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1.
Hepatol Res ; 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39329320

RESUMEN

AIM: Some patients undergoing liver resection for hepatocellular carcinoma (HCC) have poor outcomes. Therefore, we aimed to propose a new resectability classification for patients with HCC. METHODS: We classified patients into three categories: resectable (R), borderline resectable (BR), and unresectable (UR). Patients (n = 409) who underwent hepatectomy for HCC were assigned to the non-UR (R and BR classes combined; n = 285) and UR-HCC classes (n = 68; training cohort). Patient characteristics in the BR-HCC and R-HCC groups were compared. The new criteria were tested in a validation cohort (n = 295). RESULTS: Of the 285 patients, 229 and 56 were classified into the R- and BR-HCC classes, respectively, using macrovascular invasion, tumor size, and future liver remnant/modified albumin-bilirubin scores. Patients with BR-HCC demonstrated significantly worse progression-free and overall survival (p < 0.0001 and p < 0.0001, respectively) than patients with R-HCC in the training cohort. Similar results were observed in the validation cohort. Multivariate analysis of the non-UR-HCC group in the training cohort revealed that the tumor number and BR-HCC were independent predictive factors for poor overall survival. CONCLUSIONS: This classification can help select patients with BR-HCC for preoperative treatment before considering surgery.

2.
Tissue Eng Part A ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39276095

RESUMEN

A bioengineered liver has the potential to save patients with end-stage liver disease, and a three-dimensional decellularized scaffold is a promising approach for practical use. The main challenge in bioengineered liver transplantation is thrombogenicity during blood perfusion. We aimed to apply a novel antithrombotic polymer to revascularize liver scaffolds and evaluate the thrombogenicity and biosafety of the polymer-treated scaffolds. A biomimetic polymer, 2-metacryloyloxyethyl phosphorylcholine (MPC) was prepared for modification of the extracellular matrix in liver scaffolds. The polymer was injected into the rat liver scaffolds' portal vein and could extensively react to the vessel walls. In an ex vivo blood perfusion experiment, we demonstrated significantly less platelet deposition in the polymer-treated scaffolds than nontreated or re-endothelialized scaffolds with human umbilical vein endothelial cells. In the heterotopic transplantation model, liver volume was better maintained in the polymer-treated groups, and platelet deposition was suppressed in these groups. Additionally, the polymer-treated liver scaffolds maintained the metabolic function of the recellularized rat primary hepatocytes during perfusion culture. The MPC polymer treatment efficiently suppressed thrombus formation during blood perfusion in liver scaffolds and maintained the function of recellularized hepatocytes. Revascularizing liver scaffolds using this polymer is a promising approach for bioengineered liver transplantation.

3.
Transplantation ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39104012

RESUMEN

BACKGROUND: The indication of living donor liver retransplantation (re-LDLT) for retransplant candidates with chronic allograft failure (CAF) is increasing because of the high mortality rate of patients on the waiting list. However, evidence supporting re-LDLT for CAF remains scarce because of technical difficulties. We aimed to examine the feasibility based on our significant case experience. METHODS: A total of 95 retransplant cases (adult: 53, pediatric: 42) between 2000 and 2020 were retrospectively reviewed. Graft survival after re-LDLT and deceased donor liver retransplantation (re-DDLT) was compared among recipients with CAF and acute allograft failure (AAF). RESULTS: Re-LDLTs for CAF were performed in 58 (61.1%) cases, re-DDLTs for CAF in 16 (16.8%) cases, re-LDLTs for AAF in 13 (13.7%) cases, and re-DDLTs for AAF in 8 (8.4%) cases. Re-DDLTs have become increasingly prevalent over time. Retransplantation for AAF results in lower graft survival than that for CAF in both adult and pediatric cases. All adult recipients who underwent re-LDLT for AAF died within 1 y after retransplantation. The 5-y graft survival between re-LDLT and re-DDLT for CAF was not significantly different (73.8% versus 75.0%, P = 0.84). Operation time and blood loss were not significantly different. CONCLUSIONS: The survival rate of re-LDLT for recipients with CAF is permissible. Re-LDLT may be another treatment option for recipients with CAF.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39128875

