• GIP-Overexpressing Mice Demonstrate Reduced Diet-Induced Obesity and Steatosis, and Improved Glucose Homeostasis

      Kim, Su-Jin; Nian, Cuilan; Karunakaran, Subashini; Clee, Susanne M.; Isales, Carlos M.; McIntosh, Christopher H. S.; Department of Orthopaedic Surgery; Department of Cellular Biology and Anatomy (2012-07-3)
      Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that potentiates glucose-stimulated insulin secretion during a meal. Since GIP has also been shown to exert b-cell prosurvival and adipocyte lipogenic effects in rodents, both GIP receptor agonists and antagonists have been considered as potential therapeutics in type 2 diabetes (T2DM). In the present study, we tested the hypothesis that chronically elevating GIP levels in a transgenic (Tg) mouse model would increase adipose tissue expansion and exert beneficial effects on glucose homeostasis. In contrast, although GIP Tg mice demonstrated enhanced b-cell function, resulting in improved glucose tolerance and insulin sensitivity, they exhibited reduced diet-induced obesity. Adipose tissue macrophage infiltration and hepatic steatosis were both greatly reduced, and a number of genes involved in lipid metabolism/inflammatory signaling pathways were found to be down-regulated. Reduced adiposity in GIP Tg mice was associated with decreased energy intake, involving overexpression of hypothalamic GIP. Together, these studies suggest that, in the context of over-nutrition, transgenic GIP overexpression has the potential to improve hepatic and adipocyte function as well as glucose homeostasis.
    • Bilateral Hand-Assisted Laparoscopic Renal Surgery in the Supine Position: The Spleen at Risk

      Brown, James A.; Siddiqi, Kashif; Department of Surgery (2011)
      Objective
    • Ureteral Clipping Simplifies Hand-Assisted Laparoscopic Donor Nephrectomy

      Brown, James A.; Sajadi, Kamran P.; Wynn, James J.; Department of Surgery (2010)
      Objectives
    • Laparoscopic right paraduodenal hernia repair

      Bittner, James G.; Department of Surgery (2010)
      Letter To Editor
    • Regarding diagnosis and management of Spigelian hernia.

      Bittner, James G.; Department of Surgery (2009-6-26)
    • Three-dimensional visualisation and articulating instrumentation: Impact on simulated laparoscopic tasks.

      Bittner, James G.; Hathaway, Christopher A; Brown, James A.; Virtual Education and Surgical Simulation Laboratory (VESSL), Section of Urology, Department of Surgery, Medical College of Georgia; Department of Surgery (2009-6-26)
      Laparoscopy requires the development of technical skills distinct from those used in open procedures. Several factors extending the learning curve of laparoscopy include ergonomic and technical difficulties, such as the fulcrum effect and limited degrees of freedom. This study aimed to establish the impact of four variables on performance of two simulated laparoscopic tasks. METHODS: Six subjects including novice (n=2), intermediate (n=2) and expert surgeons completed two tasks: 1) four running sutures, 2) simple suture followed by surgeon's knot plus four square knots. Task variables were suturing angle (left/right), needle holder type (standard/articulating) and visualisation (2D/3D). Each task with a given set of variables was completed twice in random order. The endpoints included suturing task completion time, average and maximum distance from marks and knot tying task completion time. RESULTS: Suturing task completion time was prolonged by 45-degree right angle suturing, articulating needle holder use and lower skill levels (all P < 0.0001). Accuracy also decreased with articulating needle holder use (both P < 0.0001). 3D vision affected only maximum distance (P=0.0108). For the knot tying task, completion time was greater with 45-degree right angle suturing (P=0.0015), articulating needle holder use (P < 0.0001), 3D vision (P=0.0014) and novice skill level (P=0.0003). Participants felt that 3D visualisation offered subjective advantages during training. CONCLUSIONS: Results suggest construct validity. A 3D personal head display and articulating needle holder do not immediately improve task completion times or accuracy and may increase the training burden of laparoscopic suturing and knot tying.
    • Sex cord-gonadal stromal tumor of the rete testis.

