Search

The combination of atezolizumab plus bevacizumab (atezo/bev) has dramatically changed the treatment landscape of advanced HCC (aHCC), achieving durable responses in some patients. Using single-cell transcriptomics, we characterize the intra-tumoural and peripheral immune context of patients with aHCC treated with atezo/bev. Tumours from patients with durable responses are enriched for PDL1 + CXCL10 + macrophages and, based on cell-cell interaction analysis, express high levels of CXCL9/10/11 and are predicted to attract peripheral CXCR3 + CD8 + effector-memory T cells (CD8 T EM ) into the tumour. Based on T cell receptor sharing and pseudotime trajectory analysis, we propose that CD8 T EM preferentially differentiate into clonally-expanded PD1 -  CD45RA + effector-memory CD8 + T cells (CD8 T EMRA ) with pronounced cytotoxicity. In contrast, in non-responders, CD8 T EM remain frozen in their effector-memory state. Finally, in responders, CD8 T EMRA display a high degree of T cell receptor sharing with blood, consistent with their patrolling activity. These findings may help understand the possible mechanisms underlying response to atezo/bev in aHCC., (© 2023. The Author(s).)

Primary liver cancer comprises a diverse group of liver tumors. The heterogeneity of these tumors is seen as one of the obstacles to finding an effective therapy. The Hippo pathway, with its downstream transcriptional co-activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), has a decisive role in the carcinogenesis of primary liver cancer. Therefore, we examined the expression pattern of YAP and TAZ in 141 patients with hepatocellular carcinoma keratin 19 positive (HCC K19⁺), hepatocellular carcinoma keratin 19 negative (HCC K19 - ), combined hepatocellular⁻cholangiocarcinoma carcinoma (cHCC-CCA), or cholangiocarcinoma (CCA). All cHCC-CCA and CCA patients showed high expression levels for YAP and TAZ, while only some patients of the HCC group were positive. Notably, we found that a histoscore of both markers is useful in the challenging diagnosis of cHCC-CCA. In addition, positivity for YAP and TAZ was observed in the hepatocellular and cholangiocellular components of cHCC-CCA, which suggests a single cell origin in cHCC-CCA. Within the K19 - HCC group, our results demonstrate that the expression of YAP is a statistically significant predictor of poor prognosis when observed in the cytoplasm. Nuclear expression of TAZ is an even more specific and independent predictor of poor disease-free survival and overall survival of K19 - HCC patients. Our results thus identify different levels of YAP/TAZ expression in various liver cancers that can be used for diagnostics.

Human hepatocellular carcinomas (HCCs) expressing the biliary/hepatic progenitor cell marker keratin 19 (K19) have been linked with a poor prognosis and exhibit an increase in platelet-derived growth factor receptor α (PDGFRα) and laminin beta 1 (LAMB1) expression. PDGFRα has been reported to induce de novo synthesis of LAMB1 protein in a Sjogren syndrome antigen B (La/SSB)-dependent manner in a murine metastasis model. However, the role of this cascade in human HCC remains unclear. This study focused on the functional role of the PDGFRα-La/SSB-LAMB1 pathway and its molecular link to K19 expression in human HCC. In surgical HCC specimens from a cohort of 136 patients, PDGFRα expression correlated with K19 expression, microvascular invasion and metastatic spread. In addition, PDGFRα expression in pre-operative needle biopsy specimens predicted poor overall survival during a 5-year follow-up period. Consecutive histological staining demonstrated that the signaling components of the PDGFRα-La/SSB-LAMB1 pathway were strongly expressed at the invasive front. K19-positive HCC cells displayed high levels of α2β1 integrin (ITG) receptor, both in vitro and in vivo. In vitro activation of PDGFRα signaling triggered the translocation of nuclear La/SSB into the cytoplasm, enhanced the protein synthesis of LAMB1 by activating its internal ribosome entry site, which in turn led to increased secretion of laminin-111. This effect was abrogated by the PDGFRα-specific inhibitor crenolanib. Importantly LAMB1 stimulated ITG-dependent focal adhesion kinase/Src proto-oncogene non-receptor tyrosine kinase signaling. It also promoted the ITG-specific downstream target Rho-associated coiled-coil containing protein kinase 2, induced K19 expression in an autocrine manner, invadopodia formation and cell invasion. Finally, we showed that the knockdown of LAMB1 or K19 in subcutaneous xenograft mouse models resulted in significant loss of cells invading the surrounding stromal tissue and reduced HepG2 colonization into lung and liver after tail vein injection. The PDGFRα-LAMB1 pathway supports tumor progression at the invasive front of human HCC through K19 expression.

