In some cases, laparoscopic cholecystectomy (LC) may be difficult to perform in patients with acute cholecystitis (AC) with severe inflammation and fibrosis. The Tokyo Guidelines 2018 (TG18) expand ...the indications for LC under difficult conditions for each level of severity of AC. As a result of expanding the indications for LC to treat AC, it is absolutely necessary to avoid any increase in bile duct injury (BDI), particularly vasculo‐biliary injury (VBI), which is known to occur at a certain rate in LC. Since the Tokyo Guidelines 2013 (TG13), an attempt has been made to assess intraoperative findings as objective indicators of surgical difficulty; based on expert consensus on these difficulty indicators, bail‐out procedures (including conversion to open cholecystectomy) have been indicated for cases in which LC for AC is difficult to perform. A bail‐out procedure should be chosen if, when the Calot's triangle is appropriately retracted and used as a landmark, a critical view of safety (CVS) cannot be achieved because of the presence of nondissectable scarring or severe fibrosis. We propose standardized safe steps for LC to treat AC. To achieve a CVS, it is vital to dissect at a location above (on the ventral side of) the imaginary line connecting the base of the left medial section (Segment 4) and the roof of Rouvière's sulcus and to fulfill the three criteria of CVS before dividing any structures. Achieving a CVS prevents the misidentification of the cystic duct and the common bile duct, which are most commonly confused. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.
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A bail‐out procedure should be chosen to prevent bile duct injury if a critical view of safety (CVS) cannot be achieved because of the presence of nondissectable scarring or severe fibrosis.
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The prognosis of patients with metastatic colorectal cancer(m CRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median ...overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies(mo Abs) cetuximab and panitumumab, directed against the epidermal growth factor receptor(EGFR), undoubtedly represent a major step forward in the treatment of m CRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase Ⅲ clinical trials among different lines of treatment. However, the anti-EGFR mo Abs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary(or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-EGFR drugs biochemically converge into MEK-ERK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-EGFR mo Abs together with the various strategies evaluated to prevent, overcame or revert them.
The Tokyo Guidelines 2013 (TG13) for acute cholangitis and cholecystitis were globally disseminated and various clinical studies about the management of acute cholecystitis were reported by many ...researchers and clinicians from all over the world. The 1st edition of the Tokyo Guidelines 2007 (TG07) was revised in 2013. According to that revision, the TG13 diagnostic criteria of acute cholecystitis provided better specificity and higher diagnostic accuracy. Thorough our literature search about diagnostic criteria for acute cholecystitis, new and strong evidence that had been released from 2013 to 2017 was not found with serious and important issues about using TG13 diagnostic criteria of acute cholecystitis. On the other hand, the TG13 severity grading for acute cholecystitis has been validated in numerous studies. As a result of these reviews, the TG13 severity grading for acute cholecystitis was significantly associated with parameters including 30‐day overall mortality, length of hospital stay, conversion rates to open surgery, and medical costs. In terms of severity assessment, breakthrough and intensive literature for revising severity grading was not reported. Consequently, TG13 diagnostic criteria and severity grading were judged from numerous validation studies as useful indicators in clinical practice and adopted as TG18/TG13 diagnostic criteria and severity grading of acute cholecystitis without any modification. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.
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The TG13 for acute cholangitis and cholecystitis are widely used and clinical studies have been reported worldwide. Yokoe and colleagues conducted a literature review to confirm the clinical impact of the TG13 diagnostic criteria and severity grading of acute cholecystitis. As a result, the TG18/TG13 version was released without modification.
