Correlation between Cancer Stem Cells, Inflammation and Malignant Transformation in a DEN-Induced Model of Hepatic Carcinogenesis.

Chronic inflammation and cancer stem cells are known risk factors for tumorigenesis. The aetiology of hepatocellular carcinoma (HCC) involves a multistep pathological process that is characterised by chronic inflammation and hepatocyte damage, but the correlation between HCC, inflammation and cancer stem cells remains unclear. In this study, we examined the role of hepatic progenitor cells in a mouse model of chemical-induced hepatocarcinogenesis to elucidate the relationship between inflammation, malignant transformation and cancer stem cells. We used diethylnitrosamine (DEN) to induce liver tumour and scored for H&E and reticulin staining. We also scored for immunohistochemistry staining for OV-6 expression and analysed the statistical correlation between them. DEN progressively induced inflammation at week 7 (40%, 2/5); week 27 (75%, 6/8); week 33 (62.5%, 5/8); and week 50 (100%, 12/12). DEN progressively induced malignant transformation at week 7 (0%, 0/5); week 27 (87.5%, 7/8); week 33 (100%, 8/8); and week 50 (100%, 12/12). The obtained data showed that DEN progressively induced high-levels of OV-6 expression at week 7 (20%, 1/5); week 27 (37.5%, 3/8); week 33 (50%, 4/8); and week 50 (100%, 12/12). DEN-induced inflammation, malignant transformation and high-level OV-6 expression in hamster liver, as shown above, as well as applying Spearman's correlation to the data showed that the expression of OV-6 was significantly correlated to inflammation (p = 0.001) and malignant transformation (p < 0.001). There was a significant correlation between the number of cancer stem cells, inflammation and malignant transformation in a DEN-induced model of hepatic carcinogenesis in the hamster.

Patient assessment of diabetes care in a pay-for-performance program.

OBJECTIVE: Few studies address quality of care in pay-for-performance (P4P) programs from the perspective of patients' perceptions. This study aimed to examine and compare the patient assessment of diabetes chronic care as perceived by diabetic patients enrolled and not enrolled in a P4P program from the patients' self-reported perspectives. DESIGN: A cross-sectional study with case and comparison group design. SETTING: A large-scale survey was conducted from February to November 2013 in 18 healthcare institutions in Taiwan. PARTICIPANTS: A total of 1458 P4P (n = 1037) and non-P4P (n = 421) diabetic patients participated in this large survey. The Chinese version of the Patient Assessment of Chronic Illness Care (PACIC) instrument was used and patients' clinical outcome data (e.g. HbA1c, LDL) were collected. INTERVENTION: None. MAIN OUTCOME MEASURES: Five subscales from the PACIC were measured, including patient activation, delivery system design/system support, goal setting/tailoring, problem solving/contextual and follow-up/coordination. Patient clinical outcomes were also measured. Multiple linear regression and logistic regression models were used and controlled for patient demographic and health institution characteristics statistically. RESULTS: After adjusting for covariates, P4P patients had higher overall scores on the PACIC and five subscales than non-P4P patients. P4P patients also had better clinical processes of care (e.g. HbA1c test) and intermediate outcomes. CONCLUSIONS: Patients who participated in the program likely received better patient-centered care given the original Chronic Care Model. Better perceptions of diabetic care assessment also better clinical outcomes. The PACIC instrument can be used for the patient assessment of chronic care in a P4P program.

Endoscopic intramural cystogastrostomy for treatment of peripancreatic fluid collection: A viewpoint from a surgeon.

Percutaneous or endoscopic drainage is the initial choice for the treatment of peripancreatic fluid collection in symptomatic patients. Endoscopic transgastric fenestration (ETGF) was first reported for the management of pancreatic pseudocysts of 20 patients in 2008. From a surgeon's viewpoint, ETGF is a similar procedure to cystogastrostomy in that they both produce a wide outlet orifice for the drainage of fluid and necrotic debris. ETGF can be performed at least 4 wk after the initial onset of acute pancreatitis and it has a high priority over the surgical approach. However, the surgical approach usually has a better success rate because surgical cystogastrostomy has a wider outlet (> 6 cm vs 2 cm) than ETGF. However, percutaneous or endoscopic drainage, ETGF, and surgical approach offer various treatment options for peripancreatic fluid collection patients based on their conditions.

