Background & Aims We aimed to develop a prognostic classification scheme with treatment guidance for Asian patients with hepatocellular carcinoma (HCC). Methods We collected data from 3856 patients ...with HCC predominantly related to hepatitis B treated at Queen Mary Hospital in Hong Kong from January 1995 through December 2008. Data on patient performance status, Child–Pugh grade, tumor status (size, number of nodules, and presence of intrahepatic vascular invasion), and presence of extrahepatic vascular invasion or metastasis were included, and randomly separated into training and test sets for analysis. Cox regression and classification and regression tree analyses were used to account for the relative effects of factors in predicting overall survival times and to classify disparate treatment decision rules, respectively; the staging system and treatment recommendation then were constructed by integration of clinical judgments. The Hong Kong Liver Cancer (HKLC) classification was compared with the Barcelona Clinic Liver Cancer (BCLC) classification in terms of discriminatory ability and effectiveness of treatment recommendation. Results The HKLC system had significantly better ability than the BCLC system to distinguish between patients with specific overall survival times (area under the receiver operating characteristic curve values, approximately 0.84 vs 0.80; concordance index, 0.74 vs 0.70). More importantly, HKLC identified subsets of BCLC intermediate- and advanced-stage patients for more aggressive treatments than what were recommended by the BCLC system, which improved survival outcomes. Of BCLC-B patients classified as HKLC-II in our system, the survival benefit of radical therapies, compared with transarterial chemoembolization, was substantial (5-year survival probability, 52.1% vs 18.7%; P < .0001). In BCLC-C patients classified as HKLC-II, the survival benefit of radical therapies compared with systemic therapy was even more pronounced (5-year survival probability, 48.6% vs 0.0%; P < .0001). Conclusions We collected data from patients with HCC in Hong Kong to create a system to identify patients who are suitable for more aggressive treatment than the currently used BCLC system. The HKLC system should be validated in non-Asian patient populations and in patients with different etiologies of HCC.
Liver function reserve estimation is important for selecting the appropriate patients for hepatectomy or ablation of tumors. Many liver function tests have been devised, but the indocyanine green ...(ICG) clearance test remains the most popular for its simplicity and perhaps accuracy. Compared with the Child–Pugh classification, the ICG retention value at 15 min (ICGR-15) after intravenous injection provides more information. Though a significant difference in ICGR-15 has been observed between patients with Child–Pugh A and B liver function, the hospital mortality rates following partial hepatectomy are not significantly different between the two groups. Yet, ICGR-15 values can differentiate patients with or without hospital mortality. The cutoff values of ICGR-15 for a safe major and minor hepatectomy are 14 and 22%, respectively.
Liver injury during hepatectomy Fan, Sheung‐tat
Surgical practice,
November 2021, 2021-11-00, 20211101, Letnik:
25, Številka:
4
Journal Article
Recenzirano
During hepatectomy the liver may sustain various forms of injury due to inflow occlusion, congestion, raised intraductal pressure from bile duct obstruction, choledochoscopy and electrohydraulic ...lithotripsy, and portal hyperperfusion related to small liver remnant. This review elaborates the possible mechanism of liver injury during hepatectomy and their prevention.
The heterogeneity and instability of human tumors hamper straightforward identification of cancer-causing mutations through genomic approaches alone. Herein we describe a mouse model of liver cancer ...initiated from progenitor cells harboring defined cancer-predisposing lesions. Genome-wide analyses of tumors in this mouse model and in human hepatocellular carcinomas revealed a recurrent amplification at mouse chromosome 9qA1, the syntenic region of human chromosome 11q22. Gene-expression analyses delineated
cIAP1, a known inhibitor of apoptosis, and
Yap, a transcription factor, as candidate oncogenes in the amplicon. In the genetic context of their amplification, both
cIAP1 and
Yap accelerated tumorigenesis and were required to sustain rapid growth of amplicon-containing tumors. Furthermore,
cIAP1 and
Yap cooperated to promote tumorigenesis. Our results establish a tractable model of liver cancer, identify two oncogenes that cooperate by virtue of their coamplification in the same genomic locus, and suggest an efficient strategy for the annotation of human cancer genes.