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We propose a new flowchart for the treatment of acute cholecystitis (AC) in the Tokyo Guidelines 2018 (TG18). Grade III AC was not indicated for straightforward laparoscopic cholecystectomy (Lap‐C). ...Following analysis of subsequent clinical investigations and drawing on Big Data in particular, TG18 proposes that some Grade III AC can be treated by Lap‐C when performed at advanced centers with specialized surgeons experienced in this procedure and for patients that satisfy certain strict criteria. For Grade I, TG18 recommends early Lap‐C if the patients meet the criteria of Charlson comorbidity index (CCI) ≤5 and American Society of Anesthesiologists physical status classification (ASA‐PS) ≤2. For Grade II AC, if patients meet the criteria of CCI ≤5 and ASA‐PS ≤2, TG18 recommends early Lap‐C performed by experienced surgeons; and if not, after medical treatment and/or gallbladder drainage, Lap‐C would be indicated. TG18 proposes that Lap‐C is indicated in Grade III patients with strict criteria. These are that the patients have favorable organ system failure, and negative predictive factors, who meet the criteria of CCI ≤3 and ASA‐PS ≤2 and who are being treated at an advanced center (where experienced surgeons practice). If the patient is not considered suitable for early surgery, TG18 recommends early/urgent biliary drainage followed by delayed Lap‐C once the patient's overall condition has improved. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.
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Okamoto and colleagues propose in the TG18 that some cases of Grade III acute cholecystitis that satisfy certain strict criteria in terms of predictive factor, Charlson Comorbidity Index, and American Society of Anesthesiologists physical status classification can be treated by laparoscopic cholecystectomy if performed at advanced centers by experienced surgeons.
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Although the diagnostic and severity grading criteria on the 2013 Tokyo Guidelines (TG13) are used worldwide as the primary standard for management of acute cholangitis (AC), they need to be ...validated through implementation and assessment in actual clinical practice. Here, we conduct a systematic review of the literature to validate the TG13 diagnostic and severity grading criteria for AC and propose TG18 criteria. While there is little evidence evaluating the TG13 criteria, they were validated through a large‐scale case series study in Japan and Taiwan. Analyzing big data from this study confirmed that the diagnostic rate of AC based on the TG13 diagnostic criteria was higher than that based on the TG07 criteria, and that 30‐day mortality in patients with a higher severity based on the TG13 severity grading criteria was significantly higher. Furthermore, a comparison of patients treated with early or urgent biliary drainage versus patients not treated this way showed no difference in 30‐day mortality among patients with Grade I or Grade III AC, but significantly lower 30‐day mortality in patients with Grade II AC who were treated with early or urgent biliary drainage. This suggests that the TG13 severity grading criteria can be used to identify Grade II patients whose prognoses may be improved through biliary drainage. The TG13 severity grading criteria may therefore be useful as an indicator for biliary drainage as well as a predictive factor when assessing the patient's prognosis. The TG13 diagnostic and severity grading criteria for AC can provide results quickly, are minimally invasive for the patients, and are inexpensive. We recommend that the TG13 criteria be adopted in the TG18 guidelines and used as standard practice in the clinical setting. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.
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Kiriyama and colleagues conducted a systematic review of the literature to validate the TG13 diagnostic and severity grading criteria for acute cholangitis. A large‐scale case series study in Japan and Taiwan served as the main basis for the validation. They recommend that the TG13 criteria be adopted in the TG18.
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Although minor laparoscopic liver resections (LLRs) appear as standardized procedures, major LLRs are still limited to few expert teams. The aim of this study was to report the combined data of 18 ...international centers performing major LLR. Variables evaluated were number and type of LLR, surgical indications, number of synchronous colorectal resections, details on technical points, conversion rates, operative time, blood loss and surgical margins. From 1996 to 2014, a total of 5388 LLR were carried out including 1184 major LLRs. The most frequent indication for laparoscopic right hepatectomy (LRH) was colorectal liver metastases (37.0%). Seven centers used hand assistance or hybrid approach selectively for LRH mostly at the beginning of their experience. Seven centers apply Pringle's maneuver routinely. The conversion rate for all major LLRs was 10% and mean operative time was 291 min. Mean estimated blood loss for all major LLR was 327 ml and negative surgical margin rate was 96.5%. Major LLRs still remain challenging procedures requiring important experience in both laparoscopy and liver surgery. Stimulating the younger generation to learn and accomplish these techniques is the better way to guarantee further development of this surgical field.