Background & Aims: Cancer stem cells (CSCs) are thought to be persistent in tumours due to their chemoresistance and to cause relapse and metastasis. Hepatic carcinomas displaying hepatic progenitor cell (HPC) features have been associated with a poor prognosis, though it remains unclear how CSCs relate to these different histological subtypes., Methods: Candidate CSCs were isolated using the side population (SP) technique from primary tissue samples diagnosed as keratin(K)19-negative or -positive hepatocellular carcinoma (HCC) or as combined hepatocellular/cholangiocarcinoma and analysed for gene and protein expression. The effect of laminin-332 was analysed in vitro by using HCC cell lines and in vivo using a xenograft mouse model., Results: The size of the SP correlated with the degree of HPC features found in human hepatic cancer, and also showed an elevated mRNA expression of biliary/HPC markers and the extracellular matrix marker LAMC2, the gene encoding the laminin γ2-chain. Immunopositivity for the γ2-chain of laminin-332 was seen in the extracellular matrix surrounding small HPC-like tumour cells with a low proliferation rate. In vitro, laminin-332 increased K19 expression, phosphorylated mTOR and decreased phospho-histone H3 expression, indicating reduced cell mitosis. The effect of laminin-332 was enhanced upon mTORC1 inhibition and diminished when inhibiting mTORC1+C2. Resistance to doxorubicin and sorafenib treatment, and the SP fraction increased in the coated condition. In vivo, laminin-332 reduced tumour growth and sustained K19 expression., Conclusions: In this study we identified a prominent role for laminin-332 as part of the specialised CSC niche in maintaining and supporting cell 'stemness', which leads to chemoresistance and quiescence., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: The purpose of this study was to retrospectively assess the technical and clinical outcomes, overall survival and prognostic factors for prolonged survival after yttrium-90 ((90)Y) radioembolization as a salvage therapy for patients with chemorefractory liver-only or liver-dominant colorectal metastases., Material and Methods: From January 2005 to January 2014, all the patients selected for (90)Y radioembolization to treat chemorefractory colorectal liver metastases were identified. Demographic, laboratory, imaging and dosimetry data were collected. Post-treatment technical and clinical outcomes were analyzed as well as overall survival; finally several factors potentially influencing survival were analyzed., Results: In total 88 patients were selected for angiographic workup; 71 patients (81%) finally underwent catheter-directed (90)Y microsphere infusion into the hepatic artery 25 days (standard deviation 13 days) after angiographic workup. Median infused activity was 1809 MBq; 30-day toxicity included: fatigue (n = 39; 55%), abdominal discomfort (n = 33; 47%), nausea (n = 5; 7%), fever (n = 14; 20%), diarrhea (n = 6; 9%), liver function abnormalities and elevated bilirubin (transient) (n = 3; 4%). Gastric ulcer was found in five patients (7%). A late complication was radioembolization-induced portal hypertension (REIPH) in three patients (4%). Median time to progression in the liver was 4.4 months. Estimated survival at six and 12 months was 65% and 30%, respectively, with a 50% estimated survival after 8.0 months in this group of chemorefractory patients. Prognostic factors for worse survival were high preprocedural bilirubin, alkaline phosphatase and tumor volume levels., Conclusion: (90)Y microsphere radioembolization for chemorefractory colorectal liver metastases has an acceptable safety profile with a 50% estimated survival after 8.0 months. Pretreatment high bilirubin, alkaline phosphatase and tumor volume levels were associated with early death.

