The role of proximal gastrectomy in gastric cancer

Over the past 30 years, the prevalence of upper third gastric cancer (GC) and gastroesophageal junction (GEJ) cancer has increased. Total gastrectomy with D2 lymph node dissection is the standard surgical treatment for non-early (T2 or higher) upper third and GEJ cancers, but total gastrectomy often results in post-gastrectomy syndrome (5-50%), consisting of weight loss, dumping syndrome, and anemia. Proximal gastrectomy (PG) has the potential to avoid these postoperative problems by preserving stomach function. However, PG has historically been discouraged by surgeons owing to the high incidence of postoperative reflux esophagitis (20-65%), anastomotic stenosis, and decreased quality of life. In recent years, anti-reflux reconstruction techniques, such as the double flap technique and double-tract reconstruction, have been developed to be performed after PG, and evidence has emerged that these techniques not only reduce the incidence of postoperative reflux esophagitis but also decrease postoperative weight loss and prevent anemia. Prospective studies are underway to determine whether PG with anti-reflux techniques improves patient-reported quality of life. In the present work, we reviewed available evidence for the use of PG for GC and GEJ cancer, including oncologically appropriate patient selection for PG, potential functional benefits of PG over TG, and various types of reconstructions that can be performed after PG, as well as future research on the use of PG.ope

Long-term Efficacy of S-1 Monotherapy or Capecitabine Plus Oxaliplatin as Adjuvant Chemotherapy for Patients with Stage II or III Gastric Cancer after Curative Gastrectomy: a Propensity Score-Matched Multicenter Cohort Study

Purpose: To compare long-term disease-free survival (DFS) between patients receiving tegafur/gimeracil/oteracil (S-1) or capecitabine plus oxaliplatin (CAPOX) adjuvant chemotherapy (AC) for gastric cancer (GC). Materials and methods: This retrospective multicenter observational study enrolled 983 patients who underwent curative gastrectomy with consecutive AC with S-1 or CAPOX for stage II or III GC at 27 hospitals in Korea between February 2012 and December 2013. We conducted propensity score matching to reduce selection bias. Long-term oncologic outcomes, including DFS rate over 5 years (over-5yr DFS), were analyzed postoperatively. Results: The median and longest follow-up period were 59.0 and 87.6 months, respectively. DFS rate did not differ between patients who received S-1 and CAPOX for pathologic stage II (P=0.677) and stage III (P=0.899) GC. Moreover, hazard ratio (HR) for recurrence did not differ significantly between S-1 and CAPOX (reference) in stage II (HR, 1.846; 95% confidence interval [CI], 0.693-4.919; P=0.220) and stage III (HR, 0.942; 95% CI, 0.664-1.337; P=0.738) GC. After adjustment for significance in multivariate analysis, pT (4 vs. 1) (HR, 11.667; 95% CI, 1.595-85.351; P=0.016), pN stage (0 vs. 3) (HR, 2.788; 95% CI, 1.502-5.174; P=0.001), and completion of planned chemotherapy (HR, 2.213; 95% CI, 1.618-3.028; P<0.001) were determined as independent prognostic factors for DFS. Conclusions: S-1 and CAPOX AC regimens did not show significant difference in over-5yr DFS after curative gastrectomy in patients with stage II or III GC. The pT, pN stage, and completion of planned chemotherapy were prognostic factors for GC recurrence.ope

Long-Term Survival Outcomes of Elderly Patients Treated With S-1 or Capecitabine Plus Oxaliplatin for Stage II or III Gastric Cancer: A Multicenter Cohort Study

Purpose: Tegafur/gimeracil/oteracil (S-1) and capecitabine plus oxaliplatin (CAPOX) are standard adjuvant chemotherapies (ACs) administered after gastrectomy to patients with stage II or III gastric cancer. However, the efficacy of AC in elderly patients remains unclear. The objective of this retrospective multicenter cohort study was to compare the efficacies of S-1 and CAPOX AC in patients aged ≥70 years. Materials and methods: Nine hundred eighty-three patients who were treated with AC using S-1 (768 patients) or CAPOX (215 patients) were enrolled in this study. Each patient underwent AC after curative gastrectomy for stage II or III gastric cancer at one of 27 hospitals in the Republic of Korea between January 2012 and December 2013. Relapse-free survival (RFS) and overall survival (OS) were analyzed according to AC regimen and age group. Results: Of the 983 patients, 254 (25.8%) were elderly. This group had a similar RFS (P=0.099) but significantly poorer OS (p=0.003) compared with the non-elderly group. Subgroup analysis of the non-elderly group revealed no AC-associated differences in survival. Subgroup analysis of the elderly group revealed significantly better survival in the S-1 group than in the CAPOX group (RFS, P<0.001; OS, P<0.001). Multivariate analysis revealed that the CAPOX regimen was an independent poor prognostic factor for RFS (hazard ratio [HR], 1.891; 95% confidence interval [CI], 1.072-3.333; P=0.028) and OS (HR, 2.970; 95% CI, 1.550-5.692; P=0.001). Conclusions: This multicenter observational cohort study found significant differences in RFS and OS between S-1 and CAPOX AC among patients with gastric cancer aged ≥70 years.ope

Surgical treatment of the esophageal diverticulum.

