.855; that of the American Joint Committee on Cancer (AJCC) clinical stage was 0.819. In the external validation procedure, the C‐indexes were 0.856 (AJCC, 0.795) in the Seoul St. Mary's cohort and 0.714 (AJCC, 0.648) in the University of Verona cohort. The nomogram performed well in the calibration and decision curve analyses when applied to both the internal and external validation cohorts. A stage‐specific subset survival analysis of the three risk groups calculated using the nomogram also showed the superiority of nomogram‐prediction when compared to AJCC. Conclusion This new pretreatment model accurately predicts OS in gastric cancer and can be used for patient counseling in clinical practice and stratification in clinical trials., The newly developed gastric cancer pretreatment nomogram can accurately predict overall survival and thereby improve risk stratification and patient selection for routine clinical decision‐making and future clinical trials. This model will improve on the traditional categorical AJCC system in the future.

Objectives This study examined the effect of metformin use on the prognosis of gastric cancer patients. Materials and methods The study population comprised 2187 patients who underwent curative gastrectomy for the treatment of gastric cancer. They were divided into 3 groups: metformin (n=103), non-metformin (n=139), and non-diabetes mellitus (DM) (n=1945) according to their history of type 2 DM and metformin use. Survival, disease recurrence, and the pathologic stage were analyzed. Results Overall survival was better in the metformin group than in the non-DM group (P=0.005). Metformin use was an independent prognostic factor of overall survival, cancer recurrence, and peritoneal recurrence. An effect of metformin use was especially notable in patients with T4 or N0 disease. Conclusions Metformin improves the survival of patients with gastric cancer and type 2 DM.

Endoscopic submucosal dissection (ESD) for gastric cancer produces an artificial ulcer, and negative effects on the surgical outcomes of additional gastrectomy after ESD are anticipated. The aim of this study is to analyze the effect of ESD on subsequent laparoscopic radical gastrectomy procedures and to compare the surgical results of post-ESD patients with the control group using propensity score (PS) methods. From 2013 to 2018, 1446 patients underwent totally laparoscopic distal gastrectomy in our center. Among these patients, the clinicopathological factors and short-term surgical outcomes of 107 patients who underwent ESD before surgery (the ESD group) were evaluated. A 1:4 PS matching and inverse probability weighting method was utilized to compare the short-term surgical outcomes of the ESD group with those of a matched control group. A longer operation time was required for the patients who underwent gastrectomy earlier than 24 days after ESD than for the patients who did not. Patients whose ulcer size, due to previous ESD, exceeded 4.6 cm required longer operation times and exhibited more intraoperative blood loss than patients whose ulcer size was small. In the PS matching analysis, patients who underwent distal gastrectomy within 24 days after ESD showed more frequent postoperative morbidity than non-ESD patients. ESD after laparoscopic distal gastrectomy is largely safe in terms of short-term surgical outcomes, but a short interval between the two procedures and a large ESD scar can make subsequent operation difficult.

The purpose of the study was to examine a long-term effect of repeated Wingate anaerobic training on anaerobic power of women basket ball players according to playing position. Participants(n=12) performed 4 sets of anaerobic training with 5-minute break between sessions twice per week during a year. Due to the games, total 7 trainings per month were given. Anaerobic capacity was measured by the Wingate power test and body composition was measured by the Bioelectrical Impedance Analysis (BIA). In addition, a line tape was used to measure leg circumference (e.g., quadriceps and calf muscles). As a result, 1. Anaerobic training showed the highest effectiveness when implementing 6-7 times per month. 2. Body composition and Leg circumference was significantly different according to playing positions 3. The Wingate anaerobic training significantly improved anaerobic capacity in majority of players whereas the center position did not show significant improvement. Findings indicate that repeated anaerobic training can be helpful interval training. Also, the optimal training strategy by playing positions may be recommended.

The purpose of this study was to examine the effects of 16 weeks of combined exercise training on daily living fitness, vascular elasticity, and blood components in elderly women with type 2 diabetes mellitus (DM). Subjects in combined exercise training group (EX: n=13) participated in combined exercise training 30-40 min/session, 4 sessions/wk for 16 weeks, whereas subjects in control group (CON: n=13) were asked to maintain their normal life pattern during the same intervention period. Main results of the present study were as follows: 1) Percent body fat and fat mass decreased significantly in the EX, and there was a significant interaction between group and test in fat-free mass. 2) Arm curl, chair stand, one leg with eyes opened, functional reach, tandem test, 10m walking, and VO2max improved significantly in the EX, and there were significant interactions between group and test in chair sit-and-reach and up & go. 3) No significant changes were shown in all variables regarding vascular elasticity, and diastolic blood pressure increased significantly in the EX. 4) TG decreased significantly in the EX, and there was a significant interaction between group and test in LDL-C. 5) There were significant interactions between group and test in fasting plasma insulin and HOMA-IR. It was concluded that 16 weeks of combined exercise training would be beneficial for improvement of body composition and physical fitness as well as for preventing senile deterioration of blood lipid profiles and insulin resistance in elderly women with type 2 DM.

