Search Results (73)

Background/Objectives: Gallbladder cancer (GBC) is a lethal malignancy curable only by surgical resection in early stages (Tis, T1, T2). Significant controversy exists regarding the optimal extent of surgery. This review summarizes recent trends and evidence on surgical strategies for Tis, T1, and T2 GBC to guide practice and research. Methods: This narrative review synthesizes recent literature on surgical management of Tis, T1a, T1b, and T2 GBC based on American Joint Committee on Cancer (AJCC) 8th edition staging. It examines simple vs. extended cholecystectomy (simple cholecystectomy (SC) vs. extended/radical cholecystectomy (EC/RC)), the role of lymphadenectomy (LND) and hepatectomy, and minimally invasive surgery (MIS). Results: Simple cholecystectomy is curative for Tis/T1a GBC. For T1b, regional LND is essential for staging/potential benefit, especially examining ≥5–6 nodes. Tumor size is critical; SC alone may suffice for T1b < 1 cm (low lymph node metastasis (LNM) risk), while EC/RC with LND is indicated for ≥1 cm (higher LNM risk). Routine hepatectomy for T1b lacks survival support. For T2 GBC, mandatory regional LND (≥6 nodes) is required for both T2a and T2b substages due to high LNM rates; T2b has higher LNM than T2a. Routine hepatectomy for T2 is debated; evidence suggests no routine benefit for T2a beyond LND, with conflicting findings for T2b. R0 resection is paramount. MIS is feasible for early stages in experienced hands. Conclusions: Management of early GBC is moving towards risk stratification. SC is standard for Tis/T1a. Adequate regional LND is crucial for T1b (especially ≥1 cm) and mandatory for T2 GBC. Routine hepatectomy, particularly for T2b, remains controversial. Tailored surgery prioritizes R0 resection and comprehensive LND, necessitating further standardized research. Full article

Background: In September 2021, pemigatinib received Health Canada approval for previously treated locally advanced/metastatic cholangiocarcinoma (CCA) with FGFR2 rearrangements/fusions. This retrospective study aimed to characterize the real-world management and outcomes of patients with CCA receiving pemigatinib through a Canadian patient support program (PSP). Methods: We evaluated a multi-centre case series of Canadian patients who were prescribed pemigatinib between September 2021 and January 2023 for eligible CCA diagnoses and enrolled in the PSP. The retrospective study data included demographic and disease-, treatment-, and outcome-related information, and these were collected using a survey of prescribing physicians. Results: Of the 26 patients who initiated pemigatinib in the PSP, we received survey responses for 18 (69%). Their median age was 57 years, 67% were female, 61% had stage IV disease, and 83% had intrahepatic CCA. Prior to pemigatinib, a partial hepatectomy was performed in 44% of the patients, and 66% of the patients received 2–4 prior lines of systemic therapy. All patients were treated with platinum-based regimens as the first-line treatment for unresectable/metastatic disease. The median follow-up time on pemigatinib was 12.6 (range: 2.3–28.4) months, and their median real-world progression-free survival (rwPFS) was 12.1 months (95% CI 7.2-NR). The physician-assessed objective response and disease control rates were 56% and 89%, respectively. For the nine patients who discontinued pemigatinib, the median treatment duration was 10.6 months (range: 0.8–21.7). Disease progression was the most common reason for discontinuation (89%). None discontinued due to adverse events. Conclusions: Objective response rates, disease control rates, and a PFS comparable to that in the phase 2 FIGHT-202 trial was reported with pemigatinib use in this Canadian PSP cohort. Full article