Purpose: Clinical presentation and surgical results of the esophageal diverticula were analyzed. Methods: Ten patients who underwent esophageal diverticulectomy with myotomy from May 1999 to May 2008 were reviewed retrospectively. Results: Three pharyngoesophageal, one midesophageal and six epiphrenic diverticula were observed and transcervical, right transthoracic and left transthoracic surgical approach were used respectively. All of these cases were pulsion type and diverticulectomy with esophageal myotomy were done. For those who had leiomyoma, enucleation was performed simultaneously. One postoperative leakage was observed and resolved with conservative management. At 3 months after surgery, all patients enjoyed satisfactory results except two patients. One patient still suffered dysphagia which was not improved after surgery and the other patient had asymptomatic gastroesophageal reflux disease which was found on the follow up esophagography. Conclusion: Crucial factors in the treatment of esophageal diverticulum are high index of suspicion indicated by clinical symptoms, differential diagnosis with other disease and confirmatory diagnosis with esophagography. Diverticulectomy with esophageal myotomy is an essential procedure for the low recurrence of diverticulumope

지능형 연성 복합재료와 형상기억합금으로 구성된 소프트 로봇 손의 개발

학위논문 (석사)-- 서울대학교 대학원 : 기계항공공학부, 2016. 2. 안성훈.전통적으로 로봇 매니퓰레이터에 대한 여러 연구들은 정교한 잡기 동작을 얻기 위해 조인트, 링크, 기어와 모터 등과 같은 강성 요소를 주로 사용하였다. 이러한 시스템은 정확, 정교한 움켜짐 동작을 얻을 수 있으나, 이러한 움직임은 통제된 환경 아래에서 구현이 가능하다. 한편, 새롭게 떠오르는 연구 의 한 분야인 소프트 로봇틱스는 유연하고 변형이 가능한 재료를 로봇 구조에 적용하는 방식을 이용하여 연구되어 왔다. 이러한 연구들은 높은 유연성과 적응성을 특징으로 가질 수 있으며, 이를 통해 간단한 설계를 이용하여 자연의 움직임을 구현할 수 있다. 본 연구에서는 지능형 연성 복합재와 형상기억합금을 이용한 굽힘 구동기에 새로운 방식의 힘줄 구동 메커니즘을 적용하였다. 첫째로, 사람 손의 인대를 모사한 슬라이딩 메커니즘을 형상기억합금을 통해 적용한 인공 손가락을 설계하였다. 형상기억합금 와이어와 지능형 연성 복합재로 이루어진 굽힘 구동기에 굽힘 성능을 강화하기 위한 연성 경첩 구조를 적용하였다. 다음으로, 구동기 성능을 평가하고 연성 복합재의 구성에 대한 최적 설계를 결정하기 위한 실험을 수행하였다. 마지막으로, 힘줄 구동 메커니즘의 지능형 연성 복합재로 이루어진 손가락들이 적용된 소프트 로봇 손의 프로토타입을 제작하였고, 여러 모양의 물체에 대한 움켜짐 성능을 평가하였다.Conventionally, various researches on robotic manipulator or hand have been developed with rigid components, such as joints, links, gears and motors, to obtain sophisticated grasping capabilities. Rigid robotic system performs a task with precise and articulated motion with integrated modeling and feedback control system, but it can be conducted under well-controlled environment. On the other hand, soft robotics, as an emerging research field, has been studied using soft and deformable materials for robot structures. It is possible to build system which obtains high compliance and adaptability with simply integrated mechanism, so biological behavior can be realized with compact design. In this research, we developed a novel design of tendon-driven bending actuator using smart soft composite (SSC) and shape memory alloy (SMA). Firstly, artificial finger was designed with SMA wire sliding mechanism which intimates human flexor in hand. This bending actuator, which composed of SMA wire and SSC, has a soft hinge to improve bending performance of the actuator. Then, experiment of actuator was conducted to evaluate capabilities and determine the optimal actuator design according to composition of soft composite. Finally, a prototype of soft robotic hand was developed with the tendon-driven SSC fingers and thumb, and grasping capabilities was shown for various shape of objects.Chapter 1. Introduction 1 1.1 Background 1 1.2 Soft Robotics 2 1.3 Goal of Research 4 Chapter 2. Materials 5 2.1 Shape Memory Alloy (SMA) 5 2.2 Smart Soft Composite (SSC) 7 Chapter 3. Design 10 3.1 Tendon-driven SSC Bending Actuator 10 3.2 Fabrication 13 Chapter 4. Experiment 14 4.1 Experimental Setting 14 4.2 Result 16 Chapter 5. Soft Robotic Hand 19 5.1 Design 19 5.2 Grasping Performance 21 Chapter 6. Conclusion 24 Bibliography 25 Abstract in Korean 30Maste