We report a rare case of hilar squamous cell carcinoma. A 62-year-old Korean woman complaining of nausea was referred to our hospital. Her biliary computed tomography revealed a 28 mm-sized protruding solid mass in the proximal common bile duct. The patient underwent left hemihepatectomy with S1 segmentectomy and segmental excision of the common bile duct. Microscopically, the tumor was a moderately differentiated squamous cell carcinoma of the extrahepatic bile duct, without any component of adenocarcinoma or metaplastic portion in the biliary epithelium. Immunohistochemically, the tumor was positive for cytokeratin (CK) 5/6, CK19, p40, and p63. Squamous cell carcinoma of the extrahepatic bile duct is rare. To date, only 24 cases of biliary squamous cell carcinomas have been reported. Here, we provide a clinicopathologic review of previously reported extrahepatic bile duct squamous cell carcinomas.

BackgroundScreening endoscopy is considered to be the most accurate tool for early detection of gastric cancer, but it is both invasive and costly. It is therefore essential to develop cost-effective and non-invasive diagnostic tools for gastric cancer. The aim of this study is to investigate the presence of certain volatile organic compounds (VOCs) associated with gastric cancer and to survey the usefulness of VOCs as screening tools of gastric cancer.MethodsThe present study was conducted prospectively to identify the relationship between gastric cancer and specific VOCs quantified by mass spectrometry. Exhaled breath samples from a total of 43 participants were analysed. This study was approved by the Institutional Review Board of the College of Medicine, Catholic University of Korea (KC16TISI0598), and registered to clinical research information service (KCT0004356).ResultsNine VOCs differed significantly between the control and cancer patient groups. When participants were divided into control, early gastric cancer (EGC), and advanced gastric cancer (AGC) groups, seven VOCs remained significantly different. Of these, four (propanal, aceticamide, isoprene and 1,3 propanediol) showed gradual increases as cancer advanced, from normal control to EGC to AGC. In receiver operating characteristic curves for these four VOCs, the area under the curve for gastric cancer prediction was highest (0.842) when more than two VOCs were present.ConclusionsThe present study offers potential directions for non-invasive gastric cancer screening, and may inspire advanced diagnostic technologies in the era of smart home healthcare. However, despite the high accuracy, cancer-specific VOCs from several studies on different populations, and analytic methods show inconsistency, it is necessary to establish standards for each analytical method, and to validate on each population.

Background This study aimed to evaluate the operative safety and long-term outcomes of additional curative gastrectomy (ACG) after non-curative endoscopic submucosal dissection (ESD), as compared with standard gastrectomy (SG) without ESD in patients with early gastric cancer. Materials and methods Data from 101 patients receiving ACG after non-curative ESD (Post-ESD group) and 1080 patients after SG without ESD (Surgery-only group), between 2009 and 2016, were reviewed retrospectively. Clinicopathologic characteristics, overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) were compared between groups, using propensity score matching analysis. Results After propensity score matching, a total of 101 patients in the post-ESD group and 202 patients in the surgery-only group were analyzed. The post-ESD group had shorter operation times than did the surgery-only group (p = 0.005). Estimated blood loss and the incidence of postoperative morbidity did not differ between the two groups, and no differences were observed in pathologic outcomes, including N stage (p = 0.268). In addition, 5-year OS, DSS, and RFS rates were not significantly different between groups (OS; 95.1% vs. 98.2%, p = 0.535, DSS; 98.2% vs. 98.7%, p = 0.956, and RFS; 98.6% vs. 98.9%, p = 0.757, respectively). Conclusion ACG can be performed safely after non-curative endoscopic submucosal dissection, with good operative outcomes.

This study presents the initial feasibility of three-port right-side approach-duet totally laparoscopic distal gastrectomy (R-duet TLDG) with uncut Roux-en-Y (R-Y) reconstruction for the treatment of lower- or middle-third gastric cancer.A total of 30 patients who underwent R-duet TLDG with uncut R-Y reconstruction for gastric cancer were enrolled. All patients were treated at the Catholic Medical Center. Reconstructions were performed intracorporeally without special instruments. The clinicopathological characteristics, operative details, postoperative short-term outcomes, and postoperative follow-up endoscopy results were analyzed retrospectively.All operations were performed by three-port R-duet TLDG. There were no conversions to an open approach, and no additional ports were placed. The mean operating time was 170 minutes, and the mean number of retrieved lymph nodes was 44. Three patients experienced mild postoperative complications, including small bowel ileus and pneumonia. Follow-up endoscopy was carried out at 3 months. No patients had experienced moderate-or-severe food stasis, alkaline gastritis, or bile reflux during the follow-up period. Recanalization of the biliopancreatic limb was not observed.R-duet TLDG with uncut R-Y reconstruction could be safely performed as a reduced port surgery without special instruments.

