High-risk Patients With Colorectal Liver Metastases Assessed by the Beppu Score Can Have Excellent Survival Through Multidisciplinary Treatment Including Local Ablation.

BACKGROUND/AIM: The Beppu score assessed by the Japanese Society of Hepato-Biliary-Pancreatic Surgery nomogram helps predict postoperative disease-free survival for patients with resectable colorectal liver metastases (CRLM). Using the Beppu score, patients with resectable CRLM were divided into three groups according to recurrence risk: low (≤6 points), moderate (7-10 points), and high-risk (≥11 points). Hepatectomy following preoperative chemotherapy is recommended for high-risk patients. The surgical outcome, local recurrence rates, and long-term survival were assessed, focusing on local ablation. PATIENTS AND METHODS: Twenty high-risk and unresectable CRLM patients were enrolled between April 2016 and April 2022. Hepatectomy with or without local ablation was performed after induction chemotherapy. Local ablation was permissive for patients with effective chemotherapy (partial response and stable disease) with CRLM ≤2 cm and ≥5 mm distant from major vessels. RESULTS: The median diameters and numbers of CRLM were 26 (10-150) mm and 9 (1-46). All 18 patients who received preoperative chemotherapy were disease controls. Local ablation was performed simultaneously on hepatectomy in 14 patients. The median diameters and numbers of the ablated nodules were 12 (5-17) mm and 3 (1-21). Local recurrence was 8.5% per 82 ablative nodules. Three-year disease-free and five-year overall survival was 57.4% and 56.2%, respectively. There was no significant difference in patients with or without local ablation. CONCLUSION: Our treatment strategy for high-risk CRLM patients is feasible and can provide an excellent long-term prognosis regardless of adding local ablation to hepatectomy.

A rare incidence of a hepatic artery pseudoaneurysm following plastic biliary stent insertion.

Hepatic artery pseudoaneurysms have been reported to occur in approximately 1% of cases after metal stenting for malignant biliary obstruction. In contrast, only a few cases have been reported as complications after plastic stenting for benign biliary disease. We report a 61-year-old man with cholangitis who presented with a rare complication of hemobilia after implantation of 7 Fr double pigtail plastic biliary stents. No bleeding was observed approximately one month after biliary stent tube removal. Contrast-enhanced CT scan revealed a circularly enhanced lesion (5 mm in diameter) in the arterial phase at the tip of the previously inserted plastic bile duct stent. Color Doppler ultrasonography enhanced the lesion and detected arterial blood flow inside. He was diagnosed with a hepatic artery pseudoaneurysm. However, he had no risk factors such as prolonged catheterization, severe cholangitis, liver abscess, or long-term steroid use. Superselective transarterial embolization using two metal microcoils was successfully completed without damage to the surrounding liver parenchyma. If hemobilia is suspected after insertion of a plastic bile duct stent, immediate monitoring using contrast-enhanced computed tomography or Doppler ultrasonography is recommended.

Recurrence-risk stratification using the Beppu score and selection of perioperative chemotherapy for colorectal liver metastases.

The annual postoperative disease-free survival for colorectal liver metastases can be easily estimated by weighting six preoperative clinical parameters (Beppu score). We identified three recurrence-risk stratification groups: the low (≤6 points), moderate (7-10 points), and high-risk (≥11 points). For low-, moderate-, and high-risk patients, hepatectomy alone, hepatectomy with adjuvant chemotherapy, and hepatectomy with preoperative chemotherapy are recommended, respectively. The Beppu score enables the decision on the necessity and timing of perioperative chemotherapy.

Surgery for Hepatocellular Carcinoma With Macroscopic Vascular Invasion in the Era of Modern Molecular Therapy.

