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.
Highlight
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.
Background and Aims
Intrahepatic cholangiocarcinoma (ICC) is a severe malignant tumor in which the standard therapies are mostly ineffective. The biological significance of the desmoplastic tumor ...microenvironment (TME) of ICC has been stressed but was insufficiently taken into account in the search for classifications of ICC adapted to clinical trial design. We investigated the heterogeneous tumor stroma composition and built a TME‐based classification of ICC tumors that detects potentially targetable ICC subtypes.
Approach and Results
We established the bulk gene expression profiles of 78 ICCs. Epithelial and stromal compartments of 23 ICCs were laser microdissected. We quantified 14 gene expression signatures of the TME and those of 3 functional indicators (liver activity, inflammation, immune resistance). The cell population abundances were quantified using the microenvironment cell population‐counter package and compared with immunohistochemistry. We performed an unsupervised TME‐based classification of 198 ICCs (training set) and 368 ICCs (validation set). We determined immune response and signaling features of the different immune subtypes by functional annotations. We showed that a set of 198 ICCs could be classified into 4 TME‐based subtypes related to distinct immune escape mechanisms and patient outcomes. The validity of these immune subtypes was confirmed over an independent set of 368 ICCs and by immunohistochemical analysis of 64 ICC tissue samples. About 45% of ICCs displayed an immune desert phenotype. The other subtypes differed in nature (lymphoid, myeloid, mesenchymal) and abundance of tumor‐infiltrating cells. The inflamed subtype (11%) presented a massive T lymphocyte infiltration, an activation of inflammatory and immune checkpoint pathways, and was associated with the longest patient survival.
Conclusion
We showed the existence of an inflamed ICC subtype, which is potentially treatable with checkpoint blockade immunotherapy.
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.
Highlight
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.
Summary
The purpose of this registry study was to provide an overview of trends and results of liver transplantation (LT) in Europe from 1968 to 2016. These data on LT were collected prospectively ...from 169 centers from 32 countries, in the European Liver Transplant Registry (ELTR) beginning in 1968. This overview provides epidemiological data, as well as information on evolution of techniques, and outcomes in LT in Europe over more than five decades; something that cannot be obtained from only a single center experience.
Hepatocellular adenomas (HCA) are rare benign liver tumors occurring in young women taking contraception. They are associated with rare complications such as bleeding or malignant transformation into ...hepatocellular carcinoma. A molecular classification has divided HCA in several subgroups linked with risk factors, clinical behaviour, histological features and imaging: HNF1A inactivated HCA, Inflammatory HCA, CTNNB1 mutated HCA in exon 3, CTNNB1 mutated in exon 7 and 8 HCA, sonic hedgehog HCA and unclassified HCA. CTNNB1 mutated HCA in exon 3 and sonic hedgehog HCA have been linked with a high risk of malignant transformation and bleeding respectively. Herein, we review how molecular classification has modified our understanding of the pathophysiology and risk factors of HCA development, analysing its impact on clinical care in the field of diagnosis and therapeutic stratification.
Somatic mutations activating telomerase reverse-trancriptase promoter were recently identified in several tumour types. Here we identify frequent similar mutations in human hepatocellular carcinomas ...(59%), cirrhotic preneoplastic macronodules (25%) and hepatocellular adenomas with malignant transformation in hepatocellular carcinomas (44%). In hepatocellular tumours, telomerase reverse-transcripase- and CTNNB1-activating mutations are significantly associated. Moreover, preliminary data suggest that telomerase reverse-trancriptase promoter mutations can increase the expression of telomerase transcript. In conclusion, telomerase reverse-trancriptase promoter mutation is the earliest recurrent genetic event identified in cirrhotic preneoplastic lesions so far and is also the most frequent genetic alteration in hepatocellular carcinomas, arising from both the cirrhotic or non-cirrhotic liver.
Background
Laparoscopic liver resection is considered a safe and feasible alternative to open surgery for malignant liver lesions. However, laparoscopic surgery in cirrhotic patients remains ...challenging. The aim of this retrospective case–control study was to compare morbidity, mortality, and long-term patient survival between laparoscopic liver resections (LLR) and open liver resections (OLR) for hepatocellular carcinoma (HCC) in patients with histologically proven cirrhosis.
Methods
A total of 45 patients treated with LLR were matched by cause of cirrhosis, Child-Pugh score, type of surgical resection (subsegmentectomy, segmentectomy, and bisegmentectomy), tumor number, tumor size, and alpha-fetoprotein value with 45 patients treated with OLR. Pre-, intra-, and post-operative variables were compared between groups.
Results
Compared with OLR, the LLR group displayed a significantly shorter operative time (140 vs. 180 min;
p
= 0.02), shorter hospital stay (7 vs. 12 days;
p
< 0.0001), and lower morbidity rate (20 vs. 45 % of patients;
p
= 0.01). A higher rate of R0 resection was observed in the LLR group than in the OLR group (95 vs. 85 %;
p
= 0.03). Postoperative ascites was more frequently observed in the OLR group (18 vs. 2 %;
p
= 0.01). Mortality, patient, and disease-free survival rates were similar between groups. The 1-, 5-, and 10-year survival rates were 88, 59, and 12 %, respectively, in the LLR group and 63, 44, and 22 % in the OLR group (
p
= 0.27).
Conclusions
Significantly shorter operative times, better resection margins, lower postoperative complications, and shorter hospital stay were observed in the LLR group compared with the OLR group. LLR and OLR have similar overall and disease-free survival rates in cirrhotic HCC patients.
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.
Highlight
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.
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.
Highlight
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.
This multicenter study compares the outcomes of patients with cirrhosis undergoing liver transplantation (LT) or liver resection (LR) between January 2002 and July 2015 who had intrahepatic ...cholangiocarcinoma (iCCA) or combined hepatocellular‐cholangiocarcinoma (cHCC‐CCA) found incidentally in the native liver. A total of 49 (65%) LT and 26 (35%) LR patients with cirrhosis and histologically confirmed iCCA/cHCC‐CCA ≤5 cm were retrospectively analyzed. LT patients had significantly lower tumor recurrence (18% versus 46%; P = 0.01), for which the median diameter of the largest nodule (hazard ratio HR, 1.07; 95% confidence interval CI, 1.02‐1.12; P = 0.006) and tumor differentiation (HR, 3.74; 95% CI 1.71‐8.17; P = 0.001) were independently predictive. The LT group had significantly higher 5‐year recurrence‐free survival (RFS; 75% versus 36%; P = 0.004). In patients with tumors >2 cm but ≤5 cm, LT patients had a lower recurrence rate (21% versus 48%; P = 0.06) and a higher 5‐year RFS (74% versus 40%; P = 0.06). Independent risk factors for recurrence were LT (protective; HR, 0.23; 95% CI, 0.07‐0.82; P = 0.02), the median diameter of the largest nodule (HR, 1.10; 95% CI, 1.02‐1.73; P = 0.007), and tumor differentiation (HR, 4.16; 95% CI, 1.37‐12.66; P = 0.01). In the LT group, 5‐year survival reached 69% and 65% (P = 0.40) in patients with tumors ≤2 cm and >2‐5 cm, respectively, and survival was also comparable between iCCA and cHCC‐CCA patients (P = 0.29). LT may offer a benefit for highly selected patients with cirrhosis and unresectable iCCA/cHCC‐CCA having tumors ≤5 cm. Efforts should be made to evaluate tumor differentiation, and these results need to be confirmed prospectively in a larger population.
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