The prognosis of gastric cancer patients is better in Asia than in the West. Genetic, environmental, and treatment factors have all been implicated. We sought to explore the extent to which the place of birth and the place of treatment influences survival outcomes in Korean and US patients with localized gastric cancer.Patients with localized gastric adenocarcinoma undergoing potentially curative gastrectomy from 1989 to 2010 were identified from the SEER registry and two single institution databases from the US and Korea. Patients were categorized into three groups: Koreans born/treated in Korea (KK), Koreans born in Korea/treated in the US (KUS), and White Americans born/treated in the US (W), and disease-specific survival rates compared.We identified 16,622 patients: 3,984 (24.0%) KK, 1,046 (6.3%) KUS, and 11,592 (69.7%) W patients. KK patients had longer unadjusted median (not reached) and 5-year disease-specific survival (81.6%) rates than KUS (87 months, 55.9%) and W (35 months, 39.2%; p 0.001 for all comparisons) patients. This finding persisted on subset analyses of patients with stage IA tumors, without cardia/GEJ tumors, with 15 examined lymph nodes, and treated at a US center of excellence. On multivariable analysis, KUS (HR 2.80, p 0.001) and W (HR 5.79, p 0.001) patients had an increased risk of mortality compared to KK patients.Both the place of birth and the place of treatment significantly contribute to the improved prognosis of patients with gastric cancer in Korea relative to those in the US, implicating both nature and nurture in this phenomenon.

This study aimed to investigate the clinicopathologic characteristics and outcomes of Borrmann type 1 gastric cancer and evaluate its clinical significance in advanced gastric cancer compared with Borrmann types 2 and 3 cancer. Between January 1989 and December 2013, 1949 patients with advanced gastric cancer who underwent curative gastrectomy at our institution were enrolled in the study. Of the 1949 patients, 59 (3%) exhibited Borrmann type 1 cancer, characterized by a large size, rare serosal invasion, lower lymph node involvement, location in the upper third of the stomach, intestinal type, and differentiated histology. The recurrence rate was higher for Borrmann type 1 than for Borrmann types 2 and 3 cancer. In addition, more than half of the Borrmann type 1 recurrences showed a hematogenous pattern. However, overall survival did not differ significantly among the three cancer types. In the multivariate analysis, Borrmann type 1 cancer, with tumor depth, node metastasis, and vascular invasion, was an independent risk factor associated with recurrence. Particularly, Borrmann type 1 cancer showed a worse prognosis in both overall survival and recurrence-free survival than the other Borrmann types in the upper third of the stomach. Borrmann type 1 gastric cancer is associated with a higher recurrence rate than Borrmann types 2 and 3, but not with a difference in the overall survival rate.

본 연구는 사회불안 경향 대학생들을 대상으로 심상재구성 훈련의 효과를 알아보고자 하였다. 이를 위해, 사회불안 수준이 높은 37명의 대학생을 선발하여 심상재구성 단독 집단, 인지재구성이 포함된 심상재구성 집단, 통제집단 중 하나에 무선할당 하였고, 훈련 집단은 각기 총 3회의 훈련이 실시되었다. 연구결과, 훈련을 실시한 두 집단은 통제집단과 비교하여 사회불안, 사후반추사고, 부정적 평가에 대한 두려움의 유의한 감소를 보였다. 두 훈련 집단 간 효과를 비교한 결과, 두 집단 모두 사전에 비해 사후에 부정심상의 선명함, 고통, 믿음, 빈도 수준의 감소를 보였다. 그러나 심상재구성 단독 집단의 경우 3회의 훈련 기간에 걸쳐 뚜렷한 감소 경향성이 나타났지만, 인지재구성이 포함된 심상재구성 집단은 인지재구성 시행 회기 이후 원 점수로 되돌아갔다. 이러한 결과는 심상재구성 훈련이 사회불안 경향이 있는 대학생의 사회불안을 감소시키는데 효과적이며, 특히 심상재구성 단독 훈련은 부정적 자기 심상과 연관된 과거기억을 재구성시킴으로써 지속적으로 사회불안을 유발시키는 심상 및 기억의 감소에 더 효과적임을 시사한다. 마지막으로 본 연구의 시사점과 제한점에 대해 논의하였다.

The prognosis of gastric cancer is generally determined by tumor depth and lymph node metastasis, while the effect of cross-sectional tumor location on prognosis remains unclear. This study recruited patients who had been diagnosed with gastric cancer and who underwent gastrectomy from 1989 to 2012. The cross-sectional locations of the gastric cancers were classified into four regions: the lesser (LC) and greater curvatures (GC), and anterior (AW) and posterior walls (PW). Overall, 4820 patients were enrolled in this study. The most common site of gastric cancer among the four cross-sectional locations was the LC (46.4%), while the proportions of PW (19.9%), AW (18.4%), and GC (15.4%) were similar. Overall survival differed statistically (p = 0.013) according to the cross-sectional location, and the 5-year overall survival of those with tumors with a GC location was significantly worse (p = 0.003) than for the other three locations. In subgroup multivariate analysis, GC location was an independent prognostic indicator for a worse clinical outcome at T stage 3–4b (hazard ratio 1.365, 95% confidence interval 1.150–1.620, p

