Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review.

BACKGROUND: Perihilar cholangiocarcinoma (phCCC) is a dismal malignancy. There is no consensus regarding the best treatment for patients with unresectable phCCC. The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice. DATA SOURCES: The search was conducted in PubMed, Embase, Cochrane, and LILACS. The related references were searched manually. Inclusion criteria were: reports in English or Portuguese literature that a) patients with confirmed diagnosis of phCCC; b) patients treated with a curative intent; c) patients with the outcomes of liver resection and liver transplantation. Case reports, reviews, letters, editorials, conference abstracts and papers with full-text unavailability were excluded from the analysis. RESULTS: Most of the current literature is based on observational retrospective studies with low grades of evidence. Liver resection has better long-term outcomes than systemic chemotherapy or palliation therapy and liver transplantation is a good alternative for selected patients with unresectable phCCC. All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahepatic diseases. As a general rule, patients presenting with a tumor having a longitudinal size > 3 cm or extending below the cystic duct, lymph node disease, confirmed extrahepatic dissemination; intraoperatively diagnosed metastatic disease; a history of other malignancies within the last five years, and did not complete chemoradiation regimen and were medically unfit should not be considered for transplantation. Some of these criteria should be individually assessed. Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers, and any decision-making must be based on a multidisciplinary evaluation. CONCLUSIONS: phCCC is a complex condition with high morbidity. Surgical therapies, including hepatectomy and liver transplantation, are the best option for better long-term disease-free survival.

Molecular Profile of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a relatively uncommon but highly aggressive primary liver cancer that originates within the liver. The aim of this study is to review the molecular profile of intrahepatic cholangiocarcinoma and its implications for prognostication and decision-making. This comprehensive characterization of ICC tumors sheds light on the disease's underlying biology and offers a foundation for more personalized treatment strategies. This is a narrative review of the prognostic and therapeutic role of the molecular profile of ICC. Knowing the molecular profile of tumors helps determine prognosis and support certain target therapies. The molecular panel in ICC helps to select patients for specific therapies, predict treatment responses, and monitor treatment responses. Precision medicine in ICC can promote improvement in prognosis and reduce unnecessary toxicity and might have a significant role in the management of ICC in the following years. The main mutations in ICC are in tumor protein p53 (TP53), Kirsten rat sarcoma virus (KRAS), isocitrate dehydrogenase 1 (IDH1), and AT-rich interactive domain-containing protein 1A (ARID1A). The rate of mutations varies significantly for each population. Targeting TP53 and KRAS is challenging due to the natural characteristics of these genes. Different stages of clinical studies have shown encouraging results with inhibitors of mutated IDH1 and target therapy for ARID1A downstream effectors. Fibroblast growth factor receptor 2 (FGFR2) fusions are an important target in patients with ICC. Immune checkpoint blockade can be applied to a small percentage of ICC patients. Molecular profiling in ICC represents a groundbreaking approach to understanding and managing this complex liver cancer. As our comprehension of ICC's molecular intricacies continues to expand, so does the potential for offering patients more precise and effective treatments. The integration of molecular profiling into clinical practice signifies the dawn of a new era in ICC care, emphasizing personalized medicine in the ongoing battle against this malignancy.

Infiltrative Tumor Borders in Colorectal Liver Metastasis: Should We Enlarge Margin Size?

