The Impact of Portal Hypertension Assessment Method on the Outcomes of Hepatocellular Carcinoma Resection: A Meta-Analysis of Matched Cohort and Prospective studies.

OBJECTIVE: Examine PHT impact on postoperative and survival outcomes in HCC patients after LR, specifically exploring distinctions between indirect signs and invasive measurements of PHT. SUMMARY BACKGROUND DATA: PHT has historically discouraged LR in individuals with HCC, due to the elevated risk of morbidity, including liver decompensation (LD). METHODS: A systematic review was conducted using 3 databases to identify prospective controlled and matched cohort studies until December 28, 2022. Focus on comparing postoperative outcomes (mortality, morbidity, and liver-related complications) and OS in HCC patients with and without PHT undergoing LR. Three meta-analysis models were utilized: For aggregated data (fixed-effects inverse variance model), for patient-level survival data (one-stage frequentist meta-analysis with gamma-shared frailty Cox proportional hazards model), and for pooled data (Freeman-Tukey exact and double arcsine method). RESULTS: Nine studies involving 1,124 patients were analyzed. Indirect signs of PHT were not significantly associated with higher mortality, overall complications, PHLF or LD. However, LR in patients with HVPG ≥10 mmHg significantly increased the risk of overall complications, PHLF and LD. Despite elevated risks, the procedure resulted in a 5-year OS rate of 55.2%. Open LR significantly increased the risk of overall complications, PHLF and LD. Conversely, PHT did not show a significant association with worse postoperative outcomes in MILR. CONCLUSIONS: LR with indirect PHT signs poses no increased risk of complications. Yet, in HVPG ≥10 mmHg patients, LR increases overall morbidity and liver-related complications risk. Transjugular HVPG assessment is crucial for LR decisions. MI approach seems to be vital for favorable outcomes, especially in HVPG ≥10 mmHg patients.

Surgery and radioembolization of liver tumors.

Surgical resection is considered the curative treatment par excellence for patients with primary or metastatic liver tumors. However, less than 40% of them are candidates for surgery, either due to non-modifiable factors (comorbidities, age, liver dysfunction…), or to the invasion or proximity of the tumor to the main vascular requirements, the lack of a future liver remnant (FLR) adequate to maintain postoperative liver function, or criteria of tumor size and number. In these last factors, hepatic radioembolization has been shown to play a role as a presurgical tool, either by hypertrophy of the FLR or by reducing tumor size that manages to reduce tumor staging (term known as "downstaging"). To these is added a third factor, which is its ability to apply the test of time, which makes it possible to identify those patients who present progression of the disease in a short period of time (both locally and at distance), avoiding a unnecessary surgery. This paper aims to review RE as a tool to facilitate liver surgery, both through the experience of our center and the available scientific evidence.

Liver Resection and Transplantation Following Yttrium-90 Radioembolization for Primary Malignant Liver Tumors: A 15-Year Single-Center Experience.

Radioembolization (RE) may help local control and achieve tumor reduction while hypertrophies healthy liver and provides a test of time. For liver transplant (LT) candidates, it may attain downstaging for initially non-candidates and bridging during the waitlist. METHODS: Patients diagnosed with HCC and ICC treated by RE with further liver resection (LR) or LT between 2005-2020 were included. All patients selected were discarded for the upfront surgical approach for not accomplishing oncological or surgical safety criteria after a multidisciplinary team assessment. Data for clinicopathological details, postoperative, and survival outcomes were retrospectively reviewed from a prospectively maintained database. RESULTS: A total of 34 patients underwent surgery following RE (21 LR and 13 LT). Clavien-Dindo grade III-IV complications and mortality rates were 19.0% and 9.5% for LR and 7.7% and 0% for LT, respectively. After RE, for HCC and ICC patients in the LR group, 10-year OS rates were 57% and 60%, and 10-year DFS rates were 43.1% and 60%, respectively. For HCC patients in the LT group, 10-year OS and DFS rates from RE were 51.3% and 43.3%, respectively. CONCLUSION: Liver resection after RE is safe and feasible with optimal short-term outcomes. Patients diagnosed with unresectable or high biological risk HCC or ICC, treated with RE, and rescued by LR may achieve optimal global and DFS rates. On the other hand, bridging or downstaging strategies to LT with RE in HCC patients show adequate recurrence rates as well as long-term survival.

International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres.

PURPOSE: A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-resin microspheres. METHODS: A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%-79%, no agreement ≤ 49%). RESULTS: Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100-120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement). CONCLUSION: Practitioners are encouraged to work towards adoption of these recommendations.