It has been reported that patients with macroscopic vascular invasion accompanying hepatocellular carcinoma have a poor prognosis. Modern molecular therapy with multitargeted tyrosine kinase inhibitors and immune checkpoint inhibitors has shown promising results in patients with metastatic hepatocellular carcinoma; however, molecular therapy is limited to patients with Child-Pugh class A disease. This review summarizes the present status of surgical therapies, including conversion hepatectomy, for patients with MVI in the developing era of novel molecular therapy. Phase III studies showed patients with macroscopic vascular invasion had significant survival benefits from sorafenib [hazard ratio (HR)=0.68] and regorafenib (HR=0.67) versus placebo, and nivolumab (HR=0.74) versus sorafenib. Lenvatinib and atezolizumab plus bevacizumab showed marginal effects. It is currently widely assumed that molecular therapy alone will not cure the disease but that additional conversion hepatectomy will be required. A response other than progressive disease is essential but a pathological complete response is not always required. A significant randomized controlled trial has already started in China to assess the necessity for conversion hepatectomy after effective atezolizumab plus bevacizumab treatment, and the results are still awaited. According to Japanese national data, upfront hepatectomy can be recommended for patients with initially resectable disease and macroscopic vascular invasion other than for those with tumors in the main portal vein and the inferior vena cava. In addition, adequate adjuvant therapies with hepatic arterial chemotherapy and transarterial chemoembolization may be beneficial but an effective adjuvant molecular therapy is currently unavailable. In conclusion, novel molecular therapies with higher response rates customized to the oncologic characteristics of each hepatocellular carcinoma with macroscopic vascular invasion are needed to increase the likelihood of conversion surgery and improve long-term outcomes.

Durable Stable Disease by Atezolizumab/Bevacizumab Can Provide Long-term Survival of Patients With Hepatocellular Carcinoma Lung Metastases.

BACKGROUND: Multiple bilateral lung metastases secondary to hepatocellular carcinoma (HCC) are mainly treated with molecular therapy. Atezolizumab plus bevacizumab can provide excellent long-term survival for patients with a good response. CASE REPORT: A 67-year-old woman underwent right hepatectomy for a primary solitary HCC, 11 cm in diameter, after portal embolization. After 2 years, she developed bilateral lung metastases with >100 nodules, <1 cm in size. She had no viral hepatitis or liver cirrhosis, and the Child-Pugh Grade was A (5 points). Lenvatinib (12 mg daily) was administered as a first-line treatment and continued for 18 months. The best response was stable disease (SD). Subsequently, intravenous atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) was administered once every three weeks. The best response was SD, which continued for 26 months. After that, cabozantinib treatment was initiated and discontinued after one cycle. Subsequently, dual immune checkpoint inhibitor treatment (durvalumab + tremelimumab) was administered. She has had multiple, but lung-only, metastases over four years. She has been well as an outpatient with the Child-Pugh Grade of A and a performance status of 0. CONCLUSION: Even if atezolizumab plus bevacizumab does not induce a good response, a durable SD could prolong survival in patients with metastatic HCC while maintaining liver function and a good quality-of-life.

Efficacy of laparoscopic liver resection for small hepatocellular carcinoma located in the posterosuperior segments: A multi-institutional study using propensity score matching by the Kyushu Study Group of Liver Surgery.

AIM: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) located in the posterosuperior segments (PS) have generally been considered more difficult than those for HCC in anterolateral segments (AL), but may be safe and feasible for selected patients with accumulated experience. In the present study, we investigated the effectiveness of LLR for single nodular HCCs ≤3 cm located in PS. METHODS: In total, 473 patients who underwent partial liver resection for single nodular HCCs ≤3 cm at the 18 institutions belonging to the Kyusyu Study Group of Liver Surgery from January 2010 to December 2018 were enrolled. The short-term outcomes of laparoscopic partial liver resection and open liver resection (OLR) for HCCs ≤3 cm, with subgroup analysis of PS and AL, were compared using propensity score-matching analysis. Furthermore, results were also compared between LLR-PS and LLR-AL. RESULTS: The original cohort of patients with HCC ≤3 cm included 328 patients with LLR and 145 with OLR. After matching, 140 patients with LLR and 140 with OLR were analyzed. Significant differences were found between groups in terms of volume of blood loss (median, 55 vs. 287 ml, p < 0.001), postoperative complications (0.71 vs. 8.57%, p = 0.003), and postoperative hospital stay (median, 9 vs. 14 days, p < 0.001). The results of subgroup analysis of PS were similar. Short-term outcomes did not differ significantly between LLR-PS and LLR-AL after matching. CONCLUSIONS: Laparoscopic partial resection could be the preferred option for single nodular HCCs ≤3 cm located in PS.