Objective: Keratin (K)19, a biliary/hepatic progenitor cell (HPC) marker, is expressed in a subset of hepatocellular carcinomas (HCC) with poor prognosis. The underlying mechanisms driving this phenotype of K19-positive HCC remain elusive., Design: Clinicopathological value of K19 was compared with EpCAM, and α-fetoprotein, in a Caucasian cohort of 242 consecutive patients (167 surgical specimens, 75 needle biopsies) with different underlying aetiologies. Using microarrays and microRNA profiling the molecular phenotype of K19-positive HCCs was identified. Clinical primary HCC samples were submitted to in vitro invasion assays and to side population analysis. HCC cell lines were transfected with synthetic siRNAs against KRT19 and submitted to invasion and cytotoxicity assays., Results: In the cohort of surgical specimens, K19 expression showed the strongest correlation with increased tumour size (p<0.01), decreased tumour differentiation (p<0.001), metastasis (p<0.05) and microvascular invasion (p<0.001). The prognostic value of K19 was also confirmed in a set of 75 needle biopsies. Profiling showed that K19-positive HCCs highly express invasion-related/metastasis-related markers (eg, VASP, TACSTD2, LAMB1, LAMC2, PDGFRA), biliary/HPC markers (eg, CD133, GSTP1, NOTCH2, JAG1) and members of the miRNA family 200 (eg, miR-141, miR-200c). In vitro, primary human K19-positive tumour cells showed increased invasiveness, and reside in the chemoresistant side population. Functionally, K19/KRT19 knockdown results in reduced invasion, loss of invadopodia formation and decreased resistance to doxorubicin, 5-fluorouracil and sorafenib., Conclusions: Giving the distinct invasive properties, the different molecular profile and the poor prognostic outcome, K19-positive HCCs should be considered as a seperate entity of HCCs.

Background: Minimally invasive liver resection (MILR) for colorectal liver metastases (CRLM) is gaining widespread acceptance. However, data are still lacking on the feasibility, long- and short-term outcomes of laparoscopic major hepatectomy (i.e., three or more liver segments)., Methods: Between October 2002 and December 2008, prospectively collected data of 117 patients who underwent major liver resection [97 open (OMLR) and 20 laparoscopic (LMLR) procedures] for CRLM were analyzed. Twenty patients in the LMLR group were matched with 20 patients of the OMLR based on 13 parameters. We compared the long- and short-term outcomes between these two groups., Results: Median duration of surgery was 257.5 (range 75-360) min in LMLR versus 232.5 (range 120-400) min in OMLR (P = 0.228). Median blood loss during surgery was 550 ml in each group (range 100-4,000 vs. 100-2,500 ml, P = 0.884). There was no statistically significant difference in the rate of postoperative complications (both severity and location). Median magnitude of tumor-free resection margin was 7.5 versus 5.5 mm in the laparoscopy versus open group, respectively (P = 0.651). Median disease-free survival (DFS) of the entire study population was 18.4 months [95% confidence interval (CI) 11.9-50.0 months]. Median overall survival (OS) was 50.7 months (95% CI 36.2 months to undetermined). The estimated DFS and OS rates at 1, 2, and 5 years were comparable in the two groups (P = 0.637 and 0.872, respectively)., Conclusion: Laparoscopic MLR for selected CRLM is feasible and might result in comparable oncologic outcomes as in open liver resection.