Biocompatibility, inflammatory response, and recannalization characteristics of nonradioactive resin microspheres: histological findings.

Intra-arterial radiotherapy with yttrium-90 microspheres (radioembolization) is a therapeutic procedure exclusively applied to the liver that allows the direct delivery of high-dose radiation to liver tumors, by means of endovascular catheters, selectively placed within the tumor vasculature. The aim of the study was to describe the distribution of spheres within the precapillaries, inflammatory response, and recannalization characteristics after embolization with nonradioactive resin microspheres in the kidney and liver. We performed a partial embolization of the liver and kidney vessels in nine white pigs. The left renal and left hepatic arteries were catheterized and filled with nonradioactive resin microspheres. Embolization was defined as the initiation of near-stasis of blood flow, rather than total occlusion of the vessels. The hepatic circulation was not isolated so that the effects of reflux of microspheres into stomach could be observed. Animals were sacrificed at 48 h, 4 weeks, and 8 weeks, and tissue samples from the kidney, liver, lung, and stomach evaluated. Microscopic evaluation revealed clusters of 10-30 microspheres (15-30 microm in diameter) in the small vessels of the kidney (the arciform arteries, vasa recti, and glomerular afferent vessels) and liver. Aggregates were associated with focal ischemia and mild vascular wall damage. Occlusion of the small vessels was associated with a mild perivascular inflammatory reaction. After filling of the left hepatic artery with microspheres, there was some evidence of arteriovenous shunting into the lungs, and one case of cholecystitis and one case of marked gastritis and ulceration at the site of arterial occlusion due to the presence of clusters of microspheres. Beyond 48 h, microspheres were progressively integrated into the vascular wall by phagocytosis and the lumen recannalized. Eight-week evaluation found that the perivascular inflammatory reaction was mild. Liver cell damage, bile duct injury, and portal space fibrosis were not observed. In conclusion, resin microspheres (15-30 microm diameter) trigger virtually no inflammatory response in target tissues (liver and kidney). Clusters rather than individual microspheres were associated with a mild to moderate perivascular inflammatory reaction. There was no evidence of either a prolonged inflammatory reaction or fibrosis in the liver parenchyma following recannalization.

Reservorio intraarterial hepático para quimioterapia. Colocación percutánea en la arteria subclavia izquierda / Intra-arterial hepatic reservoir for chemotherapy. Percutaneous placement in left subclavian artery

Objetivos: Describir la técnica empleada y valorar los resultados, en la implantación percutánea de un catéter en la arteria hepática a través de la subclavia izquierda, para administración de quimioterapia regional. Material y métodos: Entre abril de 1999 y junio de 2002, a 33 pacientes (17 varones y 16 mujeres) de 52,9 años de media y con evidencia de lesión hepática (32 metástasis hepáticas, un hepatocarcinoma fibrolamelar), se les implantaron 36 catéteres intraarteriales. El acceso en todos los casos fue la arteria subclavia izquierda con guía ecográfica. Se estudió la vascularización hepática y se emplazó el catéter distal en arteria hepática. Asimismo, se embolizaron ramas extrahepáticas de la arteria hepática, para evitar fuga del quimioterápico. La cánula se conectó al reservorio (Port-a-cath Titaniumvenous system. Daltec MN. USA) implantado, subcutáneo, próximo al punto de punción. Resultados: El éxito técnico se consiguió en todos los casos (catéter en arteria hepática común en 31 casos, tres en la arteria hepática derecha, uno en la arteria hepática izquierda procedente de la gástrica izquierda y uno en la arteria hepática derecha procedente de la mesentérica superior). La permanencia de los reservorios osciló entre 22 y 740 días (media, 222,4 días). Se registraron complicaciones en 13 casos (36,1%): cinco migraciones de cánula, cuatro vainas de fibrina, tres obstrucciones del vaso cateterizado, una contaminación y una fuga en la conexión. Se solucionaron de modo percutáneo o con retirada del dispositivo. Conclusión: La implantación percutánea de un catéter intraarterial hepático y reservorio, a través de la subclavia izquierda con ayuda ecográfica, es técnicamente factible, y con una tasa de complicaciones aceptable además de solucionables percutáneamente