Prognostic Impact of Surgical Margin Width in Hepatectomy for Colorectal Liver Metastasis.

As for resection for colorectal liver metastasis (CRLM), securing an adequate surgical margin is important for achieving a better prognosis. However, it is often difficult to achieve adequate margins for the resection of CRLM. So the current survival impact of sub-centi/millimeter surgical margins in hepatectomy for CRLM should be evaluated. In the current era of multidisciplinary treatment options, this review focused on the prognostic impact of a sub-centi/millimeter surgical margin width in hepatectomy for CRLM. We systematically reviewed retrospective studies that clearly described the surgical margin width for hepatectomy for CRLM. We selected studies conducted since 2000 that involved patients diagnosed as having CRLM. We focused on studies that investigated not only surgical margins, but also microscopic surgical curability such as R0 (microscopically complete resection) or R1 (microscopically incomplete resection), which clearly describe their definitions. Based on our literature review, 1, 2, or 5 mm was considered the minimum surgical margin width for hepatectomy for CRLM. Although a surgical margin width of 1 mm is acceptable for hepatectomy for CRLM, submillimeter margins, which are defined as R1 in many reports, are only acceptable for limited patients such as those who have undergone preoperative chemotherapy. Zero-mm margins are also acceptable in limited patients such as those who show a good response to preoperative chemotherapy. New chemotherapy agents have been reported to reduce the prognostic impact of a narrow surgical margin width. The incidence of margin recurrence, which is a major concern regarding R1 resection of CRLM, is about 20-30% according to the majority of earlier reports. As evaluations of the actual prognostic impact of the surgical margin remain difficult, further study is warranted.

Risk Factors of Complications from Central Bisectionectomy (H458) for Hepatocellular Carcinoma: A Multi-Institutional Single-Arm Analysis.

BACKGROUND: This study aims to clarify the perioperative risk factors and short-term prognosis of central bisectionectomy (CB) for hepatocellular carcinoma (HCC). METHODS: Surgical data from 142 selected patients out of 171 HCC patients who underwent anatomical CB (H458) between 2005 and 2020 were collected from 17 expert institutions in a single-arm retrospective study. RESULTS: Morbidities recorded by the International Study Group of Liver Surgery (ISGLS) from grade BC post-hepatectomy liver failure (PHLF) and bile leakage (PHBL), or complications requiring intervention were observed in 37% of patients. A multivariate analysis showed that increased blood loss (iBL) > 1500 mL from PHLF (risk ratio [RR]: 2.79), albumin level < 4 g/dL for PHBL (RR, 2.99), involvement of segment 1, a large size > 6 cm, or compression of the hepatic venous confluence or cava by HCC for all severe complications (RR: 5.67, 3.75, 6.51, and 8.95, respectively) (p < 0.05) were significant parameters. Four patients (3%) died from PHLF. HCC recurred in 50% of 138 surviving patients. The three-year recurrence-free and overall survival rates were 48% and 81%, respectively. CONCLUSIONS: Large tumor size and surrounding tumor involvement, or compression of major vasculatures and the related iBL > 1500 mL were independent risk factors for severe morbidities in patients with HCC undergoing CB.

A Laparoscopically Treated Case of Peritoneal Dissemination Mimicking Liver Metastases from Distal Cholangiocarcinoma Four Years After the Initial Pancreaticoduodenectomy.