Biomarkers for Evaluating the Inflammation Status in Patients with Cancer

Inflammation can be a causative factor for carcinogenesis or can result from a consequence of cancer progression. Moreover, cancer therapeutic interventions can also induce an inflammatory response. Various inflammatory parameters are used to assess the inflammatory status during cancer treatment. It is important to select the most optimal biomarker among these parameters. Additionally, suitable biomarkers must be examined if there are no known parameters. We briefly reviewed the published literature for the use of inflammatory parameters in the treatment of patients with cancer. Most studies on inflammation evaluated the correlation between host characteristics, effect of interventions, and clinical outcomes. Additionally, the levels of C-reactive protein, albumin, lymphocytes, and platelets were the most commonly used laboratory parameters, either independently or in combination with other laboratory parameters and clinical characteristics. Furthermore, the immune parameters are classically examined using flow cytometry, immunohistochemical staining, and enzyme-linked immunosorbent assay techniques. However, gene expression profiling can aid in assessing the overall peri-interventional immune status. The checklists of guidelines, such as STAndards for Reporting of Diagnostic accuracy and REporting recommendations for tumor MARKer prognostic studies should be considered when designing studies to investigate the inflammatory parameters. Finally, the data should be interpreted after adjusting for clinically important variables, such as age and cancer stage.ope

비분문부암과 다른 국소-전신 면역반응을 보이는 분문부암

학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의학과, 2018. 2. 이혁준.Introduction: This study sought to investigate the prognostic significance of tumor infiltrating lymphocytes (TILs) in respect to the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), and the topographic location of gastric tumors. Methods: Retrospective data from a prospectively maintained database of gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center were retrieved. The distribution and prognostic significance of a subset of TILs using immunohistochemical staining for CD3, CD4, CD8, Foxp3, and granzyme B in 416 gastric cancer patients were evaluated. The PNI was calculated using preoperative laboratory values of 7781 gastric cancer patients. TILs and PNI were analyzed according to topographic location. Results: Gastric cancers in the cardia, compared to other locations, were associated with significantly lower CD8 and higher Foxp3 and granzyme B counts, without significant differences in PNI or NLR values. In cardia- localized cancer, multivariate analysis for clinicopathological and immunological factors revealed that lymph node metastasis and a high Foxp3/CD4 ratio were independent poor prognostic factors for overall survival. In non-cardia cancer, total gastrectomy, advanced T-classification, lymph node metastasis, low Foxp3, and low PNI were all poor prognostic factors. Conclusions: The distribution and prognostic impact of TILs and PNIs varied according to the longitudinal location of the cancer. Regulatory T lymphocytes were an unfavorable prognostic factor in cardia cancer and a favorable prognostic factor in non-cardia cancer.General Introduction 1 Chapter I: Local immune responses in cardia cancer 4 Introduction 5 Methods 7 Results 12 Discussion 17 Chapter II: Systemic immune responses in gastric cancer 20 Introduction 21 Methods 23 Results 26 Discussion 36 Chapter III: Local and systemic immune responses in cardia and non-cardia cancer 39 Introduction 40 Methods 42 Results 47 Discussion 55 References 58 Abstract in Korean 71Docto

Salivary Levels of Cortisol, 17β-Estradiol, Progesterone, Dehydroepiandrosterone and α-Amylase in Patients with Burning Mouth Syndrome