Objetives: To describe the technique used and to assed about the results obtained in the percutaneous implantation of a catheter in hepatic artery (HA) through left subclavian artery to administer regional chemotherapy. Material and methods: Between April 1999 and June 2002, 33 patients (17 men and 16 women) with a mean age of 52.9 years and with evidence of hepatic lesion (32 hepatic metastases, 1 fibrolamellar hepatocarcinoma (HCC), 36 intra-arterial catheters were implanted. Access in every case was the left subclavian artery with ultrasonographic guide. Hepatic vascularization was studied and distal catheter was located in the HA. Furthermore, extrahepatic branches of the HA were embolized to avoid chemotherapeutic escape. The cannula was connected to the subcutaneous implanted reservoir (Port-a-cath Titaniumvenous system. Daltec. M.N. USA) close to the puncture point. Results: Technical success was achieved in every case (catheter in common HA 31 cases, 3 in right HA, 1 in left HA from left gastric artery and 1 in right HA from upper mesenteric artery). The permanence of the reservoirs ranged from 22 to 740 days (mean 222.4 days). Complications were recorded in 13 cases (36.1%): 5 canula migrations, 4 fibrin sheath, 3 obstruction of catheterized vessel, 12 contamination and 1 escape from the connection. They were solved percutaneously or by withdrawal of the device. Conclusion: Percutaneous implantation of an intra-arterial hepatic catheter and reservoir through the left subclavian artery with ultrasonographic guidance is technically feasible and has an acceptable rate of complications besides being percutaneously solutionable

Embolización portal prequirúrgica / Presurgical portal embolization

En pacientes con tumores hepáticos, el tratamiento más eficaz es la cirugía. Sin embargo, no todos pueden ser tratados de esta manera. Uno de los motivos que contraindican el tratamiento quirúrgico es que el parénquima hepático que queda tras la resección de la zona tumoral sea insuficiente para asegurar la función hepática del paciente. Es conocido que el hepatocito, tras determinados estímulos, tiene la posibilidad de desdiferenciarse y clonarse. La embolización portal prequirúrgica (EPP) del volumen hepático que se va a resecar puede generar, tras este estímulo y respuesta (que será diferente en hígados fibróticos y no fibróticos), un crecimiento hepático que alcanzará niveles adecuados en 3-4 semanas. Por tanto, la EPP puede incrementar el número de candidatos a recibir tratamiento quirúrgico y, del mismo modo, puede disminuir la aparición de posibles complicaciones postoperatorias. En este artículo se presentan lo criterios de inclusión y exclusión que, de forma comúnmente aceptada, se utilizan para realizar una EPP. No hay acuerdo, sin embargo, sobre la técnica más adecuada para acceder al sistema portal, por ejemplo, la vía contralateral (con punción de los segmentos portales que no van a ser resecados) tiene considerables ventajas técnicas, pero pone en riesgo de trombosis a las ramas portales del tejido hepático sano. Son muchos los materiales embolizantes que se han usado en EPP, algunos autores recomiendan el empleo de «pegamentos», pues son relativamente sencillos de utilizar, de bajo coste y altamente eficaces pero, por otra parte, generan una importante inflamación periportal que puede dificultar la resección quirúrgica. Si se emplean partículas, éstas deben ser de un tamaño que oscile entre las 100 y las 300 micras. En conclusión, aunque todavía hay muchos aspectos de la EPP que requieren ser investigados, la técnica debería de estar disponible en todos los centros en los que se realice cirugía hepática, pues los beneficios clínicos derivados de ésta son muy satisfactorios

Surgery is the most efficacious treatment for hepatic tumors; however, not all patients with hepatic tumors can be treated surgically. One condition in which surgery is contraindicated is when the amount of liver parenchyma remaining after resection of the affected zone is considered to be insufficient to ensure hepatic function. The hepatocyte is known to be able to dedifferentiate and clone itself after certain stimuli. Presurgical portal embolization (PPE) of the hepatic volume to be resected can generate hepatic growth after this stimulus and response (which will be different in fibrotic and nonfibrotic livers), achieving adequate levels within 3-4 weeks. Therefore, PPE can increase the number of candidates for surgical treatment and decrease the number of possible postsurgical complications. This article describes the commonly accepted inclusion and exclusion criteria used for PPE. There is no consensus, however, regarding the most appropriate technique for accessing the portal system. For example, the contralateral approach (with puncture of the portal segments that are not to be resected) has considerable technical advantages, but places the portal branches of healthy liver tissue at risk for thrombosis. Many different materials have been used for embolization in PPE. Some authors recommend the use of "glues", as these are relatively easy to use, low cost, and highly efficacious; however, they also generate significant periportal inflammation that can make surgical resection more difficult. If particles are used, they should measure between 100-300 micras. In conclusion, although many aspects of PPE still need to be investigated, this technique should be made available in all centers performing hepatic surgery, as it can result in significant clinical benefits