Network meta-analysis of the prognosis of curative treatment strategies for recurrent hepatocellular carcinoma after hepatectomy.

BACKGROUND: Recurrent hepatocellular carcinoma (rHCC) is a common outcome after curative treatment. Retreatment for rHCC is recommended, but no guidelines exist. AIM: To compare curative treatments such as repeated hepatectomy (RH), radiofrequency ablation (RFA), transarterial chemoembolization (TACE) and liver transplantation (LT) for patients with rHCC after primary hepatectomy by conducting a network meta-analysis (NMA). METHODS: From 2011 to 2021, 30 articles involving patients with rHCC after primary liver resection were retrieved for this NMA. The Q test was used to assess heterogeneity among studies, and Egger's test was used to assess publication bias. The efficacy of rHCC treatment was assessed using disease-free survival (DFS) and overall survival (OS). RESULTS: From 30 articles, a total of 17, 11, 8, and 12 arms of RH, RFA, TACE, and LT subgroups were collected for analysis. Forest plot analysis revealed that the LT subgroup had a better cumulative DFS and 1-year OS than the RH subgroup, with an odds ratio (OR) of 0.96 (95%CI: 0.31-2.96). However, the RH subgroup had a better 3-year and 5-year OS compared to the LT, RFA, and TACE subgroups. Hierarchic step diagram of different subgroups measured by the Wald test yielded the same results as the forest plot analysis. LT had a better 1-year OS (OR: 1.04, 95%CI: 0.34-03.20), and LT was inferior to RH in 3-year OS (OR: 10.61, 95%CI: 0.21-1.73) and 5-year OS (OR: 0.95, 95%CI: 0.39-2.34). According to the predictive P score evaluation, the LT subgroup had a better DFS, and RH had the best OS. However, meta-regression analysis revealed that LT had a better DFS (P < 0.001) as well as 3-year OS (P = 0.881) and 5-year OS (P = 0.188). The differences in superiority between DFS and OS were due to the different testing methods used. CONCLUSION: According to this NMA, RH and LT had better DFS and OS for rHCC than RFA and TACE. However, treatment strategies should be determined by the recurrent tumor characteristics, the patient's general health status, and the care program at each institution.

Risk factors for the development of metachronous liver metastasis in colorectal cancer patients after curative resection.

BACKGROUND: Metachronous liver metastasis (MLM) occurs in 20-40% of colorectal cancer (CRC) patients following surgical treatment. The aim of the present study was to determine the risk factors affecting the development of MLM in CRC patients following curative resection. METHODS: A total of 1,356 patients who underwent curative intent resection for CRC were retrospectively studied. Of these patients, those who with 30 days postoperative mortality (n=23), incomplete medical record (n=32), synchronous liver metastasis (n=148) and UICC stage IV (n=54) were excluded, and finally 1,099 patients were analyzed, including 977 patients without liver metastasis and 122 patients with MLM-only. Clinical and pathological records for each patient were reviewed from medical charts. The clinicopathologic characteristics of 1,099 patients were investigated. RESULTS: The median timing of developing MLM was 13 months with a range of 4 to 79 months. Univariate analysis identified that preoperative serum carcinoembryonic antigen (CEA) level, depth of invasion, lymph nodes metastasis, vascular invasion, and perineural invasion were significantly correlated with the development of MLM (all P<0.05). Meanwhile, a multivariate analysis showed that preoperative serum carcinoembryonic antigen (CEA) level>5 ng/ml (Odds Ratio [OR]=1.591; 95% Confidence Interval [CI], 1.065-2.377; P=0.024), tumor depth (OR=2.294; 95% CI, 1.103-4.768; P=0.026), positive lymph node metastasis (OR=2.004; 95% CI, 1.324-3.031; P=0.001) and positive vascular invasion (OR=1.872; 95% CI, 1.225-2.861; P=0.004) were independent prognostic factors contributing to the occurrence of MLM. CONCLUSIONS: The present study demonstrates that preoperative serum CEA level, tumor depth, lymph node metastasis, and positive vascular invasion could affect the occurrence of MLM in CRC patients following curative resection, and thus could help to define these high-risk patients who would benefit from enhanced surveillance and therapeutic program(s).

