Best Management of Sigmoid Volvulus: a Prospective Randomized Trial

描述(由申请人提供)：乔纳森·塞缪尔博士是一名正在崛起的外科重症监护研究员，目前正在北卡罗来纳大学(UNC)外科系完成他的普通外科住院医师资格。自2007年以来，他一直通过与马拉维利隆圭的卡穆祖中心医院(KCH)外科合作，与北卡罗来纳大学进行研究。他在马拉维的利隆圭生活了两年，在KCH和UNC的外科部门之间建立了伙伴关系。他开发并实施了创伤登记和烧伤数据库。在第二年，他被授予著名的Fogarty国际临床研究员奖(2009-2010；R24 TW007988)，此外，他还在第一年获得了北卡罗来纳大学艾滋病研究发展中心奖(P30 AI50410)和北卡罗来纳大学医学院校友基金会赠款。到目前为止，他已经出版了九本第一作者出版物和一本第二作者出版物，在这些出版物中，他担任一名医科学生研究实习生的导师。他还协助其他北卡罗来纳大学教职员工和Fogarty实习生进行合作，协助肿瘤活检，并就项目实施提供指导和建议。他在为KCH的马拉维医生制定外科住院医生计划方面发挥了重要作用。尽管他已经拥有公共卫生硕士学位和出色的研究记录，但他还将接受热带医学、生物统计学、伦理学和领导力方面的额外培训，并积极参加国家委员会和会议。作为一名外科科学家，塞缪尔博士领导着一个跨学科团队，研究乙状结肠扭转、创伤和烧伤等外科疾病，并具有双向适用性，为了充分发展他的职业生涯，塞缪尔博士需要国际研究领域知名领导者的进一步指导。北卡罗来纳大学的威廉·米勒博士和安东尼·查尔斯博士将分别担任美国和LMIC的导师。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，该小组包括马拉维外科医生和来自北卡罗来纳大学传染病分部和北卡罗来纳大学外科部门的教职员工。米勒博士是国际临床研究的领先者，包括马拉维的几项大型研究，他将继续提供监督和 指导包括研究设计和实施。他是一位专家导师、讲师和调查员。他是北卡罗来纳大学KL2研讨会的课程主任，指导过的公共卫生硕士、K奖和博士生比北卡罗来纳大学的其他任何人都多。Anthony Charles博士在尼日利亚出生和长大，在临床护理和研究方面成功地指导了申请人和其他几名美国和马拉维学员，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，它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%，令人无法接受。在KCH，每年大约有60个病例，其中15人死亡，大多数是在其他方面健康和有生产力的人中。乙状结肠扭转的手术决定类似于穿孔憩室炎，这是另一种左侧结肠急症。憩室炎在美国很常见，发病率随着年龄的增长而增加，85岁以上的人中发病率高达65%以上。这项拟议的研究不仅将指导乙状结肠扭转的治疗，还将指导穿孔憩室炎的治疗，这在我们人口老龄化的情况下是至关重要的。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，只进行过一次前瞻性随机试验，而且这项试验受到几个限制，包括登记不足和与发病率和随访有关的数据有限。忽视这一往往致命的疾病进程的部分原因是，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(NG-SV)或坏疽(G-SV)。NG-SV采用乙状结肠系膜固定术或切除吻合术(单期)治疗。此外，在处理NG-SV时，一些临床医生推荐术前结肠减压术，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进行研究。G-SV采用切除吻合术(单期)或切除造口造口后翻转造口(两期)治疗。在NG-SV中，乙状结肠系膜固定术具有手术时间短、恢复快、手术感染率低、死亡率低等优点，但复发率较高(与单期手术相比)。在G-SV中，单期手术具有避免临时造口的优点，但可能有较高的初始死亡率。受试者将在手术时被分配到两个研究组中的一个，G-SV或NG-SV。G-SV组的受试者将被随机分成单期或两期，NG-SV组的受试者将被随机分成单期或中乙状结肠固定术。本研究的目的是(1)确定单期或乙状结肠系膜固定术的NG-SV的死亡率差异(定义为存活到出院)；(2)确定单期和两期的G-SV的死亡率差异(定义为存活到无造口出院)；(3)确定术前结肠减压术对存活到出院的影响。

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.