Background: Few reports exist on long-term survival after minimally invasive liver surgery (MILS) for colorectal liver metastases (CRLM). No data are available assessing prognostic factors in the era of current modern treatment strategies., Methods: Between October 2002 and December 2008, 274 consecutive patients were analyzed on an intention-to-treat basis. Open liver surgery (OLS) was performed in 193 patients for a total of 437 metastases, and MILS was performed in 81 patients for 176 metastases. Systemic chemotherapy was administered preoperatively in 173 and postoperatively in 174 patients. The impact of 23 potential prognostic factors on disease-free (DFS) and overall survival (OS) was evaluated using univariable and multivariable Cox regression models., Results: Postoperative complications were observed in 54 patients after OLS and in 11 after MILS (p = 0.016). The median postoperative length of hospital stay was 9 days after OLS and 5 days after MILS (p < 0.0001). For the entire patient population, the 5 year DFS and OS rates were 29.9 and 59.5%, respectively. No differences in survival between patients treated with MILS and OLS were observed (p = 0.63). In univariable analyses, the number of liver metastases and the overall Fong's clinical risk score (CRS) were the only two variables that predicted DFS (p ≤ 0.0035) and OS (p ≤ 0.0005). In multivariable analyses, the total CRS was the only independent predictor of both DFS (p = 0.0002) and OS (p = 0.002)., Conclusion: The long-term oncologic outcome of surgically treated patients with CRLM is determined by the Fong's CRS. Although MILS does not influence long-term survival, it has a beneficial impact on the immediate postoperative clinical outcome.

In the treatment of metastatic colorectal cancer, the subset of patients with liver-only metastases shows the greatest promise for prolonged survival and cure. Advances in surgery and medical treatment have encouraged multimodality treatment strategies and therefore require a true multidisciplinary approach. The current standard of care includes peri-operative chemotherapy and surgery. The new era of biologically targeted therapy requires an in-depth look at the possible efficacy and risks of adding these agents to the treatment protocol., (© 2010 Wiley-Liss, Inc.)

Aims: Microwave ablation (MWA) is the most recent development in the field of local ablative therapies. The aim of this study was to evaluate the variability and reproducibility of single-probe MWA vs. radiofrequency ablation (RFA) of liver metastases smaller than 3cm in patients without underlying liver disease., Methods: Sixteen liver metastases were treated using MWA, and matched for size and localisation with 13 metastases treated by RFA. Tumour diameters and postoperative ablation diameters were recorded (D1 transverse; D2 antero-posterior; D3 cranio-caudal; mm) on computed tomography scans., Results: Median D1, D2, and D3 ablation diameters after MWA vs. RFA were 18.5 (12-64) vs. 34 (16-41)mm (p=0.003), 26 (14-60) vs. 35 (28-40)mm (p=0.046), and 20 (10-73) vs. 32 (20-45)mm (p=0.025), respectively. As compared to RFA, the variability between the lesions after MWA was significantly higher for D2 (p<0.0001) and D3 (p=0.002) but not for D1 (p=0.15). The ablation diameters were less uniform after MWA than after RFA (p<0.001)., Conclusion: Ablation diameters after single-probe MWA of metastatic liver tumours are highly variable and suboptimal. Improvements are needed before MWA can be implemented routinely., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Background: In several malignancies extracapsular lymph node involvement (ECLNI) identifies a subgroup of patients with worse prognosis but no data are available on its significance in pancreatic ductal adenocarcinoma (PDAC). The aim of our study was to assess the prognostic relevance of ECLNI in resectable PDAC., Methods: A retrospective analysis was performed of 137 consecutive pancreatic resections for PDAC. Two investigators blinded for survival data systematically reviewed all pathological data. Survival curves were estimated using the Kaplan-Meier method. Multivariable Cox regression models were used to identify predictors of disease-free survival (DFS) and overall survival (OS). The median follow-up after surgery was 19 months., Results: ECLNI was identified in 59 of 99 node-positive patients. The median DFS in patients with ECLNI vs. intracapsular LNI (ICLNI) was 6.8 vs. 12.0 months, respectively (P=.027). The median OS in patients with ECLNI vs. ICLNI was 16.1 and 21.8 months, respectively (P=.098). On multivariable analysis extracapsular lymph node ratio (ECLNR) was identified as an independent predictor of OS (P=.003). In patients with ECLNI, both OS and DFS were improved after adjuvant chemoradiation compared with those who did not receive adjuvant treatment (P=.01)., Conclusions: Extracapsular lymph node ratio is an independent predictor of survival in patients with PDAC. Patients with ECLNI from pancreatic cancer seem to benefit from adjuvant chemoradiation but not from chemotherapy alone.