RESUMEN

We introduce a novel notation system for pancreatectomy designed to provide a clear and concise representation of surgical procedures. As surgical techniques and the scope of pancreatic surgeries continue to diversify, existing communication methods among medical professionals regarding the specifics of the surgeries have proven inadequate. Our proposed notation system clearly indicates the approach (open, laparoscopic, or robot-assisted), type of surgery (e.g., pancreatoduodenectomy, distal pancreatectomy), and extent of resection and accompanying resected organs or vasculature. These elements are all recorded in this order by using abbreviations. For example, a pancreatoduodenectomy with pancreatic transection just above the SMA and combined resection of the SMV would be noted as "OPD(hb')-SMV". This new notation system allows for concise expression of the essential information on performed procedures of pancreatic resection, leading to smooth information sharing. This initiative is an essential step towards standardizing pancreatic surgery documentation on a global scale. Here, we present the development and application of this system, highlighting its potential to transform surgical communication and documentation.

5.
J Clin Oncol ; : JCO2400645, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39197119

RESUMEN

PURPOSE: Durable partial response (PR) and durable stable disease (SD) are often seen in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab (atezo-bev). This study investigates the outcome of these patients and the histopathology of the residual tumors. PATIENTS AND METHODS: The IMbrave150 study's atezo-bev group was analyzed. PR or SD per RECIST v1.1 lasting more than 6 months was defined as durable. For histologic analysis, a comparable real-world group of patients from Japan and Taiwan who had undergone resection of residual tumors after atezo-bev was investigated. RESULTS: In the IMbrave150 study, 56 (77.8%) of the 72 PRs and 41 (28.5%) of the 144 SDs were considered durable. The median overall survival was not estimable for patients with durable PR and 23.7 months for those with durable SD. The median progression-free survival was 23.2 months for patients with durable PR and 13.2 months for those with durable SD. In the real-world setting, a total of 38 tumors were resected from 32 patients (23 PRs and nine SDs) receiving atezo-bev. Pathologic complete responses (PCRs) were more frequent in PR tumors than SD tumors (57.7% v 16.7%, P = .034). PCR rate correlated with time from atezo-bev initiation to resection and was 55.6% (5 of 9) for PR tumors resected beyond 8 months after starting atezo-bev, a time practically corresponding to the durable PR definition used for IMbrave150. We found no reliable radiologic features to predict PCR of the residual tumors. CONCLUSION: Durable PR patients from the atezo-bev group showed a favorable outcome, which may be partly explained by the high rate of PCR lesions. Early recognition of PCR lesions may help subsequent treatment decision.

7.
Hepatol Res ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-39031833

RESUMEN

AIMS: This study aimed to identify the genetic risk factors from donors or recipients that contribute to postliver transplantation (LT) steatotic liver disease (SLD), focusing on the genetic risk score (GRS) based on single nucleotide polymorphisms (SNPs) in SLD patients. METHODS: This retrospective study included 55 Japanese SLD recipients and their respective donors. Genotyping of PNPLA3, TM6SF2, and HSD17B13 was undertaken, and the combined GRS was calculated. The relationship between the GRS and the incidence of posttransplant SLD was also evaluated. RESULTS: The SLD recipients had a high prevalence of post-LT graft steatosis/steatohepatitis (76.4% and 58.2%, respectively). Although the recipients had a high frequency of risk alleles, there was no relationship between the number of risk alleles for each SNP and the incidence of posttransplant SLD. In contrast, an increased number of risk alleles for any SNP in the donor was correlated with high incidence rates of both post-LT steatosis and steatohepatitis. A multivariable analysis showed that a high donor GRS was an independent risk factor for graft steatosis (odds ratio 8.77; 95% CI, 1.94-52.94; p = 0.009). Similarly, a high donor GRS was an independent risk factor (odds ratio 6.76; 95% CI, 1.84-30.78; p = 0.007) for post-LT graft steatohepatitis. CONCLUSIONS: Donor risk alleles of PNPLA3, TM6SF2, and HSD17B13, rather than recipient risk alleles, have been implicated in the development of posttransplant SLD. The combination of these donor risk alleles into a GRS could predict the development of posttransplant SLD.