CKS1B overexpression implicates clinical aggressiveness of hepatocellular carcinomas but not p27(Kip1) protein turnover: an independent prognosticator with potential p27 (Kip1)-independent oncogenic attributes?

BACKGROUND: Through data mining the Stanford Microarray Database, the CKS1B transcript was found to be frequently upregulated in hepatocellular carcinomas (HCCs) with low alpha-fetal protein (AFP) expression. Together with SKP2, CKS1B is known to implicate p27(Kip1) protein turnover promoting cell-cycle progression. METHODS: CKS1B, p27(Kip1), and SKP2 were immunostained in 75 HCCs and correlated with clinicopathological features, local recurrence-free survival (LRFS), and overall survival (OS). Silencing of CKS1B and SKP2 with interference short-hairpin RNA (shRNA) was performed in SK-Hep1 and Hep-3B cell lines. RESULTS: Immunohistochemically, increased CKS1B and SKP2, and attenuated p27(Kip1) were all associated with tumor multiplicity (P < 0.05) and increasing American Joint Committee on Cancer (AJCC) stage (P < 0.05). Overexpression of CKS1B significantly correlated with advanced Okuda stages (P = 0.048) and SKP2 overexpression (P = 0.047). Neither CKS1B nor SKP2 was inversely related to p27(Kip1), which was reinforced by no alteration in p27(Kip1) abundance in HCC-derived cells with CKS1B or SKP2 silencing. Both CKS1B overexpression (P = 0.0011 and P = 0.0017) and p27(Kip1) attenuation (P = 0.0079 and P = 0.0085) were predictive of OS and LRFS, respectively, while SKP2 overexpression was associated with worse OS alone (P = 0.0043). Combined assessment of CKS1B and p27(Kip1) was able to robustly distinguish three prognostically different groups (P < 0.0001). In multivariate comparison, CKS1B overexpression represented the strongest independent adverse prognosticator [OS, P = 0.0235, hazard ratio (HR): 4.193; LRFS, P = 0.0204, HR: 4.262], followed by p27(Kip1) attenuation (OS, P = 0.0320, HR: 2.553; LRFS, P = 0.0262, HR: 2.533). CONCLUSIONS: CKS1B protein overexpression in HCCs is implicated in clinical aggressiveness but not in p27(Kip1) turnover, implying presence of p27(Kip1)-independent oncogenic attributes. The combined assessment of CKS1B and p27(Kip1) immunoexpressions effectively risk-stratifies HCCs with different prognoses, which may aid in the management of this deadly malignancy.

Progesterone increases epirubicin's apoptotic effects in HepG2 cells by S phase cell cycle arrest.