Primary hepatic gastrointestinal stromal tumours (PHGISTs) are rare and frequently misdiagnosed due to their atypical presentation and uncertain origin. The purpose of this article is to present the case of a 79-year-old female patient with a gigantic PHGIST characterized by a predominantly cystic nature—an extremely rare presentation, as most cases of PHGIST are solid. Despite extensive imaging and exploratory laparotomy, the primary origin remained uncertain, leading to questioning about whether it was a true primary hepatic GIST or an atypical metastatic lesion. The initial therapeutic approach involved a surgical procedure aimed to confirm the diagnosis and achieve reductive tumourectomy. Following the surgery, the patient was administered imatinib with a favourable clinical response for four and a half years—an atypical pattern of resistance, as most patients typically develop therapeutic resistance within two to three years. A second surgical intervention was performed to address a cystic lesion localized in the left hepatic lobe, followed by an atypical segment III hepatectomy to achieve macroscopic resection. Subsequently, the patient received sunitinib for two and a half years, which resulted in temporary disease stabilization. However, the sunitinib treatment was associated with hypertension and leukopenia. The patient’s overall survival was 8 years, suggesting that individualized therapeutic strategies and close monitoring might be the key in such cases. Furthermore, this case confirms the role of surgical intervention even in advanced disease stages, with multiple major resections contributing significantly to prolonged survival. The interplay between surgical and oncologic therapies remains essential to guiding clinical decisions. Given the unusual cystic presentation, this case highlights the necessity to expand the pathological and molecular profiling of PHGISTs. Furthermore, the atypical timeline of resistance development and treatment-related toxicity emphasizes the importance of further research into the genetic and pharmacological determinants of PHGISTs. These findings advocate for the refinement of diagnostic, therapeutic, and surveillance protocols tailored to rare GIST subtypes. Full article

Background/Objectives: Extrahepatic recurrence (EHR) is a significant negative prognostic factor in hepatocellular carcinoma (HCC). Although EHR is commonly observed in high-risk patients following HCC hepatectomy, its occurrence without concurrent intrahepatic HCC remains poorly understood. Therefore, this study aims to examine the clinical characteristics and risk factors associated with EHR in patients without intrahepatic HCC at diagnosis. Methods: This study included 1066 treatment-naïve patients who underwent curative hepatectomy for HCC at four tertiary academic centers between January 2004 and December 2019. After excluding those with intrahepatic recurrence (IHR), concurrent EHR, or incomplete clinical records, 569 patients were included in the final analysis. Risk factors for EHR were assessed using multivariate Cox regression over a median follow-up period of 3.91 years. Results: Among the cohort, 38 patients developed EHR post-surgery without residual intrahepatic HCC, with a median follow-up of 1.04 years. These patients experienced earlier initial HCC recurrence than those without EHR (1.73 vs. 4.43 years). Multivariate analysis revealed significant associations between EHR and microvascular invasion (hazard ratio [HR]: 2.418, p = 0.020), tumor necrosis (HR: 2.592, p = 0.009), and initial tumor staging beyond the Milan criteria (HR: 3.008, p = 0.001). Moreover, Cox regression analysis revealed that EHR strongly correlated with decreased post-hepatectomy survival (HR: 14.044, p < 0.001). Cumulative EHR and survival rates were closely linked to the number of risk factors present. Conclusions: EHR without detectable IHR is significant and warrants close monitoring in high-risk patients. Full article

Background/Objectives: Although immunotherapy is the primary treatment option for intermediate-stage hepatocellular carcinoma (HCC), its efficacy varies. This study aimed to identify non-invasive imaging biomarkers predictive of the immunoscore linked to dynamic contrast-enhanced computed tomography (CECT). Methods: We performed immunohistochemical staining with CD3⁺ and CD8⁺ antibodies and counted the positive cells in the invasive margin (IM) and central tumor (CT), converting them to an immunoscore of 0 to 4 points. We assessed the dynamic CECT findings obtained from 96 patients who underwent hepatectomy for HCC and evaluated the relationship between dynamic CECT findings and immunoscores. For validation, we assessed the treatment effects on 81 nodules using the Response Evaluation Criteria in Solid Tumors in another cohort of 41 patients who received combined immunotherapy with atezolizumab and bevacizumab (n = 27) and durvalumab and tremelizumab (n = 14). Results: HCCs with peritumoral enhancement in the arterial phase (p < 0.001) and rim APHE (p = 0.009) were associated with the immunoscore in univariate linear regression analysis and peritumoral enhancement in the arterial phase (p = 0.004) in multivariate linear regression analysis. The time to nodular progression in HCCs with peritumoral enhancement in the arterial phase was significantly longer than that in HCCs without this feature (p < 0.001). Conclusions: We identified HCCs with peritumoral enhancement in the arterial phase as a noninvasive imaging biomarker to predict immune-inflamed HCC with a high immunoscore tendency. These HCCs were most likely to respond to combined immunotherapy. Full article

