Best Management of Sigmoid Volvulus: a Prospective Randomized Trial

描述（由申请人提供）：乔纳森·塞缪尔博士是一位正在崛起的外科重症监护研究员，目前正在北卡罗来纳州大学（北卡罗来纳州）外科系完成他的普通外科住院医师实习。自2007年以来，他一直通过与马拉维利隆圭的Kamuzu中心医院（KCH）外科合作，与ECONOMY进行研究。他在马拉维的利隆圭生活了两年，并在KCH和KCN外科部门之间建立伙伴关系方面发挥了重要作用。他开发并实施了创伤登记和烧伤数据库。在他的第二年，他被授予著名的福格蒂国际临床研究员奖（2009-2010; R24 TW 007988），除了接受他的第一年艾滋病研究中心发展奖在北卡罗来纳州大学（P30 AI 50410）和医学院校友基金会补助金。到目前为止，他已经有9个第一作者出版物和一个第二作者出版物，他担任导师的医学生研究实习生。他还通过协助肿瘤活检和项目实施的指导和建议，协助与其他大学教师和福格蒂学员的合作。他在为KCH的马拉维医生制定外科住院医师计划方面发挥了重要作用。虽然他已经拥有公共卫生硕士学位和良好的研究记录，但他将接受热带医学，生物统计学，伦理学和领导力方面的额外培训，并积极参与国家委员会和会议。为了充分发展他作为外科医生科学家的职业生涯，领导一个跨学科团队，研究外科疾病，如乙状结肠扭转，创伤性损伤和烧伤，具有双向适用性，塞缪尔博士需要国际研究领域的知名领导者进一步指导。威廉米勒博士和安东尼查尔斯博士在斯坦福大学将分别担任美国和LMIC导师。塞缪尔博士和他的主要导师是一个已经成立的小组的一部分，其中包括马拉维外科医生和教师从传染病科和外科学系。米勒博士是国际临床研究的领导者，包括马拉维的几项大型研究，他将继续提供监督， 指导，包括研究设计和执行。他是一位专家导师、讲师和调查员。他是KL 2研讨会的课程主任，指导了更多的MPH，K奖，博士生比其他任何人在KL 2。安东尼·查尔斯博士在尼日利亚出生和长大，他成功地指导了申请人和其他几名美国和马拉维的实习生进行临床护理和研究，并继续在KCH提供现场监督。塞缪尔博士计划研究乙状结肠扭转，这是马拉维和许多其他国家大肠梗阻的主要原因，死亡率高达20- 25%。在KCH，每年约有60例病例，其中15人死亡，大多数是健康和有生产力的人。乙状结肠扭转的手术决定与穿孔性憩室炎类似，后者是另一种左结肠急症。憩室炎在美国很常见，在85岁以上的人群中，随着年龄的增长，发病率增加至65%以上。这项研究不仅将指导乙状结肠扭转的治疗，还将指导穿孔性憩室炎的治疗，这对我们的人口老龄化至关重要。尽管乙状结肠扭转 在许多发展中国家，这是一种常见的死亡原因，迄今为止只进行了一项前瞻性随机试验，该试验存在一些局限性，包括招募人数不足以及与发病率和随访相关的数据有限。对这一往往致命的疾病过程的忽视，部分原因是它主要是发展中国家的一种疾病，没有得到熟练的调查人员和供资机构的注意。乙状结肠扭转在手术时可分为非坏疽性（NG-SV）或坏疽性（G-SV）。NG-SV可采用乙状窦系膜固定术或切除吻合术（一期）治疗。此外，在治疗NG-SV时，一些临床医生建议术前结肠减压，但这种做法既没有普遍应用，也没有任何良好的前瞻性试验对其进行研究。G-SV可采用切除和吻合术（一期）或切除和结肠造口术后结肠造口术逆转（二期）治疗。在NG-SV中，乙状窦系膜固定术具有手术时间短、恢复快、手术感染率低和死亡率低的优势，但疾病复发率较高（与单期相比）。在G-SV中，单阶段具有避免临时结肠造口术的优点，但可能具有较高的初始死亡率。受试者将在手术时被分配至两个研究组（G-SV或NG-SV）之一。G-SV中的受试者将随机分配至一期或二期，NG-SV中的受试者将随机分配至一期或系膜乙状结肠固定术。拟定研究的目的是（1）确定通过单期或乙状结肠系膜固定术治疗的NG-SV的死亡率差异（定义为存活至出院），（2）确定通过单期或二期治疗的G-SV的死亡率差异（定义为存活至无结肠造口出院），以及（3）确定术前结肠减压对存活至出院的影响。 公共卫生相关性：发展中国家的外科疾病负担很高，主要是急性外科疾病，包括乙状结肠扭转。了解乙状结肠扭转的理想管理是必要的，以提供最好的照顾，病人与此和相关的条件影响左结肠，如乙状结肠憩室炎，并将推进药物科学和受益患者在马拉维和美国。

DESCRIPTION (provided by applicant): Dr Jonathan Samuel is a rising surgical critical care fellow and currently completing his general surgery residency at the Department of Surgery at the University of North Carolina (UNC). Since 2007 he has been conducting research with UNC through a partnership with Kamuzu Central Hospital (KCH) Department of Surgery in Lilongwe, Malawi. He lived in Lilongwe, Malawi for two years and was instrumental in establishing a partnership between the Departments of Surgery at KCH and UNC. He developed and implemented both a trauma registry and burn database. During his second year he was awarded the prestigious Fogarty International Clinical Research Fellow award (2009-2010; R24 TW007988) in addition to receiving his first year the Center for AIDS Research development award at the University of North Carolina (P30 AI50410) and the UNC School of Medicine Alumni Foundation grant. So far he has had nine first author publications and one second author publication in which he served as a mentor for a medical student research trainee. He also assisted in collaborative work with other UNC faculty and Fogarty trainees by assisting in biopsies of tumors and guidance and advice on project implementation. He was instrumental in developing a surgical residency program for Malawian doctors at KCH. Though he already has an MPH and a strong research record, he will undergo additional training in tropical medicine, biostatistics, ethics and leadership, and become active in national committees and conference sessions. To fully develop his career as a surgeon scientist leading an interdisciplinary team studying surgical diseases such as sigmoid volvulus, traumatic injury and burns with bidirectional applicability, Dr Samuel requires further mentorship from established leaders in international research. Dr William Miller and Dr Anthony Charles at UNC will serve as US and LMIC mentors, respectively. Dr Samuel and his primary mentors are part of an already established group which