// Jongmi Lee 1 , Ki Hyun Park 2 , Ji Hyeong Ryu 2 , Hyun Jin Bae 2 , Aeran Choi 1 , Hyeyoung Lee 1, 3 , Jihyang Lim 1 , Kyungja Han 1 , Cho Hyun Park 4 , Eun Sun Jung 5 and Eun-Jee Oh 1 1 Department of Laboratory Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea 2 Department of Biomedical Science, Graduate School, The Catholic University of Korea, Seoul, Korea 3 SamKwang Medical Laboratories, Seoul, Korea 4 Division of Gastrointestinal Surgery, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea 5 Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea Correspondence to: Eun-Jee Oh, email: ejoh@catholic.ac.kr Keywords: natural killer cell activity, interferon-gamma, diagnostic marker, gastric cancer Received: May 10, 2017 Accepted: June 28, 2017 Published: July 31, 2017 ABSTRACT Background/Aim: Decreased Natural killer cell activity (NKA) for interferon-gamma production (NKA-IFNγ) has been reported in cancer patients. The aim of this study was to determine the diagnostic performance of NKA-IFNγ for gastric cancer (GC). Results: NKA-IFNγ levels were decreased in 261 GC patients with all stages of tumor compared to those in 48 healthy donors ( P < 0.001), and lower levels of NKA-IFNγ were associated with higher GC stages. NKA-IFNγ levels were also associated with clinicopathological parameters including tumor size, depth of invasion, and lymph node metastasis. NKA-INFγ assay had better diagnostic value (AUC = 0.822) compared to serum CEA (0.624) or CA19-9 assay (0.566) ( P < 0.001). Using different cut-off levels, serum CEA and CA19-9 showed sensitivities of 6.1-14.2% and 4.2-28.0%, respectively, which were much lower than that of NKA-IFNγ (55.6-66.7%). Methods: This study included 261 patients with newly diagnosed GC and 48 healthy donors. NKA for IFNγ was determined by enzyme immunoassay after incubation of whole blood, and diagnostic performance was evaluated. Conclusions: NK cell activities for IFNγ production could be used as a supportive non-invasive tumor marker for GC diagnosis.

Background We sought to assess the prognostic significance of lymph node ratio (LNR) and N stage in patients undergoing D2 gastrectomy and adjuvant chemotherapy, S-1, and XELOX and to compare the efficacy of them according to LNRs and N stages to evaluate the clinical impact of using LNRs compared with using N staging. Methods Patients undergoing D2 gastrectomy with adequate lymph node dissection and adjuvant chemotherapy for stage II/III gastric cancer between Mar 2011 and Dec 2016 were analysed. Of the 477 patients enrolled, 331 received S-1 and 146 received XELOX. LNR groups were segregated as 0, 0–0.1, 0.1–0.25, and > 0.25 (LNR0, 1, 2, and 3, respectively). Propensity score matching (PSM) was used to minimise potential selection bias and compare DFS and OS stratified by LNRs and N stages in the two treatment groups. Results After PSM, the sample size of each group was 110 patients, and variables were well balanced. All patients had more than 15 examined lymph nodes (median 51, range 16~124). In multivariate analysis, LNR (> 0.25) and N stage (N3) showed independent prognostic value in OS and DFS, but LNR (> 0.25) showed better prognostic value. In subgroup analysis, the LNR3 group showed better 5-year DFS (20% vs 54%; HR 0.29; p = 0.004) and 5-year OS (26% vs 67%; HR 0.28; p = 0.020) in the XELOX group. The N3 group showed better 5-year DFS (38% vs 66%; HR 0.40; p = 0.004) and 5-year OS (47% vs 71%; HR 0.45; p = 0.019) in the XELOX group. Stage IIIC showed better 5-year DFS (22% vs 57%; HR 0.32; p = 0.004) and 5-year OS (27% vs 68%; HR 0.32; p = 0.009) in the XELOX group. The LNR3 group within N3 patients showed better 5-year DFS (21% vs 55%; HR 0.31; p = 0.004) and 5-year OS (27% vs 68%; HR 0.34; p = 0.018) in the XELOX group. Conclusions LNR showed better prognostic value than N staging. LNR3, N3 and stage IIIC groups showed the superior efficacy of XELOX to that of S-1. And the LNR3 group within N3 patients showed more survival benefit from XELOX. LNR > 0.25, N3 stage and stage IIIC were the discriminant factors for selecting XELOX over S-1. Trial registration Not applicable (retrospective study).

