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Journal: Journal of hepato-biliary-pancreatic sciences

28

Therapy with appropriate antimicrobial agents is an important component in the management of patients with acute cholangitis and/or acute cholecystitis. In the updated Tokyo Guidelines (TG13), we recommend antimicrobial agents that are suitable from a global perspective for management of these infections. These recommendations focus primarily on empirical therapy (presumptive therapy), provided before the infecting isolates are identified. Such therapy depends upon knowledge of both local microbial epidemiology and patient-specific factors that affect selection of appropriate agents. These patient-specific factors include prior contact with the health care system, and we separate community-acquired versus healthcare-associated infections because of the higher risk of resistance in the latter. Selection of agents for community-acquired infections is also recommended on the basis of severity (grades I-III). Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html .

Concepts: Medicine, Microbiology, Antimicrobial, Ascending cholangitis, Cholecystitis

28

We propose a management strategy for acute cholangitis and cholecystitis according to the severity assessment. For Grade I (mild) acute cholangitis, initial medical treatment including the use of antimicrobial agents may be sufficient for most cases. For non-responders to initial medical treatment, biliary drainage should be considered. For Grade II (moderate) acute cholangitis, early biliary drainage should be performed along with the administration of antibiotics. For Grade III (severe) acute cholangitis, appropriate organ support is required. After hemodynamic stabilization has been achieved, urgent endoscopic or percutaneous transhepatic biliary drainage should be performed. In patients with Grade II (moderate) and Grade III (severe) acute cholangitis, treatment for the underlying etiology including endoscopic, percutaneous, or surgical treatment should be performed after the patient’s general condition has been improved. In patients with Grade I (mild) acute cholangitis, treatment for etiology such as endoscopic sphincterotomy for choledocholithiasis might be performed simultaneously, if possible, with biliary drainage. Early laparoscopic cholecystectomy is the first-line treatment in patients with Grade I (mild) acute cholecystitis while in patients with Grade II (moderate) acute cholecystitis, delayed/elective laparoscopic cholecystectomy after initial medical treatment with antimicrobial agent is the first-line treatment. In non-responders to initial medical treatment, gallbladder drainage should be considered. In patients with Grade III (severe) acute cholecystitis, appropriate organ support in addition to initial medical treatment is necessary. Urgent or early gallbladder drainage is recommended. Elective cholecystectomy can be performed after the improvement of the acute inflammatory process.Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html .

Concepts: Medicine, Microbiology, Surgery, Hepatology, Laparoscopic surgery, Antimicrobial, Ascending cholangitis, Gallstone

28

While referring to the evidence adopted in the Tokyo Guidelines 2007 (TG07) as well as subsequently obtained evidence, further discussion took place on terminology, etiology, and epidemiological data. In particular, new findings have accumulated on the occurrence of symptoms in patients with gallstones, frequency of severe cholecystitis and cholangitis, onset of cholecystitis and cholangitis after endoscopic retrograde cholangiopancreatography and medications, mortality rate, and recurrence rate. The primary etiology of acute cholangitis/cholecystitis is the presence of stones. Next to stones, the most significant etiology of acute cholangitis is benign/malignant stenosis of the biliary tract. On the other hand, there is another type of acute cholecystitis, acute acalculous cholecystitis, in which stones are not involved as causative factors. Risk factors for acute acalculous cholecystitis include surgery, trauma, burn, and parenteral nutrition. After 2000, the mortality rate of acute cholangitis has been about 10 %, while that of acute cholecystitis has generally been less than 1 %. After the publication of TG07, diagnostic criteria and severity assessment criteria were standardized, and the distribution of cases according to severity and comparison of clinical data among target populations have become more subjective. The concept of healthcare-associated infections is important in the current treatment of infection. The treatment of acute cholangitis and cholecystitis substantially differs from that of community-acquired infections. Cholangitis and cholecystitis as healthcare-associated infections are clearly described in the updated Tokyo Guidelines (TG13).Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html .