The purpose of this study was to evaluate the accuracy of diffusion-weighted magnetic resonance imaging (DW-MRI) in differentiating HCC from benign cirrhotic lesions compared with conventional dynamic contrast-enhanced MRI. Fifty-five patients with cirrhosis underwent conventional and DW-MRI at 1.5 Tesla. Signal intensity ratios (SI(ratio)) of solid liver lesions to adjacent hepatic parenchyma were measured for b0, b100, b600 and b1000, and the apparent diffusion coefficients (ADC) were calculated. In 27 patients, imaging results were compared to histopathology, and in 28 patients, to imaging follow-up. Based on predetermined thresholds, sensitivity and specificity of DW-MRI and conventional MRI were compared. SI(ratio) was significantly different between malignant and benign lesions at all b-values (P < 0.0001). No significant difference in ADC was seen (P = 0.47). For detection of malignant lesions, DW-MRI with b600-SI(ratio) yielded a sensitivity of 95.2% compared to 80.6% for conventional MRI (P = 0.023) and a specificity of 82.7% compared to 65.4% (P = 0.064). The improved accuracy was most beneficial for differentiating malignant lesions smaller than 2 cm. DW-MRI with b600-SI(ratio) improved the detection of small HCC and the differentiation of pseudotumoral lesions compared with conventional MRI.

Background: Concerns have been raised regarding outcome after laparoscopic resection of hepatic neoplasms. This prospective study compared morbidity and adequacy of surgical margins in laparoscopic (LLR) versus open liver resection (OLR)., Methods: Outcome in 359 consecutive patients [male/female ratio 187/172; median age 60 years (range 18-84 years)] who underwent partial hepatectomy was analysed. Cirrhosis was present in 32 patients and preoperative chemotherapy was administered in 141 patients. Comparative analyses were performed using propensity scores for all and for matched patients (n=76 per group)., Results: Complications occurred in 68/250 (27.2%) patients after OLR and in 6/109 (5.5%) after LLR [odds ratio (OR) 0.16; 95% confidence interval (CI) 0.07-0.37; p<0.0001]. Median intraoperative blood loss was 500 ml (range 10-7,000 ml) in OLR and 100 ml (range 5-4,000 ml) in LLR (p<0.0001). Postoperative hospital stay was 8 days (range 0-155 days) after OLR and 6 days (range 0-41 days) after LLR (p<0.0001). In patients treated for liver malignancy, the surgical resection margin was positive on histopathological examination in 5/237 after OLR and in 1/77 after LLR. The magnitude of the resection margin was 7.5 mm (range 0-45 mm) in OLR and 10.0 mm (range 0-30 mm) in LLR (p=0.087)., Conclusions: LLR for hepatic neoplasms seems to be noninferior to OLR regarding adequacy of surgical margins, and superior to OLR regarding short-term postoperative outcome.