Background Gastric cancer (GC) follow-up schedule after curative surgery is universally recommended based on the pathologic stage, but their details, including intervals and modalities of surveillance have not yet been standardised. The aim of this study was to investigate the characteristics of GC recurrence by stage to establish optimal postoperative surveillance strategies. Methods Medical information on 5095 patients with GC who underwent curative intent gastrectomy in our institution between January 1989 and December 2013 was reviewed retrospectively. Moreover, 656 patients who had recurrences after radical surgery were identified. Clinicopathologic characteristics, timing and pattern of recurrence, and survival data of these patients were analysed. Results Among the 656 patients, 50 (7.6%), 123 (18.8%), and 483 (73.6%) had stages I, II, and III GC, respectively. The median times to initial recurrence in patients with stages I, II, and III GC were 23.5 months (interquartile range [IQR], 13.0–33.0 months), 13.0 months (IQR, 9.0–25.0 months), and 12.0 months (IQR, 7.0–21.0 months), respectively. In patients with stage I GC, more than half (58%) of them had distant organ metastasis; otherwise, peritoneal dissemination (39%) was the most common pattern in patients with stage III GC. Conclusions Despite the low incidence, the time of initial recurrence in stage I GC was longer than those in stage II and III GC. Moreover, the pattern of initial recurrence was also different according to the pathologic stage. Therefore, clinicians should consider stage-specific differences of recurrence in setting up surveillance strategies after curative surgery for GC patients.

Endoscopic submucosal dissection (ESD) is an alternative to surgical resection for treating early gastric cancer (EGC). However, there have been limited reports on the long-term outcome of ESD compared to that of surgical resection. The aim of this study was to evaluate the immediate and long-term clinical and oncologic outcomes of ESD compared to surgical resection. We retrospectively reviewed data of patients in five centers who were treated with ESD or surgical resection for EGC within expanded criteria for ESD from 2006 to 2008. ESD group had significantly shorter procedure times, shorter fasting period, and shorter hospital stay than the surgical resection group. Immediate complications in the surgical resection group were more common compared to those in the ESD group. Five-year cancer recurrence rate of the ESD group was 12.3 % and significantly higher than 2.1 % of the surgical resection group (P = 0.001). Five-year disease-free survival rate of the surgical resection group was 97 %, which was significantly higher than 85 % of the ESD group (P = 0.001). Metachronous lesions were equally found every year during the follow-up period in the ESD group. Five-year overall survival rates were 100 % for both groups. ESD might be an acceptable and effective treatment for EGC considering overall survival rates with fewer early complication rates and shorter duration of hospital stay compared to surgical resection. However, intensive and persistent endoscopic surveillance should be performed after ESD for early detection of metachronous lesions.

Summary Background Chemotherapy is the standard of care for incurable advanced gastric cancer. Whether the addition of gastrectomy to chemotherapy improves survival for patients with advanced gastric cancer with a single non-curable factor remains controversial. We aimed to investigate the superiority of gastrectomy followed by chemotherapy versus chemotherapy alone with respect to overall survival in these patients. Methods We did an open-label, randomised, phase 3 trial at 44 centres or hospitals in Japan, South Korea, and Singapore. Patients aged 20–75 years with advanced gastric cancer with a single non-curable factor confined to either the liver (H1), peritoneum (P1), or para-aortic lymph nodes (16a1/b2) were randomly assigned (1:1) in each country to chemotherapy alone or gastrectomy followed by chemotherapy by a minimisation method with biased-coin assignment to balance the groups according to institution, clinical nodal status, and non-curable factor. Patients, treating physicians, and individuals who assessed outcomes and analysed data were not masked to treatment assignment. Chemotherapy consisted of oral S-1 80 mg/m 2 per day on days 1–21 and cisplatin 60 mg/m 2 on day 8 of every 5-week cycle. Gastrectomy was restricted to D1 lymphadenectomy without any resection of metastatic lesions. The primary endpoint was overall survival, analysed by intention to treat. This study is registered with UMIN-CTR, number UMIN000001012. Findings Between Feb 4, 2008, and Sept 17, 2013, 175 patients were randomly assigned to chemotherapy alone (86 patients) or gastrectomy followed by chemotherapy (89 patients). After the first interim analysis on Sept 14, 2013, the predictive probability of overall survival being significantly higher in the gastrectomy plus chemotherapy group than in the chemotherapy alone group at the final analysis was only 13·2%, so the study was closed on the basis of futility. Overall survival at 2 years for all randomly assigned patients was 31·7% (95% CI 21·7–42·2) for patients assigned to chemotherapy alone compared with 25·1% (16·2–34·9) for those assigned to gastrectomy plus chemotherapy. Median overall survival was 16·6 months (95% CI 13·7–19·8) for patients assigned to chemotherapy alone and 14·3 months (11·8–16·3) for those assigned to gastrectomy plus chemotherapy (hazard ratio 1·09, 95% CI 0·78–1·52; one-sided p=0·70). The incidence of the following grade 3 or 4 chemotherapy-associated adverse events was higher in patients assigned to gastrectomy plus chemotherapy than in those assigned to chemotherapy alone: leucopenia (14 patients [18%] vs two [3%]), anorexia (22 [29%] vs nine [12%]), nausea (11 [15%] vs four [5%]), and hyponatraemia (seven [9%] vs four [5%]). One treatment-related death occurred in a patient assigned to chemotherapy alone (sudden cardiopulmonary arrest of unknown cause during the second cycle of chemotherapy) and one occurred in a patient assigned to chemotherapy plus gastrectomy (rapid growth of peritoneal metastasis after discharge 12 days after surgery). Interpretation Since gastrectomy followed by chemotherapy did not show any survival benefit compared with chemotherapy alone in advanced gastric cancer with a single non-curable factor, gastrectomy cannot be justified for treatment of patients with these tumours. Funding The Ministry of Health, Labour and Welfare of Japan and the Korean Gastric Cancer Association.

