Malignant liver tumours include a wide range of primary and secondary tumours. Although surgery remains the mainstay of curative treatment, modern therapies integrate a variety of neoadjuvant and ...adjuvant strategies and have achieved dramatic improvements in survival. Extensive tumour loads, which have traditionally been considered unresectable, are now amenable to curative treatment through systemic conversion chemotherapies followed by a variety of interventions such as augmentation of the healthy liver through portal vein occlusion, staged surgeries or ablation modalities. Liver transplantation is established in selected patients with hepatocellular carcinoma but is now emerging as a promising option in many other types of tumour such as perihilar cholangiocarcinomas, neuroendocrine or colorectal liver metastases. In this Review, we summarize the available therapies for the treatment of malignant liver tumours, with an emphasis on surgical and ablative approaches and how they align with other therapies such as modern anticancer drugs or radiotherapy. In addition, we describe three complex case studies of patients with malignant liver tumours. Finally, we discuss the outlook for future treatment, including personalized approaches based on molecular tumour subtyping, response to targeted drugs, novel biomarkers and precision surgery adapted to the specific tumour.
OBJECTIVES:To critically assess centralization policies for highly specialized surgeries in Europe and North America and propose recommendations.
BACKGROUND/METHODS:Most countries are increasingly ...forced to maintain quality medicine at a reasonable cost. An all-inclusive perspective, including health care providers, payers, society as a whole and patients, has ubiquitously failed, arguably for different reasons in environments. This special article follows 3 aimsfirst, analyze health care policies for centralization in different countries, second, analyze how centralization strategies affect patient outcome and other aspects such as medical education and cost, and third, propose recommendations for centralization, which could apply across continents.
RESULTS:Conflicting interests have led many countries to compromise for a health care system based on factors beyond best patient-oriented care. Centralization has been a common strategy, but modalities vary greatly among countries with no consensus on the minimal requirement for the number of procedures per center or per surgeon. Most national policies are either partially or not implemented. Data overwhelmingly indicate that concentration of complex care or procedures in specialized centers have positive impacts on quality of care and cost. Countries requiring lower threshold numbers for centralization, however, may cause inappropriate expansion of indications, as hospitals struggle to fulfill the criteria. Centralization requires adjustments in training and credentialing of general and specialized surgeons, and patient education.
CONCLUSION/RECOMMENDATIONS:There is an obvious need in most areas for effective centralization. Unrestrained, purely “market driven” approaches are deleterious to patients and society. Centralization should not be based solely on minimal number of procedures, but rather on the multidisciplinary treatment of complex diseases including well-trained specialists available around the clock. Audited prospective database with monitoring of quality of care and cost are mandatory.
Background Blood loss during liver transplantation is not incorporated into the dominant models for post-transplant survival. Our objective was to investigate blood transfusion requirement as a risk ...factor for mortality after liver transplantation, and to further analyze risk factors for intraoperative blood transfusion requirement and hepatectomy time. Study Design We conducted a retrospective analysis of 233 consecutive liver transplant recipients over a span of 3 years by a single experienced surgeon. Mean follow-up was 2.5 years. Independent risk factors for patient survival after liver transplantation were identified using Cox proportion hazard regression. Independent risk factors for intraoperative blood transfusion requirement and hepatectomy time were identified using logistic regression. Results Two factors were identified as significant predictors in multivariate analysis for survival after liver transplantation: hepatocellular carcinoma (hazard ratio HR 1.9, 95% CI 1.1 to 3.2) and intraoperative blood transfusion requirement per unit (HR 1.01, 95% CI 1.0 to 1.02). Threshold analysis revealed that intraoperative blood transfusion volume ≥28 units or 85th percentile (HR 2.5, 95% CI 1.3 to 4.7) was a significant risk factor for patient survival. Four covariates were identified as significant risk factors for intraoperative blood requirement: warm ischemia time (odds ratio OR 1.12, 95% CI 1.06 to 1.18), bilirubin (OR 1.04, 95% CI 1.02 to 1.08), previous surgery (OR 1.7, 95% CI 1.02 to 2.9), and hepatectomy time (OR 1.01, 95% CI 1.00 to 1.02). The only risk factor for prolonged hepatectomy time was previous major abdominal surgery (OR 4.0, 95% CI 1.7 to 9.5). Conclusions Intraoperative blood transfusion requirement is an important risk factor for mortality after liver transplantation. The strongest risk factors for intraoperative blood transfusion requirement are warm ischemia time and bilirubin levels. Intraoperative blood loss and its risk factors should be incorporated into models to predict survival after liver transplantation.