8.
BJR Case Rep ; 10(3): uaae012, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38716145

RESUMEN

We report a case of a cystic liver tumour in a 47-year-old man with Peutz-Jeghers syndrome (PJS) who had undergone sclerotherapy at another hospital for a cyst in hepatic segment IV (S4) 7 years earlier. Based on the preoperative imaging findings, the patient was diagnosed with an intraductal papillary neoplasm of the bile duct. Percutaneous transhepatic portal vein embolization was performed to increase the residual liver volume, followed by resection of the three right hepatic lobes and the caudate lobe, biliary reconstruction, and portal vein reconstruction. Pathological examination revealed an adenoma arising in an intrahepatic biliary duplication cyst. Retrospectively, the preoperative diagnosis was difficult, but it aligned with previous reports of biliary duplication cysts due to its continuity with the bile duct. Additionally, intrahepatic biliary duplication cysts with tumour lesions or cases in which 18F-fluorodeoxyglucose positron emission tomography was performed have not been previously reported. Therefore, preoperatively listing this disease as a differential diagnosis was difficult. PJS and chronic inflammation associated with cyst sclerotherapy may have contributed to tumour development in the intrahepatic biliary duplication cyst.

9.
Surg Case Rep ; 10(1): 121, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38739347

RESUMEN

BACKGROUND: Malignant perineurioma is a rare malignant counterpart of perineurioma derived from perineural cells. Resection is the primary option for the treatment of malignant perineuriomas; however, patients often develop recurrence after resection, and effective treatment for advanced or recurrent lesions needs to be established. This report describes a 51-year-old female with a rare malignant perineurioma in the retroperitoneum, which contributing valuable insights to the literature. CASE PRESENTATION: The patient presented with abdominal distension and the imaging work-up revealed a huge hemorrhagic tumor in the retroperitoneum and obstruction of inferior vena cava by the tumor. The patient underwent surgery retrieving the tumor combined with left hemiliver and retrohepatic vena cava, which confirmed the diagnosis of a malignant perineurioma based on histopathological and immunohistochemical examination. Cancer gene panel testing identified mutations in NF2. Radiotherapy was administered for peritoneal dissemination 2 months after surgery, and the patient died from disease progression 6 months after surgery. CONCLUSIONS: This rare case highlights the challenges in managing retroperitoneal malignant perineuriomas. The aggressive characteristics and limited treatment options for advanced malignant perineuriomas underscore the need for understanding the pathogenesis and developing effective systemic therapies. The identification of an NF2 mutation provides significant insights into potential therapeutic target.

10.
HPB (Oxford) ; 26(6): 731-740, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38580611

RESUMEN

BACKGROUND/PURPOSE: This meta-analysis aimed to elucidate the therapeutic effects of routine lymph node dissection (LND) with liver resection on intrahepatic cholangiocarcinoma (ICC). METHODS: Databases, including MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials, were searched to identify studies comparing LND and non-LND for ICC liver resection. The primary outcome was overall survival (OS), and secondary outcomes were disease-free survival (DFS), in-hospital morbidity, blood loss, and R0 rate. RESULTS: Seventeen studies involving 4407 patients were included. The OS did not differ between the LND (n = 2158) and non-LND (n = 2249) groups (HR, 1.05; 95% CI, 0.83-1.32). The secondary outcomes did not differ significantly between the groups. Subgroup analyses stratified by the risk of bias showed a significant difference in OS between the high- and low-risk groups (P = 0.0008). In the low-risk group, LND (vs. non-LND) was associated with superior OS (HR, 0.76; 95% CI, 0.59-0.98). Most studies in low-risk groups involved patients who were clinically node-negative. CONCLUSIONS: The therapeutic effects of routine LND for ICC have not been demonstrated. However, LND had a positive impact on OS in studies with a low risk of bias, thus suggesting that there may be a subset of ICC patients who would benefit from LND.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Hepatectomía , Escisión del Ganglio Linfático , Humanos , Colangiocarcinoma/cirugía , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Factores de Riesgo , Metástasis Linfática , Supervivencia sin Enfermedad , Resultado del Tratamiento , Femenino , Masculino , Factores de Tiempo , Persona de Mediana Edad , Medición de Riesgo
11.
J Pathol ; 263(1): 32-46, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38362598