BACKGROUND/AIMS: The use of chemotherapy in hepatocellular carcinoma is still controversial. The aim of this study was to investigate whether the combined use of epirubicin and progesterone has a synergistic effect on cell proliferation and apoptosis in HepG2 cells. METHODOLOGY: Different concentrations of epirubicin (0.1 microg/ml, 0.25 microg/ml and 0.5microg/ml) or progesterone (12.5 microM, 25 microM and 50 microM) were added to HepG2 cells either alone or in combinations consisting of different concentrations of the two. Their effects on HepG2 cells were studied by (1) XTT assay for analysis of cell proliferation, (2) 3H-Thymidine incorporation for DNA synthesis, (3) annexin V-FITC/ propidium iodide (PI) flowcytometery for cell apoptosis, (4) flowcytometry for cell cycle distributions, and (5) reverse transcription-polymerase chain reaction for expression of cell cycle modulator, cyclin D1. RESULTS: 50 microM progesterone increased both the cytotoxic and apoptotic effects of 0.1 microg/ml epirubicin on HepG2 cells at 48 hr culture due to 50 microM progesterone accumulated cells in S phase of the cell cycle and subsequently reduced cyclin D1 expression. These effects on HepG2 cells induced by this combination were comparable to those induced by 0.5 microg/ml epirubicin alone. CONCLUSIONS: In vitro, progesterone can increase the cytotoxicity and apoptosis induced by epirubicin on HepG2 cells.

Decreased retinol binding protein 4 concentrations are associated with cholesterol gallstone disease.

BACKGROUND/PURPOSE: Circulating retinol binding protein 4 (RBP4) is associated with a variety of obesity-related diseases. This study investigated whether there were aberrant concentrations of RBP4 in cholesterol gallstone disease. METHODS: Serum RBP4 levels of 100 cholesterol gallstone patients and 147 healthy controls were measured by enzyme-linked immunosorbent assay and further correlated with clinical and biochemical characteristics, including insulin resistance and renal function. Gallstone specimens were obtained during laparoscopic cholecystectomy and analyzed for their chemical composition using Fourier transform infrared spectroscopy RESULTS: Significantly lower serum RBP4 levels were found in patients with cholesterol gallstones in comparison with controls (30.57 +/- 13.64 mg/L vs. 41.52 +/- 20.25 mg/L, p<0.001). Lower serum RBP4 levels were also associated with gallstone occurrence (odds ratio = 0.93; 95% confidence interval = 0.88-0.96; p = 0.004). Serum RBP4 levels of all subjects were positively correlated with total cholesterol, triglyceride, creatinine, insulin resistance and albumin, and inversely correlated with aspartate aminotransferase and alanine aminotransferase. In multivariate analysis, cholesterol gallstone formation was significantly associated with a lower serum RBP4 level (odds ratio = 4.2; 95% confidence interval= 1.40-12.57; p = 0.010). RBP4 levels were significantly decreased regardless of renal function in patients with gallstones, but levels increased proportionate to renal dysfunction in people without gallstones. CONCLUSION: Circulating RBP4 decreases in cholesterol gallstone disease independent of renal function. Further studies are needed to investigate the relationship between liver function and RBP4 levels in these patients.

The international position on laparoscopic liver surgery: The Louisville Statement, 2008.