BACKGROUND/AIM: Operable peritoneal dissemination from distal cholangiocarcinoma after pancreaticoduodenectomy is rare. Furthermore, peritoneal dissemination mimicking liver metastasis has scarcely been reported. CASE REPORT: An 81-year-old woman received pancreaticoduodenectomy for distal cholangiocarcinoma. She was diagnosed with stage IIA (T3a N0 M0) and received curative resection. She did not receive adjuvant chemotherapy. As a result of the examination in our department, she showed two tumors, 20 mm and 8 mm in segments 7/8 and 7, respectively, in the subphrenic liver surface four and half years after the initial pancreaticoduo-denectomy. The larger tumor was slow-growing, and cystic degeneration was inside. Plain computed tomography imaging revealed an isodense tumor with a marginal high ring and weak early enhancement, and prolonged peripheral enhancement was recognized at the marginal portion. Magnetic resonance imaging showed a heterogeneous mass with peripheral hypointensity ring that may be caused by fibrous tissue. Although the smaller tumor was diagnosed only after admission, it presented similar imaging findings to the larger tumor. The preoperative diagnosis was suspected to be liver metastases from DCC or inflammatory pseudotumor. Laparoscopic partial liver resection with diaphragm dissection was performed for both tumors. Pathologically, the tumors were diagnosed as peritoneal dissemination from distal cholangiocarcinoma. In the disseminated cancer cells, the expression of Ki67 was decreased, which was suspected to be one of the reasons for the long recurrence-free interval. The patient is doing well without any recurrence three months after the second operation. CONCLUSION: Laparoscopic surgery can provide excellent results for diagnosing and treating unknown subphrenic tumors.

Comprehensive data of 4502 patients newly diagnosed with colorectal liver metastasis between 2015 and 2017, and prognostic data of 2427 patients newly diagnosed with colorectal liver metastasis in 2013 and 2014: Third report of a nationwide survey in Japan.

To improve treatment outcomes in patients with colorectal liver metastasis (CRLM), the Joint Committee for Nationwide Survey on CRLM was established by the Japanese Society for Cancer of the Colon and Rectum and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. The aim of the study was to evaluate transition in the characteristics and treatment strategy in CRLM patients and analyze prognostic factors using large-scale data. The present study summarizes the data of patients newly diagnosed between 2015 and 2017 and presents prognostic data of patients newly diagnosed in 2013 and 2014. Survival curves were generated by the Kaplan-Meier method and compared by log-rank test. Multivariate analyses were carried out using Cox proportional hazard modeling. The data of 4502 patients newly diagnosed with CRLM between 2015 and 2017 and the prognostic data of 2427 patients diagnosed in 2013 and 2014 are included. Regarding the 2013 and 2014 prognostic data, the 5-year overall survival (OS) rates of patients who underwent hepatectomy alone was 59.8%. Multivariate analyses identified age at diagnosis of CRLM ≥70 years, concomitant extrahepatic metastasis at diagnosis of CRLM, tumor depth of primary lesion ≥subserosa/pericolic or perirectal tissue, mutant KRAS status, number of CRLM ≥5, maximum diameter of CRLM >5 cm, and surgical curability R1/R2 as independent predictors of OS. Analysis of the latest nationwide database of patients diagnosed with CRLM revealed changes in patients and oncological characteristics, a transition in treatment strategy, and different independent prognosticators to those reported previously.

Validation study of the JSHBPS nomogram for patients with colorectal liver metastases who underwent hepatic resection in the recent era - a nationwide survey in Japan.

BACKGROUND: The Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) nomogram was developed to predict disease-free survival in patients with colorectal liver metastases (CRLM) undergoing upfront hepatectomy. However, the utility of the nomogram in patients with resected CRLM remains unknown in the current situation in which treatment strategies are changing with advances in drugs. METHODS: Patients in the initial nomogram cohort (n = 727) and validation cohort (n = 2225) were divided into the upfront hepatectomy and preoperative chemotherapy groups. The nomogram was validated by measuring calibration and discrimination in the two cohorts. Calibration curves were plotted, and survival probabilities were compared. Finally, to quantify the discrimination power, we estimated the concordance index (C-index). RESULTS: In the upfront hepatectomy group, the C-index was 0.63, the suitable cutoff value of the Beppu score was 7, and adjuvant chemotherapy was significantly effective limited to high-risk patients (Beppu score ≥7). The C-index was 0.56 in the preoperative chemotherapy group. CONCLUSIONS: The JSHBPS nomogram remains beneficial for patients undergoing upfront hepatectomy in the recent era but is less effective for patients undergoing hepatectomy after chemotherapy. Patients with a Beppu score ≥7 showed high-risk recurrence, and adjuvant chemotherapy should be recommended for these patients.

Vater Papilla-preserving Strategy for Advanced Hepatocellular Carcinoma With Excessive Bile Duct Tumor Thrombus.