RESUMEN

Cholangiolocarcinoma (CLC) is a primary liver carcinoma that resembles the canals of Hering and that has been reported to be associated with stem cell features. Due to its rarity, the nature of CLC remains unclear, and its pathological classification remains controversial. To clarify the positioning of CLC in primary liver cancers and identify characteristics that could distinguish CLC from other liver cancers, we performed integrated analyses using whole-exome sequencing (WES), immunohistochemistry, and a retrospective review of clinical information on eight CLC cases and two cases of recurrent CLC. WES demonstrated that CLC includes IDH1 and BAP1 mutations, which are characteristic of intrahepatic cholangiocarcinoma (iCCA). A mutational signature analysis showed a pattern similar to that of iCCA, which was different from that of hepatocellular carcinoma (HCC). CLC cells, including CK7, CK19, and EpCAM, were positive for cholangiocytic differentiation markers. However, the hepatocytic differentiation marker AFP and stem cell marker SALL4 were completely negative. The immunostaining patterns of CLC with CD56 and epithelial membrane antigen were similar to those of the noncancerous bile ductules. In contrast, mutational signature cluster analyses revealed that CLC formed a cluster associated with mismatch-repair deficiency (dMMR), which was separate from iCCA. Therefore, to evaluate MMR status, we performed immunostaining of four MMR proteins (PMS2, MSH6, MLH1, and MSH2) and detected dMMR in almost all CLCs. In conclusion, CLC had highly similar characteristics to iCCA but not to HCC. CLC can be categorized as a subtype of iCCA. In contrast, CLC has characteristics of dMMR tumors that are not found in iCCA, suggesting that it should be treated distinctly from iCCA. © 2024 The Pathological Society of Great Britain and Ireland.


Asunto(s)
Neoplasias de los Conductos Biliares , Neoplasias Encefálicas , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Colorrectales , Neoplasias Hepáticas , Síndromes Neoplásicos Hereditarios , Humanos , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Colangiocarcinoma/patología , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/patología
12.
Ann Gastroenterol Surg ; 8(1): 133-142, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38250678

RESUMEN

Backgrounds: The success of direct-acting antiviral (DAA) therapy provides a cure for patients chronically infected with hepatitis C virus (HCV); however, outcomes after hepatectomy for HCV-associated hepatocellular carcinoma (HCC) before and after DAA introduction remain poorly studied. Methods: Patients who underwent R0/R1 hepatectomy for HCV-associated HCC were retrospectively analyzed. Two time periods were defined: Pre-DAA (2007-2011, December 2013 was defined as the end of follow-up) and Post-DAA groups (2014-2018, December 2020 was defined as the end of follow-up). Propensity score matching (PSM) analyses were performed to highlight the effect of DAA therapy. Results: A total of 155 patients with HCV-associated HCC were included in this study (Pre-DAA group, n = 103 and post-DAA group, n = 52). In the Post-DAA group, DAA therapy was performed in 26 patients (50.0%), and all of these patients achieved sustained virologic response (SVR) (preoperative SVR, n = 7; postoperative SVR, n = 19). There was no significant difference between the two groups regarding surgical settings and tumor pathology. There was no significant difference in the 5-year overall survival (OS) rate (61.1% and 64.8%, pre- and post-DAA group, respectively, p = 0.441); meanwhile, the 5-year recurrence-free survival (RFS) rate in the post-DAA group was better than the pre-DAA group (21.1% and 40.2%, p = 0.073) with a trend toward significance. After PSM except for the postoperative SVR status, there were no significant differences in OS (p = 0.586) and RFS (p = 0.888). Conclusions: This study showed that survival outcomes were not changed in hepatectomized cases of HCV-associated HCC before and after the introduction of DAA therapy.