Concepts: Epidemiology, Gastroenterology, Hepatology, Endoscopic retrograde cholangiopancreatography, Endoscopy, Primary sclerosing cholangitis, Ascending cholangitis, Cholecystitis

28

In 2007, the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07) were first published in the Journal of Hepato-Biliary-Pancreatic Surgery. The fundamental policy of TG07 was to achieve the objectives of TG07 through the development of consensus among specialists in this field throughout the world. Considering such a situation, validation and feedback from the clinicians' viewpoints were indispensable. What had been pointed out from clinical practice was the low diagnostic sensitivity of TG07 for acute cholangitis and the presence of divergence between severity assessment and clinical judgment for acute cholangitis. In June 2010, we set up the Tokyo Guidelines Revision Committee for the revision of TG07 (TGRC) and started the validation of TG07. We also set up new diagnostic criteria and severity assessment criteria by retrospectively analyzing cases of acute cholangitis and cholecystitis, including cases of non-inflammatory biliary disease, collected from multiple institutions. TGRC held meetings a total of 35 times as well as international email exchanges with co-authors abroad. On June 9 and September 6, 2011, and on April 11, 2012, we held three International Meetings for the Clinical Assessment and Revision of Tokyo Guidelines. Through these meetings, the final draft of the updated Tokyo Guidelines (TG13) was prepared on the basis of the evidence from retrospective multi-center analyses. To be specific, discussion took place involving the revised new diagnostic criteria, and the new severity assessment criteria, new flowcharts of the management of acute cholangitis and cholecystitis, recommended medical care for which new evidence had been added, new recommendations for gallbladder drainage and antimicrobial therapy, and the role of surgical intervention. Management bundles for acute cholangitis and cholecystitis were introduced for effective dissemination with the level of evidence and the grade of recommendations. GRADE systems were utilized to provide the level of evidence and the grade of recommendations. TG13 improved the diagnostic sensitivity for acute cholangitis and cholecystitis, and presented criteria with extremely low false positive rates adapted for clinical practice. Furthermore, severity assessment criteria adapted for clinical use, flowcharts, and many new diagnostic and therapeutic modalities were presented. The bundles for the management of acute cholangitis and cholecystitis are presented in a separate section in TG13.Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html .

Concepts: Clinical trial, Medical terms, Diagnosis, Surgery, Hepatology, Clinical psychology, Antimicrobial, Ascending cholangitis

27

Since its publication in 2007, the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07) have been widely adopted. The validation of TG07 conducted in terms of clinical practice has shown that the diagnostic criteria for acute cholecystitis are highly reliable but that the definition of definite diagnosis is ambiguous. Discussion by the Tokyo Guidelines Revision Committee concluded that acute cholecystitis should be suspected when Murphy’s sign, local inflammatory findings in the gallbladder such as right upper quadrant abdominal pain and tenderness, and fever and systemic inflammatory reaction findings detected by blood tests are present but that definite diagnosis of acute cholecystitis can be made only on the basis of the imaging of ultrasonography, computed tomography or scintigraphy (HIDA scan). These proposed diagnostic criteria provided better specificity and accuracy rates than the TG07 diagnostic criteria. As for the severity assessment criteria in TG07, there is evidence that TG07 resulted in clarification of the concept of severe acute cholecystitis. Furthermore, there is evidence that severity assessment in TG07 has led to a reduction in the mean duration of hospital stay. As for the factors used to establish a moderate grade of acute cholecystitis, such as leukocytosis, ALP, old age, diabetes, being male, and delay in admission, no new strong evidence has been detected indicating that a change in the criteria used in TG07 is needed. Therefore, it was judged that the severity assessment criteria of TG07 could be applied in the updated Tokyo Guidelines (TG13) with minor changes. TG13 presents new standards for the diagnosis, severity grading and management of acute cholecystitis.Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html .

Concepts: Inflammation, Diagnosis, Medical imaging, Abdominal pain, Hepatology, Murphy's sign, Ascending cholangitis, Cholecystitis

27

Bundles that define mandatory items or procedures to be performed in clinical practice have been increasingly used in guidelines in recent years. Observance of bundles enables improvement of the prognosis of target diseases as well as guideline preparation. There were no bundles adopted in the Tokyo Guidelines 2007, but the updated Tokyo Guidelines 2013 (TG13) have adopted this useful tool. Items or procedures strongly recommended in clinical practice have been prepared in the practical guidelines and presented as management bundles. TG13 defined the mandatory items for the management of acute cholangitis and acute cholecystitis. Critical parts of the bundles in TG13 include diagnostic process, severity assessment, transfer of patients if necessary, therapeutic approach, and time course. Their observance should improve the prognosis of acute cholangitis and cholecystitis. When utilizing TG13 management bundles, further clinical research needs to be conducted to evaluate the effectiveness and outcomes of the bundles. It is also expected that the present report will lead to evidence construction and contribute to further updating of the Tokyo Guidelines.Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html .