OBJECTIVE: To summarize the current world position on laparoscopic liver surgery. SUMMARY BACKGROUND DATA: Multiple series have reported on the safety and efficacy of laparoscopic liver surgery. Small and medium sized procedures have become commonplace in many centers, while major laparoscopic liver resections have been performed with efficacy and safety equaling open surgery in highly specialized centers. Although the field has begun to expand rapidly, no consensus meeting has been convened to discuss the evolving field of laparoscopic liver surgery. METHODS: On November 7 to 8, 2008, 45 experts in hepatobiliary surgery were invited to participate in a consensus conference convened in Louisville, KY, US. In addition, over 300 attendees were present from 5 continents. The conference was divided into sessions, with 2 moderators assigned to each, so as to stimulate discussion and highlight controversies. The format of the meeting varied from formal presentation of experiential data to expert opinion debates. Written and video records of the presentations were produced. Specific areas of discussion included indications for surgery, patient selection, surgical techniques, complications, patient safety, and surgeon training. RESULTS: The consensus conference used the terms pure laparoscopy, hand-assisted laparoscopy, and the hybrid technique to define laparoscopic liver procedures. Currently acceptable indications for laparoscopic liver resection are patients with solitary lesions, 5 cm or less, located in liver segments 2 to 6. The laparoscopic approach to left lateral sectionectomy should be considered standard practice. Although all types of liver resection can be performed laparoscopically, major liver resections (eg, right or left hepatectomies) should be reserved for experienced surgeons facile with more advanced laparoscopic hepatic resections. Conversion should be performed for difficult resections requiring extended operating times, and for patient safety, and should be considered prudent surgical practice rather than failure. In emergent situations, efforts should be made to control bleeding before converting to a formal open approach. Utilization of a hand assist or hybrid technique may be faster, safer, and more efficacious. Indications for surgery for benign hepatic lesions should not be widened simply because the surgery can be done laparoscopically. Although data presented on colorectal metastases did not reveal an adverse effect of the laparoscopic approach on oncological outcomes in terms of margins or survival, adequacy of margins and ability to detect occult lesions are concerns. The pure laparoscopic technique of left lateral sectionectomy was used for adult to child donation while the hybrid approach has been the only one reported to date in the case of adult to adult right lobe donation. Laparoscopic liver surgery has not been tested by controlled trials for efficacy or safety. A prospective randomized trial appears to be logistically prohibitive; however, an international registry should be initiated to document the role and safety of laparoscopic liver resection. CONCLUSIONS: Laparoscopic liver surgery is a safe and effective approach to the management of surgical liver disease in the hands of trained surgeons with experience in hepatobiliary and laparoscopic surgery. National and international societies, as well as governing boards, should become involved in the goal of establishing training standards and credentialing, to ensure consistent standards and clinical outcomes.

The effect of preoperative transarterial chemoembolization of resectable hepatocellular carcinoma on clinical and economic outcomes.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most malignant cancers in the world. The effect of preoperative transarterial chemoembolization (TACE) for resectable HCC is still controversial and cost-associated treatments are unknown. METHODS: We retrospectively compared clinical outcomes and resource utilization after liver resection between patients who underwent preoperative TACE (TACE-LR group, n = 114) and those who did not (LR group, n = 236). RESULTS: The overall mortality rate was 27.54% for the LR group versus 39.47% for the TACE-LR group (P < 0.05). The overall recurrent rates were 29.36% for the LR group versus 35.90% for the TACE-LR group (P > 0.05). Multivariate Cox regression analysis showed that preoperative TACE was a significant risk factor (P = 0.002, HR = 1.995, 95% CI 1.297-3.069) for overall long-term survival for HCC. The TACE-LR group had longer mean lengths of stay and higher hospital charges, both at index hospitalization and at 6 months for follow-up. CONCLUSION: Preoperative TACE is not only associated with higher medical utilizations, but it is also correlated with higher mortality rates over a 5-year period. The preoperative TACE does not benefit patients with resectable HCC. The golden standard or clinical guidelines should be developed to provide better clinical decisions and decision support for HCC patients.

The impact of body mass index on laparoscopic cholecystectomy in Taiwan: an oriental experience.

BACKGROUND/PURPOSE: The outcome analysis of obese patients undergoing laparoscopic cholecystectomy (LC) in Asia-Pacific countries is rarely reported. This study examined associations between body mass index (BMI) and clinical outcomes of elective LC in Taiwan. METHODS: A total of 627 patients with gallbladder disease due to gallstones undergoing LC were divided into three groups based on BMI: <25.0 kg/m2 (normal, NO; n = 310), 25.0-29.9 kg/m2 (overweight, OW; n = 252), and >30 kg/m2 (obese, OB; n = 65). RESULTS: Both overweight and obesity were not associated with conversion and complication rates. The conversion rates of the three groups were 5.5 (NO), 6.0 (OW), and 4.6% (OB), and the complication rates were 3.2 (NO), 2.4% (OW), and 4.6% (OB), respectively. However, overweight and obesity were related to a trend toward longer operating time (NO 67.4 +/- 31.8; OW 77.8 +/- 35.6; OB 79.0 +/- 37.9 min) (P trend <0.001). One death (BMI 40.6 kg/m2) was due to septic complications. In the multivariable logistic analysis, only acute cholecystitis, but not BMI, was a predictor for conversion and complications. CONCLUSIONS: Based on these results, it appears that BMI was not associated with clinical outcomes and that LC is a safe procedure in obese patients with uncomplicated gallstone disease in Taiwan.