This randomized, controlled trial assessed the efficacy of transarterial Lipiodol (Lipiodol Ultrafluide, Laboratoire Guerbet, Aulnay-Sous-Bois, France) chemoembolization in patients with unresectable ...hepatocellular carcinoma. From March 1996 to October 1997, 80 out of 279 Asian patients with newly diagnosed unresectable hepatocellular carcinoma fulfilled the entry criteria and randomly were assigned to treatment with chemoembolization using a variable dose of an emulsion of cisplatin in Lipiodol and gelatin-sponge particles injected through the hepatic artery (chemoembolization group, 40 patients) or symptomatic treatment (control group, 40 patients). One patient assigned to the control group secondarily was excluded because of unrecognized systemic metastasis. Chemoembolization was repeated every 2 to 3 months unless there was evidence of contraindications or progressive disease. Survival was the main end point. The chemoembolization group received a total of 192 courses of chemoembolization with a median of 4.5 (range, 1-15) courses per patient. Chemoembolization resulted in a marked tumor response, and the actuarial survival was significantly better in the chemoembolization group (1 year, 57%; 2 years, 31%; 3 years, 26%) than in the control group (1 year, 32%; 2 years, 11%; 3 years, 3%;
P = .002). When adjustments for baseline variables that were prognostic on univariate analysis were made with a multivariate Cox model, the survival benefit of chemoembolization remained significant (relative risk of death, 0.49; 95% CI, 0.29-0.81;
P = .006). Although death from liver failure was more frequent in patients who received chemoembolization, the liver functions of the survivors were not significantly different. In conclusion, in Asian patients with unresectable hepatocellular carcinoma, transarterial Lipiodol chemoembolization significantly improves survival and is an effective form of treatment. (H
EPATOLOGY 2002;35:1164-1171.)
TG13 surgical management of acute cholecystitis Yamashita, Yuichi; Takada, Tadahiro; Strasberg, Steven M. ...
Journal of hepato-biliary-pancreatic sciences,
01/2013, Letnik:
20, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background
Laparoscopic cholecystectomy is now accepted as a surgical procedure for acute cholecystitis when it is performed by an expert surgeon. There are several lines of strong evidence, such as ...randomized controlled trials (RCTs) and meta-analyses, supporting the introduction of laparoscopic cholecystectomy for patients with acute cholecystitis. The updated Tokyo Guidelines 2013 (TG13) describe the surgical treatment for acute cholecystitis according to the grade of severity, the timing, and the procedure used for cholecystitis in a question-and-answer format using the evidence concerning surgical management of acute cholecystitis.
Methods and materials
Forty-eight publications were selected for a careful examination of their full texts, and the types of surgical management of acute cholecystitis were investigated using this evidence. The items concerning the surgical management of acute cholecystitis were the optimal surgical treatment for acute cholecystitis according to the grade of severity, optimal timing for the cholecystectomy, surgical procedure used for cholecystectomy, optimal timing of the conversion of cholecystectomy from laparoscopic to open surgery, and the complications of laparoscopic cholecystectomy.
Results
There were eight RCTs and four meta-analyses concerning the optimal timing of the cholecystectomy. Consequently, it was found that cholecystectomy is preferable early after admission. There were three RCTs and two meta-analyses concerning the surgical procedure, which concluded that laparoscopic cholecystectomy is preferable to open procedures. Literature concerning the surgical treatment according to the grade of severity could not be quoted, because there have been no publications on this topic. Therefore, the treatment was determined based on the general opinions of professionals.
Conclusion
Surgical management of acute cholecystitis in the updated TG13 is fundamentally the same as in the Tokyo Guidelines 2007 (TG07), and the concept of a critical view of safety and the existence of extreme vasculobiliary injury are added in the text to call the surgeon’s attention to the need to reduce the incidence of bile duct injury.
Free full-text articles and a mobile application of TG13 are available via
http://www.jshbps.jp/en/guideline/tg13.html
.
Background & Aims The roles of alternatively activated (M2) macrophages on pro-tumour phenotypes have been well documented in many cancers except hepatocellular carcinoma (HCC). Considering their ...close relationship with chronic tissue injuries as well as enhanced tumour invasiveness and growth, we aimed to investigate the direct effects of M2 macrophages on HCC. Methods M2 macrophages in 95 HCC clinical specimens were quantified using immunohistochemistry and quantitative PCR. The pro-tumour functions and the underlying molecular mechanisms of M2 macrophages in HCC were investigated in vivo and in an in vitro co-culture system. Results In the clinical study, high M2-specific CD163 (hazard ratio = 2.693; p = 0.043) and scavenger receptor A (hazard ratio = 3.563; p = 0.044) levels indicated poor prognosis and correlated with increased tumour nodules and venous infiltration in HCC patients. In an orthotopic model, the liver tumour volume was increased 3.26-fold (1.27 cm3 ± 0.36) after M2 macrophage injection compared with the control (0.39 cm3 ± 0.05) ( p = 0.032). An increased rate of lung metastasis was also found in the treatment group. In vitro , co-cultivation with M2 macrophages elevated the number of HCC cells (MHCC97L) and migration events by 1.3-fold and 3.2-fold, respectively ( p <0.05). Strongly induced by MHCC97L, M2 macrophage-derived CCL22 was proven to enhance tumour migration capacities and correlate with venous infiltration in HCC patients. Increased epithelial-mesenchymal transition (EMT) via Snail activation in MHCC97L was found to be promoted by M2 macrophages and CCL22. Conclusions M2 macrophages contribute to poor prognosis in HCC and promote tumour invasiveness through CCL22-induced EMT.