Abstract
Hypoxia is prominent in solid tumors and a recognized driver of malignancy. Thus far, targeting tumor hypoxia has remained unsuccessful. Myo-inositol trispyrophosphate (ITPP) is a ...re-oxygenating compound without apparent toxicity. In preclinical models, ITPP potentiates the efficacy of subsequent chemotherapy through vascular normalization. Here, we report the results of an unrandomized, open-labeled, 3 + 3 dose-escalation phase Ib study (NCT02528526) including 28 patients with advanced primary hepatopancreatobiliary malignancies and liver metastases of colorectal cancer receiving nine 8h-infusions of ITPP over three weeks across eight dose levels (1'866-14'500 mg/m
2
/dose), followed by standard chemotherapy. Primary objectives are assessment of the safety and tolerability and establishment of the maximum tolerated dose, while secondary objectives include assessment of pharmacokinetics, antitumor activity via radiological evaluation and assessment of circulatory tumor-specific and angiogenic markers. The maximum tolerated dose is 12,390 mg/m
2
, and ITPP treatment results in 32 treatment-related toxicities (mostly hypercalcemia) that require little or no intervention. 52% of patients have morphological disease stabilization under ITPP monotherapy. Following subsequent chemotherapy, 10% show partial responses while 60% have stable disease. Decreases in angiogenic markers are noted in ∼60% of patients after ITPP and tend to correlate with responses and survival after chemotherapy.
IMPORTANCE: Long-term oncologic outcomes of robotic surgery remain a hotly debated topic in surgical oncology, but sparse data have been published thus far. OBJECTIVE: To analyze short- and long-term ...outcomes of robotic liver resection (RLR) for hepatocellular carcinoma (HCC) from Western high-volume centers to assess the safety, reproducibility, and oncologic efficacy of this technique. DESIGN, SETTING, AND PARTICIPANTS: This cohort study evaluated the outcomes of patients receiving RLR vs open liver resection (OLR) for HCC between 2010 and 2020 in 5 high-volume centers. After 1:1 propensity score matching, a group of patients who underwent RLR was compared with a validation cohort of OLR patients from a high-volume center that did not perform RLR. MAIN OUTCOMES AND MEASURES: A retrospective analysis was performed of prospectively maintained databases at 2 European and 2 US institutions of patients who underwent RLR for HCC between January 1, 2010, and September 30, 2020. The main outcomes were safety and feasibility of RLR for HCC and its oncologic outcomes compared with a European OLR validation cohort. A 2-sided P < .05 was considered significant. RESULTS: The study included 398 patients (RLR group: 125 men, 33 women, median IQR age, 66 58-71 years; OLR group: 315 men, 83 women; median IQR age, 70 64-74 years), and 106 RLR patients were compared with 106 OLR patients after propensity score matching. The RLR patients had a significantly longer operative time (median IQR, 295 190-370 minutes vs 200 165-255 minutes, including docking; P < .001) but a significantly shorter hospital length of stay (median IQR, 4 3-6 days vs 10 7-13 days; P < .001) and a lower number of admissions to the intensive care unit (7 6.6% vs 21 19.8%; P = .002). Incidence of posthepatectomy liver failure was significantly lower in the RLR group (8 7.5% vs 30 28.3%; P = .001), with no cases of grade C failure. The 90-day overall survival rate was comparable between the 2 groups (RLR, 99.1% 95% CI, 93.5%-99.9%; OLR, 97.1% 95% CI, 91.3%-99.1%), as was the cumulative incidence of death related to tumor recurrence (RLR, 8.8% 95% CI, 3.1%-18.3%; OLR, 10.2% 95% CI, 4.9%-17.7%). CONCLUSIONS AND RELEVANCE: This study represents the largest Western experience to date of full RLR for HCC. Compared with OLR, RLR performed in tertiary centers represents a safe treatment strategy for patients with HCC and those with compromised liver function while achieving oncologic efficacy.