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The initial management of patients with suspected acute biliary infection starts with the measurement of vital signs to assess whether or not the situation is urgent. If the case is judged to be ...urgent, initial medical treatment should be started immediately including respiratory/circulatory management if required, without waiting for a definitive diagnosis. The patient's medical history is then taken; an abdominal examination is performed; blood tests, urinalysis, and diagnostic imaging are carried out; and a diagnosis is made using the diagnostic criteria for cholangitis/cholecystitis. Once the diagnosis has been confirmed, initial medical treatment should be started immediately, severity should be assessed according to the severity grading criteria for acute cholangitis/cholecystitis, and the patient's general status should be evaluated. For mild acute cholangitis, in most cases initial treatment including antibiotics is sufficient, and most patients do not require biliary drainage. However, biliary drainage should be considered if a patient does not respond to initial treatment. For moderate acute cholangitis, early endoscopic or percutaneous transhepatic biliary drainage is indicated. If the underlying etiology requires treatment, this should be provided after the patient's general condition has improved; endoscopic sphincterotomy and subsequent choledocholithotomy may be performed together with biliary drainage. For severe acute cholangitis, appropriate respiratory/circulatory management is required. Biliary drainage should be performed as soon as possible after the patient's general condition has been improved by initial treatment and respiratory/circulatory management. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.
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Miura and colleagues present the recommended initial management of acute biliary infection along with the TG18 flowchart for management of acute cholangitis. The section of the flowchart on management of moderate acute cholangitis has been revised from the corresponding TG13 flowchart. No other revisions have been made to the flowchart.
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Antimicrobial therapy is a mainstay of the management for patients with acute cholangitis and/or cholecystitis. The Tokyo Guidelines 2018 (TG18) provides recommendations for the appropriate use of ...antimicrobials for community‐acquired and healthcare‐associated infections. The listed agents are for empirical therapy provided before the infecting isolates are identified. Antimicrobial agents are listed by class‐definitions and TG18 severity grade I, II, and III subcategorized by clinical settings. In the era of emerging and increasing antimicrobial resistance, monitoring and updating local antibiograms is underscored. Prudent antimicrobial usage and early de‐escalation or termination of antimicrobial therapy are now important parts of decision‐making. What is new in TG18 is that the duration of antimicrobial therapy for both acute cholangitis and cholecystitis is systematically reviewed. Prophylactic antimicrobial usage for elective endoscopic retrograde cholangiopancreatography is no longer recommended and the section was deleted in TG18. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.
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Following a systematic review of the TG13 and consensus by the Tokyo Guidelines Revision Committee, Gomi and colleagues provide recommendations for antimicrobial agents for community‐acquired and healthcare‐associated acute cholangitis and cholecystitis. New in the TG18 is a systematic review of the duration of antimicrobial therapy for both cholangitis and cholecystitis.
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Management bundles that define items or procedures strongly recommended in clinical practice have been used in many guidelines in recent years. Application of these bundles facilitates the adaptation ...of guidelines and helps improve the prognosis of target diseases. In Tokyo Guidelines 2013 (TG13), we proposed management bundles for acute cholangitis and cholecystitis. Here, in Tokyo Guidelines 2018 (TG18), we redefine the management bundles for acute cholangitis and cholecystitis. Critical parts of the bundles in TG18 include the diagnostic process, severity assessment, transfer of patients if necessary, and therapeutic approach at each time point. Observance of these items and procedures should improve the prognosis of acute cholangitis and cholecystitis. Studies are now needed to evaluate the dissemination of these TG18 bundles and their effectiveness. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.
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Management bundles for acute cholangitis and cholecystitis were proposed for the first time in the TG13. In the TG18, Mayumi and colleagues redefine these management bundles. Critical parts of the bundles in the TG18 include the diagnostic process, severity assessment, transfer of patients, and therapeutic approach at each time point.
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