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is highly malignant; therefore, continual, multidisciplinary treatments are essential. CASE REPORT: In this study, two 78- and 81-year-old men were treated with the Vater papilla-preserving strategy. Case 1 had advanced HCC with BDTT expanding to the common bile duct (B4) and portal vein tumor thrombus (PVTT) of the umbilical portion. He showed triple-positive tumor markers. He underwent an extended left hepatectomy without bile duct resection following percutaneous transhepatic biliary drainage and transarterial chemoembolization (TACE). Later, TACE in combination with percutaneous microwave ablation was performed to treat four intrahepatic recurrent HCCs. Case 2 had diffuse-type HCCs accompanied by BDTT (B4) and PVTT to the right portal vein. He underwent liver partition associated with portal vein ligation for staged hepatectomy without bile duct resection. Six months later, he developed a solitary recurrent BDTT with obstructive jaundice. After percutaneous transhepatic biliary drainage, he was treated with two TACE from the various feeding arteries. Both patients achieved complete responses and are doing well without viable tumors approximately 2 years after the initial treatment. CONCLUSION: The Vater papilla-preserving strategy is essential for obtaining long-term survival and recurrent-free status for patients with HCC with highly extended BDTT.

Clinical impact of atrophic changes in remnant pancreas on the development of nonalcoholic fatty liver disease after pancreaticoduodenectomy.

Aim: The aim of this study was to evaluate risk factors for nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD), with a special focus on remnant pancreatic volume (RPV) as assessed using computed tomography (CT). Methods: From February 2004 to June 2017, 101 patients who underwent PD in our institution were enrolled. We defined a CT attenuation value of less than 40 HU as hepatic steatosis and measured RPV at 7 days, 3 months, and 1 year after PD using the SYNAPSE VINCENT system. The incidence of NAFLD and RPV were compared between the two groups according to reconstruction with pancreaticogastrostomy (PG) or pancreaticojejunostomy (PJ). Results: The incidence of NAFLD at 3 months after PD was 39.6% (40/101). The RPV ratio (RPV at 3 months or 1 year divided by RPV at 7 days after PD) at both 3 months and 1 year was significantly smaller in the PG group than in the PJ group (59% vs 73%, P < .001 and 53% vs 67% P < .01, respectively). A positive correlation between the RPV ratio and liver CT value at 3 months was found. The multivariate analysis identified three independent risk factors for NAFLD: female sex (odds ratio [OR] 8.16, 95% confidence interval [95% CI] 2.27-35.9, P < .001), PG reconstruction (OR 3.87, 95% CI 1.04-15.6, P = .04), and RPV ratio ≤60% (OR 3.44, 95% CI 1.06-11.8, P = .001). Conclusion: Atrophic change in the remnant pancreas is significantly associated with the development of NAFLD, and PJ reconstruction may be superior to PG from the viewpoint of NAFLD development.

Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease.

Prediction of hepatocellular carcinoma (HCC) risk is an urgent unmet need in patients with nonalcoholic fatty liver disease (NAFLD). In cohorts of 409 patients with NAFLD from multiple global regions, we defined and validated hepatic transcriptome and serum secretome signatures predictive of long-term HCC risk in patients with NAFLD. A 133-gene signature, prognostic liver signature (PLS)-NAFLD, predicted incident HCC over up to 15 years of longitudinal observation. High-risk PLS-NAFLD was associated with IDO1+ dendritic cells and dysfunctional CD8+ T cells in fibrotic portal tracts along with impaired metabolic regulators. PLS-NAFLD was validated in independent cohorts of patients with NAFLD who were HCC naïve (HCC incidence rates at 15 years were 22.7 and 0% in high- and low-risk patients, respectively) or HCC experienced (de novo HCC recurrence rates at 5 years were 71.8 and 42.9% in high- and low-risk patients, respectively). PLS-NAFLD was bioinformatically translated into a four-protein secretome signature, PLSec-NAFLD, which was validated in an independent cohort of HCC-naïve patients with NAFLD and cirrhosis (HCC incidence rates at 15 years were 37.6 and 0% in high- and low-risk patients, respectively). Combination of PLSec-NAFLD with our previously defined etiology-agnostic PLSec-AFP yielded improved HCC risk stratification. PLS-NAFLD was modified by bariatric surgery, lipophilic statin, and IDO1 inhibitor, suggesting that the signature can be used for drug discovery and as a surrogate end point in HCC chemoprevention clinical trials. Collectively, PLS/PLSec-NAFLD may enable NAFLD-specific HCC risk prediction and facilitate clinical translation of NAFLD-directed HCC chemoprevention.