This study characterized cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) cell lines, tumor specimens, and blood samples. The CD90
+ cells, but not the CD90
− cells, from HCC cell lines ...displayed tumorigenic capacity. All the tumor specimens and 91.6% of blood samples from liver cancer patients bore the CD45
−CD90
+ population, which could generate tumor nodules in immunodeficient mice. The CD90
+CD44
+ cells demonstrated a more aggressive phenotype than the CD90
+CD44
− counterpart and formed metastatic lesions in the lung of immunodeficient mice. CD44 blockade prevented the formation of local and metastatic tumor nodules by the CD90
+ cells. Differential gene expression profiles were identified in the CD45
−CD90
+ and CD45
−CD90
− cells isolated from tissue and blood samples from liver cancer patients and controls.
Increasing evidence has revealed the importance of cancer stem cells (CSCs) in carcinogenesis. Although liver CSCs have been identified in hepatocellular carcinoma (HCC) cell lines, no data have ...shown the presence of these cells in human settings. The present study was designed to delineate CSCs serially from HCC cell lines, human liver cancer specimens to blood samples, using CD90 as a potential marker. The number of CD90+ cells increased with the tumorigenicity of HCC cell lines. CD45−CD90+ cells were detected in all the tumor specimens, but not in the normal, cirrhotic, and parallel nontumorous livers. In addition, CD45−CD90+ cells were detectable in 90% of blood samples from liver cancer patients, but none in normal subjects or patients with cirrhosis. A significant positive correlation between the number of CD45−CD90+ cells in the tumor tissues and the number of CD45−CD90+ cells in the blood samples was identified. CD90+ cells sorted from cell lines and CD45−CD90+ cells from the tumor tissues and blood samples of liver cancer patients generated tumor nodules in immunodeficient mice. Serial transplantation of CD90+ cells from tumor xenografts generated tumor nodules in a second and subsequently third batch of immunodeficient mice. Treatment of CD90+ CSCs with anti‐human CD44 antibody induced cell apoptosis in a dose‐dependent manner. Conclusion: Identification of CD45−CD90+ CSCs in both tumor tissues and circulation suggests that CD45−CD90+ could be used as a marker for human liver cancer and as a target for the diagnosis and therapy of this malignancy. (HEPATOLOGY 2008.)
Hepatic resection and liver transplantation are considered the only curative treatments for hepatocellular carcinoma (HCC). Liver transplantation for HCCs ≤ 5 cm in diameter has been shown to produce ...favorable survival results, but its application is limited by the lack of donors. Hepatic resection remains the treatment of choice for patients who are not transplantation candidates because of large tumor, macroscopic vascular invasion, or advanced age. For small HCCs associated with Child's A cirrhosis, hepatic resection should still be considered the first‐line treatment, but salvage transplantation for intrahepatic recurrence may be a feasible strategy. Recent improvement in surgical techniques and perioperative care has increased the safety and expanded the indication of hepatic resection for HCC to include large tumors that require extended hepatectomy in cirrhotic patients. Selection of appropriate candidates for hepatectomy depends on careful assessment of the tumor status and liver function reserve. Evaluation of the general fitness of patients is also critical because comorbid illness is an important cause of postoperative mortality, even if the patients have good liver function reserve. With careful patient selection and surgical expertise, the current operative mortality of hepatectomy for HCC is about 5% or less in major centers. Improved long‐term survival results after resection of HCC have also been reported recently, with an overall 5‐year survival rate of about 50%. The improved perioperative and long‐term survival results have strengthened the role of hepatectomy as the mainstay of treatment for HCC despite the availability of a number of other treatment options for localized HCC. (Liver Transpl 2004;10:S39–S45.)
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