Background/Objectives: The post-hepatectomy survival of patients with hepatocellular carcinoma (HCC) faces challenges due to high recurrence rates, especially early recurrence (ER). We investigated DNA methylation in HCC and developed a methylation-based model for ER prediction (MER). Methods: We studied HCC patients with ER within a year post-hepatectomy, comparing them to those who remained recurrence-free (RF) for 5 years. In a testing set, we examined genome-wide methylation profiles to identify differences between ER and RF. Validation in an independent cohort confirmed candidate markers using real-time quantitative methylation-specific PCR (qMSP). We constructed MER by incorporating identified gene methylation, clinical information, and serum protein marker, and evaluated its predictive performance using ROC analysis and Cox regression. Results: Distinct signatures of hypermethylation and hypomethylation were observed between ER and RF, as well as between cirrhotic and non-cirrhotic groups. Significant aberrant methylation pathways, including FGFR signaling, the PI3K network, and the MAPK pathway, were observed in non-cirrhotic ER patients. Conversely, cirrhotic ER patients showed notable associations with Wnt/β-catenin signaling, cell adhesion, and migration mechanisms. Through qMSP analysis, we identified ER-associated genes, including BDNF, FOXL2, LMO7, NCAM1, NEIS3, PLA2G7, and LTB4R. MER demonstrated strong predictive ability for ER, with an AUC of 0.855, surpassing current indicators such as AFP, tumor size, and BCLC stage. Combining different predictors resulted in heightened AUC values. Importantly, the inclusion of MER yielded to the highest AUC of 0.952, underscoring the substantial contribution of MER to predictive accuracy. Conclusions: This study discovered the involvement of aberrant DNA methylation in HCC with early recurrence. The MER outperforms clinicopathological predictors and achieves robust prediction capabilities in identifying patients at risk of ER. Full article

Background: Surgical resection remains an important treatment of choice for a large number of liver tumors in children. Sometimes, if a tumor infiltrates a large part of the liver, after resection, the future liver remnant (FLR) is not enough for normal liver function. The size of the FLR is one of the determining factors for resectability as postoperative liver failure (PLF) is the most severe complication after partial hepatectomy. A new strategy for treating marginally resectable liver tumors in adult patients which were initially considered as unresectable was formally reported in 2011. This operative technique is a hepatectomy consisting of two stages with initial portal vein ligation and in situ splitting of the liver parenchyma. In 2012, the acronym “ALPPS” (associating liver partition and portal vein ligation for staged hepatectomy) was proposed for this novel technique. However, there is a small number of ALPPS procedures performed in pediatric patients published in the literature. Objectives: The aim of this paper is to present the first case of a pediatric patient with a marginally resectable rhabdoid tumor of the liver which was initially considered unresectable and who was treated with two-stage hepatectomy. We report a case of a 4-month-old girl with a large rhabdoid tumor of the liver who underwent this procedure. Conclusions: ALPPS can be a valuable technique to achieve complete resection of pediatric liver tumors although indications for ALPPS in children still need further research mainly focused on validation of the minimally needed FLR in children undergoing extended liver resections. To our knowledge, this is the youngest patient on whom ALPPS was performed, and the only one with a rhabdoid tumor. Full article