      Sajadi, Kamran P.; Dalton, Rory R; Brown, James A.; Department of Surgery; Department of Pathology (2009-01-06)
      A 34-year-old tetraplegic patient with suppurative epididymitis was found on follow-up examination and ultrasonography to have a testicular mass. The radical orchiectomy specimen contained an undifferentiated spindled sex cord-stromal tumor arising in the rete testis. Testicular sex cord-stromal tumors are far less common than germ cell neoplasms and are usually benign. The close relationship between sex cords and ductules of the rete testis during development provides the opportunity for these uncommon tumors to arise anatomically within the rete tesis. This undifferentiated sex cord-stromal tumor, occurring in a previously unreported location, is an example of an unusual lesion mimicking an intratesticular malignant neoplasm.
    • Laparoscopic Repair of a Right Paraduodenal Hernia

      Bittner, James G.; Edwards, Michael A.; Harrison, Steven J.; Li, Kelvin; Karmin, Paul N.; Mellinger, John D.; Department of Surgery; Department of Medical Illustration; Department of Radiology (2009)
      Background and Objectives
    • Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines.

      Kimura, Yasutoshi; Takada, Tadahiro; Kawarada, Yoshifumi; Nimura, Yuji; Hirata, Koichi; Sekimoto, Miho; Yoshida, Masahiro; Mayumi, Toshihiko; Wada, Keita; Miura, Fumihiko; et al. (2007-01-25)
      This article discusses the definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis. Acute cholangitis and cholecystitis mostly originate from stones in the bile ducts and gallbladder. Acute cholecystitis also has other causes, such as ischemia; chemicals that enter biliary secretions; motility disorders associated with drugs; infections with microorganisms, protozoa, and parasites; collagen disease; and allergic reactions. Acute acalculous cholecystitis is associated with a recent operation, trauma, burns, multisystem organ failure, and parenteral nutrition. Factors associated with the onset of cholelithiasis include obesity, age, and drugs such as oral contraceptives. The reported mortality of less than 10% for acute cholecystitis gives an impression that it is not a fatal disease, except for the elderly and/or patients with acalculous disease. However, there are reports of high mortality for cholangitis, although the mortality differs greatly depending on the year of the report and the severity of the disease. Even reports published in and after the 1980s indicate high mortality, ranging from 10% to 30% in the patients, with multiorgan failure as a major cause of death. Because many of the reports on acute cholecystitis and cholangitis use different standards, comparisons are difficult. Variations in treatment and risk factors influencing the mortality rates indicate the necessity for standardized diagnostic, treatment, and severity assessment criteria.
    • Need for criteria for the diagnosis and severity assessment of acute cholangitis and cholecystitis: Tokyo Guidelines.

      Sekimoto, Miho; Takada, Tadahiro; Kawarada, Yoshifumi; Nimura, Yuji; Yoshida, Masahiro; Mayumi, Toshihiko; Miura, Fumihiko; Wada, Keita; Hirota, Masahiko; Yamashita, Yuichi; et al. (2007-01-25)
      The Tokyo Guidelines formulate clinical guidance for healthcare providers regarding the diagnosis, severity assessment, and treatment of acute cholangitis and acute cholecystitis. The Guidelines were developed through a comprehensive literature search and selection of evidence. Recommendations were based on the strength and quality of evidence. Expert consensus opinion was used to enhance or formulate important areas where data were insufficient. A working group, composed of gastroenterologists and surgeons with expertise in biliary tract surgery, supplemented with physicians in critical care medicine, epidemiology, and laboratory medicine, was selected to formulate draft guidelines. Several other groups (including members of the Japanese Society for Abdominal Emergency Medicine, the Japan Biliary Association, and the Japanese Society of Hepato-Biliary-Pancreatic Surgery) have reviewed and revised the draft guidelines. To build a global consensus on the management of acute biliary infection, an international expert panel, representing experts in this area, was established. Between April 1 and 2, 2006, an International Consensus Meeting on acute biliary infections was held in Tokyo. A consensus was determined based on best available scientific evidence and discussion by the panel of experts. This report describes the highlights of the Tokyo International Consensus Meeting in 2006. Some important areas focused on at the meeting include proposals for internationally accepted diagnostic criteria and severity assessment for both clinical and research purposes.
    • Background: Tokyo Guidelines for the management of acute cholangitis and cholecystitis.