Background: Hemorrhage from portal and hepatic veins is a major concern with laparoscopic right hepatectomy (LRH). The standard hilar approach is dissection of the portal pedicle outside the liver parenchyma with separate transection of the right hepatic artery, portal vein, and bile duct. Variations in anatomy can hamper vascular and biliary control. The intrahepatic Glissonian access avoids these risks by en masse ligation of the portal structures without dissection for each separately. This technique was performed laparoscopically for the last 2 among 10 LRHs, and the results are presented., Methods: Total LRH was performed under ultrasound assistance for two patients with malignancy. After lymph node sampling at the hepatoduodenal ligament, dissection was started with the incision of liver parenchyma posterior and anterior to the hilum, then continued outside the portal pedicle bifurcation toward the right and left sheaths. An endoscopic vascular stapling device was placed to transect the right portal pedicle en masse under direct laparoscopic vision and cholangiography guidance. Parenchymal transection and vascular control of the right hepatic vein was accomplished with harmonic scalpel, cavitron ultrasonic aspirator, bipolar diathermy, clips, and endoscopic stapling device, as appropriate. No Pringle's maneuver was used. The specimen was extracted through a suprapubic incision using an endobag., Results: The operative times for the two patients were, respectively, 180 and 240 min. No blood loss occurred during the intrahepatic Glissonian dissection. Intraoperative blood loss (from the right hepatic vein) of 700 and 800 ml, respectively, was controlled laparoscopically. The postoperative periods were uneventful, with discharge, respectively, on days 6 and 7. The surgical resection margins were free of tumor., Conclusions: The laparoscopic intrahepatic Glissonian approach used for right hepatectomy is safe, simple, and reproducible. It facilitates the hepatic hilar dissection with minimal operative risk. Further implementation of this technique is encouraged to improve the outcome for patients undergoing laparoscopic liver resection.

Aims: Surgical radiofrequency ablation (RFA) of hepatic malignancies is associated with superior oncological outcome as compared to percutaneous RFA. The aim of this prospective non-randomized cohort study was to compare morbidity and mortality of laparoscopic (LRFA) vs. open (ORFA) radiofrequency ablation of liver cancer., Methods: Between October 1999 and November 2006, RFA was performed in 154 consecutive patients (percutaneous 12, LRFA 93, ORFA 49) for a total of 291 hepatic tumours (HCC 81, colorectal metastases 157, other 53). Seventy-four patients simultaneously underwent additional surgery. Laparoscopic RFA was performed in 45/54 patients with HCC, and in 44/54 patients with cirrhosis. Laparotomy was performed in 14/22 patients who underwent simultaneous colorectal resection, and in 12/22 patients with hepatic resection., Results: Postoperative complications occurred in 25 patients with subsequent mortality in 2. As compared with LRFA, ORFA was associated with significantly (p<0.01) higher intra-operative blood loss (median 20 (range 0-1700) vs. 10 (0-900) ml), longer duration of surgery (180 (25-440) vs. 75 (30-390) min), more postoperative complications (17 vs. 8), and longer postoperative hospital stay (8 (1-127) vs. 4 (1-51) d). According to the therapy-oriented severity grading system (TOSGS) classification, postoperative complications in the ORFA-group were more severe than those in the LRFA-group (p<0.01). These findings were consistent in patients without simultaneous colorectal and/or hepatic resection and in patients with liver tumours measuring 3cm or less. In univariate analysis the following factors were significantly (p<0.01) related to the presence of postoperative complications: simultaneous colorectal resection, laparotomy, duration of surgery, tumour location in right liver, liver segment 7 (p=0.01), absence of cirrhosis (p=0.02), liver segment 8 (p=0.03), and metastatic liver cancer (p=0.04)., Conclusion: LRFA for hepatic malignancies seems preferable above ORFA, provided good patient selection, surgical expertise, and long-term oncological control.