Background The relationship between preoperative body mass index (BMI) and the survival of postoperative gastric cancer patients is not clear. Furthermore, the survival impact with postoperative BMI is not known, even though weight loss is inevitable after gastrectomy. Methods Patients who underwent gastrectomy for gastric cancer between 2000 and 2008 were included in the study (n = 1909). Patients were divided into three groups based on their BMIs: low ( 2 ), normal (18.5–24.9 kg/m 2 ), and high BMI (≥25.0 kg/m 2 ). Patient survival was compared according to BMI at two time points: baseline and 1 year after surgery. Results Regarding BMI 1 year after surgery, overall survival, disease-specific survival, and recurrence-free survival were longer in the high BMI group than the low and normal BMI groups. In a Cox proportional hazards model, adjusting for the patient's age, sex, type of surgery, tumour stage, histology, curative resection, and BMI at baseline, a high BMI 1 year after surgery was associated with lower overall mortality compared to normal BMI (hazard ratio 0.51; 95% confidence interval, 0.26–0.98). However, BMI at baseline was not an independent prognostic factor. Conclusion BMI 1 year after surgery significantly predicted the long-term survival of patients with gastric cancer compared with the preoperative BMI.

Purpose Expanded indications for endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) remain controversial due to the potential risk of undertreatment after adequate lymph node dissection (LND). Regional LND (RLND) is a novel technique used for limited lymphadenectomy to avoid gastrectomy. This study established the safety and effectiveness of RNLD as an additional treatment option after ESD for expanded indications. Materials and methods A total of 69 patients who met the expanded indications for ESD were prospectively enrolled from 2014 to 2017. The tumors were localized using intraoperative esophagogastroduodenoscopy (EGD) before RLND. All patients underwent RLND first, followed by conventional radical gastrectomy with LND. The locations of the preoperative and intraoperative EGD were compared. Pathologic findings of the primary lesion and the RLND status were analyzed. Results The concordance rates of tumor location between the preoperative and intraoperative EGD were 79.7%, 76.8%, and 63.8% according to the longitudinal, circumferential, and regional locations, respectively. Of the 4 patients (5.7%) with metastatic LNs, 3 were pathologically classified as beyond the expanded indication for ESD and 1 had a single LN metastasis in the regional lymph node. Conclusions RLND is a safe additional option for the treatment of EGC in patients meeting expanded indications after ESD.

According to 8th AJCC/UICC TNM criteria, stage IIB includes pT1N3M0, pT2N2M0, pT3N1M0, and pT4aN0M0, which includes not only early gastric cancer but also locally advanced cancer. There are currently no data about whether there is any additional impact of serosal exposed cancer without nodal metastasis (pT4aN0) on patients’ survival outcomes compared with other subgroups in IIB. Patients who underwent radical gastrectomy for gastric cancer patients were enrolled, including 427 patients in stage IIB; 20 (4.68%), 104 (24.35%), 172 (40.28%), and 131 (30.67%) patients were classified as pT1N3a, pT2N2, pT3N1, and pT4aN0, respectively. Clinicopathological characteristics, recurrence pattern, and survival and recurrence rates were analyzed according to the TNM subgroups. Cancer-specific and relapse-free survival were significantly worse in serosal exposed cancer than in nonserosal exposed cancer in stage IIB (P = 0.019 and P = 0.015). Recurrence rate was highest in the pT4aN0 subgroup (29.0%) in stage IIB, and peritoneal metastasis was the most common pattern. Survival outcomes of the pT4aN0 subgroup were not significantly different from those of the stage IIIA or pT4aN1 subgroups. Patients with serosal exposed cancer without nodal metastasis shows worse cancer specific and disease-free survival with higher incidence of peritoneal metastasis than other subgroups in stage IIB. Further surveillance studies, including staging laparoscopy and active adjuvant therapy, are required in this subgroup of patients.