학위논문 (박사)-- 서울대학교 대학원 : 치의과학과, 2013. 2. 고홍섭.Burning mouth syndrome (BMS) is characterized by a painful burning sensation or other dysesthesias of the oral mucosa, with no visible mucosal abnormalities upon clinical examination, so that seriously exacerbates quality of life. The anatomical proximity between saliva and the area of BMS symptoms and the importance of steroid hormones in the pathophysiology of BMS have resulted in the investigation of possible salivary biomarkers. The aim of this study was to investigate salivary cortisol, 17β-estradiol, progesterone, dehydroepiandrosterone (DHEA) and α-amylase levels in patients with BMS compared with controls and to investigate whether these levels could be predictors for treatment outcome in patients with BMS. Thirty female patients with BMS and twenty female control subjects were included. Unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) samples were collected, and their flow rates were determined. Salivary levels of cortisol, 17β-estradiol, progesterone and DHEA were analyzed using enzyme immunoassay kits. The enzymatic activity of α-amylase was determined using maltotriose as a substrate. Salivary transferrin level was measured to determine the level of blood contamination in saliva samples. Symptom checklist-90-revision (SCL-90-R) was used for psychological characteristics of patients with BMS. Treatment protocols of patients with BMS included control of parafunctional habits, use of artificial saliva, and clonazepam medication. The obtained results were as follows: 1. The patient group showed significantly higher levels of cortisol in UWS (P < 0.05) and of 17β-estradiol in SWS (P < 0.05). 2. When the patients were divided into older (≥60 years) and younger (<60 years) groups, the older group showed a significantly lower level of progesterone in UWS (P < 0.05). 3. There was no significant correlation between all scales of SCL-90-R and the levels of salivary analytes. 4. There was no significant correlation between the treatment efficacy and the levels of salivary analytes. In conclusion, patients with BMS had significantly higher levels of cortisol in UWS and of 17β-estradiol in SWS. These indicate that dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis and gonadal steroids are involved in the pathogenesis of BMS.I. INTRODUCTION II. REVIEW OF LITERATURE III. MATERIALS AND METHODS IV. RESULTS V. DISCUSSION VI. CONCLUSIONS REFERENCES FIGURE TABLES KOREAN ABSTRACTDocto

Photodynamic Diagnosis and Therapy for Peritoneal Carcinomatosis from Gastrointestinal Cancers: Status, Opportunities, and Challenges

Selective accumulation of a photosensitizer and the subsequent response in only the light-irradiated target are advantages of photodynamic diagnosis and therapy. The limited depth of the therapeutic effect is a positive characteristic when treating surface malignancies, such as peritoneal carcinomatosis. For photodynamic diagnosis (PDD), adjunctive use of aminolevulinic acid- protoporphyrin IX-guided fluorescence imaging detects cancer nodules, which would have been missed during assessment using white light visualization only. Furthermore, since few side effects have been reported, this has the potential to become a vital component of diagnostic laparoscopy. A variety of photosensitizers have been examined for photodynamic therapy (PDT), and treatment protocols are heterogeneous in terms of photosensitizer type and dose, photosensitizer-light time interval, and light source wavelength, dose, and dose rate. Although several studies have suggested that PDT has favorable effects in peritoneal carcinomatosis, clinical trials in more homogenous patient groups are required to identify the true benefits. In addition, major complications, such as bowel perforation and capillary leak syndrome, need to be reduced. In the long term, PDD and PDT are likely to be successful therapeutic options for patients with peritoneal carcinomatosis, with several options to optimize the photosensitizer and light delivery parameters to improve safety and efficacy.ope

Prospective multicentre randomised clinical trial comparing survival rates, quality of life and nutritional status between advanced gastric cancer patients with different follow-up intensities: study protocol for the STOFOLUP trial

Introduction: Patients who underwent curative gastrectomy for gastric cancer are regularly followed-up for the early detection of recurrence and postoperative symptom management. However, there is a lack of evidence with regard to proper surveillance intervals and diagnostic tools. This study aims to evaluate whether frequent surveillance tests have a survival benefit or improve the quality of life in patients who underwent curative resection for advanced gastric cancer. Methods and analysis: The STOFOLUP trial is an investigator-initiated, parallel-assigned, multicentre randomised controlled trial involving 16 hospitals in the Republic of Korea. Patients (n=886) diagnosed with pathological stage II or III gastric adenocarcinoma will be randomised to either the 3-month or the 6-month group at a 1:1 ratio, stratified by trial site and tumour stage. Patients allocated to the 3-month group will undergo an abdominal CT scan every 3 months postoperatively and those allocated to the 6-month group will undergo CT every 6 months. The primary endpoint is 3-year overall survival and the secondary endpoints are quality of life, as assessed using KOrean QUality of life in Stomach cancer patients Study group-40, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the stomach cancer-specific module (STO22), and nutritional outcomes. Other survival data including data concerning 3-year disease-free survival, recurrence-free survival, gastric cancer-specific survival and postrecurrence survival will also be estimated. The first patient was enrolled on July 2021 and active patient enrolment is currently underway. Ethics and dissemination: This study has been approved by the Institutional Review Board of eight of the participating hospitals (NCC 2021-0085, KBSMC2021-01-059, SMC 2021-01-140, KC21OEDE0082, 4-2021-0281, AJIRB-MED-INT-20-608, 2021-0515 and H-2102-093-1198). This study will be disseminated through peer-reviewed publications, national or international conferences. Trial registration number: NCT04740346.ope