Aim: The amount of cancer cells disseminated during curative surgery for colorectal liver metastases (CRLM) may be responsible for recurrence. Haematogenous and intrahepatic cancer cell dissemination was evaluated, and its impact on cancer recurrence was assessed., Method: Twenty patients with resectable CRLM were included in a prospective study. Twelve patients underwent curative resection for 21 metastases. Ten selected metastases in eight patients were treated with radiofrequency ablation (RFA) followed by resection at the same operative session. Cancer cell dissemination was determined before, during and after surgery using 'real time' quantitative RT-PCR assay, based on detection and quantification of CEA and CK20 mRNA transcripts., Results: Circulating cancer cells were detected in 80% and intrahepatic cancer cells in 37% of the patients, though without impact on cancer recurrence. The amounts of disseminated cancer cells were significantly increased after surgery. This increase was similar in patients treated with and without RFA. RFA caused complete tumour destruction., Conclusion: Curative surgery for CRLM significantly increases the amount of disseminated cancer cells. Radiofrequency ablation can completely destroy selected resectable CRLM without excessive cancer cell dissemination. Neither haematogenous nor intrahepatic cancer cell dissemination were related to cancer recurrence in this small patient series.

Background: It remains unclear whether aggregated colon cancer cells have a higher tendency for metastasis formation than nonaggregated cells. Also, the absolute number of cancer cells required for hepatic metastasis remains undefined. The aim of the present study was to compare in the liver the metastatic efficiency of viable nonaggregated colon cancer cells versus cell aggregates for equivalent numbers of cancer cells., Materials and Methods: DHD/K12/TRb colon cancer cells were administered through the portal vein in syngeneic male BD IX rats. Surgical exploration was performed 8 weeks after injection. Four groups of rats were injected with 0.25 or 0.5 x 10(6) DHD/K12/TRb viable cancer cells, either as single nonaggregated cells or as cell aggregates., Results: Hepatic metastases were observed in 81% of the rats after intraportal injection of cell aggregates equivalent to 0.5 x 10(6) cancer cells. A significant lower metastatic efficiency was found after the injection of 0.5 x 10(6) non-aggregated, and 0.25 x 10(6) aggregated or nonaggregated cancer cells i.e., 16%, 32%, and 27%, respectively., Conclusion: Aggregated colon cancer cells have a higher metastatic efficiency in the liver compared with non-aggregated cells, although a critical number of cancer cells are necessary.

Aims: Several studies have focused on factors determining recurrence and survival rate after curative resection of colorectal liver metastases (LM). Data are lacking with regard to patterns of failure indicating where and when recurrences arise., Methods: One-hundred-and-five consecutive patients [F/M: 31/74; mean age 61 years (range 36-80 y)] with primary colorectal liver metastases underwent surgical R0 curative resection between 1990-1999. Patient follow-up was closed in January 2002. The common closing date method was used for survival analysis. Multivariate analysis was performed with the Cox proportional hazard technique., Results: The overall (OS) vs disease free survival (DFS) rates at 1, 2, and 5 years were 88.5 vs 63.3, 73.4 vs 40.2, and 36.8 vs 18.1%, respectively. Elevated serum CEA level was the only factor independently related to recurrent disease. Elevated serum CEA level, maximum diameter of liver metastases (LM), and satellitosis were factors significantly related to poor OS. Recurrent liver metastases developed in 43% and extra-hepatic metastases in 60% of the patients. In about half of the patients cancer recurrence was observed within 18 months, almost equally distributed between hepatic and extra-hepatic sites., Conclusion: Despite optimal patient selection and curative resection of colorectal liver metastases, more than a half of the patients developed cancer recurrence within 2 years.

Radiofrequency ablation (RFA) is a safe and effective treatment in patients with unresectable liver malignancies. Since there is little information on its optimal approach, the feasibility, clinical outcome, and efficacy of laparoscopic RFA need further investigation. Twenty-three consecutive patients with unresectable hepatic malignancies were treated with RFA. RFA was performed percutaneously in 5 patients (5 tumors; median maximum diameter of 25 mm [range, 20-73]), via laparotomy in 9 (28 tumors; median maximum diameter of 38 mm [5-90]), and via laparoscopy in 9 (16 tumors; median maximum diameter of 35 mm [8-58]). Mortality and intraoperative complication rates were 0. In the laparoscopy and laparotomy groups, mean blood loss was 13 mL versus 421 mL and mean hospital stay was 5.7 versus 11.2 days, respectively (P = 0.0008 and P = 0.04). Postoperative complications occurred in one patient after laparoscopic RFA and in three after RFA via laparotomy. After a median follow-up of 12.2 months, local recurrence occurred in 2 patients (laparoscopic RFA, 1; percutaneous RFA, 1), and new hepatic tumors developed in 7 (laparoscopic RFA, 2/9; RFA via laparotomy, 5/9). Laparoscopic RFA is a safe and feasible treatment modality to achieve tumor destruction in selected patients with unresectable hepatic malignancies.