BACKGROUND: Surgery is the only potentially curative treatment for colorectal cancer liver metastases (CRLMs). Despite an improvement in results following resection, recurrence rates remain high. Many histopathological features have been reported as prognostic factors. Infiltrative borders are known to be associated with worse prognosis; however, margin size has never been evaluated together with the type of tumor border. In the present study, we analyzed the prognosis of patients with resected CRLM according to tumor growth pattern (TGP) and whether a larger margin size would bring any prognostic benefit. PATIENTS AND METHODS: Medical records from a prospective database of 645 patients who underwent hepatic resection for CRLM between January 2004 and December 2019 at a single center were reviewed, and 266 patients were included in the analytic cohort. TGP (pushing or infiltrative) was evaluated regarding the impact in overall and disease-free survival. The impact of margin size (≤ or > 1 cm) on survival and hepatic recurrence according to TGP was also evaluated. RESULTS: TGP was defined as infiltrative in 182 cases (68.4%) and pushing in 84 patients (31.6%). Patients with infiltrative-type border presented worse overall survival and disease-free survival, as well as higher intrahepatic recurrence (p < 0.05). Larger margin size did not impact the prognosis of patients with infiltrative borders. CONCLUSIONS: Patients with infiltrative-type border present worse prognosis and higher intrahepatic recurrence. Larger margin size (> 1 cm) does not change the prognosis in patients with infiltrative border, showing that tumor biology is the most important factor for survival.

The role of living donor liver transplantation in treating intrahepatic cholangiocarcinoma.

Introduction: Intrahepatic cholangiocarcinoma (iCC) is the liver's second most common neoplasm. Until now, surgery is the only curative option, but only 35% of the cases are considered resectable at the diagnosis, with a post-resection survival of around 30%. Advancements in surgical techniques and perioperative care related to liver transplantation (LT) have facilitated the expansion of indications for hepatic neoplasms. Method: This study is a comprehensive review of the global experience in living donor LT (LDLT) for treating iCC and describes our first case of LDLT for an unresectable iCC. Results: While exploring LT for intrahepatic cholangiocarcinoma dates to the 1990s, the initial outcomes were discouraging, marked by poor survival and high recurrence rates. Nevertheless, contemporary perspectives underscore a reinvigorated emphasis on extending the frontiers of LT indications within the context of the "oncologic era." The insights gleaned from examining explants, wherein incidental iCC was categorized as hepatocellular carcinoma in the preoperative period, have demonstrated comparable survival rates to small hepatocellular carcinoma. These findings substantiate the potential viability of LT as a curative alternative for iCC. Another investigated scenario pertains to "unresectable tumors with favorable biological behavior," LT presents a theoretical advantage by providing free margins without the concern of a small future liver remnant. The constraint of organ shortage persists, particularly in nations with low donation rates. LDLT emerges as a viable and secure alternative for treating iCC. Conclusion: LDLT is an excellent option for augmenting the graft pool, particularly in carefully selected patients.

Nuclear factor kappa-light-chain-enhancer of activated B cells gene expression involvement in porcine liver transplant experimental model.

PURPOSE: Gene expressions of vascular Endothelial Growth Factor Alpha (VEGFa), Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B cells (NFkB) and cytokines could be useful for identifying potential therapeutic targets to alleviate ischemia-reperfusion injury after liver transplantation. Cytokine gene expressions, VEGFa and NFkB were investigated in a preclinical swine model of liver transplantation. METHODS: A total of 12 pigs were used as donors and recipients in liver transplantation without venovenous bypass or aortic clamping. NFkB, IL-6, IL-10, VEGFa and Notch1 gene expression were assessed. These samples were collected in two specific times: group 1 (n= 6) - control, samples were collected before recipient's total hepatectomy and group 2 - liver transplantation group (n=6), where the samples were collected one hour after graft reperfusion. RESULTS: Liver transplantation was successfully performed in all recipients. Liver enzymes were elevated in the transplantation group. NFkB gene expression was significantly decreased in the transplantation group in comparison with the control group (0.62±0.19 versus 0.39±0.08; p= 0.016). No difference was observed between groups Interleucine 6 (IL-6), interleucine 10 (IL-10), VEGFa and Notch homolog 1 (Notch1). CONCLUSIONS: In this survey a decreased NFkB gene expression in a porcine model of liver transplantation was observed.

Objective Tumor Response of Hepatocellular Carcinoma Obtained by Transarterial Radioembolization with Iodine-131-Lipiodol Versus Transarterial Chemoembolization for Patients with and without Portal Venous Thrombosis: A Controlled Interventional Trial.