      Takada, Tadahiro; Kawarada, Yoshifumi; Nimura, Yuji; Yoshida, Masahiro; Mayumi, Toshihiko; Sekimoto, Miho; Miura, Fumihiko; Wada, Keita; Hirota, Masahiko; Yamashita, Yuichi; et al. (2007-01-25)
      There are no evidence-based-criteria for the diagnosis, severity assessment, of treatment of acute cholecystitis or acute cholangitis. For example, the full complement of symptoms and signs described as Charcot's triad and as Reynolds' pentad are infrequent and as such do not really assist the clinician with planning management strategies. In view of these factors, we launched a project to prepare evidence-based guidelines for the management of acute cholangitis and cholecystitis that will be useful in the clinical setting. This research has been funded by the Japanese Ministry of Health, Labour, and Welfare, in cooperation with the Japanese Society for Abdominal Emergency Medicine, the Japan Biliary Association, and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. A working group, consisting of 46 experts in gastroenterology, surgery, internal medicine, emergency medicine, intensive care, and clinical epidemiology, analyzed and examined the literature on patients with cholangitis and cholecystitis in order to produce evidence-based guidelines. During the investigations we found that there was a lack of high-level evidence, for treatments, and the working group formulated the guidelines by obtaining consensus, based on evidence categorized by level, according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence of May 2001 (version 1). This work required more than 20 meetings to obtain a consensus on each item from the working group. Then four forums were held to permit examination of the Guideline details in Japan, both by an external assessment committee and by the working group participants (version 2). As we knew that the diagnosis and management of acute biliary infection may differ from country to country, we appointed a publication committee and held 12 meetings to prepare draft Guidelines in English (version 3). We then had several discussions on these draft guidelines with leading experts in the field throughout the world, via e-mail, leading to version 4. Finally, an International Consensus Meeting took place in Tokyo, on 1-2 April, 2006, to obtain international agreement on diagnostic criteria, severity assessment, and management.
    • Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines.

      Wada, Keita; Takada, Tadahiro; Kawarada, Yoshifumi; Nimura, Yuji; Miura, Fumihiko; Yoshida, Masahiro; Mayumi, Toshihiko; Strasberg, Steven M; Pitt, Henry A; Gadacz, Thomas R; et al. (2007-01-25)
      Because acute cholangitis sometimes rapidly progresses to a severe form accompanied by organ dysfunction, caused by the systemic inflammatory response syndrome (SIRS) and/or sepsis, prompt diagnosis and severity assessment are necessary for appropriate management, including intensive care with organ support and urgent biliary drainage in addition to medical treatment. However, because there have been no standard criteria for the diagnosis and severity assessment of acute cholangitis, practical clinical guidelines have never been established. The aim of this part of the Tokyo Guidelines is to propose new criteria for the diagnosis and severity assessment of acute cholangitis based on a systematic review of the literature and the consensus of experts reached at the International Consensus Meeting held in Tokyo 2006. Acute cholangitis can be diagnosed if the clinical manifestations of Charcot's triad, i.e., fever and/or chills, abdominal pain (right upper quadrant or epigastric), and jaundice are present. When not all of the components of the triad are present, then a definite diagnosis can be made if laboratory data and imaging findings supporting the evidence of inflammation and biliary obstruction are obtained. The severity of acute cholangitis can be classified into three grades, mild (grade I), moderate (grade II), and severe (grade III), on the basis of two clinical factors, the onset of organ dysfunction and the response to the initial medical treatment. "Severe (grade III)" acute cholangitis is defined as acute cholangitis accompanied by at least one new-onset organ dysfunction. "Moderate (grade II)" acute cholangitis is defined as acute cholangitis that is unaccompanied by organ dysfunction, but that does not respond to the initial medical treatment, with the clinical manifestations and/or laboratory data not improved. "Mild (grade I)" acute cholangitis is defined as acute cholangitis that responds to the initial medical treatment, with the clinical findings improved.
    • Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines.