includes Malawian surgeons and faculty from the UNC Division of Infectious Diseases and the UNC Department of Surgery. Dr Miller, a leader in international clinical research including several large studies in Malawi, will continue to provide oversight and guidance including study design and execution. He is an expert mentor, instructor and investigator. He is course director of the KL2 seminar at UNC and has mentored more MPH, K award, and doctoral students than anyone else at UNC. Dr Anthony Charles, born and raised in Nigeria, has successfully mentored the applicant and several other US and Malawian trainees in both clinical care and research and continues to provide on-site supervision at KCH. Dr Samuel plans to study sigmoid volvulus which is the leading cause of large bowel obstruction in Malawi and many other countries, with an unacceptably high mortality rate of 20-25%. At KCH there are approximately 60 cases per year with 15 deaths, mostly among otherwise healthy and productive individuals. Operative decisions in sigmoid volvulus are analogous to those of perforated diverticulitis, another left-sided colonic emergency. Diverticulitis is common in the United States with an increasing incidence with age to upwards of 65% among those older than 85. The proposed research will guide management of not only sigmoid volvulus but also perforated diverticulitis, which is critical as our population ages. Despite sigmoid volvulus being a frequent cause of death in many developing countries, only one prospective randomized trial has ever been conducted and this trial suffered from several limitations including insufficient enrollment and limited data related to morbidity and follow-up. The neglect of this often fatal disease process is in part because it is predominately a disease of developing countries and has not received attention from skilled investigators and funding agencies. Sigmoid volvulus can be classified at the time of surgery as either non-gangrenous (NG-SV) or gangrenous (G-SV). NG-SV is treated with either mesosigmoidopexy or resection and anastomosis (single-stage). Additionally, in managing NG-SV some clinicians recommend preoperative colonic decompression, but this practice is neither universally applied nor has it been studied by any good prospective trials. G-SV is treated with either resection and anastomosis (single-stage) or resection and colostomy followed by colostomy reversal (two-stage). In NG-SV, mesosigmoidopexy has the advantage of being a shorter procedure with faster recovery, lower surgical infection rate, and lower mortality, but a higher disease recurrence rate (compared to single-stage). In G-SV, single-stage has the advantage of avoiding a temporary colostomy, but likely has a higher initial mortality rate. Subjects will be allocated at the time of surgery to on of two study arms, G-SV or NG-SV. Subjects in G-SV will be randomized to either single-stage or two-stage, and subjects in NG-SV will be randomized to either single-stage or mesosigmoidopexy. The aims of the proposed study are to (1) determine the mortality difference (defined as survival to discharge) in NG-SV managed by single-stage or mesosigmoidopexy, (2) determine mortality difference (defined as survival to colostomy-free discharge) in G-SV managed by single- stage or two-stage, and (3) determine the effect of preoperative colonic decompression on survival to discharge. PUBLIC HEALTH RELEVANCE: Developing countries have a high burden of surgical disease predominantly in acute surgical conditions including sigmoid volvulus. Understanding the ideal management of sigmoid volvulus is necessary to provide the best care to patients with this and related conditions affecting the left colon such as sigmoid diverticulitis, and will advance surgicl sciences and benefit patients in both Malawi and the United States.