OBJECTIVE:The aim of this study was to use the concept of benchmarking to establish robust and standardized outcome references after the procedure ALPPS (Associating Liver Partition and Portal Vein ...Ligation for Staged hepatectomy).
BACKGROUND AND AIMS:The recently developed ALPPS procedure, aiming at removing primarily unresectable liver tumors, has been criticized for safety issues with high variations in the reported morbidity/mortality rates depending on patient, disease, technical characteristics, and center experience. No reference values for relevant outcome parameters are available.
METHODS:Among 1036 patients registered in the international ALPPS registry, 120 (12%) were benchmark cases fulfilling 4 criteriapatients ≤67 years of age, with colorectal metastases, without simultaneous abdominal procedures, and centers having performed ≥30 cases. Benchmark values, defined as the 75th percentile of the median outcome parameters of the centers, were established for 10 clinically relevant domains.
RESULTS:The benchmark values were completion of stage 2≥96%, postoperative liver failure (ISGLS-criteria) after stage 2≤5%, ICU stay after ALPPS stages 1 and 2≤1 and ≤2 days, respectively, interstage interval≤16 days, hospital stay after ALPPS stage 2≤10 days, rates of overall morbidity in combining both stage 1 and 2≤65% and for major complications (grade ≥3a)≤38%, 90-day comprehensive complication index was ≤22, the 30-, 90-day, and 6-month mortality was ≤4%, ≤5%, and 6%, respectively, the overall 1-year, recurrence-free, liver-tumor-free, and extrahepatic disease-free survival was ≥86%, ≥50%, ≥57%, and ≥65%, respectively.
CONCLUSIONS:This benchmark analysis sets key reference values for ALPPS, indicating similar outcome as other types of major hepatectomies. Benchmark cutoffs offer valid tools not only for comparisons with other procedures, but also to assess higher risk groups of patients or different indications than colorectal metastases.
Colorectal cancer is the third most common cancer worldwide. Half of CRC patients develop liver metastases during the course of the disease, with a 5-year survival rate close to zero in the absence ...of therapy. Surgical resection remains the only possible curative option, and current guidelines recommend adjuvant chemotherapy, resulting in a 5-year survival rate exceeding 50%. Neoadjuvant systemic therapy is not indicated in cases with simple resection but should be offered to all patients with extensive bilobar disease. Personalised systemic treatment is essential to convert upfront non-resectable lesions to resectable ones. Anatomical resections, non-anatomical resections and two-stage hepatectomies can be performed though open or minimally invasive (laparoscopic or robotic) surgery. The extent of a hepatic resection is limited by the risk of postoperative liver failure due to a too small liver remnant, inflow or outflow obstruction or insufficient biliary drainage. About 75% of patients are diagnosed with non-resectable liver metastases not amenable to a standard upfront resection. In recent years, effective therapeutic approaches have revolutionised liver surgery and new strategies have enabled the conversion of primarily non-resectable metastatic disease for resection. These strategies include oncological and surgical therapies, as well as combinations of the two. From an oncological perspective, colorectal liver metastases may be treated by systemic chemotherapy or immunotherapy, or selective intra-hepatic arterial infusion chemotherapy, depending on the extent of the disease and the mutational status. In surgery, we often apply two-stage strategies using portal vein occlusion, such as portal vein embolisation or ligation, or complex two-stage hepatectomy such as associating liver partition and portal vein ligation for staged hepatectomy. Other additive tools to reach curative resection are tumour ablations (electroporation, microwave or radiofrequency). The role of stereotactic radiation of liver metastases is not yet well defined. Modern radiation techniques, including image guidance, breath hold and gating, were only introduced for a larger patient population in recent years. Therefore, prospective studies with larger patient cohorts are still pending. Over the last decade, liver transplantation has gained increasing attention in selective cases of non-resectable colorectal liver metastases, with promising cohort studies, but definitive recommendations must await the results of ongoing randomised controlled trials. The optimal treatment of patients with colorectal liver metastases requires the timely association of various strategies, and all cases must be discussed at multidisciplinary team conferences. While colorectal liver metastases was a uniformly lethal condition a few decades ago, it has become amenable to curative therapies, with excellent quality of life in many scenarios. This review reports on up-to-date treatment modalities and their combinations in the treatment algorithm of colorectal liver metastases.  .
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