Post-hepatectomy liver failure (PHLF) remains a significant risk for patients undergoing partial hepatectomy (PHx). Reliable prognostic markers and treatments to enhance liver regeneration are lacking. Plasma nanoparticles, including lipoproteins, exosomes, and extracellular vesicles (EVs), can reflect systemic and tissue-wide proteostasis and stress, potentially aiding liver regeneration. However, their role in PHLF is still unknown. Methods: Our study included nine patients with hepatocellular carcinoma (HCC) undergoing PHx: three patients with PHLF, three patients undergoing the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure, and three matched controls without complications after PHx. Patient plasma was collected before PHx as well as 1 and 5 days after. EVs were isolated by ultracentrifugation, and extracted proteins were subjected to quantitative mass spectrometry using a super-SILAC mix prepared from primary and cancer cell lines. Results: We identified 2625 and quantified 2570 proteins in the EVs of PHx patients. Among these, 53 proteins were significantly upregulated and 32 were downregulated in patients with PHLF compared to those without PHLF. Furthermore, 110 proteins were upregulated and 78 were downregulated in PHLF patients compared to those undergoing ALPPS. The EV proteomic signature in PHLF indicates significant disruptions in protein translation, proteostasis, and intracellular vesicle biogenesis, as well as alterations in proteins involved in extracellular matrix (ECM) remodelling and the metabolic and cell cycle pathways, already present before PHx. Conclusions: Longitudinal proteomic analysis of the EVs circulating in the plasma of human patients undergoing PHx uncovers proteomic signatures associated with PHLF, which reflect dying hepatocytes and endothelial cells and were already present before PHx. Full article

The incidence of colorectal cancer and colorectal liver metastases (CRLM) is increasing globally due to an interaction of environmental and genetic factors. A minority of patients with CRLM have surgically resectable disease, but for those who have resection as part of multimodal therapy for their disease, long-term survival has been shown. Precision surgery—the idea of careful patient selection and targeting of surgical intervention, such that treatments shown to be proven to benefit on a population level are the optimal treatment for each individual patient—is the new paradigm of care. Key to this is the understanding of tumour molecular biology and clinically relevant mutations, such as KRAS, BRAF, and microsatellite instability (MSI), which can predict poorer overall outcomes and a poorer response to systemic therapy. The emergence of immunotherapy and hepatic artery infusion (HAI) pumps show potential to convert previously unresectable disease to resectable disease, in addition to established systemic and locoregional therapies, but the surgeon must be wary of poor-quality livers and the spectre of post-hepatectomy liver failure (PHLF). Volume modulation, a cornerstone of hepatic surgery for a generation, has been given a shot in the arm with the advent of liver venous depletion (LVD) ensuring significantly more hypertrophy of the future liver remnant (FLR). The optimal timing of liver resection for those patients with synchronous disease is yet to be truly established, but evidence would suggest that those patients requiring complex colorectal surgery and major liver resection are best served with a staged approach. In the operating room, parenchyma-preserving minimally invasive surgery (MIS) can dramatically reduce the surgical insult to the patient and lead to better perioperative outcomes, with quicker return to function. Full article

Partial hepatectomy and ablation therapy are two widely used surgical procedures for localized early-stage hepatocellular carcinoma (HCC) patients. This article aimed to evaluate their relative effectiveness in terms of overall survival. An emulation analysis approach was first developed based on the Bayesian technique. We estimated propensity scores via Bayesian logistic regression and adopted a weighted Bayesian Weibull accelerated failure time (AFT) model incorporating prior information contained in the published literature. With the Surveillance, Epidemiology, and End Results (SEER)-Medicare data, an emulated target trial with rigorously defined inclusion/exclusion criteria and treatment regimens for early-stage HCC patients over 66 years old was developed. For the main cohort with tumor size less than or equal to 5 cm, a total of 1146 patients were enrolled in the emulated trial, with 301 and 845 in the partial hepatectomy and ablation arms, respectively. The analysis suggested ablation to be significantly associated with inferior overall survival (hazard ratio [HR] = 1.35; 95% credible interval [CrI]: 1.14, 1.60). For the subgroup with tumor size less than or equal to 3 cm, there was no significant difference in overall survival between the two arms (HR = 1.15; 95% CrI: 0.88, 1.52). Overall, the comparative treatment effect of ablation and partial hepatectomy on survival remains inconclusive. This finding may provide further insight into HCC clinical treatment. Full article

Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies. Full article

(1) Background: Despite advances in surgical technique and systemic chemotherapy, some patients with multifocal, bilobar colorectal liver metastases (CRLM) remain unresectable. These patients may benefit from surgical debulking of liver tumors in combination with chemotherapy compared to chemotherapy alone. (2) Methods: A retrospective study including patients evaluated for curative intent resection of CRLM was performed. Patients were divided into three groups: those who underwent liver resection with recurrence within 6 months (subtotal debulked, SD), those who had the first stage only of a two-stage hepatectomy (partially debulked, PD), and those never debulked (ND). Kaplan–Meier survival curves and log-rank test were performed to assess the median survival of each group. (3) Results: 174 patients underwent liver resection, and 34 patients recurred within 6 months. Of the patients planned for two-stage hepatectomy, 35 underwent the first stage only. Thirty-two patients were never resected. Median survival of the SD, PD, and ND groups was 31 months, 31 months, and 19.5 months, respectively (p = 0.012); (4) Conclusions: Patients who underwent a debulking of CRLM demonstrated a survival benefit compared to patients who did not undergo any surgical resection. This study provides support for the evaluation of intentional debulking versus palliative chemotherapy alone in a randomized trial. Full article

Colorectal cancer is the third most common cancer in the United States and the second most common cause of cancer-related death. Approximately 20–30% of patients will develop hepatic metastasis in the form of synchronous or metachronous disease. The treatment of colorectal liver metastasis (CRLM) has evolved into a multidisciplinary approach, with chemotherapy and a variety of locoregional treatments, such as ablation and portal vein embolization, playing a crucial role. However, resection remains a core tenet of management, serving as the gold standard for a curative-intent therapy. As such, the input of a dedicated hepatobiliary surgeon is paramount for appropriate patient selection and choice of surgical approach, as significant advances in the field have made management decisions extremely nuanced and complex. We herein aim to review the contemporary surgical management of colorectal liver metastasis with respect to both perioperative and operative considerations. Full article

Background: Two-staged hepatectomy (TSH) including portal vein embolization (PVE) may offer surgical treatment for extensive bilobar colorectal liver metastases (CRLM). This study aimed to investigate the feasibility and outcomes of extended right hepatectomy (ERH) within TSH including PVE for patients with extended CRLM. Methods: We retrospectively collected data of patients who underwent TSH for extended CRLM between 2015 and 2021 at our institution. Clearance of the left liver lobe (clear-up, CU) associated with PVE was followed by ERH. Results: Minimally invasive (n = 12, 46%, MIH) or open hepatectomy (n = 14, 54%, OH) was performed. Postoperative major morbidity and 90-day mortality were 54% and 0%. Three-year overall survival was 95%. Baseline characteristics, postoperative and long-term outcomes were comparable between MIH and OH. However, hospital stay was significantly shorter after MIH (8 vs. 15 days, p = 0.008). Additionally, the need for intraoperative transfusions tended to be lower in the MIH group (17% vs. 50%, p = 0.110). Conclusions: ERH following CU and PVE for extended CRLM is feasible and safe in laparoscopic and open approaches. MIH for ERH may result in shorter postoperative hospital stays. Further high-volume, multicenter studies are required to evaluate the potential superiority of MIH. Full article

Background: ALPPS popularity is increasing among surgeons worldwide and its indications are expanding to cure patients with primarily unresectable liver tumors. Few reports recommended limitations or even contraindications of ALPPS in perihilar cholangiocarcinoma (phCC). Here, we discuss the results of ALPPS in patients with phCC in a systematic review as well as a pooled data analysis. Methods: MEDLINE and Web of Science databases were systematically searched for relevant literature up to December 2023. All studies reporting ALPPS in the management of phCC were included. A single-arm meta-analysis of proportions was carried out to estimate the overall rate of outcomes. Results: After obtaining 207 articles from the primary search, data of 18 studies containing 112 phCC patients were included in our systematic review. Rates of major morbidity and mortality were calculated to be 43% and 22%, respectively. The meta-analysis revealed a PHLF rate of 23%. One-year disease-free survival was 65% and one-year overall survival was 69%. Conclusions: ALPPS provides a good chance of cure for patients with phCC in comparison to alternative treatment options, but at the expense of debatable morbidity and mortality. With refinement of the surgical technique and better perioperative patient management, the results of ALPPS in patients with phCC were improved. Full article