Laparoscopic cholecystectomy in aged patients.

BACKGROUND/AIM: The life-span of humans increased and the prevalence of gallstones has also increased with age. The aim of this study is to examine the associations between age and clinical outcomes in the patients undergoing elective laparoscopic cholecystectomy (LC). METHODOLOGY: A total of 627 patients receiving LC were categorized into three different age groups. Group I was defined as less than 65 years of age (n = 510), group II as 65 to 79 (n = 100) and group III as more than 80 (n = 17). Clinical characteristics of these patients and surgical outcomes were analyzed. RESULTS: Rates of conversion and major complications were similar among three age groups. Group III had a significantly longer length of perioperative hospital stay compared to groups I or II. However, rates of minor complication appeared to be higher as age progressed (group I: 0.6%; group II: 6.0%; group III: 17.6%). In multivariable-adjusted modeling, groups II and III respectively, had a 7.1-fold (95% CI: 1.3-38.1, p = 0.023) and 34.1 (95% CI: 3.8-310.8, p = 0.002) higher risk of having minor complications than group I patients. CONCLUSION: LC is a safe and accepted procedure in aged patients with uncomplicated gallbladder stones disease, but it may be associated with increased postoperative morbidity.

Laparoscopic liver surgery for patients with hepatocellular carcinoma.

BACKGROUND: Laparoscopic hepatectomy is feasible for hepatocellular carcinoma (HCC) today. This is a retrospective study of the patients with HCC treated by liver resection with a totally laparoscopic approach. METHODS: This study recruited 116 patients (92 male, 24 female) that underwent laparoscopic liver resection (LR) for HCC. Patients were divided into two groups: group I: (n = 97, 78 male,19 female) those with a volume of resection less than two segments; group II: (n = 19, 14 male, 5 female) those with a volume of resection of more than two segments. The distribution of the tumor-node-metastasis (TNM) stage of patients in the two groups was not significantly different. RESULTS: Patients resumed full diet on the second or third day after the operation, and the average length of hospital stay was 6 days. The operation time was 152.4 +/- 336.3 min and 175.8 +/- 57.4 min, while blood loss was 101.6 +/- 324.4 mL and 329.2 +/- 338.0 ml, for groups I and II, respectively. Five patients (5.2%) in group I and three patients (15.8%) in group II required blood transfusion (p = 0.122). The mortality rate was zero among our patients and complication rates were 6.2% and 5.2% for groups I and II, respectively. The 1-year, 3-year, and 5-year survival rates were 85.4%, 66.4%, and 59.4% for group I, and 94.7%, 74.2%, and 61.7% for group II, respectively, with no significant difference between two groups (p = 0.1237). CONCLUSION: Laparoscopic liver resection is a procedure of significant risk and is more technically demanding in comparison with traditional open method. There was no significant difference in survival rates, based on the volume of resection. Laparoscopic surgery should be performed in selected patients as the postoperative quality of life of patients is better than that with open resection.

Albumin and prealbumin may predict retinol status in patients with liver cirrhosis.