RATIONALE AND OBJECTIVES: Hepatocellular carcinoma (HCC) treatment often requires transarterial chemoembolization (TACE). However, TACE efficacy is controversial in the presence of portal vein thrombosis (PVT). Although transarterial radioembolization (TARE) benefit was previously documented in PVT, neither the objective tumor response (OTR) after TARE with Iodine-131-lipiodol (131I-lipiodol) nor the PVT effect on the results of locoregional therapies was accurately measured in prospective clinical trials. The aim of this study was to compare OTR and survival obtained by TARE with 131I-lipiodol versus TACE in patients with cirrhosis and HCC, as well as between those with and without PVT. MATERIALS AND METHODS: 33 patients were included, from whom 38 tumors were assessed. OTR was quantified by a special algorithm to measure hypervascular HCC tissue. RESULTS: 19 tumors received each therapy. Nine subjects (27%) had PVT, most of them in the TARE group (p = 0.026). Mean OTR according to the tumor volumes was 24.2% ± 56% after TARE and 32.8% ± 48.9% after TACE, with no difference between the treatments (p = 0.616). Similar values were also observed between those with and without PVT (p = 0.704). Mean survival was 340 days and did not differ between the two treatments (p = 0.596), but was 194 days in PVT cases (p = 0.007). CONCLUSIONS: This is the first study in which OTR obtained by TARE with 131I-lipiodol is accurately measured. Additionally, PVT impact on survival after TARE and TACE was precisely documented. Although the TARE group had more PVT subjects (who had shorter survival), TARE and TACE achieved similar OTR and OS rates.

Liver transplantation after DRESS syndrome: A case report and review of the literature.

This study reports a patient with DRESS syndrome, associated with liver failure, treated with orthotopic liver transplantation.

Abdominal and inguinal hernia in cirrhotic patients: what's the best approach?

BACKGROUND: Traditionally, elective abdominal procedures in cirrhotic patients have been largely discouraged due to high morbidity and mortality consequent to complications of cirrhosis, described by several authors. Other services, however, obtained different results, advocating in favor of elective surgery. METHODS: A literature review using as key-words "abdominal wall hernia" and "cirrhotic patients" was performed using PubMed database. Twenty-eight articles were considered. RESULTS: The incidence of abdominal wall hernias is relatively high in cirrhotic patients, specially those with ascites, and many of these are unfavorable and require specific surgical treatment. Currently, with the advent of MELD score for organ allocation, many centers are reconsidering their approach on leading these situations, since most of patients in question are on waiting list for liver transplantation. Thus elective surgery has achieved major position in managing this condition in order to reduce morbidity and mortality in these patients. Moreover, the quality of life was an important factor to be considered, being badly damaged in this condition. CONCLUSION: Few studies with large samples have been conducted so far and there is no consensus on which conduct is the most suitable taking into consideration rates of morbidity and mortality.

Hérnias abdominais e inguinais em pacientes cirróticos: qual é a melhor conduta? / Abdominal and inguinal hernia in cirrhotic patients: what's the best approach?

INTRODUÇÃO: Tradicionalmente os procedimentos abdominais eletivos em pacientes cirróticos têm sido amplamente desencorajados graças à elevada morbi-mortalidade consequente às complicações da cirrose, descritas por diversos autores. Outros serviços, em contrapartida, obtiveram resultados distintos, advogando a favor de cirurgia eletiva. MÉTODOS: Uma revisão de artigos utilizando-se a palavras "abdominal wall hernia" e "cirrhotic patients" foi realizada na base de dados PubMed. Dos resultados obtidos, 28 artigos foram considerados para elaboração desta revisão. RESULTADOS: Pôde-se observar que a incidência de hérnias em parede abdominal é relativamente elevada em pacientes cirróticos, sendo que muitas delas têm evolução desfavorável e requerem tratamento cirúrgico específico. Com o advento do sistema de alocação de órgãos baseados no escore de MELD, muitos centros estão repensando suas condutas em situações como esta, dado que muitos dos pacientes em questão encontram-se em lista de espera para transplante hepático. Dessa forma a cirurgia eletiva tem conquistado maior papel no manejo desta condição com intuito de diminuir morbi-mortalidade nesses pacientes. Além disso, a qualidade de vida mostrou-se um importante fator a ser considerado, estando muito prejudicada nesta condição. CONCLUSÃO: Poucos estudos com grandes amostragens foram conduzidos até o momento e não há consenso sobre qual conduta é a mais indicada levando em consideração taxas de morbi-mortalidade.