13.
Hepatol Res ; 54(1): 103-115, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37699724

RESUMEN

AIM: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer that has two different tumor phenotypes in a single tumor nodule. The relationship between genetic mutations and clinicopathological features of cHCC-CCA remains to be elucidated. METHODS: Whole-exome sequencing analyses were carried out in 13 primary and 2 recurrent cHCC-CCAs. The whole-exome analyses and clinicopathological information were integrated. RESULTS: TP53 was the most frequently mutated gene in this cohort, followed by BAP1, IDH1/2, and NFE2L2 mutations in multiple cases. All tumors with diameters <3 cm had TP53 mutations. In contrast, six of seven tumors with diameters ≥3 cm did not have TP53 mutations, but all seven tumors had mutations in genes associated with various pathways, including Wnt, RAS/PI3K, and epigenetic modulators. In the signature analysis, the pattern of mutations shown in the TP53 mutation group tended to be more similar to HCC than the TP53 nonmutation group. Mutations in recurrent cHCC-CCA tumors were frequently identical to those in the primary tumor, suggesting that those tumors originated from identical clones of the primary cHCC-CCA tumors. Recurrent and co-occurrent HCC tumors in the same patients with cHCC-CCA had either common or different mutation patterns from the primary cHCC-CCA tumors in each case. CONCLUSIONS: The study suggested that there were two subtypes of cHCC-CCA, one involving TP53 mutations in the early stage of the carcinogenic process and the other not involving such mutations. The comparison of the variants between primary and recurrent tumors suggested that cHCC-CCA was derived from an identical clone.

14.
J Hepatobiliary Pancreat Sci ; 31(3): 133-142, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37984829

RESUMEN

BACKGROUND/PURPOSE: The anterior approach (AA) in liver resection has proven more effective with regard to short-term outcomes than the conventional approach (CA). However, its superiority over the CA concerning long-term outcomes remains unclear. This meta-analysis compared the short- and long-term outcomes of the AA and CA. METHODS: Databases, including MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials, were searched to identify studies comparing the AA and CA for hepatocellular carcinoma (HCC) liver resection. The primary outcomes were the in-hospital mortality, in-hospital morbidity, disease-free survival (DFS), and overall survival (OS). Secondary outcomes were operative time, blood loss, blood transfusion, R0 rate, and length of hospital stay. RESULTS: Ten studies involving 1369 patients were included (AA, n = 595; CA, n = 774). Despite no significant differences in the in-hospital mortality or morbidity, the AA demonstrated a superior DFS (hazard ratio [HR], 0.63; 95% confidence interval [CI]: 0.51-0.77) and OS (HR, 0.56; 95% CI: 0.48-0.65) and was associated with a longer operative time, less blood loss, and less transfusion than the CA. No marked differences in other outcomes were noted. CONCLUSIONS: The AA for HCC liver resection helped reduce blood loss and need for transfusion, improving the DFS and OS.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Hepatectomía , Supervivencia sin Enfermedad
15.
Asian J Surg ; 47(1): 497-498, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37105811

RESUMEN

TECHNIQUE: Hepatoduodenal ligamentectomy (HL) is a challenging surgery for advanced perihilar cholangiocarcinoma extensively invading the hepatoduodenal ligament1-3. A liver-transection first approach in HL is a no-touch technique wherein liver transection is performed first, and the affected liver and hepatoduodenal ligament are removed en bloc. This approach allows for the early assessment of resectability and feasibility of vascular reconstruction4. RESULTS: This video shows a 57-year-old man with advanced intrahepatic cholangiocarcinoma in the left hepatic lobe, which had directly invaded the perihilar region and the hepatoduodenal ligament via lymph node metastasis. The lymph node was extensively invasive into both the proper hepatic artery and portal vein. The case was initially deemed unresectable, but after three months of chemotherapy, conversion surgery was considered feasible. The common hepatic artery and gastroduodenal artery and then the common bile duct and main trunk of portal vein were secured at the pancreatic superior border. Hepatic dissection was performed along the Cantlie line. The right Glissonean pedicle was secured, including the right hepatic duct, right hepatic artery and right portal vein, and the operation was deemed feasible. The portal vein was dissected and reconstructed using the right external iliac vein. The left and caudate lobe with the middle hepatic vein and hepatoduodenal ligament were resected en bloc. Subsequentially, the common hepatic artery and right hepatic artery were reconstructed using the jejunal artery. CONCLUSION: The liver-transection first approach allowed us to determine the resectability of en bloc resection of the hepatoduodenal ligament at an early stage of surgery.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Masculino , Humanos , Persona de Mediana Edad , Hepatectomía/métodos , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Hígado/irrigación sanguínea , Colangiocarcinoma/cirugía , Conductos Biliares Intrahepáticos , Ligamentos/cirugía
16.
Asian J Surg ; 47(3): 1383-1388, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38160154