      Miura, Fumihiko; Takada, Tadahiro; Kawarada, Yoshifumi; Nimura, Yuji; Wada, Keita; Hirota, Masahiko; Nagino, Masato; Tsuyuguchi, Toshio; Mayumi, Toshihiko; Yoshida, Masahiro; et al. (2007-01-25)
      Diagnostic and therapeutic strategies for acute biliary inflammation/infection (acute cholangitis and acute cholecystitis), according to severity grade, have not yet been established in the world. Therefore we formulated flowcharts for the management of acute biliary inflammation/infection in accordance with severity grade. For mild (grade I) acute cholangitis, medical treatment may be sufficient/appropriate. For moderate (grade II) acute cholangitis, early biliary drainage should be performed. For severe (grade III) acute cholangitis, appropriate organ support such as ventilatory/circulatory management is required. After hemodynamic stabilization is achieved, urgent endoscopic or percutaneous transhepatic biliary drainage should be performed. For patients with acute cholangitis of any grade of severity, treatment for the underlying etiology, including endoscopic, percutaneous, or surgical treatment should be performed after the patient's general condition has improved. For patients with mild (grade I) cholecystitis, early laparoscopic cholecystectomy is the preferred treatment. For patients with moderate (grade II) acute cholecystitis, early laparoscopic or open cholecystectomy is preferred. In patients with extensive local inflammation, elective cholecystectomy is recommended after initial management with percutaneous gallbladder drainage and/or cholecystostomy. For the patient with severe (grade III) acute cholecystitis, multiorgan support is a critical part of management. Biliary peritonitis due to perforation of the gallbladder is an indication for urgent cholecystectomy and/or drainage. Delayed elective cholecystectomy may be performed after initial treatment with gallbladder drainage and improvement of the patient's general medical condition.
    • Diagnostic criteria and severity assessment of acute cholecystitis: Tokyo Guidelines.

      Hirota, Masahiko; Takada, Tadahiro; Kawarada, Yoshifumi; Nimura, Yuji; Miura, Fumihiko; Hirata, Koichi; Mayumi, Toshihiko; Yoshida, Masahiro; Strasberg, Steven M; Pitt, Henry A; et al. (2007-01-25)
      The aim of this article is to propose new criteria for the diagnosis and severity assessment of acute cholecystitis, based on a systematic review of the literature and a consensus of experts. A working group reviewed articles with regard to the diagnosis and treatment of acute cholecystitis and extracted the best current available evidence. In addition to the evidence and face-to-face discussions, domestic consensus meetings were held by the experts in order to assess the results. A provisional outcome statement regarding the diagnostic criteria and criteria for severity assessment was discussed and finalized during an International Consensus Meeting held in Tokyo 2006. Patients exhibiting one of the local signs of inflammation, such as Murphy's sign, or a mass, pain or tenderness in the right upper quadrant, as well as one of the systemic signs of inflammation, such as fever, elevated white blood cell count, and elevated C-reactive protein level, are diagnosed as having acute cholecystitis. Patients in whom suspected clinical findings are confirmed by diagnostic imaging are also diagnosed with acute cholecystitis. The severity of acute cholecystitis is classified into three grades, mild (grade I), moderate (grade II), and severe (grade III). Grade I (mild acute cholecystitis) is defined as acute cholecystitis in a patient with no organ dysfunction and limited disease in the gallbladder, making cholecystectomy a low-risk procedure. Grade II (moderate acute cholecystitis) is associated with no organ dysfunction but there is extensive disease in the gallbladder, resulting in difficulty in safely performing a cholecystectomy. Grade II disease is usually characterized by an elevated white blood cell count; a palpable, tender mass in the right upper abdominal quadrant; disease duration of more than 72 h; and imaging studies indicating significant inflammatory changes in the gallbladder. Grade III (severe acute cholecystitis) is defined as acute cholecystitis with organ dysfunction.