Purpose The surgical outcomes of end-stage renal disease (ESRD) patients undergoing radical gastrectomy for gastric cancer were inferior compared with those of non-ESRD patients. This study aimed to evaluate the short- and long-term surgical outcomes of ESRD patients undergoing laparoscopic gastrectomy (LG) and open gastrectomy (OG) for gastric cancer. Materials and methods Between 2004 and 2014, 38 patients (OG: 21 patients, LG: 17 patients) with ESRD underwent gastrectomy for gastric cancer. Comparisons were made based on the clinicopathological characteristics, surgical outcomes, and long-term survival rates. Results No significant differences were noted in the clinicopathological characteristics of either group. LG patients had lower estimated blood loss volumes than OG patients (LG vs. OG: 94 vs. 275 mL, P=0.005). The operation time and postoperative hospital stay were similar in both the groups. The postoperative morbidity for LG and OG patients was 41.1% and 33.3%, respectively (P=0.873). No significant difference was observed in the long-term overall survival rates between the 2 groups (5-year overall survival, LG vs. OG: 82.4% vs. 64.7%, P=0.947). Conclusions In ESRD patients, LG yielded non-inferior short- and long-term surgical outcomes compared to OG. Laparoscopic procedures might be safely adopted for ESRD patients who can benefit from the advantages of minimally invasive surgery.

BACKGROUND: Despite the development of newer treatments, the prognosis for patients with stage IV gastric cancer remains grave. This study evaluated the efficacy of gastrectomy following response to chemotherapy in patients with stage IV gastric cancer.A total of 419 patients who were diagnosed with stage IV gastric cancer were identified from the multi-institutional Catholic Gastric Cancer Study Group database. The patients were divided into four groups: 212 were in the chemotherapy only (CTx) group, 124 were in the chemotherapy after palliative gastrectomy (G-CTx) group, 23 were in the radical gastrectomy after chemotherapy (CTx-G) group, and 60 were in the best supportive care group. To compensate for the effects of chemotherapy, cases of chemotherapy responsive were analyzed separately. To identify factors affecting survival rates, cure rates for surgery in the surgery group were analyzed.The 3-year survival rate of the CTx-G group was significantly higher than that of the CTx group (42.8 vs. 12.0%, p = 0.001). Moreover, the CTx-G group's 3-year survival rate was greater than that of the G-CTx group (42.8 vs. 37.1%, p = 0.207). Chemotherapy-responsive patients in the CTx-G group had a better 3-year survival rate than those in the G-CTx group (46.1 vs. 18.4%, respectively, p = 0.011). In the surgery group, R0 resection led to a significantly better 3-year survival rate than palliative gastrectomy (61.1 vs. 16.2%, p = 0.003).Adjuvant surgery might improve the survival rate of patients with stage IV gastric cancer, particularly in R0 resection cases.

Our goal was to evaluate changes in PD-L1 expression in primary tumours of metastatic gastric cancer before and after chemotherapy. We evaluated the PD-L1 expression of 72 patients with primary gastric cancer, before and after palliative first-line platinum-based chemotherapy, between January 2015 and March 2017. The PD-L1 ratio was defined as pre-chemotherapy PD-L1 expression divided by the post-chemotherapy PD-L1 expression. In 30 patients with PD-L1 negative pre-chemotherapy, 12 (40%) were positive post-chemotherapy; among the 42 patients with PD-L1 positive pre-chemotherapy, 24 (57.1%) were negative post-chemotherapy. The degree of PD-L1 expression decreased from 58.3% before chemotherapy to 41.7% after chemotherapy (P = 0.046). Among patients with complete response/partial response (CR/PR), the degree of PD-L1 expression decreased (P = 0.002), as well as PD-L1 positivity with statistical significance (P = 0.013) after chemotherapy, but not among patients with stable disease/progressive disease (SD/PD). Higher disease control rates (CR/PR/SD) were observed in patients with an elevated PD-L1 ratio (P = 0.043). Patients with a high PD-L1 ratio (> 1) were found to be associated with a better progression-free survival (HR 0.34, 95% CI 0.17–0.67, P = 0.002). PD-L1 expression can change during chemotherapy. Moreover, changes in patterns of PD-L1 expression might be associated with patient prognosis and response to chemotherapy.

Purpose To analyze the benefit and feasibility of this procedure compared with those of open method. Methods Abdominal procedure includes laparoscopic gastric mobilization, celiac axis lymph node dissection, formation of the gastric tube, and pyloromyotomy. The actual procedure performed during open surgery is the same as those of laparoscopic surgery except for the main incision. Minimally invasive esophagectomy (MIE) was performed on 54 patients with esophageal cancer. The short-term outcomes, including postoperative complications were analyzed and compared with 44 cases of open method. Results Although the total operative time was not different between 2 groups (349.8 minutes vs. 374.8 minutes, P = 0.153), the operation time of abdominal procedure was shorter in laparoscopic group (90.6 minutes vs. 162.1 minutes, P < 0.001). Operation related complications and hospital stay were not significantly different between the 2 groups. The number of transfused patients was significantly smaller in laparoscopic group (11.1% vs. 27.9%, P = 0.030). Conclusion Laparoscopic gastric tubing with pyloromyotomy is a feasible and safe treatment option for patients with esophageal cancer.