Concepts: Present, Medicine, Clinical trial, Clinical research, Ascending cholangitis, Cholecystitis

27

The Tokyo Guidelines of 2007 (TG07) described the techniques and recommendations of biliary decompression in patients with acute cholangitis. TG07 recommended that endoscopic transpapillary biliary drainage should be selected as a first-choice therapy for acute cholangitis because it is associated with a low mortality rate and shorter duration of hospitalization. However, TG07 did not include the whole technique of standard endoscopic transpapillary biliary drainage, for example, biliary cannulation techniques including contrast medium-assisted cannulation, wire-guided cannulation, and treatment of duodenal major papilla using endoscopic papillary balloon dilation (EPBD). Furthermore, recently single- or double-balloon enteroscopy-assisted biliary drainage (BE-BD) and endoscopic ultrasonography-guided biliary drainage (EUS-BD) have been reported as special techniques for biliary drainage. Nevertheless, the updated Tokyo Guidelines (TG13) recommends that endoscopic drainage should be first-choice treatment for biliary decompression in patients with non-surgically altered anatomy and suggests that the choice of cannulation technique or drainage method (endoscopic naso-biliary drainage and stenting) depends on the endoscopist’s preference but EST should be selected rather than EPBD from the aspect of procedure-related complications. In terms of BE-BD and EUS-BD, although there are many reports on the their usefulness, they should be performed by skilled endoscopists in high-volume institutes, who are good at enteroscopy or echoendosonography, respectively, because procedures and devices are not yet established.Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html .

Concepts: Mortality rate, Digestive system, Decompression sickness, Esophagogastroduodenoscopy, Endoscopy, Ascending cholangitis, Enteroscopy, Cholangitis

26

The most common postoperative complication after distal pancreatectomy (DP) is still postoperative pancreatic fistula (POPF), which is closely associated with other major complications and remains an unsolved problem.

23

An expert recommendation conference was conducted to identify factors associated with adverse events during laparoscopic cholecystectomy (LC) with the goal of deriving expert recommendations for the reduction of biliary and vascular injury. Nineteen hepato-pancreato-biliary (HPB) surgeons from high-volume surgery centers in six countries comprised the Research Institute Against Cancer of the Digestive System (IRCAD) Recommendations Group. Systematic search of PubMed, Cochrane, and Embase was conducted. Using nominal group technique, structured group meetings were held to identify key items for safer LC. Consensus was achieved when 80% of respondents ranked an item as 1 or 2 (Likert scale 1-4). Seventy-one IRCAD HPB course participants assessed the expert recommendations which were compared to responses of 37 general surgery course participants. The IRCAD recommendations were structured in seven statements. The key topics included exposure of the operative field, appropriate use of energy device and establishment of the critical view of safety (CVS), systematic preoperative imaging, cholangiogram and alternative techniques, role of partial and dome-down (fundus-first) cholecystectomy. Highest consensus was achieved on the importance of the CVS as well as dome-down technique and partial cholecystectomy as alternative techniques. The put forward IRCAD recommendations may help to promote safe surgical practice of LC and initiate specific training to avoid adverse events.

Concepts: Surgery, Surgeon, Digestion, Laparoscopic surgery, Cholecystectomy, Likert scale, Prime number, Gallstone

2

iPS-ML are myeloid lineage cells with a proliferative capacity derived from induced pluripotent stem (iPS) cells. This study aimed to examine therapeutic effect of iPS-ML producing interferon-β (iPS-ML/IFN-β) towards primary and metastatic liver cancer and investigate the mechanism of that effect.

Concepts: Cancer, Oncology, Stem cell, Therapy