Objective: The objective of this study was to assess the feasibility, safety, and outcome of laparoscopic liver resection for benign liver tumors in a multicenter setting., Background: Despite restrictive, tailored indications for resection in benign liver tumors, an increasing number of articles have been published concerning laparoscopic liver resection of these tumors., Methods: A retrospective study was performed in 18 surgical centres in Europe regarding their experience with laparoscopic resection of benign liver tumors. Detailed standardized questionnaires were used that focused on patient's characteristics, clinical data, type and characteristics of the tumor, technical details of the operation, and early and late clinical outcome., Results: From March 1992 to September 2000, 87 patients suffering from benign liver tumor were included in this study: 48 patients with focal nodular hyperplasia (55%), 17 patients with liver cell adenoma (21%), 13 patients with hemangioma (15%), 3 patients with hamartoma (3%), 3 patients with hydatid liver cysts (3%), 2 patients with adult polycystic liver disease (APLD) (2%), and 1 patient with liver cystadenoma (1%). The mean size of the tumor was 6 cm, and 95% of the tumors were located in the left liver lobe or in the anterior segments of the right liver. Liver procedures included 38 wedge resections, 25 segmentectomies, 21 bisegmentectomies (including 20 left lateral segmentectomies), and 3 major hepatectomies. There were 9 conversions to an open approach (10%) due to bleeding in 45% of the patients. Five patients (6%) received autologous blood transfusion. There was no postoperative mortality, and the postoperative complication rate was low (5%). The mean postoperative hospital stay was 5 days (range, 2-13 days). At a mean follow-up of 13 months (median, 10 months; range, 2-58 months), all patients are alive without disease recurrence, except for the 2 patients with APLD., Conclusions: Laparoscopic resection of benign liver tumors is feasible and safe for selected patients with small tumors located in the left lateral segments or in the anterior segments of the right liver. Despite the use of a laparoscopic approach, selective indications for resection of benign liver tumors should remain unchanged. When performed by expert liver and laparoscopic surgeons in selected patients and tumors, laparoscopic resection of benign liver tumor is a promising technique.

Aims: In selected patients with colorectal liver metastases, hepatic resection offers an opportunity for cure, with a 25-38% 5-year survival rate. The aim of this prospective study was to evaluate whether patient selection could be improved with pre-operative whole-body 18-fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) scan., Methods: Ninety-one consecutive patients were considered to be eligible for liver resection after investigation with conventional diagnostic methods (CDM). In all these patients a whole-body PET scan with FDG was performed prior to surgery. Follow-up was complete with a mean of 23 months (2 weeks-92 months). All PET images were reviewed blinded to intraoperative and follow-up data., Results: PET confirmed liver metastases in 90 (99%) patients, while it provided additional information in 10 (11%) patients, i.e., seven intra-abdominal, and three extra-abdominal. PET falsely upstaged six (6.6%) patients in whom malignancy was excluded by additional investigation, at the time of surgery, or during follow-up. PET falsely understaged seven (7.7%) patients with small intra-abdominal lesions., Conclusion: In patients with potentially curable colorectal liver metastases according to conventional diagnostic methods, whole-body FDG-PET can be considered as a complementary examination in order to further select patients for potentially curative liver resection, and to optimize therapeutic strategy.