Background Previous comparisons of gastric cancer between the West and the East have focused predominantly on Japan and Korea, where early gastric cancer is prevalent, and have not included the Chinese experience, which accounts for approximately half the world's gastric cancer. Methods Patient characteristics, surgical procedures, pathologic information, and survival were compared among gastric cancer patients who underwent curative intent gastrectomy at two large volume cancer centers in China and the US between 1995 and 2005. Results Median age and body mass index were significantly higher in US patients. The proportion of proximal gastric cancer was comparable. Gastric cancer patients in China had larger tumors and a later stage at presentation. The median number of positive lymph nodes was higher (5 vs 4, P

To compare the incidences of postoperative pancreatic fistula (POPF) between robot-assisted distal gastrectomy (RADG) and laparoscopy-assisted distal gastrectomy (LADG).A total of 40 patients with gastric cancer who underwent RADG were compared with 40 initial patients who underwent LADG by a single surgeon. We evaluated and compared the clinicopathologic characteristics, surgical outcomes, and operative complications including POPF in two groups.The POPF was observed more frequently in the LADG group than in the RADG group (22.5% versus 10%, P 0.001). Although the serum amylase levels in the 20 first-half cases did not statistically differ between LADG and RADG (P = 0.32), those in the 20 latter-half cases were significantly lower in the RADG group (P 0.05). Univariate and multivariate analyses identified laparoscopic surgery and visceral fat area as POPF-associated risk factors.RADG is feasible and safe for distal gastrectomy in terms of POPF.

PURPOSE The aim of this study was to compare the short-term surgical and long-term functional outcomes of Billroth I, Billroth II, and Roux-en-Y reconstruction after laparoscopic distal gastrectomy. MATERIALS AND METHODS We retrospectively collected data from 697 patients who underwent laparoscopic distal gastrectomy for operable gastric cancer between January 2009 and December 2012. The patients were classified into three groups according to the reconstruction methods: Billroth I, Billroth II, and Roux-en-Y. The parameters evaluated included patient and tumor characteristics, operative details, and postoperative complications classified according to the Clavien-Dindo classification. Endoscopic findings of the remnant stomach were evaluated according to the residue, gastritis, bile (RGB) classification and the Los Angeles classification 1 year postoperatively. RESULTS Billroth I, Billroth II, and Roux-en-Y were performed in 165 (23.7%), 371 (53.2%), and 161 patients (23.1%), respectively. Operation time was significantly shorter (173.4±44.7 minute, P

The aim of this study was to evaluate the incidence and clinical characteristics of splenic infarction (SI) in gastric cancer patients who have undergone gastrectomy. For this study, the medical records of 1084 patients were reviewed and 877 patients were ultimately enrolled. The times of symptom onset, diagnosis of SI, and complete resolution on CT were calculated from the day of the operation. Based on the wedge shape of the SI in all cases, the total volume of the SI was measured based on that of a corn kernel. Thirty-six patients (4.10%) were diagnosed with SI after gastrectomy; four of these patients (0.45%) developed complications associated with the SI. Total gastrectomy and extended lymph node dissection were risk factors for development of SI. Patients with complications exhibited inflammatory signs between 7 and 10 days after surgery. The mean volume of the SI was 4025.69 mm3. The mean time to complete resolution on the CT scan was 327 days postoperatively. In 30 cases, small branched arteries from the splenic artery that could have caused the SI were retrospectively detected on the preoperative CT scans. Although the incidence of the SI was low, large volume of the SI is associated with complication development. Measuring the infarction volume via a CT scan may be useful to decide on the treatment strategy. Preoperative 3-D reconstruction of the splenic artery tributaries may help reduce the risk of inadvertent SI.

Background Slug is a transcription factor that activates the epithelial–mesenchymal transition (EMT) process in cancer progression. The aim of our study was to evaluate the clinical significance of Slug expression in gastric cancer. Methods The expression of Slug in gastric cancer tissues of 456 patients who underwent gastrectomy was evaluated by immunohistochemistry using tissue microarrays. Slug expression level was defined by the composite score determined by multiplying the tumor staining scores for intensity and extent. The associations of Slug expression with clinicopathological characteristics and overall and recurrence-free survival were analyzed. Results Patients were divided into three groups according to Slug composite score (≤4, 6, and 9). Low, mid, and high expression of Slug was observed in 104 (22.7%), 130 (28.3%), and 225 (49.0%) of cases, respectively. Overall survival and recurrence-free survival progressively increased from high to low Slug expression. In terms of lymph node metastasis, the rate of positive lymph node metastasis was 38/104 (36.5%), 79/130 (60.8%), and 178/225 (79.1%) in low, mid, and high Slug expression groups, respectively, displaying a tendency to increase with higher Slug expression. In a multivariate analysis adjusting for patient age, tumor size, tumor depth, and histology, high Slug expression was associated with a high rate of positive lymph node metastasis compared with low Slug expression (odds ratio 3.42; 95% confidence interval, 1.74–6.69). In a subgroup analysis of T1 cancer, patients with negative Slug expression (defined as