Successful Treatment of Intrahepatic Cholangiocarcinoma With Liver/Lung Metastasis and Peritoneal Dissemination After Liver Resection.

BACKGROUND/AIM: Intrahepatic cholangiocarcinoma (ICC) is increasing in incidence and has a poor prognosis. CASE REPORT: A 79-year-old woman with two liver tumors was referred to our institution. The tumors demonstrated irregular margins and continuous peripheral enhancement. She had a good liver function and an elevated CA19-9 level. Extended left hepatectomy, and partial hepatectomy was performed. The patient was diagnosed with poorly differentiated ICC. Two lung metastases, one liver metastasis, and localized intraperitoneal dissemination occurred 19, 24, and 32 months after the initial hepatectomy. The lung metastases were treated with computed tomography-guided radiofrequency ablation approximately after one year of observation. The liver metastasis was resected immediately. The peritoneal dissemination was removed entirely after effective 3-month chemotherapy using gemcitabine and S-1. The patient is alive with no tumor 44 months after the first surgery. CONCLUSION: Multidisciplinary treatment considering a metastatic site and tumor malignancy might be effective for patients with ICC who have multiple recurrences.

Major postoperative complications are associated with early recurrence of hepatocellular carcinoma following hepatectomy.

BACKGROUND AND AIM: Early recurrence (ER) is a strong predictor of poor prognosis in patients with hepatocellular carcinoma (HCC) after hepatectomy. The aim of this study was to examine manageable factors associated with ER. METHODS: Overall, 475 consecutive patients with primary HCC who underwent curative hepatectomy were included (R0/R1). We defined ER as recurrence within 2 years after hepatectomy and analyzed predictors for ER. We also defined postoperative complication as Clavien-Dindo classification grade III or IV. RESULTS: ER after hepatectomy was observed in 209 cases (44.0%). Patients with ER had a significantly poor prognosis compared with those with late recurrence (log-rank p < 0.0001) and were more likely to be diagnosed with extrahepatic metastasis (p = 0.009). Significant predictors for ER were des-γ-carboxyprothrombin > 40 mAU/mL (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.36-3.14, p = 0.001), multiple tumors (OR 2.80 95%CI 1.83-4.32, p < 0.0001), cirrhosis (OR 1.53, 95%CI 1.01-2.32, p = 0.043), and postoperative complications (OR 1.72, 95% CI 1.05-2.85, p = 0.032). Blood loss (OR 1.09, 95%CI 1.05-1.13, p < 0.0001) and cirrhosis (OR 1.74, 95%CI 1.05-2.86, p = 0.031) were significant predictors for postoperative complications. CONCLUSIONS: We should pay close attention to surgical associated- and disease-specific factors in hepatectomy for HCC to prevent ER.

Highly Advanced Colorectal Liver Metastases Successfully Treated With Fluorouracil Plus Leucovorin Monotherapy and Microwave Ablation.

BACKGROUND: Fluorouracil plus leucovorin (5-FU/LV) is a less toxic but mild chemotherapy. CASE REPORT: A 63-year-old male patient with rectal cancer and multiple colorectal liver metastases (CRLM, total volume of 1,826 ml) was hospitalized. He had several poor prognostic factors, including elevated levels of tumor markers, with carcinoembryonic antigen and carbohydrate antigen 19-9 levels of 17,119 ng/ml and 7,617 U/ml, respectively. Additionally, the patient had a low body mass index, poor performance status, and a history of apparent weight loss. After capecitabine and oxaliplatin for four cycles, 5-FU/LV has been lasting for nine months. Interestingly, tumor marker levels returned close to normal limits, and the total CRLM volume decreased to 154 ml without any enhancements. The patient's general condition clearly improved after a year of chemotherapy. CONCLUSION: Chemotherapy with 5-FU/LV and percutaneous microwave ablation is beneficial to achieve tumor control in patients with highly advanced liver-only CRLM and poor general condition.