BACKGROUND/AIMS: Impaired retinol status may be associated with development of cirrhosis to hepatocellular carcinoma (HCC). Besides cirrhotic severity, retinol may be influenced by compromised nutrition status. This study investigated the interrelations among retinol, malnutrition, and severity of cirrhosis and further aimed to examine whether malnutrition proxies commonly measured in hospital would be useful to predict retinol concentrations in different cirrhosis stages. METHODOLOGY: Fifty patients with liver cirrhosis, but without HCC were classified into the three Child-Pugh stages. Nutrition assessment was performed and fasting plasma retinol was analyzed using high-pressure liquid chromatography. RESULTS: Plasma retinol concentrations were significantly reduced as cirrhotic stage progressed accordingly (p for trend < 0.05). Stratified by each Child-Pugh class, subjects having albumin < 3.5 g/dL, prealbumin < 15 mg/dL and transferrin < 200 mg/dL showed significantly lower retinol concentrations compared to their respective counterparts (p<0.05), except that all Child-Pugh C patients had prealbumin < 15 mg/dL or transferrin < 200 mg/dL. After adjusting for confounders, albumin < 3.5 g/dL (beta = -14.2, SE = 6.5, p=0.028) or prealbumin < 15 mg/dL, (beta = -34.0, SE = 7.6, p<0.001) was negatively associated with retinol levels; transferrin < 200 mg/dL however. was not related. CONCLUSIONS: Retinol status was independently associated with malnutrition defined by albumin and prealbumin in cirrhosis patients. These malnutrition indicators are routinely measured by laboratory devices available in hospitals and may be used for prediction of retinol status in patients in different stages.

Tokyo Guidelines 2018: management bundles for acute cholangitis and cholecystitis.

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.

Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos).

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.

Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis (with videos).

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.

Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis.

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.

Tokyo Guidelines 2018: management strategies for gallbladder drainage in patients with acute cholecystitis (with videos).

Since the publication of the Tokyo Guidelines in 2007 and their revision in 2013, appropriate management for acute cholecystitis has been more clearly established. Since the last revision, several manuscripts, especially for alternative endoscopic techniques, have been reported; therefore, additional evaluation and refinement of the 2013 Guidelines is required. We describe a standard drainage method for surgically high-risk patients with acute cholecystitis and the latest developed endoscopic gallbladder drainage techniques described in the updated Tokyo Guidelines 2018 (TG18). Our study confirmed that percutaneous transhepatic gallbladder drainage should be considered the first alternative to surgical intervention in surgically high-risk patients with acute cholecystitis. Also, endoscopic transpapillary gallbladder drainage or endoscopic ultrasound-guided gallbladder drainage can be considered in high-volume institutes by skilled endoscopists. In the endoscopic transpapillary approach, either endoscopic naso-gallbladder drainage or gallbladder stenting can be considered for gallbladder drainage. We also introduce special techniques and the latest outcomes of endoscopic ultrasound-guided gallbladder drainage studies. 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.

Role of cystic fluid in diagnosis of the pancreatic cystadenoma and cystadenocarcinoma.

BACKGROUND/AIMS: Early and accurate diagnosis of cystic neoplasm of the pancreas is difficult especially for the differentiation of benign or malignancy. In this study, we try to compare EUS-guided fine needle aspiration biopsy combined with measurement of the cyst fluid and serum levels of CEA, and CA19-9 for the preoperative diagnosis of pancreatic cystadenoma or cystadenocarcinoma. METHODOLOGY: Retrospective analysis was made on the clinical data of 37 patients with pancreatic cystadenoma and 48 patients with cystadenocarcinoma from 1998 to 2005. RESULTS: Carcinoembryonic antigen (CEA), and CA19-9 of the cyst fluid and serum combined with EUS-guided fine needle aspiration biopsy was made. Examination of serum CEA, and CA19-9 resulted in 21.0+/-18.0, 2.7+/-1.7 U/L and 18.7+/-17.5, 269.0+/-182.0 U/L for cystadenoma and cystadenocarcinoma respectively (P<0.05). The sensitivity of cyst fluid combined with biopsy was higher than that of a single marker. However, the sensitivity and specificity of tumor markers of cystic fluid were much higher than that of the serum (P<0.05). CONCLUSIONS: EUS-guided fine needle aspiration biopsy combined with examination of cyst fluid level of CEA and CA19-9 will be a credible means for early diagnosis of pancreatic cystadenoma and cystadenocarcinoma.