RESUMEN

BACKGROUNDS: A recent randomized control trial (JCOG1202; ASCOT trial) demonstrated the efficacy of adjuvant S-1 chemotherapy (ASC) for biliary tract cancer (BTC) after surgical resection; however, the significance of the completion of ASC in the real-world setting remains unknown. METHODS: Data of consecutive patients who underwent surgical resection for biliary tract cancer (BTC) from 2011 to 2021 were retrospectively reviewed. Of these, patients who underwent ASC were enrolled in this study. Patients were divided into two groups according to whether ASC was completed: the completion group and the non-completion group. Clinicopathological features and survival outcomes were assessed. RESULTS: Of the 223 patients with BTC who underwent surgical resection, 75 patients who underwent ASC were included for analysis. Among them, 48 (64.0 %) completed the intended ASC course, while 27 cases (36.0 %) discontinued the treatment. The most common reason for the discontinuation was adverse event (n = 16, 59.3 %), followed by disease recurrence (n = 9, 33.3 %). Patients in the completion group showed significantly better overall survival (OS) (p < 0.001) and recurrence-free survival (RFS) (p < 0.001) compared to the non-completion group. Further, after excluding the patients in the non-completion group who discontinued ASC due to disease recurrence, the significance of ASC completion was retained for both OS and RFS. CONCLUSION: The completion of ASC was associated with improved prognosis in patients with BTC after surgical resection. The achievement of ASC should be the goal after surgical resection, while further study may be warranted regarding the resistance of ASC.


Asunto(s)
Neoplasias del Sistema Biliar , Recurrencia Local de Neoplasia , Humanos , Estudios Retrospectivos , Quimioterapia Adyuvante , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/cirugía , Pronóstico
17.
Carcinogenesis ; 45(3): 119-130, 2024 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-38123365

RESUMEN

The role of the ferroptosis-related gene glutathione peroxidase 4 (GPX4) in oncology has been extensively investigated. However, the clinical implications of GPX4 in patients with intrahepatic cholangiocarcinoma (ICC) remain unknown. This study aimed to evaluate the prognostic impact of GPX4 and its underlying molecular mechanisms in patients with ICC. Fifty-seven patients who underwent surgical resection for ICC between 2010 and 2017 were retrospectively analyzed. Based on the immunohistochemistry, patients were divided into GPX4 high (n = 15) and low (n = 42) groups, and clinical outcomes were assessed. Furthermore, the roles of GPX4 in cell proliferation, migration and gene expression were analyzed in ICC cell lines in vitro and in vivo. The results from clinical study showed that GPX4 high group showed significant associations with high SUVmax on 18F-fluorodeoxyglucose-positron emission tomography (≥8.0, P = 0.017), multiple tumors (P = 0.004), and showed glucose transporter 1 (GLUT1) high expression with a trend toward significance (P = 0.053). Overall and recurrence-free survival in the GPX4 high expression group were significantly worse than those in the GPX4 low expression group (P = 0.038 and P < 0.001, respectively). In the experimental study, inhibition of GPX4 attenuated cell proliferation and migration in ICC cell lines. Inhibition of GPX4 also decreased the expression of glucose metabolism-related genes, such as GLUT1 or HIF1α. Mechanistically, these molecular changes are regulated in Akt-mechanistic targets of rapamycin axis. In conclusion, this study suggested the pivotal value of GPX4 serving as a prognostic marker for patients with ICC. Furthermore, GPX4 can mediate glucose metabolism of ICC.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Ferroptosis , Humanos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ferroptosis/genética , Transportador de Glucosa de Tipo 1/genética , Estudios Retrospectivos , Colangiocarcinoma/genética , Colangiocarcinoma/cirugía , Colangiocarcinoma/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/patología , Glucosa
18.
Ann Gastroenterol Surg ; 7(6): 871-886, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37927928