BACKGROUND: Traditionally, elective abdominal procedures in cirrhotic patients have been largely discouraged due to high morbidity and mortality consequent to complications of cirrhosis, described by several authors. Other services, however, obtained different results, advocating in favor of elective surgery. METHODS: A literature review using as key-words "abdominal wall hernia" and "cirrhotic patients" was performed using PubMed database. Twenty-eight articles were considered. RESULTS: The incidence of abdominal wall hernias is relatively high in cirrhotic patients, specially those with ascites, and many of these are unfavorable and require specific surgical treatment. Currently, with the advent of MELD score for organ allocation, many centers are reconsidering their approach on leading these situations, since most of patients in question are on waiting list for liver transplantation. Thus elective surgery has achieved major position in managing this condition in order to reduce morbidity and mortality in these patients. Moreover, the quality of life was an important factor to be considered, being badly damaged in this condition. CONCLUSION: Few studies with large samples have been conducted so far and there is no consensus on which conduct is the most suitable taking into consideration rates of morbidity and mortality.

Avaliação da qualidade de vida em pacientes cirróticos com hérnia da parede abdominal / Quality of life in patients with abdominal hernia and cirrhosis

RACIONAL: As hérnias de parede abdominal são um problema frequente no paciente cirrótico. Elas costumam ser volumosas e muito sintomáticas. OBJETIVO: Avaliar a qualidade de vida, através da aplicação do questionário Short Form-36 (SF-36), nos pacientes com hérnia e cirrose. MÉTODOS: Foram avaliados 39 pacientes cirróticos com hérnia de parede abdominal estratificados pela classificação de Child e submetidos ao questionário SF-36 por um mesmo profissional. RESULTADOS: A média dos escores obtidos no SF-36 mostra diminuição em todos os domínios nos pacientes cirróticos, principalmente no aspecto físico. O grupo Child B mostrou pior avaliação ao estado geral de saúde e capacidade funcional em relação ao grupo Child A, contudo não houve diferença em relação ao aspecto físico. CONCLUSÃO: A presença de hérnia de parede abdominal ocasiona piora na qualidade de vida do paciente cirrótico. A deterioração da função hepática está relacionada a pior qualidade de vida. A hérnia abdominal leva a restrição importante no aspecto físico também no Child A.

BACKGROUND: Abdominal hernias are frequent issue in cirrhotic patients. These hernias tend to be large and symptomatic. AIM: To analyze the quality of life using a Short Form-36 (SF-36) questionnaire in cirrhotic patients with abdominal hernia. METHODS: Thirty nine cirrhotic patients with abdominal wall hernia were analyzed. They were stratified according to Child´s classification and answered the SF-36 questionnaire administered by a same professional. RESULTS: The scores from SF-36 show impairment in all questionnaire domains in cirrhotic patients, especially in the physical aspect. The Child B group showed worse health general condition and functional capacity comparing with Child A group; however it did not show any significant difference related to physical aspect. CONCLUSION: The presence of abdominal hernia leads to worse quality of life in cirrhotic patients. Hepatic function deterioration is related to a worse quality of life. Abdominal hernia causes an important restriction in physical aspect even in Child A.