RESUMEN

Liver resection is an effective therapeutic option for patients with hepatocellular carcinoma. However, posthepatectomy liver failure (PHLF) remains a major cause of hepatectomy-related mortality, and the accurate prediction of PHLF based on preoperative assessment of liver functional reserve is a critical issue. The definition of PHLF proposed by the International Study Group for Liver Surgery has gained acceptance as a standard grading criterion. Liver function can be estimated using a variety of parameters, including routine blood biochemical examinations, clinical scoring systems, dynamic liver function tests, liver stiffness and fibrosis markers, and imaging studies. The Child-Pugh score and model for end-stage liver disease scores are conventionally used for estimating liver decompensation, although the alternatively developed albumin-bilirubin score shows superior performance for predicting hepatic dysfunction. Indocyanine green clearance, a dynamic liver function test mostly used in Japan and other Asian countries, serves as a quantitative estimation of liver function reserve and helps determine indications for surgical procedures according to the estimated risk of PHLF. In an attempt to improve predictive accuracy, specific evaluation of liver fibrosis and portal hypertension has gained popularity, including liver stiffness measurements using ultrasonography or magnetic resonance elastography, as well as noninvasive fibrosis markers. Imaging modalities, including Tc-99m-labeled galactosyl serum albumin scintigraphy and gadolinium-enhanced magnetic resonance imaging, are used for preoperative evaluation in combination with liver volume. This review aims to provide an overview of the usefulness of current options for the preoperative assessment of liver function in predicting PHLF.

19.
J Gastrointest Surg ; 27(11): 2414-2423, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37592191

RESUMEN

PURPOSE: Our objective was to investigate the impact of albumin-bilirubin (ALBI) score at the time of post-hepatectomy hepatocellular carcinoma (HCC) recurrence on survival after recurrence (SAR). We further explored the perioperative factors associated with the ALBI score at recurrence. METHODS: Patients who underwent primary hepatectomy for HCC between 2007 and 2018 and developed recurrence were included in the study. Cox regression models were used to assess the association between the ALBI score at recurrence and SAR. Linear regression models were used to explore factors associated with ALBI score at recurrence. RESULTS: Of the 233 patients analyzed, 158 developed recurrence within the Milan criteria (RWM) and 76 developed recurrence beyond the Milan criteria (RBM). Multivariable cox regression analysis demonstrated that higher ALBI scores at recurrence were associated with poorer SAR in both RWM and RBM groups (hazard ratios 4.5, 5.0; 95% confidence intervals 2.3-8.8, 2.2-11.6, respectively). In addition, multivariable linear regression analysis revealed that higher ALBI scores at hepatectomy and post-hepatectomy liver failure (PHLF) ≥ grade B were associated with higher ALBI scores at recurrence (ß = 0.21, 0.11; 95% confidence intervals 0.15-0.26, 0.06-0.17, respectively). CONCLUSIONS: The ALBI score at recurrence was a significant prognostic factor for SAR, and the ALBI scores at hepatectomy and PHLF ≥ Grade B were independently associated with the ALBI score at recurrence. Prevention of PHLF and consequent preservation of liver function at recurrence may be paramount to achieving better survival after HCC recurrence.


Asunto(s)
Carcinoma Hepatocelular , Fallo Hepático , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Hepatectomía/efectos adversos , Neoplasias Hepáticas/patología , Bilirrubina , Albúmina Sérica , Pronóstico , Fallo Hepático/etiología , Fallo Hepático/cirugía , Estudios Retrospectivos
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